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Sample records for respiratory disease orthopedic

  1. LANL spinoff receives NIH grant for respiratory disease diagnostic...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    LANL spinoff receives NIH grant LANL spinoff receives NIH grant for respiratory disease diagnostic device Mesa Tech has been awarded a grant to develop an inexpensive, ...

  2. Respiratory disease in Utah coal miners

    SciTech Connect (OSTI)

    Rom, W.N.; Kanner, R.E.; Renzetti, A.D. Jr.; Shigeoka, J.W.; Barkman, H.W.; Nichols, M.; Turner, W.A.; Coleman, M.; Wright, W.E.

    1981-04-01

    Two hundred forty-two Utah underground coal miners volunteered to participate in a respiratory disease study. They were an older group (mean, 56 years of age) and had spent a mean of 29 years in the coal-mining industry. The prevalence of chronic bronchitis was 57%, and that of coal worker's pneumoconiosis, 25%; only one worker had progressive massive fibrosis. Significant impairment of pulmonary function was found among those with a history of cigarette smoking. Chronic bronchitis or coal worker's penumoconiosis among nonsmokers did not impair pulmonary function. There was a significant association among the nonsmokers between increasing exposure to coal dust and coal worker's pneumoconiosis, but not for changes in pulmonary function. Coal mine dust had a significant influence in causing the symptom complex of chronic cough and sputum production, and coal worker's pneumoconiosis.

  3. Respiratory disease in Utah coal miners

    SciTech Connect (OSTI)

    Rom, W.N.; Kanner, R.E.; Renzetti, A.D. Jr.; Shigeoka, J.W.; Barkman, H.W.; Nichols, M.; Turner, W.A.; Coleman, M.; Wright, W.E.

    1981-04-01

    Two hundred forty-two Utah underground coal miners volunteered to participate in a respiratory disease study. They were an older group (mean, 56 years of age) and had spent a mean of 29 years in the coal-mining industry. The prevalence of chronic bronchitis was 57%, and that of coal worker's pneumoconiosis, 25%; only one worker had progressive massive fibrosis. Significant impairment of pulmonary function was found among those with a history of cigarette smoking. Chronic bronchitis or coal worker's pneumoconiosis among nonsmokers did not impair pulmonary function. There was a significant association among the nonsmokers between increasing exposure to coal dust and coal worker's pneumoconiosis, but not for changes in pulmonary function. Coal mine dust had a significant influence in causing the symptom complex of chronic cough and sputum production, and coal worker's pneumoconiosis.

  4. LANL spinoff receives NIH grant for respiratory disease diagnostic device

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    LANL spinoff receives NIH grant LANL spinoff receives NIH grant for respiratory disease diagnostic device Mesa Tech has been awarded a grant to develop an inexpensive, instrument-free, nucleic-acid testing device to diagnose various respiratory diseases in record time. October 19, 2011 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience, sustainable

  5. Respiratory diseases research at NIOSH: reviews of research programs of the National Institute for Occupational Safety and Health

    SciTech Connect (OSTI)

    2008-07-01

    Respiratory diseases caused by exposures to dangerous materials in the workplace have tremendous implications for worker health and, by extension, the national economy. The National Institute for Occupational Safety and Health (NIOSH) estimates that deaths from work-related respiratory diseases and cancers account for about 70% of all occupational disease deaths. NIOSH conducts research in order to detect and reduce work-related hazardous exposures, injuries, and diseases; its Respiratory Disease Research Program (RDRP) focuses on respiratory diseases. This National Research Council book reviews the RDRP to evaluate the 1) relevance of its work to improvements in occupational safety and health and 2) the impact of research in reducing workplace respiratory illnesses. The assessment reveals that the program has made essential contributions to preventing occupational respiratory disease. The National Research Council has rated the Program a 5 out of 5 for relevance, and a 4 out of 5 for impact. To further increase its effectiveness, the Respiratory Disease Research Program should continue and expand its current efforts, provide resources for occupational disease surveillance, and include exposure assessment scientists in its activities. There are numerous references to respiratory systems diseases caused by coal mining. 4 apps.

  6. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease

    SciTech Connect (OSTI)

    Johnson, Reed F.; Hammoud, Dima A.; Lackemeyer, Matthew G.; Yellayi, Srikanth; Solomon, Jeffrey; Bohannon, Jordan K.; Janosko, Krisztina B.; Jett, Catherine; Cooper, Kurt; Blaney, Joseph E.; Jahrling, Peter B.

    2015-07-15

    Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412). Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many similarities to smallpox; however, severe respiratory tract disease was observed (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease after small particle aerosol exposure of rhesus monkeys using computed tomography (CT) to monitor respiratory disease progression. Subjects developed a severe respiratory disease that was uniformly lethal at 5.7 log{sub 10} PFU of CPXV-BR. CT indicated changes in lung architecture that correlated with changes in peripheral blood monocytes and peripheral oxygen saturation. While the small particle aerosol inoculation route does not accurately mimic human smallpox, the data suggest that CT can be used as a tool to monitor real-time disease progression for evaluation of animal models for human diseases. - Highlights: • Small particle aerosol exposure of rhesus results in a severe respiratory disease. • CT findings correlated with peripheral oxygen saturation and monocyte increases. • Virus dissemination was limited and mainly confined to the respiratory tract. • CT provides insight into pathogenesis to aid development of animal models of disease.

  7. Prevalence of respiratory symptoms and diseases in schoolchildren living in a polluted and in a low polluted area in Israel

    SciTech Connect (OSTI)

    Goren, A.I.; Hellmann, S.

    1988-02-01

    Second and fifth grade schoolchildren living in two communities with different levels of air pollution were studied. The parents of these children filled out ATS-NHLI health questionnaires. The prevalence of reported respiratory symptoms and pulmonary diseases was found to be significantly higher among children growing up in the polluted community (Ashdod) as compared with the low-pollution area (Hadera). Logistic models fitted for the respiratory conditions which differed significantly between both areas of residence also included background variables that could be responsible for these differences. Relative risk values, which were calculated from the logistic models, were in the range of 1.47 for cough without cold to 2.66 for asthma for children from Ashdod, as compared with 1.00 for children from Hadera.

  8. Bioactive glass coatings for orthopedic metallic implants

    SciTech Connect (OSTI)

    Lopez-Esteban, Sonia; Saiz, Eduardo; Fujino, Sigheru; Oku, Takeo; Suganuma, Katsuaki; Tomsia, Antoni P.

    2003-06-30

    The objective of this work is to develop bioactive glass coatings for metallic orthopedic implants. A new family of glasses in the SiO2-Na2O-K2O-CaO-MgO-P2O5 system has been synthesized and characterized. The glass properties (thermal expansion, softening and transformation temperatures, density and hardness) are in line with the predictions of established empirical models. The optimized firing conditions to fabricate coatings on Ti-based and Co-Cr alloys have been determined and related to the glass properties and the interfacial reactions. Excellent adhesion to alloys has been achieved through the formation of 100-200 nm thick interfacial layers (Ti5Si3 on Ti-based alloys and CrOx on Co-Cr). Finally, glass coatings, approximately 100 mu m thick, have been fabricated onto commercial Ti alloy-based dental implants.

  9. CFD modeling and image analysis of exhaled aerosols due to a growing bronchial tumor: Towards non-invasive diagnosis and treatment of respiratory obstructive diseases

    SciTech Connect (OSTI)

    Xi, Jinxiang [Central Michigan Univ., Mount Pleasant, MI (United States); Kim, JongWon [Central Michigan Univ., Mount Pleasant, MI (United States); Si, Xiuhua A. [California Baptist Univ., Riverside, CA (United States); Corley, Richard A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kabilan, Senthil [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Wang, Shengyu [First Affiliated Hospital of Xi'an Medical Univ., Shaanxi (China); Mayo Clinic, Rochester, MN (United States)

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 ?m at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.

  10. CFD modeling and image analysis of exhaled aerosols due to a growing bronchial tumor: Towards non-invasive diagnosis and treatment of respiratory obstructive diseases

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Kabilan, Senthil; Wang, Shengyu

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treatmore » the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 μm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.« less

  11. CFD modeling and image analysis of exhaled aerosols due to a growing bronchial tumor: Towards non-invasive diagnosis and treatment of respiratory obstructive diseases

    SciTech Connect (OSTI)

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Kabilan, Senthil; Wang, Shengyu

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 μm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.

  12. CFD Modeling and Image Analysis of Exhaled Aerosols due to a Growing Bronchial Tumor: towards Non-Invasive Diagnosis and Treatment of Respiratory Obstructive Diseases

    SciTech Connect (OSTI)

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Kabilan, Senthil; Wang, Shengyu

    2015-02-06

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure vari-ations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagran-gian tracking approach were used to model respiratory airflows and aerosol dynamics. Respira-tions of tracer aerosols of 1 m at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug de-livery protocol.

  13. Respiratory Protection Program

    Broader source: Energy.gov [DOE]

    This page is supported by the Respiratory Protection Program Administrators Group. The Respiratory Protection Program Administrators Group is a volunteer organization co-sponsored by the DOE Office of Worker Safety and Health Policy and the Energy Facility Contractors Group (EFCOG) to provide a forum for DOE and DOE contractor personnel to identify respiratory protection issues of concern to the DOE and pursue solutions to issues identified.

  14. In-vivo orthopedic implant diagnostic device for sensing load, wear, and infection

    DOE Patents [OSTI]

    Evans, III, Boyd McCutchen; Thundat, Thomas G.; Komistek, Richard D.; Dennis, Douglas A.; Mahfouz, Mohamed

    2006-08-29

    A device for providing in vivo diagnostics of loads, wear, and infection in orthopedic implants having at least one load sensor associated with the implant, at least one temperature sensor associated with the implant, at least one vibration sensor associated with the implant, and at least one signal processing device operatively coupled with the sensors. The signal processing device is operable to receive the output signal from the sensors and transmit a signal corresponding with the output signal.

  15. Multiplex detection of respiratory pathogens

    DOE Patents [OSTI]

    McBride, Mary; Slezak, Thomas; Birch, James M.

    2012-07-31

    Described are kits and methods useful for detection of respiratory pathogens (influenza A (including subtyping capability for H1, H3, H5 and H7 subtypes) influenza B, parainfluenza (type 2), respiratory syncytial virus, and adenovirus) in a sample. Genomic sequence information from the respiratory pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

  16. Hanford Site Respiratory Protection Program (HSRPP)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    DOE-0352 Revision 0 Hanford Site Respiratory Protection Program (HSRPP) Prepared for the U.S. Department of Energy Assistant Secretary for Environmental Management DOE-0352, Hanford Site Respiratory Protection Program (HSRPP) HSRPP Page 2 of 44 DOE-0352, Hanford Site Respiratory Protection Program (HSRPP) HSRPP Page 3 of 44 Contents 1.0 Purpose ............................................................................................................................. 6 2.0 Scope

  17. Navajo Coal Combustion and Respiratory Health Near Shiprock, New Mexico

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Bunnell, Joseph E.; Garcia, Linda V.; Furst, Jill M.; Lerch, Harry; Olea, Ricardo A.; Suitt, Stephen E.; Kolker, Allan

    2010-01-01

    Indoormore » air pollution has been identified as a major risk factor for acute and chronic respiratory diseases throughout the world. In the sovereign Navajo Nation, an American Indian reservation located in the Four Corners area of the USA, people burn coal in their homes for heat. To explore whether/how indoor coal combustion might contribute to poor respiratory health of residents, this study examined respiratory health data, identified household risk factors such as fuel and stove type and use, analyzed samples of locally used coal, and measured and characterized fine particulate airborne matter inside selected homes. In twenty-five percent of homes surveyed coal was burned in stoves not designed for that fuel, and indoor air quality was frequently found to be of a level to raise concerns. The average winter 24-hour PM 2.5 concentration in 20 homes was 36.0  μ g/ m 3 . This is the first time that PM 2.5 has been quantified and characterized inside Navajo reservation residents' homes.« less

  18. Effects of air pollution on the respiratory health of children: a cross-sectional study

    SciTech Connect (OSTI)

    Spinaci, S.; Arossa, W.; Bugiani, M.; Natale, P.; Bucca, C.; de Candussio, G.

    1985-09-01

    To investigate the effects of air pollution on the respiratory health of children, a subject of some controversy, a comparative study was undertaken of 2,385 school children who lived in central urban, peripheral urban, and suburban areas. Daily monitoring of sulfur dioxide and total suspended particle concentrations in all areas showed that pollutant concentrations in central and peripheral urban areas were above commonly accepted safety levels for respiratory health, while concentrations in the suburban area were within acceptable limits. A questionnaire administered to each mother assessed environmental exposure to pollutants in the household, the occurrence of respiratory symptoms as well as lung diseases as diagnosed by a physician, and general information. Children were interviewed about smoking habits and any acute respiratory symptoms. Children also performed standard lung function tests. Results showed that children from both urban areas had lessened pulmonary function and a higher prevalence of bronchial secretion with common colds than did those from the suburban area. These differences persisted after corrections for exposure to indoor pollutants, active or passive smoking, socioeconomic status, and sex. Parental cigarette smoking was related to a fall in forced expiratory volume in 1 second and an increased incidence of acute respiratory illnesses and chronic cough in children. Although boys had higher lung volumes and lower air flow, regression analysis showed no significant influence of the interactions sex-geographic area and sex-smoking on lung function. It was concluded that air pollution has a significant effect on the respiratory health of children.

  19. Workers Deliver Award-Winning Respiratory Safety | Department of Energy

    Office of Environmental Management (EM)

    Deliver Award-Winning Respiratory Safety Workers Deliver Award-Winning Respiratory Safety April 2, 2013 - 12:00pm Addthis Workers wear air purifying respirators in the Plutonium Finishing Plant. Workers wear air purifying respirators in the Plutonium Finishing Plant. A program developed by employees enhances use of respiratory equipment in the Plutonium Finishing Plant. A program developed by employees enhances use of respiratory equipment in the Plutonium Finishing Plant. Workers wear air

  20. Nitrogen dioxide and respiratory illnesses in infants

    SciTech Connect (OSTI)

    Samet, J.M.; Lambert, W.E.; Skipper, B.J.; Cushing, A.H.; Hunt, W.C.; Young, S.A.; McLaren, L.C.; Schwab, M.; Spengler, J.D. )

    1993-11-01

    Nitrogen dioxide is an oxidant gas that contaminates outdoor air and indoor air in homes with unvented gas appliances. A prospective cohort study was carried out to test the hypothesis that residential exposure to NO2 increases incidence and severity of respiratory illnesses during the first 18 months of life. A cohort of 1,205 healthy infants from homes without smokers was enrolled. The daily occurrence of respiratory symptoms and illnesses was reported by the mothers every 2 wk. Illnesses with wheezing or wet cough were classified as lower respiratory tract. Indoor NO2 concentrations were serially measured with passive samplers place in the subjects' bedrooms. In stratified analyses, illness incidence rates did not consistently increase with exposure to NO2 or stove type. In multivariate analyses that adjusted for potential confounding factors, odds ratios were not significantly elevated for current or lagged NO2 exposures, or stove type. Illness duration, a measure of illness severity, was not associated with NO2 exposure. The findings can be extended to homes with gas stoves in regions of the United States where the outdoor air is not heavily polluted by NO2.

  1. Returning to Work After a Respiratory Infection | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Returning to Work After a Respiratory Infection Occ Med Guidance: Returning to Work After a Respiratory Infection All, In recent weeks I've noticed that many staff members were recovering from upper respiratory infections (usually a cold). I've received questions about the criteria for safe return to work during convalescence from such illnesses. This can be a difficult decision. It's not necessary or feasible to require yourself to be completely asymptomatic before returning to work. For

  2. Chronic respiratory effects of indoor formaldehyde exposure

    SciTech Connect (OSTI)

    Krzyzanowski, M.; Quackenboss, J.J.; Lebowitz, M.D.

    1990-01-01

    The relation of chronic respiratory symptoms and pulmonary function to formaldehyde (HCHO) in homes was studied in a sample of 298 children (6-15 years of age) and 613 adults. HCHO measurements were made with passive samplers two one-week periods. Data on chronic cough and phlegm, wheeze, attacks of breathlessness, and doctor diagnoses of chronic bronchitis and asthma were collected with self-completed questionnaires. Peak expiratory flow rates (PEFR) were obtained during the evenings and mornings for up to 14 consecutive days for each individual. Significantly greater prevalence rates of asthma and chronic bronchitis were found in children from houses with HCHO levels 60-120 ppb than in those less exposed, especially in children also exposed to environmental tobacco smoke. In children, levels of PEFR linearly decreased with HCHO exposure, with estimated decrease due to 60 ppb of HCHO equivalent to 22% of PEFR level in nonexposed children.

  3. NICS report links VOCs to respiratory problems

    SciTech Connect (OSTI)

    Kirschner, E.

    1992-04-22

    Children who live near the chemical plants of Kanawha Valley, WV, suffer more acute and chronic respiratory aliments than those farther away, says a Harvard University School of Public Health report. In the $1-million, five-year study commissioned by the National Institute for Chemical Studies (NICS:Charleston, WV) and funded by the Environmental Protection Agency, proximity to chemical plants that emit volatile organic compounds (VOCs) was linked to higher incidence of asthma, acute eye irritation, shortness of breath, and chronic cough. The researchers say they adjusted for most other factors, such as parental smoking and petroleum. {open_quotes}The research hypothesis was whether children in the valley had more symptoms,{close_quotes} says NICS president Paul Hill. {open_quotes}Yes, there is a difference.{close_quotes} The study showed that some ailments were up to 28% more prevalent in children in the valley than in other Kanawha County children.

  4. Chronic respiratory effects of indoor formaldehyde exposure

    SciTech Connect (OSTI)

    Krzyzanowski, M.; Quackenboss, J.J.; Lebowitz, M.D. )

    1990-08-01

    The relation of chronic respiratory symptoms and pulmonary function to formaldehyde (HCHO) in homes was studied in a sample of 298 children (6-15 years of age) and 613 adults. HCHO measurements were made with passive samplers during two 1-week periods. Data on chronic cough and phlegm, wheeze, attacks of breathlessness, and doctor diagnoses of chronic bronchitis and asthma were collected with self-completed questionnaires. Peak expiratory flow rates (PEFR) were obtained during the evenings and mornings for up to 14 consecutive days for each individual. Significantly greater prevalence rates of asthma and chronic bronchitis were found in children from houses with HCHO levels 60-120 ppb than in those less exposed, especially in children also exposed to environmental tobacco smoke. In children, levels of PEFR decreased linearly with HCHO exposure, with the estimated decrease due to 60 ppb of HCHO equivalent to 22% of PEFR level in nonexposed children. The effects in asthmatic children exposed to HCHO below 50 ppb were greater than in healthy ones. The effects in adults were less evident: decrements in PEFR due to HCHO over 40 ppb were seen only in the morning, and mainly in smokers.

  5. Occupational exposures and chronic respiratory symptoms. A population-based study

    SciTech Connect (OSTI)

    Korn, R.J.; Dockery, D.W.; Speizer, F.E.; Ware, J.H.; Ferris, B.G. Jr.

    1987-08-01

    Data from a random sample of 8515 white adults residing in 6 cities in the eastern and midwestern United States were used to examine the relationships between occupational exposures to dust or to gases and fumes and chronic respiratory symptoms; 31% of the population had a history of occupational dust exposure and 30% reported exposure to gas or fumes. After adjusting for smoking habits, age, gender, and city of residence, subjects with either occupational exposure had significantly elevated prevalences of chronic cough, chronic phlegm, persistent wheeze, and breathlessness. The adjusted relative odds of chronic respiratory symptoms for subjects exposed to dust ranged from 1.32 to 1.60. Subjects with gas or fume exposure had relative odds of symptoms between 1.27 and 1.43 when compared with unexposed subjects. Occupational dust exposure was associated with a higher prevalence of chronic obstructive pulmonary disease as defined by an FEV1/FVC ratio of less than 0.6, when comparing exposed and unexposed participants (OR = 1.53, 95% Cl = 1.17-2.08). Gas or fume exposure was associated with a small, but not significant, increase in COPD prevalence. Significant trends were noted for wheeze and phlegm with increasing duration of dust exposure. Although 36% of exposed subjects reported exposure to both dust and fumes, there was no evidence of a multiplicative interaction between the effects of the individual exposures. Smoking was a significant independent predictor of symptoms, but did not appear to modify the effect of dust or fumes on symptom reporting. These data, obtained in random samples of general populations, demonstrate that chronic respiratory symptoms and disease can be independently associated with occupational exposures.

  6. Occupational exposures and chronic respiratory symptoms: a population-based study

    SciTech Connect (OSTI)

    Korn, R.J.; Dockery, D.W.; Speizer, F.E.; Ware, J.H.; Ferris, B.G.

    1987-01-01

    Data from a random sample of 8515 white adults residing in six cities in the eastern and midwestern United States were used to examine the relationships between occupational exposures to dust or to gases and fumes and chronic respiratory symptoms. 31% of the population had a history of occupational dust exposure and 30% reported exposure to gas or to fumes. After adjusting for smoking habits, age, gender, and city of residence, subjects with either occupational exposure had significantly elevated prevalence of chronic cough, chronic phlegm, persistent wheeze, and breathlessness. The adjusted relative odds of chronic respiratory symptoms for subjects exposed to dust ranged from 1.32 to 1.60. Subjects with gas or fume exposure had relative odds of symptoms between 1.27 and 1.43 when compared to unexposed subjects. Occupational dust exposure was associated with a higher prevalence of chronic obstructive pulmonary disease (COPD) as defined by an FEV1/FVC ratio of less than 0.6, when comparing exposed and unexposed participants (OR=1.53, 95% CI=1.17-2.08). Gas or fume exposure was associated with a small, but not significant, increase in COPD prevalence. Significant trends were noted for wheeze and phlegm with increasing duration of dust exposure. Although 36% of exposed subjects reported exposure to both dust and fumes, there was no evidence of a multiplicative interaction between the effects of the individual exposures. Smoking was a significant independent predictor of symptoms, but did not appear to modify the effect of dust or fumes on symptom reporting. These data, obtained in random samples of general populations, demonstrate that chronic respiratory disease can be independently associated with occupational exposures.

  7. Regional respiratory tract absorption of inhaled reactive gases

    SciTech Connect (OSTI)

    Miller, F.J.; Overton, J.H.; Kimbell, J.S.; Russell, M.L.

    1992-06-29

    Highly reactive gases present unique problems due to the number of factors which must be taken into account to determine regional respiratory tract uptake. The authors reviewed some of the physical, chemical, and biological factors that affect dose and that must be understood to interpret toxicological data, to evaluate experimental dosimetry studies, and to develop dosimetry models. Selected dosimetry experiments involving laboratory animals and humans were discussed, showing the variability and uptake according to animal species and respiratory tract region for various reactive gases. New experimental dosimetry approaches, such as those involving isotope ratio mass spectroscopy and cyclotron generation reactive gases, were discussed that offer great promise for improving the ability to study regional respiratory tract absorption of reactive gases. Various dosimetry modeling applications were discussed which demonstrate: the importance of airflow patterns for site-specific dosimetry in the upper respiratory tract, the influence of the anatomical model used to make inter- and intraspecies dosimetric comparisons, the influence of tracheobronchial path length on predicted dose curves, and the implications of ventilatory unit structure and volume on dosimetry and response. Collectively, these examples illustrate important aspects of regional respiratory tract absorption of inhaled reactive gases. Given the complex nature of extent and pattern of injury in the respiratory tract from exposure to reactive gases, understanding interspecies differences in the absorption of reactive gases will continue to be an important area for study.

  8. Human torso phantom for imaging of heart with realistic modes of cardiac and respiratory motion

    DOE Patents [OSTI]

    Boutchko, Rostyslav; Balakrishnan, Karthikayan; Gullberg, Grant T; O'Neil, James P

    2013-09-17

    A human torso phantom and its construction, wherein the phantom mimics respiratory and cardiac cycles in a human allowing acquisition of medical imaging data under conditions simulating patient cardiac and respiratory motion.

  9. TH-E-17A-01: Internal Respiratory Surrogate for 4D CT Using Fourier...

    Office of Scientific and Technical Information (OSTI)

    E-17A-01: Internal Respiratory Surrogate for 4D CT Using Fourier Transform and Anatomical Features Citation Details In-Document Search Title: TH-E-17A-01: Internal Respiratory...

  10. SU-E-I-63: Quantitative Evaluation of the Effects of Orthopedic Metal Artifact Reduction (OMAR) Software On CT Images for Radiotherapy Simulation

    SciTech Connect (OSTI)

    Jani, S [Sharp Memorial Hospital, San Diego, CA (United States)

    2014-06-01

    Purpose: CT simulation for patients with metal implants can often be challenging due to artifacts that obscure tumor/target delineation and normal organ definition. Our objective was to evaluate the effectiveness of Orthopedic Metal Artifact Reduction (OMAR), a commercially available software, in reducing metal-induced artifacts and its effect on computed dose during treatment planning. Methods: CT images of water surrounding metallic cylindrical rods made of aluminum, copper and iron were studied in terms of Hounsfield Units (HU) spread. Metal-induced artifacts were characterized in terms of HU/Volume Histogram (HVH) using the Pinnacle treatment planning system. Effects of OMAR on enhancing our ability to delineate organs on CT and subsequent dose computation were examined in nine (9) patients with hip implants and two (2) patients with breast tissue expanders. Results: Our study characterized water at 1000 HU with a standard deviation (SD) of about 20 HU. The HVHs allowed us to evaluate how the presence of metal changed the HU spread. For example, introducing a 2.54 cm diameter copper rod in water increased the SD in HU of the surrounding water from 20 to 209, representing an increase in artifacts. Subsequent use of OMAR brought the SD down to 78. Aluminum produced least artifacts whereas Iron showed largest amount of artifacts. In general, an increase in kVp and mA during CT scanning showed better effectiveness of OMAR in reducing artifacts. Our dose analysis showed that some isodose contours shifted by several mm with OMAR but infrequently and were nonsignificant in planning process. Computed volumes of various dose levels showed <2% change. Conclusions: In our experience, OMAR software greatly reduced the metal-induced CT artifacts for the majority of patients with implants, thereby improving our ability to delineate tumor and surrounding organs. OMAR had a clinically negligible effect on computed dose within tissues. Partially funded by unrestricted

  11. Effects of inhalable particles on respiratory health of children

    SciTech Connect (OSTI)

    Dockery, D.W.; Speizer, F.E.; Stram, D.O.; Ware, J.H.; Spengler, J.D.; Ferris, B.G. Jr.

    1989-03-01

    Results are presented from a second cross-sectional assessment of the association of air pollution with chronic respiratory health of children participating in the Six Cities Study of Air Pollution and Health. Air pollution measurements collected at quality-controlled monitoring stations included total suspended particulates (TSP), particulate matter less than 15 microns (PM15) and 2.5 microns (PM2.5) aerodynamic diameter, fine fraction aerosol sulfate (FSO4), SO2, O3, and No2. Reported rates of chronic cough, bronchitis, and chest illness during the 1980-1981 school year were positively associated with all measures of particulate pollution (TSP, PM15, PM2.5, and FSO4) and positively but less strongly associated with concentrations of two of the gases (SO2 and NO2). Frequency of earache also tended to be associated with particulate concentrations, but no associations were found with asthma, persistent wheeze, hay fever, or nonrespiratory illness. No associations were found between pollutant concentrations and any of the pulmonary function measures considered (FVC, FEV1, FEV0.75, and MMEF). Children with a history of wheeze or asthma had a much higher prevalence of respiratory symptoms, and there was some evidence that the association between air pollutant concentrations and symptom rates was stronger among children with these markers for hyperreactive airways. These data provide further evidence that rates of respiratory illnesses and symptoms are elevated among children living in cities with high particulate pollution. They also suggest that children with hyperreactive airways may be particularly susceptible to other respiratory symptoms when exposed to these pollutants.

  12. SU-E-I-75: Evaluation of An Orthopedic Metal Artifact Reduction (O-MAR) Algorithm On Patients with Spinal Prostheses Near Spinal Tumors

    SciTech Connect (OSTI)

    Shen, Z; Xia, P; Djemil, T; Klahr, P

    2014-06-01

    Purpose: To evaluate the impact of a commercial orthopedic metal artifact reduction (O-MAR) algorithm on CT image quality and dose calculation for patients with spinal prostheses near spinal tumors. Methods: A CT electron density phantom was scanned twice: with tissue-simulating inserts only, and with a titanium insert replacing solid water. A patient plan was mapped to the phantom images in two ways: with the titanium inside or outside of the spinal tumor. Pinnacle and Eclipse were used to evaluate the dosimetric effects of O-MAR on 12-bit and 16-bit CT data, respectively. CT images from five patients with spinal prostheses were reconstructed with and without O-MAR. Two observers assessed the image quality improvement from O-MAR. Both pencil beam and Monte Carlo dose calculation in iPlan were used for the patient study. The percentage differences between non-OMAR and O-MAR datasets were calculated for PTV-min, PTV-max, PTV-mean, PTV-V100, PTV-D90, OAR-V10Gy, OAR-max, and OAR-D0.1cc. Results: O-MAR improved image quality but did not significantly affect the dose distributions and DVHs for both 12-bit and 16- bit CT phantom data. All five patient cases demonstrated some degree of image quality improvement from O-MAR, ranging from small to large metal artifact reduction. For pencil beam, the largest discrepancy was observed for OARV-10Gy at 5.4%, while the other seven parameters were ≤0.6%. For Monte Carlo, the differences between non-O-MAR and O-MAR datasets were ≤3.0%. Conclusion: Both phantom and patient studies indicated that O-MAR can substantially reduce metal artifacts on CT images, allowing better visualization of the anatomical structures and metal objects. The dosimetric impact of O-MAR was insignificant regardless of the metal location, image bit-depth, and dose calculation algorithm. O-MAR corrected images are recommended for radiation treatment planning on patients with spinal prostheses because of the improved image quality and no need to modify

  13. Respiratory motion effects on whole breast helical tomotherapy

    SciTech Connect (OSTI)

    Moeckly, Steven R.; Lamba, Michael; Elson, Howard R.

    2008-04-15

    The effects of intrafraction respiratory motion on nonhelical intensity-modulated radiotherapy have been well addressed in the literature, both theoretically and experimentally. However, the consequences of respiratory motion on helical tomotherapy, for patient-specific treatment plans, are less well known. Parameters specific to this treatment modality such as pitch, gantry speed, and degree of modulation may play prominent roles in radiation delivery with respect to intrafraction respiratory motion. This phantom-based study specifically addressed the effects of intrafraction respiratory motion on whole breast helical tomotherapy. A device capable of driving an acrylic phantom with reproducible, one-dimensional, anterior-posterior motion resembling a sinusoid of 4.6 mm crest-trough amplitude was developed. A plan to irradiate the corner of an acrylic phantom using parameters typical of a whole breast helical tomotherapy technique was developed using the TomoTherapy Hi-Art-II System registered . The treatment was delivered to the phantom, with Kodak EDR2 film in the axial plane, for each of the following conditions: (i) phantom at 270 deg. initial sinusoidal phase and 12 cycles/min motion, (ii) phantom at 270 deg. initial sinusoidal phase and 18 cycles/min motion, and (iii)-(v) phantom at 18 cycles/min motion with 0 deg., 90 deg., and 180 deg. initial sinusoidal phases. A measure of technique reproducibility was also performed for several irradiations with the phantom static at 270 deg. initial sinusoidal phase. Films were processed using a Kodak MIN-R mammography film processor, scanned with a Vidar NXR-16 Dosimetry Pro scanner and analyzed with RIT113 v.4.2 software. Films were compared to a reference film irradiated under the conditions of no motion and 270 deg. sinusoidal phase. For all comparisons, 5% dose difference threshold, 3% dose difference and 2 mm distance-to-agreement gamma analysis, and isodose plots were generated. The results of this study show a

  14. Respiratory effects of diesel exhaust in salt miners

    SciTech Connect (OSTI)

    Gamble, J.F.; Jones, W.G.

    1983-09-01

    The respiratory health of 259 white males working at 5 salt (NaCl) mines was assessed by questionnaire, chest radiographs, and air and He-O/sup 2/ spirometry. Response variables were symptoms, pneumoconiosis, and spirometry. Predictor variables included age, height, smoking, mine, and tenure in diesel-exposed jobs. The purpose was to assess the association of response measures of respiratory health with exposure to diesel exhaust. There were only 2 cases of Grade 1 pneumoconiosis, so no further analysis was done. Comparisons within the study population showed a statistically significant dose-related association of phlegm and diesel exposure. There was a nonsignificant trend for cough and dyspnea, and no association with spirometry. Age- and smoking-adjusted rates of cough, phlegm, and dyspnea were 145, 159, and 93% of an external comparison population. Percent predicted flow rates showed statistically significant reductions, but the reductions were small and there were no dose-response relations. Percent predicted FEV1 and FVC were about 96% of predicted.

  15. SU-E-J-48: Development of An Abdominal Compression Device for Respiratory Correlated Radiation Therapy

    SciTech Connect (OSTI)

    Kim, T; Kang, S; Kim, D; Suh, T; Kim, S

    2014-06-01

    Purpose: The aim of this study is to develop the abdominal compression device which could control pressure level according to the abdominal respiratory motion and evaluate its feasibility. Methods: In this study, we focused on developing the abdominal compression device which could control pressure level at any point of time so the developed device is possible to use a variety of purpose (gating technique or respiratory training system) while maintaining the merit of the existing commercial device. The compression device (air pad form) was designed to be able to compress the front and side of abdomen and the pressure level of the abdomen is controlled by air flow. Pressure level of abdomen (air flow) was determined using correlation data between external abdominal motion and respiratory volume signal measured by spirometer. In order to verify the feasibility of the device, it was necessary to confirm the correlation between the abdominal respiratory motion and respiratory volume signal and cooperation with respiratory training system also checked. Results: In the previous study, we could find that the correlation coefficient ratio between diaphragm and respiratory volume signal measured by spirometer was 0.95. In this study, we confirmed the correlation between the respiratory volume signal and the external abdominal motion measured by belt-transducer (correlation coefficient ratio was 0.92) and used the correlated respiratory volume data as an abdominal pressure level. It was possible to control the pressure level with negligible time delay and respiratory volume data based guiding waveforms could be properly inserted into the respiratory training system. Conclusion: Through this feasibility study, we confirmed the correlation between the respiratory volume signal and the external abdominal motion. Also initial assessment of the device and its compatibility with the respiratory training system were verified. Further study on application in respiratory gated

  16. Effects of ozone on the respiratory health, allergic sensitization, and cellular immune system in children

    SciTech Connect (OSTI)

    Zwick, H.; Popp, W.; Wagner, C.; Reiser, K.; Schmoeger, J.B.; Boeck, A.H.; Herkner, K.; Radunsky, K. )

    1991-11-01

    To investigate the lasting effects of high ozone concentrations under environmental conditions, we examined the respiratory health, pulmonary function, bronchial hyperresponsiveness to methacholine, allergic sensitization, and lymphocyte subpopulations of 10- to 14-yr-old children. A total of 218 children recruited from an area with high ozone concentrations (Group A) were tested against 281 children coming from an area with low ozone concentrations (Group B). As to subjective complaints, categorized as 'usually cough with or without phlegm,' 'breathlessness,' and 'susceptibility to chest colds,' there was no difference between the two groups. The lung function parameters were similar, but in Group A subjects' bronchial hyperresponsiveness occurred more frequently and was found to be more severe than in Group B (29.4 versus 19.9%, p less than 0.02; PD20 2,100 {plus minus} 87 versus 2,350 {plus minus} 58 micrograms, p less than 0.05). In both groups the number of children who had been suffering from allergic diseases and sensitization to aeroallergens, found by means of the skin test, was the same. Comparison of the total IgE levels showed no difference at all between the two groups. As far as the white blood cells are concerned, the total and differential cell count was the same, whereas lymphocyte subpopulations showed readily recognizable changes.

  17. Effects of air pollution on children's respiratory health in three Chinese cities

    SciTech Connect (OSTI)

    Qian, Z.; Chapman, R.S.; Tian, Q.; Chen, Y.; Lioy, P.J.; Zhang, J.

    2000-04-01

    During the winter of 1988--1989, parents of 2,789 elementary-school students completed standardized questionnaires. The students were 5--14 y of age and were from three urban districts and one suburban district of three large Chinese cities. The 4-y average ambient levels of total suspended particles in the three cities differed greatly during the period 1985--1988: Lanzhou, 1,067 {micro}g/m{sup 3}; urban Wuhan, 406 {micro}g/m{sup 3}; Guangzhou, 296 {micro}g/m{sup 3}; and suburban Wuhan, 191 {micro}g/m{sup 3}. The authors constructed unconditional logistic-regression models to calculate odds ratios and 95% confidence intervals for prevalences of several respiratory symptoms and illnesses, adjusted for district, use of coal in the home, and parental smoking status. There was a positive and significant association between total suspended particle levels and the adjusted odds ratios for couch, phlegm, hospitalization for diseases, and pneumonia. This association was derived from only the 1,784 urban children and, therefore, the authors were unable to extrapolate it to the suburban children. The results also indicated that parental smoking status was associated with cough and phlegm, and use of coal in the home was associated only with cough prevalence.

  18. Pulmonary function and respiratory symptoms in potash workers

    SciTech Connect (OSTI)

    Graham, B.L.; Dosman, J.A.; Cotton, D.J.; Weisstock, S.R.; Lappi, V.G.; Froh, F.

    1984-03-01

    Over 94% of the workers in each of four Saskatchewan potash mines participated in a respiratory health surveillance program that included a questionnaire and pulmonary function tests. Compared with a nonexposed control group, potash workers had higher prevalences of cough, dyspnea, and chronic bronchitis but better pulmonary function. Prevalences of symptoms and pulmonary function abnormalities were similar among workers at the four mines tested and at the various job locations. Potash dust, diesel fumes, and other air contaminants may have an irritant effect that leads to the increased prevalences of cough and chronic bronchitis. Although we found no adverse effects of the potash mine environment on pulmonary function, these findings reflect a healthy worker effect or some selection process that makes the potash workers appear healthier in a cross-sectional study.

  19. Pulmonary function and respiratory symptoms in potash workers

    SciTech Connect (OSTI)

    Graham, B.L.; Dosman, J.A.; Cotton, D.J.; Weisstock, S.R.; Lappi, V.G.; Froh, F.

    1984-03-01

    Over 94% of the workers in each of four Saskatchewan potash mines participated in a respiratory health surveillance program that included a questionnaire and pulmonary function tests. Compared with a nonexposed control group, potash workers had higher prevalences of cough, dyspnea, and chronic bronchitis but better pulmonary function. Prevalences of symptoms and pulmonary function abnormalities were similar among workers at the four mines tested and at the various job locations. Potash dust, diesel fumes, and other air contaminants may have an irritant effect that leads to the increased prevalences of cough and chronic bronchitis. Although no adverse effects of the potash mine environment on pulmonary function were found, these findings reflect a healthy worker effect or some selection process that makes the potash workers appear healthier in a cross-sectional study.

  20. Design and performance of a respiratory amplitude gating device for PET/CT imaging

    SciTech Connect (OSTI)

    Chang Guoping; Chang Tingting; Clark, John W. Jr.; Mawlawi, Osama R.

    2010-04-15

    Purpose: Recently, the authors proposed a free-breathing amplitude gating (FBAG) technique for PET/CT scanners. The implementation of this technique required specialized hardware and software components that were specifically designed to interface with commercial respiratory gating devices to generate the necessary triggers required for the FBAG technique. The objective of this technical note is to introduce an in-house device that integrates all the necessary hardware and software components as well as tracks the patient's respiratory motion to realize amplitude gating on PET/CT scanners. Methods: The in-house device is composed of a piezoelectric transducer coupled to a data-acquisition system in order to monitor the respiratory waveform. A LABVIEW program was designed to control the data-acquisition device and inject triggers into the PET list stream whenever the detected respiratory amplitude crossed a predetermined amplitude range. A timer was also programmed to stop the scan when the accumulated time within the selected amplitude range reached a user-set interval. This device was tested using a volunteer and a phantom study. Results: The results from the volunteer and phantom studies showed that the in-house device can detect similar respiratory signals as commercially available respiratory gating systems and is able to generate the necessary triggers to suppress respiratory motion artifacts. Conclusions: The proposed in-house device can be used to implement the FBAG technique in current PET/CT scanners.

  1. Nitrogen dioxide and respiratory illness in children. Part I: Health outcomes

    SciTech Connect (OSTI)

    Samet, J.M.; Lambert, W.E.; Skipper, B.J.; Cushing, A.H.; Hunt, W.C.; Young, S.A.; McLaren, L.C.; Schwab, M.; Spengler, J.D. )

    1993-06-01

    We have carried out a prospective cohort study to test the hypothesis that exposure to nitrogen dioxide increases the incidence and severity of respiratory infections during the first 18 months of life. Between January 1988 and June 1990, 1,315 infants were enrolled into the study at birth and followed with prospective surveillance for the occurrence of respiratory infections and monitoring of nitrogen dioxide concentrations in their homes. The subjects were healthy infants from homes without smokers; they were selected with stratification by type of cooking stove at a ratio of four to one for gas and electric stoves. Illness experience was monitored by a daily diary of symptoms completed by the mother and a telephone interview conducted every two weeks. Illnesses with wheezing or wet cough were classified as involving the lower respiratory tract; all other respiratory illnesses were designated as involving the upper respiratory tract. Exposure to nitrogen dioxide was estimated by two-week average concentrations measured in the subjects' bedrooms with passive samplers. This analysis is limited to the 1,205 subjects completing at least one month of observation; of these, 823 completed the full protocol, contributing 82.8% of the total number of days during which the subjects were under observation. Incidence rates for all respiratory illnesses, all upper respiratory illness, all lower respiratory illnesses, and lower respiratory illness further divided into those with any wheezing, or wet cough without wheezing, were examined within strata of nitrogen dioxide exposure at the time of the illness, nitrogen dioxide exposure during the prior month, and type of cooking stove. Consistent trends of increasing illness incidence rates with increasing exposure to nitrogen dioxide were not evident for either the lagged or unlagged exposure variables.

  2. Disease Diagnostics Research at Los Alamos National Laboratory

    SciTech Connect (OSTI)

    Mukundan, Harshini

    2015-04-10

    Human evolution and persistent diseases have existed side-by-side. A recent concern is the re-emergence of tuberculosis, one of the oldest and most challenging diseases known to man. Effective diagnosis can save lives and prevent its spread. This talk will cover how our immune system discriminates between itself and foreign entities and how a new laboratory and nature inspired strategy can detect tuberculosis equally well in human and animal populations. The approach is being extended to other applications such as the identification of strep throat and respiratory infections.

  3. Beryllium disease

    SciTech Connect (OSTI)

    Not Available

    1991-12-20

    After two workers at the nuclear weapons plant at Oak Ridge National Laboratory in Tennessee were diagnosed earlier this year with chronic beryllium disease (CBD), a rare and sometimes fatal scarring of the lungs, the Department of Energy ordered up a 4-year probe. Now, part of that probe has begun - tests conducted by the Oak Ridge Associated Universities' Center for Epidemiological Research measuring beryllium sensitivity in 3,000 people who've been exposed to the metal's dust since Manhattan Project managers opened the Y-12 plant at Oak Ridge in 1943. Currently, 119 Y-12 employees process beryllium, which has a number of industrial uses, including rocket heat shields and nuclear weapon and electrical components. The disease often takes 20 to 25 years to develop, and the stricken employees haven't worked with beryllium for years. There is no cure for CBD, estimated to strike 2% of people exposed to the metal. Anti-inflammatory steroids alleviate such symptoms as a dry cough, weight loss, and fatigue. Like other lung-fibrosis diseases that are linked to lung cancer, some people suspect CBD might cause some lung cancer. While difficult to diagnose, about 900 cases of CBD have been reported since a Beryllium Case Registry was established in 1952. The Department of Energy (DOE) estimates that about 10,000 DOE employees and 800,000 people in private industry have worked with beryllium.

  4. Passive cigarette smoke, coal heating, and respiratory symptoms of nonsmoking women in China

    SciTech Connect (OSTI)

    Pope, C.A. III Brigham Young Univ., Provo, UT ); Xu, X. )

    1993-09-01

    In this study the authors evaluated data from a sample of 973 never-smoking women, ages 20-40, who worked in three similar textile mills in Anhui Province, China. They compared prevalence rates of respiratory symptoms across homes with and without coal heating and homes with different numbers of smokers. Multiple logistic regression models that controlled for age, job title, and mill of employment were also estimated. Respiratory symptoms were associated with combined exposure to passive cigarette smoke and coal heating. Effects of passive cigarette smoke and coal heating on respiratory symptoms appeared to be nearly additive, suggesting a dose-response relationship between respiratory symptoms and home indoor air pollution from these two sources. The prevalence of chest illness, cough, phlegm, and shortness of breath (but not wheeze) was significantly elevated for women living in homes with both smokers and coal heating.

  5. Building-related risk factors and work-related lower respiratory symptoms in 80 office buildings

    SciTech Connect (OSTI)

    Mendell, M.J.; Naco, G.M.; Wilcox, T.G.; Sieber, W.K.

    2002-01-01

    We assessed building-related risk factors for lower respiratory symptoms in office workers. The National Institute for Occupational Safety and Health in 1993 collected data during indoor environmental health investigations of workplaces. We used multivariate logistic regression analyses to assess relationships between lower respiratory symptoms in office workers and risk factors plausibly related to microbiologic contamination. Among 2,435 occupants in 80 office buildings, frequent, work-related multiple lower respiratory symptoms were strongly associated, in multivariate models, with two risk factors for microbiologic contamination: poor pan drainage under cooling coils and debris in outside air intake. Associations tended to be stronger among those with a history of physician-diagnosed asthma. These findings suggest that adverse lower respiratory health effects from indoor work environments, although unusual, may occur in relation to poorly designed or maintained ventilation systems, particularly among previously diagnosed asthmatics. These findings require confirmation in more representative buildings.

  6. Association of residential dampness and mold with respiratory tract infections and bronchitis: a meta-analysis

    SciTech Connect (OSTI)

    Fisk, William J.; Eliseeva, Ekaterina A.; Mendell, Mark J.

    2010-11-15

    Dampness and mold have been shown in qualitative reviews to be associated with a variety of adverse respiratory health effects, including respiratory tract infections. Several published meta-analyses have provided quantitative summaries for some of these associations, but not for respiratory infections. Demonstrating a causal relationship between dampness-related agents, which are preventable exposures, and respiratory tract infections would suggest important new public health strategies. We report the results of quantitative meta-analyses of published studies that examined the association of dampness or mold in homes with respiratory infections and bronchitis. For primary studies meeting eligibility criteria, we transformed reported odds ratios (ORs) and confidence intervals (CIs) to the log scale. Both fixed and random effects models were applied to the log ORs and their variances. Most studies contained multiple estimated ORs. Models accounted for the correlation between multiple results within the studies analyzed. One set of analyses was performed with all eligible studies, and another set restricted to studies that controlled for age, gender, smoking, and socioeconomic status. Subgroups of studies were assessed to explore heterogeneity. Funnel plots were used to assess publication bias. The resulting summary estimates of ORs from random effects models based on all studies ranged from 1.38 to 1.50, with 95% CIs excluding the null in all cases. Use of different analysis models and restricting analyses based on control of multiple confounding variables changed findings only slightly. ORs (95% CIs) from random effects models using studies adjusting for major confounding variables were, for bronchitis, 1.45 (1.32-1.59); for respiratory infections, 1.44 (1.31-1.59); for respiratory infections excluding nonspecific upper respiratory infections, 1.50 (1.32-1.70), and for respiratory infections in children or infants, 1.48 (1.33-1.65). Little effect of publication

  7. SU-E-T-113: Dose Distribution Using Respiratory Signals and Machine Parameters During Treatment

    SciTech Connect (OSTI)

    Imae, T; Haga, A; Saotome, N; Kida, S; Nakano, M; Takeuchi, Y; Shiraki, T; Yano, K; Yamashita, H; Nakagawa, K; Ohtomo, K

    2014-06-01

    Purpose: Volumetric modulated arc therapy (VMAT) is a rotational intensity-modulated radiotherapy (IMRT) technique capable of acquiring projection images during treatment. Treatment plans for lung tumors using stereotactic body radiotherapy (SBRT) are calculated with planning computed tomography (CT) images only exhale phase. Purpose of this study is to evaluate dose distribution by reconstructing from only the data such as respiratory signals and machine parameters acquired during treatment. Methods: Phantom and three patients with lung tumor underwent CT scans for treatment planning. They were treated by VMAT while acquiring projection images to derive their respiratory signals and machine parameters including positions of multi leaf collimators, dose rates and integrated monitor units. The respiratory signals were divided into 4 and 10 phases and machine parameters were correlated with the divided respiratory signals based on the gantry angle. Dose distributions of each respiratory phase were calculated from plans which were reconstructed from the respiratory signals and the machine parameters during treatment. The doses at isocenter, maximum point and the centroid of target were evaluated. Results and Discussion: Dose distributions during treatment were calculated using the machine parameters and the respiratory signals detected from projection images. Maximum dose difference between plan and in treatment distribution was −1.8±0.4% at centroid of target and dose differences of evaluated points between 4 and 10 phases were no significant. Conclusion: The present method successfully evaluated dose distribution using respiratory signals and machine parameters during treatment. This method is feasible to verify the actual dose for moving target.

  8. Daily air pollution effects on children's respiratory symptoms and peak expiratory flow

    SciTech Connect (OSTI)

    Vedal, S.; Schenker, M.B.; Munoz, A.; Samet, J.M.; Batterman, S.; Speizer, F.E.

    1987-06-01

    To identify acute respiratory health effects associated with air pollution due to coal combustion, a subgroup of elementary school-aged children was selected from a large cross-sectional study and followed daily for eight months. Children were selected to obtain three equal-sized groups: one without respiratory symptoms, one with symptoms of persistent wheeze, and one with cough or phlegm production but without persistent wheeze. Parents completed a daily diary of symptoms from which illness constellations of upper respiratory illness (URI) and lower respiratory illness (LRI) and the symptom of wheeze were derived. Peak expiratory flow rate (PEFR) was measured daily for nine consecutive weeks during the eight-month study period. Maximum hourly concentrations of sulfur dioxide, nitrogen dioxide, ozone, and coefficient of haze for each 24-hour period, as well as minimum hourly temperature, were correlated with daily URI, LRI, wheeze, and PEFR using multiple regression models adjusting for illness occurrence or level of PEFR on the immediately preceding day. Respiratory illness on the preceding day was the most important predictor of current illness. A drop in temperature was associated with increased URI and LRI but not with increased wheeze or with a decrease in level of PEFR. No air pollutant was strongly associated with respiratory illness or with level of PEFR, either in the group of children as a whole, or in either of the symptomatic subgroups; the pollutant concentrations observed, however, were uniformly lower than current ambient air quality standards.

  9. Biomarkers of acute respiratory allergen exposure: Screening for sensitization potential

    SciTech Connect (OSTI)

    Pucheu-Haston, Cherie M.; Copeland, Lisa B.; Vallanat, Beena; Boykin, Elizabeth; Ward, Marsha D.W.

    2010-04-15

    Effective hazard screening will require the development of high-throughput or in vitro assays for the identification of potential sensitizers. The goal of this preliminary study was to identify potential biomarkers that differentiate the response to allergens vs non-allergens following an acute exposure in naive individuals. Female BALB/c mice received a single intratracheal aspiration exposure to Metarhizium anisopliae crude antigen (MACA) or bovine serum albumin (BSA) in Hank's Balanced Salt Solution (HBSS) or HBSS alone. Mice were terminated after 1, 3, 6, 12, 18 and 24 h. Bronchoalveolar lavage fluid (BALF) was evaluated to determine total and differential cellularity, total protein concentration and LDH activity. RNA was isolated from lung tissue for microarray analysis and qRT-PCR. MACA administration induced a rapid increase in BALF neutrophils, lymphocytes, eosinophils and total protein compared to BSA or HBSS. Microarray analysis demonstrated differential expression of genes involved in cytokine production, signaling, inflammatory cell recruitment, adhesion and activation in 3 and 12 h MACA-treated samples compared to BSA or HBSS. Further analyses allowed identification of approx 100 candidate biomarker genes. Eleven genes were selected for further assessment by qRT-PCR. Of these, 6 demonstrated persistently increased expression (Ccl17, Ccl22, Ccl7, Cxcl10, Cxcl2, Saa1), while C3ar1 increased from 6-24 h. In conclusion, a single respiratory exposure of mice to an allergenic mold extract induces an inflammatory response which is distinct in phenotype and gene transcription from the response to a control protein. Further validation of these biomarkers with additional allergens and irritants is needed. These biomarkers may facilitate improvements in screening methods.

  10. SU-E-J-159: Analysis of Total Imaging Uncertainty in Respiratory-Gated Radiotherapy

    SciTech Connect (OSTI)

    Suzuki, J; Okuda, T; Sakaino, S; Yokota, N

    2015-06-15

    Purpose: In respiratory-gated radiotherapy, the gating phase during treatment delivery needs to coincide with the corresponding phase determined during the treatment plan. However, because radiotherapy is performed based on the image obtained for the treatment plan, the time delay, motion artifact, volume effect, and resolution in the images are uncertain. Thus, imaging uncertainty is the most basic factor that affects the localization accuracy. Therefore, these uncertainties should be analyzed. This study aims to analyze the total imaging uncertainty in respiratory-gated radiotherapy. Methods: Two factors of imaging uncertainties related to respiratory-gated radiotherapy were analyzed. First, CT image was used to determine the target volume and 4D treatment planning for the Varian Realtime Position Management (RPM) system. Second, an X-ray image was acquired for image-guided radiotherapy (IGRT) for the BrainLAB ExacTrac system. These factors were measured using a respiratory gating phantom. The conditions applied during phantom operation were as follows: respiratory wave form, sine curve; respiratory cycle, 4 s; phantom target motion amplitude, 10, 20, and 29 mm (which is maximum phantom longitudinal motion). The target and cylindrical marker implanted in the phantom coverage of the CT images was measured and compared with the theoretically calculated coverage from the phantom motion. The theoretical position of the cylindrical marker implanted in the phantom was compared with that acquired from the X-ray image. The total imaging uncertainty was analyzed from these two factors. Results: In the CT image, the uncertainty between the target and cylindrical marker’s actual coverage and the coverage of CT images was 1.19 mm and 2.50mm, respectively. In the Xray image, the uncertainty was 0.39 mm. The total imaging uncertainty from the two factors was 1.62mm. Conclusion: The total imaging uncertainty in respiratory-gated radiotherapy was clinically acceptable. However

  11. Asbestos-related pulmonary disease in boilermakers

    SciTech Connect (OSTI)

    Demers, R.Y.; Neale, A.V.; Robins, T.; Herman, S.C. )

    1990-01-01

    Boilermakers are skilled building tradesmen who construct, repair, and dismantle boilers. The present study reports on the evaluation of members of a Michigan boilermaker's union for the presence of signs and symptoms of chronic pulmonary disease. Study variables included standardized evaluations of chest x-ray findings, pulmonary function testing, physical examination, and respiratory symptoms. An overall participation rate of 69% was achieved. A non-participant survey identified no significant differences between participants and non-participants in dyspnea, cough, age, or smoking history. Among participants with greater than 20 years experience in the trade, the mean FVC was 91% of predicted; the FEV1 was 86% of predicted; 25% showed at least a 1/0 profusion of interstitial markings on chest x-ray; 30% had bilateral pleural abnormalities; and 52% had audible inspiratory rales on physical examination. Forced vital capacity and forced expiratory volume at one second both decreased with years in the trade. Chest x-ray findings of interstitial fibrosis and pleural plaques were related to ten or more years in the trade, as were respiratory symptoms of pulmonary rales, wheeze, and dyspnea.

  12. A bidirectional coupling procedure applied to multiscale respiratory modeling

    SciTech Connect (OSTI)

    Kuprat, A.P.; Kabilan, S.; Carson, J.P.; Corley, R.A.; Einstein, D.R.

    2013-07-01

    In this study, we present a novel multiscale computational framework for efficiently linking multiple lower-dimensional models describing the distal lung mechanics to imaging-based 3D computational fluid dynamics (CFDs) models of the upper pulmonary airways in order to incorporate physiologically appropriate outlet boundary conditions. The framework is an extension of the modified Newton’s method with nonlinear Krylov accelerator developed by Carlson and Miller [1], Miller [2] and Scott and Fenves [3]. Our extensions include the retention of subspace information over multiple timesteps, and a special correction at the end of a timestep that allows for corrections to be accepted with verified low residual with as little as a single residual evaluation per timestep on average. In the case of a single residual evaluation per timestep, the method has zero additional computational cost compared to uncoupled or unidirectionally coupled simulations. We expect these enhancements to be generally applicable to other multiscale coupling applications where timestepping occurs. In addition we have developed a “pressure-drop” residual which allows for stable coupling of flows between a 3D incompressible CFD application and another (lower-dimensional) fluid system. We expect this residual to also be useful for coupling non-respiratory incompressible fluid applications, such as multiscale simulations involving blood flow. The lower-dimensional models that are considered in this study are sets of simple ordinary differential equations (ODEs) representing the compliant mechanics of symmetric human pulmonary airway trees. To validate the method, we compare the predictions of hybrid CFD–ODE models against an ODE-only model of pulmonary airflow in an idealized geometry. Subsequently, we couple multiple sets of ODEs describing the distal lung to an imaging-based human lung geometry. Boundary conditions in these models consist of atmospheric pressure at the mouth and intrapleural

  13. A Bidirectional Coupling Procedure Applied to Multiscale Respiratory Modeling

    SciTech Connect (OSTI)

    Kuprat, Andrew P.; Kabilan, Senthil; Carson, James P.; Corley, Richard A.; Einstein, Daniel R.

    2013-07-01

    In this study, we present a novel multiscale computational framework for efficiently linking multiple lower-dimensional models describing the distal lung mechanics to imaging-based 3D computational fluid dynamics (CFD) models of the upper pulmonary airways in order to incorporate physiologically appropriate outlet boundary conditions. The framework is an extension of the Modified Newton’s Method with nonlinear Krylov accelerator developed by Carlson and Miller [1, 2, 3]. Our extensions include the retention of subspace information over multiple timesteps, and a special correction at the end of a timestep that allows for corrections to be accepted with verified low residual with as little as a single residual evaluation per timestep on average. In the case of a single residual evaluation per timestep, the method has zero additional computational cost compared to uncoupled or unidirectionally coupled simulations. We expect these enhancements to be generally applicable to other multiscale coupling applications where timestepping occurs. In addition we have developed a “pressure-drop” residual which allows for stable coupling of flows between a 3D incompressible CFD application and another (lower-dimensional) fluid system. We expect this residual to also be useful for coupling non-respiratory incompressible fluid applications, such as multiscale simulations involving blood flow. The lower-dimensional models that are considered in this study are sets of simple ordinary differential equations (ODEs) representing the compliant mechanics of symmetric human pulmonary airway trees. To validate the method, we compare the predictions of hybrid CFD-ODE models against an ODE-only model of pulmonary airflow in an idealized geometry. Subsequently, we couple multiple sets of ODEs describing the distal lung to an imaging-based human lung geometry. Boundary conditions in these models consist of atmospheric pressure at the mouth and intrapleural pressure applied to the multiple

  14. Hamilton study: distribution of factors confounding the relationship between air quality and respiratory health

    SciTech Connect (OSTI)

    Pengelly, L.D.; Kerigan, A.T.; Goldsmith, C.H.; Inman, E.M.

    1984-10-01

    Hamilton, Ontario is an industrial city with a population of 300,000 which is situated at the western end of Lake Ontario. Canada's two largest iron and steel mills are located here; the city historically has had relatively poor air quality, which has improved markedly in the last 25 years. Concern about the health effects of current air quality recently led us to carry out an epidemiological study of the effects of air pollution on the respiratory health of over 3500 school children. Respiratory health was measured by pulmonary function testing of each child, and by an assessment of each child's respiratory symptoms via a questionnaire administered to the parents. Previous studies had shown that other environmental factors (e.g. parental smoking, parental cough, socioeconomic level, housing, and gas cooking) might also affect respiratory health, and thus confound any potential relationships between health and air pollution. The questionnaire also collected information on many of these confounding factors. For the purposes of initial analysis, the city was divided into five areas in which differences in air quality were expected. In general, factors which have been associated with poor respiratory health were observed to be more prevalent in areas of poorer air quality.

