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Vigilance deficits account for a substantial number of accidents and errors. Current techniques to detect vigilance impairment measure only the most severe level evident in eyelid closure and falling asleep, which is often too late to avoid an accident or error. The present study sought to identify ocular biometrics of intermediate impairment of vigilance and develop a new technique that could detect a range of deficits in vigilant attention (VA). Sixteen healthy adults performed well-validated Psychomotor Vigilance Test (PVT) for tracking vigilance attention while undergoing simultaneous recording of eye metrics every 2 hours during 38 hours of continuous wakefulness. A novel marker was found that measured VA when the eyes were open—the prevalence of microsaccades. Notably, the prevalence of microsaccades decreased in response to sleep deprivation and time-on-task. In addition, a novel algorithm for detecting multilevel VA was developed, which estimated performance on the PVT by integrating the novel marker with other eye-related indices. The novel algorithm also tracked changes in intermediate level of VA (specific reaction times in the PVT, i.e. 300–500 ms) during prolonged time-on-task and sleep deprivation, which had not been tracked previously by conventional techniques. The implication of the findings is that this novel algorithm, named “eye-metrical estimation version of the PVT: PVT-E,” can be used to reduce human-error-related accidents caused by vigilance impairment even when its level is intermediate.

STUDY OBJECTIVES Prescription sleep aids are frequently used in the general population and even more frequently in spaceflight. To evaluate the risk to operational safety, a ground-based, double-blind, placebo-controlled study on the emergent awakening effects of zolpidem and zaleplon was conducted. METHODS N = 34 participants (age M = 42.1 ± 9.7; 25 males; 9 Astronauts, 7 Astronaut candidates, and 18 Flight Controllers) were investigated for three nights separated by M = 10 days. They were randomized to ingestion of one of the following at lights out: placebo, 10 mg zaleplon, and either 5 mg (N = 20) or 10 mg (N = 14) zolpidem. They were awakened abruptly by alarm at the expected PK,max (1 hr after lights out for zaleplon; 1.5 hr for placebo/zolpidem). Participants were required to turn off the alarm and perform a cognitive test battery twice, separated by a 20-30 min reading break. They then returned to sleep and were awakened to perform the same cognitive tasks at an average of 6.7 hr after drug ingestion. RESULTS Relative to placebo, the effects of 10 mg zaleplon and 5 mg zolpidem on cognitive performance were minor. In contrast, 10 mg zolpidem adversely affected cognitive throughput (p < 0.001), psychomotor vigilance (p < 0.001), working memory (p < 0.01), delayed word recall (p < 0.05), and subjective sleepiness (p < 0.01) at the first emergent awakening. At terminal awakening, neither cognitive performance nor subjective sleepiness was impaired after ingestion of zaleplon or zolpidem (5 mg and 10 mg) compared with placebo. CONCLUSIONS Presleep ingestion of sleep medications, especially 10 mg zolpidem, poses a risk for performance errors after emergent awakenings near the expected PK,max. REGISTRATION Optimize Astronaut Sleep Medication Efficacy and Individual Effects (clinicaltrials.gov ID NCT03526575).

Introduction As of March 2020, most U.S. states and territories issued statements advising people “stay at home” to avoid spreading the novel Coronavirus (COVID-19). This resulted in an unprecedented number of people practicing physical confinement and social distancing. This study examined self-reported changes in sleep duration, quality and timing in response to confinement and isolation. Methods We developed the “Anonymous Survey on Confinement during the COVID-19 Pandemic” to collect information on the American population practicing social distancing and some level of confinement. The survey collected information on demographics, duration and degree of confinement, and sleep-wake dynamics. The online survey was available for completion by any individual ≥18 years of age through the Penn Medicine Clinical Research page from May 16th to November 11th 2020. Descriptive statistics characterized the nature of confinement and non-parametric correlations evaluated the relationships between confinement and sleep-wake dynamics. Results N=226 participants completed the survey (n=176 female [77.8%]; n=47 male [20.8%]). The average age was 44.9±17.4 years. N=215[95.1%] reported confinement since March 2020 for an average of 89.3±41.7 days in confinement. Surveyed participants in confinement reported sleeping more than before confinement [40.0%], taking the same amount of time to fall asleep [56.6%], and felt that they were getting enough sleep [66.3%]. However, 36.3% of participants reported going to bed earlier and waking up earlier. Participants that engaged in naps prior to confinement reported taking more naps in confinement [50.8%]. Participants reported more daytime sleepiness [42.9%] and more disturbed sleep quality during confinement relative to before confinement [42.5%]. There were no significant correlations between time in confinement and sleep outcomes. Conclusion During the confinement amid the COVID-19 pandemic, participants responded by sleeping more and at different times, which could reflect circadian disruption of sleep. Changes in sleep amount and sleeping timing were accompanied by increased daytime sleepiness and a reduction in sleep quality. These changes may have been due to age, stressors experienced during the pandemic, social isolation, and/or a change in behavioral routines in response to changing demands and schedules. Our findings suggest that attention to changes in sleep-wake dynamics due to prolonged confinement is likely important to maintain healthy behaviors. Support (if any)

