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Title: Sleep deprivation impairs recognition of specific emotions

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Journal Article: Published Article
Journal Name:
Neurobiology of Sleep and Circadian Rhythms
Additional Journal Information:
Journal Volume: 3; Journal Issue: C; Related Information: CHORUS Timestamp: 2017-06-26 19:49:33; Journal ID: ISSN 2451-9944
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Citation Formats

Killgore, William D. S., Balkin, Thomas J., Yarnell, Angela M., and Capaldi, II, Vincent F.. Sleep deprivation impairs recognition of specific emotions. Country unknown/Code not available: N. p., 2017. Web. doi:10.1016/j.nbscr.2017.01.001.
Killgore, William D. S., Balkin, Thomas J., Yarnell, Angela M., & Capaldi, II, Vincent F.. Sleep deprivation impairs recognition of specific emotions. Country unknown/Code not available. doi:10.1016/j.nbscr.2017.01.001.
Killgore, William D. S., Balkin, Thomas J., Yarnell, Angela M., and Capaldi, II, Vincent F.. 2017. "Sleep deprivation impairs recognition of specific emotions". Country unknown/Code not available. doi:10.1016/j.nbscr.2017.01.001.
title = {Sleep deprivation impairs recognition of specific emotions},
author = {Killgore, William D. S. and Balkin, Thomas J. and Yarnell, Angela M. and Capaldi, II, Vincent F.},
abstractNote = {},
doi = {10.1016/j.nbscr.2017.01.001},
journal = {Neurobiology of Sleep and Circadian Rhythms},
number = C,
volume = 3,
place = {Country unknown/Code not available},
year = 2017,
month = 6

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Publisher's Version of Record at 10.1016/j.nbscr.2017.01.001