  15. Respiratory health effects of the indoor environment in a population of Dutch children

    SciTech Connect (OSTI)

    Dijkstra, L.; Houthuijs, D.; Brunekreef, B.; Akkerman, I.; Boleij, J.S. )

    1990-11-01

    The effect of indoor exposure to nitrogen dioxide on respiratory health was studied over a period of 2 yr in a population of nonsmoking Dutch children 6 to 12 yr of age. Lung function was measured at the schools, and information on respiratory symptoms was collected from a self-administered questionnaire completed by the parents of the children. Nitrogen dioxide was measured in the homes of all children with Palmes' diffusion tubes. In addition, information on smoking and dampness in the home was collected by questionnaire. There was no relationship between exposure to nitrogen dioxide in the home and respiratory symptoms. Respiratory symptoms were found to be associated with exposure to tobacco smoke and home dampness. There was a weak, negative association between maximal midexpiratory flow (MMEF) and exposure to nitrogen dioxide. FEV1, peak expiratory flow, and MMEF were all negatively associated with exposure to tobacco smoke. Home dampness was not associated with pulmonary function. Lung function growth, measured over a period of 2 yr, was not consistently associated with any of the indoor exposure variables. The development of respiratory symptoms over time was not associated with indoor exposure to nitrogen dioxide. There was a significant association between exposure to environmental tobacco smoke in the home and the development of wheeze. There was also a significant association between home dampness and the development of cough.

  16. TH-E-17A-01: Internal Respiratory Surrogate for 4D CT Using Fourier Transform and Anatomical Features

    SciTech Connect (OSTI)

    Hui, C; Suh, Y; Robertson, D; Pan, T; Das, P; Crane, C; Beddar, S

    2014-06-15

    Purpose: To develop a novel algorithm to generate internal respiratory signals for sorting of four-dimensional (4D) computed tomography (CT) images. Methods: The proposed algorithm extracted multiple time resolved features as potential respiratory signals. These features were taken from the 4D CT images and its Fourier transformed space. Several low-frequency locations in the Fourier space and selected anatomical features from the images were used as potential respiratory signals. A clustering algorithm was then used to search for the group of appropriate potential respiratory signals. The chosen signals were then normalized and averaged to form the final internal respiratory signal. Performance of the algorithm was tested in 50 4D CT data sets and results were compared with external signals from the real-time position management (RPM) system. Results: In almost all cases, the proposed algorithm generated internal respiratory signals that visibly matched the external respiratory signals from the RPM system. On average, the end inspiration times calculated by the proposed algorithm were within 0.1 s of those given by the RPM system. Less than 3% of the calculated end inspiration times were more than one time frame away from those given by the RPM system. In 3 out of the 50 cases, the proposed algorithm generated internal respiratory signals that were significantly smoother than the RPM signals. In these cases, images sorted using the internal respiratory signals showed fewer artifacts in locations corresponding to the discrepancy in the internal and external respiratory signals. Conclusion: We developed a robust algorithm that generates internal respiratory signals from 4D CT images. In some cases, it even showed the potential to outperform the RPM system. The proposed algorithm is completely automatic and generally takes less than 2 min to process. It can be easily implemented into the clinic and can potentially replace the use of external surrogates.

  17. Full-spectrum disease response : beyond just the flu.

    SciTech Connect (OSTI)

    Knazovich, Michael Ward; Cox, Warren B.; Henderson, Samuel Arthur

    2010-04-01

    Why plan beyond the flu: (1) the installation may be the target of bioterrorism - National Laboratory, military base collocated in large population center; and (2) International Airport - transport of infectious agents to the area - Sandia is a global enterprise and staff visit many foreign countries. In addition to the Pandemic Plan, Sandia has developed a separate Disease Response Plan (DRP). The DRP addresses Category A, B pathogens and Severe Acute Respiratory Syndrome (SARS). The DRP contains the Cities Readiness Initiative sub-plan for disbursement of Strategic National Stockpile assets.

  18. Smoking cessation among coal miners as predicted by baseline respiratory function and symptoms: a 5-year prospective study

    SciTech Connect (OSTI)

    Ames, R.G.; Hall, D.S.

    1985-03-01

    A prospective analysis was used to test whether respiratory impairment or the presence of respiratory symptoms predicts 5-year cigarette smoking cessation in a sample of 1,118 U.S. white, male, underground coal miners. Miners were examined in 1977 and re-examined in 1982 by NIOSH, and all miners with test abnormalities were so informed by letter. Respiratory impairment was measured by an index of airways obstruction combining the spirometric measures of Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 sec (FEV1). Bronchitis symptoms were measured by an index that combined chronic cough (3+ months/year) and chronic phlegm (3 + months/year). Among these coal miners, the presence of chronic respiratory symptoms initially was inversely associated with cigarette smoking cessation. Respiratory impairment, however, was positively associated with cigarette smoking cessation but did not reach statistical significance.

  19. Pulmonary function and respiratory symptoms of school children exposed to ambient air pollution

    SciTech Connect (OSTI)

    Kim, Yoon Shin; Ko, Ung Ring

    1996-12-31

    This study was undertaken to evaluate the health effect of air pollution on pulmonary function and respiratory symptoms of Korean school children between 7 and 10 years of age during November 1995-January 1996. A standard respiratory symptom questionnaire was administered and spirometry was performed to examine pulmonary function of 121 children in an urban polluted area, Seoul, and of 119 children in non-polluted area, Sokcho, respectively. There was significant difference in the level of pulmonary function [forced expiratory volume in second (FEV{sub 1.0}) and forced vital capacity (FVC)] between exposed groups to polluted area and non-polluted area. Parental smoking was significantly related to respiratory symptoms of cough, phlegm, and the level of pulmonary function. The observed changes in FEV{sub 1.0} and FVC seemed to relate to home cooking fuel, not to respiratory symptoms. The additional longitudinal work that carefully monitors ambient and indoor air pollution and health effects data should be conducted to confirm these results.

  20. Personal exposure to nitrogen dioxide and its association with respiratory illness in Hong Kong

    SciTech Connect (OSTI)

    Koo, L.C.; Ho, J.H.; Ho, C.Y.; Matsuki, H.; Shimizu, H.; Mori, T.; Tominaga, S. )

    1990-05-01

    In 1985, 362 primary schoolchildren and their 319 mothers were surveyed in Hong Kong to study the possible relationship of air pollution to respiratory illnesses. Using nitrogen dioxide (NO{sub 2}) measured by personal samplers as a measure of air pollution, the study aimed to identify the major sources of NO{sub 2} in the indoor environment and see whether its increased presence was associated with respiratory symptoms. The levels of NO{sub 2} among the mothers was found to increase by 21% if dust exposure was reported from the workplace, 18% if they used such cooking fuels as liquid petroleum gas or kerosene, 11% when kitchens did not have ventilating fans, and 10% when incense was burned at home. In terms of respiratory symptoms, an increase in NO{sub 2} levels of 19% was reported among those with allergic rhinitis and 18% among those with chronic cough. The levels of NO2 among children were correlated with levels measured in classrooms, all of which had opened windows so that the NO{sub 2} came from outdoors. No association was found between children's NO{sub 2} levels and respiratory symptoms. With the exception of smoking by the father and the children's NO{sub 2} levels, no association was found between smoking at home and NO{sub 2} levels.

  1. Respiratory symptoms and lung function in oil mist-exposed workers

    SciTech Connect (OSTI)

    Jarvholm, B.; Bake, B.; Lavenius, B.; Thiringer, G.; Vokmann, R.

    1982-06-01

    The prevalence of respiratory symptoms was registered and ventilatory function was determined in 164 men exposed to oil mist. The average exposure time was 16.2 years. One hundred fifty-nine office workers served as controls. The exposed men reported more respiratory symptoms: 14% of the exposed nonsmokers v. 2% of the nonsmoking controls having cough at least three months a year. There were non significant differences between spirometric measurements and chest roentgenograms of the men exposed to oil mist and those of the office workers. The lung function of 25 nonsmoking exposed men was further examined with other lung function tests. The mean values for closing volume, slope of the alveolar plateau, total lung capacity, residual volume, elastic recoil at various lung volumes, and diffusion capacity did not differ significantly.

  2. Mass-transport models to predict toxicity of inhaled gases in the upper respiratory tract

    SciTech Connect (OSTI)

    Hubal, E.A.C.; Fedkiw, P.S.; Kimbell, J.S. [North Carolina State Univ., Raleigh, NC (United States)

    1996-04-01

    Mass-transport (the movement of a chemical species) plays an important role in determining toxic responses of the upper respiratory tract (URT) to inhaled chemicals. Mathematical dosimetry models incorporate physical characteristics of mass transport and are used to predict quantitative uptake (absorption rate) and distribution of inhaled gases and vapors in the respiratory tract. Because knowledge of dose is an essential component of quantitative risk assessment, dosimetry modeling plays an important role in extrapolation of animal study results to humans. A survey of existing mathematical dosimetry models for the URT is presented, limitations of current models are discussed, and adaptations of existing models to produce a generally applicable model are suggested. Reviewed URT dosimetry models are categorized as early, lumped-parameter, and distributed-parameter models. Specific examples of other relevant modeling work are also presented. 35 refs., 11 figs., 1 tab.

  3. Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Keravec, Marlène; Mounier, Jérôme; Prestat, Emmanuel; Vallet, Sophie; Jansson, Janet K.; Burgaud, Gaëtan; Rosec, Sylvain; Gouriou, Stéphanie; Rault, Gilles; Coton, Emmanuel; et al

    2015-08-09

    Pseudomonas aeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly moremore » prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state.« less

  4. The Department of Energy Respiratory Acceptance Program for Supplied-Air Suits

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2004-02-04

    The supplied-air suits that protect DOE contractor and federal employees from exposure to harmful atmospheres and radioactive contaminants are not included in the National Institute for Occupational Safety and Health (NIOSH) certification process for respiratory protective devices. Therefore, with the awareness and acknowledgement of NIOSH and the Occupational Safety and Health Administration (OSHA), the Department established a system for acceptance testing of supplied-air suits.

  5. Optimizing 4-Dimensional Magnetic Resonance Imaging Data Sampling for Respiratory Motion Analysis of Pancreatic Tumors

    SciTech Connect (OSTI)

    Stemkens, Bjorn; Tijssen, Rob H.N.; Senneville, Baudouin D. de

    2015-03-01

    Purpose: To determine the optimum sampling strategy for retrospective reconstruction of 4-dimensional (4D) MR data for nonrigid motion characterization of tumor and organs at risk for radiation therapy purposes. Methods and Materials: For optimization, we compared 2 surrogate signals (external respiratory bellows and internal MRI navigators) and 2 MR sampling strategies (Cartesian and radial) in terms of image quality and robustness. Using the optimized protocol, 6 pancreatic cancer patients were scanned to calculate the 4D motion. Region of interest analysis was performed to characterize the respiratory-induced motion of the tumor and organs at risk simultaneously. Results: The MRI navigator was found to be a more reliable surrogate for pancreatic motion than the respiratory bellows signal. Radial sampling is most benign for undersampling artifacts and intraview motion. Motion characterization revealed interorgan and interpatient variation, as well as heterogeneity within the tumor. Conclusions: A robust 4D-MRI method, based on clinically available protocols, is presented and successfully applied to characterize the abdominal motion in a small number of pancreatic cancer patients.

  6. SU-E-J-261: Statistical Analysis and Chaotic Dynamics of Respiratory Signal of Patients in BodyFix

    SciTech Connect (OSTI)

    Michalski, D; Huq, M; Bednarz, G; Lalonde, R; Yang, Y; Heron, D

    2014-06-01

    Purpose: To quantify respiratory signal of patients in BodyFix undergoing 4DCT scan with and without immobilization cover. Methods: 20 pairs of respiratory tracks recorded with RPM system during 4DCT scan were analyzed. Descriptive statistic was applied to selected parameters of exhale-inhale decomposition. Standardized signals were used with the delay method to build orbits in embedded space. Nonlinear behavior was tested with surrogate data. Sample entropy SE, Lempel-Ziv complexity LZC and the largest Lyapunov exponents LLE were compared. Results: Statistical tests show difference between scans for inspiration time and its variability, which is bigger for scans without cover. The same is for variability of the end of exhalation and inhalation. Other parameters fail to show the difference. For both scans respiratory signals show determinism and nonlinear stationarity. Statistical test on surrogate data reveals their nonlinearity. LLEs show signals chaotic nature and its correlation with breathing period and its embedding delay time. SE, LZC and LLE measure respiratory signal complexity. Nonlinear characteristics do not differ between scans. Conclusion: Contrary to expectation cover applied to patients in BodyFix appears to have limited effect on signal parameters. Analysis based on trajectories of delay vectors shows respiratory system nonlinear character and its sensitive dependence on initial conditions. Reproducibility of respiratory signal can be evaluated with measures of signal complexity and its predictability window. Longer respiratory period is conducive for signal reproducibility as shown by these gauges. Statistical independence of the exhale and inhale times is also supported by the magnitude of LLE. The nonlinear parameters seem more appropriate to gauge respiratory signal complexity since its deterministic chaotic nature. It contrasts with measures based on harmonic analysis that are blind for nonlinear features. Dynamics of breathing, so crucial for

  7. Interim Chronic Beryllium Disease

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    1999-12-08

    Establishes Departmental expectations for addressing chronic beryllium disease throughout the Department until a Departmental rule on beryllium is promulgated. This Notice was replaced by final rule 10 CFR Part 850, Chronic Beryllium Disease Prevention Program, published December 8, 1999.

  8. In utero and early life arsenic exposure in relation to long-term health and disease

    SciTech Connect (OSTI)

    Farzan, Shohreh F.; Karagas, Margaret R.; Chen, Yu

    2013-10-15

    Background: There is a growing body of evidence that prenatal and early childhood exposure to arsenic from drinking water can have serious long-term health implications. Objectives: Our goal was to understand the potential long-term health and disease risks associated with in utero and early life exposure to arsenic, as well as to examine parallels between findings from epidemiological studies with those from experimental animal models. Methods: We examined the current literature and identified relevant studies through PubMed by using combinations of the search terms “arsenic”, “in utero”, “transplacental”, “prenatal” and “fetal”. Discussion: Ecological studies have indicated associations between in utero and/or early life exposure to arsenic at high levels and increases in mortality from cancer, cardiovascular disease and respiratory disease. Additional data from epidemiologic studies suggest intermediate effects in early life that are related to risk of these and other outcomes in adulthood. Experimental animal studies largely support studies in humans, with strong evidence of transplacental carcinogenesis, atherosclerosis and respiratory disease, as well as insight into potential underlying mechanisms of arsenic's health effects. Conclusions: As millions worldwide are exposed to arsenic and evidence continues to support a role for in utero arsenic exposure in the development of a range of later life diseases, there is a need for more prospective studies examining arsenic's relation to early indicators of disease and at lower exposure levels. - Highlights: • We review in utero and early-life As exposure impacts on lifelong disease risks. • Evidence indicates that early-life As increases risks of lung disease, cancer and CVD. • Animal work largely parallels human studies and may lead to new research directions. • Prospective studies and individual exposure assessments with biomarkers are needed. • Assessing intermediary endpoints may

  9. Poster — Thur Eve — 37: Respiratory gating with an Elekta flattening filter free photon beam

    SciTech Connect (OSTI)

    Péloquin, S; Furstoss, C; Munger, P; Wierzbicki, W; Carrier, J-F

    2014-08-15

    In cases where surgery is not possible for lung cancer treatment, stereotactic body radiation therapy (SBRT) may be an option. One problem when treating this type of cancer is the motion of the lungs caused by the patient's respiration. It is possible to reduce the impact of this movement with the use of respiratory gating. By combining respiratory gating with a flattening filter free (FFF) photon beam linac, the increased treatment time caused by a reduced beam-on time of respiratory gating methods can be compensated by the inherent increased dose rate of FFF beams. This project's aim is to create hardware and software interfaces allowing free respiration gating on an Elekta Synergy-S linac specially modified to deliver 6 MV FFF photon beams. First, a printed circuit board was created for reading the signal from a Bellows Belt from Philips (a respiration monitor belt) and transmitting an On/Off signal to the accelerator. A software was also developed to visualize patient respiration. Secondly, a FFF model was created with the Pinnacle treatment planning system from Philips. Gamma (Γ) analysis (2%, 2 mm) was used to evaluate model. For fields going from 5.6 × 5.6 to 12 × 12 cm{sup 2}, central axis depth dose model fitting shows an average gamma value of 0.2 and 100% of gamma values remain under the Γ = 1 limit. For smaller fields (0.8 × 0.8 and 1.6 × 1.6 cm{sup 2}), Pinnacle has more trouble trying to fit the measurements, overestimating dose in penumbra and buildup regions.

  10. Air pollution and childhood respiratory health: Exposure to sulfate and ozone in 10 Canadian Rural Communities

    SciTech Connect (OSTI)

    Stern, B.R.; Raizenne, M.E.; Burnett, R.T.; Jones, L.; Kearney, J.; Franklin, C.A. )

    1994-08-01

    This study was designed to examine differences in the respiratory health status of preadolescent school children, aged 7-11 years, who resided in 10 rural Canadian communities in areas of moderate and low exposure to regional sulfate and ozone pollution. Five of the communities were located in central Saskatchewan, a low-exposure region, and five were located in southwestern Ontario, an area with moderately elevated exposures resulting from long-range atmospheric transport of polluted air masses. In this cross-sectional study, the child's respiratory symptoms and illness history were evaluated using a parent-completed questionnaire, administered in September 1985. Respiratory function was assessed once for each child in the schools between October 1985 and March 1986, by the measurement of pulmonary function for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV[sub 1.0]), peak expiratory flow rate (PEFR), mean forced expiratory flow rate during the middle half of the FVC curve (FEF[sub 25-75]), and maximal expiratory flow at 50% of the expired vital capacity (V[sub 50]max). After controlling for the effects of age, sex, parental smoking, parental education and gas cooking, no significant regional differences were observed in rates of chronic cough or phlegm, persistent wheeze, current asthma, bronchitis in the past year, or any chest illness that kept the child at home for 3 or more consecutive days during the previous year. Children living in southwestern Ontario had statistically significant (P < 0.01) mean decrements of 1.7% in FVC and 1.3% in FEV[sub 1.0] compared with Saskatchewan children, after adjusting for age, sex, weight, standing height, parental smoking, and gas cooking. There were no statistically significant regional differences in the pulmonary flow parameters (P > 0.05). 54 refs., 1 fig., 7 tabs.

  11. Respiratory symptoms among glass bottle makers exposed to stannic chloride solution and other potentially hazardous substances

    SciTech Connect (OSTI)

    Levy, B.S.; Davis, F.; Johnson, B.

    1985-04-01

    Concern about upper respiratory tract irritation and other symptoms among workers at a glass bottle manufacturing plant led to an epidemiologic and an industrial hygiene survey. Questionnaire responses from 35 hot end and 53 cold end workers indicated that the incidence of wheezing, chest pain, dyspnea on exertion, and cough was significantly elevated among hot end workers. Among both smokers and nonsmokers, hot end workers reported higher, but not significantly higher, rates of wheezing and chest pain. Among smokers, hot end workers reported significantly higher rates of dyspnea on exertion and cough than did cold end workers. Data suggest that reported exposure to stannic chloride solution likely caused these symptoms. The industrial hygiene survey, conducted when stannic chloride use had been reduced, cleaning had been done, and ventilation improved, focused on measuring air contaminants that might possibly cause symptoms. Levels of hydrogen chloride, which apparently was formed by the combination of stannic chloride and water in the presence of heat, were elevated. The finding of increased prevalence of respiratory symptoms among hot end workers was consistent with this exposure. Recommendations were made to reduce hazardous exposures at this plant. Individuals responsible for occupational health should be aware that relatively benign substances, such as stannic chloride and water, can combine spontaneously to form hazardous substances.

  12. Association of indoor nitrogen dioxide with respiratory symptoms and pulmonary function in children

    SciTech Connect (OSTI)

    Neas, L.M.; Dockery, D.W.; Ware, J.H.; Spengler, J.D.; Speizer, F.E.; Ferris, B.G. Jr. )

    1991-07-15

    The effect of indoor nitrogen dioxide on the cumulative incidence of respiratory symptoms and pulmonary function level was studied in a cohort of 1,567 white children aged 7-11 years examined in six US cities from 1983 through 1988. Week-long measurements of nitrogen dioxide were obtained at three indoor locations over 2 consecutive weeks in both the winter and the summer months. The household annual average nitrogen dioxide concentration was modeled as a continuous variable and as four ordered categories. Multiple logistic regression analysis of symptom reports from a questionnaire administered after indoor monitoring showed that a 15-ppb increase in the household annual nitrogen dioxide mean was associated with an increased cumulative incidence of lower respiratory symptoms (odds ratio (OR) = 1.4, 95% confidence interval (95% Cl) 1.1-1.7). The response variable indicated the report of one or more of the following symptoms: attacks of shortness of breath with wheeze, chronic wheeze, chronic cough, chronic phlegm, or bronchitis. Girls showed a stronger association (OR = 1.7, 95% Cl 1.3-2.2) than did boys (OR = 1.2, 95% Cl 0.9-1.5). An analysis of pulmonary function measurements showed no consistent effect of nitrogen dioxide. These results are consistent with earlier reports based on categorical indicators of household nitrogen dioxide sources and provide a more specific association with nitrogen dioxide as measured in children's homes.

  13. Health effects of acid aerosols on North American children: Respiratory symptoms

    SciTech Connect (OSTI)

    Dockery, D.W. |; Cunningham, J.; Damokosh, A.I.

    1996-05-01

    We examined the respiratory health effects of exposure to acidic air pollution among 13,369 white children 8 to 12 years old from 24 communities in the United States and Canada between 1988 and 1991. Each child`s parent or guardian completed a questionnaire. Air quality and meteorology were measured in each community for a 1-year period. We used a two-stage logistic regression model to analyze the data, adjusting for the period confounding effects of sex, history of allergies, parental asthma, parental education, and current smoking in the home. Children living in the community with the highest levels of particle strong acidity were significantly more likely [odds ratio (OR) = 1.66; 95% confidence interval (CI) 1.11-2.48] to report at least one episode of bronchitis in the past year compared to children living in the least-polluted community. Fine particulate sulfate was also associated with higher reporting of bronchitis (OR = 1.65; 95% CI 1.12-2.42). No other respiratory symptoms were significantly higher in association with any of the air pollutants of interest. No sensitive subgroups were identified. Reported bronchitis, but neither asthma, wheeze, cough, nor phlegm, were associated with levels of particle strong acidity for these children living in a nonurban environment. 26 refs., 3 figs., 4 tabs.

  14. Respiratory responses of vigorously exercising children to 0. 12 ppm ozone exposure

    SciTech Connect (OSTI)

    McDonnell, W.F. 3d.; Chapman, R.S.; Leigh, M.W.; Strope, G.L.; Collier, A.M.

    1985-10-01

    Changes in respiratory function have been suggested for children exposed to less than 0.12 ppm ozone (O3) while engaged in normal activities. Because the results of these studies have been confounded by other variables, such as temperature or the presence of other pollutants or have been questioned as to the adequacy of exposure measurements, the authors determined the acute response of children exposed to 0.12 ppm O3 in a controlled chamber environment. Twenty-three white males 8 to 11 yr of age were exposed once to clean air and once to 0.12 ppm O3 in random order. Exposures were for 2.5 h and included 2 h of intermittent heavy exercise. Measures of forced expiratory volume in one second (FEV1) and the symptom cough were determined prior to and after each exposure. A significant decline in FEV1 was found after the O3 exposure compared to the air exposure, and it appeared to persist for 16 to 20 h. No significant increase in cough was found due to O3 exposure. Forced vital capacity, specific airways resistance, respiratory frequency, tidal volume, and other symptoms were measured in a secondary exploratory analysis of this study.

  15. Absence of respiratory effects in subjects exposed to low concentrations of TDI and MDI

    SciTech Connect (OSTI)

    Musk, A.W.; Peters, J.M.; DiBerardinis, L.; Murphy, R.L.

    1982-10-01

    One hundred seven subjects from a polyurethane plastic manufacturing plant have been followed over a five-year period with measurements of forced expiratory volume in 1 s (FEV1), and questionnaires on respiratory symptoms and smoking habits. Environmental concentrations of toluene diisocyanate and diphenyl methyl diisocyanate were extensively monitored to provide accurate estimates of the upper-limits of exposure of the subjects. Current mean levels of FEV1 in this population were higher than those predicted for healthy subjects. The five-year change in FEV1 did not exceed that expected from aging. No acute change in FEV1 could be demonstrated over the course of a Monday either before or after a two-week vacation. No improvement in ventilatory function was observed over the vacation period. The presence of cough or sputum was related to smoking but was not related to isocyanate exposure. The results indicate that exposure of workers to extremely low levels of isocyanates (time-weighted average concentrations of the order of 0.001 parts per million (ppm)) is not associated with chronic respiratory symptoms or effects on ventilatory capacity. The results suggest that isocyanates can be controlled to the point of eliminating effects as measured by these techniques.

  16. SU-E-J-45: Design and Study of An In-House Respiratory Gating Phantom Platform for Gated Radiotherapy

    SciTech Connect (OSTI)

    Senthilkumar, S

    2014-06-01

    Purpose: The main purpose of this work was to develop an in-house low cost respiratory motion phantom platform for testing the accuracy of the gated radiotherapy system and analyze the dosimetric difference during gated radiotherapy. Methods: An in-house respiratory motion platform(RMP) was designed and constructed for testing the targeting accuracy of respiratory tracking system. The RMP consist of acrylic Chest Wall Platform, 2 DC motors, 4 IR sensors, speed controller circuit, 2 LED and 2 moving rods inside the RMP. The velocity of the movement can be varied from 0 to 30 cycles per minute. The platform mounted to a base using precision linear bearings. The base and platform are made of clear, 15mm thick polycarbonate plastic and the linear ball bearings are oriented to restrict the platform to a movement of approximately 50mm up and down with very little friction. Results: The targeting accuracy of the respiratory tracking system was evaluated using phantom with and without respiratory movement with varied amplitude. We have found the 5% dose difference to the PTV during the movement in comparison with stable PTV. The RMP can perform sinusoidal motion in 1D with fixed peak to peak motion of 5 to 50mm and cycle interval from 2 to 6 seconds. The RMP was designed to be able to simulate the gross anatomical anterior posterior motion attributable to respiration-induced motion of the thoracic region. Conclusion: The unique RMP simulates breathing providing the means to create a comprehensive program for commissioning, training, quality assurance and dose verification of gated radiotherapy treatments. Create the anterior/posterior movement of a target over a 5 to 50 mm distance to replicate tumor movement. The targeting error of the respiratory tracking system is less than 1.0 mm which shows suitable for clinical treatment with highly performance.

  17. Adventures in Infectious Diseases

    ScienceCinema (OSTI)

    Fisher-Hoch, Susan [University of Texas School of Public Health

    2014-06-25

    Dr. Susan Fisher-Hoch, Virologist and Epidemiologist, will discuss her research and travels associated with viral hemorrhagic fevers. From the Ebola outbreak in Reston, Virginia to outbreaks of Crimean Congo Hemorrhagic Fever in South Africa, Senegal, and Saudi Arabia, Dr. Fisher-Hoch has studied and tracked the pathophysiology of these viral diseases. These studies have led her from the Center for Disease Control in the United States, to Lyon, France where she was instrumental in designing, constructing, and rendering operational a laboratory capable of containing some of the world's most dangerous diseases.

  18. SU-E-J-190: Development of Abdominal Compression & Respiratory Guiding System Using Gas Pressure Sensor

    SciTech Connect (OSTI)

    Kim, T; Kim, D; Kang, S; Cho, M; Kim, K; Shin, D; Suh, T; Kim, S

    2015-06-15

    Purpose: Abdominal compression is known to be effective but, often makes external-marker-based monitoring of breathing motion not feasible. In this study, we developed and evaluated a system that enables both abdominal compression and monitoring of residual abdominal motion simultaneously. The system can also provide visual-biofeedback capability. Methods: The system developed consists of a compression belt, an abdominal motion monitoring sensor (gas pressure sensor) and a visual biofeedback device. The compression belt was designed to be able to compress the frontal side of the abdomen. The pressure level of the belt is controlled by air volume and monitored in real time using the gas pressure sensor. The system displays not only the real-time monitoring curve but also a guiding respiration model (e.g., a breath hold or shallow breathing curve) simultaneously on the head mounted display to help patients keep their breathing pattern as consistent as possible. Three healthy volunteers were enrolled in this pilot study and respiratory signals (pressure variations) were obtained both with and without effective abdominal compression to investigate the feasibility of the developed system. Two guidance patterns, breath hold and shallow breathing, were tested. Results: All volunteers showed smaller abdominal motion with compression (about 40% amplitude reduction compared to without compression). However, the system was able to monitor residual abdominal motion for all volunteers. Even under abdominal compression, in addition, it was possible to make the subjects successfully follow the guide patterns using the visual biofeedback system. Conclusion: The developed abdominal compression & respiratory guiding system was feasible for residual abdominal motion management. It is considered that the system can be used for a respiratory motion involved radiation therapy while maintaining the merit of abdominal compression. This work was supported by the Radiation Technology R

  19. Meta-Analyses of the Associations of Respiratory Health Effectswith Dampness and Mold in Homes

    SciTech Connect (OSTI)

    Fisk, William J.; Lei-Gomez, Quanhong; Mendell, Mark J.

    2006-01-01

    The Institute of Medicine (IOM) of the National Academy of Sciences recently completed a critical review of the scientific literature pertaining to the association of indoor dampness and mold contamination with adverse health effects. In this paper, we report the results of quantitative meta-analysis of the studies reviewed in the IOM report. We developed point estimates and confidence intervals (CIs) to summarize the association of several respiratory and asthma-related health outcomes with the presence of dampness and mold in homes. The odds ratios and confidence intervals from the original studies were transformed to the log scale and random effect models were applied to the log odds ratios and their variance. Models were constructed both accounting for the correlation between multiple results within the studies analyzed and ignoring such potential correlation. Central estimates of ORs for the health outcomes ranged from 1.32 to 2.10, with most central estimates between 1.3 and 1.8. Confidence intervals (95%) excluded unity except in two of 28 instances, and in most cases the lower bound of the CI exceeded 1.2. In general, the two meta-analysis methods produced similar estimates for ORs and CIs. Based on the results of the meta-analyses, building dampness and mold are associated with approximately 30% to 80% increases in a variety of respiratory and asthma-related health outcomes. The results of these meta-analyses reinforce the IOM's recommendation that actions be taken to prevent and reduce building dampness problems.

  20. Effects of ambient sulfur oxides and suspended particles on respiratory health of preadolescent children

    SciTech Connect (OSTI)

    Ware, J.H.; Ferris, B.G. Jr.; Dockery, D.W.; Spengler, J.D.; Stram, D.O.; Speizer, F.E.

    1986-05-01

    Reported here are the results from an ongoing study of outdoor air pollution and respiratory health of children living in six cities in the eastern and midwestern United States. The study enrolled 10,106 white preadolescent children between 1974 and 1977 in 3 successive annual visits to each city. Each child received a spirometric examination, and a parent completed a standard questionnaire. Of this cohort, 8,380 children were seen for a second examination 1 yr later. An air pollution monitoring program was begun in each community at about the time of the first examination. For this report, measurements of total suspended particulates (TSP), the sulfate fraction of TSP (TSO/sub 4/), and sulfur dioxide (SO2) concentrations at study-affiliated outdoor stations were combined with measurements at other public and private monitoring sites to create a record of TSP, TSO/sub 4/, and SO/sub 2/ concentrations in each of 9 air pollution regions during the 1-yr period preceding each examination and, for TSP, during each child's lifetime up to the time of testing. Across the 6 cities, frequency of cough was significantly associated with the average of 24-h mean concentrations of all 3 air pollutants during the year preceding the health examination (p less than 0.01). Rates of bronchitis and a composite measure of lower respiratory illness were significantly associated with average particulate concentrations (p less than 0.05). In analyses restricted to lifetime residents, these outcomes were significantly associated with measures of lifetime mean TSP concentration. Within the cities, however, temporal and spatial variation in air pollutant concentrations and illness and symptom rates were not positively associated.

  1. Effects of ambient ozone on respiratory function and symptoms in Mexico City schoolchildren

    SciTech Connect (OSTI)

    Castillejos, M.; Gold, D.R.; Dockery, D.; Tosteson, T.; Baum, T.; Speizer, F.E. )

    1992-02-01

    The effects of ambient ozone (O3) on respiratory function and acute respiratory symptoms were evaluated in 143 7- to 9-yr-old schoolchildren followed longitudinally at 1- to 2-wk intervals over a period of 6 months at three schools in Pedregal, Mexico City. The maximum O3 level exceeded the World Health Organization guideline of 80 ppb and the U.S. standard of 120 ppb in every week. For an increase from lowest to highest in the mean O3 level during the 48 hr before spirometry (53 ppb), logistic regression estimated relative odds of 1.7 for a child reporting cough/phlegm on the day of spirometry. For the full population, the mean O3 level during the hour before spirometry, not adjusted for temperature and humidity, predicted a significant decrement in FVC but not in FEV1 or FEF25-75. In contrast, the mean O3 level during the previous 24-, 48-, and 168-h periods predicted significant decrements in FEV1 and FEF25-75 but not in FVC. Ozone was consistently associated with a greater decrement in lung function for the 15 children with chronic phlegm as compared with the children without chronic cough, chronic phlegm, or wheeze. Ozone in the previous 24-, 48-, and 168-h periods predicted decrements in FEV1 for children of mothers who were current or former smokers, but not for children of mothers who were never smokers. Many of these effects were reduced in multiple regression analyses including temperature and humidity, as temperature and O3 were highly correlated.

  2. Associations of symptoms related to isocyanate, ureaformol, and formophenolic exposures with respiratory symptoms and lung function in coal miners

    SciTech Connect (OSTI)

    Bertrand, J.P.; Simon, V.; Chau, N.

    2007-04-15

    The respiratory effects of diphenylmethane diisocyanate (MDI)-based resins and ureaformol- and formophenolic-based resins, used in coal mining, are unknown. This cross-sectional study of 354 miners evaluated respiratory health in miners with MDI-related symptoms (IS) and ureaformol/formophenolic-related symptoms (UFS). The protocol included clinical examination, chest radiograph, questionnaire on respiratory symptoms, smoking habit, job history, resin handling, and spirometry. Resin handling concerned 27.7% of the miners. IS affected 5.6%, and 1.4% also after work. UFS affected 22.6%, and 2.3% also after work. Wheezing affected 35.6%; chronic cough, expectoration, or bronchitis about 10%; dyspnea 5.4%; and asthma 2.8%. The miners with UFS had significantly more frequent chronic cough, expectoration, chronic bronchitis, dyspnea, and wheezing, whereas those with IS at and after work had markedly lower FVC, FEV1, MMEF, FEF50% and FEF25%. These findings raise the possibility of deleterious effects of exposures to MDI and ureaformol/ ormophenolic resins on respiratory health and lung function in coal miners during their working life.

  3. Dynamic keyhole: A novel method to improve MR images in the presence of respiratory motion for real-time MRI

    SciTech Connect (OSTI)

    Lee, Danny; Pollock, Sean; Whelan, Brendan; Keall, Paul; Kim, Taeho

    2014-07-15

    Purpose: In this work, the authors present a novel magnetic resonance imaging reconstruction method to improve the quality of MR images in the presence of respiratory motion for real-time thoracic image-guided radiotherapy. Methods: This new reconstruction method is called dynamic keyhole and utilizes a library of previously acquired, peripheral k-space datasets from the same (or similar) respiratory state in conjunction with central k-space datasets acquired in real-time. Internal or external respiratory signals are utilized to sort, match, and combine the two separate peripheral and central k-space datasets with respect to respiratory displacement, thereby reducing acquisition time and improving image quality without respiratory-related artifacts. In this study, the dynamic keyhole, conventional keyhole, and zero-filling methods were compared to full k-space acquisition (ground truth) for 60 coronal datasets acquired from 15 healthy human subjects. Results: For the same image-quality difference from the ground-truth image, the dynamic keyhole method reused 79% of the prior peripheral phase-encoding lines, while the conventional keyhole reused 73% and zero-filling 63% (p-value < 0.0001), corresponding to faster acquisition speed of dynamic keyhole for real-time imaging applications. Conclusions: This study demonstrates that the dynamic keyhole method is a promising technique for clinical applications such as image-guided radiotherapy requiring real-time MR monitoring of the thoracic region. Based on the results from this study, the dynamic keyhole method could increase the temporal resolution by a factor of five compared with full k-space methods.

  4. SU-E-CAMPUS-J-01: TG142 Complied Comprehensive Commissioning and Quality Assurance Procedure for Respiratory Gating

    SciTech Connect (OSTI)

    Woods, K; Rong, Y; Weldon, M; Gupta, N

    2014-06-15

    Purpose: To develop and establish a comprehensive gating commissioning and quality assurance procedure in compliance with TG142. Methods: Quality assurance tests on three Varian LINACs included beam output and energy constancy, calibration of surrogate, as well as phase and amplitude gating temporal accuracy. A diode array (MapCHECK 2) and film (Gafchromic EBT2) were used to measure the temporal accuracy of phase and amplitude gating windows. A motion simulation device (MotionSim) was used to simulate respiratory motion for both detectors. An end-to-end test was also performed on all three machines. The overall accuracy and uncertainty was analyzed and compared. Results: The end-to-end test using an anthropomorphic lung phantom (CIRS) results in an OSL dose difference reading within 5% (within measurement uncertainty) for both phase and amplitude gated treatment. Film results showed < 1% agreement between profiles for gated delivery and predicted dose. The diode array demonstrated an 80% passing rate for gamma criteria of 2%/0.2 mm, which results in a 111 msec temporal accuracy. However, the diode array is limited by its spatial resolution of measurements, due to its 7.07 mm diode spacing. Film provided higher measuring resolution, thus demonstrated a temporal accuracy of <100 msec. Conclusion: Results showed consistent respiratory gating stability and accuracy. MapCHECK 2 may not be sufficient for the temporal accuracy test in the respiratory gating treatment in order to meet the corresponding tolerance in TG142. One would need to decrease respiratory motion speed from the surrogate or tighten the gating window in order to be within tolerance of 100 msec temporal accuracy per TG-142. The end-to-end test offers insight to the overall accuracy and uncertainties with a gated protocol. Compared to static delivery, respiratory motion increases the overall uncertainty of treatment delivery from 3% to 5% dose difference.

  5. Microbiome associations in pigs with the best and worst clinical outcomes following co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2)

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Niederwerder, Megan C.; Jaing, Crystal J.; Thissen, James B.; Cino-Ozuna, Ada Giselle; McLoughlin, Kevin S.; Rowland, Raymond R. R.

    2016-03-10

    Co-infections involving porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) are common and contribute to a range of polymicrobial disease syndromes in swine and on a world-wide basis. Both viruses compromise host defenses, resulting in increased susceptibility to infections by primary and secondary pathogens that can affect growth performance as well as increased morbidity and mortality. An experimental population of 95 pigs was co-infected with PRRSV and PCV2. At 70 days post-infection (dpi), 20 representative pigs were selected as having the best or worst clinical outcome based on average daily gain (ADG) and the presencemore » of clinical disease. Moreover, the worst clinical outcome pigs had prolonged and greater levels of viremia as measured by qPCR. Serum, lung and fecal samples collected at 70 dpi were analyzed using a comprehensive DNA microarray technology, the Lawrence Livermore Microbial Detection Array, to detect over 8000 microbes. Bacterial species, such as Bacillus cereus, were detected at a higher rate in the serum of worst performing pigs. At the level of the fecal microbiome, the overall microbial diversity was lower in the worst clinical outcome group. The results reinforce the importance of pathogen load in determining clinical outcome and suggest an important role of microbial diversity as a contributing factor in disease.« less

  6. Gas bubble disease: introduction

    SciTech Connect (OSTI)

    Fickeisen, D.H.; Schneider, M.J.; Wedemeyer, G.A.

    1980-11-01

    In 1970, gas bubble disease was identified as a serious problem affecting salmonids in the Columbia and Snake river systems. The source of supersaturation was entrainment of air into water spilling over hydroelectric dams. Regional research projects focusing on tolerance bioassays were immediately implemented. Since then, the scope of gas bubble disease research has broadened to include problems in other aquatic systems, with other species. Emphasis has shifted from defining tolerance limits in bioassay systems to exploring behavioral and physiological aspects. Various methods of degasifying supersaturated water have been developed.

  7. Using Wikipedia to forecast diseases

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Using Wikipedia to forecast diseases Using Wikipedia to forecast diseases Scientists can now monitor and forecast diseases around the globe more effectively by analyzing views of Wikipedia articles. November 13, 2014 Del Valle and her team observe findings from their research on disease patterns from analyzing Wikipedia articles. Del Valle and her team observe findings from their research on disease patterns from analyzing Wikipedia articles. Contact Nancy Ambrosiano Communications Office (505)

  8. Association between occupational exposure to arsenic and neurological, respiratory and renal effects

    SciTech Connect (OSTI)

    Halatek, Tadeusz Sinczuk-Walczak, Halina; Rabieh, Sasan; Wasowicz, Wojciech

    2009-09-01

    Occupational exposure by inhalation in copper smelter is associated with several subclinical health phenomena. The respiratory tract is usually involved in the process of detoxication of inhaled noxious agents which, as arsenic, can act as inductors of oxidative stress (Lantz, R.C., Hays, A.M., 2006. Role of oxidative stress in arsenic-induced toxicity. Drug Metab. Rev. 38, 791-804). It is also known that irritating fumes affect distal bronchioles of non-ciliated, epithelial Clara cells, which secrete anti-inflammatory and immunosuppressive Clara cell protein (CC16) into the respiratory tract. The study group comprised 39 smelters employed at different workplaces in a copper foundry, matched for age and smoking habits with the control group (n = 16). Subjective neurological symptoms (SNS), visual evoked potentials (VEP), electroneurographic (EneG) and electroencephalographic (EEG) results were examined in the workers and the relationships between As concentration in the air (As-Air) and urine (As-U) were assessed. Effects of exposure were expressed in terms of biomarkers: CC16 as early pulmonary biomarker and {beta}{sub 2}-microglobulin ({beta}{sub 2}M) in urine and serum and retinol binding protein (RBP) as renal markers, measured by sensitive latex immunoassay. The concentrations of arsenic exceeded about two times the Threshold Limit Values (TLV) (0.01 mg/m{sup 3}). The contents of lead did not exceed the TLV (0.05 mg/m{sup 3}). Low CC16 levels in serum (12.1 {mu}g/l) of workers with SNS and VEP symptoms and highest level As-U (x{sub a} 39.0 {mu}g/l) were noted earliest in relation to occupational time. Moreover, those effects were associated with increased levels of urinary and serum {beta}{sub 2}M and urinary RBP. Results of our study suggested the initiative key role of oxidative stress in triggering the processes that eventually lead to the subclinical effects of arsenic on the nervous system.

  9. Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein

    SciTech Connect (OSTI)

    Li, Yan; Jain, Neeraj; Limpanawat, Suweeraya; To, Janet; Quistgaard, Esben M.; Nordlund, Par; Thanabalu, Thirumaran; Torres, Jaume

    2015-08-15

    The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a library from human lung cDNA to detect proteins that bind SH protein. This led to the identification of a membrane protein, B-cell associated protein 31 (BAP31). Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls down endogenous BAP31. Titration of purified C-terminal endodomain of BAP31 against isotopically labeled SH protein in detergent micelles suggests direct interaction between the two proteins. Given the key role of BAP31 in protein trafficking and its critical involvement in pro- and anti-apoptotic pathways, this novel interaction may constitute a potential drug target. - Highlights: • A yeast two-hybrid system (MbY2H) detected BAP31 as a binder of RSV SH protein. • Transfected SH and BAP31 co-localize in lung epithelial cells. • Endogenous BAP31 is pulled down by RSV SH protein. • BAP31 endodomain interacts with the N-terminal α-helix of SH protein in micelles. • This interaction is proposed to be a potential drug target.

  10. Dynamic gating window for compensation of baseline shift in respiratory-gated radiation therapy

    SciTech Connect (OSTI)

    Pepin, Eric W.; Wu Huanmei; Shirato, Hiroki

    2011-04-15

    Purpose: To analyze and evaluate the necessity and use of dynamic gating techniques for compensation of baseline shift during respiratory-gated radiation therapy of lung tumors. Methods: Motion tracking data from 30 lung tumors over 592 treatment fractions were analyzed for baseline shift. The finite state model (FSM) was used to identify the end-of-exhale (EOE) breathing phase throughout each treatment fraction. Using duty cycle as an evaluation metric, several methods of end-of-exhale dynamic gating were compared: An a posteriori ideal gating window, a predictive trend-line-based gating window, and a predictive weighted point-based gating window. These methods were evaluated for each of several gating window types: Superior/inferior (SI) gating, anterior/posterior beam, lateral beam, and 3D gating. Results: In the absence of dynamic gating techniques, SI gating gave a 39.6% duty cycle. The ideal SI gating window yielded a 41.5% duty cycle. The weight-based method of dynamic SI gating yielded a duty cycle of 36.2%. The trend-line-based method yielded a duty cycle of 34.0%. Conclusions: Dynamic gating was not broadly beneficial due to a breakdown of the FSM's ability to identify the EOE phase. When the EOE phase was well defined, dynamic gating showed an improvement over static-window gating.

  11. Relationship of respiratory symptoms and pulmonary function to tar, nicotine, and carbon monoxide yield of cigarettes

    SciTech Connect (OSTI)

    Krzyzanowski, M.; Sherrill, D.L.; Paoletti, P.; Lebowitz, M.D. )

    1991-02-01

    The data from consecutive surveys of the Tucson Epidemiologic Study (1981-1988) were used to evaluate the relationship in cigarette smokers of respiratory symptoms and pulmonary function to tar, nicotine, and carbon monoxide (CO) yields of the cigarette. There were 690 subjects who reported smoking regularly in at least one survey, over age 15. After adjustment for intensity and duration of smoking and for depth of inhalation, the risk of chronic phlegm, cough, and dyspnea were not related to the tar and nicotine yields. In 414 subjects with pulmonary function tested in at least one of the three surveys the spirometric indices used were significantly related to the daily dose of tar, nicotine, and CO (product of the cigarette yield and daily number of cigarettes smoked). The effects were more pronounced for past than for current doses. However, the differentiation of pulmonary function due to various yields of cigarettes was small in comparison to the difference in pulmonary function between smokers and nonsmokers.

  12. The respiratory health and lung function of Anglo-American children in a smelter town

    SciTech Connect (OSTI)

    Dodge, R.

    1983-02-01

    Cooper smelters are large, usually isolated, sources of air pollution. Arizona has several such plants on the periphery of small communities. The smelters emit predominantly sulfur oxides and particulates, and the residents of these communities intermittently are exposed to high concentrations (24-h sulfur dioxide (SO2) . 250 to 500 micrograms/m3) of smelter smoke but little other pollution. This study compared the respiratory health of Anglo-American school children who lived in one smelter community with children living in another small community in Arizona that was free of smelter air pollution. The prevalence of cough, as determined by questionnaire, was 25.6% in the smelter town children and 14.3% in the nonsmelter town children (p less than 0.05). Pulmonary function at the study onset was equal in the two groups. Over the course of the 4 yr of study, lung function growth (measured as actual forced expiratory volume in one second (FEV1) after 4 yr of study minus predicted FEV1) was also equal in the smelter town and nonsmelter town children. These results suggest that children in smelter communities have slightly more cough when compared with children living in other communities, but no differences in initial lung function or lung function at yearly testing over the period of the study.

  13. Daily diaries of respiratory symptoms and air pollution: Methodological issues and results

    SciTech Connect (OSTI)

    Schwartz, J. ); Wypij, D.; Dockery D.; Ware, J.; Spengler, J.; Ferris, B. Jr. ); Zeger, S. )

    1991-01-01

    Daily diaries of respiratory symptoms are a powerful technique for detecting acute effects of air pollution exposure. While conceptually simple, these diary studies can be difficult to analyze. The daily symptom rates are highly correlated, even after adjustment for covariates, and this lack of independence must be considered in the analysis. Possible approaches include the use of incidence instead of prevalence rates and autoregressive models. Heterogeneity among subjects also induces dependencies in the data. These can be addressed by stratification and by two-stage models such as those developed by Korn and Whittemore. These approaches have been applied to two data sets: a cohort of school children participating in the Harvard Six Cities Study and a cohort of student nurses in Los Angeles. Both data sets provide evidence of autocorrelation and heterogeneity. Controlling for autocorrelation corrects the precision estimates, and because diary data are usually positively autocorrelated, this leads to larger variance estimates. Controlling for heterogeneity among subjects appears to increase the effect sizes for air pollution exposure. Preliminary results indicate associations between sulfur dioxide and cough incidence in children and between nitrogen dioxide and phlegm incidence in student nurses.

  14. Spirometry variability criteria--association with respiratory morbidity and mortality in a cohort of coal miners

    SciTech Connect (OSTI)

    Kellie, S.E.; Attfield, M.D.; Hankinson, J.L.; Castellan, R.M.

    1987-03-01

    To clarify the association between spirometry variability and respiratory morbidity and mortality, the authors analyzed data for miners examined in the first round of the National Coal Study, 1969-1971, and they compared groups of miners who failed with those who met each of two spirometry variability criteria: a 5% criterion recommended by the American Thoracic Society, and a 200 ml criterion used in prior research studies. Compared with miners who met the 5% criterion (the best two forced vital capacities must be within 5% or 100 ml of one another), the group that failed had a lower mean for forced expiratory volume in one second (FEV1), and odds ratios for cough, phlegm, wheeze, shortness of breath, and death of 1.75, 1.67, 1.76, 2.71, and 1.30, respectively. The findings for the 200 ml criterion (the best two FEV1s must be within 200 ml of one another) were somewhat different. The group that failed versus the group that met this criterion had a higher mean for FEV1, and odds ratios for cough, phlegm, wheeze, shortness of breath, and death of 1.13, 1.07, 1.15, 1.43, and 0.94, respectively. Although the findings differ for the two criteria, the findings demonstrate that increased spirometry variability is associated with poorer health.

  15. Middle East Respiratory Syndrome Coronavirus Intra-Host Populations Are Characterized by Numerous High Frequency Variants

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Borucki, Monica K.; Lao, Victoria; Hwang, Mona; Gardner, Shea; Adney, Danielle; Munster, Vincent; Bowen, Richard; Allen, Jonathan E.

    2016-01-20

    Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen related to SARS virus. In vitro studies indicate this virus may have a broad host range suggesting an increased pandemic potential. Genetic and epidemiological evidence indicate camels serve as a reservoir for MERS virus but the mechanism of cross species transmission is unclear and many questions remain regarding the susceptibility of humans to infection. Deep sequencing data was obtained from the nasal samples of three camels that had been experimentally infected with a human MERS-CoV isolate. A majority of the genome was covered and average coverage was greater thanmore » 12,000x depth. Although only 5 mutations were detected in the consensus sequences, 473 intrahost single nucleotide variants were identified. Lastly, many of these variants were present at high frequencies and could potentially influence viral phenotype and the sensitivity of detection assays that target these regions for primer or probe binding.« less

  16. Epidemiological-environmental study of diesel bus garage workers: chronic effects of diesel exhaust on the respiratory system

    SciTech Connect (OSTI)

    Gamble, J.; Jones, W.; Minshall, S.

    1987-10-01

    Two hundred and eighty-three (283) male diesel bus garage workers from four garages in two cities were examined to determine if there was excess chronic respiratory morbidity related to diesel exposure. The dependent variables were respiratory symptoms, radiographic interpretation for pneumoconiosis, and pulmonary function (FVC, FEV1, and flow rates). Independent variables included race, age, smoking, drinking, height, and tenure (as surrogate measure of exposure). Exposure-effect relationships within the study population showed no detectable associations of symptoms with tenure. There was an apparent association of pulmonary function and tenure. Seven workers (2.5%) had category 1 pneumoconiosis (three rounded opacities, two irregular opacities, and one with both rounded and irregular). The study population was also compared to a nonexposed blue-collar population. After indirect adjustment for age, race, and smoking, the study population had elevated prevalences of cough, phlegm, and wheezing, but there was no association with tenure. Dyspnea showed a dose-response trend but no apparent increase in prevalence. Mean percent predicted pulmonary function of the study population was greater than 100%, i.e., elevated above the comparison population. These data show there is an apparent effect of diesel exhaust on pulmonary function but not chest radiographs. Respiratory symptoms are high compared to blue-collar workers, but there is no relationship with tenure.

  17. Expedient Respiratory and Physical Protection: Does a Wet Towel Work to Prevent Chemical Warfare Agent Vapor Infiltration?

    SciTech Connect (OSTI)

    Sorensen, J.H.

    2002-08-30

    The purpose of this paper is to examine the effectiveness of expedient protection strategies to reduce exposure to vapors from chemical warfare agents. This includes an examination of the physical and the psychological effectiveness of measures such as using a wet towel to seal a door jam against the infiltration of chemicals while sheltering in place or to provide expedient respiratory protection. Respiratory protection for civilians has never been considered a viable option for population protection in the CSEPP. Problems of storage, ability to effectively don respirators, and questionable fit have been primary factors in rejecting this option. Expedient respiratory protection seems to offer little benefits for population protection for chemical agent vapors. Furthermore, using wet towels as a vapor barrier at the bottom of a door should be discouraged. The wetted towel provides no vapor filtration and its effectiveness in infiltration reduction is unknown. Taping the bottom of the door will still likely provide greater infiltration reduction and is recommended as the current method for use in sheltering.

  18. Effects of breathing variation on gating window internal target volume in respiratory gated radiation therapy

    SciTech Connect (OSTI)

    Cai Jing; McLawhorn, Robert; Read, Paul W.; Larner, James M.; Yin, Fang-fang; Benedict, Stanley H.; Sheng, Ke

    2010-08-15

    Purpose: To investigate the effects of breathing variation on gating window internal target volume (ITV{sub GW}) in respiratory gated radiation therapy. Method and Materials: Two-dimensional dynamic MRI (dMRI) of lung motion was acquired in ten volunteers and eight lung cancer patients. Resorted dMRI using 4DCT acquisition method (RedCAM) was generated for selected subjects by simulating the image rebinning process. A dynamic software generated phantom (dSGP) was created by moving a solid circle (to mimic the ''tumor'') with dMRI-determined motion trajectories. The gating window internal target area (ITA{sub GW}, 2D counterpart of ITV{sub GW}) was determined from both RedCAM and dSGP/dMRI. Its area (A), major axis (L1), minor axis (L2), and similarity (S) were calculated and compared. Results: In the phantom study of 3 cm tumor, measurements of the ITA{sub GW} from dSGP (A=10.0{+-}1.3 cm{sup 2}, L1=3.8{+-}0.4 cm, and L2=3.3{+-}0.1 cm) are significantly (p<0.001) greater than those from RedCAM (A=8.5{+-}0.7 cm{sup 2}, L1=3.5{+-}0.2 cm, and L2=3.1{+-}0.1 cm). Similarly, the differences are significantly greater (p<0.001) for the 1 cm tumor (A=1.9{+-}0.5 cm{sup 2}, L1=1.9{+-}0.4 cm, and L2=1.3{+-}0.1 cm in dSGP; A=1.3{+-}0.1 cm{sup 2}, L1=1.5{+-}0.2 cm, and L2=1.1{+-}0.1 cm in RedCAM). In patient studies, measurements of the ITA{sub GW} from dMRI (A=15.5{+-}8.2 cm{sup 2}, L1=5.0{+-}1.1 cm, and L2=3.8{+-}1.2 cm) are also significantly greater (p<0.05) than those from RedCAM (A=13.2{+-}8.5 cm{sup 2}, L1=4.3{+-}1.4 cm, and L2=3.7{+-}1.2 cm). Similarities were 0.9{+-}0.1, 0.8{+-}0.1, and 0.8{+-}0.1 in the 3 cm tumor phantom, 1 cm tumor phantom, and patient studies, respectively. Conclusion: ITV{sub GW} can be underestimated by 4DCT due to breathing variations. An additional margin may be needed to account for this potential error in generating a PTV{sub GW}. Cautions need to be taken when generating ITV{sub GW} from 4DCT in respiratory gated radiation therapy, especially

  19. Exposure assessment approaches to evaluate respiratory health effects of particulate matter and nitrogen dioxide

    SciTech Connect (OSTI)

    Quackenboss, J.J.; Krzyzanowski, M.; Lebowitz, M.D. )

    1991-01-01

    Several approaches can be taken to estimate or classify total personal exposures to air pollutants. While personal exposure monitoring (PEM) provides the most direct measurements, it is usually not practical for extended time periods or large populations. This paper describes the use of indirect approaches to estimate total personal exposure for NO2 and particulate matter (PM), summarizes the distributions of these estimates, and compares the effectiveness of these estimates with microenvironmental concentrations for evaluating effects on respiratory function and symptoms. Pollutant concentrations were measured at several indoor and outdoor locations for over 400 households participating in an epidemiological study in Tucson, Arizona. Central site monitoring data were significantly correlated with samples collected directly outside homes, but the former usually had higher pollutant concentrations. Integrated indices of daily total personal exposure were calculated using micro-environmental (ME) measurements or estimates and time-budget diary information. Peak expiratory flow rates (PEFR) were measured for up to four times a day during two-week study periods. In thirty children (ages 6-15 years) with current diagnosed asthma, a significant reduction in PEFR was associated with NO2 levels measured outside of their homes. Additional decrements of morning PEFR were found in those children sleeping in bedrooms with higher measured NO2 levels. Morning and noon PEFR decrements were also linked to higher morning NO2 levels that were measured at central monitoring stations. Effects of PM were also found, but were limited to morning PEFR. No effects were found in non-asthmatic children. The relationship of PEFR to the calculated indices of daily average total exposure were weaker than to the microenvironment concentrations.

  20. SU-E-J-63: Estimating the Effects of Respiratory Motion On Dose Heterogeneity for ITV-Based Treatments

    SciTech Connect (OSTI)

    Williams, C; Lewis, J

    2014-06-01

    Purpose: To quantify the relationship between the amount of dose heterogeneity in a treatment plan that uses an internal target volume (ITV) to account for respiratory motion and the true amount of heterogeneity in the dose delivered to the tumor contained within that ITV. Methods: We develop a convolution-based framework for calculating dose delivered to a tumor moving inside an ITV according to a common sinusoid-based breathing model including asymmetry. We model the planned ITV dose distribution as a centrally peaked analytic function approximating the profile of clinical stereotactic body radiotherapy treatments. Expressions for the minimum and maximum dose received by the tumor are derived and evaluated for a range of clinically relevant parameters. Results of the model are validated with phantom measurements using an ion chamber array. Results: An analytic expression is presented for the maximum and minimum doses received by the tumor relative to the planned ITV dose. The tumor dose heterogeneity depends solely on the ratio of tumor size to ITV size, the peak dose in the planned ITV dose distribution, and the respiratory asymmetry parameter. Under the assumptions of this model, using a typical breathing asymmetry parameter and a dose distribution with a fixed size ITV covered by the 100% line and with a 130% hotspot, the maximum dose to the tumor varies between 113%130%, and the minimum dose varies between 100%116% depending on the amount of tumor motion. Conclusion: This modeling exercise demonstrates the interplay between motion and dose heterogeneity. Tumors that exhibit large amounts of respiratory motion relative to their size will receive a more homogeneous dose and a larger minimum dose than would be inferred from the ITV dose distribution. This effect is not captured in current clinical treatment planning methods unless 4D dose calculation techniques are used. This work was partially supported by a Varian Medical Systems research grant.