Introduction We conducted a childhood sleep promotion study between March 2019 and December 2020 in Philadelphia. COVID19 was first detected in Pennsylvania in March 2020 and non-essential services were strictly curtailed (including school closures), with easing of curtailments by the fall 2020 (including hybrid schooling in some districts). We determined if changes in sleep duration were consistent during pre-, earlier, and later COVID19 periods. Methods Typically developing children (9-12y) with sleep duration Results Mean age of participants was 11.6y (51% female and 29% Black participants). Pre-COVID19 (N=59), average sleep duration increased from baseline by 21 (95% CI: 10, 30) minutes per weeknight during the intervention. In spring 2020 (N=18), the average sleep duration increase was two times larger in magnitude at 41 (95% CI: 25, 59) minutes per weeknight. For fall 2020 (N=20), the average sleep duration increase was 24 (95% CI: 7, 40) minutes per weeknight. Changes in sleep timing from baseline during the intervention were consistent pre-COVID19 and in the fall 2020 (e.g., ≈15 minutes earlier sleep onset throughout the intervention period), whereas sleep timing changes were dynamic in the spring 2020 (e.g., 41 minutes earlier for week 1, and 44 minutes later for week 7). Conclusion This sleep intervention demonstrated increases in sleep duration pre-COVID19, with marked duration increases and dynamic timing changes coinciding with COVID19 restrictions during earlier (Spring 2020), but not later (Fall 2020), weeks of the COVID19 pandemic in Pennsylvania. Support (if any) K0 1 HL1 2 3 6 1 2 and CHOP

Introduction In March 2020, an unprecedented number of individuals were confined to their homes in an effort to stem the spread of the novel Coronavirus (Covid-19), however the impact of this confinement on health and behavior is unknown. Long-duration confinement studies have found effects on homeostatic biology and neurobehavioral functions, including reduced sleep durations. This study evaluated how confinement due to Covid-19 has impacted health and stress through changes in sleep. Methods The Anonymous Survey on Confinement during the COVID-19 Pandemic was available online to any individual ≥18 years of age through the Penn Medicine Clinical Research webpage on May 14, 2020 and the data presented are through October 24, 2020. The survey collected self-reported information on demographics, the amount and quality of sleep, as well as ratings of health and stress. To determine the impact of confinement on these domains, participants were asked to answer questions relative to pre-confinement levels. To test associations between sleep amounts and sleep quality on health and stress, generalized linear models were used and adjusted for age, sex, and race. Results N=228 participants (n=180 female [79.0%]) were on average 45.0±17.1 years of age. During confinement relative to pre-confinement, 41.7% of participants reported sleeping more, 37.3% reported sleeping the same amount, and 21.0% reported less sleep, while 14.0% reported better sleep quality, 47.4% the same, and 38.6% worse quality of sleep relative to pre-confinement. Ratings of worse health during confinement were associated with both reduced sleep amount (β=0.695; P Conclusion The confinement resulting from the COVID-19 pandemic has impacted the amount and quality of sleep and good sleep may help to reduce stress and maintain health. These findings highlight the need to further examine how long-term confinement influences human health and behavior and warrant examining what factors or life-style behaviors promote resilience to the negative effects of confinement. Support (if any) CWJ supported by NHLBI NRSA (T32 HL007713).

Introduction Given the high prevalence and poor outcomes of insufficient child sleep, effective interventions for the pediatric primary care setting are needed. Collecting family perspectives on intervention strategies is critical to understand and enhance outcomes, particularly among children who do not experience improvements. This study examined variation in qualitative family sleep beliefs and behaviors by quantitative child sleep outcomes of a sleep extension intervention. Methods A total of 24 caregiver-child dyads (child age 9–12 years, M age 11.3 (SD:1.0) years; 46% male; 50% non-Latinx White; 29% Black) participated in a mobile health sleep extension intervention, between March-December 2019, and completed post-intervention semi-structured telephone interviews to solicit intervention perceptions. The intervention used a 25 factorial design consisting of sleep duration goals and weekly performance feedback, with random assignment to sleep health promotion messaging and financial incentive conditions. Sleep duration was assessed via Fitbit Flex 2 devices during 2-week baseline and 7-week intervention periods. We developed a codebook using a grounded theory approach and conducted coding in NVivo. We compared preliminary qualitative themes among children who showed a >=30-minute improvement in sleep duration (‘responders’) versus those who did not (‘non-responders’). Results Of the 24 dyads, 38% (N=9 dyads) were classified as non-responders. Preliminary qualitative themes included: family beliefs about sleep and electronics usage; the study impact on sleep behaviors; and an enhanced awareness of child sleep. Intervention responder and non-responder dyads similarly described family restrictions on evening electronics usage (e.g., electronic parental controls; physical removal of devices) to benefit child sleep. However, more children classified as intervention responders described the benefits of these restrictions and expressed beliefs about the negative impacts of electronics on sleep. Whereas caregivers of both responders and non-responders described efforts to remind their child to go to bed earlier during the intervention, caregivers in the responder group described being more focused on and active in child sleep extension strategies. These included setting bedtime reminders and adjusting family activities to ensure an extended sleep schedule. Conclusion Addressing caregiver-child beliefs about sleep behaviors and engagement in sleep extension strategies could augment sleep extension intervention outcomes in future research. Support (if any) K01HL123612 (JAM), CHOP (JAM), K23HD094905 (AAW)