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  • Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [{sup 11}C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([{sup 11}C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopaminemore » release was increased during sleep deprivation. We scanned 20 controls with [{sup 11}C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.« less
  • Objectives/Background: To determine whether a 6-month posttreatment prostate-specific antigen (PSA) value in patients with prostate cancer (PCa) treated with concurrent androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) serves as an early predictor for biochemical relapse free survival (bRFS), distant metastasis–free survival (DMFS), and prostate cancer–specific mortality (PCSM). Methods: A retrospective review of intermediate-risk and high-risk PCa patients treated with EBRT and concurrent ADT at a single institution between 1996 and 2012. All patients received high-dose radiation with either 78 Gy in 39 fractions or 70 Gy in 28 fractions. Kaplan-Meier analysis was used to estimate bRFS and DMFS, andmore » cumulative incidence was used to estimate PCSM. Results: 532 patients were identified. The median follow-up time was 7.5 years (range, 1-16.25 years). The median initial PSA (iPSA) was 13.0 ng/mL (range, 0.37-255 ng/mL), and the median duration of ADT was 6 months (range, 1-78 months). The median PSA 6 months after EBRT was 0.1 ng/mL (range, 0-19 ng/mL), and 310 patients (58.3%) had a 6-month PSA ≤0.1 ng/mL. Multivariable analysis (MVA) demonstrated that a 6-month post-EBRT PSA of >0.1 ng/mL was an independent predictor of worse bRFS (hazard ratio [HR] = 2.518; P<.0001), DMFS (HR=3.743; P<.0001), and PCSM (HR=5.435; P<.0001). On MVA, a Gleason score of 8 to 10 also correlated with worse DMFS and PCSM (P<.05). The duration of ADT (1-6 vs >6 months) was not predictive of any clinical endpoint. Conclusions: A 6-month posttreatment PSA >0.1 ng/mL in intermediate-risk and high-risk PCa patients treated with concurrent high-dose EBRT and ADT is associated with worse bRFS, DMFS, and PCSM. The duration of ADT was not predictive of any clinical endpoint. A 6-month PSA after definitive EBRT and ADT helps identify patients at higher risk of disease progression and may serve as a predictive tool to select patients for early salvage therapy on future clinical trials.« less
  • Purpose: Several large randomized prospective studies have demonstrated a survival benefit with the addition of long-term androgen deprivation to definitive radiotherapy for patients with Gleason score 8-10 or T3-T4 prostate cancer. However, these studies were performed before the routine use of prostate-specific antigen (PSA) measurement. The purpose of this study was to determine what pretreatment (initial) PSA (iPSA) level, if any, warrants the addition of long-term androgen deprivation in the PSA era. Methods and materials: The data set evaluated consisted of 1003 prostate cancer patients treated definitively with three-dimensional conformal radiotherapy between May 1, 1989 and November 30, 1999 (medianmore » follow-up, 61 months). Specifically excluded were patients with T3-T4 disease or Gleason score greater than 7 or those who had undergone androgen deprivation as a part of their initial therapy. The median radiation dose was 76 Gy. Patients were randomly split into two data sets, with the first (n = 487) used to evaluate the optimal iPSA cutpoint for which a statistically significant difference in outcome was noted. The second data set (n = 516) served as a validation data set for the initial modeling. The analysis of the optimal iPSA cutpoint was based on a recursive partitioning approach for censored data using the log-rank test for nodal separation of freedom from biochemical failure (FFBF) as defined by the American Society for Therapeutic Radiology and Oncology definition. Cox multivariate regression analysis was used to confirm independent predictors of outcome among the clinical and treatment-related factors: iPSA (grouped as defined by the recursive partitioning analysis), Gleason score (2-6 vs. 7), T stage (T1c-T2a vs. T2b-T2c), and total radiation dose (continuous). Results: The recursive partitioning analysis data set resulted in an optimal iPSA cutpoint of 35 ng/mL, such that the 5-year Kaplan-Meier estimate of FFBF was 80%, 69%, and 19% for iPSA groups of 0-9.9, 10-35, and >35 ng/mL, respectively. The validation data set demonstrated the optimal iPSA cutpoint to be 30 ng/mL. Conservatively choosing 30 ng/mL as the optimal cutpoint, the 5-year FFBF estimate for the entire 1003 patients was 82%, 69%, and 20% for iPSA groups 0-9.9 (n = 630), 10-30 (n = 329), and >30 (n = 44) ng/mL, respectively. On multivariate regression analysis, with the iPSA grouped as above, the Gleason score and radiation dose were independent predictors of outcome in this patient group (all p < 0.001). On univariate analysis, a higher radiation dose improved FFBF when the iPSA level was between 10 and 30 ng/mL (p = 0.001) but not when the iPSA level was >30 or <10 ng/mL. Conclusion: Recursive partitioning techniques defined an iPSA cutpoint of 30 ng/mL for delineating intermediate vs. high risk. Patients with a PSA level >30 ng/mL in the absence of Gleason score >7 or T3 disease do poorly when treated with radiotherapy alone and should be considered for long-term androgen deprivation or other aggressive systemic therapy.« less
  • Purpose: The accuracy of the American Society of Therapeutic Radiation Oncology consensus definition of biochemical failure (BF) after radiation therapy (RT) and androgen deprivation (AD) has been questioned, because posttreatment prostate-specific antigen (PSA) levels typically rise after release from AD, and misclassification of BF may be made. The temporal kinetics of posttreatment PSA levels was examined to define the error in the classification of BF. Methods and Materials: Between December 1, 1991 and April 30, 1998, 688 men with T1c-T3 NX/0 M0 prostate cancer received three-dimensional conformal RT alone (n = 586) or in combination with either short-term (STAD: 3more » to 12 months, n = 82) or long-term (LTAD: 12 to 36 months, n = 20) AD. Follow-up, calculated from the end of all treatment, was {>=}48 months. The mean posttreatment PSA was calculated in 3-month intervals. Results: The median posttreatment clinical follow-up period was 76 months (range, 48-152 months). The posttreatment PSA values from the end of all treatment for the RT+STAD-BF group showed an initial period of rise followed by a period of decline at 30 months and then a continued rise again. The decline in the mean posttreatment PSA is explained in part by stabilization in PSA level after 3 consecutive rises. Nonbiochemical failures (NBF) after RT+STAD had a relatively constant mean PSA over time of approximately 0.5 ng/mL. Unlike the RT+STAD-NBF profile, the RT+LTAD-NBF profile rose continuously and steadily to a level approaching 1 ng/mL. The RT+LTAD-BF profile rose continuously but at a slower rate over time. Nine RT+STAD-NBF patients (22%) and 2 RT+LTAD-BF (29%) patients experienced 3 consecutive rises followed by a subsequent decline and stabilization of PSA compared to 10 RT-BF patients (5%). Redistributing these misclassified patients to their respective NBF groups changed the mean posttreatment PSA profiles as follows: The RT+LTAD-BF profile rose constantly and steadily with a doubling time of approximately 16 months, and the RT+LAD-NF initially rose to a value of approximately 0.5 ng/mL, then at 36 months began to decline. Conclusions: The temporal kinetics of posttreatment PSA after RT+AD and RT alone are different. The American Society of Therapeutic Radiation Oncology definition for biochemical failure overestimates BF in 20-30% after RT+AD compared to 5% after RT alone.« less
  • Purpose: To assess the benefit of androgen deprivation (AD) and its optimal duration in patients with prostate cancer treated with external beam radiotherapy, who present with prostate-specific antigen levels >20 ng/mL. Methods and Materials: A total of 307 patients treated with external beam radiotherapy, AD, and presenting with a PSA level >20 ng/mL were identified from the Prostate Cancer Outcomes Initiative database of the British Columbia Cancer Agency. Androgen deprivation was defined as short term (ST-AD, <12 months) or long term (LT-AD, {>=}12 months). The endpoints analyzed were biochemical control (no evidence of disease) (bNED), overall survival, and cause-specific survival.more » Statistical analysis was conducted with Kaplan-Meier estimates, log-rank tests, and multivariate analyses with logistic and Cox regression models. Results: There were 151 patients in the ST-AD group and 156 in the LT-AD group. The distributions of Gleason score and stage were comparable in the two cohorts. Median follow-up times were 48 months for patients treated with ST-AD and 45 months for patients treated with LT-AD. The median durations of AD were 6 and 25.6 months for the ST-AD and LT-AD groups, respectively. The bNED rate was 37% for the ST-AD group and 62.5% for the LT-AD group (p < 0.0001). The 5-year overall survival rate was 75% in the ST-AD group vs. 87.5% for the LT-AD group (p = 0.0091). The 5-year cause-specific survival rate was 82% for the ST-AD group vs. 94% for the LT-AD group (p = 0.0072). Conclusions: Several randomized trials have demonstrated the benefit of LT-AD in high-risk patients with prostate cancer. In some reports, the survival advantage seems to be restricted to patients with high Gleason score. The present analysis supports the hypothesis that LT-AD improves bNED and survival rates in patients presenting with a PSA level >20, irrespective of Gleason score or T stage.« less