  1. Application of computational fluid dynamics to regional dosimetry of inhaled chemicals in the upper respiratory tract of the rat

    SciTech Connect (OSTI)

    Kimbell, J.S.; Gross, E.A.; Joyner, D.R.; Godo, M.N.; Morgan, K.T. (Chemical Industry Institute of Toxicology, Research Triangle Park, NC (United States))

    1993-08-01

    For certain inhaled air pollutants, such as reactive, water soluble gases, the distribution of nasal lesions observed in F344 rats may be closely related to regional gas uptake patterns in the nose. These uptake patterns can be influenced by the currents of air flowing through the upper respiratory tract during the breathing cycle. Since data on respiratory tract lesions in F344 rats are extrapolated to humans to make predictions of risk to human health, a better understanding of the factors affecting these responses is needed. To assess potential effects of nasal airflow on lesion location and severity, a methodology was developed for creation of computer simulations of steady-state airflow and gas transport using a three-dimensional finite element grid reconstructed from serial step-sections of the nasal passages of a male F344 rat. Simulations on a supercomputer used the computational fluid dynamics package FIDAP (FDI, Evanston, IL). Distinct streams of bulk flow evident in the simulations matched inspiratory streams reported for the F344 rat. Moreover, simulated regional flow velocities matched measured velocities in concurrent laboratory experiments with a hollow nasal mold. Computer-predicted flows were used in simulations of gas transport to nasal passage walls, with formaldehyde as a test case. Results from the uptake simulations were compared with the reported distribution of formaldehyde-induced nasal lesions observed in the F344 rat, and indicated that airflow-driven uptake patterns probably play an important role in determining the location of certain nasal lesions induced by formaldehyde. This work demonstrated the feasibility of applying computational fluid dynamics to airflow-driven dosimetry of inhaled chemicals in the upper respiratory tract.

  2. Similarities of host defense mechanisms against pulmonary infectious disease in animals and man

    SciTech Connect (OSTI)

    Green, G.M.

    1984-01-01

    Evidence linking exposure to air pollutants with increased susceptibility to infectious diseases in humans comes from epidemiological, clinical, and experimental laboratory studies. The data suggest that the most common, and perhaps the most sensitive, index of the pulmonary effect of air pollutant exposure is on post upper respiratory infection, prolonged cough, phlegm, and purulent sputum. Experimental models of these relationships for extrapolation to humans should be able to measure such minor changes in symptomatology and physiology rather than require major lethal events. The bacterial aerosol model for quantifying nonspecific defense mechanisms of the bronchopulmonary tree utilizing nonpathogenic organisms fulfills this criterion. The function of the six major components of pulmonary antimicrobial defense mechanisms - including aerodynamic filtration, secretory respiratory tract fluid, fluid transport at the alveolar and bronchial levels, the phagocytic function of alveolar macrophages, the augmenting mechanisms of blood-derived inflammatory cells, and the secretory and cellular-specific immune mechanisms and their mediator products - can all be quantified by this experimental animal model system. The defensive functions are remarkably similar across animal species, and available human data suggest that findings obtained using the model may be extrapolatred to humans.

  3. Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization

    SciTech Connect (OSTI)

    Keravec, Marlène; Mounier, Jérôme; Prestat, Emmanuel; Vallet, Sophie; Jansson, Janet K.; Burgaud, Gaëtan; Rosec, Sylvain; Gouriou, Stéphanie; Rault, Gilles; Coton, Emmanuel; Barbier, Georges; Héry-Arnaud, Geneviève

    2015-08-09

    Pseudomonas aeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state.

  4. COMPARATIVE COMPUTATIONAL MODELING OF AIRFLOWS AND VAPOR DOSIMETY IN THE RESPIRATORY TRACTS OF RAT, MONKEY, AND HUMAN

    SciTech Connect (OSTI)

    Corley, Richard A.; Kabilan, Senthil; Kuprat, Andrew P.; Carson, James P.; Minard, Kevin R.; Jacob, Rick E.; Timchalk, Charles; Glenny, Robb W.; Pipavath, Sudhaker; Cox, Timothy C.; Wallis, Chris; Larson, Richard; Fanucchi, M.; Postlewait, Ed; Einstein, Daniel R.

    2012-07-01

    Coupling computational fluid dynamics (CFD) with physiologically based pharmacokinetic (PBPK) models is useful for predicting site-specific dosimetry of airborne materials in the respiratory tract and elucidating the importance of species differences in anatomy, physiology, and breathing patterns. Historically, these models were limited to discrete regions of the respiratory system. CFD/PBPK models have now been developed for the rat, monkey, and human that encompass airways from the nose or mouth to the lung. A PBPK model previously developed to describe acrolein uptake in nasal tissues was adapted to the extended airway models as an example application. Model parameters for each anatomic region were obtained from the literature, measured directly, or estimated from published data. Airflow and site-specific acrolein uptake patterns were determined under steadystate inhalation conditions to provide direct comparisons with prior data and nasalonly simulations. Results confirmed that regional uptake was dependent upon airflow rates and acrolein concentrations with nasal extraction efficiencies predicted to be greatest in the rat, followed by the monkey, then the human. For human oral-breathing simulations, acrolein uptake rates in oropharyngeal and laryngeal tissues were comparable to nasal tissues following nasal breathing under the same exposure conditions. For both breathing modes, higher uptake rates were predicted for lower tracheo-bronchial tissues of humans than either the rat or monkey. These extended airway models provide a unique foundation for comparing dosimetry across a significantly more extensive range of conducting airways in the rat, monkey, and human than prior CFD models.

  5. Early detection of contagious diseases

    DOE Patents [OSTI]

    Colston, Jr., Billy W.; Milanovich, Fred P.; Estacio, Pedro; Chang, John

    2011-08-09

    This invention provides an electronic proximity apparatus and a surveillance method using such an apparatus for alerting individuals that are exposed to a contagious disease. When a person becomes symptomatic and is diagnosed as positive for a given contagious agent, individuals that have recently maintained a threshold proximity with respect to an infected individual are notified and advised to seek immediate medial care. Treatment of individuals in the very early phases of infection (pre-symptomatic) significantly reduces contagiousness of the infected population first exposed to the contagious disease, thus preventing spread of the disease throughout the general population.

  6. SU-E-J-73: Generation of Volumetric Images with a Respiratory Motion Model Based On An External Surrogate Signal

    SciTech Connect (OSTI)

    Hurwitz, M; Williams, C; Mishra, P; Dhou, S; Lewis, J

    2014-06-01

    Purpose: Respiratory motion during radiotherapy treatment can differ significantly from motion observed during imaging for treatment planning. Our goal is to use an initial 4DCT scan and the trace of an external surrogate marker to generate 3D images of patient anatomy during treatment. Methods: Deformable image registration is performed on images from an initial 4DCT scan. The deformation vectors are used to develop a patient-specific linear relationship between the motion of each voxel and the trajectory of an external surrogate signal. Correlations in motion are taken into account with principal component analysis, reducing the number of free parameters. This model is tested with digital phantoms reproducing the breathing patterns of ten measured patient tumor trajectories, using five seconds of data to develop the model and the subsequent thirty seconds to test its predictions. The model is also tested with a breathing physical anthropomorphic phantom programmed to reproduce a patient breathing pattern. Results: The error (mean absolute, 95th percentile) over 30 seconds in the predicted tumor centroid position ranged from (0.8, 1.3) mm to (2.2, 4.3) mm for the ten patient breathing patterns. The model reproduced changes in both phase and amplitude of the breathing pattern. Agreement between prediction and truth over the entire image was confirmed by assessing the global voxel intensity RMS error. In the physical phantom, the error in the tumor centroid position was less than 1 mm for all images. Conclusion: We are able to reconstruct 3D images of patient anatomy with a model correlating internal respiratory motion with motion of an external surrogate marker, reproducing the expected tumor centroid position with an average accuracy of 1.4 mm. The images generated by this model could be used to improve dose calculations for treatment planning and delivered dose estimates. This work was partially funded by a research grant from Varian Medical Systems.

  7. SU-E-T-538: Does Abdominal Compression Through Prone Patient Position Reduce Respiratory Motion in Lung Cancer Radiotherapy?

    SciTech Connect (OSTI)

    Catron, T; Rosu, M; Weiss, E

    2014-06-01

    Purpose: This study assesses the effect of physiological abdominal compression from prone positioning by comparing respiratory-induced tumor movements in supine and prone positions. Methods: 19 lung cancer patients underwent repeated supine and prone free-breathing 4DCT scans. The effect of patient position on motion magnitude was investigated for tumors, lymph nodes (9 cases), and subgroups of central (11 cases), peripheral (8 cases) and small peripheral tumors (5 cases), by evaluating the population average excursions, absolute and relative to a carina-point. Results: Absolute motion analysis: In prone, motion increased by ~20% for tumors and ~25% for lymph nodes. Central tumors moved more compared to peripheral tumors in both supine and prone (~22%, and ~4% respectively). Central tumors movement increased by ~12% in prone. For peripheral tumors the increase in prone position was ~25% (~40% and 29% changes on along RL and AP directions). Motion relative to carina-point analysis: Overall, tumor excursions relative to carina-point increased by ~17% in prone. Lymph node relative magnitudes were lower by ~4%. Likewise, the central tumors moved ~7% less in prone. The subgroup of peripheral tumors exhibited increased amplitudes by ~44%; the small peripheral tumors had even larger relative displacements in prone (~46%). Conclusion: Tumor and lymph node movement in the patient population from this study averaged to be higher in prone than in supine position. Results from carina analysis also suggest that peripheral tissues have more physiologic freedom of motility when placed in the prone position, regardless of size. From these observations we should continue to avoid prone positioning for all types of primary lung tumor, suggesting that patients should receive radiotherapy for primary lung cancer in supine position to minimize target tissue mobility during normal respiratory effort. Further investigation will include more patients with peripheral tumors to validate our

  8. SU-E-T-452: Impact of Respiratory Motion On Robustly-Optimized Intensity-Modulated Proton Therapy to Treat Lung Cancers

    SciTech Connect (OSTI)

    Liu, W; Schild, S; Bues, M [Mayo Clinic Arizona, Phoenix, AZ (United States); Liao, Z; Sahoo, N [MD Anderson Cancer Center, Houston, TX (United States); Park, P [Scottsdale, GA (United States); Li, H [M.D. Anderson Cancer Center, Houston, TX (United States); Li, Y [Varian Medical Systems, Houston, TX (United States); Li, X; Shen, J [Mayo Clinic Arizona, Phoenix, AA (United States); Anand, A [Mayo Clinic Arizona, Phoenix (United States); Dong, L [Scripps Proton Therapy Center, San Diego, CA (United States); Zhu, X; Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

    2014-06-01

    Purpose: We compared conventionally optimized intensity-modulated proton therapy (IMPT) treatment plans against the worst-case robustly optimized treatment plans for lung cancer. The comparison of the two IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient set-up, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. Methods: For each of the 9 lung cancer cases two treatment plans were created accounting for treatment uncertainties in two different ways: the first used the conventional Method: delivery of prescribed dose to the planning target volume (PTV) that is geometrically expanded from the internal target volume (ITV). The second employed the worst-case robust optimization scheme that addressed set-up and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of the changes in patient anatomy due to respiratory motion was investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the two groups were compared using two-sided paired t-tests. Results: Without respiratory motion considered, we affirmed that worst-case robust optimization is superior to PTV-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, robust optimization still leads to more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality [D95% ITV: 96.6% versus 96.1% (p=0.26), D5% - D95% ITV: 10.0% versus 12.3% (p=0.082), D1% spinal cord: 31.8% versus 36.5% (p =0.035)]. Conclusion: Worst-case robust optimization led to superior solutions for lung IMPT. Despite of the fact that robust optimization did not explicitly

  9. Effects of Respiratory Motion on Passively Scattered Proton Therapy Versus Intensity Modulated Photon Therapy for Stage III Lung Cancer: Are Proton Plans More Sensitive to Breathing Motion?

    SciTech Connect (OSTI)

    Matney, Jason; Park, Peter C. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Bluett, Jaques [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chen, Yi Pei [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Liu, Wei; Court, Laurence E. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Li, Heng [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe, E-mail: rmohan@mdanderson.org [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-11-01

    Purpose: To quantify and compare the effects of respiratory motion on paired passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT) plans; and to establish the relationship between the magnitude of tumor motion and the respiratory-induced dose difference for both modalities. Methods and Materials: In a randomized clinical trial comparing PSPT and IMRT, radiation therapy plans have been designed according to common planning protocols. Four-dimensional (4D) dose was computed for PSPT and IMRT plans for a patient cohort with respiratory motion ranging from 3 to 17 mm. Image registration and dose accumulation were performed using grayscale-based deformable image registration algorithms. The dosevolume histogram (DVH) differences (4D-3D [3D = 3-dimensional]) were compared for PSPT and IMRT. Changes in 4D-3D dose were correlated to the magnitude of tumor respiratory motion. Results: The average 4D-3D dose to 95% of the internal target volume was close to zero, with 19 of 20 patients within 1% of prescribed dose for both modalities. The mean 4D-3D between the 2 modalities was not statistically significant (P<.05) for all dosevolume histogram indices (mean SD) except the lung V5 (PSPT: +1.1% 0.9%; IMRT: +0.4% 1.2%) and maximum cord dose (PSPT: +1.5 2.9 Gy; IMRT: 0.0 0.2 Gy). Changes in 4D-3D dose were correlated to tumor motion for only 2 indices: dose to 95% planning target volume, and heterogeneity index. Conclusions: With our current margin formalisms, target coverage was maintained in the presence of respiratory motion up to 17 mm for both PSPT and IMRT. Only 2 of 11 4D-3D indices (lung V5 and spinal cord maximum) were statistically distinguishable between PSPT and IMRT, contrary to the notion that proton therapy will be more susceptible to respiratory motion. Because of the lack of strong correlations with 4D-3D dose differences in PSPT and IMRT, the extent of tumor motion was not an adequate predictor of potential

  10. Patching genes to fight disease

    SciTech Connect (OSTI)

    Holzman, D.

    1990-09-03

    The National Institutes of Health has approved the first gene therapy experiments, one of which will try to cure cancer by bolstering the immune system. The applications of such therapy are limited, but the potential aid to people with genetic diseases is great.

  11. Polar lipid fatty acids, LPS-hydroxy fatty acids, and respiratory quinones of three Geobacter strains, and variation with electron acceptor

    SciTech Connect (OSTI)

    Hedrick, David B.; Peacock, Aaron; Lovley, Derek; Woodard, Trevor L.; Nevin, Kelly P.; Long, Philip E.; White, David C.

    2009-02-01

    The polar lipid fatty acids, lipopolysaccharide hydroxy-fatty acids, and respiratory quinones of Geobacter metallireducens str. GS-15, Geobacter sulfurreducens str. PCA, and Geobacter bemidjiensis str. Bem are reported. Also, the lipids of G. metallireducens were compared when grown with Fe3+ or nitrate as electron acceptors and G. sulfurreducens with Fe3+ or fumarate. In all experiments, the most abundant polar lipid fatty acids were 14:0, i15:0, 16:1*7c, 16:1*5c, and 16:0; lipopolysaccharide hydroxyfatty acids were dominated by 3oh16:0, 3oh14:0, 9oh16:0, and 10oh16:0; and menaquinone-8 was the most abundant respiratory quinone. Some variation in lipid proWles with strain were observed, but not with electron acceptor.

  12. A Community-Based Approach to Developing a Mobile Device for Measuring Ambient Air Exposure, Location, and Respiratory Health

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Rohlman, Diana; Syron, Laura; Hobbie, Kevin; Anderson, Kim A.; Scaffidi, Christopher; Sudakin, Daniel; Peterson, Elena S.; Waters, Katrina M.; Haynes, Erin; Arkin, Lisa; et al

    2015-08-15

    In west Eugene (Oregon), community research indicates residents are disproportionately exposed to industrial air pollution and exhibit increased asthma incidence. In Carroll County (Ohio), recent increases in unconventional natural gas drilling sparked air quality concerns. These community concerns led to the development of a prototype mobile device to measure personal chemical exposure, location, and respiratory function. Working directly with the environmental justice (EJ) communities, the prototype was developed to (1) meet the needs of the community and; (2) evaluate the use in EJ communities. The prototype was evaluated in 3 community focus groups (n=25) to obtain feedback on the prototypemore » and feasibility study design to evaluate the efficacy of the device to address community concerns. Focus groups were recorded and qualitatively analyzed with discrete feedback tabulated for further refinement. The prototype was improved by community feedback resulting in 8 alterations/additions to software and instructional materials. Overall, focus group participants were supportive of the device and believed it would be a useful environmental health tool. The use of focus groups ensured that community members were engaged in the research design and development of a novel environmental health tool. We found that community-based research strategies resulted in a refined device as well as relevant research questions, specific to the EJ community needs and concerns.« less

  13. A Community-Based Approach to Developing a Mobile Device for Measuring Ambient Air Exposure, Location, and Respiratory Health

    SciTech Connect (OSTI)

    Rohlman, Diana; Syron, Laura; Hobbie, Kevin; Anderson, Kim A.; Scaffidi, Christopher; Sudakin, Daniel; Peterson, Elena S.; Waters, Katrina M.; Haynes, Erin; Arkin, Lisa; Feezel, Paul; Kincl, Laurel

    2015-08-15

    In west Eugene (Oregon), community research indicates residents are disproportionately exposed to industrial air pollution and exhibit increased asthma incidence. In Carroll County (Ohio), recent increases in unconventional natural gas drilling sparked air quality concerns. These community concerns led to the development of a prototype mobile device to measure personal chemical exposure, location, and respiratory function. Working directly with the environmental justice (EJ) communities, the prototype was developed to (1) meet the needs of the community and; (2) evaluate the use in EJ communities. The prototype was evaluated in 3 community focus groups (n=25) to obtain feedback on the prototype and feasibility study design to evaluate the efficacy of the device to address community concerns. Focus groups were recorded and qualitatively analyzed with discrete feedback tabulated for further refinement. The prototype was improved by community feedback resulting in 8 alterations/additions to software and instructional materials. Overall, focus group participants were supportive of the device and believed it would be a useful environmental health tool. The use of focus groups ensured that community members were engaged in the research design and development of a novel environmental health tool. We found that community-based research strategies resulted in a refined device as well as relevant research questions, specific to the EJ community needs and concerns.

  14. Real-Time Target Position Estimation Using Stereoscopic Kilovoltage/Megavoltage Imaging and External Respiratory Monitoring for Dynamic Multileaf Collimator Tracking

    SciTech Connect (OSTI)

    Cho, Byungchul; Poulsen, Per Rugaard; Sawant, Amit; Ruan, Dan; Keall, Paul J.

    2011-01-01

    Purpose: To develop a real-time target position estimation method using stereoscopic kilovoltage (kV)/megavoltage (MV) imaging and external respiratory monitoring, and to investigate the performance of a dynamic multileaf collimator tracking system using this method. Methods and Materials: The real-time three-dimensional internal target position estimation was established by creating a time-varying correlation model that connected the external respiratory signals with the internal target motion measured intermittently using kV/MV imaging. The method was integrated into a dynamic multileaf collimator tracking system. Tracking experiments were performed for 10 thoracic/abdominal traces. A three-dimensional motion platform carrying a gold marker and a separate one-dimensional motion platform were used to reproduce the target and external respiratory motion, respectively. The target positions were detected by kV (1 Hz) and MV (5.2 Hz) imaging, and external respiratory motion was captured by an optical system (30 Hz). The beam-target alignment error was quantified as the positional difference between the target and circular beam center on the MV images acquired during tracking. The correlation model error was quantified by comparing a model estimate and measured target positions. Results: The root-mean-square errors in the beam-target alignment that had ranged from 3.1 to 7.6 mm without tracking were reduced to <1.5 mm with tracking, except during the model building period (6 s). The root-mean-square error in the correlation model was submillimeters in all directions. Conclusion: A novel real-time target position estimation method was developed and integrated into a dynamic multileaf collimator tracking system and demonstrated an average submillimeter geometric accuracy after initializing the internal/external correlation model. The method used hardware tools available on linear accelerators and therefore shows promise for clinical implementation.

  15. Etiology of gas bubble disease

    SciTech Connect (OSTI)

    Bouck, G.R.

    1980-11-01

    Gas bubble disease is a noninfectious, physically induced process caused by uncompensated hyperbaric pressure of total dissolved gases. When pressure compensation is inadequate, dissolved gases may form emboli (in blood) and emphysema (in tissues). The resulting abnormal physical presence of gases can block blood vessels (hemostasis) or tear tissues, and may result in death. Population mortality is generally skewed, in that the median time to death occurs well before the average time to death. Judged from mortality curves, three stages occur in gas bubble disease: (1) a period of gas pressure equilibrium, nonlethal cavitation, and increasing morbidity; (2) a period of rapid and heavy mortality; and (3) a period of protracted survival, despite lesions, and dysfunction that eventually terminates in total mortality. Safe limits for gas supersaturation depend on species tolerance and on factors that differ among hatcheries and rivers, between continuous and intermittent exposures, and across ranges of temperature and salinity.

  16. Management of the baseline shift using a new and simple method for respiratory-gated radiation therapy: Detectability and effectiveness of a flexible monitoring system

    SciTech Connect (OSTI)

    Tachibana, Hidenobu; Kitamura, Nozomi; Ito, Yasushi; Kawai, Daisuke; Nakajima, Masaru; Tsuda, Akihisa; Shiizuka, Hisao

    2011-07-15

    Purpose: In respiratory-gated radiation therapy, a baseline shift decreases the accuracy of target coverage and organs at risk (OAR) sparing. The effectiveness of audio-feedback and audio-visual feedback in correcting the baseline shift in the breathing pattern of the patient has been demonstrated previously. However, the baseline shift derived from the intrafraction motion of the patient's body cannot be corrected by these methods. In the present study, the authors designed and developed a simple and flexible system. Methods: The system consisted of a web camera and a computer running our in-house software. The in-house software was adapted to template matching and also to no preimage processing. The system was capable of monitoring the baseline shift in the intrafraction motion of the patient's body. Another marker box was used to monitor the baseline shift due to the flexible setups required of a marker box for gated signals. The system accuracy was evaluated by employing a respiratory motion phantom and was found to be within AAPM Task Group 142 tolerance (positional accuracy <2 mm and temporal accuracy <100 ms) for respiratory-gated radiation therapy. Additionally, the effectiveness of this flexible and independent system in gated treatment was investigated in healthy volunteers, in terms of the results from the differences in the baseline shift detectable between the marker positions, which the authors evaluated statistically. Results: The movement of the marker on the sternum [1.599 {+-} 0.622 mm (1 SD)] was substantially decreased as compared with the abdomen [6.547 {+-} 0.962 mm (1 SD)]. Additionally, in all of the volunteers, the baseline shifts for the sternum [-0.136 {+-} 0.868 (2 SD)] were in better agreement with the nominal baseline shifts than was the case for the abdomen [-0.722 {+-} 1.56 mm (2 SD)]. The baseline shifts could be accurately measured and detected using the monitoring system, which could acquire the movement of the marker on the

  17. New Clues in Predicting Alzheimer's Disease

    ScienceCinema (OSTI)

    Jagust, William

    2013-05-29

    Theres a new clue in the search to identify the harbingers of Alzheimers disease. More info: http://newscenter.lbl.gov/feature-stories/2008/12/16/predict-alzheimers-disease/

  18. SU-E-J-126: Respiratory Gating Quality Assurance: A Simple Method to Achieve Millisecond Temporal Resolution

    SciTech Connect (OSTI)

    McCabe, B; Wiersma, R

    2014-06-01

    Purpose: Low temporal latency between a gating on/off signal and a linac beam on/off during respiratory gating is critical for patient safety. Although, a measurement of temporal lag is recommended by AAPM Task Group 142 for commissioning and annual quality assurance, there currently exists no published method. Here we describe a simple, inexpensive, and reliable method to precisely measure gating lag at millisecond resolutions. Methods: A Varian Real-time Position Management™ (RPM) gating simulator with rotating disk was modified with a resistive flex sensor (Spectra Symbol) attached to the gating box platform. A photon diode was placed at machine isocenter. Output signals of the flex sensor and diode were monitored with a multichannel oscilloscope (Tektronix™ DPO3014). Qualitative inspection of the gating window/beam on synchronicity were made by setting the linac to beam on/off at end-expiration, and the oscilloscope's temporal window to 100 ms to visually examine if the on/off timing was within the recommended 100-ms tolerance. Quantitative measurements were made by saving the signal traces and analyzing in MatLab™. The on and off of the beam signal were located and compared to the expected gating window (e.g. 40% to 60%). Four gating cycles were measured and compared. Results: On a Varian TrueBeam™ STx linac with RPM gating software, the average difference in synchronicity at beam on and off for four cycles was 14 ms (3 to 30 ms) and 11 ms (2 to 32 ms), respectively. For a Varian Clinac™ 21EX the average difference at beam on and off was 127 ms (122 to 133 ms) and 46 ms (42 to 49 ms), respectively. The uncertainty in the synchrony difference was estimated at ±6 ms. Conclusion: This new gating QA method is easy to implement and allows for fast qualitative inspection and quantitative measurements for commissioning and TG-142 annual QA measurements.

  19. The South Karelia Air Pollution Study. The effects of malodorous sulfur compounds from pulp mills on respiratory and other symptoms

    SciTech Connect (OSTI)

    Jaakkola, J.J.; Vilkka, V.; Marttila, O.; Jaeppinen, P.H.; Haahtela, T. )

    1990-12-01

    The paper mills in South Karelia, the southeast part of Finland, are responsible for releasing a substantial amount of malodorous sulfur compounds such as hydrogen sulfide (H2S), methyl mercaptan (CH3SH), and methyl sulfides ((CH3)2S and (CH3)2S2), into ambient air. In the most polluted residential area the annual mean concentrations of hydrogen sulfide and methyl mercaptan are estimated to be 8 and 2 to 5 micrograms/m3 and the highest daily average concentration 100 and 50 micrograms/m3. The annual mean and highest daily concentrations of sulfur dioxide (SO2) are very low. We studied the effects of malodorous sulfur compounds on eye, nasal and respiratory symptoms, and headache in adults. A cross-sectional self-administered questionnaire was distributed in February 1987 and responded to by 488 adults living in a severely (n = 198), a moderately (n = 204), and a nonpolluted community (n = 86). This included questions about occurrence of the symptoms of interest during the previous 4 wk and 12 months and individual, behavioral, and other environmental determinants of the symptoms. The response rate was 83%. The odds ratios (OR) for symptoms experienced often or constantly in severely versus nonpolluted and moderately versus nonpolluted communities were estimated in logistic regression analysis controlling potential confounders. The odds ratios for eye (moderate exposure OR 11.70, Cl95% 2.33 to 58.65; severe exposure OR 11.78, Cl95% 2.35 to 59.09) and nasal symptoms (OR 2.01, Cl95% 0.97 to 4.15; OR 2.19, Cl95% 1.06 to 4.55) and cough (OR 1.89, Cl95% 0.61 to 5.86; OR 3.06, Cl95% 1.02 to 9.29) during the previous 12 months were increased, with a dose-response pattern.

  20. RNA simulations boost understanding of retroviral diseases

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    RNA simulations boost understanding of retroviral diseases RNA simulations boost understanding of retroviral diseases New molecular dynamics research into how RNA folds into hairpin-shaped structures called tetraloops could provide important insights into new treatments for retroviral diseases. May 31, 2016 An example of RNA folded into a tetraloop, in this case the "Z-form duplex" under study that could provide medical treatment opportunities for retroviral diseases such as Zika and

  1. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Protein Instability and Lou Gehrig's Disease Protein Instability and Lou Gehrig's Disease Print Wednesday, 25 March 2015 00:00 A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called

  2. SciSat AM: Stereo 09: Accuracy of Liver Cancer Treatment on Cyberknife with Synchrony Optical Tracking Throughout the Respiratory Cycle

    SciTech Connect (OSTI)

    Winter, J.; Chow, T; Wong, R.

    2014-08-15

    The Cyberknife robotic stereotactic body radiation therapy system is well-suited for treating liver lesions over the respiratory cycle as it includes room-mounted orthogonal x-ray tracking of internal fiducial markers and optical tracking of external markers. The Synchrony software generates a model of internal target positions during patient respiration and correlates it to the external optical tracking system for real-time optical-based position corrections of the linear accelerator during beam delivery. Although clinical studies have provided preliminary outcomes for liver lesions treated with the Cyberknife system, to date, there is little data demonstrating the ability of the Synchrony software to track targets in the liver, which deforms throughout the respiratory cycle. In this study, we investigated the respiratory motion model performance for predicting tumour motion. We conducted a retrospective analysis of fifteen liver cancer patients treated on the Cyberknife using the Synchrony optical tracking system. We analyzed Cyberknife tracking information stored in the log files to extract the left-right (LR), anterior-posterior (AP) and superior-inferior (SI) correlation errors between the model-predicted position and the internal fiducial centroid position determined by x-ray imaging. Only translational tracking and corrections were applied during treatment. Overall, the correlation errors were greatest in the SI direction. We calculated radial correlation errors, and determined that the 95{sup th}, 98{sup th} and 99{sup th} percentile errors were 3.4 mm, 4.4 mm and 5.1 mm, respectively. Based on translational correlation tracking errors we expect the clinical target volume will be within 3.4 mm of the planning target volume for 95 % of beam delivery time.

  3. SciThur AM: YIS - 01: Dosimetric Analysis of Respiratory Induced Cardiac Intrafraction Motion in Left-sided Breast Cancer Radiotherapy

    SciTech Connect (OSTI)

    El-Sherif, O; Xhaferllari, I; Patrick, J; Yu, E; Gaede, S

    2014-08-15

    Introduction: Long-term cardiac side effects in left-sided breast cancer patients (BREL) after post-operative radiotherapy has become one of the most debated issues in radiation oncology. Through breathing-adapted radiotherapy the volume of the heart exposed to radiation can be significantly reduced by delivering the radiation only at the end of inspiration phase of the respiratory cycle, this is referred to as inspiration gating (IG). The purpose of this study is to quantify the potential reduction in cardiac exposure during IG compared to conventional BREL radiotherapy and to assess the dosimetric impact of cardiac motion due to natural breathing. Methods: 24 BREL patients treated with tangential parallel opposed photon beams were included in this study. All patients received a standard fast helical planning CT (FH-CT) and a 4D-CT. Treatment plans were created on the FH-CT using a clinical treatment planning system. The original treatment plan was then superimposed onto the end of inspiration CT and all 10 phases of the 4D-CT to quantify the dosimetric impact of respiratory motion and IG through 4D dose accumulation. Results: Through IG the mean dose to the heart, left ventricle, and left anterior descending artery (LAD) can be reduced in comparison to the clinical standard BREL treatment by as much as 8.39%, 10.11%, and 13.71% respectively (p < 0.05). Conclusion: Failure to account for respiratory motion can lead to under or overestimation in the calculated DVH for the heart, and it's sub-structures. IG can reduce cardiac exposure especially to the LAD during BREL radiotherapy.

  4. SU-E-T-66: Characterization of Radiation Dose Associated with Dark Currents During Beam Hold for Respiratory-Gated Electron Therapy

    SciTech Connect (OSTI)

    Hessler, J; Gupta, N; Rong, Y; Weldon, M

    2014-06-01

    Purpose: The main objective of this study was to estimate the radiation dose contributed by dark currents associated with the respiratory-gated electron therapy during beam hold. The secondary aim was to determine clinical benefits of using respiratory-gated electron therapy for left-sided breast cancer patients with positive internal mammary nodes (IMN). Methods: Measurements of the dark current-induced dose in all electron modes were performed on multiple Siemens and Varian linear accelerators by manually simulating beam-hold during respiratory gating. Dose was quantified at the machine isocenter by comparing the collected charge to the known output for all energies ranging from 6 to 18 MeV for a 10cm × 10cm field at 100 SSD with appropriate solid-water buildup. Using the Eclipse treatment planning system, we compared the additional dose associated with dark current using gated electron fields to the dose uncertainties associated with matching gated photon fields and ungated electron fields. Dose uncertainties were seen as hot and cold spots along the match line of the fields. Results: The magnitude of the dose associated with dark current is highly correlated to the energy of the beam and the amount of time the beam is on hold. For lower energies (6–12 MeV), there was minimal dark current dose (0.1–1.3 cGy/min). Higher energies (15–18 MeV) showed measurable amount of doses. The dark current associated with the electron beam-hold varied between linear accelerator vendors and depended on dark current suppression and the age of the linear accelerator. Conclusion: For energies up to 12 MeV, the dose associated with the dark current for respiratorygated electron therapy was shown to be negligible, and therefore should be considered an option for treating IMN positive left-sided breast cancer patients. However, at higher energies the benefit of respiratory gating may be outweighed by dose due to the dark current.

  5. Therapeutic target for protozoal diseases

    DOE Patents [OSTI]

    Rathore, Dharmendar; Jani, Dewal; Nagarkatti, Rana

    2008-10-21

    A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

  6. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Protein Instability and Lou Gehrig's Disease Print A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins linked

  7. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Protein Instability and Lou Gehrig's Disease Print A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins linked

  8. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Protein Instability and Lou Gehrig's Disease Print A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins linked

  9. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Protein Instability and Lou Gehrig's Disease Print A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins linked

  10. Imaging of occupational and environmental lung diseases

    SciTech Connect (OSTI)

    Akira, M.

    2008-03-15

    The chest radiograph is the basic tool for identifying occupational and environmental lung diseases; however, its sensitivity and specificity for the diagnosis of occupational and environmental lung diseases are low. High-resolution CT is the optimal method of recognizing parenchymal abnormalities in occupational and environmental disease. With the exception of pleural plaques, the CT findings of occupational and environmental lung diseases are nonspecific. Therefore, correlation of imaging features with history of exposure, other clinical features, and sometimes pathology is needed for the diagnosis of pneumoconiosis.

  11. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    called superoxide dismutase (SOD). The study provides evidence that those proteins linked to more severe forms of the disease are less stable structurally and more prone to...

  12. Epidemiological-environmental study of diesel bus garage workers: acute effects of NO/sub 2/ and respirable particulate on the respiratory system

    SciTech Connect (OSTI)

    Gamble, J.; Jones, W.; Minshall, S.

    1987-02-01

    Personal samples of nitrogen dioxide (NO/sub 2/) and respirable particulate (RP) were collected over the shift on 232 workers in four diesel bus garages. Response was assessed by an acute respiratory questionnaire and before and after shift spirometry. Measures of exposure to NO/sub 2/ and RP were associated with work-related symptoms of cough; itching, burning, or watering eyes; difficult or labored breathing; chest tightness; and wheeze. The prevalence of burning eyes, headaches, difficult or labored breathing, nausea, and wheeze experienced at work were higher in the diesel bus garage workers than in a comparison population of battery workers, while the prevalence of headaches was reduced. Mean reductions in forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), peak flow, and flows at 50 and 75% of FVC were not obviously different from zero. There was no detectable association of exposure to NO/sub 2/ or respirable particulate and acute reductions in pulmonary function. Workers who often had respiratory work-related symptoms generally had a slightly greater mean acute reduction in FEV1 and FEF50 than did those who did not have these symptoms, but these differences were not statistically significant.

  13. Disease Ontology 2015 update: An expanded and updated database of human diseases for linking biomedical knowledge through disease data

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Kibbe, Warren A.; Arze, Cesar; Felix, Victor; Mitraka, Elvira; Bolton, Evan; Fu, Gang; Mungall, Christopher J.; Binder, Janos X.; Malone, James; Vasant, Drashtti; et al

    2014-10-27

    The current version of the Human Disease Ontology (DO) (http://www.disease-ontology.org) database expands the utility of the ontology for the examination and comparison of genetic variation, phenotype, protein, drug and epitope data through the lens of human disease. DO is a biomedical resource of standardized common and rare disease concepts with stable identifiers organized by disease etiology. The content of DO has had 192 revisions since 2012, including the addition of 760 terms. Thirty-two percent of all terms now include definitions. DO has expanded the number and diversity of research communities and community members by 50+ during the past two years.more » These community members actively submit term requests, coordinate biomedical resource disease representation and provide expert curation guidance. Since the DO 2012 NAR paper, there have been hundreds of term requests and a steady increase in the number of DO listserv members, twitter followers and DO website usage. DO is moving to a multi-editor model utilizing Protégé to curate DO in web ontology language. In conclusion, this will enable closer collaboration with the Human Phenotype Ontology, EBI's Ontology Working Group, Mouse Genome Informatics and the Monarch Initiative among others, and enhance DO's current asserted view and multiple inferred views through reasoning.« less

  14. SU-E-T-582: On-Line Dosimetric Verification of Respiratory Gated Volumetric Modulated Arc Therapy Using the Electronic Portal Imaging Device

    SciTech Connect (OSTI)

    Schaly, B; Gaede, S; Xhaferllari, I

    2015-06-15

    Purpose: To investigate the clinical utility of on-line verification of respiratory gated VMAT dosimetry during treatment. Methods: Portal dose images were acquired during treatment in integrated mode on a Varian TrueBeam (v. 1.6) linear accelerator for gated lung and liver patients that used flattening filtered beams. The source to imager distance (SID) was set to 160 cm to ensure imager clearance in case the isocenter was off midline. Note that acquisition of integrated images resulted in no extra dose to the patient. Fraction 1 was taken as baseline and all portal dose images were compared to that of the baseline, where the gamma comparison and dose difference were used to measure day-to-day exit dose variation. All images were analyzed in the Portal Dosimetry module of Aria (v. 10). The portal imager on the TrueBeam was calibrated by following the instructions for dosimetry calibration in service mode, where we define 1 calibrated unit (CU) equal to 1 Gy for 10×10 cm field size at 100 cm SID. This reference condition was measured frequently to verify imager calibration. Results: The gamma value (3%, 3 mm, 5% threshold) ranged between 92% and 100% for the lung and liver cases studied. The exit dose can vary by as much as 10% of the maximum dose for an individual fraction. The integrated images combined with the information given by the corresponding on-line soft tissue matched cone-beam computed tomography (CBCT) images were useful in explaining dose variation. For gated lung treatment, dose variation was mainly due to the diaphragm position. For gated liver treatment, the dose variation was due to both diaphragm position and weight loss. Conclusion: Integrated images can be useful in verifying dose delivery consistency during respiratory gated VMAT, although the CBCT information is needed to explain dose differences due to anatomical changes.

  15. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    1941 at the age of only 38. Recently, an award-winning movie about the famous physicist, Stephen Hawking, depicted the disease's devastating physical toll. ALS kills by destroying...

  16. Zika Virus Disease and Prevention Presentation

    Broader source: Energy.gov [DOE]

    A “Zika Virus Disease and Prevention” presentation was made by Bonnie S. Richter, MPH, PhD, at the May 19 Office of Environment, Health, Safety and Security (EHSS) All Hands Meeting.

  17. Metabolomics reveals metabolic biomarkers of Crohn's disease

    SciTech Connect (OSTI)

    Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

    2009-06-01

    The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

  18. Counting small RNA in disease-causing organisms

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    in disease-causing organisms Los Alamos researchers demonstrated improved technical methods capable of directly counting small RNA molecules in pathogenic (disease-causing)...

  19. Geometric validation of self-gating k-space-sorted 4D-MRI vs 4D-CT using a respiratory motion phantom

    SciTech Connect (OSTI)

    Yue, Yong Yang, Wensha; McKenzie, Elizabeth; Tuli, Richard; Wallace, Robert; Fraass, Benedick; Fan, Zhaoyang; Pang, Jianing; Deng, Zixin; Li, Debiao

    2015-10-15

    Purpose: MRI is increasingly being used for radiotherapy planning, simulation, and in-treatment-room motion monitoring. To provide more detailed temporal and spatial MR data for these tasks, we have recently developed a novel self-gated (SG) MRI technique with advantage of k-space phase sorting, high isotropic spatial resolution, and high temporal resolution. The current work describes the validation of this 4D-MRI technique using a MRI- and CT-compatible respiratory motion phantom and comparison to 4D-CT. Methods: The 4D-MRI sequence is based on a spoiled gradient echo-based 3D projection reconstruction sequence with self-gating for 4D-MRI at 3 T. Respiratory phase is resolved by using SG k-space lines as the motion surrogate. 4D-MRI images are reconstructed into ten temporal bins with spatial resolution 1.56 × 1.56 × 1.56 mm{sup 3}. A MRI-CT compatible phantom was designed to validate the performance of the 4D-MRI sequence and 4D-CT imaging. A spherical target (diameter 23 mm, volume 6.37 ml) filled with high-concentration gadolinium (Gd) gel is embedded into a plastic box (35 × 40 × 63 mm{sup 3}) and stabilized with low-concentration Gd gel. The phantom, driven by an air pump, is able to produce human-type breathing patterns between 4 and 30 respiratory cycles/min. 4D-CT of the phantom has been acquired in cine mode, and reconstructed into ten phases with slice thickness 1.25 mm. The 4D images sets were imported into a treatment planning software for target contouring. The geometrical accuracy of the 4D MRI and CT images has been quantified using target volume, flattening, and eccentricity. The target motion was measured by tracking the centroids of the spheres in each individual phase. Motion ground-truth was obtained from input signals and real-time video recordings. Results: The dynamic phantom has been operated in four respiratory rate (RR) settings, 6, 10, 15, and 20/min, and was scanned with 4D-MRI and 4D-CT. 4D-CT images have target

  20. Transgenic Mouse Model of Chronic Beryllium Disease

    SciTech Connect (OSTI)

    Gordon, Terry

    2009-05-26

    Animal models provide powerful tools for dissecting dose-response relationships and pathogenic mechanisms and for testing new treatment paradigms. Mechanistic research on beryllium exposure-disease relationships is severely limited by a general inability to develop a sufficient chronic beryllium disease animal model. Discovery of the Human Leukocyte Antigen (HLA) - DPB1Glu69 genetic susceptibility component of chronic beryllium disease permitted the addition of this human beryllium antigen presentation molecule to an animal genome which may permit development of a better animal model for chronic beryllium disease. Using FVB/N inbred mice, Drs. Rubin and Zhu, successfully produced three strains of HLA-DPB1 Glu 69 transgenic mice. Each mouse strain contains a haplotype of the HLA-DPB1 Glu 69 gene that confers a different magnitude of odds ratio (OR) of risk for chronic beryllium disease: HLA-DPB1*0401 (OR = 0.2), HLA-DPB1*0201 (OR = 15), HLA-DPB1*1701 (OR = 240). In addition, Drs. Rubin and Zhu developed transgenic mice with the human CD4 gene to permit better transmission of signals between T cells and antigen presenting cells. This project has maintained the colonies of these transgenic mice and tested the functionality of the human transgenes.

  1. Chronic beryllium disease: Diagnosis and management

    SciTech Connect (OSTI)

    Rossman, M.D.

    1996-10-01

    Chronic beryllium disease is predominantly a pulmonary granulomatosis that was originally described in 1946. Symptoms usually include dyspnea and cough. Fever, anorexia, and weight loss are common. Skin lesions are the most common extrathoracic manifestation. Granulomatous hepatitis, hypercalcemia, and kidney stones can also occur. Radiographic and physiologic abnormalities are similar to those in sarcoidosis. While traditionally the pathologic changes included granulomas and cellular interstitial changes, the hallmark of the disease today is the well-formed granuloma. Immunologic studies have demonstrated a cell-mediated response to beryllium that is due to an accumulation of CD4{sup +} T cells at the site of disease activity. Diagnosis depends on the demonstration of pathologic changes (i.e., granuloma) and evidence that the granuloma was caused by a hypersensitivity to beryllium (i.e., positive lung proliferative response to beryllium). Using these criteria, the diagnosis of chronic beryllium disease can now be made before the onset of clinical symptoms. Whether, with early diagnosis, the natural course of this condition will be the same as when it was traditionally diagnosed is not known. Currently, corticosteroids are used to treat patients with significant symptoms or evidence of progressive disease. 21 refs.

  2. Global disease monitoring and forecasting with Wikipedia

    SciTech Connect (OSTI)

    Generous, Nicholas; Fairchild, Geoffrey; Deshpande, Alina; Del Valle, Sara Y.; Priedhorsky, Reid; Salathé, Marcel

    2014-11-13

    Infectious disease is a leading threat to public health, economic stability, and other key social structures. Efforts to mitigate these impacts depend on accurate and timely monitoring to measure the risk and progress of disease. Traditional, biologically-focused monitoring techniques are accurate but costly and slow; in response, new techniques based on social internet data, such as social media and search queries, are emerging. These efforts are promising, but important challenges in the areas of scientific peer review, breadth of diseases and countries, and forecasting hamper their operational usefulness. We examine a freely available, open data source for this use: access logs from the online encyclopedia Wikipedia. Using linear models, language as a proxy for location, and a systematic yet simple article selection procedure, we tested 14 location-disease combinations and demonstrate that these data feasibly support an approach that overcomes these challenges. Specifically, our proof-of-concept yields models with up to 0.92, forecasting value up to the 28 days tested, and several pairs of models similar enough to suggest that transferring models from one location to another without re-training is feasible. Based on these preliminary results, we close with a research agenda designed to overcome these challenges and produce a disease monitoring and forecasting system that is significantly more effective, robust, and globally comprehensive than the current state of the art.

  3. Global disease monitoring and forecasting with Wikipedia

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Generous, Nicholas; Fairchild, Geoffrey; Deshpande, Alina; Del Valle, Sara Y.; Priedhorsky, Reid; Salathé, Marcel

    2014-11-13

    Infectious disease is a leading threat to public health, economic stability, and other key social structures. Efforts to mitigate these impacts depend on accurate and timely monitoring to measure the risk and progress of disease. Traditional, biologically-focused monitoring techniques are accurate but costly and slow; in response, new techniques based on social internet data, such as social media and search queries, are emerging. These efforts are promising, but important challenges in the areas of scientific peer review, breadth of diseases and countries, and forecasting hamper their operational usefulness. We examine a freely available, open data source for this use: accessmore » logs from the online encyclopedia Wikipedia. Using linear models, language as a proxy for location, and a systematic yet simple article selection procedure, we tested 14 location-disease combinations and demonstrate that these data feasibly support an approach that overcomes these challenges. Specifically, our proof-of-concept yields models with up to 0.92, forecasting value up to the 28 days tested, and several pairs of models similar enough to suggest that transferring models from one location to another without re-training is feasible. Based on these preliminary results, we close with a research agenda designed to overcome these challenges and produce a disease monitoring and forecasting system that is significantly more effective, robust, and globally comprehensive than the current state of the art.« less

  4. Treatment of Anthrax Disease Frequently Asked Questions

    SciTech Connect (OSTI)

    Judd, Kathleen S.; Young, Joan E.; Lesperance, Ann M.; Malone, John D.

    2010-05-14

    This document provides a summary of Frequently Asked Questions (FAQs) on the treatment of anthrax disease caused by a wide-area release of Bacillus anthracis spores as an act bioterrorism. These FAQs are intended to provide the public health and medical community, as well as others, with guidance and communications to support the response and long-term recovery from an anthrax event.

  5. Associations of indoor carbon dioxide concentrations and environmental susceptibilities with mucous membrane and lower respiratory building related symptoms in the BASE study: Analyses of the 100 building dataset

    SciTech Connect (OSTI)

    Erdmann, Christine A.; Apte, Michael G.

    2003-09-01

    Using the US EPA 100 office-building BASE Study dataset, they conducted multivariate logistic regression analyses to quantify the relationship between indoor CO{sub 2} concentrations (dCO{sub 2}) and mucous membrane (MM) and lower respiratory system (LResp) building related symptoms, adjusting for age, sex, smoking status, presence of carpet in workspace, thermal exposure, relative humidity, and a marker for entrained automobile exhaust. In addition, they tested the hypothesis that certain environmentally-mediated health conditions (e.g., allergies and asthma) confer increased susceptibility to building related symptoms within office buildings. Adjusted odds ratios (ORs) for statistically significant, dose-dependent associations (p < 0.05) for dry eyes, sore throat, nose/sinus congestion, and wheeze symptoms with 100 ppm increases in dCO{sub 2} ranged from 1.1 to 1.2. These results suggest that increases in the ventilation rates per person among typical office buildings will, on average, reduce the prevalence of several building related symptoms by up to 70%, even when these buildings meet the existing ASHRAE ventilation standards for office buildings. Building occupants with certain environmentally-mediated health conditions are more likely to experience building related symptoms than those without these conditions (statistically significant ORs ranged from 2 to 11).

  6. Epidemiological-environemental study of lead acid battery workers. III. Chronic effects of sulfuric acid on the respiratory system and teeth

    SciTech Connect (OSTI)

    Gamble, J.; Jones, W.; Hancock, J.; Meckstroth, R.L.

    1984-10-01

    The effects of long-term exposure to sulfuric acid mist on the teeth and respiratory system were studied in 248 workers in five plants manufacturing lead acid batteries. The prevalence of cough, phlegm, dyspnea, and wheezing as determined by questionnaire were not associated with estimates of cumulative acid exposure. There was only one case of irregular opacities seen on the chest radiographs. There was no statistically significant association of reduced FEV/sub 1/ peak flow, FEF/sub 50/, and FEF/sub 75/ with acid exposure although the higher exposed group had lower mean values. FVC in the high exposure group showed a statistically significant reductioon compared to the low exposure group but there was no significant association when exposure was analyzed as a continuous variable. The ratio of observed to expected prevalence of teeth etching and erosion was about four times greater in the high acid-exposure group. The earliest case of etching occured after 4 months exposure to an estimated average exposure of 0.23 mg/m/sup 3/ sulfuric acid.

  7. Binding of the Respiratory Chain Inhibitor Antimycin to theMitochondrial bc1 Complex: A New Crystal Structure Reveals an AlteredIntramolecular Hydrogen-Bonding Pattern

    SciTech Connect (OSTI)

    Huang, Li-shar; Cobessi, David; Tung, Eric Y.; Berry, Edward A.

    2005-05-10

    Antimycin A (antimycin), one of the first known and most potent inhibitors of the mitochondrial respiratory chain, binds to the quinone reduction site of the cytochrome bc1 complex.Structure-activity-relationship studies have shown that the N-formylamino-salicyl-amide group is responsible for most of the binding specificity, and suggested that a low pKa for the phenolic OH group and an intramolecular H-bond between that OH and the carbonyl O of the salicylamide linkage are important. Two previous X-ray structures of antimycin bound to vertebrate bc1 complex gave conflicting results. A new structure reported here of the bovine mitochondrial bc1 complex at 2.28Angstrom resolution with antimycin bound, allows us for the first time to reliably describe the binding of antimycin and shows that the intramolecular hydrogen bond described in solution and in the small-molecule structure is replaced by one involving the NH rather than carbonyl O of the amide linkage, with rotation of the amide group relative to the aromatic ring. The phenolic OH and formylamino N form H-bonds with conserved Asp228 of cyt b, and the formylamino O H-bonds via a water molecule to Lys227. A strong density the right size and shape for a diatomic molecule is found between the other side of the dilactone ring and the alpha-A helix.

  8. Microdistribution and Long-Term Retention of 239Pu (NO3)4 in the Respiratory Tracts of an Acutely Exposed Plutonium Worker and Experimental Beagle Dogs

    SciTech Connect (OSTI)

    Nielsen, Christopher E.; Wilson, Dulaney A.; Brooks, Antone L.; McCord, Stacey; Dagle, Gerald E.; James, Anthony C.; Tolmachev, Sergei Y.; Thrall, Brian D.; Morgan, William F.

    2012-11-01

    The long-term retention of inhaled soluble forms of plutonium raises concerns as to the potential health effects in persons working in nuclear energy or the nuclear weapons program. The distributions of long-term retained inhaled plutonium-nitrate [239Pu (NO3)4] deposited in the lungs of an accidentally exposed nuclear worker (Human Case 0269) and in the lungs of experimentally exposed beagle dogs with varying initial lung depositions were determined via autoradiographs of selected histological lung, lymph node, trachea, and nasal turbinate tissue sections. These studies showed that both the human and dogs had a non-uniform distribution of plutonium throughout the lung tissue. Fibrotic scar tissue effectively encapsulated a portion of the plutonium and prevented its clearance from the body or translocation to other tissues and diminished dose to organ parenchyma. Alpha radiation activity from deposited plutonium in Human Case 0269 was observed primarily along the sub-pleural regions while no alpha activity was seen in the tracheobronchial lymph nodes of this individual. However, relatively high activity levels in the tracheobronchial lymph nodes of the beagles indicated the lymphatic system was effective in clearing deposited plutonium from the lung tissues. In both the human case and beagle dogs, the appearance of retained plutonium within the respiratory tract was inconsistent with current biokinetic models of clearance for soluble forms of plutonium. Bound plutonium can have a marked effect on the dose to the lungs and subsequent radiation exposure has the potential increase in cancer risk.

  9. Isotoxic Dose Escalation in the Treatment of Lung Cancer by Means of Heterogeneous Dose Distributions in the Presence of Respiratory Motion

    SciTech Connect (OSTI)

    Baker, Mariwan; Nielsen, Morten [Laboratory of Radiation Physics, Odense University Hospital, Odense (Denmark); Hansen, Olfred [Department of Oncology, Odense University Hospital, Odense (Denmark); Jahn, Jonas Westberg [Laboratory of Radiation Physics, Odense University Hospital, Odense (Denmark); Korreman, Stine [Department of Radiation Oncology, Copenhagen University Hospital, Copenhagen (Denmark); Brink, Carsten, E-mail: carsten.brink@ouh.regionsyddanmark.dk [Laboratory of Radiation Physics, Odense University Hospital, Odense (Denmark); Institute of Clinical Research, University of Southern Denmark, Odense (Denmark)

    2011-11-01

    Purpose: To test, in the presence of intrafractional respiration movement, a margin recipe valid for a homogeneous and conformal dose distribution and to test whether the use of smaller margins combined with heterogeneous dose distributions allows an isotoxic dose escalation when respiratory motion is considered. Methods and Materials: Twenty-three Stage II-III non-small-cell lung cancer patients underwent four-dimensional computed tomography scanning. The gross tumor volume and clinical target volume (CTV) were outlined in the mid-ventilation phase. The CTV-to-planning target volume (PTV) margin was calculated by use of a standard margin recipe and the patient-specific respiration pattern. Standard three-dimensional treatment plans were generated and recalculated on the remaining respiration phases. The planning was repeated for a CTV-to-PTV margin decreased by 2.5 and 5 mm relative to the initial margin in all directions. Time-averaged dose-volume histograms (four-dimensional dose-volume histograms) were calculated to evaluate the CTV-to-PTV margin. Finally, the dose was escalated in the plans with decreased PTV such that the mean lung dose (predictor of radiation-induced pneumonitis) was equal to mean lung dose in the plan by use of the initially calculated margin. Results: A reduction of the standard margin by 2.5 mm compared with the recipe resulted in too low of a minimum dose for some patients. A combination of dose escalation and use of heterogeneous dose distribution was able to increase the minimum dose to the target by approximately 10% and 20% for a CTV-to-PTV margin reduction of 2.5 mm and 5.0 mm, respectively. Conclusion: The margin recipe is valid for intrafractional respiration-induced tumor motions. It is possible to increase the dose to the target without increased mean lung dose with an inhomogeneous dose distribution.

  10. Science On Tap - Understanding HIV and Infectious Diseases

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Science On Tap - Understanding HIV and Infectious Diseases Science On Tap - Understanding HIV and Infectious Diseases WHEN: Sep 17, 2015 5:30 PM - 7:00 PM WHERE: UnQuarked Wine...

  11. Software speeds detection of diseases and cancer-treatment targets

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Software speeds detection of diseases Software speeds detection of diseases and cancer-treatment targets The Lab has released an updated version of software that is now capable of ...

  12. NIOSH Alert-Preventing Sentization and Disease from Beryllium | Department

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    of Energy NIOSH Alert-Preventing Sentization and Disease from Beryllium NIOSH Alert-Preventing Sentization and Disease from Beryllium February 3, 2011 Preventing Sensitization and Disease from Beryllium Exposure The National Institute for Occupational Safety and Health (NIOSH) requests assistance in preventing beryllium sensitization and chronic beryllium disease. Development of these conditions requires exposure to beryllium and is affected by both job tasks and genetic factors. Some jobs

  13. Presentation, Zika Virus Disease and Prevention | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Presentation, Zika Virus Disease and Prevention Presentation, Zika Virus Disease and Prevention May 19, 2016 Dr. Richter presented information about the rapid evolution of the Zika virus, the regions reporting active mosquito transmission of the Zika virus, the disease symptoms and preventative steps. Presentation, Zika Virus Disease and Prevention (678.7 KB) More Documents & Publications Worker Health Summary, 1995-2004 CAIRS Direct Data Entry (CDDE) Online Training Package FAQS Reference

  14. A customizable model for chronic disease coordination: Lessons learned from the coordinated chronic disease program

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Voetsch, Karen; Sequeira, Sonia; Chavez, Amy Holmes

    2016-03-31

    In 2012, the Centers for Disease Control and Prevention provided funding and technical assistance to all states and territories to implement the Coordinated Chronic Disease Program, marking the first time that all state health departments had federal resources to coordinate chronic disease prevention and control programs. This article describes lessons learned from this initiative and identifies key elements of a coordinated approach. We analyzed 80 programmatic documents from 21 states and conducted semistructured interviews with 7 chronic disease directors. Six overarching themes emerged: 1) focused agenda, 2) identification of functions, 3) comprehensive planning, 4) collaborative leadership and expertise, 5) managedmore » resources, and 6) relationship building. Furthermore, these elements supported 4 essential activities: 1) evidence-based interventions, 2) strategic use of staff, 3) consistent communication, and 4) strong program infrastructure. On the basis of these elements and activities, we propose a conceptual model that frames overarching concepts, skills, and strategies needed to coordinate state chronic disease prevention and control programs.« less

  15. Visualizing Brain Metals in Health and Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Visualizing Brain Metals in Health and Disease figure 1 Fig. 1. Rapid-scanning x-ray fluorescence mapping ex perimental setup. Synchrotron x-rays at 11 keV passed through a 50 µm aperture (Ap). The beam intensity was monitored with a N2-filled ion chamber (I0). The brain slice was mounted vertically on a motorized stage (St) at 45° to the incident x-ray beam and raster scanned in the beam. A 13-element Ge detector (Ge) was positioned at a 90° angle to the beam. We all require iron, copper and

  16. Chronic Beryllium Disease Prevention Program Report

    SciTech Connect (OSTI)

    Lee, S

    2012-03-29

    This document describes how Lawrence Livermore National Laboratory (LLNL) meets the requirements and management practices of federal regulation 10 CFR 850, 'Chronic Beryllium Disease Prevention Program (CBDPP).' This revision of the LLNL CBDPP incorporates clarification and editorial changes based on lessons learned from employee discussions, observations and reviews of Department of Energy (DOE) Complex and commercial industry beryllium (Be) safety programs. The information is used to strengthen beryllium safety practices at LLNL, particularly in the areas of: (1) Management of small parts and components; and (2) Communication of program status to employees. Future changes to LLNL beryllium activities and on-going operating experience will be incorporated into the program as described in Section S, 'Performance Feedback.'

  17. Optical detection dental disease using polarized light

    DOE Patents [OSTI]

    Everett, Matthew J.; Colston, Jr., Billy W.; Sathyam, Ujwal S.; Da Silva, Luiz B.; Fried, Daniel

    2003-01-01

    A polarization sensitive optical imaging system is used to detect changes in polarization in dental tissues to aid the diagnosis of dental disease such as caries. The degree of depolarization is measured by illuminating the dental tissue with polarized light and measuring the polarization state of the backscattered light. The polarization state of this reflected light is analyzed using optical polarimetric imaging techniques. A hand-held fiber optic dental probe is used in vivo to direct the incident beam to the dental tissue and collect the reflected light. To provide depth-resolved characterization of the dental tissue, the polarization diagnostics may be incorporated into optical coherence domain reflectometry and optical coherence tomography (OCDR/OCT) systems, which enables identification of subsurface depolarization sites associated with demineralization of enamel or bone.

  18. Automated diagnostic kiosk for diagnosing diseases

    SciTech Connect (OSTI)

    Regan, John Frederick; Birch, James Michael

    2014-02-11

    An automated and autonomous diagnostic apparatus that is capable of dispensing collection vials and collections kits to users interesting in collecting a biological sample and submitting their collected sample contained within a collection vial into the apparatus for automated diagnostic services. The user communicates with the apparatus through a touch-screen monitor. A user is able to enter personnel information into the apparatus including medical history, insurance information, co-payment, and answer a series of questions regarding their illness, which is used to determine the assay most likely to yield a positive result. Remotely-located physicians can communicate with users of the apparatus using video tele-medicine and request specific assays to be performed. The apparatus archives submitted samples for additional testing. Users may receive their assay results electronically. Users may allow the uploading of their diagnoses into a central databank for disease surveillance purposes.