STUDY OBJECTIVES Little is known about the effect of lead exposure on children's sleep. This study examined the association between blood lead levels (BLL) and sleep problems in a longitudinal study of children. SETTING Four community-based elementary schools in Jintan City, China. PARTICIPANTS 1,419 Chinese children. MEASUREMENT AND RESULTS BLL were measured when children were aged 3-5 y, and sleep was assessed at ages 9-13 y. Sleep was assessed by both parents' report, using the Children's Sleep Habits Questionnaire (CSHQ), and children's report, using an adolescent sleep questionnaire. A total of 665 children with complete data on BLL and sleep at both ages were included in the current study. Mean age of the sample at BLL assessment was 4.74 y (standard deviation [SD] = 0.89) and at sleep assessment was 11.05 y (SD = 0.88). Mean BLL was 6.26 μg/dL (SD = 2.54). There were significant positive correlations between BLL and 3 CSHQ subscales: Sleep onset delay (r = 0.113, P < 0.01), sleep duration (r = 0.139, P < 0.001), and night waking (r = 0.089, P < 0.05). Excessive daytime sleepiness (EDS) (26.1% versus 9.0%, P < 0.001) and use of sleeping pills (6.5% versus 1.8%, P = 0.03) were more prevalent in children BLL ≥ 10.0 μg/dL than in those children BLL < 10.0 μg/dL. After adjusting for demographics, BLL ≥ 10.0 μg/dL was significantly associated with increased risk for insomnia symptoms (odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.03-3.95) and EDS (OR = 2.90, 95% CI = 1.27-6.61). CONCLUSION The findings indicate that elevated blood lead levels in early childhood are associated with increased risk for sleep problems and excessive daytime sleepiness in later childhood.

Sleep restriction (SR) reliably increases caloric intake. It remains unknown whether such intake cumulatively increases with repeated SR exposures and is impacted by the number of intervening recovery sleep opportunities. Healthy adults (33.9 &plusmn, 8.9y, 17 women, Body Mass Index: 24.8 &plusmn, 3.6) participated in a laboratory protocol. N = 35 participants experienced two baseline nights (10 h time-in-bed (TIB)/night, 22:00&ndash, 08:00) followed by 10 SR nights (4 h TIB/night, 04:00&ndash, 08:00), which were divided into two exposures of five nights each and separated by one (n = 13), three (n = 12), or five (n = 10) recovery nights (12 h TIB/night, 10:00). Control participants (n = 10) were permitted 10 h TIB (22:00&ndash, 08:00) on all nights. Food and drink consumption were ad libitum and recorded daily. Compared to baseline, sleep-restricted participants increased daily caloric (+527 kcal) and saturated fat (+7 g) intake and decreased protein (&minus, 1.2% kcal) intake during both SR exposures, however, intake did not differ between exposures or recovery conditions. Similarly, although sleep-restricted participants exhibited substantial late-night caloric intake (671 kcal), such intake did not differ between exposures or recovery conditions. By contrast, control participants showed no changes in caloric intake across days. We found consistent caloric and macronutrient intake increases during two SR exposures despite varying intervening recovery nights. Thus, energy intake outcomes do not cumulatively increase with repeated restriction and are unaffected by recovery opportunities.

Introduction Chronic sleep restriction negatively effects working memory. Recovery sleep following sleep restriction partially restores working memory performance. This study examines the impact of chronic sleep restriction and subsequent recovery sleep dose on the N-Back Task (N-Back), a valid measure of working memory. Methods N=223 participants (29.9±6.9 years; 48.4% female), completed two baseline nights of 8h time in bed (TIB), followed by five nights of 4h TIB, and were then randomized to a sleep dose of 0, 2, 4, 6, 8, 10, or 12 h TIB. A subset of participants (n=73) were re-exposed to another five nights of 4h TIB. Participants completed the three versions of the N-Back (i.e. 1-Back, 2-Back, and B-back) every two hours during wakefulness and daily averages were computed. Mixed effects and linear regression models were used to assess the impact of sleep restriction and the sleep dose response on percent correct on the N-Back corrected for baseline. Results N=219 participants had valid working memory data. The 2-Back (β =-4.5%; P0.41). Conclusion These data indicate that working memory is adversely impacted by sleep restriction, and that sufficient recovery sleep, possibly across consecutive days, is necessary to maintain optimal working memory performance. Support Funded by National Institute of Health NIH R01NR004281 and National Space and Biomedical Research Institute NSRBI NCC 5–98

Introduction Locus coeruleus (LC) is the major source of norepinephrine (NE) in the brain, which plays a key role in maintaining arousal and alertness. Sleep loss significantly impairs arousal and alertness. However, it is unknown whether sleep loss disrupts LC integrity, which can be measured non-invasively by diffusion tensor imaging (DTI). In the current study, we used DTI to examine the effects of one night of acute total sleep deprivation (TSD) on fractional anisotropy (FA), an index reflecting fiber density, axonal diameter and myelination. Methods We analyzed DTI and psychomotor vigilance test (PVT) data from N=54 health adults (23 females, age range 21–50 years) from a well controlled in-laboratory sleep deprivation study. Participants were randomized to either a TSD condition (n=40) without sleep on night 2, or a control condition (n=14) with no sleep loss. Standard DTI scans were conducted on the morning of day 2 and day 3 between 0700h-1000h. The PVT reciprocal response time (RRT) was used to measure individual’s response speed at baseline without sleep loss. LC regions-of-interest (ROI) were defined by standard templates from Keren et al. (2009). Imaging data were analyzed using FSL toolbox. Results For the whole TSD group, no differences were found in the LC FA values before and after sleep deprivation (p > .2). However, when dividing the TSD group to a slow group and a fast group based on their baseline PVT response speed, significantly increased LC FA were found in the slow group (p = .007) but not in the fast group (p > .4). The PVT RRT negatively correlated with LC FA value changes after TSD (r = -.44, p = .004). No correlations were found between the PVT RRT and LC FA changes in the control group. Conclusion Our results showed that baseline vigilance response speed correlated with LC integrity change after sleep deprivation, with slower response exhibiting greater changes in LC integrity. These findings support the key role of LC-NE system in the regulation of alertness and arousal. Support Supported in part by NIH grants R01-HL102119, R01-MH107571, R21-AG051981. CTRC UL1RR024134, and P30-NS045839.