  19. Chronic Beryllium Disease Prevention Program (10 CFR 850) | Department of

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Energy Chronic Beryllium Disease Prevention Program (10 CFR 850) Chronic Beryllium Disease Prevention Program (10 CFR 850) The DOE established a chronic beryllium disease prevention program (CBDPP) to reduce the number of workers currently exposed to beryllium in the course of their work at DOE facilities managed by DOE or its contractors, minimize the levels of, and potential for, exposure to beryllium, and establish medical surveillance requirements to ensure early detection of the

  20. Analyzing genetic tree sheds new light on disease outbreaks

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Analyzing genetic tree sheds new light on disease outbreaks Analyzing genetic tree sheds new light on disease outbreaks The team used computational phylogenetic analysis to examine how strains of HIV, both in computer modeling and compared with real-life case studies, would be transmitted. February 25, 2016 Using computational techniques, scientists at Los Alamos National Laboratory are working to more clearly understand how diseases such as HIV are spread. In this image, arrows indicate actual

  1. Recombinant herpes simplex virus useful for treating neoplastic disease

    DOE Patents [OSTI]

    Whitley, Richard J.; Roizman, Bernard

    2010-06-29

    Recombinant herpes simplex viruses comprising DNA encoding cytokines and methods for treating neoplastic diseases using the inventive recombinant viruses are disclosed.

  2. Indoor air quality & airborne disease control in healthcare facilities...

    Office of Scientific and Technical Information (OSTI)

    Subject: 32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATION; MEDICAL ESTABLISHMENTS; INDOOR AIR POLLUTION; CONTROL SYSTEMS; DISEASES; THERMAL COMFORT; SPACE HVAC SYSTEMS Word ...

  3. AND NUCLEAR MEDICINE; DIAGNOSIS; DISEASES; GAMMA CAMERAS; GENETICS...

    Office of Scientific and Technical Information (OSTI)

    Converting energy to medical progress nuclear medicine NONE 62 RADIOLOGY AND NUCLEAR MEDICINE; DIAGNOSIS; DISEASES; GAMMA CAMERAS; GENETICS; NUCLEAR MEDICINE; PATIENTS; RADIATION...

  4. Update on the Hanford Site Chronic Beryllium Disease Prevention...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Chronic Beryllium Disease Prevention Program (CBDPP) Stan Branch Richland Operations Office Hanford Advisory Board Health, Safety and Environmental Protection Committee January 7,...

  5. Methods of treating parkinson's disease using viral vectors

    DOE Patents [OSTI]

    Bankiewicz, Krys; Cunningham, Janet

    2009-05-19

    Methods of delivering viral vectors, particularly recombinant AAV virions, to the CNS are provided. Also provided are methods of treating Parkinson's Disease.

  6. Structure of the Newcastle disease virus hemagglutinin-neuraminidase...

    Office of Scientific and Technical Information (OSTI)

    virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk Citation Details In-Document Search Title: Structure of the Newcastle disease virus ...

  7. Polymorphic microsatellites and Wilson disease (WD)

    SciTech Connect (OSTI)

    Stewart, E.A.; Cavalli-Sforza, L.L. ); White, A.; Tomfohrde, J.; Osborne-Lawrence, S.; Prestidge, L.; Bowcock, A.M. ); Bonne-Tamir, B.; Scheinberg, I.H.; George-Hyslop, P.; Giagheddu, M.; Kim, J.W.; Seo, J.K.; Lo, W.H.Y.; Ivanova-Smolenskaya, I.A.; Limborska, S.A.; Farrer, L.A.

    1993-10-01

    Wilson disease (WD), an autosomal recessive disorder of copper metabolism, has been previously mapped to chromosome 13q. Highly informative PCR-based polymorphic microsatellites closely linked to the WD locus (WND) at 13q14.3, as well as sequence-tagged sites for closely linked loci, are described. Two polymorphic microsatellite markers at D13S118 and D13S119 lie within 3 cM of WND. Two others (D13S227 and D13S228) were derived from a yeast artificial chromosome containing D13S31. These were placed on a genetic linkage map of chromosome 13 and were typed in 74 multiplex WD families from a variety of geographic origins (166 affected members). Multipoint analysis provides very high odds that the location of WND is between D13S31/D13S227/D13S228 and D13S59. Previous odds with RFLP-based markers were only 7:1 more likely than any other location. Current odds are 5,000:1. Preclinical testing of three cases of WD by using the highly informative polymorphic microsatellite markers is described. The markers described ensure that 95% of predictive tests using DNA from both parents and from at least one affected sib will have an accuracy >99%. 29 refs., 2 figs., 3 tabs.

  8. Adaptation of the modified BoucWen model to compensate for hysteresis in respiratory motion for the list-mode binning of cardiac SPECT and PET acquisitions: Testing using MRI

    SciTech Connect (OSTI)

    Dasari, Paul K. R.; Shazeeb, Mohammed Salman; Knik, Arda; Lindsay, Clifford; Mukherjee, Joyeeta M.; Johnson, Karen L.; King, Michael A.

    2014-11-01

    Purpose: Binning list-mode acquisitions as a function of a surrogate signal related to respiration has been employed to reduce the impact of respiratory motion on image quality in cardiac emission tomography (SPECT and PET). Inherent in amplitude binning is the assumption that there is a monotonic relationship between the amplitude of the surrogate signal and respiratory motion of the heart. This assumption is not valid in the presence of hysteresis when heart motion exhibits a different relationship with the surrogate during inspiration and expiration. The purpose of this study was to investigate the novel approach of using the BoucWen (BW) model to provide a signal accounting for hysteresis when binning list-mode data with the goal of thereby improving motion correction. The study is based on the authors previous observations that hysteresis between chest and abdomen markers was indicative of hysteresis between abdomen markers and the internal motion of the heart. Methods: In 19 healthy volunteers, they determined the internal motion of the heart and diaphragm in the superiorinferior direction during free breathing using MRI navigators. A visual tracking system (VTS) synchronized with MRI acquisition tracked the anteriorposterior motions of external markers placed on the chest and abdomen. These data were employed to develop and test the BoucWen model by inputting the VTS derived chest and abdomen motions into it and using the resulting output signals as surrogates for cardiac motion. The data of the volunteers were divided into training and testing sets. The training set was used to obtain initial values for the model parameters for all of the volunteers in the set, and for set members based on whether they were or were not classified as exhibiting hysteresis using a metric derived from the markers. These initial parameters were then employed with the testing set to estimate output signals. Pearsons linear correlation coefficient between the abdomen, chest

  9. Development and Characterization of A Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out

    SciTech Connect (OSTI)

    Smith, S M; Danganan, L; Tammero, L; Vitalis, B; Lenhoff, R; Naraghi-arani, P; Hindson, B

    2007-08-06

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed candidate multiplexed assays that may potentially be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the ability to improve our nation's capability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect food and agricultural resources with a diagnostic test which could enhance the nation's capabilities for early detection of a foreign animal disease. In FY2005 with funding from the DHS, LLNL developed the first version (Version 1.0) of a multiplexed (MUX) nucleic-acid-based RT-PCR assay that included signatures for foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases (FADs) of swine, Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease Virus (SVDV), and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus [BPSV], Orf of sheep, and Pseudocowpox). In FY06, LLNL has developed Bovine and Porcine species-specific panel which included existing signatures from Version 1.0 panel as well as new signatures. The MUX RT-PCR porcine assay for detection of FMDV includes the FADs, VESV and SVD in addition to vesicular stomatitis virus (VSV) and porcine reproductive and respiratory syndrome (PRRS). LLNL has also developed a MUX RT-PCR bovine assay for detection of FMDV with rule out tests for the two bovine FADs malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV

  10. Associations of indoor carbon dioxide concentrations, VOCS, environmental susceptibilities with mucous membrane and lower respiratory sick building syndrome symptoms in the BASE study: Analyses of the 100 building dataset

    SciTech Connect (OSTI)

    Apte, M.G.; Erdmann, C.A.

    2002-10-01

    Using the 100 office-building Building Assessment Survey and Evaluation (BASE) Study dataset, we performed multivariate logistic regression analyses to quantify the associations between indoor minus outdoor CO{sub 2} (dCO{sub 2}) concentrations and mucous membrane (MM) and lower respiratory system (Lresp) Sick Building Syndrome (SBS) symptoms, adjusting for age, sex, smoking status, presence of carpet in workspace, thermal exposure, relative humidity, and a marker for entrained automobile exhaust. Using principal components analysis we identified a number of possible sources of 73 measured volatile organic compounds in the office buildings, and assessed the impact of these VOCs on the probability of presenting the SBS symptoms. Additionally we included analysis adjusting for the risks for predisposition of having SBS symptoms associated with the allergic, asthmatic, and environmentally sensitive subpopulations within the office buildings. Adjusted odds ratios (ORs) for statistically significant, dose-dependant associations (p<0.05) for dry eyes, sore throat, nose/sinus congestion, and wheeze symptoms with 100-ppm increases in dCO{sub 2} ranged from 1.1 to 1.2. These results suggest that increases in the ventilation rates per person among typical office buildings will, on average significantly reduce the prevalence of several SBS symptoms, up to 80%, even when these buildings meet the existing ASHRAE ventilation standards for office buildings. VOC sources were observed to play an role in direct association with mucous membrane and lower respiratory irritation, and possibly to be indirectly involved in indoor chemical reactions with ozone that produce irritating compounds associated with SBS symptoms. O-xylene, possibly emitted from furniture coatings was associated with shortness of breath (OR at the maximum concentration = 8, p < 0.05). The environmental sensitivities of a large subset of the office building population add to the overall risk of SBS symptoms (ORs

  11. Development and Characterization of a Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out Supplemental Materials

    SciTech Connect (OSTI)

    Smith, S; Danganan, L; Tammero, L; Lenhoff, R; Naraghi-arani, P; Hindson, B

    2007-08-06

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed advanced rapid diagnostics that may be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the potential to improve our nation's ability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect animal populations of high economic importance in the United States. Under 2005 DHS funding we have developed multiplexed (MUX) nucleic-acid-based PCR assays that combine foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease (SVD) and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1 or Infectious Bovine Rhinotracheitus IBR), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus BPSV, Orf of sheep, and Pseudocowpox). Under 2006 funding we have developed a Multiplexed PCR [MUX] porcine assay for detection of FMDV with rule out tests for VESV and SVD foreign animal diseases in addition to one other domestic vesicular animal disease vesicular stomatitis virus (VSV) and one domestic animal disease of swine porcine reproductive and respiratory syndrome (PRRS). We have also developed a MUX bovine assay for detection of FMDV with rule out tests for the two bovine foreign animal diseases malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV), bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitus virus (BHV-1), bluetongue virus (BTV), and the Parapox viruses

  12. Reductions in (/sup 3/H)nicotinic acetylcholine binding in Alzheimer's disease and Parkinson's disease: an autoradiographic study

    SciTech Connect (OSTI)

    Whitehouse, P.J.; Martino, A.M.; Wagster, M.V.; Price, D.L.; Mayeux, R.; Atack, J.R.; Kellar, K.J.

    1988-05-01

    In Alzheimer's disease (AD) and Parkinson's disease (PD), dysfunction in the basal forebrain cholinergic system is accompanied by a consistent loss of presynaptic cholinergic markers in cortex, but changes in cholinergic receptor binding sites are poorly understood. In the present study, we used receptor autoradiography to map the distribution of nicotinic (/sup 3/H)acetylcholine binding sites in cortices of individuals with AD and PD and matched control subjects. In both diseases, a profound loss of nicotinic receptors occurs in all cortical layers, particularly the deepest layers.

  13. Timing of testing and treatment for asymptomatic diseases

    SciTech Connect (OSTI)

    K?rk?zlar, Eser; Faissol, Daniel M.; Griffin, Paul M.; Swann, Julie L.

    2010-07-01

    Many papers in the medical literature analyze the cost-effectiveness of screening for diseases by comparing a limited number of a priori testing policies under estimated problem parameters. However, this may be insufficient to determine the best timing of the tests or incorporate changes over time. In this paper, we develop and solve a Markov Decision Process (MDP) model for a simple class of asymptomatic diseases in order to provide the building blocks for analysis of a more general class of diseases. We provide a computationally efficient method for determining a cost-effective dynamic intervention strategy that takes into account (i) the results of the previous test for each individual and (ii) the change in the individuals behavior based on awareness of the disease. We demonstrate the usefulness of the approach by applying the results to screening decisions for Hepatitis C (HCV) using medical data, and compare our findings to current HCV screening recommendations.

  14. Update on the Hanford Site Chronic Beryllium Disease Prevention...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    by DOE- EM on March 13, 2013 2 Be CAP Status * Rev. 1 of the Hanford site wide Chronic Beryllium Disease Prevention Program (CBDPP) was approved by DOE March 7, 2012 * Rev....

  15. Array-based detection of genetic alterations associated with disease

    DOE Patents [OSTI]

    Pinkel, Daniel; Albertson, Donna G.; Gray, Joe W.

    2007-09-11

    The present invention relates to DNA sequences from regions of copy number change on chromosome 20. The sequences can be used in hybridization methods for the identification of chromosomal abnormalities associated with various diseases.

  16. Inexpensive handheld tests for diseases are in sight

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cai has a passion: to use her expertise in biochemistry and genetics to create a non-invasive, point-of-care diagnostic device for disease detection. In following her passion, she...

  17. Science On Tap - Understanding HIV and Infectious Diseases

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Science On Tap - Understanding HIV and Infectious Diseases Science On Tap - Understanding HIV and Infectious Diseases WHEN: Sep 17, 2015 5:30 PM - 7:00 PM WHERE: UnQuarked Wine Room 145 Central Park Square, Los Alamos, New Mexico, 87544 USA SPEAKER: Ruy Ribeiro, Los Alamos National Laboratory CONTACT: Jessica Privette 505 667-0375 CATEGORY: Bradbury INTERNAL: Calendar Login Science On Tap - Every Third Thursday Event Description Science On Tap happens every third Thursday of the month, featuring

  18. Engineering disease resistance with pectate lyase-like genes

    DOE Patents [OSTI]

    Vogel, John; Somerville, Shauna

    2005-03-08

    A mutant gene coding for pectate lyase and homologs thereof is provided, which when incorporated in transgenic plants effect an increased level disease resistance in such plants. Also is provided the polypeptide sequence for the pectate lyase of the present invention. Methods of obtaining the mutant gene, producing transgenic plants which include the nucleotide sequence for the mutant gene and producing improved disease resistance in a crop of such transgenic plants are also provided.

  19. Software speeds detection of diseases and cancer-treatment targets

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Software speeds detection of diseases Software speeds detection of diseases and cancer-treatment targets The Lab has released an updated version of software that is now capable of identifying DNA from viruses and all parts of the Tree of Life. December 1, 2014 With Sequedex, a laptop computer can analyze DNA sequences faster than any current DNA sequencer can create them. With Sequedex, a laptop computer can analyze DNA sequences faster than any current DNA sequencer can create them. Contact

  20. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    SciTech Connect (OSTI)

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil K.; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.

    2012-10-05

    Acute Lyme disease results from transmission of and infection by the bacterium Borrelia burgdorferi following a tick bite. During acute infection, bacteria can disseminate to the central nervous system (CNS) leading to the development of Lyme meningitis. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing for a deep view into the proteome for a cohort of patients with early-disseminated Lyme disease and CSF inflammation leading to the identification of proteins that reflect host responses, which are distinct for subjects with acute Lyme disease. Additionally, we analyzed individual patient samples and quantified changes in protein abundance employing label-free quantitative mass spectrometry based methods. The measured changes in protein abundances reflect the impact of acute Lyme disease on the CNS as presented in CSF. We have identified 89 proteins that differ significantly in abundance in patients with acute Lyme disease. A number of the differentially abundant proteins have been found to be localized to brain synapse and thus constitute important leads for better understanding of the neurological consequence of disseminated Lyme disease.

  1. Airborne spread of foot-and-mouth disease - model intercomparison

    SciTech Connect (OSTI)

    Gloster, J; Jones, A; Redington, A; Burgin, L; Sorensen, J H; Turner, R; Dillon, M; Hullinger, P; Simpson, M; Astrup, P; Garner, G; Stewart, P; D'Amours, R; Sellers, R; Paton, D

    2008-09-04

    Foot-and-mouth disease is a highly infectious vesicular disease of cloven-hoofed animals caused by foot-and-mouth disease virus. It spreads by direct contact between animals, by animal products (milk, meat and semen), by mechanical transfer on people or fomites and by the airborne route - with the relative importance of each mechanism depending on the particular outbreak characteristics. Over the years a number of workers have developed or adapted atmospheric dispersion models to assess the risk of foot-and-mouth disease virus spread through the air. Six of these models were compared at a workshop hosted by the Institute for Animal Health/Met Office during 2008. A number of key issues emerged from the workshop and subsequent modelling work: (1) in general all of the models predicted similar directions for 'at risk' livestock with much of the remaining differences strongly related to differences in the meteorological data used; (2) determination of an accurate sequence of events is highly important, especially if the meteorological conditions vary substantially during the virus emission period; and (3) differences in assumptions made about virus release, environmental fate, and subsequent infection can substantially modify the size and location of the downwind risk area. Close relationships have now been established between participants, which in the event of an outbreak of disease could be readily activated to supply advice or modelling support.

  2. MO-G-BRF-01: BEST IN PHYSICS (JOINT IMAGING-THERAPY) - Sensitivity of PET-Based Texture Features to Respiratory Motion in Non-Small Cell Lung Cancer (NSCLC)

    SciTech Connect (OSTI)

    Yip, S; Aerts, H; Berbeco, R; McCall, K; Aristophanous, M; Chen, A

    2014-06-15

    Purpose: PET-based texture features are used to quantify tumor heterogeneity due to their predictive power in treatment outcome. We investigated the sensitivity of texture features to tumor motion by comparing whole body (3D) and respiratory-gated (4D) PET imaging. Methods: Twenty-six patients (34 lesions) received 3D and 4D [F-18]FDG-PET scans before chemo-radiotherapy. The acquired 4D data were retrospectively binned into five breathing phases to create the 4D image sequence. Four texture features (Coarseness, Contrast, Busyness, and Complexity) were computed within the the physician-defined tumor volume. The relative difference (δ) in each measure between the 3D- and 4D-PET imaging was calculated. Wilcoxon signed-rank test (p<0.01) was used to determine if δ was significantly different from zero. Coefficient of variation (CV) was used to determine the variability in the texture features between all 4D-PET phases. Pearson correlation coefficient was used to investigate the impact of tumor size and motion amplitude on δ. Results: Significant differences (p<<0.01) between 3D and 4D imaging were found for Coarseness, Busyness, and Complexity. The difference for Contrast was not significant (p>0.24). 4D-PET increased Busyness (∼20%) and Complexity (∼20%), and decreased Coarseness (∼10%) and Contrast (∼5%) compared to 3D-PET. Nearly negligible variability (CV=3.9%) was found between the 4D phase bins for Coarseness and Complexity. Moderate variability was found for Contrast and Busyness (CV∼10%). Poor correlation was found between the tumor volume and δ for the texture features (R=−0.34−0.34). Motion amplitude had moderate impact on δ for Contrast and Busyness (R=−0.64− 0.54) and no impact for Coarseness and Complexity (R=−0.29−0.17). Conclusion: Substantial differences in textures were found between 3D and 4D-PET imaging. Moreover, the variability between phase bins for Coarseness and Complexity was negligible, suggesting that similar

  3. Remote sensing, global warming, and vector-borne disease

    SciTech Connect (OSTI)

    Wood, B.; Beck, L.; Dister, S.; Lobitz, B.

    1997-12-31

    The relationship between climate change and the pattern of vector-borne disease can be viewed at a variety of spatial and temporal scales. At one extreme are changes such as global warming, which are continental in scale and occur over periods of years, decades, or longer. At the opposite extreme are changes associated with severe weather events, which can occur at local and regional scales over periods of days, weeks, or months. Key ecological factors affecting the distribution of vector-borne diseases include temperature, precipitation, and habitat availability, and their impact on vectors, pathogens, reservoirs, and hosts. Global warming can potentially alter these factors, thereby affecting the spatial and temporal patterns of disease.

  4. Investigation of saliva of patients with periodontal disease using NAA

    SciTech Connect (OSTI)

    Zamboni, C. B.; Metairon, S.; Medeiros, I. M. M. A.

    2013-05-06

    In this study the non-stimulated whole saliva of 26 healthy subjects (mean age 33.9 {+-} 11.0 years, range: 26 to 49 years) and 11 patients with periodontal disease (mean age 41.7 {+-} 11.5 years; range 29 to 55 years) was investigated using Neutron Activation Analysis (NAA) technique. The samples were obtained from donors at Sao Paulo city (Brazil). The analyses were performed in the nuclear reactor IEA-R1 (3.5-4.5MW, pool type) at IPEN/CNEN-SP (Brazil). Considerable changes in Ca and S saliva's level were identified in patients with periodontal disease suggesting they can be used as monitors of periodontal diseases.

  5. Association between environmental exposure to pesticides and neurodegenerative diseases

    SciTech Connect (OSTI)

    Parron, Tesifon; Requena, Mar; Hernandez, Antonio F.; Alarcon, Raquel

    2011-11-15

    Preliminary studies have shown associations between chronic pesticide exposure in occupational settings and neurological disorders. However, data on the effects of long-term non-occupational exposures are too sparse to allow any conclusions. This study examines the influence of environmental pesticide exposure on a number of neuropsychiatric conditions and discusses their underlying pathologic mechanisms. An ecological study was conducted using averaged prevalence rates of Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebral degeneration, polyneuropathies, affective psychosis and suicide attempts in selected Andalusian health districts categorized into areas of high and low environmental pesticide exposure based on the number of hectares devoted to intensive agriculture and pesticide sales per capita. A total of 17,429 cases were collected from computerized hospital records (minimum dataset) between 1998 and 2005. Prevalence rates and the risk of having Alzheimer's disease, Parkinson's disease, multiple sclerosis and suicide were significantly higher in districts with greater pesticide use as compared to those with lower pesticide use. The multivariate analyses showed that the population living in areas with high pesticide use had an increased risk for Alzheimer's disease and suicide attempts and that males living in these areas had increased risks for polyneuropathies, affective disorders and suicide attempts. In conclusion, this study supports and extends previous findings and provides an indication that environmental exposure to pesticides may affect the human health by increasing the incidence of certain neurological disorders at the level of the general population. -- Highlights: Black-Right-Pointing-Pointer Environmental exposure to pesticides and neurodegenerative-psychiatric disorders. Black-Right-Pointing-Pointer Increased risk for Alzheimer's disease and suicide attempts in high exposure areas. Black-Right-Pointing-Pointer Males from

  6. Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Xia, Jing; Rocke, David M.; Perry, George; Ray, Monika

    2014-01-01

    In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

  7. Device, array, and methods for disease detection and analysis

    DOE Patents [OSTI]

    Rao, Rupa S.; Lane, Stephen M.; Matthews, Dennis L.; Coleman, Matthew A.

    2016-06-14

    A device and array coupled to capture molecules are provided. Specifically, the device and array can be used for detecting the presence and concentration of biomarkers in a sample from a subject. The device and array can also allow the use of a method for scoring a sample for, e.g., the purpose of diagnosing a disease. The method can also be advantageous to applications where there is a need to accurately determine the disease stage of a subject for the purpose of making therapeutic decisions.

  8. Compositions and Methods for the Treatment of Pierce's Disease

    DOE Patents [OSTI]

    Gupta, Goutam

    2008-10-07

    Chimeric anti-microbial proteins, compositions, and methods for the therapeutic and prophylactic treatment of plant diseases caused by the bacterial pathogen Xylella fastidiosa are provided. The anti-microbial proteins of the invention generally comprise a surface recognition domain polypeptide, capable of binding to a bacterial membrane component, fused to a bacterial lysis domain polypeptide, capable of affecting lysis or rupture of the bacterial membrane, typically via a fused polypeptide linker. In particular, methods and compositions for the treatment or prevention of Pierce's disease of grapevines are provided. Methods for the generation of transgenic Vitus vinefera plants expressing xylem-secreted anti-microbial chimeras are also provided.

  9. Azasugar inhibitors as pharmacological chaperones for Krabbe disease

    SciTech Connect (OSTI)

    Hill, Chris H.; Viuff, Agnete H.; Spratley, Samantha J.; Salamone, Stéphane; Christensen, Stig H.; Read, Randy J.; Moriarty, Nigel W.; Jensen, Henrik H.; Deane, Janet E.

    2015-03-23

    Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.

  10. Ventilation assessment of an infectious disease ward housing TB patients

    SciTech Connect (OSTI)

    Crandall, M.S.; Hughes, R.T.

    1996-05-01

    The National Institute for Occupational Safety and Health (NIOSH) assisted the National Center for Infectious Diseases and the National Center for Prevention Services, Centers for Disease Control (CDC), in their investigation of nosocomial transmission of tuberculosis (TB) at a Veterans Administration Medical Center. NIOSH was asked to determine whether ventilation requirements expected of TB patient isolation facilities were being met. In the Infectious Disease ward (513), 24 staff were given a tuberculin skin test (TST) in the summer of 1991. Eleven (46%) were positive then, and 13 were negative. Ten of the 13 testing negative in 1991 were retested within a year, and 5 (50%) converted to a positive TST. NIOSH investigators made ventilation measurements on Ward 5B, an infectious diseases ward housing patients with acquired immune deficiency syndrome (AIDS), two of them with infectious TB, to determine the status of the systems serving the area. Airflow measurements showed that in all the single-patient rooms, exhaust airflow was essentially zero. The average supply airflow varied above and below the designed value. These rooms were all positively pressurized, which would be recommended for the isolation of infectious patients. Based on the measurements made during this evaluation, it was recommended that a separate isolation facility be constructed in the hospital to house infectious patients. Interim corrective measures for the systems in place were also recommended.

  11. Azasugar inhibitors as pharmacological chaperones for Krabbe disease

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hill, Chris H.; Viuff, Agnete H.; Spratley, Samantha J.; Salamone, Stéphane; Christensen, Stig H.; Read, Randy J.; Moriarty, Nigel W.; Jensen, Henrik H.; Deane, Janet E.

    2015-03-23

    Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe amore » new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.« less

  12. Possible mechanisms for arsenic-induced proliferative diseases

    SciTech Connect (OSTI)

    Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A.

    1996-12-31

    Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

  13. The Human Phenotype Ontology: Semantic Unification of Common and Rare Disease

    SciTech Connect (OSTI)

    Groza, Tudor; Khler, Sebastian; Moldenhauer, Dawid; Vasilevsky, Nicole; Baynam, Gareth; Zemojtel, Tomasz; Schriml, LynnMarie; Kibbe, WarrenAlden; Schofield, PaulN.; Beck, Tim; Vasant, Drashtti; Brookes, AnthonyJ.; Zankl, Andreas; Washington, NicoleL.; Mungall, ChristopherJ.; Lewis, SuzannaE.; Haendel, Melissa A.; Parkinson, Helen; Robinson, PeterN.

    2015-06-25

    The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000 rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available.

  14. Glycoprotein 5 of porcine reproductive and respiratory syndrome virus strain SD16 inhibits viral replication and causes G2/M cell cycle arrest, but does not induce cellular apoptosis in Marc-145 cells

    SciTech Connect (OSTI)

    Mu, Yang; Li, Liangliang; Zhang, Beibei; Huang, Baicheng; Gao, Jiming; and others

    2015-10-15

    Cell apoptosis is common after infection with porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV GP5 has been reported to induce cell apoptosis. To further understand the role of GP5 in PRRSV induced cell apoptosis, we established Marc-145 cell lines stably expressing full-length GP5, GP5{sup Δ84-96} (aa 84-96 deletion), and GP5{sup Δ97-119} (aa 97-119 deletion). Cell proliferation, cell cycle progression, cell apoptosis and virus replication in these cell lines were evaluated. Neither truncated nor full-length GP5 induced cell apoptosis in Marc-145 cells. However, GP5{sup Δ97-119}, but not full-length or GP5{sup Δ84-96}, induced a cell cycle arrest at the G2/M phase resulting in a reduction in the growth of Marc-145 cells. Additionally, GP5{sup Δ84-96} inhibited the replication of PRRSV in Marc-145 cells through induction of IFN-β. These findings suggest that PRRSV GP5 is not responsible for inducing cell apoptosis in Marc-145 cells under these experimental conditions; however it has other important roles in virus/host cell biology. - Highlights: • Marc-145 cell lines stable expression PRRSV GP5 or truncated GP5 were constructed. • GP5{sup Δ97-119} expression in Marc-145 cell induced cell cycle arrest at G2/M phase. • Expression of GP5 and truncated GP5 could not induce Marc-145 cells apoptosis. • PRRSV replication in Marc-145-GP5{sup Δ84-96} was significantly inhibited.

  15. Using Genomics to Study Human Biology and Disease

    SciTech Connect (OSTI)

    Myers, Ricard M.

    2005-04-06

    The Human Genome Project culminated in April 2003 with the finished DNA sequence of all of the human chromosomes. This book of information, particularly in conjunction with the genome sequences of many other organisms, has already begun to revolutionize the way that biomedical scientists study our species. The identification of essentially all of our genes has provided a template upon which researchers can discover basic processes that govern cells, organs, and the whole organism, and to understand the fundamental causes of the diseases that occur when something goes wrong with a gene or a set of genes. The Genome Project has already made it possible to identify the genes that are defective in more than 1,000 rare inherited diseases, and these discoveries have helped to understand the mechanisms of the more common forms of these disorders. This understanding of primary defects in diseases - which is translated as mutations in genes that encode proteins that serve specific functions - is transforming the way that biotechnology and pharmaceutical companies identify drug targets, and a few notable cases have already had a striking impact on specific diseases. In addition, it has become clear that the differential response to drugs in human populations is heavily influenced by genes, and a whole field called pharmacogenetics has begun to identify these genetic factors. Such knowledge will allow physicians to prescribe drugs targeted to each individual, with the potential to increase efficacy and decrease side-effects. Determining the DNA sequence of the human genome and identifying the genes has been an exciting endeavor, but we are only just beginning to understand the treasures present in all of our DNA. My presentation will briefly describe the road we took to get the sequence, as well as the tools that we are developing to unlock its secrets.

  16. Modeling the Molecular Basis of Parkinson's Disease | Argonne Leadership

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Computing Facility Alpha-synuclein pentamer constructed with 4ns molecular dynamics (MD) conformers after equilibration on the membrane with MD. Alpha-synuclein pentamer constructed with 4ns molecular dynamics (MD) conformers after equilibration on the membrane with MD. Modeling the Molecular Basis of Parkinson's Disease PI Name: Igor Tsigelny PI Email: itsigeln@ucsd.edu Institution: University of California-San Diego/SDSC Allocation Program: INCITE Allocation Hours at ALCF: 1.2 Million

  17. Radiological approaches in the evaluation of joint disease in children

    SciTech Connect (OSTI)

    Poznanski, A.K.; Conway, J.J.; Shkolnik, A.; Pachman, L.M.

    1987-04-01

    In summary, the newer technologies in radiology have allowed us to visualize more clearly the manifestation of joint disease in children. The presence of small erosions and cartilage damage can be seen much better with magnetic resonance imaging than with any other modality short of arthrography, a much more invasive examination. Joint effusion, although sometimes visualized with conventional radiography, is probably best recognized with ultrasound or magnetic resonance imaging, although it can be detected with computed tomography as well. For the evaluation of avascular necrosis that can be associated with steroid use in joint disease, bone scintigraphy is a simple, sensitive method. Magnetic resonance may be as or more sensitive and gives additional information as well. In the detection of change with time, conventional radiography probably will remain the standard as it is still the simplest, least expensive examination; however, it has many limitations in specific cases. Bone scintigraphy may be of value in selected cases. Although we have still not had enough experience with magnetic resonance imaging to use it as a way of evaluating progress of joint disease, it promises to be the most sensitive radiologic measure of evaluating progress as small anatomical changes can be detected within the cartilage, which cannot be done easily with other means. 27 references.

  18. Vesicular Disease in 9-Week-Old Pigs Experimentally Infected with Senecavirus A

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Montiel, Nestor; Buckley, Alexandra; Guo, Baoqing; Kulshreshtha, Vikas; VanGeelen, Albert; Hoang, Hai; Rademacher, Christopher; Yoon, Kyoung-Jin; Lager, Kelly

    2016-07-01

    Senecavirus A has been infrequently associated with vesicular disease in swine since 1988. However, clinical disease has not been reproduced after experimental infection with this virus. Here we report vesicular disease in 9-week-old pigs after Sencavirus A infection by the intranasal route under experimental conditions.

  19. Advancements in Orthopedic Intervention: Retrograde Drilling and Bone Grafting of Osteochondral Lesions of the Knee Using Magnetic Resonance Imaging Guidance

    SciTech Connect (OSTI)

    Seebauer, Christian J.; Bail, Hermann J.; Rump, Jens C. Walter, Thula Teichgraeber, Ulf K. M.

    2010-12-15

    Computer-assisted surgery is currently a novel challenge for surgeons and interventional radiologists. Magnetic resonance imaging (MRI)-guided procedures are still evolving. In this experimental study, we describe and assess an innovative passive-navigation method for MRI-guided treatment of osteochondritis dissecans of the knee. A navigation principle using a passive-navigation device was evaluated in six cadaveric knee joint specimens for potential applicability in retrograde drilling and bone grafting of osteochondral lesions using MRI guidance. Feasibility and accuracy were evaluated in an open MRI scanner (1.0 T Philips Panorama HFO MRI System). Interactive MRI navigation allowed precise drilling and bone grafting of osteochondral lesions of the knee. All lesions were hit with an accuracy of 1.86 mm in the coronal plane and 1.4 mm the sagittal plane. Targeting of all lesions was possible with a single drilling. MRI allowed excellent assessment of correct positioning of the cancellous bone cylinder during bone grafting. The navigation device and anatomic structures could be clearly identified and distinguished throughout the entire drilling procedure. MRI-assisted navigation method using a passive navigation device is feasible for the treatment of osteochondral lesions of the knee under MRI guidance and allows precise and safe drilling without exposure to ionizing radiation. This method may be a viable alternative to other navigation principles, especially for pediatric and adolescent patients. This MRI-navigated method is also potentially applicable in many other MRI-guided interventions.

  20. Supratentorial Ependymoma: Disease Control, Complications, and Functional Outcomes After Irradiation

    SciTech Connect (OSTI)

    Landau, Efrat; Boop, Frederick A.; Conklin, Heather M.; Wu, Shengjie; Xiong, Xiaoping; Merchant, Thomas E.

    2013-03-15

    Purpose: Ependymoma is less commonly found in the supratentorial brain and has known clinical and molecular features that are unique. Our single-institution series provides valuable information about disease control for supratentorial ependymoma and the complications of supratentorial irradiation in children. Methods and Materials: A total of 50 children with newly diagnosed supratentorial ependymoma were treated with adjuvant radiation therapy (RT); conformal methods were used in 36 after 1996. The median age at RT was 6.5 years (range, 1-18.9 years). The entire group was characterized according to sex (girls 27), race (white 43), extent of resection (gross-total 46), and tumor grade (anaplastic 28). The conformal RT group was prospectively evaluated for neurologic, endocrine, and cognitive effects. Results: With a median follow-up time of 9.1 years from the start of RT for survivors (range, 0.2-23.2 years), the 10-year progression-free and overall survival were 73% + 7% and 76% + 6%, respectively. None of the evaluated factors was prognostic for disease control. Local and distant failures were evenly divided among the 16 patients who experienced progression. Eleven patients died of disease, and 1 of central nervous system necrosis. Seizure disorders were present in 17 patients, and 4 were considered to be clinically disabled. Clinically significant cognitive effects were limited to children with difficult-to-control seizures. The average values for intelligence quotient and academic achievement (reading, spelling, and math) were within the range of normal through 10 years of follow-up. Central hypothyroidism was the most commonly treated endocrinopathy. Conclusion: RT may be administered with acceptable risks for complications in children with supratentorial ependymoma. These results suggest that outcomes for these children are improving and that complications may be limited by use of focal irradiation methods.

  1. Development of Biomarkers for Chronic Beryllium Disease in Mice

    SciTech Connect (OSTI)

    Gordon, Terry

    2013-01-25

    Beryllium is a strategic metal, indispensable for national defense programs in aerospace, telecommunications, electronics, and weaponry. Exposure to beryllium is an extensively documented occupational hazard that causes irreversible, debilitating granulomatous lung disease in as much as 3 - 5% of exposed workers. Mechanistic research on beryllium exposure-disease relationships has been severely limited by a general lack of a sufficient CBD animal model. We have now developed and tested an animal model which can be used for dissecting dose-response relationships and pathogenic mechanisms and for testing new diagnostic and treatment paradigms. We have created 3 strains of transgenic mice in which the human antigen-presenting moiety, HLA-DP, was inserted into the mouse genome. Each mouse strain contains HLA-DPB1 alleles that confer different magnitude of risk for chronic beryllium disease (CBD): HLA-DPB1*0401 (odds ratio = 0.2), HLA-DPB1*0201 (odds ratio = 15), HLA-DPB1*1701 (odds ratio = 240). Our preliminary work has demonstrated that the *1701 allele, as predicted by human studies, results in the greatest degree of sensitization in a mouse ear swelling test. We have also completed dose-response experiments examining beryllium-induced lung granulomas and identified susceptible and resistant inbred strains of mice (without the human transgenes) as well as quantitative trait loci that may contain gene(s) that modify the immune response to beryllium. In this grant application, we propose to use the transgenic and normal inbred strains of mice to identify biomarkers for the progression of beryllium sensitization and CBD. To achieve this goal, we propose to compare the sensitivity and accuracy of the lymphocyte proliferation test (blood and bronchoalveolar lavage fluid) with the ELISPOT test in the three HLA-DP transgenic mice strains throughout a 6 month treatment with beryllium particles. Because of the availability of high-throughput proteomics, we will also identify

  2. Hanford Site Chronic Beryllium Disease Prevention Program (CBDPP) Contact List

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Chronic Beryllium Disease Prevention Program (CBDPP) Contact List Page 1 of 2 Updated 5/31/16 Primary and Alternate Membership Organization Primary Office Number Cell Number Alternate Office Number Cell Number BAG Fisher, Mark N/A 539-5588 Artzer, Josh 376-2463 430-5062 CHPRC/HAMTC Sherman, Larry 376-6436 438-2171 Spier, Tracy 373-1993 440-9118 CHPRC Bean, Tonya 376-6503 (303) 709-3047 Robinson, Roby Seydel, Scott (509) 699-9307 373-4860 (509) 699-9307 430-0184 CWB&CTC Park, Rick 372-9941

  3. Physiologically guided approach to characterizing respiratory motion

    SciTech Connect (OSTI)

    White, Benjamin M. Lamb, James M.; Low, Daniel A.; Zhao, Tianyu; Bradley, Jeffrey D.

    2013-12-15

    Purpose: To characterize radiation therapy patient breathing patterns based on measured external surrogate information. Methods: Breathing surrogate data were collected during 4DCT from a cohort of 50 patients including 28 patients with lung cancer and 22 patients without lung cancer. A spirometer and an abdominal pneumatic bellows were used as the surrogates. The relationship between these measurements was assumed to be linear within a small phase difference. The signals were correlated and drift corrected using a previously published method to convert the signal into tidal volume. The airflow was calculated with a first order time derivative of the tidal volume using a window centered on the point of interest and with a window length equal to the CT gantry rotation period. The airflow was compared against the tidal volume to create ellipsoidal patterns that were binned into 25 ml × 25 ml/s bins to determine the relative amount of time spent in each bin. To calculate the variability of the maximum inhalation tidal volume within a free-breathing scan timeframe, a metric based on percentile volume ratios was defined. The free breathing variability metric (κ) was defined as the ratio between extreme inhalation tidal volumes (defined as >93 tidal volume percentile of the measured tidal volume) and normal inhalation tidal volume (defined as >80 tidal volume percentile of the measured tidal volume). Results: There were three observed types of volume-flow curves, labeled Types 1, 2, and 3. Type 1 patients spent a greater duration of time during exhalation withκ = 1.37 ± 0.11. Type 2 patients had equal time duration spent during inhalation and exhalation with κ = 1.28 ± 0.09. The differences between the mean peak exhalation to peak inhalation tidal volume, breathing period, and the 85th tidal volume percentile for Type 1 and Type 2 patients were statistically significant at the 2% significance level. The difference between κ and the 98th tidal volume percentile for Type 1 and Type 2 patients was found to be statistically significant at the 1% significance level. Three patients did not display a breathing stability curve that could be classified as Type 1 or Type 2 due to chaotic breathing patterns. These patients were classified as Type 3 patients. Conclusions: Based on an observed volume-flow curve pattern, the cohort of 50 patients was divided into three categories called Type 1, Type 2, and Type 3. There were statistically significant differences in breathing characteristics between Type 1 and Type 2 patients. The use of volume-flow curves to classify patients has been demonstrated as a physiological characterization metric that has the potential to optimize gating windows in radiation therapy.

  4. Osteogenic Sarcoma of the Maxilla: Neutron Therapy for Unresectable Disease

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Smoron, Geoffrey L.; Lennox, Arlene J.; Mcgee, James L.

    1999-01-01

    Purpose. To present a case study involving the use of fast neutron therapy to treat an extensive unresectable osteogenic sarcoma arising from the left maxilla. Patient. A 14-year-old male presented with a massive tumor producing severe distortion of his facial structures. He had already received six courses of chemotherapy, which had reduced his pain, but had not measurably reduced the tumor. Methods. The patient was treated with 66 MeV fast neutrons to a dose of 20.4 Gy in 13 fractions over 35 days. Results. CT assessments indicate gradually increasing calcification and noticeable reduction of soft-tissue disease in the frontalmore » sinus, orbit and maxillary antrum.There has been some recontouring of the facial structures.The boy conducts an active life, has no pain, and feels well. He was 17 years old at the last follow-up. Discussion. Fast neutrons have a greater biological effectiveness than conventional photon beams. Their use has been associated with improved chance for local control of unresectable disease.This case illustrates their effectiveness in controlling an unusual and aggressive osteogenic sarcoma of the facial bone and sinuses.« less

  5. Bead-based microfluidic immunoassay for diagnosis of Johne's disease

    SciTech Connect (OSTI)

    Wadhwa, Ashutosh [University of Tennessee, Center for Wildlife Health, Department of Forestry; Foote, Robert [ORNL; Shaw, Robert W [ORNL; Eda, Shigetoshi [ORNL

    2012-01-01

    Microfluidics technology offers a platform for development of point-of-care diagnostic devices for various infectious diseases. In this study, we examined whether serodiagnosis of Johne s disease (JD) can be conducted in a bead-based microfluidic assay system. Magnetic micro-beads were coated with antigens of the causative agent of JD, Mycobacterium avium subsp. paratuberculosis. The antigen-coated beads were incubated with serum samples of JD-positive or negative serum samples and then with a fluorescently-labeled secondary antibody (SAB). To confirm binding of serum antibodies to the antigen, the beads were subjected to flow cytometric analysis. Different conditions (dilutions of serum and SAB, types of SAB, and types of magnetic beads) were optimized for a great degree of differentiation between the JD-negative and JD-positive samples. Using the optimized conditions, we tested a well-classified set of 155 serum samples from JD negative and JD-positive cattle by using the bead-based flow cytometric assay. Of 105 JD-positive samples, 63 samples (60%) showed higher antibody binding levels than a cut-off value determined by using antibody binding levels of JD-negative samples. In contrast, only 43-49 JD-positive samples showed higher antibody binding levels than the cut-off value when the samples were tested by commercially-available immunoassays. Microfluidic assays were performed by magnetically immobilizing a number of beads within a microchannel of a glass microchip and detecting antibody on the collected beads by laser-induced fluorescence. Antigen-coated magnetic beads treated with bovine serum sample and fluorescently-labeled SAB were loaded into a microchannel to measure the fluorescence (reflecting level of antibody binding) on the beads in the microfluidic system. When the results of five bovine serum samples obtained with the system were compared to those obtained with the flow cytometer, a high level of correlation (linear regression, r2 = 0.994) was

  6. Ulcerative colitis and steroid-responsive, diffuse interstitial lung disease

    SciTech Connect (OSTI)

    Balestra, D.J.; Balestra, S.T.; Wasson, J.H.

    1988-07-01

    The authors describe a patient with ulcerative colitis and extracolonic manifestations in whom diffuse interstitial pulmonary disease developed that was responsive to glucocorticoid therapy one year after total proctocolectomy. The patient presented in December 1983 with a subacute course marked by cough and progressive exertional dyspnea, abnormal chest examination results, and a chest roentgenogram that revealed diffuse interstitital and alveolar infiltrates. A transbronchial biopsy specimen revealed a polymorphic interstitial infiltrate, mild interstitial fibrosis without apparent intraluminal fibrosis, and no vasculitis, granulomas, or significant eosinophilic infiltration. Within one week of the initiation of daily high-dose steroid therapy, the patient's symptoms dramatically improved; chest roentgenogram and forced vital capacity (60%) improved at a slower rate. All three measures deteriorated when alternate-day prednisone therapy was started but once again improved until the patient was totally asymptomatic, chest roentgenograms were normal, and forced vital capacity was 80% of the predicted value 2 1/2 years later.

  7. Resource Requirements Planning for Hospitals Treating Serious Infectious Disease Cases.

    SciTech Connect (OSTI)

    Vugrin, Eric D.; Verzi, Stephen Joseph; Finley, Patrick D.; Turnquist, Mark A.; Wyte-Lake, Tamar; Griffin, Ann R.; Ricci, Karen J.; Plotinsky, Rachel

    2015-02-01

    This report presents a mathematical model of the way in which a hospital uses a variety of resources, utilities and consumables to provide care to a set of in-patients, and how that hospital might adapt to provide treatment to a few patients with a serious infectious disease, like the Ebola virus. The intended purpose of the model is to support requirements planning studies, so that hospitals may be better prepared for situations that are likely to strain their available resources. The current model is a prototype designed to present the basic structural elements of a requirements planning analysis. Some simple illustrati ve experiments establish the mo del's general capabilities. With additional inve stment in model enhancement a nd calibration, this prototype could be developed into a useful planning tool for ho spital administrators and health care policy makers.

  8. OSTIblog Articles in the disease Topic | OSTI, US Dept of Energy Office of

    Office of Scientific and Technical Information (OSTI)

    Scientific and Technical Information disease Topic Sharing Data Leads to Progress by Nena Moss 19 Aug, 2010 in Personal Perspectives My mother died in March 2010 after a 15-year battle with Alzheimer's, so I pay particular attention to news about this dreadful disease. A recent New York Times article caught my eye: "Sharing of Data Leads to Progress on Alzheimer's." How did sharing data lead to progress on Alzheimer's? A collaborative effort, the Alzheimer's Disease Neuroimaging

  9. Edge effects, not connectivity, determine the incidence and development of a foliar fungal plant disease.

    SciTech Connect (OSTI)

    Johnson, Brenda, L.; Haddad, Nick, M.

    2011-08-01

    Using a model plant-pathogen system in a large-scale habitat corridor experiment, we found that corridors do not facilitate the movement of wind-dispersed plant pathogens, that connectivity of patches does not enhance levels of foliar fungal plant disease, and that edge effects are the key drivers of plant disease dynamics. Increased spread of infectious disease is often cited as a potential negative effect of habitat corridors used in conservation, but the impacts of corridors on pathogen movement have never been tested empirically. Using sweet corn (Zea mays) and southern corn leaf blight (Cochliobolus heterostrophus) as a model plant-pathogen system, we tested the impacts of connectivity and habitat fragmentation on pathogen movement and disease development at the Savannah River Site, South Carolina, USA. Over time, less edgy patches had higher proportions of diseased plants, and distance of host plants to habitat edges was the greatest determinant of disease development. Variation in average daytime temperatures provided a possible mechanism for these disease patterns. Our results show that worries over the potentially harmful effects of conservation corridors on disease dynamics are misplaced, and that, in a conservation context, many diseases can be better managed by mitigating edge effects.

  10. The Human Phenotype Ontology: Semantic Unification of Common and Rare Disease

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Groza, Tudor; Köhler, Sebastian; Moldenhauer, Dawid; Vasilevsky, Nicole; Baynam, Gareth; Zemojtel, Tomasz; Schriml, Lynn Marie; Kibbe, Warren Alden; Schofield, Paul N.; Beck, Tim; et al

    2015-06-25

    The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000more »rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available.« less

  11. Toxicological and pharmacological concerns on oxidative stress and related diseases

    SciTech Connect (OSTI)

    Saeidnia, Soodabeh; Abdollahi, Mohammad

    2013-12-15

    Although reactive oxygen species (ROS) such as superoxide, hydrogen peroxide and hydroxyl radical are generated as the natural byproduct of normal oxygen metabolism, they can create oxidative damage via interaction with bio-molecules. The role of oxidative stress as a remarkable upstream part is frequently reported in the signaling cascade of inflammation as well as chemo attractant production. Even though hydrogen peroxide can control cell signaling and stimulate cell proliferation at low levels, in higher concentrations it can initiate apoptosis and in very high levels may create necrosis. So far, the role of ROS in cellular damage and death is well documented with implicating in a broad range of degenerative alterations e.g. carcinogenesis, aging and other oxidative stress related diseases (OSRDs). Reversely, it is cleared that antioxidants are potentially able to suppress (at least in part) the immune system and to enhance the normal cellular protective responses to tissue damage. In this review, we aimed to provide insights on diverse OSRDs, which are correlated with the concept of oxidative stress as well as its cellular effects that can be inhibited by antioxidants. Resveratrol, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statins, nebivolol and carvedilol, pentaerythritol tetranitrate, mitochondria-targeted antioxidants, and plant-derived drugs (alone or combined) are the potential medicines that can be used to control OSRD.

  12. Metabonomic Profiling of TASTPM Transgenic Alzheimer's Disease Mouse Model

    SciTech Connect (OSTI)

    Hu, Zeping; Browne, Edward R.; Liu, Tao; Angel, Thomas E.; Ho, Paul C.; Chun Yong Chan, Eric

    2012-12-07

    Identification of molecular mechanisms underlying early stage Alzheimer’s disease (AD) is important for the development of new therapies against and diagnosis of AD. In this study, non-targeted metabotyping of TASTPM transgenic AD mice was performed. The metabolic profiles of both brain and plasma of TASTPM mice were characterized using gas chromatography-mass spectrometry and compared to those of wild type C57BL/6J mice. TASTPM mice were metabolically distinct compared to wild type mice (Q28 Y = 0.587 and 0.766 for PLS-DA models derived from brain and plasma, respectively). A number of metabolites were found to be perturbed in TASTPM mice in both brain (D11 fructose, L-valine, L-serine, L-threonine, zymosterol) and plasma (D-glucose, D12 galactose, linoleic acid, arachidonic acid, palmitic acid and D-gluconic acid). In addition, enzyme immunoassay confirmed that selected endogenous steroids were significantly perturbed in brain (androstenedione and 17-OH-progesterone) and plasma (cortisol and testosterone) of TASTPM mice. Ingenuity pathway analysis revealed that perturbations related to amino acid metabolism (brain), steroid biosynthesis (brain), linoleic acid metabolism (plasma) and energy metabolism (plasma) accounted for the differentiation of TASTPM and wild-type

  13. The temporal patterns of disease severity and prevalence in schistosomiasis

    SciTech Connect (OSTI)

    Ciddio, Manuela; Gatto, Marino Casagrandi, Renato

    2015-03-15

    Schistosomiasis is one of the most widespread public health problems in the world. In this work, we introduce an eco-epidemiological model for its transmission and dynamics with the purpose of explaining both intra- and inter-annual fluctuations of disease severity and prevalence. The model takes the form of a system of nonlinear differential equations that incorporate biological complexity associated with schistosome's life cycle, including a prepatent period in snails (i.e., the time between initial infection and onset of infectiousness). Nonlinear analysis is used to explore the parametric conditions that produce different temporal patterns (stationary, endemic, periodic, and chaotic). For the time-invariant model, we identify a transcritical and a Hopf bifurcation in the space of the human and snail infection parameters. The first corresponds to the occurrence of an endemic equilibrium, while the latter marks the transition to interannual periodic oscillations. We then investigate a more realistic time-varying model in which fertility of the intermediate host population is assumed to seasonally vary. We show that seasonality can give rise to a cascade of period-doubling bifurcations leading to chaos for larger, though realistic, values of the amplitude of the seasonal variation of fertility.

  14. Multi-analyte analysis of saliva biomarkers as predictors of periodontal and pre-implant disease

    DOE Patents [OSTI]

    Braun, Thomas; Giannobile, William V; Herr, Amy E; Singh, Anup K; Shelburne, Charlie

    2015-04-07

    The present invention relates to methods of measuring biomarkers to determine the probability of a periodontal and/or peri-implant disease. More specifically, the invention provides a panel of biomarkers that, when used in combination, can allow determination of the probability of a periodontal and/or peri-implant disease state with extremely high accuracy.

  15. Milk production and distribution in low-dose counties for the Hanford Thyroid Disease Study

    SciTech Connect (OSTI)

    Schimmel, J.G. . Social and Economic Sciences Research Center); Beck, D.M. )

    1992-06-01

    This report identifies sources of milk consumed by residents of Ferry, Okanogan, and Stevens Counties. This information will be used by the Hanford thyroid Disease Study to determine whether thyroid disease has been increased among people exposed to past iodine--131 emissions from Hanford Site Facilities.

  16. Proceedings of the 2nd workshop on lyme disease in the Southeast

    SciTech Connect (OSTI)

    Apperson, C.S.; Levine, J.F.; Snoddy, E.L.

    1993-12-31

    This volume provides author prepared abstracts of oral presentation at the Second Workshop on Lyme Disease in the Southeast head in Raleigh, North Carolina September 7-9, 1993. The 33 presentations covered various aspects of the epidemic including geographical distribution of various species of ticks, transmission risks, Lyme Disease epidemiology, and taxonomic aspects.

  17. Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C.; Liu, Yang; Gao, Yang; Hess, Jeremy; et al

    2014-11-02

    Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delaymore » China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.« less

  18. Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

    SciTech Connect (OSTI)

    Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C.; Liu, Yang; Gao, Yang; Hess, Jeremy; Remais, Justin V.

    2014-11-02

    Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delay China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.

  19. Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

    SciTech Connect (OSTI)

    Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C.; Liu, Yang; Gao, Yang; Hess, Jeremy; Remais, Justin V.

    2014-12-01

    Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delay China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.

  20. Health Detectives: Uncovering the Mysteries of Disease (LBNL Science at the Theater)

    ScienceCinema (OSTI)

    Bissell, Mina; Canaria, Christie; Celnicker, Susan; Karpen, Gary

    2014-05-06

    In this April 23, 2012 Science at the Theater event, Berkeley Lab scientists discuss how they uncover the mysteries of disease in unlikely places. Speakers and topics include: World-renowned cancer researcher Mina Bissell's pioneering research on the role of the cellular microenvironment in breast cancer has changed the conversation about the disease. How does DNA instability cause disease? To find out, Christie Canaria images neural networks to study disorders such as Huntington's disease. Fruit flies can tell us a lot about ourselves. Susan Celniker explores the fruit fly genome to learn how our genome works. DNA is not destiny. Gary Karpen explores how environmental factors shape genome function and disease through epigenetics.

  1. Mineral density volume gradients in normal and diseased human tissues

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.; Aikawa, Elena

    2015-04-09

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-raymore » fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.« less

  2. Mineral density volume gradients in normal and diseased human tissues

    SciTech Connect (OSTI)

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.; Aikawa, Elena

    2015-04-09

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

  3. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    SciTech Connect (OSTI)

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2014-12-04

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.

  4. Using social media for actionable disease surveillance and outbreak management. A systematic literature review

    SciTech Connect (OSTI)

    Charles-Smith, Lauren E.; Reynolds, Tera L.; Cameron, Mark A.; Conway, Mike; Lau, Eric H. Y.; Olsen, Jennifer M.; Pavlin, Julie A.; Shigematsu, Mika; Streichert, Laura C.; Suda, Katie J.; Corley, Courtney D.; Braunstein, Lidia Adriana

    2015-10-05

    Here, research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals’ ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: 1) Can social media be integrated into disease surveillance practice and outbreak management to support and improve public health? 2) Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes? Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n=15), Infectious Diseases (n = 6), Non-infectious Diseases (n=4), Medication and Vaccines (n=3), and Other (n=5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n=10), Infectious Diseases (n = 3), Non-infectious Diseases (n=9), and Other (n=10). The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review is to

  5. Using social media for actionable disease surveillance and outbreak management. A systematic literature review

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Charles-Smith, Lauren E.; Reynolds, Tera L.; Cameron, Mark A.; Conway, Mike; Lau, Eric H. Y.; Olsen, Jennifer M.; Pavlin, Julie A.; Shigematsu, Mika; Streichert, Laura C.; Suda, Katie J.; et al

    2015-10-05

    Here, research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals’ ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: 1) Can social media be integrated into disease surveillance practice and outbreak management to support and improvemore » public health? 2) Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes? Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n=15), Infectious Diseases (n = 6), Non-infectious Diseases (n=4), Medication and Vaccines (n=3), and Other (n=5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n=10), Infectious Diseases (n = 3), Non-infectious Diseases (n=9), and Other (n=10). The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review

  6. Using Social Media for Actionable Disease Surveillance and Outbreak Management: A Systematic Literature Review

    SciTech Connect (OSTI)

    Charles-Smith, Lauren E.; Reynolds, Tera; Cameron, Mark; Conway, Mike; Lau, Eric H.; Olsen, Jennifer; Pavlin, Julie A.; Shigematsu, Mika; Streichert, Laura; Suda, Katie; Corley, Courtney D.

    2015-10-05

    Research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: 1) Can social media be integrated into disease surveillance practice and outbreak management to support and improve public health? 2) Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes? Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n=15), Infectious Diseases (n = 6), Non-infectious Diseases (n=4), Medication and Vaccines (n=3), and Other (n=5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n=10), Infectious Diseases (n = 3), Non-infectious Diseases (n=9), and Other (n=10). The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review is to identify

  7. Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

    SciTech Connect (OSTI)

    Casjens, S.R.; Dunn, J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Fraser-Liggett, C. M.; Schutzer, S. E.

    2011-12-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04.

  8. Integrating Heterogeneous Healthcare Datasets and Visual Analytics for Disease Bio-surveillance and Dynamics

    SciTech Connect (OSTI)

    Ramanathan, Arvind; Pullum, Laura L; Steed, Chad A; Quinn, Shannon; Chennubhotla, Chakra; Parker, Tara L

    2013-01-01

    n this paper, we present an overview of the big data chal- lenges in disease bio-surveillance and then discuss the use of visual analytics for integrating data and turning it into knowl- edge. We will explore two integration scenarios: (1) combining text and multimedia sources to improve situational awareness and (2) enhancing disease spread model data with real-time bio-surveillance data. Together, the proposed integration methodologies can improve awareness about when, where and how emerging diseases can affect wide geographic regions.

  9. Speaker for Nov. 1 Lecture to Discuss Deadliest Viral Diseases | Jefferson

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Lab Speaker for Nov. 1 Lecture to Discuss Deadliest Viral Diseases Speaker for Nov. 1 Lecture to Discuss Deadliest Viral Diseases NEWPORT NEWS, Va., Oct. 27, 2011 - A noted scientist will discuss some of the world's deadliest viruses as guest speaker at Jefferson Lab's Fall Science Series lecture to be held at the lab on Tuesday, Nov. 1. Susan Fisher-Hoch, a virologist and epidemiologist from the University of Texas School of Public Health will present: Studying Deadly Diseases. She will

  10. Medical Screening Protocol for the Former Worker Medical Screening...

    Broader source: Energy.gov (indexed) [DOE]

    recommendations; repeat CT scan offered on an annual basis after initial baseline Welding Lung Asthma Chronic obstructive lung disease Respiratory symptoms...

  11. One Vaccine Leads to Another

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    One Vaccine Leads to Another Print Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines...

  12. ARM - Field Campaign - Observations and Modeling of the Green...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    The results will be correlated with meteorological and health data of the local population. This relation between respiratory diseases and environmental factors about air pollution ...

  13. Global warming and the potential spread of vector-borne diseases

    SciTech Connect (OSTI)

    Patz, J.