Introduction The locus coeruleus (LC) plays a key role in the regulation of arousal and autonomic function. Homeostatic sleep pressure refers to the drive for sleep that increases as a saturating exponential when we stay awake and decreases exponentially when we sleep. The current study used arterial spin labeling (ASL) functional magnetic resonance imaging (fMRI) to investigate the relationship between homeostatic sleep pressure (sleepiness) and LC activity during the psychomotor vigilance test (PVT). Methods We analyzed sleepiness and ASL imaging data from N=70 health adults (40 males, age range 21–50 years) who participated in a controlled in-laboratory sleep study. All participants were scanned at rest and during the PVT on the morning between 0700h-1000h after 9 hour time-in-bed (TIB) baseline sleep. LC regions-of-interest (ROI) were defined by standard templates from Keren et al. (2009). Sleepiness was assessed by the Karolinska Sleepiness Scale (KSS) every two hours from 10:30 am to 10:30 pm. Results Sleepiness scores gradually increased over wakefulness time and reached its peak in the evening at about 10:20pm. PVT-induced CBF changes did not correlate with sleepiness scores on the morning (p > 0.05), but showed significant negative correlations with sleepiness scores on later day when sleep pressure became higher, especially during the night-time (r = -0.41, p < 0.001). Specifically, LC CBF showed significant increases during the PVT scan as compared to the resting scan (p = 0.04) in individuals with less nigh-time sleepiness (KSS < 4), but no differences (p > 0.1) in individuals with greater nigh-time sleepiness (KSS ≥ 5). After controlling for age, gender, and total sleep time, PVT-induced regional CBF difference in the LC still negatively predicted sleepiness (β = -0.325, p = 0.005). Conclusion Our findings showed that individuals with greater LC CBF increases during the PVT were less sleepy during the night, supporting the key role of LC activity in promoting wakefulness and maintaining sleep homeostasis. PVT-induced LC activation may provide a non-invasive bio-marker of homeostatic sleep pressure in healthy adults. Support Supported in part by NIH grants R01-HL102119, R01-MH107571, R21-AG051981. CTRC UL1RR024134, and P30-NS045839.

Introduction Over half of school-aged children sleep insufficiently and sleep promoting interventions are urgently needed. To effectively promote pediatric sleep health, it is critical to obtain feedback from youth and their families about acceptable intervention strategies. This qualitative study examined perceptions about healthy sleep promotion in parent-child dyads participating in a mobile health sleep extension intervention. Methods A total of 26 parent-child dyads (child mean age 11 years, SD = 0.67; 46% non-Latinx White; 19% Black) participated in a mobile intervention to extend child sleep duration over 11 weeks (2-week baseline; 7-week intervention; 2-week follow-up). Participants wore a FitBit during the study, were provided with a sleep duration goal, and received general sleep health-promoting electronic messages using the University of Pennsylvania’s Way to Health platform. Following the intervention, parents and their children separately completed a semi-structured telephone interview to capture perceptions of the intervention strategies. Three coders developed a codebook using an inductive approach to identify emergent themes and conducted coding in NVivo. Results Emergent themes fell into domains of intervention acceptability/feasibility and barriers. Mobile messaging about the child’s sleep duration goal was well-received, although child participants in particular desired more personalized messaging, with sleep promotion targeted to their specific sleep habits. Parents and children both discussed ancillary benefits to intervention participation, including an enhanced focus on sleep. Barriers to sleep extension during the intervention and maintenance of any gains post-intervention were related to: competing child academic, social, and extracurricular demands; family factors (work schedules; family rules and norms); and the challenges of limiting ubiquitous electronic devices. Conclusion Despite high parent-child acceptability of a mobile child sleep extension intervention, individual and contextual barriers may limit long-term adherence. Tailoring healthy sleep messages to target these factors could improve sustained benefits to child sleep. Support Sleep Research Society Foundation and K23HD094905 (AAW); NIH/NCATS UL1TR001878 (JAM and DFD) and K01HL123612 (JAM).

Introduction Mood progressively deteriorates over consecutive days of sleep restriction. The neurobiological processes active during sleep that influence the risk of mood disturbance are unknown. This study investigated the relationships between physiological sleep parameters (i.e., slow-wave activity (SWA), slow-wave energy (SWE), rapid eye-movement (REM) sleep duration and latency), and self-reported measures of mood across sleep restriction. Methods N=181 healthy participants (48.1% female; 30±6.8 yrs) had valid polysomnography (PSG) and mood data. The study design included two baseline nights (8h time in bed [TIB]) followed by five nights of 4h TIB. PSG (EEG derivations C3-A2, Fz-A1, O2-A1) was collected on the second baseline night (B2), first night of 4h TIB (SR1), and the fifth night of 4h TIB (SR5). The Profile of Mood States was assayed on days following PSG. Power spectral analysis for SWE and SWA was conducted (delta power; band: 0.5-4.5 Hz). General linear regression models were used to independently assess the slope of SWE, SWA, percent REM of total sleep time (TST), and REM latency on mood disturbance across sleep restriction. Results At baseline, higher SWE (unadjusted; r=0.21; P=0.004) and SWA (unadjusted; r=0.19; P=0.007) were associated with greater mood disturbance; these relations were attenuated when adjusted for age and sex. No relation was found between mood and REM latency or REM percent of TST. The slope of mood disturbance from B2 to SR5 was associated with greater percentage increases in C3 SWA on SR5 relative to B2 (β=0.039; P=0.008); this association was not observed for SWE (β=-0.016; P=0.48). The slope of REM latency and REM percent of TST were not associated with the slope of mood disturbance. Conclusion Our results indicate that greater SWA due to sleep restriction was associated with greater mood disturbance, suggesting that less SWA may confer resilience to mood disturbances resulting from sleep restriction. Support This work was supported by National Institute of Health NIH R01NR004281 and National Space and Biomedical Research Institute NSRBI NCC 5-98.

Introduction Little is known about the impact of specific rotations on medical residents’ sleep. The purpose of this analysis was to examine the difference in sleep duration and alertness among internal-medicine resident interns during intensive care unit (ICU) compared to general medicine (GM) rotations. Methods This is a secondary report of a randomized non-inferiority trial of 63 United States internal-medicine residency programs. Programs were assigned to either standard duty-hour (80h workweek/16h shifts) or flexible (80h workweek/no shift-length limit) policies. Interns were followed for 2 weeks during either a GM or ICU rotation. The primary outcome was sleep duration/24h (actigraphy). Secondary outcomes were sleepiness (Karolinska Sleepiness Scale [KSS]) and alertness (number of Brief Psychomotor Vigilance Test [PVT-B] lapses). Data were averaged across days (thirteen 24-hour periods). Linear mixed-effect models with random program intercept were used to determine the association between each outcome by rotation, controlling for age, sex, and policy followed. Results N=386 interns were included (mean age 27.9±2.1y, 194 (50.3%) males), with n=261 (67.6%) in GM, and n=125 (32.4%) in ICU. Average sleep duration was 7.00±0.08h and 6.84±0.10h for GM and ICU respectively (p=.09; 95%CI -0.02;0.33h). Percent of days with self-reports of excessive sleepiness were significantly more likely for ICU vs GM from 12am-6am (ICU: 20.2%; GM: 12.5%) and 6am-12pm (ICU: 20.5%; GM: 14.3%). GM had significantly more days with no excessive sleepiness (GM: 40.5%; ICU: 28.1%). Average KSS was 4.8±0.1 for both GM and ICU (p=.60; 95%CI -0.18;0.32). Average number of PVT-B lapses were 5.5±0.5 and 5.7±0.7 for GM and ICU respectively (p=.83; 95%CI -1.48;1.18 lapses). There were no significant differences in PVT-B response speed or false starts between rotations. Conclusion Interns in ICU may experience more excessive sleepiness compared to GM interns, especially in early morning hours. However, sleep duration and alertness were not significantly different between rotations. Support Funded by the National Heart, Lung, and Blood Institute and American Council for Graduate Medical Education

Introduction Fatigue is one contributor to mood disturbance observed following sleep restriction; however, the contribution of other factors remains unclear. This study examined contributions to mood disturbance resulting from sleep restriction beyond that of fatigue, evaluated the benefit of recovery sleep, and assessed whether recovery sleep buffered the re-emergence of mood disturbance upon re-exposure to sleep restriction. Methods N=223 healthy participants (48% female; n=108) approximately 30-years-old (SD=6.89, range=22–45 years) completed two baseline nights of 8h time in bed (TIB), followed by five nights of 4h TIB, and were then then randomized to one of 7 sleep recovery opportunities (i.e., 0, 2, 4, 6, 8, 10, or 12 hours TIB). Following the sleep period, a subset of participants (n=72) were re-exposed to five consecutive nights of 4h TIB. The profile of mood states (POMS) was completed every 2h during wakefulness and daily averages were calculated. The POMS total mood disturbance (TMD) score without the fatigue subscale (i.e., mood disturbance = TMD - fatigue) was the primary outcome to isolate changes in mood disturbance beyond fatigue. Individual growth curve models were applied to the trajectory of mood disturbance. General linear models were used to evaluate the dose-response function of mood disturbance after recovery sleep. Results Mood disturbance (absent the POMS fatigue scale) increased with each day of sleep restriction (β=1.550 per day; P Conclusion The study findings suggest that fatigue is not the only contributor to mood disturbance following sleep restriction. Recovery sleep attenuates mood disturbance in a dose-dependent manner, albeit transiently. Candidate pathways linking sleep restriction and mood include the immune system and the dynamics of sleep physiology. Support This work was funded by National Institute of Health NIH R01NR004281 and National Space and Biomedical Research Institute NSRBI NCC 5–98.

IntroductionMedical trainees’ duty hours have received attention globally; restrictions in Europe, New Zealand and some Canadian provinces are much lower than the 80 hours per week enforced in USA. In USA, resident duty hours have been implemented without evidence simultaneously reflecting competing concerns about patient safety and physician education. The objective is to prospectively evaluate the implications of alternative resident duty hour rules for patient safety, trainee education and intern sleep and alertness.Methods and analysis63 US internal medicine training programmes were randomly assigned 1:1 to the 2011 Accreditation Council for Graduate Medical Education resident duty hour rules or to rules more flexible in intern shift length and number of hours off between shifts for academic year 2015–2016. The primary outcome is calculated for each programme as the difference in 30-day mortality rate among Medicare beneficiaries with any of several prespecified principal diagnoses in the intervention year minus 30-day mortality in the preintervention year among Medicare beneficiaries with any of several prespecified principal diagnoses. Additional safety outcomes include readmission rates, prolonged length of stay and costs. Measures derived from trainees’ and faculty responses to surveys and from time-motion studies of interns compare the educational experiences of residents. Measures derived from wrist actigraphy, subjective ratings and psychomotor vigilance testing compare the sleep and alertness of interns. Differences between duty hour groups in outcomes will be assessed by intention-to-treat analyses.Ethics and disseminationThe University of Pennsylvania Institutional Review Board (IRB) approved the protocol and served as the IRB of record for 40 programmes that agreed to sign an Institutional Affiliation Agreement. Twenty-three programmes opted for a local review process.Trial registration numberNCT02274818; Pre-results.