    1996-12-31

    Climatic factors influence many vector-borne infectious diseases, in addition to demographic, biological, and ecological determinants. The United Nation`s Intergovernmental Panel on Climate Change (IPCC) estimates an unprecedented global rise of 2.0 C by the year 2100. Of major concern is that these changes can affect the spread of many serious infectious diseases, including malaria and dengue fever. Global warming would directly affect disease transmission by shifting the mosquito`s geographic range, increasing reproductive and biting rates, and shortening pathogen incubation period. Human migration and damage to health infrastructures from the projected increase in climate variability and sea level rise could indirectly contribute to disease transmission. A review of this literature, as well as preliminary data from ongoing studies will be presented.

  14. Independent Oversight Inspection of the Hanford Site Chronic Beryllium Disease Prevention Program

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Independent Oversight Inspection of the Hanford Site Chronic Beryllium Disease Prevention Program June 2010 Office of Independent Oversight Office of Health, Safety and Security Office of Health, Safety and Security HSS x Hanford Site Chronic Beryllium Disease Prevention Program | i Abbreviations iii Executive Summary v 1 Introduction 1 2 Management and Oversight 3 3 Findings Requiring Corrective Action 14 4 Conclusions and Cross-Cutting Opportunities for Improvement 17 Appendix A - Supplemental

  15. Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells

    SciTech Connect (OSTI)

    Vi, Linda; Feng, Lucy; Zhu, Rebecca D.; Wu, Yan; Lawson Health Research Institute, London, Ontario ; Satish, Latha; Gan, Bing Siang; Lawson Health Research Institute, London, Ontario; Department of Surgery, University of Western Ontario, London, Ontario; Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario; Department of Medical Biophysics, University of Western Ontario, London, Ontario ; O'Gorman, David B.

    2009-12-10

    Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostin was found to differentially regulate the apoptosis, proliferation, {alpha} smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.

  16. Percutaneous Cholangioscopy in the Management of Biliary Disease: Experience in 25 Patients

    SciTech Connect (OSTI)

    Hatzidakis, Adam A.; Alexandrakis, George; Kouroumalis, Helias; Gourtsoyiannis, Nicholas C.

    2000-11-15

    Purpose: To present our experience performing percutaneous cholangioscopy in the management of 25 patients with biliary disease.Methods: During the last 3 years, 26 percutaneous cholangioscopies were performed in 25 patients with common bile duct disease (n = 16), intrahepatic ducts disease (n = 6), and gallbladder disease (n = 4). Our patient population group included seven with common bile duct stones, three with intrahepatic lithiasis, and eight with benign strictures (six iatrogenic and two postinflammatory). In four patients malignancy was to be excluded, in two the tumor extent was to be evaluated, whereas in one case the correct placement of a metallic stent needed to be controlled. A 9.9 Fr flexible endoscope URF-P (Olympus, 1.2 mm working channel, 70-cm length) was used.Results: In total, percutaneous cholangioscopy answered 30 diagnostic questions, was technically helpful in 19 cases (performing lithotripsy or biopsy or guiding a wire), and of therapeutic help in 12 (performing stone retrieval). In 24 of 26 cases the therapeutic decision and the patient management changed because of the findings or because of the help of the method. In two cases biliary intervention failed to treat the cause of the disease. No major complication due to the use of the endoscopy was noted.Conclusions: Percutaneous cholangioscopy is a very useful tool in the management of patients with biliary disease. The method can help in diagnosis, in performing complex interventional procedures, and in making or changing therapeutic decisions.

  17. Role of paraoxonase 1 (PON1) in organophosphate metabolism: Implications in neurodegenerative diseases

    SciTech Connect (OSTI)

    Androutsopoulos, Vasilis P.; Kanavouras, Konstantinos; Tsatsakis, Aristidis M.

    2011-11-15

    Organophosphate pesticides are a class of compounds that are widely used in agricultural and rural areas. Paraoxonase 1 (PON1) is a phase-I enzyme that is involved in the hydrolysis of organophosphate esters. Environmental poisoning by organophosphate compounds has been the main driving force of previous research on PON1 enzymes. Recent discoveries in animal models have revealed the important role of the enzyme in lipid metabolism. However although PON1 function is well established in experimental models, the contribution of PON1 in neurodegenerative diseases remains unclear. In this minireview we summarize the involvement of PON1 genotypes in the occurrence of Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. A brief overview of latest epidemiological studies, regarding the two most important PON1 coding region polymorphisms PON1-L55M and PON1-Q192R is presented. Positive and negative associations of PON1 with disease occurrence are reported. Notably the MM and RR alleles contribute a risk enhancing effect for the development of some neurodegenerative diseases, which may be explained by the reduced lipoprotein free radical scavenging activity that may give rise to neuronal damage, through distinct mechanism. Conflicting findings that fail to support this postulate may represent the human population ethnic heterogeneity, different sample size and environmental parameters affecting PON1 status. We conclude that further epidemiological studies are required in order to address the exact contribution of PON1 genome in combination with organophosphate exposure in populations with neurodegenerative diseases.

  18. HepatoProteomics: Applying Proteomic Technologies to the Study of Liver Function and Disease

    SciTech Connect (OSTI)

    Diamond, Deborah L.; Proll, Sean; Jacobs, Jon M.; Chan, Eric Y.; Camp, David G.; Smith, Richard D.; Katze, Michael G.

    2006-08-01

    The wealth of human genome sequence information now available, coupled with technological advances in robotics, nanotechnology, mass spectrometry, and information systems, has given rise to a method of scientific inquiry known as functional genomics. By using these technologies to survey gene expression and protein production on a near global scale, the goal of functional genomics is to assign biological function to genes with currently unknown roles in physiology. This approach carries particular appeal in disease research, where it can uncover the function of previously unknown genes and molecular pathways that are directly involved in disease progression. With this knowledge may come improved diagnostic techniques, prognostic capabilities, and novel therapeutic approaches. In this regard, the continuing evolution of proteomic technologies has resulted in an increasingly greater impact of proteome studies in many areas of research and hepatology is no exception. Our laboratory has been extremely active in this area, applying both genomic and proteomic technologies to the analysis of virus-host interactions in several systems, including the study of hepatitis C virus (HCV) infection and HCV-associated liver disease. Since proteomic technologies are foreign to many hepatologists (and to almost everyone else), this article will provide an overview of proteomic methods and technologies and describe how they're being used to study liver function and disease. We use our studies of HCV infection and HCV-associated liver disease to present an operational framework for performing high throughput proteome analysis and extracting biologically meaningful information.

  19. The Biosurveillance Analytics Resource Directory (BARD): Facilitating the use of epidemiological models for infectious disease surveillance

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Margevicius, Kristen J.; Generous, Nicholas; Abeyta, Esteban; Althouse, Ben; Burkom, Howard; Castro, Lauren; Daughton, Ashlynn; Del Valle, Sara Y.; Fairchild, Geoffrey; Hyman, James M.; et al

    2016-01-28

    Epidemiological modeling for infectious disease is important for disease management and its routine implementation needs to be facilitated through better description of models in an operational context. A standardized model characterization process that allows selection or making manual comparisons of available models and their results is currently lacking. A key need is a universal framework to facilitate model description and understanding of its features. Los Alamos National Laboratory (LANL) has developed a comprehensive framework that can be used to characterize an infectious disease model in an operational context. The framework was developed through a consensus among a panel of subjectmore » matter experts. In this paper, we describe the framework, its application to model characterization, and the development of the Biosurveillance Analytics Resource Directory (BARD; http://brd.bsvgateway.org/brd/), to facilitate the rapid selection of operational models for specific infectious/communicable diseases. We offer this framework and associated database to stakeholders of the infectious disease modeling field as a tool for standardizing model description and facilitating the use of epidemiological models.« less

  20. Multiplexed Molecular Assays for Rapid Rule-Out of Foot-and-Mouth Disease

    SciTech Connect (OSTI)

    Lenhoff, R; Naraghi-Arani, P; Thissen, J; Olivas, J; Carillo, C; Chinn, C; Rasmussen, M; Messenger, S; Suer, L; Smith, S M; Tammero, L; Vitalis, E; Slezak, T R; Hullinger, P J; Hindson, B J; Hietala, S; Crossley, B; Mcbride, M

    2007-06-26

    A nucleic acid-based multiplexed assay was developed that combines detection of foot-and-mouth disease virus (FMDV) with rule-out assays for two other foreign animal diseases and four domestic animal diseases that cause vesicular or ulcerative lesions indistinguishable from FMDV infection in cattle, sheep and swine. The FMDV 'look-alike' diagnostic assay panel contains five PCR and twelve reverse transcriptase PCR (RT-PCR) signatures for a total of seventeen simultaneous PCR amplifications for seven diseases plus incorporating four internal assay controls. It was developed and optimized to amplify both DNA and RNA viruses simultaneously in a single tube and employs Luminex{trademark} liquid array technology. Assay development including selection of appropriate controls, a comparison of signature performance in single and multiplex testing against target nucleic acids, as well of limits of detection for each of the individual signatures is presented. While this assay is a prototype and by no means a comprehensive test for FMDV 'look-alike' viruses, an assay of this type is envisioned to have benefit to a laboratory network in routine surveillance and possibly for post-outbreak proof of freedom from foot-and-mouth disease.

  1. Introduction to Focus Issue: Rhythms and Dynamic Transitions in Neurological Disease: Modeling, Computation, and Experiment

    SciTech Connect (OSTI)

    Kaper, Tasso J. Kramer, Mark A.; Rotstein, Horacio G.

    2013-12-15

    Rhythmic neuronal oscillations across a broad range of frequencies, as well as spatiotemporal phenomena, such as waves and bumps, have been observed in various areas of the brain and proposed as critical to brain function. While there is a long and distinguished history of studying rhythms in nerve cells and neuronal networks in healthy organisms, the association and analysis of rhythms to diseases are more recent developments. Indeed, it is now thought that certain aspects of diseases of the nervous system, such as epilepsy, schizophrenia, Parkinson's, and sleep disorders, are associated with transitions or disruptions of neurological rhythms. This focus issue brings together articles presenting modeling, computational, analytical, and experimental perspectives about rhythms and dynamic transitions between them that are associated to various diseases.

  2. A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

    SciTech Connect (OSTI)

    Aderem, Alan; Adkins, Joshua N.; Ansong, Charles; Galagan, James; Kaiser, Shari; Korth, Marcus J.; Law, G. L.; McDermott, Jason E.; Proll, Sean; Rosenberger, Carrie; Schoolnik, Gary; Katze, Michael G.

    2011-02-01

    The 20th century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and water borne illnesses are frequent, multi-drug resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the pastincluding the intense focus on individual genes and proteins typical of molecular biologyhave not been sufficient to address these challenges. The first decade of the 21st century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program we think that the time is at hand to redefine the pathogen-host research paradigm.

  3. Severe gas bubble disease in a warmwater fishery in the midwestern united states

    SciTech Connect (OSTI)

    Crunkilton, R.L.; Czarnezki, J.M.; Trial, L.

    1980-11-01

    Supersaturation of the water of the Osage River below the Harry S. Truman Dam resulted in an epidemic of gas bubble disease that caused the largest fish kill in the history of Missouri. This is the first recorded evidence of serious supersaturation in the midwestern U.S. Total gas saturation levels up to 139% killed nearly 500,000 fish in the Osage River and the Lake of the Ozarks during April-May 1978. Nitrogen was the primary gas responsible for gas bubble disease mortalities. Instream cage bioassays defined the zone of lethal supersaturation. Significant mortality occurred in pelagic and near-shore species, deepwater species, and bottom-dwelling species. Susceptibility to disease was related to fish size.

  4. Severe gas bubble disease in a warmwater fishery in the midwestern United States

    SciTech Connect (OSTI)

    Crunkilton, R.L.; Czarnezki, J.M.; Trial, L.

    1980-11-01

    Gas bubble disease below Harry S. Truman Dam, sited on the upper Osage River and spilling into Lake of the Ozarks, caused the largest fish kill on record in Missouri. This is the first recorded evidence of serious supersaturation in the Midwest. Total gas saturation levels up to 139% killed nearly a half million fish in the upper 85 km of the Osage Arm, Lake of the Ozarks, during April to June, 1978 and 1979. Gas supersaturation occurred throughout the 150 km of this main-stem reservoir. Nitrogen was the primary gas responsible for gas bubble disease mortalities. Pelagic and near-shore species suffered the earliest and heaviest mortalities, but fish characteristic of deeper waters were increasingly killed as supersaturation persisted. Instream cage bioassays defined the zone of lethal supersaturation. Significant mortality occurred in bottom-dwelling fish of several species, due to long-term intermittent exposure. Susceptibility to gas bubble disease was related to fish size.

  5. Linkage disequilibrium in the region of the autosomal dominant polycystic kidney disease gene (PKD1)

    SciTech Connect (OSTI)

    Snarey, A. ); Thomas, S.; Harris, P.C. ); Schneider, M.C. ); Pound, S.E.; Wright, A.F. ); Barton, N.; Somlo, S.; Germino, G.G.; Reeders, S.T.

    1994-08-01

    The gene for autosomal dominant polycystic kidney disease (PKD1) is located on chromosome 16p, between the flanking markers D16S84 and D16S125 (26.6 prox). This region is 750 kb long and has been cloned. The authors have looked at the association of 10 polymorphic markers from the region, with the disease and with each other. This was done in a set of Scottish families that had previously shown association with D16S94, a marker proximal to the PKD1 region. They report significant association between two CA repeat markers and the disease but have not found evidence for a single founder haplotype in these families, indicating the presence of several mutations in this population. Their results favor a location of the PKD1 gene in the proximal part of the candidate region. 25 refs., 1 fig., 4 tabs.

  6. Serum Proteome Profiles in Stricturing Crohn’s Disease: A pilot study.

    SciTech Connect (OSTI)

    Townsend, Peter; Zhang, Qibin; Shapiro, Jason; Webb-Robertson, Bobbie-Jo M.; Bramer, Lisa M.; Schepmoes, Athena A.; Weitz, Karl K.; Mallette, Meaghan; Moniz, Heather; Bright, Renee; Merrick, Marjorie; Shah, Samir A.; Sands, Bruce E.; Leleiko, Neal

    2015-08-01

    Background: Crohn’s disease (CD) is a form of inflammatory bowel disease (IBD) with different described behaviors, including stricture. At present, there are no laboratory studies that can differentiate stricturing CD from other phenotypes of IBD. We performed a pilot study to examine differences in the proteome among patients with stricturing Crohn’s disease, non-stricturing Crohn’s disease, and ulcerative colitis (UC). Methods: Serum samples were selected from the Ocean State Crohn’s and Colitis Area Registry (OSCCAR), an established cohort of patients with IBD. Crohn’s disease patients with surgically-resected stricture were matched with similar patients with Crohn’s disease without known stricture, and with UC. Serum samples from each patient were digested and analyzed using liquid chromatography-mass spectrometry to characterize the proteome. Statistical analyses were performed to identify peptides and proteins that can differentiate CD with stricture. Results: Samples from 9 patients in each group (27 total patients) were analyzed. Baseline demographic characteristics were similar among the three groups. We quantified 7668 peptides and 897 proteins for analysis. ROC analysis identified a subset of peptides with an area under the curve greater than 0.9, indicating greater separation potential. Partial least squares discriminant analysis was able to distinguish among the three groups with up to 70% accuracy by peptides, and up to 80% accuracy by proteins. We identified the significantly different proteins and peptides, and determined their function based on previously published literature. Conclusions: The serum of patients with stricturing CD, non-stricturing CD, and UC are distinguishable via proteomic analysis. Some of the proteins that differentiate the stricturing phenotype have been implicated in complement activation, fibrinolytic pathways, and lymphocyte adhesion.

  7. Gas Bubble Disease Monitoring and Research of Juvenile Salmonids : Annual Report 1996.

    SciTech Connect (OSTI)

    Maule, Alec G.; Beeman, John W.; Hans, Karen M.; Mesa, M.G.; Haner, P.; Warren, J.J.

    1997-10-01

    This document describes the project activities 1996--1997 contract year. This report is composed of three chapters which contain data and analyses of the three main elements of the project: field research to determine the vertical distribution of migrating juvenile salmonids, monitoring of juvenile migrants at dams on the Snake and Columbia rivers, and laboratory experiments to describe the progression of gas bubble disease signs leading to mortality. The major findings described in this report are: A miniature pressure-sensitive radio transmitter was found to be accurate and precise and, after compensation for water temperature, can be used to determine the depth of tagged-fish to within 0.32 m of the true depth (Chapter 1). Preliminary data from very few fish suggest that depth protects migrating juvenile steelhead from total dissolved gas supersaturation (Chapter 1). As in 1995, few fish had any signs of gas bubble disease, but it appeared that prevalence and severity increased as fish migrated downstream and in response to changing gas supersaturation (Chapter 2). It appeared to gas bubble disease was not a threat to migrating juvenile salmonids when total dissolved gas supersaturation was < 120% (Chapter 2). Laboratory studies suggest that external examinations are appropriate for determining the severity of gas bubble disease in juvenile salmonids (Chapter 3). The authors developed a new method for examining gill arches for intravascular bubbles by clamping the ventral aorta to reduce bleeding when arches were removed (Chapter 3). Despite an outbreak of bacterial kidney disease in the experimental fish, the data indicate that gas bubble disease is a progressive trauma that can be monitored (Chapter 3).

  8. Geek-Up[04.01.2011]: A Discovery to Fight Cancer and Other Diseases |

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Department of Energy 4.01.2011]: A Discovery to Fight Cancer and Other Diseases Geek-Up[04.01.2011]: A Discovery to Fight Cancer and Other Diseases April 1, 2011 - 5:52pm Addthis Two structures of the Mre11-Rad50 complex were solved independently and overlaid, further revealing a flexible hinge in Rad50 near the Mre11 binding site | Courtesy of Lawrence Berkeley National Laboratory Two structures of the Mre11-Rad50 complex were solved independently and overlaid, further revealing a flexible

  9. Suppression of somatic expansion delays the onset of pathophysiology in a mouse model of Huntington’s Disease

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Budworth, Helen; Harris, Faye R.; Williams, Paul; Lee, Do Yup; Holt, Amy; Pahnke, Jens; Szczesny, Bartosz; Acevedo-Torres, Karina; Ayala-Peña, Sylvette; McMurray, Cynthia T.; et al

    2015-08-06

    Huntington’s Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the effects of the inherited and somatic expansions. We show here that suppressing somatic expansion substantially delays the onset of disease in littermates that inherit the same disease-length allele. Furthermore, a pharmacological inhibitor, XJB-5-131, inhibits the lengthening of the repeat tracks, and correlates with rescue of motormore » decline in these animals. The results provide evidence that pharmacological approaches to offset disease progression are possible.« less

  10. Suppression of somatic expansion delays the onset of pathophysiology in a mouse model of Huntington’s Disease

    SciTech Connect (OSTI)

    Budworth, Helen; Harris, Faye R.; Williams, Paul; Lee, Do Yup; Holt, Amy; Pahnke, Jens; Szczesny, Bartosz; Acevedo-Torres, Karina; Ayala-Peña, Sylvette; McMurray, Cynthia T.; McKinnon, Peter

    2015-08-06

    Huntington’s Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the effects of the inherited and somatic expansions. We show here that suppressing somatic expansion substantially delays the onset of disease in littermates that inherit the same disease-length allele. Furthermore, a pharmacological inhibitor, XJB-5-131, inhibits the lengthening of the repeat tracks, and correlates with rescue of motor decline in these animals. The results provide evidence that pharmacological approaches to offset disease progression are possible.

  11. Higher coronary heart disease and heart attack morbidity in Appalachian coal mining regions

    SciTech Connect (OSTI)

    Hendryx, M.; Zullig, K.J.

    2009-11-15

    This study analyzes the U.S. 2006 Behavioral Risk Factor Surveillance System survey data (N = 235,783) to test whether self-reported cardiovascular disease rates are higher in Appalachian coal mining counties compared to other counties after control for other risks. Dependent variables include self-reported measures of ever (1) being diagnosed with cardiovascular disease (CVD) or with a specific form of CVD including (2) stroke, (3) heart attack, or (4) angina or coronary heart disease (CHD). Independent variables included coal mining, smoking, BMI, drinking, physician supply, diabetes co-morbidity, age, race/ethnicity, education, income, and others. SUDAAN Multilog models were estimated, and odds ratios tested for coal mining effects. After control for covariates, people in Appalachian coal mining areas reported significantly higher risk of CVD (OR = 1.22, 95% CI = 1.14-1.30), angina or CHO (OR = 1.29, 95% C1 = 1.19-1.39) and heart attack (OR = 1.19, 95% C1 = 1.10-1.30). Effects were present for both men and women. Cardiovascular diseases have been linked to both air and water contamination in ways consistent with toxicants found in coal and coal processing. Future research is indicated to assess air and water quality in coal mining communities in Appalachia, with corresponding environmental programs and standards established as indicated.

  12. Implementation Guide for use with 10 CFR Part 850, Chronic Beryllium Disease Prevention Program

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2001-01-04

    The Department of Energy (DOE) has established regulatory requirements for the Chronic Beryllium Disease Prevention Program (CBDPP) in Title 10 of the Code of Federal Regulations (CFR), Part 850 (10 CFR 850) [64 Federal Register (FR) 68854]. Supersedes DOE G 440.1-7. Certified 9-23-10.

  13. Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak.

    SciTech Connect (OSTI)

    Brozik, Susan Marie; Manginell, Ronald Paul; Moorman, Matthew Wallace; Xiao, Xiaoyin; Edwards, Thayne L.; Anderson, John Moses; Pfeifer, Kent Bryant; Branch, Darren W.; Wheeler, David Roger; Polsky, Ronen; Lopez, DeAnna M.; Ebel, Gregory D.; Prasad, Abhishek N.; Brozik, James A.; Rudolph, Angela R.; Wong, Lillian P.

    2013-09-01

    Bioweapons and emerging infectious diseases pose growing threats to our national security. Both natural disease outbreak and outbreaks due to a bioterrorist attack are a challenge to detect, taking days after the outbreak to identify since most outbreaks are only recognized through reportable diseases by health departments and reports of unusual diseases by clinicians. In recent decades, arthropod-borne viruses (arboviruses) have emerged as some of the most significant threats to human health. They emerge, often unexpectedly, from cryptic transmission foci causing localized outbreaks that can rapidly spread to multiple continents due to increased human travel and trade. Currently, diagnosis of acute infections requires amplification of viral nucleic acids, which can be costly, highly specific, technically challenging and time consuming. No diagnostic devices suitable for use at the bedside or in an outbreak setting currently exist. The original goals of this project were to 1) develop two highly sensitive and specific diagnostic assays for detecting RNA from a wide range of arboviruses; one based on an electrochemical approach and the other a fluorescent based assay and 2) develop prototype microfluidic diagnostic platforms for preclinical and field testing that utilize the assays developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were developed for DNA-RNA hybridization detection and were implemented in microfluidic diagnostic sensing platforms that were developed in this project.

  14. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; Conway, Jessica M.; Crespo, Gonzalo; Navasa, Miquel; D’Amato, Massimo; Ferenci, Peter; Cotler, Scott J.; Forns, Xavier; et al

    2014-06-10

    HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). Amore » biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver disease (εmax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.« less

  15. Milk production and distribution in low-dose counties for the Hanford Thyroid Disease Study. Hanford Environmental Dose Reconstruction Project

    SciTech Connect (OSTI)

    Schimmel, J.G.; Beck, D.M.

    1992-06-01

    This report identifies sources of milk consumed by residents of Ferry, Okanogan, and Stevens Counties. This information will be used by the Hanford thyroid Disease Study to determine whether thyroid disease has been increased among people exposed to past iodine--131 emissions from Hanford Site Facilities.

  16. SU-D-204-06: Dose and Image Quality Evaluation of a Low-Dose Slot-Scanning X-Ray System for Pediatric Orthopedic Studies

    SciTech Connect (OSTI)

    Liu, Z; Hoerner, M; Lamoureux, R; Rill, L; Arreola, M

    2015-06-15

    Purpose: Children in early teens with scoliosis require repeated radiographic exams over a number of years. The EOS (EOS imaging S.A., Paris, France) is a novel low-dose slot-scanning digital radiographic system designed to produce full-spine images of a free-standing patient. The radiation dose and image quality characteristics of the EOS were evaluated relative to those of a Computed Radiography (CR) system for scoliosis imaging. Methods: For dose evaluation, a full-torso anthropomorphic phantom was scanned five times using the default standard clinical protocols for both the EOS and a CR system, which include both posteroanterior and lateral full-spine views. Optically stimulated luminescent dosimeters (OSLDs), also known as nanoDots™ (Landauer, Inc., Glenwood, IL), were placed on the phantom’s surface to measure entrance skin dose. To assess image quality, MTF curves were generated from sampling the noise levels within the high-contrast regions of a line-pair phantom. Vertical and horizontal distortions were measured for the square line-pair phantom with the EOS system to evaluate the effects of geometric magnification and misalignment with the indicated imaging plane. Results: The entrance skin dose was measured to be 0.4 to 1.1 mGy for the EOS, and 0.7 to 3.6 mGy for the CR study. MTF comparison shows that CR greatly outperforms the EOS, despite both systems having a limiting resolution at 1.8 line-pairs per mm. Vertical distortion was unaffected by phantom positioning, because of the EOS slot-scanning geometry. Horizontal distortion increased linearly with miscentering distance. Conclusion: The EOS system resulted in approximately 70% lower radiation dose than CR for full-spine images. Image quality was found to be inferior to CR. Further investigation is required to see if EOS system is an acceptable modality for performing clinically diagnostic scoliosis examinations.

  17. Septal myocardial perfusion imaging with thallium-201 in the diagnosis of proximal left anterior descending coronary artery disease

    SciTech Connect (OSTI)

    Pichard, A.D.; Wiener, I.; Martinez, E.; Horowitz, S.; Patterson, R.; Meller, J.; Goldsmith, S.J.; Gorlin, R.; Herman, M.V.

    1981-07-01

    The use of myocardial perfusion imaging (MPI) to identify obstructive coronary disease of the left anterior descending coronary artery proximal to the first septal perforator (prox LAD) was studied in 60 patients. Perfusion of the septum and anteroapical areas with thallium-201 injected during exercise was compared to results of coronary arteriography. Septal MPI defect was found in 92.3% of patients with obstruction of the proximal LAD, 27.7% of patients with obstruction of LAD distal to first septal perforator, 0% in patients with obstructions involving right or circumflex arteries, and in 10.5% of patients without coronary disease. Anteroapical MPI defects were found with similar frequency in the three groups with obstructive coronary disease. Septal MPI defect had a sensitivity of 92.3% and specificity of 85.4% in the diagnosis of proximal LAD disease. Normal septal perfusion with thallium-201 virtually excluded proximal LAD disease.

  18. Portable microfluidic raman system for rapid, label-free early disease signature detection

    SciTech Connect (OSTI)

    Wu, Meiye; Davis, Ryan Wesley; Hatch, Anson

    2015-09-01

    In the early stages of infection, patients develop non-specific or no symptoms at all. While waiting for identification of the infectious agent, precious window of opportunity for early intervention is lost. The standard diagnostics require affinity reagents and sufficient pathogen titers to reach the limit of detection. In the event of a disease outbreak, triaging the at-risk population rapidly and reliably for quarantine and countermeasure is more important than the identification of the pathogen by name. To expand Sandia's portfolio of Biological threat management capabilities, we will utilize Raman spectrometry to analyze immune subsets in whole blood to rapidly distinguish infected from non-infected, and bacterial from viral infection, for the purpose of triage during an emergency outbreak. The goal of this one year LDRD is to determine whether Raman spectroscopy can provide label-free detection of early disease signatures, and define a miniaturized Raman detection system meeting requirements for low- resource settings.

  19. Occupational obstructive airway diseases in Germany: Frequency and causes in an international comparison

    SciTech Connect (OSTI)

    Latza, U.; Baur, X.

    2005-08-01

    Occupational inhalative exposures contribute to a significant proportion of obstructive airway diseases (OAD), namely chronic obstructive pulmonary disease (COPD) and asthma. The number of occupational OAD in the German industrial sector for the year 2003 are presented. Other analyses of surveillance data were retrieved from Medline. Most confirmed reports of OAD are cases of sensitizer induced occupational asthma (625 confirmed cases) followed by COPD in coal miners (414 cases), irritant induced occupational asthma (156 cases), and isocyanate asthma (54 cases). Main causes of occupational asthma in Germany comprise flour/flour constituents (35.9%), food/feed dust (9.0%), and isocyanates (6.5%). Flour and grain dust is a frequent cause of occupational asthma in most European countries and South Africa. Isocyanates are still a problem worldwide. Although wide differences in the estimated incidences between countries exist due to deficits in the coverage of occupational OAD, the high numbers necessitate improvement of preventive measures.

  20. Determining the risk of cardiovascular disease using ion mobility of lipoproteins

    DOE Patents [OSTI]

    Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

    2010-05-11

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  1. Mechanisms of disease: epithelial-mesenchymal transition and back again: does cellular plasticity fuel neoplastic progression?

    SciTech Connect (OSTI)

    Bissell, Mina J; Turley, Eva A.; Veiseh, Mandana; Radisky, Derek C.; Bissell, Mina J.

    2008-02-13

    Epithelial-mesenchymal transition (EMT) is a conversion that facilitates organ morphogenesis and tissue remodeling in physiological processes such as embryonic development and wound healing. A similar phenotypic conversion is also detected in fibrotic diseases and neoplasia, which is associated with disease progression. EMT in cancer epithelial cells often seems to be an incomplete and bi-directional process. In this Review, we discuss the phenomenon of EMT as it pertains to tumor development, focusing on exceptions to the commonly held rule that EMT promotes invasion and metastasis. We also highlight the role of the RAS-controlled signaling mediators, ERK1, ERK2 and PI3-kinase, as microenvironmental responsive regulators of EMT.

  2. Disease Mutations in Rab7 Result in Unregulated Nucleotide Exchange and Inappropriate Activation

    SciTech Connect (OSTI)

    B McCray; E Skordalakes; J Taylor

    2011-12-31

    Rab GTPases are molecular switches that orchestrate vesicular trafficking, maturation and fusion by cycling between an active, GTP-bound form, and an inactive, GDP-bound form. The activity cycle is coupled to GTP hydrolysis and is tightly controlled by regulatory proteins. Missense mutations of the GTPase Rab7 cause a dominantly inherited axonal degeneration known as Charcot-Marie-Tooth type 2B through an unknown mechanism. We present the 2.8 A crystal structure of GTP-bound L129F mutant Rab7 which reveals normal conformations of the effector binding regions and catalytic site, but an alteration to the nucleotide binding pocket that is predicted to alter GTP binding. Through extensive biochemical analysis, we demonstrate that disease-associated mutations in Rab7 do not lead to an intrinsic GTPase defect, but permit unregulated nucleotide exchange leading to both excessive activation and hydrolysis-independent inactivation. Consistent with augmented activity, mutant Rab7 shows significantly enhanced interaction with a subset of effector proteins. In addition, dynamic imaging demonstrates that mutant Rab7 is abnormally retained on target membranes. However, we show that the increased activation of mutant Rab7 is counterbalanced by unregulated, GTP hydrolysis-independent membrane cycling. Notably, disease mutations are able to rescue the membrane cycling of a GTPase-deficient mutant. Thus, we demonstrate that disease mutations uncouple Rab7 from the spatial and temporal control normally imposed by regulatory proteins and cause disease not by a gain of novel toxic function, but by misregulation of native Rab7 activity.

  3. "Artificial" brains, electrical grids, and disease modeling: Los Alamos

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    science discoveries unveiled September 15 Science discoveries unveiled "Artificial" brains, electrical grids, and disease modeling: Los Alamos science discoveries unveiled September 15 The event is an opportunity for business leaders and community members to learn about where science is heading, as well as for students to discover potential new career directions. September 8, 2009 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez

  4. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    SciTech Connect (OSTI)

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the classical (neutral) and alternative (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ? Altered hepatic bile acid composition is observed in progressive NAFLD. ? Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ? Increased levels of taurine and conjugated bile acids are observed in

  5. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    SciTech Connect (OSTI)

    Wu, Weibin; Institutes of Biomedical Science, Fudan University, Shanghai 200032 ; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin; Institutes of Biomedical Science, Fudan University, Shanghai 200032

    2014-01-03

    Highlights: FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR attenuated alcohol-induced liver injury and steatosis. Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  6. Respiratory Protection Requirements Reduced in Parts of WIPP Underground

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Resources Resources The Office of Technology Transitions' mission extends across DOE's many programs, sites, and national laboratories. The links in this tab connect visitors with the numerous elements and resources that play a role in transitioning ideas into commercialized, impactful technologies. One of the best ways to expand the commercial impact of the Department is raising awareness to investors and industry about the capabilities and expertise housed in the agency's national laboratories

  7. Evidence and control of bifurcations in a respiratory system

    SciTech Connect (OSTI)

    Goldin, Matas A. Mindlin, Gabriel B.

    2013-12-15

    We studied the pressure patterns used by domestic canaries in the production of birdsong. Acoustically different sound elements (syllables) were generated by qualitatively different pressure gestures. We found that some ubiquitous transitions between syllables can be interpreted as bifurcations of a low dimensional dynamical system. We interpreted these results as evidence supporting a model in which different timescales interact nonlinearly.

  8. A support vector machine classifier reduces interscanner variation in the HRCT classification of regional disease pattern in diffuse lung disease: Comparison to a Bayesian classifier

    SciTech Connect (OSTI)

    Chang, Yongjun; Lim, Jonghyuck; Kim, Namkug; Seo, Joon Beom; Lynch, David A.

    2013-05-15

    Purpose: To investigate the effect of using different computed tomography (CT) scanners on the accuracy of high-resolution CT (HRCT) images in classifying regional disease patterns in patients with diffuse lung disease, support vector machine (SVM) and Bayesian classifiers were applied to multicenter data. Methods: Two experienced radiologists marked sets of 600 rectangular 20 Multiplication-Sign 20 pixel regions of interest (ROIs) on HRCT images obtained from two scanners (GE and Siemens), including 100 ROIs for each of local patterns of lungs-normal lung and five of regional pulmonary disease patterns (ground-glass opacity, reticular opacity, honeycombing, emphysema, and consolidation). Each ROI was assessed using 22 quantitative features belonging to one of the following descriptors: histogram, gradient, run-length, gray level co-occurrence matrix, low-attenuation area cluster, and top-hat transform. For automatic classification, a Bayesian classifier and a SVM classifier were compared under three different conditions. First, classification accuracies were estimated using data from each scanner. Next, data from the GE and Siemens scanners were used for training and testing, respectively, and vice versa. Finally, all ROI data were integrated regardless of the scanner type and were then trained and tested together. All experiments were performed based on forward feature selection and fivefold cross-validation with 20 repetitions. Results: For each scanner, better classification accuracies were achieved with the SVM classifier than the Bayesian classifier (92% and 82%, respectively, for the GE scanner; and 92% and 86%, respectively, for the Siemens scanner). The classification accuracies were 82%/72% for training with GE data and testing with Siemens data, and 79%/72% for the reverse. The use of training and test data obtained from the HRCT images of different scanners lowered the classification accuracy compared to the use of HRCT images from the same scanner. For

  9. Changes in Gas Bubble Disease Signs for Migrating Juvenile Salmonids Experimentally Exposed to Supersaturated Gasses, 1996-1997 Progress Report.

    SciTech Connect (OSTI)

    Absolon, Randall F.

    1999-03-01

    This study was designed to answer the question of whether gas bubble disease (GBD) signs change as a result of the hydrostatic conditions juvenile salmonids encounter when they enter the turbine intake of hydroelectric projects during their downstream migration.

  10. Cadmium exposure and cardiovascular disease in the 2005 Korea National Health and Nutrition Examination Survey

    SciTech Connect (OSTI)

    Lee, Mi-Sun; Park, Sung Kyun; Hu, Howard; Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI ; Lee, Sundong; Department of Preventive Medicine, School of Oriental Medicine, Sangji University, Wonju, Kangwon

    2011-01-15

    Background: Limited epidemiologic data are available concerning the cardiovascular effects of cadmium exposure, although recent studies suggest associations with myocardial infarction and peripheral arterial disease. We examined the associations of cadmium exposure with cardiovascular disease in nationally representative general Korean adults. Methods: We used cross-sectional data on blood cadmium and self-reported diagnoses of ischemic heart disease (IHD), stroke, and hypertension in a sub-sample of 1908 adults, aged 20 years and older, who participated in the 2005 Korea National Health and Nutrition Examination Survey (KNHANES). We used survey logistic regression models accounting for the complex sampling design to estimate the odds ratios (OR), adjusting for age, education, income, alcohol, smoking, body mass index, waist circumference, family history of hypertension, blood pressure, and blood lead. Results: The geometric mean of blood cadmium was 1.53 {mu}g/L. After adjusting for potential confounders, an interquartile range (IQR) increase in blood cadmium (0.91 {mu}g/L) was found to be associated with an increased risk for IHD (OR 2.1, 95% confidence interval (CI) 1.3-3.4). An IQR increase in blood cadmium was found to be associated with an elevated risk for hypertension only among men (OR 1.4, 95% CI 1.1-1.8) but not among women. No association was observed with stroke in both genders. Conclusions: These findings suggest that cadmium in blood may be associated with an increased risk for IHD and hypertension in the general Korean adult population.

  11. Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Mohammed, Nasiruddin [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Kestin, Larry Llyn, E-mail: lkestin@beaumont.ed [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Wong, Ching-yee Oliver [Department of Nuclear Medicine, William Beaumont Hospital, Royal Oak, MI (United States); Margolis, Jeffrey Harold [Department of Medical Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Chmielewski, Gary William; Welsh, Robert James [Department of Thoracic Surgery, William Beaumont Hospital, Royal Oak, MI (United States)

    2011-02-01

    Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

  12. Discovery of Disease Co-occurrence Patterns from Electronic Healthcare Reimbursement Claims Data

    SciTech Connect (OSTI)

    Ramanathan, Arvind; Pullum, Laura L; Hobson, Tanner C; Quinn, Shannon; Chennubhotla, Chakra; Valkova, Silvia

    2014-01-01

    Effective public health surveillance is important for national secu- rity. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build effective bio- surveillance systems that can track, monitor and report such events in a timely manner. Additionally, there is a need to identify sus- ceptible geographic regions/populations where these diseases may have a significant impact and design preemptive strategies to tackle them. With the digitization of health related information through electronic health records (EHR) and electronic healthcare claim re- imbursements (eHCR), there is a tremendous opportunity to ex- ploit these datasets for public health surveillance. In this paper, we present our analysis on the use of eHCR data for bio-surveillance by studying the 2009-2010 H1N1 pandemic flu season. We present a novel approach to extract spatial and temporal patterns of flu in- cidence across the United States (US) from eHCRs and find that a small, but distinct set of break-out patterns govern the flu and asthma incidence rates across the entire country. Further, we ob- serve a distinct temporal lag in the onset of flu when compared to asthma across geographic regions in the US. The patterns extracted from the data collectively indicate how these break-out patterns are coupled, even though the flu represents an infectious disease whereas asthma represents a typical chronic condition. Taken to- gether, our approach demonstrates how mining eHCRs can provide novel insights in tackling public health concerns.

  13. Tracers for monitoring the activity of sodium/glucose cotransporters in health and disease

    DOE Patents [OSTI]

    Wright, Ernest M; Barrio, Jorge R; Hirayama, Bruce A; Kepe, Vladimir

    2014-09-30

    Radiolabeled tracers for sodium/glucose cotransporters (SGLTs), their synthesis, and their use are provided. The tracers are methyl or ethyl pyranosides having an equatorial hydroxyl group at carbon-2 and a C 1 preferred conformation, radiolabeled with .sup.18F, .sup.123I, or .sup.124I, or free hexoses radiolabeled with .sup.18F, .sup.123I, or .sup.124. Also provided are in vivo and in vitro techniques for using these and other tracers as analytical and diagnostic tools to study glucose transport, in health and disease, and to evaluate therapeutic interventions.

  14. Epidemiology and Control of Infectious Diseases of Salmonids in the Columbia River Basin, 1987 Annual Report.

    SciTech Connect (OSTI)

    Fryer, John L.

    1989-01-01

    The Department of Microbiology at Oregon State University with funding from the Bonneville Power Administration has been conducting a study concerning the epidemiology and control of three fish pathogens which cause major disease problems in salmonids of the Columbia River basin. The pathogens studied include Cera to myxa Shasta, the myxosporean parasite which causes ceratomyxosis; Renibacterium salmoninarum, the bacterium which is the etiological agent of bacterial kidney disease; and the rhabdovirus which causes infectious hematopoietic necrosis (IHN). During this project, the host and geographic range of C. Shasta have been more precisely determined and the known geographic range has been significantly expanded. The effects of the parasite on fish migrating through the Columbia River and on their introduction into salt water have been examined. Similar studies have been conducted with R. salmoninarum and it has been shown that bacterial kidney disease occurs at all life stages of salmonids and is responsible for mortality in both fresh and salt water. It has also been demonstrated that different isolates of R. salmoninarum have different antigenic composition. Results of demonstration projects designed to control IHN by using UV treated water for early rearing of salmonid fry were equivocal. The scope of the project was considerably narrowed and focused during the past two years The project has concentrated on a study concerning the biology of C. Shasta and the identification of potential chemotherapeutants for control of bacterial kidney disease. The emphasis of work on C. Shasta has been its pathogenesis. This aspect of the parasite has been investigated using histopathologic and immunologic methodology. Mode of transmission, the nature of the infectious stage, and potential intermediate hosts of the parasite have also been areas of active research. Classes of chemotherapeutants with the highest potential for efficacy against R. salmoninarum have been

  15. Gas bubble disease in smallmouth bass and northern squawfish from the Snake and Columbia Rivers

    SciTech Connect (OSTI)

    Montgomery, J.C.; Becker, C.D.

    1980-11-01

    Supersaturation of the Columbia and Snake River systems was caused by entrainment of air into water spilling over hydroelectric dams. Total gas saturations of 100% or more have occurred during the spring in each river system. External signs of gas bubble diseases were noted in adult Smallmouth bass and northern squawfish collected from the lower Snake and mid-Columbia rivers during 1975-76. Emboli occurred beneath membranes of the opercula body, and fins of 72% of the smallmouth bass and 84% of the northern squawfish. Hemorrhage was also noted on the caudal, anal, and pectoral fins of several fish.

  16. Root Diseases and Exotic Ecosystems: Implications for Long-Term Site Productivity

    SciTech Connect (OSTI)

    Otrosina, W. J.; Garbelotto, M.

    1997-09-01

    Management activities and various land uses have taken place recently that have dramatically altered edaphic and environmental conditions under which forest tree species and ecosystems have evolved. Sequoia giganteum stands, fire suppression in this fire dependent ecosystem has resulted in increased mortality due to Heterobasidion annosum. On hypothesis is that fire suppression results in increased encroachment of true firs, easily infected by S-group Heterobasidion annosum, thereby transferring the disease via root contacts with S. giganteum. Existence of a hybrid with S and P ISG's of H. annosum may be evidence for anthropogenic influences on evolutionary pathways in this pathogen.

  17. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease

    SciTech Connect (OSTI)

    Willing, B.; Halfvarson, J.; Dicksved, J.; Rosenquist, M.; Jarnerot, G.; Engstrand, L.; Tysk, C.; Jansson, J. K

    2008-08-15

    Large inter-individual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease. To reduce variations in exposure during establishment of the gut flora and influence of genotype, we studied the mucosaassociated microbiota of monozygotic twin pairs that were discordant (n=6) or concordant (n=4) for Crohn's disease. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing and quantitative real-time PCR. The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal Crohn's had a dramatically lower abundance (P<0.001) of Faecalibacterium prausnitzii and increased abundance (P<0.03) of Escherichia coli compared to healthy co-twins and those with Crohn's localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype. The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal Crohn's disease phenotype, distinct from colonic Crohn's disease and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of Crohn's and eventually customized treatment.

  18. Evolution of a genetic disease in an ethnic isolate:. beta. -Thalassemia in the Jews of Kurdistan

    SciTech Connect (OSTI)

    Rund, D.; Cohen, T.; Filon, D.; Rachmilewitz, E.; Oppenheim, A. ); Dowling, C.E.; Warren T.C.; Kazazian, H.H. Jr. ); Barak, I. )

    1991-01-01

    {beta}-Thalassemia is a hereditary disease caused by any of 90 different point mutations in the {beta}-globin gene. Specific populations generally carry a small number of mutations, the most common of which are those that are widely distributed regionally. The present study constitutes an extensive molecular characterization of this disease in a small, highly inbred ethnic group with a high incidence of {beta}-thalassemia-the Jews of Kurdistan. An unusual mutational diversity was observed. In 42 sibships 13 different mutations were identified, of which 3 are newly discovered. Four of the mutations are unique to Kurdish Jews and have not been discovered in any other population. A fifth was found outside Kurdish Jews only in an Iranian from Khuzistan, a region bordering Kurdistan. Two-thirds of the mutant chromosomes carry the mutations unique to Kurdish Jews. The authors traced the origin of the mutations to specific geographic regions within Kurdistan. This information, supported by haplotype analysis, suggests that thalassemia in central Kurdistan (northern Iraq) has evolved primarily from multiple mutational events. They conclude that several evolutionary mechanisms contributed to the evolution of {beta}-thalassemia in this small ethnic isolate.

  19. Proteomic Analysis of Lyme Disease: Global Protein Comparison of Three Strains of Borrelia burgdorferi

    SciTech Connect (OSTI)

    Jacobs, Jon M.; Yang, Xiaohua; Luft, Benjamin J.; Dunn, John J.; Camp, David G.; Smith, Richard D.

    2005-04-01

    The Borrelia burgdorferi spirochete is the causative agent of Lyme disease, the most common tick-borne disease in the United States. It has been studied extensively to help understand its pathogenicity of infection and how it can persist in different mammalian hosts. We report the proteomic analysis of the archetype B. burgdorferi B31 strain and two other strains (ND40, and JD-1) having different Borrelia pathotypes using strong cation exchange fractionation of proteolytic peptides followed by high-resolution, reversed phase capillary liquid chromatography coupled with ion trap tandem mass spectrometric (LC-MS/MS) analysis. Protein identification was facilitated by the availability of the complete B31 genome sequence. A total of 665 Borrelia proteins were identified representing ~38 % coverage of the theoretical B31 proteome. A significant overlap was observed between the identified proteins in direct comparisons between any two strains (>72%), but distinct differences were observed among identified hypothetical and outer membrane proteins of the three strains. Such a concurrent proteomic overview of three Borrelia strains based upon only the B31 genome sequence is shown to provide significant insights into the presence or absence of specific proteins and a broad overall comparison among strains.

  20. Iron and aluminum interaction with amyloid-beta peptides associated with Alzheimer’s disease

    SciTech Connect (OSTI)

    Drochioiu, Gabi; Ion, Laura; Murariu, Manuela; Habasescu, Laura

    2014-10-06

    An elevation in the concentration of heavy metal ions in Alzheimer’s disease (AD) brain has been demonstrated in many studies. Aβ precipitation and toxicity in AD brains seem to be caused by abnormal interactions with neocortical metal ions, especially iron, copper, zinc, and aluminum [1–3]. There is increasing evidence that iron and aluminum ions are involved in the mechanisms that underlie the neurodegenerative diseases [4,5]. However, evidence was brought to demonstrate that some Aβ fragments, at physiological pH, are not able to form binary complexes with Fe(III) ions of sufficient stability to compete with metal hydroxide precipitation [6]. On the contrary, multiple metal ions are known to interact with Aβ peptides [7]. Consequently, we investigated here the interaction of Fe(II/III) and Al(III) ions with some amyloid-β peptides and fragments that results in peptide aggregation and fibrillation [8,9]. Infrared spectroscopy, atomic force microscopy, scanning electron microscopy, electrophoresis and mass spectrometry demonstrated conformational changes of peptides in the presence of such metals.

  1. Evidence for increased recombination near the human insulin gene: implication for disease association studies

    SciTech Connect (OSTI)

    Chakravarti, A.; Elbein, S.C.; Permutt, M.A.

    1986-02-01

    Haplotypes for four new restriction site polymorphisms (detected by Rsa I, Taq I, HincII, and Sac I) and a previously identified DNA length polymorphism (5'FP), all at the insulin locus, have been studied in US Blacks, African Blacks, Caucasians, and Pima Indians. Black populations are polymorphic for all five markers, whereas the other groups are polymorphic for Rsa I, Taq I, and 5'FP only. The data suggest that approx. = 1 in 550 base pairs is variant in this region. The polymorphisms, even though located within 20 kilobases, display low levels of nonrandom association. Population genetic analysis suggests that recombination within this 20-kilobase segment occurs 24 times more frequently than expected if crossing-over occurred uniformly throughout the human genome. These findings suggest that population association between DNA polymorphisms and disease susceptibility genes near the insulin gene or structural mutations in the insulin gene will be weak. Thus, population studies would probably require large sample sizes to detect association. However, the low levels of nonrandom association increase the information content of the locus for linkage studies, which is the best alternative for discovering disease susceptibility genes.

  2. A Semiautomated Framework for Integrating Expert Knowledge into Disease Marker Identification

    SciTech Connect (OSTI)

    Wang, Jing; Webb-Robertson, Bobbie-Jo M.; Matzke, Melissa M.; Varnum, Susan M.; Brown, Joseph N.; Riensche, Roderick M.; Adkins, Joshua N.; Jacobs, Jon M.; Hoidal, John R.; Scholand, Mary Beth; Pounds, Joel G.; Blackburn, Michael R.; Rodland, Karin D.; McDermott, Jason E.

    2013-10-01

    Background. The availability of large complex data sets generated by high throughput technologies has enabled the recent proliferation of disease biomarker studies. However, a recurring problem in deriving biological information from large data sets is how to best incorporate expert knowledge into the biomarker selection process. Objective. To develop a generalizable framework that can incorporate expert knowledge into data-driven processes in a semiautomated way while providing a metric for optimization in a biomarker selection scheme. Methods. The framework was implemented as a pipeline consisting of five components for the identification of signatures from integrated clustering (ISIC). Expert knowledge was integrated into the biomarker identification process using the combination of two distinct approaches; a distance-based clustering approach and an expert knowledge-driven functional selection. Results. The utility of the developed framework ISIC was demonstrated on proteomics data from a study of chronic obstructive pulmonary disease (COPD). Biomarker candidates were identified in a mouse model using ISIC and validated in a study of a human cohort. Conclusions. Expert knowledge can be introduced into a biomarker discovery process in different ways to enhance the robustness of selected marker candidates. Developing strategies for extracting orthogonal and robust features from large data sets increases the chances of success in biomarker identification.

  3. Climate, Environmental, and Socioeconomic Change Weighing up the Balance in Vector-Borne Disease Transmission

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Parham, Paul; Waldock, Johanna; Christophides, George; Hemming, Deborah; Agusto, Folashade; Evans, Katherine J; Fefferman, Nina; Gaff, Holly; Gumel, Abba; LaDeau, Shannon; et al

    2015-01-01

    Arguably one of the most important effects of climate change is the potential impact on human health. While this is likely to take many forms, the implications for future transmission of vector-borne diseases (VBDs), given their ongoing contribution to global disease burden, are both extremely important and highly uncertain. In part, this is due not only to data limitations and methodological challenges when integrating climate-driven VBD models and climate change projections, but, perhaps most crucially, the multitude of epidemiological, ecological, and socioeconomic factors that drive VBD transmission, and this complexity has generated considerable debate over the last 10-15 years. Inmore » this article, and Theme Issue, we seek to elucidate current knowledge around this topic, identify key themes and uncertainties, evaluate ongoing challenges and open research questions, and, crucially, offer some solutions for the field moving forwards. Although many of these challenges are ubiquitous across multiple VBDs, more specific issues also arise in different vector-pathogen systems. This Theme Issue seeks to cover both, reflected in the breadth and depth of the topics and VBD-systems considered, itself strongly indicative of the challenging, but necessary, multidisciplinary nature of this research field.« less

  4. Climate, Environmental, and Socioeconomic Change Weighing up the Balance in Vector-Borne Disease Transmission

    SciTech Connect (OSTI)

    Parham, Paul; Waldock, Johanna; Christophides, George; Hemming, Deborah; Agusto, Folashade; Evans, Katherine J; Fefferman, Nina; Gaff, Holly; Gumel, Abba; LaDeau, Shannon; Lenhart, Suzanne; Mickens, Ronald; Naumova, Elena; Ostfeld, Richard; Ready, Paul; Thomas, Matthew; Velasco-Hernandez, Jorge; Edwin, Michael

    2015-01-01

    Arguably one of the most important effects of climate change is the potential impact on human health. While this is likely to take many forms, the implications for future transmission of vector-borne diseases (VBDs), given their ongoing contribution to global disease burden, are both extremely important and highly uncertain. In part, this is due not only to data limitations and methodological challenges when integrating climate-driven VBD models and climate change projections, but, perhaps most crucially, the multitude of epidemiological, ecological, and socioeconomic factors that drive VBD transmission, and this complexity has generated considerable debate over the last 10-15 years. In this article, and Theme Issue, we seek to elucidate current knowledge around this topic, identify key themes and uncertainties, evaluate ongoing challenges and open research questions, and, crucially, offer some solutions for the field moving forwards. Although many of these challenges are ubiquitous across multiple VBDs, more specific issues also arise in different vector-pathogen systems. This Theme Issue seeks to cover both, reflected in the breadth and depth of the topics and VBD-systems considered, itself strongly indicative of the challenging, but necessary, multidisciplinary nature of this research field.

  5. Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease

    SciTech Connect (OSTI)

    Jiang, Pengtao; University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049 ; Huang, Zhen; Zhao, Hong; Wei, Taotao

    2013-04-19

    Highlights: Free fatty acids exposure induces elevated autophagy. H{sub 2}O{sub 2} inhibits autophagic flux through impairing the fusion between autophagosomes and lysosomes. Inhibition of autophagy potentiates H{sub 2}O{sub 2}-induced cell death. -- Abstract: Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this study was to determine whether autophagy plays a role in the pathogenesis of NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon exposure to free fatty acids, as confirmed by the increase in the number of autophagosomes. However, exposure of hepatoma cells to H{sub 2}O{sub 2} and TNF-?, two typical second hit factors, increased the initiation of autophagy but inhibited the autophagic flux. The inhibition of autophagy sensitized cells to pro-apoptotic stimuli. Taken together, our results suggest that autophagy acts as a protective mechanism in the pathogenesis of NAFLD and that impairment of autophagy might induce more severe lesions of the liver. These findings will be a benefit to the understanding of the pathogenesis of NAFLD and might suggest a strategy for the prevention and cure of NAFLD.

  6. A Semiautomated Framework for Integrating Expert Knowledge into Disease Marker Identification

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wang, Jing; Webb-Robertson, Bobbie-Jo M.; Matzke, Melissa M.; Varnum, Susan M.; Brown, Joseph N.; Riensche, Roderick M.; Adkins, Joshua N.; Jacobs, Jon M.; Hoidal, John R.; Scholand, Mary Beth; et al

    2013-01-01

    Background . The availability of large complex data sets generated by high throughput technologies has enabled the recent proliferation of disease biomarker studies. However, a recurring problem in deriving biological information from large data sets is how to best incorporate expert knowledge into the biomarker selection process. Objective . To develop a generalizable framework that can incorporate expert knowledge into data-driven processes in a semiautomated way while providing a metric for optimization in a biomarker selection scheme. Methods . The framework was implemented as a pipeline consisting of five components for the identification of signatures from integrated clustering (ISIC).more » Expert knowledge was integrated into the biomarker identification process using the combination of two distinct approaches; a distance-based clustering approach and an expert knowledge-driven functional selection. Results . The utility of the developed framework ISIC was demonstrated on proteomics data from a study of chronic obstructive pulmonary disease (COPD). Biomarker candidates were identified in a mouse model using ISIC and validated in a study of a human cohort. Conclusions . Expert knowledge can be introduced into a biomarker discovery process in different ways to enhance the robustness of selected marker candidates. Developing strategies for extracting orthogonal and robust features from large data sets increases the chances of success in biomarker identification.« less

  7. Method for detection of dental caries and periodontal disease using optical imaging

    DOE Patents [OSTI]

    Nathel, H.; Kinney, J.H.; Otis, L.L.

    1996-10-29

    A method is disclosed for detecting the presence of active and inactive caries in teeth and diagnosing periodontal disease uses non-ionizing radiation with techniques for reducing interference from scattered light. A beam of non-ionizing radiation is divided into sample and reference beams. The region to be examined is illuminated by the sample beam, and reflected or transmitted radiation from the sample is recombined with the reference beam to form an interference pattern on a detector. The length of the reference beam path is adjustable, allowing the operator to select the reflected or transmitted sample photons that recombine with the reference photons. Thus radiation scattered by the dental or periodontal tissue can be prevented from obscuring the interference pattern. A series of interference patterns may be generated and interpreted to locate dental caries and periodontal tissue interfaces. 7 figs.

  8. Method for detection of dental caries and periodontal disease using optical imaging

    DOE Patents [OSTI]

    Nathel, Howard; Kinney, John H.; Otis, Linda L.

    1996-01-01

    A method for detecting the presence of active and inactive caries in teeth and diagnosing periodontal disease uses non-ionizing radiation with techniques for reducing interference from scattered light. A beam of non-ionizing radiation is divided into sample and reference beams. The region to be examined is illuminated by the sample beam, and reflected or transmitted radiation from the sample is recombined with the reference beam to form an interference pattern on a detector. The length of the reference beam path is adjustable, allowing the operator to select the reflected or transmitted sample photons that recombine with the reference photons. Thus radiation scattered by the dental or periodontal tissue can be prevented from obscuring the interference pattern. A series of interference patterns may be generated and interpreted to locate dental caries and periodontal tissue interfaces.

  9. Low Prevalence of Chronic Beryllium Disease among Workers at a Nuclear Weapons Research and Development Facility

    SciTech Connect (OSTI)

    Arjomandi, M; Seward, J P; Gotway, M B; Nishimura, S; Fulton, G P; Thundiyil, J; King, T E; Harber, P; Balmes, J R

    2010-01-11

    To study the prevalence of beryllium sensitization (BeS) and chronic beryllium disease (CBD) in a cohort of workers from a nuclear weapons research and development facility. We evaluated 50 workers with BeS with medical and occupational histories, physical examination, chest imaging with HRCT (N=49), and pulmonary function testing. Forty of these workers also underwent bronchoscopy for bronchoalveolar lavage (BAL) and transbronchial biopsies. The mean duration of employment at the facility was 18 yrs and the mean latency (from first possible exposure) to time of evaluation was 32 yrs. Five of the workers had CBD at the time of evaluation (based on histology or HRCT); three others had evidence of probable CBD. These workers with BeS, characterized by a long duration of potential Be exposure and a long latency, had a low prevalence of CBD.

  10. Method and system for the diagnosis of disease using retinal image content and an archive of diagnosed human patient data

    DOE Patents [OSTI]

    Tobin, Kenneth W; Karnowski, Thomas P; Chaum, Edward

    2013-08-06

    A method for diagnosing diseases having retinal manifestations including retinal pathologies includes the steps of providing a CBIR system including an archive of stored digital retinal photography images and diagnosed patient data corresponding to the retinal photography images, the stored images each indexed in a CBIR database using a plurality of feature vectors, the feature vectors corresponding to distinct descriptive characteristics of the stored images. A query image of the retina of a patient is obtained. Using image processing, regions or structures in the query image are identified. The regions or structures are then described using the plurality of feature vectors. At least one relevant stored image from the archive based on similarity to the regions or structures is retrieved, and an eye disease or a disease having retinal manifestations in the patient is diagnosed based on the diagnosed patient data associated with the relevant stored image(s).

  11. DEVELOPMENT OF AUTOMATED SOFTWARE PROGRAM FOR THE ANALYSIS OF ALZHEIMER'S DISEASE BETA-AMYLOID SCANS

    SciTech Connect (OSTI)

    Mariotti, Jack; Zubal, George

    2013-12-18

    Study goal: A Phase 1 evaluation of the kinetics, clearance and cerebral distribution of one novel peripheral benzodiazepine receptors(PBR)positron emission tomography (PET) imaging agent, 18F-PBR-111 following intravenous administration in healthy volunteers and Alzheimer's disease (AD) patients. Short title: Evaluation of PET imaging with PBR-111 in HV and AD subjects Proof of Mechanism. Primary Objective: To evaluate the cerebral distribution of PBR-111 positron emission tomography (PET) for detection/exclusion of microglial activation in patients with Alzheimer's disease subjects compared to healthy volunteers. Secondary objectives: - To assess the dynamic uptake and washout of [18F]PBR-111, a potential imaging bio-marker for inflammatory changes in brain, using positron emission tomography in subjects with Alzheimer's disease (AD) and healthy volunteers (HV). - To perform blood metabolite characterization of [18F]PBR-111 in subjects with AD and HV to determine the nature of metabolites in assessment of [18F]-PBR-111 as a PET brain imaging agent. Name of radioactive drug substance: PBR-111 Dose(s): The applied PBR-111 radioactive dose will be up to 5.0 mCi, diluted in a maximum of 10 ml of saline. The radioligand will be administered as a slow intravenous bolus injection (i.e., 6 sec/ml) into a large vein (e.g., antecubital vein). Route of administration: Intravenous injection Duration of treatment: Single administration of a diagnostic agent Indication: PBR-111 positron emission tomography (PET) imaging has the potential to detect microglial activation. In the presence of PBR-111 uptake (representative of microglial activation), inflammation in the brain can be detected. Diagnosis and main criteria for inclusion: Study participants will be HVs and patients diagnosed with probable AD. HVs must be 18 years of age (at least four subjects 50 years of age) and have no evidence of cognitive impairment or other neurologic disease by medical history. The lack of

  12. Disease Control After Reduced Volume Conformal and Intensity Modulated Radiation Therapy for Childhood Craniopharyngioma

    SciTech Connect (OSTI)

    Merchant, Thomas E.; Kun, Larry E.; Hua, Chia-Ho; Wu, Shengjie; Xiong, Xiaoping; Sanford, Robert A.; Boop, Frederick A.

    2013-03-15

    Purpose: To estimate the rate of disease control after conformal radiation therapy using reduced clinical target volume (CTV) margins and to determine factors that predict for tumor progression. Methods and Materials: Eighty-eight children (median age, 8.5 years; range, 3.2-17.6 years) received conformal or intensity modulated radiation therapy between 1998 and 2009. The study group included those prospectively treated from 1998 to 2003, using a 10-mm CTV, defined as the margin surrounding the solid and cystic tumor targeted to receive the prescription dose of 54 Gy. The CTV margin was subsequently reduced after 2003, yielding 2 groups of patients: those treated with a CTV margin greater than 5 mm (n=26) and those treated with a CTV margin less than or equal to 5 mm (n=62). Disease progression was estimated on the basis of additional variables including sex, race, extent of resection, tumor interventions, target volume margins, and frequency of weekly surveillance magnetic resonance (MR) imaging during radiation therapy. Median follow-up was 5 years. Results: There was no difference between progression-free survival rates based on CTV margins (>5 mm vs ≤5 mm) at 5 years (88.1% ± 6.3% vs 96.2% ± 4.4% [P=.6386]). There were no differences based on planning target volume (PTV) margins (or combined CTV plus PTV margins). The PTV was systematically reduced from 5 to 3 mm during the time period of the study. Factors predictive of superior progression-free survival included Caucasian race (P=.0175), no requirement for cerebrospinal fluid shunting (P=.0066), and number of surveillance imaging studies during treatment (P=.0216). Patients whose treatment protocol included a higher number of weekly surveillance MR imaging evaluations had a lower rate of tumor progression. Conclusions: These results suggest that targeted volume reductions for radiation therapy using smaller margins are feasible and safe but require careful monitoring. We are currently investigating

  13. Key residues for the oligomerization of A{beta}42 protein in Alzheimer's disease

    SciTech Connect (OSTI)

    Ngo, Sam; Guo, Zhefeng

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer A{beta} oligomers are neurotoxins and likely the causing agents for Alzheimer's disease. Black-Right-Pointing-Pointer A{beta}42 fusion protein form globular oligomers. Black-Right-Pointing-Pointer A{beta}42 fusion protein oligomers contain SDS-resistant tetramers and hexamers. Black-Right-Pointing-Pointer Cysteine substitutions at residues 31, 32, 34, 39-41 disrupt A{beta}42 oligomerization. -- Abstract: Deposition of amyloid fibrils consisting of amyloid {beta} (A{beta}) protein as senile plaques in the brain is a pathological hallmark of Alzheimer's disease. However, a growing body of evidence shows that soluble A{beta} oligomers correlate better with dementia than fibrils, suggesting that A{beta} oligomers may be the primary toxic species. The structure and oligomerization mechanism of these A{beta} oligomers are crucial for developing effective therapeutics. Here we investigated the oligomerization of A{beta}42 in the context of a fusion protein containing GroES and ubiquitin fused to the N-terminus of A{beta} sequence. The presence of fusion protein partners, in combination with a denaturing buffer containing 8 M urea at pH 10, is unfavorable for A{beta}42 aggregation, thus allowing only the most stable structures to be observed. Transmission electron microscopy showed that A{beta}42 fusion protein formed globular oligomers, which bound weakly to thioflavin T and Congo red. SDS-PAGE shows that A{beta}42 fusion protein formed SDS-resistant hexamers and tetramers. In contrast, A{beta}40 fusion protein remained as monomers on SDS gel, suggesting that the oligomerization of A{beta}42 fusion protein is not due to the fusion protein partners. Cysteine scanning mutagenesis at 22 residue positions further revealed that single cysteine substitutions of the C-terminal hydrophobic residues (I31, I32, L34, V39, V40, and I41) led to disruption of hexamer and tetramer formation, suggesting that hydrophobic interactions between these

  14. The plant decapeptide OSIP108 prevents copper-induced toxicity in various models for Wilson disease

    SciTech Connect (OSTI)

    Spincemaille, Pieter; Pham, Duc-Hung; Chandhok, Gursimran; Verbeek, Jef; Zibert, Andree; Libbrecht, Louis; Schmidt, Hartmut; Esguerra, Camila V.; Witte, Peter A.M. de; Cammue, Bruno P.A.; Cassiman, David; Thevissen, Karin

    2014-10-15

    Background: Wilson disease (WD) is caused by accumulation of excess copper (Cu) due to a mutation in the gene encoding the liver Cu transporter ATP7B, and is characterized by acute liver failure or cirrhosis and neuronal cell death. We investigated the effect of OSIP108, a plant derived decapeptide that prevents Cu-induced apoptosis in yeast and human cells, on Cu-induced toxicity in various mammalian in vitro models relevant for WD and in a Cu-toxicity zebrafish larvae model applicable to WD. Methods: The effect of OSIP108 was evaluated on viability of various cell lines in the presence of excess Cu, on liver morphology of a Cu-treated zebrafish larvae strain that expresses a fluorescent reporter in hepatocytes, and on oxidative stress levels in wild type AB zebrafish larvae. Results: OSIP108 increased not only viability of Cu-treated CHO cells transgenically expressing ATP7B and the common WD-causing mutant ATP7B{sup H1069Q}, but also viability of Cu-treated human glioblastoma U87 cells. Aberrancies in liver morphology of Cu-treated zebrafish larvae were observed, which were further confirmed as Cu-induced hepatotoxicity by liver histology. Injections of OSIP108 into Cu-treated zebrafish larvae significantly increased the amount of larvae with normal liver morphology and decreased Cu-induced production of reactive oxygen species. Conclusions: OSIP108 prevents Cu-induced toxicity in in vitro models and in a Cu-toxicity zebrafish larvae model applicable to WD. General significance: All the above data indicate the potential of OSIP108 as a drug lead for further development as a novel WD treatment. - Highlights: • Wilson disease (WD) is characterized by accumulation of toxic copper (Cu). • OSIP108 increases viability of Cu-treated cellular models applicable to WD. • OSIP108 injections preserve liver morphology of Cu-treated zebrafish larvae. • OSIP108 injections into zebrafish larvae abrogates Cu-induced oxidative stress.

  15. Modeling oscillatory dynamics in brain microcircuits as a way to help uncover neurological disease mechanisms: A proposal

    SciTech Connect (OSTI)

    Skinner, F. K.; Department of Medicine , University of Toronto, 200 Elizabeth Street, Toronto, Ontario M5G 2C4; Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, Ontario M5S 1A8 ; Ferguson, K. A.; Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, Ontario M5S 1A8

    2013-12-15

    There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of neurological disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with disease. Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical mechanisms underlying neurological disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.

  16. Nanoimaging to Prevent and Treat Alzheimers and Parkinsons Diseases. Scientific/Technical report

    SciTech Connect (OSTI)

    Yuri L. Lyubchenko, PhD, DSc

    2012-12-20

    This project will develop innovative approaches to characterization of the very early stages of protein aggregation that eventually can be translated to the development of early diagnostic tools and efficient treatments for Alzheimers, Parkinsons and Huntingtons diseases. Funding will be used to acquire nanoimaging technology for nanoscale imaging, manipulation and analysis of biomedical materials to develop treatments that will repair disabled proteins and cure diseases that result from protein malfunction, specifically Alzheimers and Parkinsons diseases. Expected outcomes include tests for early diagnosis and therapeutic treatments for these devastating neurological diseases. To elucidate the mechanisms of protein misfolding, we will establish an extensive program of experimental studies using a broad arsenal of advanced nanoscale and traditional techniques that will be integrated with molecular-scale modeling of protein misfolding and the nucleation of aggregate structures. To identify intracellular machinery or/and multicomponent complexes critically involved in protein misfolding, we will characterize interactions between targeted proteins and specific intracellular components or metabolites that impact on protein conformational pathways leading to protein misfolding accompanied by formation of toxic aggregated morphologies. To design innovative nanotechnology tools for the control of intracellular protein misfolding and aggregation processes, we will develop a predictive molecular scale model for intracellular protein misfolding and the formation of toxic aggregates. Verified through experimental studies, the objective is to establish an enabling foundation for the engineering of novel molecular diagnostics and therapeutics for various cellular pathologies.

  17. Analyzing and modeling the kinetics of amyloid beta pores associated with Alzheimer’s disease pathology

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Ullah, Ghanim; Demuro, Angelo; Parker, Ian; Pearson, John E.; Xu, Shang -Zhong

    2015-09-08

    Amyloid beta (Aβ) oligomers associated with Alzheimer’s disease (AD) form Ca2+-permeable plasma membrane pores, leading to a disruption of the otherwise well-controlled intracellular calcium (Ca2+) homeostasis. The resultant up-regulation of intracellular Ca2+ concentration has detrimental implications for memory formation and cell survival. The gating kinetics and Ca2+ permeability of Aβ pores are not well understood. We have used computational modeling in conjunction with the ability of optical patch-clamping for massively parallel imaging of Ca2+ flux through thousands of pores in the cell membrane of Xenopus oocytes to elucidate the kinetic properties of Aβ pores. The fluorescence time-series data from individualmore » pores were idealized and used to develop data-driven Markov chain models for the kinetics of the Aβ pore at different stages of its evolution. Our study provides the first demonstration of developing Markov chain models for ion channel gating that are driven by optical-patch clamp data with the advantage of experiments being performed under close to physiological conditions. As a result, we demonstrate the up-regulation of gating of various Ca2+ release channels due to Aβ pores and show that the extent and spatial range of such up-regulation increases as Aβ pores with low open probability and Ca2+ permeability transition into those with high open probability and Ca2+ permeability.« less

  18. Cardiovascular and Interventional Radiological Society of Europe Guidelines on Endovascular Treatment in Aortoiliac Arterial Disease

    SciTech Connect (OSTI)

    Rossi, Michele; Iezzi, Roberto

    2013-11-06

    PurposeThese guidelines are intended for use in assessing the standard for technical success and safety in aorto-iliac percutaneous endovascular interventions.MethodsAny recommendation contained in the text comes from the highest level and extension of literature review available to date.ResultsThe success of endovascular procedures is strictly related to an accurate planning based mainly on CT- or MR-angiography. TASC II A through C lesions have an endovascular-first option Pre-procedure ASA antiplatelet therapy is advisable in all cases. The application of stents improves the immediate hemodynamic and most likely long-term clinical results. Cumulative mean complication rate is 7.51% according to the most relevant literature. Most of the complications can be managed by means of percutaneous techniques.ConclusionThe design and quality of devices, as well as the easy and accuracy of performing these procedures, have improved over the last decades, leading to the preferential treatment of aorto-iliac steno-obstructive disease via endovascular means, often as first-line therapy, with high technical success rate and low morbidity. This is mirrored by the decreasing number of patients undergoing surgical grafts over the last years with patency, limb salvage, and survival rates equivalent to open reconstruction.

  19. Etiology of Early Lifestage Diseases, Project 84-44, 1985 Final Report.

    SciTech Connect (OSTI)

    Sauter, R.W.

    1986-10-01

    Each year hatcheries experience loss of eggs, fry and fingerlings due to a group of poorly defined diseases called White Spot and Coagulated Yolk. Samples of maternal blood and ovarian fluid (coelomic fluid), as well as unfertilized eggs, were collected at spawning and subsequently tested for the presence of bacteria. Our tests reveal that there is a wide range in mortality rates experienced by the progeny of different brood salmon. Microbiologic tests revealed that these eggs contained a variety of both Gram positive and Gram negative bacteria within their yolk and that the fluids from the females who produced these lots were contaminated with a variety of bacteria. In contrast the eggs and maternal fluids from the six egg lots which experienced the lowest mortalities did not contain high numbers of Gram positive bacteria and contributed only 5% of the total mortalities observed within the 30 egg lots tested. From the 60 egg lots tested over two brood years we have isolated 18 different bacterial genera containing 32 different species from within the yolk surface sterilized, unfertilized eggs. Our tests suggest that Aeromonas hydrophila, Pseudomonas (3 species) Staphylococcus aureus, Vibrio sp., Corynebacterium hoffmanii, Listeria sp. and Bacillus sp. when detected within the yolk of eggs sampled from egg lots prior to fertilization will be associated with higher than normal mortality rates when the remainder of the egg lots containing these bacteria are incubated and reared. 36 refs., 16 figs.

  20. Thermodynamics imprinting reveals differential binding of metals to {alpha}-synuclein: Relevance to parkinson's disease

    SciTech Connect (OSTI)

    Bharathi; Rao, K.S.J. . E-mail: kjr5n@yahoo.co.in

    2007-07-20

    The aggregation of {alpha}-synuclein is a hallmark feature of Parkinson's disease (PD) and other synucleinopathies. Metals are the significant etiological factors in PD, and their interaction with {alpha}-synuclein affect dramatically the kinetics of fibrillation in vitro and are proposed to play an important and potential neurodegenerative role in vivo. In the present study, we investigated the stoichiometry of binding of copper [Cu (II)] and iron [Fe (III)] with {alpha}-synuclein (wild recombinant type and A30P, A53T, E46K mutant forms) using isothermal titration calorimetry (ITC). {alpha}-Synuclein monomer (wild and mutant forms) titrated by Cu (II), showed two binding sites, with an apparent K {sub B} of 10{sup 5} M and 10{sup 4} M, respectively. But, {alpha}-synuclein (wild type and mutant forms) titrated with Fe (III) revealed a K {sub B} of 10{sup 5} M with single binding site. The present investigation uncovers the detailed binding propensities between metals and {alpha}-synuclein and has biological implications in PD.

  1. Analysis of HLA-DP association with beryllium disease susceptibility in pooled exposed populations

    SciTech Connect (OSTI)

    Cesare Saltini, Massimo Amicosante

    2009-12-19

    Berylliosis or Chronic Beryllium Disease is a chronic granulomatous disorder primarily involving the lung associated with the exposition to low doses of Beryllium (Be) in the workplace. Berylliosis risk has been associated with the presence of a glutamate at position 69 of the HLA-DP beta chain (HLA-DPbetaGlu69) that is expressed in about 97% of disease cases and in 27% of the unaffected Be-exposed controls (p<0.0001) (Richeldi et al. Science 1993; 262: 242-244.12). Since this first observation of an immunogenetic association between berylliosis and HLA-DPbetaGlu69 a number of studies have confirmed the role of this marker as the primary gene of susceptibility of berylliosis (Richeldi et al Am J Ind Med. 1997; 32:337-40; Wang et al J. Immunol. 1999; 163: 1647-53; Saltini et al Eur Respir J. 2001 18:677-84; Rossman et al Am J Respir Crit Care Med. 2002 165:788-94). Moreover, a structure/function interaction between HLA-DP molecules carrying Glu69 and beryllium in driving and developing the immune response against beryllium itself has been observed as: (1) Be-specific T-cells clones obtained from berylliosis patients recognize beryllium as antigen only when presented in the context of the HLA-DP{beta}Glu69 molecules but not in the context of HLA-DP allelic variants carrying Lys69 (Lombardi G et al. J Immunol 2001; 166: 3549-3555), and (2) beryllium presents an affinity for the HLA-DP2, carrying the berylliosis marker of susceptibility HLA-DPGlu69, from 40 to 100 times higher that the HLA-DP molecule carrying Lys69 (Amicosante M. et al Hum. Immunol. 2001; 62: 686-93). However, although the immunogenetic studies performed have been addressed a number of different questions about the genetic association between berylliosis and/or beryllium sensitization, exposure levels to beryllium and HLA markers, a number of questions are still open in the field mainly due to the limitation imposed by the low number of subjects carrying berylliosis or beryllium sensitization enrolled

  2. Structure of the Newcastle disease virus F protein in the post-fusion conformation

    SciTech Connect (OSTI)

    Swanson, Kurt; Wen, Xiaolin; Leser, George P.; Paterson, Reay G.; Lamb, Robert A.; Jardetzky, Theodore S. (Stanford-MED); (NWU); (HHMI)

    2010-11-17

    The paramyxovirus F protein is a class I viral membrane fusion protein which undergoes a significant refolding transition during virus entry. Previous studies of the Newcastle disease virus, human parainfluenza virus 3 and parainfluenza virus 5 F proteins revealed differences in the pre- and post-fusion structures. The NDV Queensland (Q) F structure lacked structural elements observed in the other two structures, which are key to the refolding and fusogenic activity of F. Here we present the NDV Australia-Victoria (AV) F protein post-fusion structure and provide EM evidence for its folding to a pre-fusion form. The NDV AV F structure contains heptad repeat elements missing in the previous NDV Q F structure, forming a post-fusion six-helix bundle (6HB) similar to the post-fusion hPIV3 F structure. Electrostatic and temperature factor analysis of the F structures points to regions of these proteins that may be functionally important in their membrane fusion activity.

  3. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    SciTech Connect (OSTI)

    Liu, Xia; Zhao, Libo; Yang, Yongtao; Bode, Liv; Huang, Hua; Liu, Chengyu; Huang, Rongzhong; Zhang, Liang; and others

    2014-09-15

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs.

  4. Memorandum, Clarification of Title 10 of the Code of Federal Regulations, Part 850 (10 CPR 850), Chronic Beryllium Disease Prevention Program, Paragraph 850.34(g)

    Broader source: Energy.gov [DOE]

    The purpose of this memorandum is to clarification regarding the reporting of beryllium sensitization (BeS) and chronic beryllium disease (CBD) as required by paragraph 850.34(g) of the Chronic Beryllium Disease Prevention Program rule (10 CFR 850).

  5. The Impact of Preradiation Residual Disease Volume on Time to Locoregional Failure in Cutaneous Merkel Cell CarcinomaA TROG Substudy

    SciTech Connect (OSTI)

    Finnigan, Renee; Hruby, George; Wratten, Chris; Keller, Jacqui; Tripcony, Lee; Dickie, Graeme; Rischin, Danny; Poulsen, Michael

    2013-05-01

    Purpose: This study evaluated the impact of margin status and gross residual disease in patients treated with chemoradiation therapy for high-risk stage I and II Merkel cell cancer (MCC). Methods and Materials: Data were pooled from 3 prospective trials in which patients were treated with 50 Gy in 25 fractions to the primary lesion and draining lymph nodes and 2 schedules of carboplatin based chemotherapy. Time to locoregional failure was analyzed according to the burden of disease at the time of radiation therapy, comparing patients with negative margins, involved margins, or macroscopic disease. Results: Analysis was performed on 88 patients, of whom 9 had microscopically positive resection margins and 26 had macroscopic residual disease. The majority of gross disease was confined to nodal regions. The 5-year time to locoregional failure, time to distant failure, time to progression, and disease-specific survival rates for the whole group were 73%, 69%, 62%, and 66% respectively. The hazard ratio for macroscopic disease at the primary site or the nodes was 1.25 (95% confidence interval 0.57-2.77), P=.58. Conclusions: No statistically significant differences in time to locoregional failure were identified between patients with negative margins and those with microscopic or gross residual disease. These results must, however, be interpreted with caution because of the limited sample size.

  6. Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

    SciTech Connect (OSTI)

    Casjens S. R.; Dunn J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Schutzer, S. E.; Gilcrease, E. B.; Huang, W. M.; Vujadinovic, M.; Aron, J. K.; Vargas, L. C.; Freeman, S.; Radune, D.; Weidman, J. F.; Dimitrov, G. I.; Khouri, H. M.; Sosa, J. E.; Halpin, R. A.; Fraser, C. M.

    2012-03-14

    Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33-40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi {approx}900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short {le}20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

  7. Analyzing and modeling the kinetics of amyloid beta pores associated with Alzheimer’s disease pathology

    SciTech Connect (OSTI)

    Ullah, Ghanim; Demuro, Angelo; Parker, Ian; Pearson, John E.; Xu, Shang -Zhong

    2015-09-08

    Amyloid beta (Aβ) oligomers associated with Alzheimer’s disease (AD) form Ca2+-permeable plasma membrane pores, leading to a disruption of the otherwise well-controlled intracellular calcium (Ca2+) homeostasis. The resultant up-regulation of intracellular Ca2+ concentration has detrimental implications for memory formation and cell survival. The gating kinetics and Ca2+ permeability of Aβ pores are not well understood. We have used computational modeling in conjunction with the ability of optical patch-clamping for massively parallel imaging of Ca2+ flux through thousands of pores in the cell membrane of Xenopus oocytes to elucidate the kinetic properties of Aβ pores. The fluorescence time-series data from individual pores were idealized and used to develop data-driven Markov chain models for the kinetics of the Aβ pore at different stages of its evolution. Our study provides the first demonstration of developing Markov chain models for ion channel gating that are driven by optical-patch clamp data with the advantage of experiments being performed under close to physiological conditions. As a result, we demonstrate the up-regulation of gating of various Ca2+ release channels due to Aβ pores and show that the extent and spatial range of such up-regulation increases as Aβ pores with low open probability and Ca2+ permeability transition into those with high open probability and Ca2+ permeability.

  8. Environment/Health/Safety (EHS)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    has been in the news. Measles is a highly contagious respiratory disease caused by a virus. It spreads through the air through coughing and sneezing. Measles can be spread days...

  9. Fourier Transform Infrared Imaging Showing Reduced Unsaturated Lipid Content in the Hippocampus of a mouse Model of Alzheimer's Disease

    SciTech Connect (OSTI)

    Leskovjan, A.C.; Kretlow, A.; Miller, L.M.

    2010-04-01

    Polyunsaturated fatty acids are essential to brain functions such as membrane fluidity, signal transduction, and cell survival. It is also thought that low levels of unsaturated lipid in the brain may contribute to Alzheimer's disease (AD) risk or severity. However, it is not known how accumulation of unsaturated lipids is affected in different regions of the hippocampus, which is a central target of AD plaque pathology, during aging. In this study, we used Fourier transform infrared imaging (FTIRI) to visualize the unsaturated lipid content in specific regions of the hippocampus in the PSAPP mouse model of AD as a function of plaque formation. Specifically, the unsaturated lipid content was imaged using the olefinic {double_bond}CH stretching mode at 3012 cm{sup -1}. The axonal, dendritic, and somatic layers of the hippocampus were examined in the mice at 13, 24, 40, and 56 weeks old. Results showed that lipid unsaturation in the axonal layer was significantly increased with normal aging in control (CNT) mice (p < 0.01) but remained low and relatively constant in PSAPP mice. Thus, these findings indicate that unsaturated lipid content is reduced in hippocampal white matter during amyloid pathogenesis and that maintaining unsaturated lipid content early in the disease may be critical in avoiding progression of the disease.

  10. Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

    SciTech Connect (OSTI)

    Farzan, Shohreh F.; Chen, Yu; Rees, Judy R.; Zens, M. Scot; Karagas, Margaret R.

    2015-09-01

    High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. - Highlights: • Arsenic (As) has been associated with increased cardiovascular disease (CVD) risk. • Little is known about CVD effects at lower levels of As exposure common in the US. • Few have investigated the joint effects of As and smoking on CVD in US adults. • We examine chronic low-level As exposure and smoking in relation to CVD mortality. • Arsenic exposure may increase ischemic heart disease mortality among smokers in US.

  11. Percutaneous Transsplenic Access to the Portal Vein for Management of Vascular Complication in Patients with Chronic Liver Disease

    SciTech Connect (OSTI)

    Chu, Hee Ho; Kim, Hyo-Cheol Jae, Hwan Jun; Yi, Nam-Joon; Lee, Kwang-Woong; Suh, Kyung-Suk; Chung, Jin Wook; Park, Jae Hyung

    2012-12-15

    Purpose: To evaluate the safety and feasibility of percutaneous transsplenic access to the portal vein for management of vascular complication in patients with chronic liver diseases. Methods: Between Sept 2009 and April 2011, percutaneous transsplenic access to the portal vein was attempted in nine patients with chronic liver disease. Splenic vein puncture was performed under ultrasonographic guidance with a Chiba needle, followed by introduction of a 4 to 9F sheath. Four patients with hematemesis or hematochezia underwent variceal embolization. Another two patients underwent portosystemic shunt embolization in order to improve portal venous blood flow. Portal vein recanalization was attempted in three patients with a transplanted liver. The percutaneous transsplenic access site was closed using coils and glue. Results: Percutaneous transsplenic splenic vein catheterization was performed successfully in all patients. Gastric or jejunal varix embolization with glue and lipiodol mixture was performed successfully in four patients. In two patients with a massive portosystemic shunt, embolization of the shunting vessel with a vascular plug, microcoils, glue, and lipiodol mixture was achieved successfully. Portal vein recanalization was attempted in three patients with a transplanted liver; however, only one patient was treated successfully. Complete closure of the percutaneous transsplenic tract was achieved using coils and glue without bleeding complication in all patients. Conclusion: Percutaneous transsplenic access to the portal vein can be an alternative route for portography and further endovascular management in patients for whom conventional approaches are difficult or impossible.

  12. Understanding the chemical properties of macerals and minerals in coal and its potential application for occupational lung disease prevention

    SciTech Connect (OSTI)

    Huang, X.; Finkelman, R.B.

    2008-07-01

    The objective of this review was to assess whether some chemical parameters in coal play a role in producing environmental health problems. Basic properties of coal - such as chemical forms of the organic materials, structure, compositions of minerals - vary from one coal mine region to another as well as from coals of different ranks. Most importantly, changes in chemical properties of coals due to exposure to air and humidity after mining - a dynamic process - significantly affect toxicity attributed to coal and environmental fate. Although coal is an extremely complex and heterogeneous material, the fundamental properties of coal responsible for environmental and adverse health problems are probably related to the same inducing components of coal. For instance, oxidation of pyrite (FeS{sub 2}) in the coal forms iron sulfate and sulfuric acid, which produces occupational lung diseases (e.g., pneumoconiosis) and other environmental problems (e.g., acid mine drainage and acid rain). Calcite (CaCO{sub 3}) contained in certain coals alters the end products of pyrite oxidation, which may make these coals less toxic to human inhalation and less hazardous to environmental pollution. Finally, knowledge gained on understanding of the chemical properties of coals is illustrated to apply for prediction of toxicity due to coal possibly before large-scale mining and prevention of occupational lung disease during mining.

  13. Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

    SciTech Connect (OSTI)

    Patterson, Edward I.; Dombrovski, Andrew K.; Swarbrick, Crystall M.D.; Raidal, Shane R.; Forwood, Jade K.

    2013-09-06

    Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediate nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface.

  14. Effects of didecyldimethylammonium chloride on the biochemistry, swimming performance, gill histology and disease resistance of juvenile rainbow trout (Oncorhynchus mykiss)

    SciTech Connect (OSTI)

    Johnston, B.D.; Wood, A.W.; Farrell, A.P.; Kennedy, C.J.

    1995-12-31

    The acute lethal and sublethal toxicity of the antisapstain didecyldimethylammonium chloride (DDAC) to juvenile rainbow trout (Oncorhynchus mykiss) was investigated. The 96-h LC{sub 50} value in a flow-through exposure system was 0.4 mg-1{sup {minus}1}. Plasma cortisol, glucose and lactate levels were significantly elevated after an acute 24-h exposure to 0.4 mg-1{sup {minus}1}. Values for hepato-somatic index (HSI), haematocit, leucocrit, plasma haemoglobin, and liver glycogen remained unchanged. Swimming performance decreased significantly after exposure to 0.2 mg-1{sup {minus}1} for exposure durations of 12-h and 24-h and to 0.4 mg{sup {minus}1} for exposure durations of 12-h, 24-h, and 48-h. Scanning electron microscopic analysis revealed no gross lesions in gill epithelia as a result of toxicant exposure. In disease challenge experiments, exposure to sublethal concentrations of DDAC for 24-h did not effect the susceptibility of rainbow trout to the pathogen Vibrio anguilarum. Of a suite of toxicity tests, specific biochemical markers were unsatisfactory in revealing sublethal toxic effects. These were best revealed by an integrative measure of performance, namely swimming performance, but not disease resistance.

  15. Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

    SciTech Connect (OSTI)

    Filippi, Andrea Riccardo; Ragona, Riccardo; Piva, Cristina; Scafa, Davide; Fiandra, Christian; Fusella, Marco; Giglioli, Francesca Romana; Lohr, Frank; Ricardi, Umberto

    2015-05-01

    Purpose: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR{sub VMAT}-to-LAR{sub 3D-CRT}) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). Results: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. Conclusions: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by

  16. SU-E-QI-14: Quantitative Variogram Detection of Mild, Unilateral Disease in Elastase-Treated Rats

    SciTech Connect (OSTI)

    Jacob, R; Carson, J

    2014-06-15

    Purpose: Determining the presence of mild or early disease in the lungs can be challenging and subjective. We present a rapid and objective method for evaluating lung damage in a rat model of unilateral mild emphysema based on a new approach to heterogeneity assessment. We combined octree decomposition (used in three-dimensional (3D) computer graphics) with variograms (used in geostatistics to assess spatial relationships) to evaluate 3D computed tomography (CT) lung images for disease. Methods: Male, Sprague-Dawley rats (232 ± 7 g) were intratracheally dosed with 50 U/kg of elastase dissolved in 200 μL of saline to a single lobe (n=6) or with saline only (n=5). After four weeks, 3D micro-CT images were acquired at end expiration on mechanically ventilated rats using prospective gating. Images were masked, and lungs were decomposed to homogeneous blocks of 2×2×2, 4×4×4, and 8×8×8 voxels using octree decomposition. The spatial variance – the square of the difference of signal intensity – between all pairs of the 8×8×8 blocks was calculated. Variograms – graphs of distance vs. variance - were made, and data were fit to a power law and the exponent determined. The mean HU values, coefficient of variation (CoV), and the emphysema index (EI) were calculated and compared to the variograms. Results: The variogram analysis showed that significant differences between groups existed (p<0.01), whereas the mean HU (p=0.07), CoV (p=0.24), and EI (p=0.08) did not. Calculation time for the variogram for a typical 1000 block decomposition was ∼6 seconds, and octree decomposition took ∼2 minutes. Decomposing the images prior to variogram calculation resulted in a ∼700x decrease in time as compared to other published approaches. Conclusions: Our results suggest that the approach combining octree decomposition and variogram analysis may be a rapid, non-subjective, and sensitive imaging-based biomarker for quantitative characterization of lung disease.

  17. Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

    SciTech Connect (OSTI)

    Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.; Rossetti, Carlos A.; Lewin, Harris A.; Lipton, Mary S.; Turse, Joshua E.; Wylie, Dennis C.; Bai, Yu; Drake, Kenneth L.

    2011-09-22

    The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures

  18. Is Primary Prostate Cancer Treatment Influenced by Likelihood of Extraprostatic Disease? A Surveillance, Epidemiology and End Results Patterns of Care Study

    SciTech Connect (OSTI)

    Holmes, Jordan A.; Wang, Andrew Z.; University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC ; Hoffman, Karen E.; Hendrix, Laura H.; Rosenman, Julian G.; University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC ; Carpenter, William R.; Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Health Policy and Management, University of North Carolina School of Public Health, Chapel Hill, NC ; Godley, Paul A.; Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC; Division of Hematology-Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC ; Chen, Ronald C.

    2012-09-01

    Purpose: To examine the patterns of primary treatment in a recent population-based cohort of prostate cancer patients, stratified by the likelihood of extraprostatic cancer as predicted by disease characteristics available at diagnosis. Methods and Materials: A total of 157,371 patients diagnosed from 2004 to 2008 with clinically localized and potentially curable (node-negative, nonmetastatic) prostate cancer, who have complete information on prostate-specific antigen, Gleason score, and clinical stage, were included. Patients with clinical T1/T2 disease were grouped into categories of <25%, 25%-50%, and >50% likelihood of having extraprostatic disease using the Partin nomogram. Clinical T3/T4 patients were examined separately as the highest-risk group. Logistic regression was used to examine the association between patient group and receipt of each primary treatment, adjusting for age, race, year of diagnosis, marital status, Surveillance, Epidemiology and End Results database region, and county-level education. Separate models were constructed for primary surgery, external-beam radiotherapy (RT), and conservative management. Results: On multivariable analysis, increasing likelihood of extraprostatic disease was significantly associated with increasing use of RT and decreased conservative management. Use of surgery also increased. Patients with >50% likelihood of extraprostatic cancer had almost twice the odds of receiving prostatectomy as those with <25% likelihood, and T3-T4 patients had 18% higher odds. Prostatectomy use increased in recent years. Patients aged 76-80 years were likely to be managed conservatively, even those with a >50% likelihood of extraprostatic cancer (34%) and clinical T3-T4 disease (24%). The proportion of patients who received prostatectomy or conservative management was approximately 50% or slightly higher in all groups. Conclusions: There may be underutilization of RT in older prostate cancer patients and those with likely

  19. Treatment approach, delivery, and follow-up evaluation for cardiac rhythm disease management patients receiving radiation therapy: Retrospective physician surveys including chart reviews at numerous centers

    SciTech Connect (OSTI)

    Gossman, Michael S.; Wilkinson, Jeffrey D.; Mallick, Avishek

    2014-01-01

    In a 2-part study, we first examined the results of 71 surveyed physicians who provided responses on how they address the management of patients who maintained either a pacemaker or a defibrillator during radiation treatment. Second, a case review study is presented involving 112 medical records reviewed at 18 institutions to determine whether there was a change in the radiation prescription for the treatment of the target cancer, the method of radiation delivery, or the method of radiation image acquisition. Statistics are provided to illustrate the level of administrative policy; the level of communication between radiation oncologists and heart specialists; American Joint Committee on Cancer (AJCC) staging and classification; National Comprehensive Cancer Network (NCCN) guidelines; tumor site; patient's sex; patient's age; device type; manufacturer; live monitoring; and the reported decisions for planning, delivery, and imaging. This survey revealed that 37% of patient treatments were considered for some sort of change in this regard, whereas 59% of patients were treated without regard to these alternatives when available. Only 3% of all patients were identified with an observable change in the functionality of the device or patient status in comparison with 96% of patients with normal behavior and operating devices. Documented changes in the patient's medical record included 1 device exhibiting failure at 0.3-Gy dose, 1 device exhibiting increased sensor rate during dose delivery, 1 patient having an irregular heartbeat leading to device reprogramming, and 1 patient complained of twinging in the chest wall that resulted in a respiratory arrest. Although policies and procedures should directly involve the qualified medical physicist for technical supervision, their sufficient involvement was typically not requested by most respondents. No treatment options were denied to any patient based on AJCC staging, classification, or NCCN practice standards.

  20. The effects of total dissolved gas on chum salmon fry survival, growth, gas bubble disease, and seawater tolerance

    SciTech Connect (OSTI)

    Geist, David R.; Linley, Timothy J.; Cullinan, Valerie I.; Deng, Zhiqun

    2013-02-01

    Chum salmon Oncorhynchus keta alevin developing in gravel habitats downstream of Bonneville Dam on the Columbia River are exposed to elevated levels of total dissolved gas (TDG) when water is spilled at the dam to move migrating salmon smolts downstream to the Pacific Ocean. Current water quality criteria for the management of dissolved gas in dam tailwaters were developed primarily to protect salmonid smolts and are assumed to be protective of alevin if adequate depth compensation is provided. We studied whether chum salmon alevin exposed to six levels of dissolved gas ranging from 100% to 130% TDG at three development periods between hatch and emergence (hereafter early, middle, and late stage) suffered differential mortality, growth, gas bubble disease, or seawater tolerance. Each life stage was exposed for 50 d (early stage), 29 d (middle stage), or 16 d (late stage) beginning at 13, 34, and 37 d post-hatch, respectively, through 50% emergence. The mortality for all stages from exposure to emergence was estimated to be 8% (95% confidence interval (CI) of 4% to 12%) when dissolved gas levels were between 100% and 117% TDG. Mortality significantly increased as dissolved gas levels rose above 117% TDG,; with the lethal concentration that produced 50% mortality (LC50 ) was estimated to be 128.7% TDG (95% CI of 127.2% to 130.2% TDG) in the early and middle stages. By contrast, there was no evidence that dissolved gas level significantly affected growth in any life stage except that the mean wet weight at emergence of early stage fish exposed to 130% TDG was significantly less than the modeled growth of unexposed fish. The proportion of fish afflicted with gas bubble disease increased with increasing gas concentrations and occurred most commonly in the nares and gastrointestinal tract. Early stage fish exhibited higher ratios of filament to lamellar gill chloride cells than late stage fish, and these ratios increased and decreased for early and late stage fish

  1. The tale of a modern animal plague: Tracing the evolutionary history and determining the time-scale for foot and mouth disease virus

    SciTech Connect (OSTI)

    Tully, Damien C. Fares, Mario A.

    2008-12-20

    Despite significant advances made in the understanding of its epidemiology, foot and mouth disease virus (FMDV) is among the most unexpected agricultural devastating plagues. While the disease manifests itself as seven immunologically distinct strains their origin, population dynamics, migration patterns and divergence times remain unknown. Herein we have assembled a comprehensive data set of gene sequences representing the global diversity of the disease and inferred the time-scale and evolutionary history for FMDV. Serotype-specific rates of evolution and divergence times were estimated using a Bayesian coalescent framework. We report that an ancient precursor FMDV gave rise to two major diversification events spanning a relatively short interval of time. This radiation event is estimated to have taken place towards the end of the 17th and the beginning of the 18th century giving us the present circulating Euro-Asiatic and South African viral strains. Furthermore our results hint that Europe acted as a possible hub for the disease from where it successfully dispersed elsewhere via exploration and trading routes.

  2. Elastic Deformation Properties of Implanted Endobronchial Wire Stents in Benign and Malignant Bronchial Disease: A Radiographic In Vivo Evaluation

    SciTech Connect (OSTI)

    Hautmann, Hubert; Rieger, Johannes; Huber, Rudolf M.; Pfeifer, Klaus J.

    1999-03-15

    Purpose: To evaluate the long-term mechanical behavior in vivo of expandable endobronchial wire stents, we imaged three different prostheses in the treatment of tracheobronchial disease. Methods: Six patients with bronchial stenoses (three benign, three malignant) underwent insertion of metallic stents. Two self-expandable Wallstents, two balloon-expandable tantalum Strecker stents and two self-expandable nitinol Accuflex stents were used. Measurements of deformation properties were performed during voluntary cough by means of fluoroscopy, at 1 month and 7-10 months after implantation. The procedures were videotaped, their images digitized and the narrowing of stent diameters calculated at intervals of 20 msec. Results: After stent implantation all patients improved with respect to ventilatory function. Radial stent narrowing during cough reached 53% (Wallstent), 59% (tantalum Strecker stent), and 52% (nitinol Accuflex stent) of the relaxed post-implantation diameter. Stent compression was more marked in benign compared with malignant stenoses. In the long term permanent deformation occurred with the tantalum Strecker stents; the other stents were unchanged. Conclusion: Endobronchial wire stents can be helpful in the treatment of major airway collapse and obstructing bronchial lesions. However, evidence of material fatigue as a possible effect of exposure to recurrent mechanical stress on the flexible mesh tube may limit their long-term use. This seems to be predominantly important in benign bronchial collapse.

  3. Review of Monitoring Plans for Gas Bubble Disease Signs and Gas Supersaturation Levels on the Columbia and Snake Rivers.

    SciTech Connect (OSTI)

    Fidler, Larry; Elston, Ralph; Colt, John

    1994-07-01

    Montgomery Watson was retained by the Bonneville Power Administration to evaluate the monitoring program for gas bubble disease signs and dissolved gas supersaturation levels on the Columbia and Snake rivers. The results of this evaluation will provide the basis for improving protocols and procedures for future monitoring efforts. Key study team members were Dr. John Colt, Dr. Larry Fidler, and Dr. Ralph Elston. On the week of June 6 through 10, 1994 the study team visited eight monitoring sites (smolt, adult, and resident fish) on the Columbia and Snake rivers. Additional protocol evaluations were conducted at the Willard Field Station (National Biological Survey) and Pacific Northwest Laboratories at Richland (Battelle). On June 13 and 14, 1994, the study team visited the North Pacific Division office of the U.S. Corps of Engineers and the Fish Passage Center to collect additional information and data on the monitoring programs. Considering the speed at which the Gas Bubble Trauma Monitoring Program was implemented this year, the Fish Passage Center and cooperating Federal, State, and Tribal Agencies have been doing an incredible job. Thirty-one specific recommendations are presented in this report and are summarized in Section 14.

  4. Metal-sulfide mineral ores, Fenton chemistry and disease. Particle induced inflammatory stress response in lung cells

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Harrington, Andrea D.; Smirnov, Alexander; Tsirka, Stella E.; Schoonen, Martin A. A.

    2014-07-10

    The inhalation of mineral particulates and other earth materials, such as coal, can initiate or enhance disease in humans. Workers in occupations with high particulate exposure, such as mining, are particularly at risk. The ability of a material to generate an inflammatory stress response (ISR), a measure of particle toxicity, is a useful tool in evaluating said exposure risk. ISR is defined as the upregulation of cellular reactive oxygen species (ROS) normalized to cell viability. This study compares the ISR of A549 human lung epithelial cells after exposure to well-characterized common metal-sulfide ore mineral separates. The evaluation of the deleteriousmore » nature of ore minerals is based on a range of particle loadings (serial dilutions of 0.002 m2/mL stock) and exposure periods (beginning at 30 min and measured systematically for up to 24 h). There is a wide range in ISR values generated by the ore minerals. The ISR values produced by the sphalerite samples are within the range of inert materials. Arsenopyrite generated a small ISR that was largely driven by cell death. Galena showed a similar, but more pronounced response. Copper-bearing ore minerals generated the greatest ISR, both by upregulating cellular ROS and generating substantial and sustained cell death. Chalcopyrite and bornite, both containing ferrous iron, generated the greatest ISR overall. Particles containing Fenton metals as major constituents produce the highest ISR, while other heavy metals mainly generate cell death. Furthermore, this study highlights the importance of evaluating the chemistry, oxidation states and structure of a material when assessing risk management.« less

  5. Metal-sulfide mineral ores, Fenton chemistry and disease. Particle induced inflammatory stress response in lung cells

    SciTech Connect (OSTI)

    Harrington, Andrea D.; Smirnov, Alexander; Tsirka, Stella E.; Schoonen, Martin A. A.

    2014-07-10

    The inhalation of mineral particulates and other earth materials, such as coal, can initiate or enhance disease in humans. Workers in occupations with high particulate exposure, such as mining, are particularly at risk. The ability of a material to generate an inflammatory stress response (ISR), a measure of particle toxicity, is a useful tool in evaluating said exposure risk. ISR is defined as the upregulation of cellular reactive oxygen species (ROS) normalized to cell viability. This study compares the ISR of A549 human lung epithelial cells after exposure to well-characterized common metal-sulfide ore mineral separates. The evaluation of the deleterious nature of ore minerals is based on a range of particle loadings (serial dilutions of 0.002 m2/mL stock) and exposure periods (beginning at 30 min and measured systematically for up to 24 h). There is a wide range in ISR values generated by the ore minerals. The ISR values produced by the sphalerite samples are within the range of inert materials. Arsenopyrite generated a small ISR that was largely driven by cell death. Galena showed a similar, but more pronounced response. Copper-bearing ore minerals generated the greatest ISR, both by upregulating cellular ROS and generating substantial and sustained cell death. Chalcopyrite and bornite, both containing ferrous iron, generated the greatest ISR overall. Particles containing Fenton metals as major constituents produce the highest ISR, while other heavy metals mainly generate cell death. Furthermore, this study highlights the importance of evaluating the chemistry, oxidation states and structure of a material when assessing risk management.

  6. Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases

    SciTech Connect (OSTI)

    Atalar, Banu; Modlin, Leslie A.; Choi, Clara Y.H.; Adler, John R.; Gibbs, Iris C.; Chang, Steven D.; Harsh, Griffith R.; Li, Gordon; Nagpal, Seema; Hanlon, Alexandra; Soltys, Scott G.

    2013-11-15

    Purpose: We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients. Methods and Materials: We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other). Results: With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004). Conclusions: In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

  7. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect (OSTI)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  8. Arrested rearrangement of TCR V[beta] genes in thymocytes from children with x-linked severe combined immunodeficiency disease

    SciTech Connect (OSTI)

    Sleasman, J.W.; Harville, T.O.; White, G.B.; Barrett, D.J. ); George, J.F. ); Goodenow, M.M. Univ. of Alabama, Birmingham, AL )

    1994-07-01

    Human X-linked severe combined immunodeficiency disease (SCID) is an immunodeficiency disorder in which T cell development is arrested in the thymic cortex. B lymphocytes in children with X-linked SCID seem to differentiate normally. X-linked SCID is associated with a mutation in the gene that encodes the IL-2R [gamma]-chain. Because TCR-[beta] gene recombination is a pivotal initial event in T lymphocyte onteogeny within the thymus, the authors hypothesized that a failure to express normal IL-2R[gamma] could lead to impaired TCR-[beta] gene recombination in early thymic development. PCR was used to determine the status of TCR-[beta] gene-segment rearrangements in thymic DNA that had been obtained from children with X-linked SCID. The initial step in TCR-[beta] gene rearrangement, that of D[beta] to J[beta] recombination, was readily detected in all thymus samples from children with X-linked SCID; in contrast, V[beta] to DJ[beta] gene rearrangements were undetectable in the same samples. Both D[beta] to J[beta] and V[beta] to DJ[beta] TCR genes were rearranged in the thymic tissues obtained from immunologically normal children. The authors conclude that TCR[beta]-chain gene rearrangement is arrested in children with X-linked SCID. The results suggest a causative relationship between the failure of TCR [beta]-chain gene arrangements to proceed beyond DJ[beta] rearrangements and the production of a nonfunctional IL-2R [gamma]-chain. 45 refs., 3 figs.

  9. Novel mutations in the connexin 32 gene associated with X-linked Charcot-Marie-Tooth disease

    SciTech Connect (OSTI)

    Tan, C.; Ainsworth, P. |

    1994-09-01

    Charcot-Marie-Tooth disease is a pathologically and genetically hetergenous group of disorders that cause a progressive neuropathy, defined pathologically by degeneration of the myelin (CMT 1) of the axon (CMT 2) of the peripheral nerves. An X-linked type of the demyelinating form of this disorder (CMT X) has recently been linked to mutations in the connexin 32 (Cx32) gene, which codes for a 284 amino acid gap junction protein found in myelinated peripheral nerve. To date some 7 different mutations in this gene have been identified as being responsible for CMT X. The majority of these predict nonconservative amino acid substitutions, while one is a frameshift mutation which predicts a premature stop at codon 21. We report the results of molecular studies on three further local CMT X kindreds. The Cx32 gene was amplified by PCR in three overlapping fragments 300-450 bp in length using leukocyte-derived DNA as template. These were either sequenced directly using a deaza dGTP sequencing protocol, or were cloned and sequenced using a TA vector. In two of the kindreds the affected members carried a point mutation which was predicted to effect a non-conservative amino acid change within the first transmembrane domain. Both of these mutations caused a restriction site alteration (the loss of an Nla III and the creation of a Pvu II, respectively), and the former mutation was observed to segregate with the clinicial phenotype in affected family members. Affected members of the third kindred, which was a very large multigenerational family that had been extensively studied previously, were shown to carry a point mutation predicted to cause a premature truncation of the Cx32 gene product in the intracellular carboxy terminus. This mutation obliterated an Rsa I site which allowed a rapid screen of several other family members.

  10. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    SciTech Connect (OSTI)

    Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  11. Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease

    SciTech Connect (OSTI)

    Chen, Qiang; The First Affiliated Hospital of Xiamen University, Xiamen ; Jiang, Yuan; An, Yuan; Zhao, Na; Zhao, Yang; Yu, Chundong

    2011-06-17

    Highlights: {yields} Soluble FGFR4 extracellular domain (FGFR4-ECD) was effectively expressed. {yields} FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling. {yields} FGFR4-ECD reduced palmitic acid-induced steatosis of HepG2 cells. {yields} FGFR4-ECD reduced tetracycline-induced fatty liver in mice. {yields} FGFR4-ECD partially restored tetracycline-repressed PPAR{alpha} expression. -- Abstract: Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.

  12. Methods for assisting recovery of damaged brain and spinal cord and treating various diseases using arrays of x-ray microplanar beams

    DOE Patents [OSTI]

    Dilmanian, F. Avraham; Anchel, David J.; Gaudette, Glenn; Romanelli, Pantaleo; Hainfeld, James

    2010-06-29

    A method of assisting recovery of an injury site of the central nervous system (CNS) or treating a disease includes providing a therapeutic dose of X-ray radiation to a target volume through an array of parallel microplanar beams. The dose to treat CNS injury temporarily removes regeneration inhibitors from the irradiated site. Substantially unirradiated cells surviving between beams migrate to the in-beam portion and assist recovery. The dose may be staggered in fractions over sessions using angle-variable intersecting microbeam arrays (AVIMA). Additional doses are administered by varying the orientation of the beams. The method is enhanced by injecting stem cells into the injury site. One array or the AVIMA method is applied to ablate selected cells in a target volume associated with disease for palliative or curative effect. Atrial fibrillation is treated by irradiating the atrial wall to destroy myocardial cells while continuously rotating the subject.

  13. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

    SciTech Connect (OSTI)

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.; Komorowski, Richard; Fish, Brian L.; Migrino, Raymond Q.; Harmann, Leanne; Hopewell, John W.; Kronenberg, Amy; Patel, Shailendra; Moulder, John E.; Baker, John E.

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

  14. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.; Komorowski, Richard; Fish, Brian L.; Migrino, Raymond Q.; Harmann, Leanne; Hopewell, John W.; Kronenberg, Amy; Patel, Shailendra; et al

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9more » days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.« less

  15. Indoor Chemical Exposures: Humans' Non-respiratory Interactions with Room Air

    ScienceCinema (OSTI)

    Charles Weschler

    2010-09-01

    March 18, 2010 Berkeley Lab Environmental Energy Technology Division distinguished lecture: The marked difference in pollutant concentrations between an occupied and un-occupied room are only partially explained by human bio-effluents. Humans alter levels of ozone and related oxidants such as nitrate and hydroxyl radicals in the rooms they inhabit; in effect, they change the oxidative capacity of room air. Ozone-initiated reactions on exposed skin, hair and clothing generate products, including potentially irritating chemicals whose concentrations are much higher in the occupant's breathing zone than in the core of the room. Charles J. Weschler is a Professor at the School of Public Health, the Department of Environmental and Occupational Medicine and the Environmental and Occupational Health Sciences Institute (EOHSI) at the University of Medicine and Dentistry of New Jersey (UMDNJ)/Robert Wood Johnson Medical School & Rutgers University (New Jersey). He is also a Visiting Professor at the International Centre for Indoor Environment and Energy, Technical University of Denmark (DTU, Lyngby, Denmark).

  16. Indoor Chemical Exposures: Humans' Non-respiratory Interactions with Room Air

    SciTech Connect (OSTI)

    Charles Weschler

    2010-03-29

    March 18, 2010 Berkeley Lab Environmental Energy Technology Division distinguished lecture: The marked difference in pollutant concentrations between an occupied and un-occupied room are only partially explained by human bio-effluents. Humans alter levels of ozone and related oxidants such as nitrate and hydroxyl radicals in the rooms they inhabit; in effect, they change the oxidative capacity of room air. Ozone-initiated reactions on exposed skin, hair and clothing generate products, including potentially irritating chemicals whose concentrations are much higher in the occupant's breathing zone than in the core of the room. Charles J. Weschler is a Professor at the School of Public Health, the Department of Environmental and Occupational Medicine and the Environmental and Occupational Health Sciences Institute (EOHSI) at the University of Medicine and Dentistry of New Jersey (UMDNJ)/Robert Wood Johnson Medical School & Rutgers University (New Jersey). He is also a Visiting Professor at the International Centre for Indoor Environment and Energy, Technical University of Denmark (DTU, Lyngby, Denmark).

  17. Metabolic interdependencies between phylogenetically novel fermenters and respiratory organisms in an unconfined aquifer

    SciTech Connect (OSTI)

    Wrighton, Kelly C.; Castelle, Cindy; Wilkins, Michael J.; Hug, Laura A.; Sharon, I.; Thomas, Brian C.; Handley, Kim M.; Mullin, Sean W.; Nicora, Carrie D.; Singh, Andrea; Lipton, Mary S.; Long, Philip E.; Williams, Kenneth H.; Banfield, Jillian F.

    2014-07-08

    Fermentation-based metabolism is an important ecosystem function often associated with environments rich in organic carbon, such as wetlands, sewage sludge, and the mammalian gut. The diversity of microorganisms and pathways involved in carbon and hydrogen cycling in sediments and aquifers and the impacts of these processes on other biogeochemical cycles remain poorly understood. Here we used metagenomics and proteomics to characterize microbial communities sampled from an aquifer adjacent to the Colorado River at Rifle, Colorado, USA, and document interlinked microbial roles in geochemical cycling. The organic carbon content in the aquifer was elevated via two acetate-based biostimulation treatments. Samples were collected at three time points, with the objective of extensive genome recovery to enable metabolic reconstruction of the community. Fermentative community members include genomes from a new phylum (ACD20), phylogenetically novel members of the Chloroflexi and Bacteroidetes, as well as candidate phyla genomes (OD1, BD1-5, SR1, WWE3, ACD58, TM6, PER, and OP11). These organisms have the capacity to produce hydrogen, acetate, formate, ethanol, butyrate, and lactate, activities supported by proteomic data. The diversity and expression of hydrogenases suggests the importance of hydrogen currency in the subsurface. Our proteogenomic data further indicate the consumption of fermentation intermediates by Proteobacteria can be coupled to nitrate, sulfate, and iron reduction. Thus, fermentation carried out by previously unstudied members of sediment microbial communities may be an important driver of diverse subsurface biogeochemical cycles.

  18. Passive smoking, air pollution, and acute respiratory symptoms in a diary study of student nurses

    SciTech Connect (OSTI)

    Schwartz, J.; Zeger, S. )

    1990-01-01

    A cohort of approximately 100 student nurses in Los Angeles was recruited for a diary study of the acute effects of air pollution. Smoking histories and presence of asthma and other allergies were determined by questionnaire. Diaries were completed daily and collected weekly for as long as 3 yr. Air pollution was measured at a monitoring location within 2.5 miles of the school. Incidence and duration of a symptom were modeled separately. Pack-years of cigarettes were predictive of the number of episodes of coughing (p less than 0.0001) and of bringing up phlegm (p less than 0.0001). Current smoking, rather than cumulative smoking, was a better predictor of the duration of a phlegm episode (p less than 0.0001). Controlling for personal smoking, a smoking roommate increased the risk of an episode of phlegm (odds ratio (OR) = 1.41, p less than 0.001), but not of cough. Excluding asthmatics (who may be medicated), increased the odds ratio for passive smoking to 1.76 (p less than 0.0001). In logistic regression models controlling for temperature and serial correlation between days, an increase of 1 SD in carbon monoxide exposure (6.5 ppm) was associated with increased risk of headache (OR = 1.09, p less than 0.001), photochemical oxidants (7.4 pphm) were associated with increased risk of chest discomfort (OR = 1.17, p less than 0.001) and eye irritation (OR = 1.20 p less than 0.001), and nitrogen dioxide (9.1 pphm) was associated with increased risk of phlegm (OR = 1.08 p less than 0.01), sore throats (OR = 1.26, p less than 0.001), and eye irritation (OR = 1.16, p less than 0.001).

  19. Evaluation of respiratory variables in smelter and control workers before and during a shutdown period

    SciTech Connect (OSTI)

    Holness, D.L.; Batten, B.; Broder, I.; Corey, P.; Mintz, S.

    1985-05-01

    Thirty-six smelter workers examined in this pilot study were found to have a higher prevalence of cough and dyspnea and lower baseline lung function than did 31 controls. They also experienced decreases in forced vital capacity (FVC) and forced expiratory volume in 1s (FEV1) over the workweek while the controls did not. Baseline airflow rates and change in FVC and FEV1 over the workweek varied with levels of sulfur dioxide and particulates. Twenty-three smelter workers and 21 controls were seen on a second occasion, six months into an extended shutdown. The smelter workers continued to have a higher prevalence of cough and dyspnea and lower baseline lung function than the controls. There was, however, a slight increase in lung function in both the exposed workers and the controls during the shutdown. The results suggest that smelter workers may develop both acute and chronic work-related pulmonary effects and that the chronic effects may be nonreversible.

  20. Four-year prospective study of the respiratory effects of volcanic ash from Mt. St. Helens

    SciTech Connect (OSTI)

    Buist, A.S.; Vollmer, W.M.; Johnson, L.R.; Bernstein, R.S.; McCamant, L.E.

    1986-04-01

    This report describes the 4-yr follow-up of 712 loggers exposed over an extended period to varying levels of fresh volcanic ash from the 1980 eruptions of Mt. St. Helens. Concerns related to the irritant effect the ash might have on the airways and also to its fibrogenic potential if exposures were intense and continued over many years. Our subjects were divided into 3 groups: high, low, and no exposure. Baseline testing was begun in June 1980, 1 month after the major eruption, and follow-up testing continued on an annual basis through 1984; 88% of the loggers have been tested at least 3 times. Analysis of lung function data showed that a significant, exposure-related decline in FEV1 occurred during the first year after the eruption. The decline was short-lived, however, and by 1984 the differences between exposure groups were no longer significant. Self-reported symptoms of cough, phlegm, and wheeze showed a similar pattern. No ash-related changes were seen in chest roentgenograms taken in 1980 and in 1984. Our findings are consistent with the hypothesis that the inhaled ash caused mucus hypersecretion and/or airway inflammation that reversed when the exposure levels decreased. The ash levels to which the loggers were exposed were low compared with permissible occupational levels for nuisance dusts, but generally higher than the total suspended particulate levels permissible in ambient air.

  1. DOE-STD-1167-2003; Respiratory Acceptance Program for Supplied...

    Broader source: Energy.gov (indexed) [DOE]

    ... The metered air supply is needed in order to supply breathing air to the supplied- air suit being tested. 19.1.8 Spray Gun. A spray gun or equal device should be used to spray the ...

  2. Health risks associated with residence near a primary copper smelter: a preliminary report

    SciTech Connect (OSTI)

    Mattson, M.E.; Guidotti, T.L.

    1980-01-01

    Mortality for three groups of ICD codes covering acute, chronic, and malignant respiratory diseases were studied for adult white women in communities near or adjacent to primary copper smelting facilities in the United States between 1968 and 1975, a period when women had not as yet entered the industrial work force. A previous comprehensive survey, sponsored by the EPA, of all U.S. counties used multiple regression analysis as a method of statistical surveillance to assess the association of mortality with industrial activity. This preliminary study suggested an excess mortality from nonmalignant respiratory diseases in copper mining and smelting counties. We directly examined town mortality rates for white female residents, aged 35 to 74, in eight U.S. copper smelting communities and compared them to demographically and geographically matched communities without industries likely to produce significant air pollution, using death certificates obtained from state sources. Site-specific air quality data were also obtained for these communities. Our direct examination of community death rates for copper smelting towns confirmed the preliminary observation at the county level of an excess risk from acute respiratory diseases but did not detect evidence of an elevated mortality from chronic respiratory diseases or cancer of the respiratory tract.