INTRODUCTION To date, 559 humans have been flown into space, but long-duration (>300 days) missions are rare (n = 8 total). Long-duration missions that will take humans to Mars and beyond are planned by public and private entities for the 2020s and 2030s; therefore, comprehensive studies are needed now to assess the impact of long-duration spaceflight on the human body, brain, and overall physiology. The space environment is made harsh and challenging by multiple factors, including confinement, isolation, and exposure to environmental stressors such as microgravity, radiation, and noise. The selection of one of a pair of monozygotic (identical) twin astronauts for NASA’s first 1-year mission enabled us to compare the impact of the spaceflight environment on one twin to the simultaneous impact of the Earth environment on a genetically matched subject. RATIONALE The known impacts of the spaceflight environment on human health and performance, physiology, and cellular and molecular processes are numerous and include bone density loss, effects on cognitive performance, microbial shifts, and alterations in gene regulation. However, previous studies collected very limited data, did not integrate simultaneous effects on multiple systems and data types in the same subject, or were restricted to 6-month missions. Measurement of the same variables in an astronaut on a year-long mission and in his Earth-bound twin indicated the biological measures that might be used to determine the effects of spaceflight. Presented here is an integrated longitudinal, multidimensional description of the effects of a 340-day mission onboard the International Space Station. RESULTS Physiological, telomeric, transcriptomic, epigenetic, proteomic, metabolomic, immune, microbiomic, cardiovascular, vision-related, and cognitive data were collected over 25 months. Some biological functions were not significantly affected by spaceflight, including the immune response (T cell receptor repertoire) to the first test of a vaccination in flight. However, significant changes in multiple data types were observed in association with the spaceflight period; the majority of these eventually returned to a preflight state within the time period of the study. These included changes in telomere length, gene regulation measured in both epigenetic and transcriptional data, gut microbiome composition, body weight, carotid artery dimensions, subfoveal choroidal thickness and peripapillary total retinal thickness, and serum metabolites. In addition, some factors were significantly affected by the stress of returning to Earth, including inflammation cytokines and immune response gene networks, as well as cognitive performance. For a few measures, persistent changes were observed even after 6 months on Earth, including some genes’ expression levels, increased DNA damage from chromosomal inversions, increased numbers of short telomeres, and attenuated cognitive function. CONCLUSION Given that the majority of the biological and human health variables remained stable, or returned to baseline, after a 340-day space mission, these data suggest that human health can be mostly sustained over this duration of spaceflight. The persistence of the molecular changes (e.g., gene expression) and the extrapolation of the identified risk factors for longer missions (>1 year) remain estimates and should be demonstrated with these measures in future astronauts. Finally, changes described in this study highlight pathways and mechanisms that may be vulnerable to spaceflight and may require safeguards for longer space missions; thus, they serve as a guide for targeted countermeasures or monitoring during future missions.

Microgravity and elevated levels of CO

The high prevalence of chronic insufficient sleep in the population has been a concern due to the associated health and safety risks. We evaluated secular trends in sleep duration over the most recent 14-year period.The American Time Use Survey, representative of US residents ≥15 years, was used to investigate trends in self-reported sleep duration and waking activities for the period 2003-2016 (N = 181335 respondents).Sleep duration increased across survey years both on weekdays (+1.40 min/year) and weekends (+0.83 min/year, both p.0001, adjusted models). This trend was observed in students, employed respondents, and retirees, but not in those unemployed or not in the labor force. On workdays, the prevalence of short (≤7 hr), average (7-9 hr), and long (9 hr) sleep changed by -0.44% per year (p.0001), -0.03% per year (p = .5515), and +0.48% per year (p.0001), respectively. The change in sleep duration was predominantly explained by respondents retiring earlier in the evening. The percentage of respondents who watched TV or read before bed-two prominent waking activities competing with sleep-decreased over the same time period, suggesting that portions of the population are increasingly willing to trade time in leisure activities for more sleep. The results also suggest that increasing online opportunities to work, learn, bank, shop, and perform administrative tasks from home freed up time that likely contributed to increased sleep duration.The findings indicate first successes in the fight against sleep deficiency. Public health consequences of the observed increase in the prevalence of long sleep remain unclear and warrant further investigation.

Objective Short sleep duration is a significant risk factor for weight gain, particularly in African Americans and men. Increased caloric intake underlies this relationship, but it remains unclear whether decreased energy expenditure is a contributory factor. The current study assessed the impact of sleep restriction and recovery sleep on energy expenditure in African American and Caucasian men and women. Methods Healthy adults participated in a controlled laboratory study. After two baseline sleep nights, subjects were randomized to an experimental (n = 36; 4 h sleep/night for five nights followed by one night with 12 h recovery sleep) or control condition (n = 11; 10 h sleep/night). Resting metabolic rate and respiratory quotient were measured using indirect calorimetry in the morning after overnight fasting. Results Resting metabolic rate—the largest component of energy expenditure—decreased after sleep restriction (−2.6%, P = 0.032) and returned to baseline levels after recovery sleep. No changes in resting metabolic rate were observed in control subjects. Relative to Caucasians (n = 14), African Americans (n = 22) exhibited comparable daily caloric intake but a lower resting metabolic rate (P = 0.043) and higher respiratory quotient (P = 0.013) regardless of sleep duration. Conclusions Sleep restriction decreased morning resting metabolic rate in healthy adults, suggesting that sleep loss leads to metabolic changes aimed at conserving energy.

BACKGROUND: Sustained high-level cognitive performance is of paramount importance for the success of space missions, which involve environmental, physiological, and psychological stressors that may aff ect brain functions. Despite subjective symptom reports of cognitive fl uctuations in spacefl ight, the nature of neurobehavioral functioning in space has not been clarifi ed. METHODS: We developed a computerized cognitive test battery ( Cognition ) that has sensitivity to multiple cognitive domains and was specifi cally designed for the high-performing astronaut population. Cognition consists of 15 unique forms of 10 neuropsychological tests that cover a range of cognitive domains, including emotion processing, spatial orientation, and risk decision making. Cognition is based on tests known to engage specifi c brain regions as evidenced by functional neuroimaging. Here we describe the fi rst normative and acute total sleep deprivation data on the Cognition test battery as well as several eff orts underway to establish the validity, sensitivity, feasibility, and acceptability of Cognition . RESULTS: Practice eff ects and test-retest variability diff ered substantially between the 10 Cognition tests, illustrating the importance of normative data that both refl ect practice eff ects and diff erences in stimulus set diffi culty in the population of interest. After one night without sleep, medium to large eff ect sizes were observed for 3 of the 10 tests addressing vigilant attention (Cohen ’ s d 5 1.00), cognitive throughput (d 5 0.68), and abstract reasoning (d 5 0.65). CONCLUSIONS: In addition to providing neuroimaging-based novel information on the eff ects of spacefl ight on a range of cognitive functions, Cognition will facilitate comparing the eff ects of ground-based analogues to spacefl ight, increase consistency across projects, and thus enable meta-analyses.

Accurately collected 24-hour urine collections are presumed to be valid for estimating salt intake in individuals. We performed 2 independent ultralong-term salt balance studies lasting 105 (4 men) and 205 (6 men) days in 10 men simulating a flight to Mars. We controlled dietary intake of all constituents for months at salt intakes of 12, 9, and 6 g/d and collected all urine. The subjects’ daily menus consisted of 27 279 individual servings, of which 83.0% were completely consumed, 16.5% completely rejected, and 0.5% incompletely consumed. Urinary recovery of dietary salt was 92% of recorded intake, indicating long-term steady-state sodium balance in both studies. Even at fixed salt intake, 24-hour urine collection for sodium excretion (UNaV) showed infradian rhythmicity. We defined a ±25 mmol deviation from the average difference between recorded sodium intake and UNaV as the prediction interval to accurately classify a 3-g difference in salt intake. Because of the biological variability in UNaV, only every other daily urine sample correctly classified a 3-g difference in salt intake (49%). By increasing the observations to 3 consecutive 24-hour collections and sodium intakes, classification accuracy improved to 75%. Collecting seven 24-hour urines and sodium intake samples improved classification accuracy to 92%. We conclude that single 24-hour urine collections at intakes ranging from 6 to 12 g salt per day were not suitable to detect a 3-g difference in individual salt intake. Repeated measurements of 24-hour UNaV improve precision. This knowledge could be relevant to patient care and the conduct of intervention trials.

The American Academy of Sleep Medicine and Sleep Research Society recently released a Consensus Statement regarding the recommended amount of sleep to promote optimal health in adults. This paper describes the methodology, background literature, voting process, and voting results for the consensus statement. In addition, we address important assumptions and challenges encountered during the consensus process. Finally, we outline future directions that will advance our understanding of sleep need and place sleep duration in the broader context of sleep health.

Study objectives Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. Methods The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity.

Study objectives Chronic sleep restriction is prevalent in the U.S. population and associated with increased morbidity and mortality. The primary reasons for reduced sleep are unknown. Using population data on time use, we sought to identify individual characteristics and behaviors associated with short sleep that could be targeted for intervention programs. Design Analysis of the American Time Use Survey (ATUS). Setting Cross-sectional annual survey conducted by the U.S. Bureau of Labor Statistics. Participants Representative cohort (N = 124,517) of Americans 15 years and older surveyed between 2003 and 2011. Interventions None. Measurements and results Telephone survey of activities over 24 hours. Relative to all other waking activities, paid work time was the primary waking activity exchanged for sleep. Time spent traveling, which included commuting to/ from work, and immediate pre- and post-sleep activities (socializing, grooming, watching TV) were also reciprocally related to sleep duration. With every hour that work or educational training started later in the morning, sleep time increased by approximately 20 minutes. Working multiple jobs was associated with the highest odds for sleeping ≤6 hours on weekdays (adjusted OR 1.61, 95% CI 1.44; 1.81). Self-employed respondents were less likely to be short sleepers compared to private sector employees (OR 0.83, 95% CI 0.72; 0.95). Sociodemographic characteristics associated with paid work (age 25-64, male sex, high income, and employment per se) were consistently associated with short sleep. Conclusions U.S. population time use survey findings suggest that interventions to increase sleep time should concentrate on delaying the morning start time of work and educational activities (or making them more flexible), increasing sleep opportunities, and shortening morning and evening commute times. Reducing the need for multiple jobs may increase sleep time, but economic disincentives from working fewer hours will need to be offset. Raising awareness of the importance of sufficient sleep for health and safety may be necessary to positively influence discretionary behaviors that reduce sleep time, including television viewing and morning grooming.