  3. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    SciTech Connect (OSTI)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  4. Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

    SciTech Connect (OSTI)

    Feddock, Jonathan; Arnold, Susanne M.; Department of Medical Oncology, University of Kentucky, Lexington, Kentucky ; Shelton, Brent J.; Sinha, Partha; Conrad, Gary; Chen, Li; Rinehart, John; McGarry, Ronald C.

    2013-04-01

    Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (?5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ?3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

  5. IL-2R{gamma} gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease

    SciTech Connect (OSTI)

    Henthorn, P.S.; Fimiani, V.M.; Patterson, D.F.

    1994-09-01

    X-linked severe combined immunodeficiency (SCID) is characterized by profound defects in cellular and humoral immunity and, in humans, is associated with mutations in the gene for the {gamma} chain of the IL-2 receptor (IL-2R{gamma}). We have examined this gene in a colony of dogs established from a single X-linked SCID carrier female. Affected dogs have a 4-bp deletion in the first exon of the IL-2R{gamma} gene, which precludes the production of a functional protein, demonstrating that the canine disease is a true homologue of human X-linked SCID. 37 refs., 3 figs.

  6. Enhanced vector borne disease surveillance of California Culex mosquito populations reveals spatial and species-specific barriers of infection.

    SciTech Connect (OSTI)

    VanderNoot, Victoria A.; Curtis, Deanna Joy; Koh, Chung-Yan; Brodsky, Benjamin H; Lane, Todd

    2014-08-01

    Monitor i ng in f ectio n s in v ect o rs su c h as m osquit o es, s a nd fl i es, tsetse fl i es, a nd ticks to i denti f y hu m a n path o gens m a y s e r v e as a n ear l y w arn i ng det e ction system t o dir e ct loc a l g o v er n ment dise a se pr e v en t i v e m easu r e s . One major hurdle i n de t ection is the abi l i t y to scre e n l arge n u mbers of v e c t ors for h uman patho g ens w i thout t h e u s e of ge n o t y pe - s p ecific m o lecu l ar tec h nique s . N e x t genera t ion s equ e nc i ng (NG S ) pr o v i des a n unbi a sed p latfo r m capab l e of identi f y i ng k n o w n a n d unk n o w n p ath o ge n s circula t ing w i thin a v e ctor p opul a tion, but utili z ing t h is te c h nolo g y i s tim e - con s u ming a n d cos t l y for v ecto r -b o rne disease su r v e illan c e pr o gra m s. T o addr e s s this w e d e v e lop e d cos t -eff e ct i v e Ilumina(r) R NA- S eq l i bra r y p r epara t ion m e thodol o gies i n con j u n ction w i t h an automa t ed c ompu t at i onal a n a l y sis pipel i n e to ch a racter i ze t h e microbial popula t ions c ircula t i n g in Cu l e x m o squit o e s (Cul e x qui n quef a s c iatu s , C ul e x quinq u efasc i atus / pip i ens co m pl e x h y bri d s, and C u l e x ta r salis ) t hroug h out Californ i a. W e assembled 2 0 n o vel a n d w e l l -do c ume n ted a r b o v i ruses repres e nting mem b e rs of B u n y a v ir i da e , F l a v i virid a e, If a virida e , Meson i v i rida e , Nid o v iri d ae, O rtho m y x o virid a e, Pa r v o v iri d ae, Re o virid a e, R h a b d o v i rid a e, T y m o v iri d ae, a s w ell as s e v e r al u n assi g n e d v irus e s . In addit i o n, w e m app e d mRNA s pecies to d i vergent s peci e s of t r y panos o ma a nd pl a s modium eu k a r yotic parasit e s and cha r a c terized t he p r oka r yot i c microb i al c o mposit i on to i d enti f y bacteri a l tran s c r ipts der i v ed from wolba c hia, clo s tridi u m, m y c oplas m a, fusoba c

  7. A modified inflammatory bowel disease questionnaire and the Vaizey Incontinence questionnaire are more sensitive measures of acute gastrointestinal toxicity during pelvic radiotherapy than RTOG grading

    SciTech Connect (OSTI)

    Khalid, Usman; McGough, Camilla; Hackett, Claire; Blake, Peter; Harrington, Kevin J.; Khoo, Vincent S.; Tait, Diana; Norman, Andrew R.; Andreyev, H. Jervoise N. . E-mail: j@andreyev.demon.co.uk

    2006-04-01

    Purpose: Simple scales with greater sensitivity than Radiation Therapy Oncology Group (RTOG) grading to detect acute gastrointestinal toxicity during pelvic radiotherapy, could be clinically useful. Methods and Materials: Do questionnaires used in benign gastrointestinal diseases detect toxicity in patients undergoing radiotherapy? The patient-completed Inflammatory Bowel Disease (IBDQ) and Vaizey Incontinence questionnaires were compared prospectively at baseline and at Week 5 to physician-completed RTOG grading. Results: A total of 107 patients, median age 63 years, were recruited. After 5 weeks of treatment, patients with gynecologic and gastrointestinal cancer were more symptomatic than urologic patients (p 0.012; p = 0.014). Overall, 94% had altered bowel habits, 80% loose stool, 74% frequency, 65% difficult gas, 60% pain, >48% distress, 44% tenesmus, >40% restrictions in daily activity, 39% urgency, 37% fecal incontinence, and 40% required antidiarrheal medication. The median RTOG score was 1 (range, 0-2), median IBDQ score 204.5 (range, 74-224), and median Vaizey score 5 (range, 0-20). Chemotherapy preceding radiotherapy increased fecal incontinence (p 0.002). RTOG scores stabilized after 3 weeks, IBDQ scores peaked at Week 4, and Vaizey scores worsened throughout treatment. IBDQ and Vaizey scores distinguished between groups with different RTOG scores. Conclusion: The IBDQ and Vaizey questionnaires are reliable and sensitive, offering greater insight into the severity and range of symptoms compared with RTOG grading.

  8. A radiation hybrid map of the distal short arm of human chromosome II, containing the Beckwith-Weidemann and associated embroyonal tumor disease loci

    SciTech Connect (OSTI)

    Richard, C.W. III; Berg, D.J.; Meeker, T.C.; Myers, R.M.; Cox, D.R. ); Boehnke, M.; Hauser, E. ); Lichy, J.H. )

    1993-05-01

    The authors describe a high-resolution radiation hybrid (RH) map of the distal short arm of human chromosome 11 containing the Beckwith-Weidemann gene and the associated embryonal tumor disease loci. Thirteen human 11p15 genes and 17 new anonymous probes were mapped by a statistical analysis of the cosegregation of markers in 102 rodent-human radiation hybrids retaining fragments of human chromosome 11. The 17 anonymous probes were generated from lambda phage containing human 11p15.5 inserts, by using ALU-PCR. A comprehensive map of all 30 loci and a framework map of nine clusters of loci ordered at odds of 1,000:1 were constructed by a multipoint maximum-likelihood approach by using the computer program RHMAP. This RH map localizes one new gene to chromosome 11p15 (WEE1), provides more precise order information for several 11p15 genes (CTSD, H19, HPX,.ST5, RNH, and SMPD1), confirms previous map orders for other 11p15 genes (CALCA, PTH, HBBC, TH, HRAS, and DRD4), and maps 17 new anonymous probes within the 11p15.5 region. This RH map should prove useful in better defining the positions of the Beckwith-Weidemann and associated embryonal tumor disease-gene loci. 41 refs., 1 fig., 2 tabs.

  9. Update to agency for toxic substances and disease registry 2012 report on assessment of biota exposure to mercury originating from Savannah River Site.

    SciTech Connect (OSTI)

    Kuhne, W.

    2015-08-10

    The purpose of this report is to 1) update previous Savannah River National Laboratory (SRNL) assessment reports (Kvartek et al. 1994 and Halverson et al. 2008) on the fate of mercury in the Savannah River Site (SRS) environment and 2) address comments and recommendations from the review of SRS by the Agency for Toxic Substances and Disease Registry (ATSDR) concerning the evaluation of exposures to contaminants in biota originating from the SRS. The ATSDR reviewed and evaluated data from SRS, South Carolina Department of Health & Environmental Control (SCDHEC) and the Georgia Department of Natural Resources (GDNR) concerning the non-radioactive contaminant mercury. This report will provide a response and update to conclusions and recommendations made by the ATSDR.

  10. Enhanced sensitivity and specificity of thallium-201 imaging for the detection of regional ischemic coronary disease by combining SPECT with bull's eye analysis

    SciTech Connect (OSTI)

    Kasabali, B.; Woodard, M.L.; Bekerman, C.; Pinsky, S.; Blend, M.J. (Michael Reese Hospital and Medical Center, Chicago, IL (USA))

    1989-07-01

    Previous studies have indicated that the combination of single photon emission computed tomography (SPECT) and quantitative bull's eye analysis (QBA) TI-201 cardiac stress imaging may improve the detection of myocardial ischemia over that achieved with planar (PLN) imaging. This study will evaluate the sensitivity and specificity of SPECT and QBA in the detection of disease in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery. Ninety-nine patients who underwent both TI-201 stress imaging and coronary arteriography were evaluated retrospectively. Of the 99, 62 had PLN imaging and 37 were evaluated with SPECT; 23 of these 37 had QBA. The overall sensitivity and specificity were as follows: PLN, 94% and 50%; SPECT, 90% and 67%; QBA, 100% and 20%; and SPECT with QBA, 92% and 72%, respectively. The regional sensitivity and specificity of PLN for individual coronary arteries were as follows: RCA, 78% and 74%; LAD, 89% and 60%; LCX, 50% and 89%, respectively. For SPECT, the results were: RCA, 86% and 93%; LAD, 85% and 88%; and LCX, 60% and 88%. For QBA alone, the results were: RCA, 100% and 75%; LAD, 88% and 53%; and LCX, 100% and 89%. The results for QBA with SPECT were: RCA, 100% and 94%; LAD, 88% and 80%; and LCX, 67% and 95%. Thus, SPECT interpreted on conjunction with QBA showed higher sensitivity for evaluation of ischemia in the RCA and LCX arteries and higher specificity in the detection of LAD and RCA disease than did PLN TI-201 imaging. Because of the low specificity of QBA (20%), caution is advised in the interpretation of QBA alone without reviewing SPECT images.

  11. Impact of 18F-Fluoro-2-Deoxyglucose Positron Emission Tomography on Treatment Strategy and Radiotherapy Planning for Stage I-II Hodgkin Disease: A Prospective Multicenter Study

    SciTech Connect (OSTI)

    Pommier, Pascal; Dussart, Sophie; Girinsky, Theodore; Chabaud, Sylvie; Lagrange, Jean Leon; Nguyen, Tan Dat; Beckendorff, Veronique; D'Hombres, Anne; Artignan, Xavier; Bondiau, Pierre Yves; Carrie, Christian; Giammarile, Francesco

    2011-03-01

    Purpose: To quantify the impact of preradiotherapy 18F-fluoro-2-deoxyglucose positron-emission tomography (FDG-PET) on treatment strategy and radiotherapy planning for patients with Stage I/II Hodgkin disease included in a large prospective multicenter study. Patients and Methods: Conventional computed tomography and FDG-PET were performed just before the planned radiotherapy. The radiotherapy plan was first elaborated under blinded conditions for FDG-PET data. Then, the medical staff was asked to confirm or not confirm the treatment strategy and, if appropriate, to modify the radiotherapy plan based on additional information from FDG-PET. Results: Between January 2004 and January 2006, 137 patients were included (124 were available for analysis) in 11 centers (108 adults, 16 children). All but 1 patient had received chemotherapy before inclusion. Prechemotherapy work-up included FDG-PET for 61 patients, and data were available for elaboration of the first radiotherapy plan. Based on preradiotherapy FDG-PET data, the radiotherapy was cancelled in 6 patients (4.8%), and treatment plan modifications occurred in 16 patients (12.9%): total dose (11 patients), CTV volume (5 patients), number of beam incidences (6 patients), and number of CTV (6 patients). The concordance between the treatment strategies with or without preradiotherapy FDG-PET was 82.3%. Concordance results were not significantly different when prechemotherapy PET-CT information was available. Conclusion: Preradiotherapy FDG-PET for treatment planning in Hodgkin lymphoma may lead to significant modification of the treatment strategy and the radiotherapy planning in patients with Stage I or II Hodgkin disease, even in those who have undergone FDG-PET as part of the prechemotherapy work-up.

  12. A Multicenter Retrospective Analysis of Survival Outcome Following Postoperative Chemoradiotherapy in Non-Small-Cell Lung Cancer Patients With N2 Nodal Disease

    SciTech Connect (OSTI)

    Zou Bingwen; Xu Yong; Li Tao; Li Wenhui; Tang Bangxian; Zhou Lin; Li Lu; Liu Yongmei; Zhu Jiang; Huang Meijuan; Wang Jin; Ren Li; Gong Youlin; Che Guowei; Liu Lunxu; Hou Mei; Lu You

    2010-06-01

    Purpose: To retrospectively evaluate the role of postoperative chemoradiotherapy (POCRT) in patients with completely resected non-small-cell lung cancer (NSCLC) with N2 lymph node involvement. Methods and Materials: This study included 183 patients from four centers in southwest China who underwent radical section of Stage III-N2 NSCLC without any preoperative therapy. One hundred and four were treated with POCRT and 79 with postoperative chemotherapy (POCT) alone. The median radiation dose to clinical target volume (CTV) was 50 Gy (varying between 48 and 54 Gy), whereas the cycles of platinum-based chemotherapy ranged from two to six with a median of four. Results: The median duration of follow-up was 72 months. The 5-year overall survival rate (OS) was 30.5% in the POCRT group, and 14.4% in the POCT group (p = 0.007). The 5-year disease-free survival rate (DFS) was 22.2% in POCRT group and 9.3% in POCT group (p = 0.003). In a multivariate analysis, N1 nodal involvement (N1+/N2+) was associated with significantly worse OS (HR = 1.454, 95% CI, 1.012-2.087, p = 0.043) and DFS (HR = 1.685, 95% CI, 1.196-2.372, p = 0.003). Absence of radiotherapy and treatment with fewer than three cycles of chemotherapy both were poor prognostic factors for both OS and DFS. Conclusions: As compared with chemotherapy alone, adjuvant treatment with both radiotherapy and chemotherapy improves survival in patients with completely resected Stage III-N2 nodal disease in NSCLC. Future study of treatment modality with radiotherapy and chemotherapy is warranted, especially focusing on both N1 and N2 nodal status.

  13. Impact of Preoperative Radiotherapy on General and Disease-Specific Health Status of Rectal Cancer Survivors: A Population-Based Study

    SciTech Connect (OSTI)

    Thong, Melissa S.Y.; Mols, Floortje; Lemmens, Valery E.P.P.; Rutten, Harm J.T.; Roukema, Jan A.; Martijn, Hendrik; Poll-Franse, Lonneke V. van de

    2011-11-01

    Purpose: To date, few studies have evaluated the impact of preoperative radiotherapy (pRT) on long-term health status of rectal cancer survivors. Using a population-based sample, we assessed the impact of pRT on general and disease-specific health status of rectal cancer survivors up to 10 years postdiagnosis. The health status of older ({>=}75 years old at diagnosis) pRT survivors was also compared with that of younger survivors. Methods and Materials: Survivors identified from the Eindhoven Cancer Registry treated with surgery only (SU) or with pRT between 1998 and 2007 were included. Survivors completed the Short Form-36 (SF-36) health survey questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 38 (EORTC QLQ-CR38) questionnaire. The SF-36 and EORTC QLQ-CR38 (sexuality subscale) scores of the survivors were compared to an age- and sex-matched Dutch normal population. Results: A total of 340 survivors (response, 85%; pRT survivors, 71%) were analyzed. Overall, survivors had similar general health status. Both short-term (<5 years) and long-term ({>=}5 years) pRT survivors had significantly poorer body image and more problems with gastrointestinal function, male sexual dysfunction, and defecation than SU survivors. Survivors had comparable general health status but greater sexual dysfunction than the normal population. Older pRT survivors had general and disease-specific health status comparable to that of younger pRT survivors. Conclusions: For better survivorship care, rectal cancer survivors could benefit from increased clinical and psychological focus on the possible long-term morbidity of treatment and its effects on health status.

  14. Whole Abdominopelvic Radiotherapy Using Intensity-Modulated Arc Therapy in the Palliative Treatment of Chemotherapy-Resistant Ovarian Cancer With Bulky Peritoneal Disease: A Single-Institution Experience

    SciTech Connect (OSTI)

    De Meerleer, Gert; Vandecasteele, Katrien; Ost, Piet; Delrue, Louke; Denys, Hannelore; Makar, Amin; Speleers, Bruno; Van Belle, Simon; Van den Broecke, Rudy; Fonteyne, Valerie; De Neve, Wilfried

    2011-03-01

    Purpose: To retrospectively review our experience with whole abdominopelvic radiotherapy (WAPRT) using intensity-modulated arc therapy in the palliative treatment of chemotherapy-resistant ovarian cancer with bulky peritoneal disease. Methods and Materials: Between April 2002 and April 2008, 13 patients were treated with WAPRT using intensity-modulated arc therapy. We prescribed a dose of 33 Gy to be delivered in 22 fractions of 1.5 Gy to the abdomen and pelvis. All patients had International Federation of Gynecology and Obstetrics Stage III or IV ovarian cancer at the initial diagnosis. At referral, the median age was 61 years, and the patients had been heavily pretreated with surgery and chemotherapy. All patients had symptoms from their disease, including gastrointestinal obstruction or subobstruction in 6, minor gastrointestinal symptoms in 2, pain in 4, ascites in 1, and vaginal bleeding in 2. A complete symptom or biochemical response required complete resolution of the patient's symptoms or cancer antigen-125 level. A partial response required {>=}50% resolution of these parameters. The actuarial survival was calculated from the start of radiotherapy. Results: The median overall survival was 21 weeks, with a 6-month overall survival rate of 45%. The 9 patients who completed treatment obtained a complete symptom response, except for ascites (partial response). The median and mean response duration (all symptoms grouped) was 24 and 37 weeks, respectively. Of the 6 patients presenting with obstruction or subobstruction, 4 obtained a complete symptom response (median duration, 16 weeks). Conclusion: WAPRT delivered using intensity-modulated arc therapy offers important palliation in the case of peritoneal metastatic ovarian cancer. WAPRT resolved intestinal obstruction for a substantial period.

  15. AAV-mediated delivery of the transcription factor XBP1s into the striatum reduces mutant Huntingtin aggregation in a mouse model of Huntington's disease

    SciTech Connect (OSTI)

    Zuleta, Amparo [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile) [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile); Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, Santiago (Chile); Vidal, Rene L. [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile) [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile); Neurounion Biomedical Foundation, Santiago (Chile); Armentano, Donna; Parsons, Geoffrey [Department of Molecular Biology, Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States)] [Department of Molecular Biology, Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States); Hetz, Claudio, E-mail: chetz@med.uchile.cl [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile) [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile); Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, Santiago (Chile); Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Av., Boston, MA 02446 (United States); Neurounion Biomedical Foundation, Santiago (Chile)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer The contribution of ER stress to HD has not been directly addressed. Black-Right-Pointing-Pointer Expression of XBP1s using AAVs decreases Huntingtin aggregation in vivo. Black-Right-Pointing-Pointer We describe a new in vivo model of HD based on the expression of a large fragment of mHtt-RFP. -- Abstract: Huntington's disease (HD) is caused by mutations that expand a polyglutamine region in the amino-terminal domain of Huntingtin (Htt), leading to the accumulation of intracellular inclusions and progressive neurodegeneration. Recent reports indicate the engagement of endoplasmic reticulum (ER) stress responses in human HD post mortem samples and animal models of the disease. Adaptation to ER stress is mediated by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that attenuates protein folding stress by controlling the expression of distinct transcription factors including X-Box binding protein 1 (XBP1). Here we targeted the expression of XBP1 on a novel viral-based model of HD. We delivered an active form of XBP1 locally into the striatum of adult mice using adeno-associated vectors (AAVs) and co-expressed this factor with a large fragment of mutant Htt as a fusion protein with RFP (Htt588{sup Q95}-mRFP) to directly visualize the accumulation of Htt inclusions in the brain. Using this approach, we observed a significant reduction in the accumulation of Htt588{sup Q95}-mRFP intracellular inclusion when XBP1 was co-expressed in the striatum. These results contrast with recent findings indicating a protective effect of XBP1 deficiency in neurodegeneration using knockout mice, and suggest a potential use of gene therapy strategies to manipulate the UPR in the context of HD.

  16. Prognostic Importance of Gleason 7 Disease Among Patients Treated With External Beam Radiation Therapy for Prostate Cancer: Results of a Detailed Biopsy Core Analysis

    SciTech Connect (OSTI)

    Spratt, Daniel E.; Zumsteg, Zach; Ghadjar, Pirus; Pangasa, Misha; Pei, Xin; Fine, Samson W.; Yamada, Yoshiya; Kollmeier, Marisa; Zelefsky, Michael J.

    2013-04-01

    Purpose: To analyze the effect of primary Gleason (pG) grade among a large cohort of Gleason 7 prostate cancer patients treated with external beam radiation therapy (EBRT). Methods and Materials: From May 1989 to January 2011, 1190 Gleason 7 patients with localized prostate cancer were treated with EBRT at a single institution. Of these patients, 613 had a Gleason 7 with a minimum of a sextant biopsy with nonfragmented cores and full biopsy core details available, including number of cores of cancer involved, percentage individual core involvement, location of disease, bilaterality, and presence of perineural invasion. Median follow-up was 6 years (range, 1-16 years). The prognostic implication for the following outcomes was analyzed: biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM). Results: The 8-year bRFS rate for pG3 versus pG4 was 77.6% versus 61.3% (P<.0001), DMFS was 96.8% versus 84.3% (P<.0001), and PCSM was 3.7% versus 8.1% (P=.002). On multivariate analysis, pG4 predicted for significantly worse outcome in all parameters. Location of disease (apex, base, mid-gland), perineural involvement, maximum individual core involvement, and the number of Gleason 3+3, 3+4, or 4+3 cores did not predict for distant metastases. Conclusions: Primary Gleason grade 4 independently predicts for worse bRFS, DMFS, and PCSM among Gleason 7 patients. Using complete core information can allow clinicians to utilize pG grade as a prognostic factor, despite not having the full pathologic details from a prostatectomy specimen. Future staging and risk grouping should investigate the incorporation of primary Gleason grade when complete biopsy core information is used.

  17. Long none coding RNA HOTTIP/HOXA13 act as synergistic role by decreasing cell migration and proliferation in Hirschsprung disease

    SciTech Connect (OSTI)

    Xie, Hua; Zhu, Dongmei; Xu, Cao; Zhu, Hairong; Chen, Pingfa; Li, Hongxing; Liu, Xiang; Xia, Yankai; Tang, Weibing

    2015-08-07

    Long noncoding RNAs (lncRNAs) have been confirmed to be associated with various human diseases. However, whether they are associated with Hirschsprung disease (HSCR) progression remains unclear. In this study, we designed the experiment to explore the relationship between lncRNA HOTTIP and HOXA13, and their pathogenicity to HSCR. Quantitative real-time PCR and Western blot were performed to detect the levels of lncRNA, mRNAs, and proteins in colon tissues from 79 patients with HSCR and 79 controls. Small RNA interference transfection was used to study the function experiments in human 293T and SK-N-BE cell lines. The cell viability and activities were detected by the transwell assays, CCK8 assay, and flow cytometry, respectively. LncRNA HOTTIP and HOXA13 were significantly down-regulated in HSCR compared to the controls. Meanwhile, the declined extent of their expression levels makes sense between two main phenotype of HSCR. SiRNA-mediated knock-down of HOTTIP or HOXA13 correlated with decreased levels of each other and both reduced the cell migration and proliferation without affecting cell apoptosis or cell cycle. Our study demonstrates that aberrant reduction of HOTTIP and HOXA13, which have a bidirectional regulatory loop, may play an important role in the pathogenesis of HSCR. - Highlights: • LncRNA HOTTIP and HOXA13 are both down-regulated in HSCR. • HOTTIP and HOXA13 can regulate each other in 293T and SK-N-BE(2) cell lines. • Both HOTTIP and HOXA13 can decrease cell migration and proliferation.

  18. Inhalation Toxicology Research Institute annual report, October 1, 1987--September 30, 1988

    SciTech Connect (OSTI)

    Mewhinney, J.A.; Bechtold, W.E.; Sun, J.D.; Coons, T.A.

    1988-12-01

    The mission of the Inhalation Toxicology Research Institute is to investigate the nature and magnitude of human health effects that result from the inhalation of airborne materials at home, in the work place, or in the general environment. Diseases of the respiratory tract are major causes of suffering and death, and many of these diseases are directly related to the materials that people breathe. The Institute's research is directed toward obtaining a better understanding of the basic biology of the respiratory tract and the mechanisms by which inhaled materials produce respiratory disease. Special attention is focused on studying the airborne materials released by various energy technologies, as well as those associated with national defense activities. The research uses a wide-ranging, comprehensive array of investigative approaches that are directed toward characterizing the source of the airborne material, following the material through its potential transformation in the air, identifying the mechanisms that govern its inhalation and deposition in the respiratory tract, and determining the fate of these inhaled materials in the body and the health effects they produce. The ultimate objectives are to determine the roles played by inhaled materials in the development of disease processes and to estimate the risk they pose to humans who may be exposed to them.

  19. BRCA1 loss pre-existing in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

    SciTech Connect (OSTI)

    Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart; Hannemann, Juliane; Fisch, Margit; Pantel, Klaus; Weier, Heinz-Ulrich G.; Bielawski, Krzysztof P.; Brandt, Burkhard

    2010-03-19

    A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating those patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1 losses

  20. Effect of Intravascular Iodinated Contrast Media on Natural Course of End-Stage Renal Disease Progression in Hemodialysis Patients: A Prospective Study

    SciTech Connect (OSTI)

    Janousek, Radim; Krajina, Antonin; Peregrin, Jan H.; Dusilova-Sulkova, Sylvie; Renc, Ondrej; Hajek, Jan; Dvorak, Kamil; Fixa, Petr; Cermakova, Eva

    2010-02-15

    We evaluated the impact of intravascular iodinated contrast medium on residual diuresis in hemodialyzed patients. Two groups of clinically stable hemodialyzed patients with residual diuresis minimally 500 ml of urine per day were studied. The patients from the first group were given iso-osmolal contrast agent iodixanol (Visipaque, GE Healthcare, United Kingdom) in concentration of iodine 320 mg/ml with osmolality 290 mOsm/kg of water during the endovascular procedure. The second control group was followed without contrast medium administered. Residual diuresis and residual renal excretory capacity expressed as 24-h calculated creatinine clearance were evaluated in the both groups after 6 months. The evaluated group included 42 patients who were given 99.3 ml of iodixanol in average (range, 60-180 ml). The control group included 45 patients. There was no statistically significant difference found between both groups in daily volume of urine (P = 0.855) and calculated clearance of creatinine (P = 0.573). We can conclude that residual diuresis is not significantly influenced by intravascular administration of iso-osmolal iodinated contrast agent (iodixanol) in range of volume from 60 to 180 ml in comparison to natural course of urinary output and residual renal function during end-stage renal disease. This result can help the nephrologist to decide which imaging method/contrast medium to use in dialyzed patients in current practice.

  1. Using Wikipedia to forecast diseases

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    the same way we check the weather each morning, individuals ... Brazil and Thailand, and tuberculosis in China and Thailand. ... public health data in one location and use it in another. ...

  2. Zika Virus Disease and Prevention

    Broader source: Energy.gov (indexed) [DOE]

    Most common symptoms of Zika are fever, rash, joint pain, or conjunctivitis (red eyes). ... they develop a fever, rash, joint pain, or red eyes during their trip or within 2 weeks ...

  3. Using Wikipedia to forecast disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    to plan for future outbreaks. The LANL team was able to successfully monitor influenza in the United States, dengue fever in Brazil and Thailand, and tuberculosis in China...

  4. Fridges to fight childhood disease

    SciTech Connect (OSTI)

    Lerner, T.

    1983-04-01

    A solar-powered refrigerator/freezer has been installed in a medical center in Bhoorbaral, India. The installation and performance of the refrigerator/freezer are described.

  5. Improved medical implants comes from nanostructuring

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    However, cobalt-chromium superalloys, stainless steels, and titanium alloys-the most commonly used materials in today's orthopedic devices- have the potential to present serious ...

  6. Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17

    SciTech Connect (OSTI)

    Cheng, S.V.; Nadeau, J.H.; Tanzi, R.E.; Watkins, P.C.; Jagadesh, J.; Taylor, B.A.; Haines, J.L.; Sacchi, N.; Gusella, J.F. )

    1988-08-01

    Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid {beta} precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, the authors have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD-linked markers. Extending from the anonymous DNA locus D21S52 to ETS2, the linkage map of six loci spans 39% recombination in man but only 6.4% recombination in the mouse. A break in synteny occurs distal to ETS2, with the homologue of the human marker D21S56 mapping to mouse chromosome 17. Conservation of the linkage relationships of markers in the FAD region suggests that the murine homologue of the FAD locus probably maps to chromosome 16 and that detailed comparison of the corresponding region in both species could facilitate identification of the primary defect in this disorder. The break in synteny between the terminal portion of human chromosome 21 and mouse chromosome 16 indicates, however, that mouse trisomy 16 may not represent a complete model of DS.

  7. Prospective Study Evaluating Postoperative Radiotherapy Plus 2-Year Androgen Suppression for Post-Radical Prostatectomy Patients With Pathologic T3 Disease and/or Positive Surgical Margins

    SciTech Connect (OSTI)

    Choo, Richard [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)], E-mail: choo.c@mayo.edu; Danjoux, Cyril; Gardner, Sandra; Morton, Gerard; Szumacher, Ewa; Loblaw, D. Andrew; Cheung, Patrick [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, ON (Canada); Pearse, Maria [Department of Radiation Oncology, Auckland Hospital, Auckland (New Zealand)

    2009-10-01

    Purpose: To determine the efficacy of a combined approach of postoperative radiotherapy (RT) plus 2-year androgen suppression (AS) for patients with pathologic T3 disease (pT3) and/or positive surgical margins (PSM) after radical prostatectomy (RP). Methods and Materials: A total of 78 patients with pT3 and/or PSM after RP were treated with RT plus 2-year AS, as per a pilot, prospective study. Androgen suppression started within 1 month after the completion of RT and consisted of nilutamide for 4 weeks and buserelin acetate depot subcutaneously every 2 months for 2 years. Relapse-free rate, including freedom from prostate-specific antigen (PSA) relapse, was estimated using the Kaplan-Meier method. A Cox regression analysis was performed to evaluate prognostic factors for relapse. Prostate-specific antigen relapse was defined as a PSA rise above 0.2 ng/mL, with two consecutive increases over a minimum of 3 months. Results: The median age was 61 years at the time of RP. The median interval between RP and postoperative RT was 4.2 months. Forty-nine patients had undetectable PSA (<0.2 ng/mL), and 29 had persistently detectable postoperative PSA at the time of the protocol treatment. Median follow-up from RT was 6.4 years. Relapse-free rates at 5 and 7 years were 94.4% and 86.3%, respectively. Survival rates were 96% at 5 years and 93.1% at 7 years. On Cox regression analysis, persistently detectable postoperative PSA and pT3b-T4 were significant predictors for relapse. Conclusion: The combined treatment of postoperative RT plus 2-year AS yielded encouraging results for patients with pT3 and/or PSM and warrants a confirmatory study.

  8. Efficacy and Safety of a Novel Vascular Closure Device (Glubran 2 Seal) After Diagnostic and Interventional Angiography in Patients with Peripheral Arterial Occlusive Disease

    SciTech Connect (OSTI)

    Del Corso, Andrea; Bargellini, Irene Cicorelli, Antonio; Perrone, Orsola; Leo, Michele; Lunardi, Alessandro; Alberti, Aldo; Tomei, Francesca; Cioni, Roberto; Ferrari, Mauro; Bartolozzi, Carlo

    2013-04-15

    To prospectively evaluate safety and efficacy of a novel vascular closure device (Glubran 2 Seal) after peripheral angiography in patients with peripheral arterial occlusive disease (PAOD). From December 2010 to June 2011, all consecutive patients with PAOD undergoing peripheral angiography were prospectively enrolled onto the study after percutaneous antegrade or retrograde puncture of the common femoral artery. After angiography, the Glubran 2 Seal device was used to achieve hemostasis. The following data were registered: technical success and manual compression duration, patients' discomfort (scale 0-5), operators' technical difficulty (scale 0-5), and vascular complications. The site of hemostasis was evaluated by clinical inspection and color-coded Duplex ultrasound performed 1 day and 1 month after the procedure. One hundred seventy-eight patients were enrolled (112 male, mean age 70.8 years) with a total of 206 puncture sites, including 104 (50.5 %) antegrade accesses. The device was successful in 198(96.1 %) of 206 procedures, with 8 cases of manual compression lasting longer than 5 min (maximum 20 min). No major vascular complications were observed, resulting in 100 % procedural success. Minor complications occurred in seven procedures (3.4 %), including two cases of pseudoaneurysms, successfully treated by ultrasound-guided glue injection. The mean {+-} standard deviation score for patients' discomfort was 0.9 {+-} 0.7, whereas the mean score for operators' difficulty was 1.2 {+-} 0.9. In patients with PAOD, the Glubran 2 Seal represents a simple, painless, and efficient vascular closure device, able to achieve hemostasis both in antegrade and retrograde accesses.

  9. Photochemical air pollution. Part I

    SciTech Connect (OSTI)

    Goldstein E.; Hackney, J.D.; Rokaw, S.N.

    1985-03-01

    In this paper, epidemiologic studies are reported which indicate that high photochemical oxidant exposures: do not cause mortality or serious illness; may increase the risk of asthmatic attacks in a small percentage of asthmatic patients; appear to reduce pulmonary function in smokers and nonsmokers after long-term exposure; cause acute discomfort of eye and throat, chest irritation and cough; and interfere with athletic performance. Exposure to high ambient levels of NO/sub 2/ is not associated with mortality, serious disease or respiratory dysfunction, but self-limiting symptoms of respiratory irritation or illness may develop in children. 106 references, 2 figures, 1 table.

  10. TU-C-12A-12: Differentiating Bone Lesions and Degenerative Joint Disease in NaF PET/CT Scans Using Machine Learning

    SciTech Connect (OSTI)

    Perk, T; Bradshaw, T; Muzahir, S; Jeraj, R; Meyer, E

    2014-06-15

    Purpose: [F-18]NaF PET can be used to image bone metastases; however, tracer uptake in degenerative joint disease (DJD) often appears similar to metastases. This study aims to develop and compare different machine learning algorithms to automatically identify regions of [F-18]NaF scans that correspond to DJD. Methods: 10 metastatic prostate cancer patients received whole body [F-18]NaF PET/CT scans prior to treatment. Image segmentation resulted in 852 ROIs, 69 of which were identified by a nuclear medicine physician as DJD. For all ROIs, various PET and CT textural features were computed. ROIs were divided into training and testing sets used to train eight different machine learning classifiers. Classifiers were evaluated based on receiver operating characteristics area under the curve (AUC), sensitivity, specificity, and positive predictive value (PPV). We also assessed the added value of including CT features in addition to PET features for training classifiers. Results: The training set consisted of 37 DJD ROIs with 475 non-DJD ROIs, and the testing set consisted of 32 DJD ROIs with 308 non-DJD ROIs. Of all classifiers, generalized linear models (GLM), decision forests (DF), and support vector machines (SVM) had the best performance. AUCs of GLM (0.929), DF (0.921), and SVM (0.889) were significantly higher than the other models (p<0.001). GLM and DF, overall, had the best sensitivity, specificity, and PPV, and gave a significantly better performance (p<0.01) than all other models. PET/CT GLM classifiers had higher AUC than just PET or just CT. GLMs built using PET/CT information had superior or comparable sensitivities, specificities and PPVs to just PET or just CT. Conclusion: Machine learning algorithms trained with PET/CT features were able to identify some cases of DJD. GLM outperformed the other classification algorithms. Using PET and CT information together was shown to be superior to using PET or CT features alone. Research supported by the Prostate

  11. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    SciTech Connect (OSTI)

    Wahlang, Banrida; Song, Ming; Beier, Juliane I.; Cameron Falkner, K.; Al-Eryani, Laila; Clair, Heather B.; Prough, Russell A.; Osborne, Tanasa S.; Malarkey, David E.; Christopher States, J.; Cave, Matthew C.

    2014-09-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced

  12. Viscoelastic Model for Lung Parenchyma for Multi-Scale Modeling of Respiratory System, Phase II: Dodecahedral Micro-Model

    SciTech Connect (OSTI)

    Freed, Alan D.; Einstein, Daniel R.; Carson, James P.; Jacob, Rick E.

    2012-03-01

    In the first year of this contractual effort a hypo-elastic constitutive model was developed and shown to have great potential in modeling the elastic response of parenchyma. This model resides at the macroscopic level of the continuum. In this, the second year of our support, an isotropic dodecahedron is employed as an alveolar model. This is a microscopic model for parenchyma. A hopeful outcome is that the linkage between these two scales of modeling will be a source of insight and inspiration that will aid us in the final year's activity: creating a viscoelastic model for parenchyma.

  13. Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation

    SciTech Connect (OSTI)

    Rancourt, Raymond C. Veress, Livia A. Ahmad, Aftab Hendry-Hofer, Tara B. Rioux, Jacqueline S. Garlick, Rhonda B. White, Carl W.

    2013-10-01

    Sulfur mustard (SM) inhalation causes airway injury, with enhanced vascular permeability, coagulation, and airway obstruction. The objective of this study was to determine whether recombinant tissue factor pathway inhibitor (TFPI) could inhibit this pathogenic sequence. Methods: Rats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5 mg/kg) in vehicle, or vehicle alone, was instilled into the trachea. Arterial O{sub 2} saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma were analyzed for prothrombin, thrombinantithrombin complex (TAT), active plasminogen activator inhibitor-1 (PAI-1) levels, and fluid fibrinolytic capacity. Lung steady-state PAI-1 mRNA was measured by RT-PCR analysis. Airway-capillary leak was estimated by BALF protein and IgM, and by pleural fluid measurement. In additional animals, airway cast formation was assessed by microdissection and immunohistochemical detection of airway fibrin. Results: Airway obstruction in the form of fibrin-containing casts was evident in central conducting airways of rats receiving CEES. TFPI decreased cast formation, and limited severe hypoxemia. Findings of reduced prothrombin consumption, and lower TAT complexes in BALF, demonstrated that TFPI acted to limit thrombin activation in airways. TFPI, however, did not appreciably affect CEES-induced airway protein leak, PAI-1 mRNA induction, or inhibition of the fibrinolytic activity present in airway surface liquid. Conclusions: Intratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury. - Highlights: TFPI administration to rats after mustard inhalation reduces airway cast formation. Inhibition of thrombin activation is the likely mechanism for limiting casts. Rats given TFPI had improved tissue oxygenation, and mortality was prevented.

  14. Textbook of clinical occupational and environmental medicine. 2nd ed.

    SciTech Connect (OSTI)

    Rosenstock, L.; Cullen, M.; Brodkin, C.; Redlich, C.

    2004-12-15

    Comprehensive and updated throughout, this new edition makes it easy to detect, diagnose, and treat the full spectrum of problems caused by occupational or environmental factors, including physical, chemical, and biologic agents. An international cast of experts offers in-depth, authoritative guidance on clinical problems as well as the legal and regulatory issues impacting the practice of occupational and environmental medicine today. Section 1 is on principles and practice. Section 2 on work sectors and special populations includes a chapter on mining. Section 3 on occupational diseases and injuries includes several chapters of relevance to the coal mining industry, including diseases of the lung and pleura covering silicosis, respiratory diseases of coal miners, and malignancies of the respiratory tract and pleura. Section 4 on hazards in the workplace and the environment includes a chapter on mineral dusts. Section 5 covers policy, regulation and control.

  15. A case report of motor neuron disease in a patient showing significant level of DDTs, HCHs and organophosphate metabolites in hair as well as levels of hexane and toluene in blood

    SciTech Connect (OSTI)

    Kanavouras, Konstantinos; Tzatzarakis, Manolis N.; Mastorodemos, Vasileios; Plaitakis, Andreas; Tsatsakis, Aristidis M.

    2011-11-15

    Motor neuron disease is a devastating neurodegenerative condition, with the majority of sporadic, non-familial cases being of unknown etiology. Several epidemiological studies have suggested that occupational exposure to chemicals may be associated with disease pathogenesis. We report the case of a patient developing progressive motor neuron disease, who was chronically exposed to pesticides and organic solvents. The patient presented with leg spasticity and developed gradually clinical signs suggestive of amyotrophic lateral sclerosis, which was supported by the neurophysiologic and radiological findings. Our report is an evidence based case of combined exposure to organochlorine (DDTs), organophosphate pesticides (OPs) and organic solvents as confirmed by laboratory analysis in samples of blood and hair confirming systematic exposure. The concentration of non-specific dialkylphosphates metabolites (DAPs) of OPs in hair (dimethyphopshate (DMP) 1289.4 pg/mg and diethylphosphate (DEP) 709.4 pg/mg) and of DDTs (opDDE 484.0 pg/mg, ppDDE 526.6 pg/mg, opDDD 448.4 pg/mg, ppDDD + opDDT 259.9 pg/mg and ppDDT 573.7 pg/mg) were considerably significant. Toluene and n-hexane were also detected in blood on admission at hospital and quantified (1.23 and 0.87 {mu}g/l, respectively), while 3 months after hospitalization blood testing was found negative for toluene and n-hexane and hair analysis was provided decrease levels of HCHs, DDTs and DAPs. -- Highlights: Black-Right-Pointing-Pointer Exposure to pesticides and organic solvents might be a risk factor for sporadic MND. Black-Right-Pointing-Pointer We report a patient who developed progressive upper and lower motor neuron disease. Black-Right-Pointing-Pointer The patient had a history of occupational exposure to pesticides and solvents. Black-Right-Pointing-Pointer High DDTs' levels and increased levels of DMP and DEP were measured in his hair. Black-Right-Pointing-Pointer The patients' exposure to chemicals might have played

  16. One Vaccine Leads to Another

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    One Vaccine Leads to Another Print Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines have been extremely effective; studies on one vaccine in particular, the nontoxic form of the diphtheria toxin (DT), have informed other vaccines. Recently, researchers at Novartis GNF solved several structures of a nontoxic DT using data obtained at ALS Beamline 5.0.3, resolving a long-standing scientific puzzle and

  17. One Vaccine Leads to Another

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    One Vaccine Leads to Another One Vaccine Leads to Another Print Friday, 24 May 2013 11:19 Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines have been extremely effective; studies on one vaccine in particular, the nontoxic form of the diphtheria toxin (DT), have informed other vaccines. Recently, researchers at Novartis GNF solved several structures of a nontoxic DT using data obtained at ALS Beamline

  18. Understanding the Key to Henipavirus Infection

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Understanding the Key to Henipavirus Infection Understanding the Key to Henipavirus Infection Print Wednesday, 15 June 2016 00:00 In 1994, a virus emerged in Hendra, Australia, causing respiratory and neurological diseases. It was transmissible from horses to humans, with a mortality rate of 57% in humans and 89% in horses. In 1999, a similar virus, transmitted through domesticated pigs, caused over 100 human deaths in Sungai Nipah, a Malaysian village. The Hendra and Nipah viruses are

  19. Secure Healthcare Internet Employee Learning Drill

    SciTech Connect (OSTI)

    2005-08-01

    SHIELD solves the problem of rapidly training large numbers of healthcare or other facility personnel who work around the clock - especially the non-professional semi-skilled employees who usually have "first contact" with patients and visitors - about how to limit or prevent exposure of facilities to infectious illness or other disease threats. This tool provides a very brief, realistic training experience that shows a range of facility personnel how to identify and respond to possible acute infectious respiratory illness outbreaks.

  20. Structure of an Unusually Small RNA Switch Provides Insight into the

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Minimal Requirements for Microbial Gene Regulation Structure of an Unusually Small RNA Switch Provides Insight into the Minimal Requirements for Microbial Gene Regulation The emergence of drug-resistant microbes represents a major impediment in the treatment of bacterial infections. Resistance to first-choice drugs has become problematic for respiratory infections, AIDS, tuberculosis, malaria and diarrheal diseases, which are top killers among infectious agents. When second- and third-choice

  1. Substrate Recognition Strategy for Botulinum Neurotoxin

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Substrate Recognition Strategy for Botulinum Neurotoxin Print Clostridal neurotoxins (CNTs) are the causative agents of the neuroparalytic diseases botulism and tetanus. By inhibiting release of the neurotransmitter acetylcholine, for example, the neurotoxin produced by the bacterium Clostridium botulinum interferes with nerve impulses and causes a paralysis of respiratory and skeletal muscles that can cause death. Researchers from Stanford University have now determined the first structure of a

  2. Substrate Recognition Strategy for Botulinum Neurotoxin

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Substrate Recognition Strategy for Botulinum Neurotoxin Print Clostridal neurotoxins (CNTs) are the causative agents of the neuroparalytic diseases botulism and tetanus. By inhibiting release of the neurotransmitter acetylcholine, for example, the neurotoxin produced by the bacterium Clostridium botulinum interferes with nerve impulses and causes a paralysis of respiratory and skeletal muscles that can cause death. Researchers from Stanford University have now determined the first structure of a

  3. Substrate Recognition Strategy for Botulinum Neurotoxin

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Substrate Recognition Strategy for Botulinum Neurotoxin Print Clostridal neurotoxins (CNTs) are the causative agents of the neuroparalytic diseases botulism and tetanus. By inhibiting release of the neurotransmitter acetylcholine, for example, the neurotoxin produced by the bacterium Clostridium botulinum interferes with nerve impulses and causes a paralysis of respiratory and skeletal muscles that can cause death. Researchers from Stanford University have now determined the first structure of a

  4. Substrate Recognition Strategy for Botulinum Neurotoxin

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Substrate Recognition Strategy for Botulinum Neurotoxin Substrate Recognition Strategy for Botulinum Neurotoxin Print Wednesday, 25 May 2005 00:00 Clostridal neurotoxins (CNTs) are the causative agents of the neuroparalytic diseases botulism and tetanus. By inhibiting release of the neurotransmitter acetylcholine, for example, the neurotoxin produced by the bacterium Clostridium botulinum interferes with nerve impulses and causes a paralysis of respiratory and skeletal muscles that can cause

  5. Substrate Recognition Strategy for Botulinum Neurotoxin

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Substrate Recognition Strategy for Botulinum Neurotoxin Print Clostridal neurotoxins (CNTs) are the causative agents of the neuroparalytic diseases botulism and tetanus. By inhibiting release of the neurotransmitter acetylcholine, for example, the neurotoxin produced by the bacterium Clostridium botulinum interferes with nerve impulses and causes a paralysis of respiratory and skeletal muscles that can cause death. Researchers from Stanford University have now determined the first structure of a

  6. PhyloChip Tackles Coral Disease

    ScienceCinema (OSTI)

    DeSantis, Todd

    2013-05-29

    Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico. More info: http://newscenter.lbl.gov/feature-stories/2009/02/02/coral-reefs/

  7. "Artificial" brains, electrical grids, and disease modeling:...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Deputy Principal Associate Director Duncan McBranch will discuss LDRD impacts on border security and the nation's energy grid at 1 p.m. The event is an ideal opportunity...

  8. PhyloChip Tackles Coral Disease

    SciTech Connect (OSTI)

    DeSantis, Todd

    2009-01-01

    Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico. More info: http://newscenter.lbl.gov/feature-stories/2009/02/02/coral-reefs/

  9. PhyloChip Tackles Coral Disease

    SciTech Connect (OSTI)

    Todd DeSantis

    2009-01-30

    Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico.

  10. PhyloChip Tackles Coral Disease

    ScienceCinema (OSTI)

    Todd DeSantis

    2010-01-08

    Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico.

  11. OCT for diagnosis of periodontal disease

    SciTech Connect (OSTI)

    Colston, B.W., LLNL

    1998-01-01

    We have developed a hand-held in vivo scanning device for use in the oral cavity. We produced, using this scanning device, in vivo OCT images of dental tissues in human volunteers. All the OCT images were analyzed for the presence of clinically relevant anatomical structures. The gingival margin, periodontal sulcus, and dento-enamel junction were visible in all the images. The cemento-enamel junction was discernible in 64% of the images and the alveolar bone presumptively identified for 71% of the images. These images represent, to our knowledge, the first in vivo OCT images of human dental tissue.

  12. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    more prone to form clusters or aggregates, suggesting that strategies for stabilizing SOD proteins could be useful in treating or preventing SOD-linked ALS. The Other ALS...

  13. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins...

  14. Automated diagnostic kiosk for diagnosing diseases (Patent) ...

    Office of Scientific and Technical Information (OSTI)

    contained within a collection vial into the apparatus for automated diagnostic services. ... Save Share this Record Citation Formats MLA APA Chicago Bibtex Export Metadata Endnote ...

  15. Metabolic Prosthesis for Treating Ischemic Diseases - Energy...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    procedures (e.g., laser treatments andor vitrectomy in diabetic retinopathy) Safer than hyperbaric oxygen treatment regimes Reduces the potential for damage following ...

  16. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Amyotrophic lateral sclerosis is notorious for its ability to strike down people in the prime of life. It first leapt into public consciousness when it afflicted baseball star...

  17. Chronic Beryllium Disease Prevention Program What's New

    Broader source: Energy.gov [DOE]

    For additional information Contact: David Weitzman, Office of Worker Safety and Health Policy at (301) 903-5401 or: David.Weitzman@hq.doe.gov.

  18. Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APP{sub swe}/PS1{sub {Delta}E9} transgenic mouse model of Alzheimer's disease

    SciTech Connect (OSTI)

    Tang, Jun; Song, Min; Wang, Yanyan; Fan, Xiaotang; Xu, Haiwei; Bai, Yun

    2009-07-31

    In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APP{sub swe}/PS1{sub {Delta}E9} mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APP{sub swe}/PS1{sub {Delta}E9} transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.

  19. Poster — Thur Eve — 03: Application of the non-negative matrix factorization technique to [{sup 11}C]-DTBZ dynamic PET data for the early detection of Parkinson's disease

    SciTech Connect (OSTI)

    Lee, Dong-Chang; Jans, Hans; McEwan, Sandy; Riauka, Terence; Martin, Wayne; Wieler, Marguerite

    2014-08-15

    In this work, a class of non-negative matrix factorization (NMF) technique known as alternating non-negative least squares, combined with the projected gradient method, is used to analyze twenty-five [{sup 11}C]-DTBZ dynamic PET/CT brain data. For each subject, a two-factor model is assumed and two factors representing the striatum (factor 1) and the non-striatum (factor 2) tissues are extracted using the proposed NMF technique and commercially available factor analysis software “Pixies”. The extracted factor 1 and 2 curves represent the binding site of the radiotracer and describe the uptake and clearance of the radiotracer by soft tissues in the brain, respectively. The proposed NMF technique uses prior information about the dynamic data to obtain sample time-activity curves representing the striatum and the non-striatum tissues. These curves are then used for “warm” starting the optimization. Factor solutions from the two methods are compared graphically and quantitatively. In healthy subjects, radiotracer uptake by factors 1 and 2 are approximately 35–40% and 60–65%, respectively. The solutions are also used to develop a factor-based metric for the detection of early, untreated Parkinson's disease. The metric stratifies healthy subjects from suspected Parkinson's patients (based on the graphical method). The analysis shows that both techniques produce comparable results with similar computational time. The “semi-automatic” approach used by the NMF technique allows clinicians to manually set a starting condition for “warm” starting the optimization in order to facilitate control and efficient interaction with the data.

  20. Volume-Based Parameters of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Improve Disease Recurrence Prediction in Postmastectomy Breast Cancer Patients With 1 to 3 Positive Axillary Lymph Nodes

    SciTech Connect (OSTI)

    Nakajima, Naomi; Kataoka, Masaaki; Sugawara, Yoshifumi; Ochi, Takashi; Kiyoto, Sachiko; Ohsumi, Shozo; Mochizuki, Teruhito

    2013-11-15

    Purpose: To determine whether volume-based parameters on pretreatment {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography in breast cancer patients treated with mastectomy without adjuvant radiation therapy are predictive of recurrence. Methods and Materials: We retrospectively analyzed 93 patients with 1 to 3 positive axillary nodes after surgery, who were studied with {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography for initial staging. We evaluated the relationship between positron emission tomography parameters, including the maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), and clinical outcomes. Results: The median follow-up duration was 45 months. Recurrence was observed in 11 patients. Metabolic tumor volume and TLG were significantly related to tumor size, number of involved nodes, nodal ratio, nuclear grade, estrogen receptor (ER) status, and triple negativity (TN) (all P values were <.05). In receiver operating characteristic curve analysis, MTV and TLG showed better predictive performance than tumor size, ER status, or TN (area under the curve: 0.85, 0.86, 0.79, 0.74, and 0.74, respectively). On multivariate analysis, MTV was an independent prognostic factor of locoregional recurrence-free survival (hazard ratio 34.42, 95% confidence interval 3.94-882.71, P=.0008) and disease-free survival (DFS) (hazard ratio 13.92, 95% confidence interval 2.65-103.78, P=.0018). The 3-year DFS rate was 93.8% for the lower MTV group (<53.1; n=85) and 25.0% for the higher MTV group (?53.1; n=8; P<.0001, logrank test). The 3-year DFS rate for patients with both ER-positive status and MTV <53.1 was 98.2%; and for those with ER-negative status and MTV ?53.1 it was 25.0% (P<.0001). Conclusions: Volume-based parameters improve recurrence prediction in postmastectomy breast cancer patients with 1 to 3 positive nodes. The addition of MTV to ER status or TN has potential

  1. Global Proteome Response to Deletion of Genes Related to Mercury Methylation and Dissimilatory Metal Reduction Reveals Changes in Respiratory Metabolism in Geobacter sulfurreducens PCA

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Qian, Chen; Johs, Alexander; Chen, Hongmei; Mann, Benjamin F.; Lu, Xia; Abraham, Paul E.; Hettich, Robert L.; Gu, Baohua

    2016-07-27

    Geobacter sulfurreducens PCA can reduce, sorb, and methylate mercury (Hg); however, the underlying biochemical mechanisms of these processes and interdependent metabolic pathways remain unknown. In this study, shotgun proteomics was used to compare global proteome profiles between wild-type G. sulfurreducens PCA and two mutant strains: a ΔhgcAB mutant, which is deficient in two genes known to be essential for Hg methylation and a ΔomcBESTZ mutant, which is deficient in five outer membrane c-type cytochromes and thus impaired in its ability for dissimilatory metal ion reduction. We were able to delineate the global response of G. sulfurreducens PCA in both mutantsmore » and identify cellular networks and metabolic pathways that were affected by the loss of these genes. Deletion of hgcAB increased the relative abundances of proteins implicated in extracellular electron transfer, including most of the c-type cytochromes, PilA-C, and OmpB, and is consistent with a previously observed increase in Hg reduction in the hgcAB mutant. Deletion of omcBESTZ was found to significantly increase relative abundances of various methyltransferases, suggesting that a loss of dissimilatory reduction capacity results in elevated activity among one-carbon metabolic pathways and thus increased methylation. We show that G. sulfurreducens PCA encodes only the folate branch of the Wood Ljungdahl pathway, and proteins associated with the folate branch were found at lower abundance in the ΔhgcAB mutant strain than the wild type. In conclusion, this observation supports the hypothesis that the function of HgcA and HgcB may be linked to one carbon metabolism through the folate branch of the Wood-Ljungdahl pathway by providing methyl groups required for Hg methylation.« less

  2. A study of mortality in workers engaged in the mining, smelting, and refining of nickel. II. Mortality from cancer of the respiratory tract and kidney

    SciTech Connect (OSTI)

    Roberts, R.S.; Julian, J.A.; Muir, D.C.; Shannon, H.S. )

    1989-12-01

    This paper describes observed and expected mortality from cancers of the lung, larynx, nose, and kidney in a cohort of 54,509 nickel workers followed for 35 years. For analysis purposes the cohort was subdivided into men with and without service in one of the three high nickel dust areas of the operation: the Sinter Plants at Copper Cliff and Coniston, and the Leaching, Calcining and Sintering (LC S) department at Port Colborne. At Copper Cliff Sinter Plant workers experienced three times the expected number of lung cancer deaths; the SMR rose steeply with increasing duration of service peaking at 943 with 10 to 15 years. A similar overall excess risk of lung cancer was seen in the smaller Coniston Sinter Plant again with an indication of an exposure risk gradient. Men in the LC S department at Port Colborne also experienced a dose related excess risk of lung cancer death that rose to an SMR of 806 with 20 to 25 years of service. Nasal cancer deaths were increased at both the Copper Cliff Sinter Plant (6 deaths) and the LC S department at Port Colborne (19 deaths), representing SMRs of 3,704 and 7,755, respectively, for this rare cancer. Laryngeal cancer and kidney cancer, both previously associated with nickel, were not in excess in these high risk groups. A further exploration of death from these causes in the lower exposure remainder of the cohort revealed an epidemiologically modest elevation in lung cancer death in miners (probably not nickel related) and parts of the Copper Refinery. No evidence of laryngeal cancer excess was found.

  3. Viscoelastic Model for Lung Parenchyma for Multi-Scale Modeling of Respiratory System Phase I: Hypo-Elastic Model for CFD Implementation

    SciTech Connect (OSTI)

    Freed, Alan D.; Einstein, Daniel R.

    2011-04-14

    An isotropic constitutive model for the parenchyma of lung has been derived from the theory of hypo-elasticity. The intent is to use it to represent the mechanical response of this soft tissue in sophisticated, computational, fluid-dynamic models of the lung. This demands that the continuum model be accurate, yet simple and effcient. An objective algorithm for its numeric integration is provided. The response of the model is determined for several boundary-value problems whose experiments are used for material characterization. The effective elastic, bulk, and shear moduli, and Poissons ratio, as tangent functions, are also derived. The model is characterized against published experimental data for lung. A bridge between this continuum model and a dodecahedral model of alveolar geometry is investigated, with preliminary findings being reported.

  4. Respiratory effects of two-hour exposure with intermittent exercise to ozone, sulfur dioxide and nitrogen dioxide alone and in combination in normal subjects

    SciTech Connect (OSTI)

    Kagawa, J.

    1983-01-01

    Seven adult male healthy volunteer subjects were exposed to 0.15 ppm each of O/sub 3/, SO/sub 2/ and NO/sub 2/ alone and in combination, with intermittent light exercise for two hours. Three of the 7 subjects developed cough during deep inspiration and one subject had chest pain during exposure to O/sub 3/ alone. Among the various indices of pulmonary function tests, specific airway conductane (G/sub aw//V/sub tg/) was the most sensitive index to examine the changes produced by the exposure to O/sub 3/ and other pollutants. Significant decrease of G/sub aw//V/sub tg/ in comparison with control measurements was observed in 6 of 7 subjects during exposure to O/sub 3/ alone, and in all subjects during exposures to the mixture of O/sub 3/ and other pollutants. However, no significant enhancement of effect was observed in the mixture of O/sub 3/ and other pollutants, although a slightly greater decrease of airway resistance/volume of thoracic gas (G/sub aw//V/sub tg/) was observed for the mixture of O/sub 3/ and other pollutants than for O/sub 3/ alone.

  5. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    medical implants comes from nanostructuring April 3, 2012 Quality of treatment for those with medical implants improves as science and medicine unite once more Metals have provided the strength, durability, and other characteristics that have been needed in bone implants since the inception of orthopedics. However, cobalt-chromium superalloys, stainless steels, and titanium alloys-the most commonly used materials in today's orthopedic devices- have the potential to present serious side effects.

  6. Secure Healthcare Internet Employee Learning Drill

    Energy Science and Technology Software Center (OSTI)

    2005-08-01

    SHIELD solves the problem of rapidly training large numbers of healthcare or other facility personnel who work around the clock - especially the non-professional semi-skilled employees who usually have "first contact" with patients and visitors - about how to limit or prevent exposure of facilities to infectious illness or other disease threats. This tool provides a very brief, realistic training experience that shows a range of facility personnel how to identify and respond to possiblemore » acute infectious respiratory illness outbreaks.« less

  7. ALSNews Vol. 342

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 Print New Staff Photo On May 14, ALS staff gathered in front of the iconic dome to take a new group photo. The new picture is featured in a photo exhibit showcasing ALS people and events over the last 20 years. See the full-sized version and download a copy here. One Vaccine Leads to Another Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines have been extremely effective; studies on one vaccine in

  8. ALSNews Vol. 342

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 ALSNews Vol. 342 Print Tuesday, 28 May 2013 14:11 New Staff Photo On May 14, ALS staff gathered in front of the iconic dome to take a new group photo. The new picture is featured in a photo exhibit showcasing ALS people and events over the last 20 years. See the full-sized version and download a copy here. One Vaccine Leads to Another Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines have been

  9. ALSNews Vol. 342

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 Print New Staff Photo On May 14, ALS staff gathered in front of the iconic dome to take a new group photo. The new picture is featured in a photo exhibit showcasing ALS people and events over the last 20 years. See the full-sized version and download a copy here. One Vaccine Leads to Another Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines have been extremely effective; studies on one vaccine in

  10. ALSNews Vol. 342

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 Print New Staff Photo On May 14, ALS staff gathered in front of the iconic dome to take a new group photo. The new picture is featured in a photo exhibit showcasing ALS people and events over the last 20 years. See the full-sized version and download a copy here. One Vaccine Leads to Another Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines have been extremely effective; studies on one vaccine in

  11. ALSNews Vol. 342

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 Print New Staff Photo On May 14, ALS staff gathered in front of the iconic dome to take a new group photo. The new picture is featured in a photo exhibit showcasing ALS people and events over the last 20 years. See the full-sized version and download a copy here. One Vaccine Leads to Another Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines have been extremely effective; studies on one vaccine in

  12. ALSNews Vol. 342

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 Print New Staff Photo On May 14, ALS staff gathered in front of the iconic dome to take a new group photo. The new picture is featured in a photo exhibit showcasing ALS people and events over the last 20 years. See the full-sized version and download a copy here. One Vaccine Leads to Another Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines have been extremely effective; studies on one vaccine in

  13. ALSNews Vol. 342

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALSNews Vol. 342 Print New Staff Photo On May 14, ALS staff gathered in front of the iconic dome to take a new group photo. The new picture is featured in a photo exhibit showcasing ALS people and events over the last 20 years. See the full-sized version and download a copy here. One Vaccine Leads to Another Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines have been extremely effective; studies on one

  14. ALSNews Vol. 342

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALSNews Vol. 342 Print New Staff Photo On May 14, ALS staff gathered in front of the iconic dome to take a new group photo. The new picture is featured in a photo exhibit showcasing ALS people and events over the last 20 years. See the full-sized version and download a copy here. One Vaccine Leads to Another Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines have been extremely effective; studies on one

  15. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to ... porcine response to porcine reproductive and respiratory syndrome virus (PRRSV) infection. ...

  16. Search for: microbes OR Microbiomes | DOE PAGES

    Office of Scientific and Technical Information (OSTI)

    ... reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 ... reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 ...

  17. Microbiome associations in pigs with the best and worst clinical...

    Office of Scientific and Technical Information (OSTI)

    reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 ... reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 ...

  18. Inhalation Toxicology Research Institute. Annual report, October 1, 1995--September 30, 1996

    SciTech Connect (OSTI)

    Bice, D.E.; Hahn, F.F.; Henderson, R.F.

    1996-12-01

    The Inhalation Toxicology Research Institute (ITRI) is a Government-owned facility leased and operated by the Lovelace Biomedical and Environmental Research Institute (LBERI) as a private, nonprofit research and testing laboratory. LBERI is an operating subsidiary of the Lovelace Respiratory Research Institute. Through September 30, 1996, ITRI was a Federally Funded Research and Development Center operated by Lovelace for the US Department of Energy (DOE) as a {open_quotes}Single Program Laboratory{close_quotes} within the DOE Office of Health and Environmental Research, Office of Energy Research. Work for DOE continues in the privatized ITRI facility under a Cooperative Agreement. At the time of publication, approximately 70% of the Institute`s research is funded by DOE, and the remainder is funded by a variety of Federal agency, trade association, individual industry, and university customers. The principal mission of ITRI is to conduct basic and applied research to improve our understanding of the nature and magnitude of the human health impacts of inhaling airborne materials in the home, workplace, and general environment. Institute research programs have a strong basic science orientation with emphasis on the nature and behavior of airborne materials, the fundamental biology of the respiratory tract, the fate of inhaled materials and the mechanisms by which they cause disease, and the means by which data produced in the laboratory can be used to estimate risks to human health. Disorders of the respiratory tract continue to be a major health concern, and inhaled toxicants are thought to contribute substantially to respiratory morbidity. As the country`s largest facility dedicated to the study of basic inhalation toxicology, ITRI provides a national resource of specialized facilities, personnel, and educational activities serving the needs of government, academia, and industry.

  19. Cross-sectional health study in polluted and nonpolluted agricultural settlements in Israel

    SciTech Connect (OSTI)

    Goren, A.I.; Brenner, S.; Hellmann, S.

    1988-08-01

    During the summer of 1984 a health survey was carried out among the population of six rural settlements, three in a polluted and three in a low polluted area. Residents of these settlements between 6 and 65 years of age filled out an ATS-NHLI health questionnaire and performed the following pulmonary function tests (PFT): FVC, FEV/sub 1/, FEV/sub 1//FVC, PEF, FEF/sub 50/, and FEF/sub 75/. A trend of higher prevalence of reported respiratory symptoms and diseases characterizes children growing up in a polluted rural as compared with a low polluted rural area. The relative risks (calculated from logistic models) for children from the polluted area to have sputum with cold is 2.13, cough accompanied by sputum 3.89, and for their siblings to have respiratory diseases 3.02, as compared with 1.00 in the low polluted area. A trend of lower PFT characterizes children from the polluted area, with significantly reduced PEF. The trends for adults in the two areas were similar to those for the children. The relative risks for adults from the polluted area to have sputum is 1.7 and cough accompanied by sputum 2.6, as compared with 1.0 in the low polluted area. PEF is significantly lower among adults from the polluted area, while FEF/sub 50/ and FEF/sub 75/ are lower (not significantly) among adults from the low polluted area.

  20. Relationship Between Composition and Toxicity of Engine Emissions

    Broader source: Energy.gov [DOE]

    2004 Diesel Engine Emissions Reduction (DEER) Conference Presentation: Lovelace Respiratory Research Instiitute

  1. Assessment of Health Hazards of Repeated Inhalation of Diesel Emissions, with Comparisons to Other Source Emissions

    Broader source: Energy.gov [DOE]

    2004 Diesel Engine Emissions Reduction (DEER) Conference Presentation: National Environmental Respiratory Center

  2. Preliminary Notice of Violation, Fluor Fernald, Inc.- EA-2004-07

    Broader source: Energy.gov [DOE]

    Issued to Fluor Fernald, Inc., related to Respiratory Protection Issues at the Fernald Environmental Management Project

  3. A New Approach to a Lyme Disease Vaccine

    SciTech Connect (OSTI)

    Livey, I.; Dunn, J.; O'Rourke, M.; Traweger, A.; Savidis-Dacho, H.; Crowe, B. A.; Barrett, P. N.; Yang, X.; Luft, B. J.

    2011-02-01

    A single recombinant outer surface protein A (OspA) antigen designed to contain protective elements from 2 different OspA serotypes (1 and 2) is able to induce antibody responses that protect mice against infection with either Borrelia burgdorferi sensu stricto (OspA serotype-1) or Borrelia afzelii (OspA serotype-2). Protection against infection with B burgdorferi ss strain ZS7 was demonstrated in a needle-challenge model. Protection against B. afzelii species was shown in a tick-challenge model using feral ticks. In both models, as little as .03 {micro}g of antigen, when administered in a 2-dose immunization schedule with aluminum hydroxide as adjuvant, was sufficient to provide complete protection against the species targeted. This proof of principle study proves that knowledge of protective epitopes can be used for the rational design of effective, genetically modified vaccines requiring fewer OspA antigens and suggests that this approach may facilitate the development of an OspA vaccine for global use.

  4. Title 10 CFR Part 850, Chronic Beryllium Disease Prevention Program

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... Any radiological implications of the two radioisotopic forms of beryllium would be addressed under the provisions of 10 CFR part 835, Occupational Radiation Protection. III. ...

  5. Low density lipoprotein fraction assay for cardiac disease risk

    DOE Patents [OSTI]

    Krauss, Ronald M.; Blanche, Patricia J.; Orr, Joseph

    1999-01-01

    A variable rate density gradient electrophoric gel is described which separate LDL subfractions with the precision of ultracentrifugation techniques. Also, an innovative bottom inlet mixing chamber particularly useful for producing these gels is described.

  6. A State-Wide Research Network for Alzheimer's Disease

    SciTech Connect (OSTI)

    Mintzer, Jacobo E.; Bachman, D. L.; Stuckey, M.; Ebeling, M.; Wagner, M. T.; Evans, W. J.; Hirth, V.; Walker, A.; Joglekar, R.; Faison, W.

    2014-03-13

    The Specific Aim of the proposal was to develop an administrative structure that will facilitate the development of AD research across the state of SC by providing key services such as (but not limited to) seeking funding research opportunities, financial tracking, regulatory management, central recruitment, training for investigators and coordinators, data collection, data storing, and data processing to researchers across the state.

  7. Statistical Mechanics of Prion Diseases (Journal Article) | SciTech...

    Office of Scientific and Technical Information (OSTI)

    Publication Date: 2001-07-30 OSTI Identifier: 40277303 Resource Type: Journal Article Resource Relation: Journal Name: Physical Review Letters; Journal Volume: 87; Journal Issue: ...

  8. Methods of treating Parkinson's disease using viral vectors

    DOE Patents [OSTI]

    Bankiewicz, Krys; Cunningham, Janet

    2012-11-13

    Methods of delivering viral vectors, particularly recombinant AAV virions, to the central nervous system (CNS) are provided for the treatment of CNS disorders, particularly those disorders which involve the neurotransmitter dopamine. The methods entail providing rAAV virions that comprise a transgene encoding aromatic amino acid decarboxylase (AADC) and administering the virions to the brain of a mammal using a non-manual pump.

  9. Low density lipoprotein fraction assay for cardiac disease risk

    DOE Patents [OSTI]

    Krauss, R.M.; Blanche, P.J.; Orr, J.

    1999-07-20

    A variable rate density gradient electrophoric gel is described which separates LDL subfractions with the precision of ultracentrifugation techniques. Also, an innovative bottom inlet mixing chamber particularly useful for producing these gels is described. 8 figs.

  10. A State-Wide Research Network for Alzheimer's Disease (Technical...

    Office of Scientific and Technical Information (OSTI)

    Contributing Orgs: MUSC & Ralph H. Johnson VAMC, Charleston, SC Senior Primary Care, Columbia, SC Comprehensive Neurological Services, Florence, SC Hospital Medicine Consultants, ...

  11. disease outbreak. Brozik, Susan Marie; Manginell, Ronald Paul...

    Office of Scientific and Technical Information (OSTI)

    developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were...

  12. Diseases of the kidney. Fourth edition. Volume 1

    SciTech Connect (OSTI)

    Schrier, R.W.; Gottschalk, C.W.

    1988-01-01

    This book contains over 100 chapters. Some of the chapter titles are: Intravenous Urography, Ultrasonography, and Radionuclide Studies; Computed Tomography and Magnetic Resonance Imaging; Diagnostic and Therapeutic Imaging of the Renal Circulation: Film-Screen Arteriography, Digital Subtraction Angiography, and Percutaneous Angioplasty and Embolization; Alport Syndrome; and Medullary Sponge Kidney.

  13. Bush Administration to Expand Beryllium Disease Screening Program...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    harmful, but small particles of beryllium-containing materials produced as by-products of machining or other processes can spread through the air and be breathed into the lungs. ...

  14. ORISE Research Participation Programs at the Centers for Disease...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dr. Feng Liu Research Profile - Dr. Feng Liu Dr. Feng Liu performed research on influenza vaccines with the Pandemic Preparedness Team in the National Center for Immunization...

  15. Title 10 CFR Part 850, Chronic Beryllium Disease Prevention Program

    Office of Environmental Management (EM)

    Department of Energy Thousands of Students Prepare to Compete in the National Science Bowl Thousands of Students Prepare to Compete in the National Science Bowl January 29, 2013 - 5:00pm Addthis Members of the Los Alamos High School team, Los Alamos, New Mexico, concentrates on the answer to a question at the 2012 National Science Bowl in Washington D.C. on April 29, 2012. | Photograph by Dennis Brack, Office of Science Members of the Los Alamos High School team, Los Alamos, New Mexico,

  16. HOPM1 mediated disease resistance to Pseudomonas syringae in Arabidopsis

    DOE Patents [OSTI]

    He, Sheng Yang; Nomura, Kinya

    2011-11-15

    The present invention relates to compositions and methods for enhancing plant defenses against pathogens. More particularly, the invention relates to enhancing plant immunity against bacterial pathogens, wherein HopM1.sub.1-300 mediated protection is enhanced, such as increased protection to Pseudomonas syringae pv. tomato DC3000 HopM1 and/or there is an increase in activity of an ATMIN associated plant protection protein, such as ATMIN7. Reagents of the present invention further provide a means of studying cellular trafficking while formulations of the present inventions provide increased pathogen resistance in plants.

  17. Update on the Hanford Site Chronic Beryllium Disease Prevention...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Training and Implementation Medical Clearance and Restriction Language- Communication ... as follows: *Medical Referrals *Medical Clearance & Restriction *Beryllium Work Permit ...

  18. Platform for Pre-Symptomatic Detection of Citrus Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... non-exclusive right to practice any LANS-owned patents andor copyrighted software. ... Preferred Partner Attributes Demonstrated knowledge of product marketing, sales, and ...

  19. Platform for Pre-Symptomatic Detection of Citrus Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    non-exclusive right to practice any LANS-owned patents andor copyrighted software. ... Preferred Partner Attributes * Demonstrated knowledge of product marketing, sales, and ...

  20. Collaborative Initiative in Biomedical Imaging to Study Complex Diseases

    SciTech Connect (OSTI)

    Lin, Weili; Fiddy, Michael A.

    2012-03-31

    The work reported addressed these topics: Fluorescence imaging; Optical coherence tomography; X-ray interferometer/phase imaging system; Quantitative imaging from scattered fields, Terahertz imaging and spectroscopy; and Multiphoton and Raman microscopy.

  1. Hanford Site Chronic Beryllium Disease Prevention Program (CBDPP...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    (406) 544-4502 Cowley, Dana Phillips MD, Karen 372-0015 376-4716 (509) 961-5609 NA MSA... Cell Number WHL (WAI Hanford Laboratory) Leonard, Bill 373-1820 554-7522 Temple, Ley ...

  2. Proteins' Amazing Origami Powers: Insight for Potential Disease...

    Broader source: Energy.gov (indexed) [DOE]

    that instead of creating a crane or a cat, you actually produce a working machine. ... be critical in determining the final form (whether a bat or a hat or a crane or a cat). ...

  3. Diagnosis and assessment of skeletal related disease using calcium 41

    DOE Patents [OSTI]

    Hillegonds, Darren J.; Vogel, John S.; Fitzgerald, Robert L.; Deftos, Leonard J.; Herold, David; Burton, Douglas W.

    2013-03-05

    A method of determining calcium metabolism in a patient comprises the steps of administering radioactive calcium isotope .sup.41Ca to the patient, allowing a period of time to elapse sufficient for dissemination and reaction of the radioactive calcium isotope .sup.41Ca by the patient, obtaining a sample of the radioactive calcium isotope .sup.41Ca from the patient, isolating the calcium content of the sample in a form suitable for precise measurement of isotopic calcium concentrations, and measuring the calcium content to determine parameters of calcium metabolism in the patient.

  4. Diagnosis and assessment of skeletal related disease using calcium 41

    DOE Patents [OSTI]

    Hillegonds, Darren J.; Vogel, John S.; Fitzgerald, Robert L.; Deftos, Leonard J.; Herold, David; Burton, Douglas W.

    2012-05-15

    A method of determining calcium metabolism in a patient comprises the steps of administering radioactive calcium isotope .sup.41Ca to the patient, allowing a period of time to elapse sufficient for dissemination and reaction of the radioactive calcium isotope .sup.41Ca by the patient, obtaining a sample of the radioactive calcium isotope .sup.41Ca from the patient, isolating the calcium content of the sample in a form suitable for precise measurement of isotopic calcium concentrations, and measuring the calcium content to determine parameters of calcium metabolism in the patient.

  5. Software speeds detection of diseases and cancer-treatment targets

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Software Tools Software Tools AMO's tools help manufacturers increase industrial energy efficiency at the plant-level and in specific systems. Learn step-by-step ways to identify opportunities, monitor progress, and improve efficiency in any facility. Some tools help facilities implement an energy management system and prepare to become ISO 50001 and Superior Energy Performance certified. Managing Your Plant's Energy Use The following tools help manufacturers track energy, identify areas of

  6. Counting small RNA in disease-causing organisms

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Counterterrorism A snapshot of NNSA's counterterrorism mission NNSA's mission of counterterrorism and counterproliferation is supported through innovative science and technology. Recently, Associate Administrator and Deputy Undersecretary for Counterterrorism and Counterproliferation Jay Tilden visited Oak Ridge National Laboratory (ORNL) and met with... Tilden appointed as Associate Administrator of Counterterrorism and Counterproliferation We are delighted to announce two key personnel

  7. Network Science: From the Web to Human Diseases

    SciTech Connect (OSTI)

    Barabasi, Albert-Laszlo

    2008-06-09

    Systems as diverse as the world wide web, Internet or the cell are described by highly interconnected networks with amazingly complex topology. Recent studies indicate that the evolution of these complex networks is governed by simple but generic laws, resulting in apparently universal architectural features. I will discuss this amazing order characterizing our interconnected work, and its implications to how we perceive the impact on communications and medicine, as well as touch upon the next challenge of network research, going beyond the structure and quantifying the dynamics of interconnected systems.

  8. Health effects of global warming: Problems in assessment

    SciTech Connect (OSTI)

    Longstreth, J.

    1993-06-01

    Global warming is likely to result in a variety of environmental effects ranging from impacts on species diversity, changes in population size in flora and fauna, increases in sea level and possible impacts on the primary productivity of the sea. Potential impacts on human health and welfare have included possible increases in heat related mortality, changes in the distribution of disease vectors, and possible impacts on respiratory diseases including hayfever and asthma. Most of the focus thus far is on effects which are directly related to increases in temperature, e.g., heat stress or perhaps one step removed, e.g., changes in vector distribution. Some of the more severe impacts are likely to be much less direct, e.g., increases in migration due to agricultural failure following prolonged droughts. This paper discusses two possible approaches to the study of these less-direct impacts of global warming and presents information from on-going research using each of these approaches.

  9. Carbohydrate biofuels II: The need and the potential for rootfuel in the Navajo Nation

    SciTech Connect (OSTI)

    Shultz, E.B.; Jr.; Bragg, W.G.; Whittier, J.

    1995-11-01

    Over 80% of rural Navajos and about two-thirds of all Navajos use scarce woodfuel and low-grade coal for home heating half the year, with coal used mainly as a nighttime adjunct. Serious health problems arise because stoves are old and leak smoke and carbon monoxide. The impacts are gender-biased to women and small children. Respiratory disease is a major cause of Navajo mortality and unusually high admissions to Navajo Indian Health Service hospitals. A 1990 study at a Navajo hospital showed that Navajo children under two years of age from homes with woodstoves are nearly five times more likely to contract acute lower respiratory tract infections than children from homes with no stove. Correctives include improved stoves and fuels. Our previous studies on clean-burning starchy/cellulosic {open_quotes}rootfuels{close_quotes} in Latin America, Africa, and Asia are applicable. We discuss our preliminary work on the Navajo reservation, the current status of household stoves and stovefuels, the health impacts of woodsmoke and coalsmoke from old, faulty stoves, the conditions for growing rootfuel on the reservation, and policy and strategy for coping with the problem.

  10. Radiation-induced lung injury

    SciTech Connect (OSTI)

    Rosiello, R.A.; Merrill, W.W. )

    1990-03-01

    The use of radiation therapy is limited by the occurrence of the potentially fatal clinical syndromes of radiation pneumonitis and fibrosis. Radiation pneumonitis usually becomes clinically apparent from 2 to 6 months after completion of radiation therapy. It is characterized by fever, cough, dyspnea, and alveolar infiltrates on chest roentgenogram and may be difficult to differentiate from infection or recurrent malignancy. The pathogenesis is uncertain, but appears to involve both direct lung tissue toxicity and an inflammatory response. The syndrome may resolve spontaneously or may progress to respiratory failure. Corticosteroids may be effective therapy if started early in the course of the disease. The time course for the development of radiation fibrosis is later than that for radiation pneumonitis. It is usually present by 1 year following irradiation, but may not become clinically apparent until 2 years after radiation therapy. It is characterized by the insidious onset of dyspnea on exertion. It most often is mild, but can progress to chronic respiratory failure. There is no known successful treatment for this condition. 51 references.

  11. Surveillance study of health effects associated with cleanup of a hazardous waste site, Ralph Gray Trucking Company (a/k/a Westminster Tract Number 2633), Westminster, Orange County, California, Region 9: CERCLIS number CAD981995947

    SciTech Connect (OSTI)

    Hoshiko, S.; Underwood, M.C.; Smith, D.; DeLorenze, G.; Neuhaus, J.

    1999-04-01

    Excavation of a Superfund site, the Ralph Gray Truncking Company located in Westminster Orange County, California was anticipated to release sulfur dioxide and other chemicals. The California Department of Health Services, under cooperative agreement with the Agency for Toxic Substances and Disease Registry, conducted a surveillance study to assess whether illnesses were associated with cleanup activities. A panel primarily composed of more sensitive persons (n = 36) was selected to report daily respiratory symptoms and odors. Exposures included sulfur dioxide (SO{sub 2}) measurements and daily tonnage of waste removed. Analysis used Conditional Likelihood Regression and Generalized Estimating Equations (GEE) methods. Levels of SO{sub 2} were generally higher than usual ambient air, at times exceeding levels which can cause health effects among asthmatics in laboratory settings. Wheeze and cough were significantly associated with tonnage of waste removed, especially on days when the highest amounts of waste were removed. Upper respiratory symptoms were found to be associated with SO{sub 2}, and weak relationships were found with nausea and burning nose and SO{sub 2}.

  12. Evaluation of candidate vaccine approaches for MERS-CoV

    SciTech Connect (OSTI)

    Wang, Lingshu; Shi, Wei; Joyce, M. Gordon; Modjarrad, Kayvon; Zhang, Yi; Leung, Kwanyee; Lees, Christopher R.; Zhou, Tongqing; Yassine, Hadi M.; Kanekiyo, Masaru; Yang, Zhi-yong; Chen, Xuejun; Becker, Michelle M.; Freeman, Megan; Vogel, Leatrice; Johnson, Joshua C.; Olinger, Gene; Todd, John P.; Bagci, Ulas; Solomon, Jeffrey; Mollura, Daniel J.; Hensley, Lisa; Jahrling, Peter; Denison, Mark R.; Rao, Srinivas S.; Subbarao, Kanta; Kwong, Peter D.; Mascola, John R.; Kong, Wing-Pui; Graham, Barney S.

    2015-07-28

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.

  13. Evaluation of candidate vaccine approaches for MERS-CoV

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wang, Lingshu; Shi, Wei; Joyce, M. Gordon; Modjarrad, Kayvon; Zhang, Yi; Leung, Kwanyee; Lees, Christopher R.; Zhou, Tongqing; Yassine, Hadi M.; Kanekiyo, Masaru; et al

    2015-07-28

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanismsmore » were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.« less

  14. Case study of a solid-waste-scavenger community with respect to health and environment

    SciTech Connect (OSTI)

    Kungskulniti, Nipapun.

    1991-01-01

    This study was an investigation of a solid waste scavenger community at the On-Nooch Dump Site in Bangkok, Thailand. The purpose was to identify the dimensions of the public health conditions of solid waste scavengers and their community. Cross-sectional field surveys and measurements were undertaken to characterize the distribution and magnitude of health-related problems and environmental conditions. Scavengers were found to be exposed to hazardous conditions due to the waste materials at the dump site. Cuts and punctures from sharp materials were the most common complaints among scavengers. Health symptoms like headache, diarrhea, respiratory illness, skin diseases and back pain were also reported. There was a high prevalence of childhood respiratory illness especially among those children of households where cigarette smoking was present. Children had poor nutritional status and were commonly infected by intestinal protozoa and helminths. An appreciable proportion of adult respondents was below the normal range for lung function performance. Seroprevalence of HBV infection was found to be high among male respondents in addition to six respondents that had possible HIV infections. The quality of the community water supply was low. Air pollution measurements showed acceptable ambient air levels except for particulate levels (TSP and RSP). Levels of indoor, outdoor, and personal exposure NO{sub 2} were found to be similar. Data for an inner-city project apartment community named Din-Dang were also collected for comparison. A priority rating index and recommendations for public health condition improvements were presented.

  15. Geology of coal fires: case studies from around the world

    SciTech Connect (OSTI)

    Glenn B. Stracher

    2008-01-15

    Coal fires are preserved globally in the rock record as burnt and volume-reduced coal seams and by pyrometamorphic rocks, explosion breccias, clinker, gas-vent-mineral assemblages, fire-induced faulting, ground fissures, slump blocks, and sinkholes. Coal fires are responsible for coronary and respiratory diseases and fatalities in humans, as well as arsenic and fluorine poisoning. Their heat energy, toxic fumes, and solid by-products of combustion destroy floral and faunal habitats while polluting the air, water, and soil. This volume includes chapters devoted to spontaneous combustion and greenhouse gases, gas-vent mineralogy and petrology, paralavas and combustion metamorphic rocks, geochronology and landforms, magnetic signatures and geophysical modeling, remote-sensing detection and fire-depth estimation of concealed fires, and coal fires and public policy.

  16. Waste collection in developing countries - Tackling occupational safety and health hazards at their source

    SciTech Connect (OSTI)

    Bleck, Daniela; Wettberg, Wieland

    2012-11-15

    Waste management procedures in developing countries are associated with occupational safety and health risks. Gastro-intestinal infections, respiratory and skin diseases as well as muscular-skeletal problems and cutting injuries are commonly found among waste workers around the globe. In order to find efficient, sustainable solutions to reduce occupational risks of waste workers, a methodological risk assessment has to be performed and counteractive measures have to be developed according to an internationally acknowledged hierarchy. From a case study in Addis Ababa, Ethiopia suggestions for the transferral of collected household waste into roadside containers are given. With construction of ramps to dump collected household waste straight into roadside containers and an adaptation of pushcarts and collection procedures, the risk is tackled at the source.

  17. Review of health and productivity gains from better IEQ

    SciTech Connect (OSTI)

    Fisk, William J.

    2000-08-01

    The available scientific data suggest that existing technologies and procedures can improve indoor environmental quality (IEQ) in a manner that significantly increases productivity and health. While there is considerable uncertainty in the estimates of the magnitudes of productivity gains that may be obtained, the projected gains are very large. For the U.S., the estimated potential annual savings and productivity gains are $6 to $14 billion from reduced respiratory disease, $2 to $4 billion from reduced allergies and asthma, $10 to $30 billion from reduced sick building syndrome symptoms, and $20 to $160 billion from direct improvements in worker performance that are unrelated to health. Productivity gains that are quantified and demonstrated could serve as a strong stimulus for energy efficiency measures that simultaneously improve the indoor environment.

  18. Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein

    SciTech Connect (OSTI)

    McBride, Corrin E.; Machamer, Carolyn E.

    2010-09-15

    Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell-cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein and may point to important differences in assembly and infectivity of these two coronaviruses.

  19. Economic benefits of an economizer system: Energy savings and reduced sick leave

    SciTech Connect (OSTI)

    Fisk, William J.; Seppanen, Olli; Faulkner, David; Huang, Joe

    2004-02-01

    This study estimated the health, energy, and economic benefits of an economizer ventilation control system that increases outside air supply during mild weather to save energy. A model of the influence of ventilation rate on airborne transmission of respiratory illnesses was used to extend the limited data relating ventilation rate with illness and sick leave. An energy simulation model calculated ventilation rates and energy use versus time for an office building in Washington, D.C. with fixed minimum outdoor air supply rates, with and without an economizer. Sick leave rates were estimated with the disease transmission model. In the modeled 72-person office building, our analyses indicate that the economizer reduces energy costs by approximately $2000 and, in addition, reduces sick leave. The annual financial benefit of the decrease in sick leave is estimated to be between $6,000 and $16,000. This modeling suggests that economizers are much more cost effective than currently recognized.

  20. Economizer system cost effectiveness: Accounting for the influence of ventilation rate on sick leave

    SciTech Connect (OSTI)

    Fisk, William J.; Seppanen, Olli; Faulkner, David; Huang, Joe

    2003-06-01

    This study estimated the health, energy, and economic benefits of an economizer ventilation control system that increases outside air supply during mild weather to save energy. A model of the influence of ventilation rate on airborne transmission of respiratory illnesses was used to extend the limited data relating ventilation rate with illness and sick leave. An energy simulation model calculated ventilation rates and energy use versus time for an office building in Washington, DC with fixed minimum outdoor air supply rates, with and without an economizer. Sick leave rates were estimated with the disease transmission model. In the modeled 72-person office building, our analyses indicate that the economizer reduces energy costs by approximately $2000 and, in addition, reduces sick leave. The financial benefit of the decrease in sick leave is estimated to be between $6,000 and $16,000. This modelling suggests that economizers are much more cost effective than currently recognized.

  1. Defense programs beryllium good practice guide

    SciTech Connect (OSTI)

    Herr, M.

    1997-07-01

    Within the DOE, it has recently become apparent that some contractor employees who have worked (or are currently working) with and around beryllium have developed chronic beryllium disease (CBD), an occupational granulomatous lung disorder. Respiratory exposure to aerosolized beryllium, in susceptible individuals, causes an immunological reaction that can result in granulomatous scarring of the lung parenchyma, shortness of breath, cough, fatigue, weight loss, and, ultimately, respiratory failure. Beryllium disease was originally identified in the 1940s, largely in the fluorescent light industry. In 1950, the Atomic Energy Commission (AEC) introduced strict exposure standards that generally curtailed both the acute and chronic forms of the disease. Beginning in 1984, with the identification of a CBD case in a DOE contractor worker, there was increased scrutiny of both industrial hygiene practices and individuals in this workforce. To date, over 100 additional cases of beryllium-specific sensitization and/or CBD have been identified. Thus, a disease previously thought to be largely eliminated by the adoption of permissible exposure standards 45 years ago is still a health risk in certain workforces. This good practice guide forms the basis of an acceptable program for controlling workplace exposure to beryllium. It provides (1) Guidance for minimizing worker exposure to beryllium in Defense Programs facilities during all phases of beryllium-related work, including the decontamination and decommissioning (D&D) of facilities. (2) Recommended controls to be applied to the handling of metallic beryllium and beryllium alloys, beryllium oxide, and other beryllium compounds. (3) Recommendations for medical monitoring and surveillance of workers exposed (or potentially exposed) to beryllium, based on the best current understanding of beryllium disease and medical diagnostic tests available. (4) Site-specific safety procedures for all processes of beryllium that is likely to

  2. 2010 GORDON RESEARCH CONFERENCE ON MITOCHONDRIA & CHLOROPLASTS, LUCCA, ITALY, JULY 11-16, 2010

    SciTech Connect (OSTI)

    Alice Barkan

    2010-07-16

    The 2010 GRC on Mitochondria & Chloroplasts will assemble an international group of molecular, structural and cellular biologists, biochemists and geneticists investigating a broad spectrum of fundamental problems related to the biology of these organelles in animal, plant and fungal cells. This field has witnessed an extraordinary expansion in recent years, fueled by the discovery of the role of mitochondria in human disease and ageing, and of the synergy of chloroplasts and mitochondria in energetic output, the identification of novel factors involved in organelle division, movement, signaling and acclimation to changing environmental conditions, and by the powerful tools of organelle proteomics. The 2010 GRC will highlight advances in the elucidation of molecular mechanisms of organelle biogenesis including regulation of genome structure, evolution and expression, organellar protein import, assembly and turnover of respiratory and photosynthetic complexes, bidirectional signaling between organelles and nucleus, organelle morphology and dynamics, and the integration of cellular metabolism. We will also explore progress in mechanisms of disease and ageing/ senescence in animals and plants. The organellar field has forged new fronts toward a global and comprehensive understanding of mitochondrial and chloroplast biology at the molecular level. Many of the molecules under study in model organisms are responsible for human diseases, providing significant impetus for a meeting that encourages interactions between mammalian, fungal and plant organellar biologists.

  3. Aluminium induced oxidative stress results in decreased mitochondrial biogenesis via modulation of PGC-1? expression

    SciTech Connect (OSTI)

    Sharma, Deep Raj; Sunkaria, Aditya; Wani, Willayat Yousuf; Sharma, Reeta Kumari; Kandimalla, Ramesh J.L.; Bal, Amanjit; Gill, Kiran Dip

    2013-12-01

    The present investigation was carried out to elucidate a possible molecular mechanism related to the effects of aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of Peroxisome proliferator activated receptor gamma co-activator 1? (PGC-1?) and its downstream targets i.e. Nuclear respiratory factor-1(NRF-1), Nuclear respiratory factor-2(NRF-2) and Mitochondrial transcription factor A (Tfam) in mitochondrial biogenesis. Aluminium lactate (10 mg/kg b.wt./day) was administered intragastrically to rats for 12 weeks. After 12 weeks of exposure, we found an increase in ROS levels, mitochondrial DNA oxidation and decrease in citrate synthase activity in the Hippocampus (HC) and Corpus striatum (CS) regions of rat brain. On the other hand, there was a decrease in the mRNA levels of the mitochondrial encoded subunitsNADH dehydrogenase (ND) subunits i.e. ND1, ND2, ND3, Cytochrome b (Cytb), Cytochrome oxidase (COX) subunits i.e. COX1, COX3, ATP synthase (ATPase) subunit 6 along with reduced expression of nuclear encoded subunits COX4, COX5A, COX5B of Electron transport chain (ETC). Besides, a decrease in mitochondrial DNA copy number and mitochondrial content in both regions of rat brain was observed. The PGC-1? was down-regulated in aluminium treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC-1? in aluminium treated rats. Electron microscopy results revealed a significant increase in the mitochondrial swelling, loss of cristae, chromatin condensation and decreases in mitochondrial number in case of aluminium treated rats as compared to control. So, PGC-1? seems to be a potent target for aluminium neurotoxicity, which makes it an almost ideal target to control or limit the damage that has been associated with the defective mitochondrial function seen in neurodegenerative diseases. - Highlights: Aluminium decreases the mRNA levels of mitochondrial and nuclear encoded subunits

  4. Method for detecting and diagnosing disease caused by pathological protein aggregation

    DOE Patents [OSTI]

    Stevens, Fred J.; Myatt, Elizabeth A.; Solomon, Alan

    2000-01-01

    A method is provided for detecting pathological macromolecules in a patient, comprising obtaining body fluid from the patient, pretreating the body fluid, subjecting the pretreated body fluid to size-exclusion chromatography to create an excluded fluid, and analyzing the excluded fluid to detect macromolecules having a predetermined molecular weight. The method also allows for comparing elution spectra with reference spectra of suspect pathologic proteins.

  5. Surface-enhanced Raman medical probes and system for disease diagnosis and drug testing

    DOE Patents [OSTI]

    Vo-Dinh, T.

    1999-01-26

    A probe for a surface-enhanced Raman scattering spectrometer includes a member of optically transmissive material for receiving the excitation radiation from a laser and for carrying the radiation emitted from a specimen to a detector. An end of the member for placing against the specimen has a coating that produces surface enhancement of the specimen during Raman scattering spectroscopic analysis. Specifically the coating is formed by a first layer of microparticles on the member and a metal layer over the first layer. The first layer may form a microstructure surface over which a metal layer is applied. Alternatively the coating may be a material containing microparticles of a metal. An optional layer of a material may be applied to the metal layer to concentrate onto the probe compounds of analytical interest onto the probe. 39 figs.

  6. Gene by Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction

    SciTech Connect (OSTI)

    Alia-Klein, N.; Alia-Klein, N.; Parvaz, M.A.; Woicik, P.A.; Konova, A.; Maloney, T.; Shumay, E.; Wang, R.; Telang, F.; Biegon, A.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Volkow, N.D.; Goldstein, R.Z.

    2010-12-05

    Chronic cocaine use has been associated with structural deficits in brain regions having dopamine receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability. We therefore examined variations in gray matter volume (GMV) as a function of lifetime drug use and the monoamine oxidase A (MAOA) genotype in cocaine use disorders (CUD) and healthy controls.

  7. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; Burdet, Frédéric; Sheta, Razan; Nemir, Mohamed; Gonzales, Christine; Sarre, Alexandre; Alexanian, Michael; Blow, Matthew J.; et al

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Throughmore » a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.« less

  8. Surface-enhanced raman medical probes and system for disease diagnosis and drug testing

    DOE Patents [OSTI]

    Vo-Dinh, Tuan

    1999-01-01

    A probe for a surface-enhanced Raman scattering spectrometer includes a member of optically transmissive material for receiving the excitation radiation from a laser and for carrying the radiation emitted from a specimen to a detector. An end of the member for placing against the specimen has a coating that produces surface enhancement of the specimen during Raman scattering spectroscopic analysis. Specifically the coating is formed by a first layer of microparticles on the member and a metal layer over the first layer. The first layer may form a microstructure surface over which a metal layer is applied. Alternatively the coating may be a material containing microparticles of a metal. An optional layer of a material may be applied to the metal layer to concentrate onto the probe compounds of analytical interest onto the probe.

  9. Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Huang, Edmond Y.; Inoue, Takuya; Leone, Vanessa A.; Dalal, Sushila; Touw, Ketrija; Wang, Yunwei; Musch, Mark W.; Theriault, Betty; Higuchi, Kazuhide; Donovan, Sharon; et al

    2015-05-01

    Introduction—Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. Here we sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. Methods—Adult male C57Bl/6 mice, germ-free (GF), Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for four weeks. Fecal samples were collected for gut microbiota analysis via 16S rRNA T-RFLP and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. GF mice were conventionalized withmore » gut microbes from treated- and non-treated groups to determine their functional capacities in recipient hosts. Results—Exposure to DEX in WT mice led to substantial shifts in gut microbiota over a four-week period. Furthermore, a significant down-regulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a pro-inflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout (IL10-KO) mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pre-treated with DEX, however, ameliorated symptoms of inflammation. We conclude that commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after GC exposure. These findings underscore the notion that intestinal microbes comprise a “microbial organ” essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.« less

  10. Disease Control and Ototoxicity Using Intensity-Modulated Radiation Therapy Tumor-Bed Boost for Medulloblastoma

    SciTech Connect (OSTI)

    Polkinghorn, William R.; Dunkel, Ira J.; Souweidane, Mark M.; Khakoo, Yasmin; Lyden, David C.; Gilheeney, Stephen W.; Becher, Oren J.; Budnick, Amy S.; Wolden, Suzanne L.

    2011-11-01

    Purpose: We previously reported excellent local control for treating medulloblastoma with a limited boost to the tumor bed. In order to decrease ototoxicity, we subsequently implemented a tumor-bed boost using intensity-modulated radiation therapy (IMRT), the clinical results of which we report here. Patients and Methods: A total of 33 patients with newly diagnosed medulloblastoma, 25 with standard risk, and 8 with high risk, were treated on an IMRT tumor-bed boost following craniospinal irradiation (CSI). Six standard-risk patients were treated with an institutional protocol with 18 Gy CSI in conjunction with intrathecal iodine-131-labeled monoclonal antibody. The majority of patients received concurrent vincristine and standard adjuvant chemotherapy. Pure-tone audiograms were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: Median age was 9 years old (range, 4-46 years old). Median follow-up was 63 months. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) rates for standard-risk patients who received 23.4 or 36 Gy CSI (not including those who received 18 Gy CSI with radioimmunotherapy) were 81.4% and 88.4%, respectively, at 5 years; 5-year PFS and OS rates for high-risk patients were both 87.5%. There were no isolated posterior fossa failures outside of the boost volume. Posttreatment audiograms were available for 31 patients, of whom 6%, at a median follow-up of 19 months, had developed Grade 3 hearing loss. Conclusion: An IMRT tumor-bed boost results in excellent local control while delivering a low mean dose to the cochlea, resulting in a low rate of ototoxicity.

  11. Indoor Measurements of Environmental Tobacco Smoke Final Report to the Tobacco Related Disease Research Program

    SciTech Connect (OSTI)

    Apte, Michael G.; Gundel, Lara A.; Dod, Raymond L.; Russell, Marion L.; Singer, Brett C.; Sohn, Michael D.; Sullivan, Douglas P.; Chang, Gee-Minn; Sextro, Richard G.

    2004-03-02

    The objective of this research project was to improve the basis for estimating environmental tobacco smoke (ETS) exposures in a variety of indoor environments. The research utilized experiments conducted in both laboratory and ''real-world'' buildings to (1) study the transport of ETS species from room to room, (2) examine the viability of using various chemical markers as tracers for ETS, and (3) to evaluate to what extent re-emission of ETS components from indoor surfaces might add to the ETS exposure estimates. A three-room environmental chamber was used to examine multi-zone transport and behavior of ETS and its tracers. One room (simulating a smoker's living room) was extensively conditioned with ETS, while a corridor and a second room (simulating a child's bedroom) remained smoking-free. A series of 5 sets of replicate experiments were conducted under different door opening and flow configurations: sealed, leaky, slightly ajar, wide open, and under forced air-flow conditions. When the doors between the rooms were slightly ajar the particles dispersed into the other rooms, eventually reaching the same concentration. The particle size distribution took the same form in each room, although the total numbers of particles in each room depended on the door configurations. The particle number size distribution moved towards somewhat larger particles as the ETS aged. We also successfully modeled the inter-room transport of ETS particles from first principles--using size fractionated particle emission factors, predicted deposition rates, and thermal temperature gradient driven inter-room flows, This validation improved our understanding of bulk inter-room ETS particle transport. Four chemical tracers were examined: ultraviolet-absorbing particulate matter (UVPM), fluorescent particulate matter (FPM), nicotine and solanesol. Both (UVPM) and (FPM) traced the transport of ETS particles into the non-smoking areas. Nicotine, on the other hand, quickly adsorbed on unconditioned surfaces so that nicotine concentrations in these rooms remained very low, even during smoking episodes. These findings suggest that using nicotine as a tracer of ETS particle concentrations may yield misleading concentration and/or exposure estimates. The results of the solanesol analyses were compromised, apparently by exposure to light during collection (lights in the chambers were always on during the experiments). This may mean that the use of solanesol as a tracer is impractical in ''real-world'' conditions. In the final phase of the project we conducted measurements of ETS particles and tracers in three residences occupied by smokers who had joined a smoking cessation program. As a pilot study, its objective was to improve our understanding of how ETS aerosols are transported in a small number of homes (and thus, whether limiting smoking to certain areas has an effect on ETS exposures in other parts of the building). As with the chamber studies, we examined whether measurements of various chemical tracers, such as nicotine, solanesol, FPM and UVPM, could be used to accurately predict ETS concentrations and potential exposures in ''real-world'' settings, as has been suggested by several authors. The ultimate goal of these efforts, and a future larger multiple house study, is to improve the basis for estimating ETS exposures to the general public. Because we only studied three houses no firm conclusions can be developed from our data. However, the results for the ETS tracers are essentially the same as those for the chamber experiments. The use of nicotine was problematic as a marker for ETS exposure. In the smoking areas of the homes, nicotine appeared to be a suitable indicator; however in the non-smoking regions, nicotine behavior was very inconsistent. The other tracers, UVPM and FPM, provided a better basis for estimating ETS exposures in the ''real world''. The use of solanesol was compromised--as it had been in the chamber experiments.

  12. Chronic disease and early exposure to air-borne mixtures. 2. Exposure assessment

    SciTech Connect (OSTI)

    James Argo

    2007-10-15

    This work is part of a larger study of the impact of early exposure to releases from industry on the etiology of cancer. Releases from all kraft and sulfite mills, coke ovens, oil refineries, copper, nickel, and lead/zinc smelters operating in Canada during the exposure period of 1967-1970 have been determined. All plumes have been expressed in g BaP eq/d using the RASH methodology. The releases have been divided into process, boiler fuel, dioxin, and SO{sub 2} emissions. Combustion sources have been defined with FIREv6.23. Dioxin congenors are expected in all source types when the boiler fuel is heavy fuel oil, wood or wood bark, or coal. All about 90 communities examined have an inverted sex ratio. 53 refs., 2 figs., 4 tabs.

  13. Update on the Hanford Site Chronic Beryllium Disease Prevention Program (CBDPP)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    June 18, 2015 Be Corrective Action Plan (CAP) * Be CAP was approved by DOE-HQ in September 2010 * CAP supplement addressing new consensus process and high-priority Phase 1 products was approved by DOE Office of Environmental Management (DOE-EM) in September 2011 * CAP supplement addressing lower priority Phase 2 and Phase 3 products was approved by DOE-EM on March 13, 2012 Be CAP Status * DOE HQ Enterprise Assessment review March 2015, awaiting final report, no findings, 3 Opportunities for

  14. Structure of an aprataxin?DNA complex with insights into AOA1 neurodegenerative disease

    SciTech Connect (OSTI)

    Tumbale, Percy; Appel, C. Denise; Kraehenbuehl, Rolf; Robertson, Patrick D.; Williams, Jessica S.; Krahn, Joe; Ahel, Ivan; Williams, R. Scott (NIEHS); (Manchester)

    2012-09-17

    DNA ligases finalize DNA replication and repair through DNA nick-sealing reactions that can abort to generate cytotoxic 5'-adenylation DNA damage. Aprataxin (Aptx) catalyzes direct reversal of 5'-adenylate adducts to protect genome integrity. Here the structure of a Schizosaccharomyces pombe Aptx-DNA-AMP-Zn{sup 2+} complex reveals active site and DNA interaction clefts formed by fusing a histidine triad (HIT) nucleotide hydrolase with a DNA minor groove-binding C{sub 2}HE zinc finger (Znf). An Aptx helical 'wedge' interrogates the base stack for sensing DNA ends or DNA nicks. The HIT-Znf, the wedge and an '[F/Y]PK' pivot motif cooperate to distort terminal DNA base-pairing and direct 5'-adenylate into the active site pocket. Structural and mutational data support a wedge-pivot-cut HIT-Znf catalytic mechanism for 5'-adenylate adduct recognition and removal and suggest that mutations affecting protein folding, the active site pocket and the pivot motif underlie Aptx dysfunction in the neurodegenerative disorder ataxia with oculomotor apraxia 1 (AOA1).

  15. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    SciTech Connect (OSTI)

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; Burdet, Frédéric; Sheta, Razan; Nemir, Mohamed; Gonzales, Christine; Sarre, Alexandre; Alexanian, Michael; Blow, Matthew J.; May, Dalit; Johnson, Rory; Dauvillier, Jérôme; Pennacchio, Len A.; Pedrazzini, Thierry

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.

  16. AtMIN7 mediated disease resistance to Pseudomonas syringae in Arabidopsis

    DOE Patents [OSTI]

    He, Sheng Yang; Nomura, Kinya

    2011-07-26

    The present invention relates to compositions and methods for enhancing plant defenses against pathogens. More particularly, the invention relates to enhancing plant immunity against bacterial pathogens, wherein AtMIN7 mediated protection is enhanced and/or there is a decrease in activity of an AtMIN7 associated virulence protein such as a Pseudomonas syringae pv. tomato DC3000 HopM1. Reagents of the present invention provide a means of studying cellular trafficking while formulations of the present inventions provide increased pathogen resistance in plants.

  17. Method of treating inflammatory diseases using a radiolabeled ferric hydroxide calloid

    DOE Patents [OSTI]

    Atcher, Robert W.; Hines, John J.

    1992-01-01

    A ferric hydroxide colloid having an alpha-emitting radionuclide essentially on the outer surfaces and a method of forming same. The method includes oxidizing a ferrous hydroxide to ferric hydroxide in the presence of a preselected radionuclide to form a colloid having the radionuclide on the outer surface thereof, and thereafter washing the colloid, and suspending the washed colloid in a suitable solution. The labelled colloid is useful in cancer therapy and for the treatment of inflamed joints.

  18. OSTIblog Articles in the disease Topic | OSTI, US Dept of Energy...

    Office of Scientific and Technical Information (OSTI)

    John Q. Trojanowski, an Alzheimer's researcher at the University of Pennsylvania, "It's not science the way most of us have practiced it in our careers. But we all realized that we ...

  19. Premier Tools of Energy Research Also Probe Secrets of Viral Disease

    DOE R&D Accomplishments [OSTI]

    Chui, Glennda

    2011-03-28

    Advanced light sources peer into matter at the atomic and molecular scales, with applications ranging from physics, chemistry, materials science, and advanced energy research, to biology and medicine.

  20. Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases

    SciTech Connect (OSTI)

    Huang, Edmond Y.; Inoue, Takuya; Leone, Vanessa A.; Dalal, Sushila; Touw, Ketrija; Wang, Yunwei; Musch, Mark W.; Theriault, Betty; Higuchi, Kazuhide; Donovan, Sharon; Gilbert, Jack; Chang, Eugene B.

    2015-05-01

    Introduction—Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. Here we sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. Methods—Adult male C57Bl/6 mice, germ-free (GF), Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for four weeks. Fecal samples were collected for gut microbiota analysis via 16S rRNA T-RFLP and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. GF mice were conventionalized with gut microbes from treated- and non-treated groups to determine their functional capacities in recipient hosts. Results—Exposure to DEX in WT mice led to substantial shifts in gut microbiota over a four-week period. Furthermore, a significant down-regulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a pro-inflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout (IL10-KO) mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pre-treated with DEX, however, ameliorated symptoms of inflammation. We conclude that commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after GC exposure. These findings underscore the notion that intestinal microbes comprise a “microbial organ” essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.

  1. Gas bubble disease in smallmouth bass and northern squawfish from the Snake and Columbia Rivers

    SciTech Connect (OSTI)

    Montgomery, J.C.; Becker, C.D.

    1980-11-01

    In 1975 and 1976, 179 smallmouth bass (Micropterus dolomieui) and 85 northern squawfish (Ptychocheilus oregonensis) were collected by angling from the lower Snake and mid-Columbia rivers, southeastern Washington. All fish were examined externally for gas bubble syndrome. Emboli were found beneath membranes of the opercula, body, and fins of 72% of the smallmouth bass and 84% of the northern squawfish. Hemorrhage was also noted on the caudal, anal, and pectoral fins of several smallmouth bass. Presence of gas bubble syndrome corresponded to the spring runoff when total dissolved gas supersaturations in river water exceeded 115%.

  2. Evaluation of Novel Design Strategies for Developing Zinc Finger Nucleases Tools for Treating Human Diseases

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Bach, Christian; Sherman, William; Pallis, Jani; Patra, Prabir; Bajwa, Hassan

    2014-01-01

    Zinc finger nucleases (ZFNs) are associated with cell death and apoptosis by binding at countless undesired locations. This cytotoxicity is associated with the binding ability of engineered zinc finger domains to bind dissimilar DNA sequences with high affinity. In general, binding preferences of transcription factors are associated with significant degenerated diversity and complexity which convolutes the design and engineering of precise DNA binding domains. Evolutionary success of natural zinc finger proteins, however, evinces that nature created specific evolutionary traits and strategies, such as modularity and rank-specific recognition to cope with binding complexity that are critical for creating clinical viable toolsmore » to precisely modify the human genome. Our findings indicate preservation of general modularity and significant alteration of the rank-specific binding preferences of the three-finger binding domain of transcription factor SP1 when exchanging amino acids in the 2nd finger.« less

  3. A comprehensive collection of systems biology data characterizing the host response to viral infection

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Aevermann, Brian D.; Pickett, Brett E.; Kumar, Sanjeev; Klem, Edward B.; Agnihothram, Sudhakar; Askovich, Peter S.; Bankhead, Armand; Bolles, Meagan; Carter, Victoria; Chang, Jean H.; et al

    2014-10-14

    The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archivedmore » at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). As a result, by comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection.« less

  4. Prognostic Impact of Radiation Therapy to the Primary Tumor in Patients With Non-small Cell Lung Cancer and Oligometastasis at Diagnosis

    SciTech Connect (OSTI)

    Lopez Guerra, Jose Luis [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States) [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Instituto Madrileno de Oncologia/Grupo IMO, Madrid (Spain); Gomez, Daniel, E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan; Hong, David S. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Heymach, John V. [Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G. [Department of Thoracic Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Thoracic Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H.; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-09-01

    Purpose: We investigated prognostic factors associated with survival in patients with non-small cell lung cancer (NSCLC) and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis. Methods and Materials: From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC (<5 metastases) at diagnosis underwent definitive chemoradiation therapy ({>=}45 Gy) to the primary site. Forty-four of these patients also received definitive local treatment for the oligometastases. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results: Univariate Cox proportional hazard analysis revealed better overall survival (OS) for those patients who received at least 63 Gy of radiation to the primary site (P=.002), received definitive local treatment for oligometastasis (P=.041), had a Karnofsky performance status (KPS) score >80 (P=.007), had a gross tumor volume {<=}124 cm{sup 3} (P=.002), had adenocarcinoma histology (P=.002), or had no history of respiratory disease (P=.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=.004, P=.006, and P<.001, respectively). The radiation dose also maintained significance when patients with and without brain metastases were analyzed separately. Conclusions: Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from definitive local therapy.

  5. Health-hazard evaluation report HETA 84-484-1754, Detroit Fire Fighters, Detroit, Michigan

    SciTech Connect (OSTI)

    Anderson, K.E.; Melius, J.M.

    1986-12-01

    In response to a request from the International Association of Fire Fighters on behalf of the Detroit Fire Fighters Association, Detroit, Michigan, a health hazard evaluation was made of respiratory symptoms and skin irritation in fire fighters involved in a large fire and explosion at a warehouse. Over 200 fire fighters from fire-fighting organizations in three communities were involved in the incident. Site runoff water contained chlordane and malathion in low parts per million; other samples were negative. Nose and throat irritation, cough, and shortness of breath were experienced by a large proportion of fire fighters following the fire, and in 14, 15, and 17 percent, respectively, symptoms persisted over 2 months. Symptoms were significantly associated with time spent at the scene and time spent in heavy smoke. Pulmonary function tests were abnormal in 14 cases, ten due to obstructive lung disease, three to restrictive lung disease, and one to a combination. The authors conclude that better protective equipment is needed for fire fighters at chemical fires. Recommendations include development of a hazardous-materials response team, and implementation of a routine medical surveillance program.

  6. A comprehensive collection of systems biology data characterizing the host response to viral infection

    SciTech Connect (OSTI)

    Aevermann, Brian D.; Pickett, Brett E.; Kumar, Sanjeev; Klem, Edward B.; Agnihothram, Sudhakar; Askovich, Peter S.; Bankhead, Armand; Bolles, Meagan; Carter, Victoria; Chang, Jean H.; Clauss, Therese R. W.; Dash, Pradyot; Diercks, Alan H.; Eisfeld, Amie J.; Ellis, Amy L.; Fan, Shufang; Ferris, Martin T.; Gralinski, Lisa; Green, Richard; Gritsenko, Marina A.; Hatta, Masato; Heegel, Robert A.; Jacobs, Jon M.; Jeng, Sophia; Josset, Laurence; Kaiser, Shari M.; Kelly, Sarah; Law, Gale Lynn; Li, Chengjun; Li, Jiangning; Long, Casey; Luna, Maria L.; Matzke, Melissa M.; McDermott, Jason E.; Menachery, Vineet; Metz, Thomas O.; Mitchell, Hugh D.; Monroe, Matthew E.; Navarro, Garnet; Neumann, Gabriele; Podyminogin, Rebecca L.; Purvine, Samuel O.; Rosenberger, Carrie; Sanders, Catherine J.; Schepmoes, Athena A.; Shukla, Anil K.; Sims, Amy; Sova, Pavel; Tam, Vincent C.; Tchitchek, Nicholas; Thomas, Paul G.; Tilton, Susan C.; Totura, Allison L.; Wang, Jing; Webb-Robertson, Bobbie-Jo M.; Wen, Ji; Weiss, Jeffrey M.; Yang, Feng; Yount, Boyd; Zhang, Qibin; Mcweeney, Shannon K.; Smith, Richard D.; Waters, Katrina M.; Kawaoka, Yoshihiro; Baric, Ralph; Aderem, Alan; Katze, Michael G.; Scheuermann, Richard H.

    2014-10-14

    The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). As a result, by comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection.

  7. Correlation of Clinical and Dosimetric Factors With Adverse Pulmonary Outcomes in Children After Lung Irradiation

    SciTech Connect (OSTI)

    Venkatramani, Rajkumar; Kamath, Sunil; Wong, Kenneth; Malvar, Jemily; Sposto, Richard; Goodarzian, Fariba; Freyer, David R.; Keens, Thomas G.; and others

    2013-08-01

    Purpose: To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. Methods and Materials: We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. Results: We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The following pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V{sub 22} (volume of lung exposed to a radiation dose ≥22 Gy) and V{sub 30} (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and V{sub dose} (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01). Conclusions: Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed

  8. DOE-HDBK-1122-99; Radiological Control Technician Training

    Energy Savers [EERE]

    Detection and Measurement", Knoll, G., John Wiley and Sons, New York, 1979. 9. 10 CFR 835, "Occupational Radiation Protection", 1998. 10. "Practices of Respiratory ...

  9. Microsoft Word - Call for Abstracts Student Research Forum.docx

    Energy Savers [EERE]

    Environmental Sciences Preferred abstract submissions will address environmental exposures and triggers, e.g., air pollution and respiratory health, proximity to hazardous waste, ...

  10. Substrate Recognition Strategy for Botulinum Neurotoxin

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    due to respiratory failure resulting from paralysis of the muscles used in breathing. The muscle paralysis is caused by the neurotoxin produced by the bacterium Clostridium...

  11. Nuclear Safety Enforcement Documents | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Flats Environmental Technology Site August 9, 2004 Preliminary Notice of Violation, Fluor Fernald, Inc. - EA-2004-07 Issued to Fluor Fernald, Inc., related to Respiratory...

  12. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    computed tomography (CT) images. Methods: The proposed algorithm extracted multiple time resolved features as potential respiratory signals. These features were taken from the...

  13. TEEMP | Open Energy Information

    Open Energy Info (EERE)

    matter linked to respiratory illness and safety issues like traffic fatalities addressing air pollution reductions and increases in physical activity that improve public health,...

  14. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Severe Acute Respiratory Syndrome corona virus (SARS-CoV) represent a serious public ... genesproteins likely related to the pathogenicity of SARS-CoV and influenza virus. ...

  15. UNITED STATES OF AMERICA DEPARTMENT OF ENERGY OFFICE OF FOSSIL...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    premature death, heart failure, chronic respiratory damage, and premature aging of the lungs. Sierra Club states that significant ozone pollution also damages plants and...

  16. SEA and DOE Extension Comments

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    These microscopic particles are the most dangerous to public health since they are breathed directly into the lungs, causing respiratory infections, asthma attacks, bronchitis, ...

  17. BSL Fact Sheet_r02_12-08-2005_keb.pub

    National Nuclear Security Administration (NNSA)

    virus, severe acute respiratory syndrome (SARS), monkeypox, and annual outbreaks of influenza. To control epidemics and protect the public health, medical researchers must...

  18. Final Technical Report (Technical Report) | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    a process that underpins respiratory metal reduction by bacteria in nature and in bioremediation strategies, including reductive immobilization of radioactive contaminants. ...

  19. SO2907, A Putative TonB-dependent Receptor, Is Involved in Dissimilato...

    Office of Scientific and Technical Information (OSTI)

    The components of respiratory metabolism are localized in the membrane fractions which include the outer membrane and cytoplasmic membrane. Many of the biological components that ...

  20. DOE - Office of Legacy Management -- ITL

    Office of Legacy Management (LM)

    All documents are Adobe Acrobat files. pdficon Key Documents Fact Sheet Please be green. ... Other Documents Quitclaim Deed between Department of Energy and the Lovelace Respiratory ...