Study objectives The Psychomotor Vigilance Test (PVT) is reported to be free of practice effects that can otherwise confound the effects of sleep loss and circadian misalignment on performance. This differentiates the PVT from more complex cognitive tests. To the best of our knowledge, no study has systematically investigated practice effects on the PVT across multiple outcome domains, depending on administration interval, and in ecologically more valid settings. Methods We administered a validated 3-minute PVT (PVT-B) 16 times in 45 participants (23 male, mean ± SD age 32.6 ± 7.3 years, range 25-54 years) with administration intervals of ≥10 days, ≤5 days, or 4 times per day. We investigated linear and logarithmic trends across repeated administrations in 10 PVT-B outcome variables. Results The fastest 10% of response times (RT; plin = .0002), minimum RT (plog = .0010), and the slowest 10% of reciprocal RT (plog = .0124) increased while false starts (plog = 0.0050) decreased with repeated administration, collectively decreasing RT variability (plog = .0010) across administrations. However, the observed absolute changes were small (e.g., -0.03 false starts per administration, linear fit) and are probably irrelevant in practice. Test administration interval did not modify the effects of repeated administration on PVT-B performance (all p > .13 for interaction). Importantly, mean and median RT, response speed, and lapses, which are among the most frequently used PVT outcomes, did not change systematically with repeated administration. Conclusions PVT-B showed stable performance across repeated administrations. Combined with its high sensitivity, this corroborates the status of the PVT as the de facto gold standard measure of the neurobehavioral effects of sleep loss and circadian misalignment.

Background Neuropsychological changes that may occur due to the environmental and psychological stressors of prolonged spaceflight motivated the development of the Cognition Test Battery. The battery was designed to assess multiple domains of neurocognitive functions linked to specific brain systems. Tests included in Cognition have been validated, but not in high-performing samples comparable to astronauts, which is an essential step toward ensuring their usefulness in long-duration space missions. Methods We administered Cognition (on laptop and iPad) and the WinSCAT, counterbalanced for order and version, in a sample of 96 subjects (50% women; ages 25-56 yr) with at least a Master's degree in science, technology, engineering, or mathematics (STEM). We assessed the associations of age, sex, and administration device with neurocognitive performance, and compared the scores on the Cognition battery with those of WinSCAT. Confirmatory factor analysis compared the structure of the iPad and laptop administration methods using Wald tests. Results Age was associated with longer response times (mean β = 0.12) and less accurate (mean β = -0.12) performance, women had longer response times on psychomotor (β = 0.62), emotion recognition (β = 0.30), and visuo-spatial (β = 0.48) tasks, men outperformed women on matrix reasoning (β = -0.34), and performance on an iPad was generally faster (mean β = -0.55). The WinSCAT appeared heavily loaded with tasks requiring executive control, whereas Cognition assessed a larger variety of neurocognitive domains. Discussion Overall results supported the interpretation of Cognition scores as measuring their intended constructs in high performing astronaut analog samples.Moore TM, Basner M, Nasrini J, Hermosillo E, Kabadi S, Roalf DR, McGuire S, Ecker AJ, Ruparel K, Port AM, Jackson CT, Dinges DF, Gur RC. Validation of the Cognition Test Battery for spaceflight in a sample of highly educated adults. Aerosp Med Hum Perform. 2017; 88(10):937-946.

Study objectives Significant interindividual variability in sleepiness is observed in clinical populations with obstructive sleep apnea (OSA). This phenomenon is only partially explained by the apnea-hypopnea index (AHI). Understanding factors that lead to sleepiness is critical to effective management of patients with OSA. We examined demographic and other factors associated with sleepiness in OSA. Methods Prospective study of 283 patients with newly diagnosed OSA by polysomnography (AHI ≥ 5 per hour). Subjective sleepiness (Epworth Sleep Scale [ESS] ≥ 11) and objective sleepiness (psychomotor vigilance task [PVT] mean lapse ≥ 2) were assessed. Results Participants were classified into four groups (1: sleepy by ESS and PVT, 2: sleepy by PVT only, 3: sleepy by ESS only, and 4: nonsleepy reference group) and compared by generalized logit model. Shorter daily sleep duration by actigraphy and less morningness were associated with higher risk of sleepiness (Odds ratio [OR] = 0.52, 95% confidence interval [CI] 0.33-0.82 and OR = 0.89, CI 0.80-0.98, respectively). African-American race was associated with sleepiness (group 1, OR = 8.8, CI 2.8-27.3; group 2, OR = 16.6, CI 3.3-83.6; and group 3, OR = 3.3, CI 1.0-10.1). IL-6 level was higher in groups 1 and 3 (OR = 1.9, CI 1.0-3.4 and OR 2.0, CI 1.1-3.7, respectively). Conclusions African-American race, short sleep duration, chronotype, and increased proinflammatory cytokine IL-6 level were associated with sleepiness in OSA. These findings will inform future investigations determining mechanisms of sleepiness in OSA.

Study Objectives Fatigue from sleep loss is a risk to physician and patient safety, but objective data on physician sleep and alertness on different duty hour schedules is scarce. This study objectively quantified differences in sleep duration and alertness between medical interns working extended overnight shifts and residents not or rarely working extended overnight shifts. Methods Sleep-wake activity of 137 interns and 87 PGY-2/3 residents on 2-week Internal Medicine and Oncology rotations was assessed with wrist-actigraphy. Alertness was assessed daily with a brief Psychomotor Vigilance Test (PVT) and the Karolinska Sleepiness Scale. Results Interns averaged 6.93 hours (95% confidence interval [CI] 6.84-7.03 hours) sleep per 24 hours across shifts, significantly less than residents not working overnight shifts (7.18 hours, 95% CI 7.06-7.30 hours, p = .007). Interns obtained on average 2.19 hours (95% CI 2.02-2.36 hours) sleep during on-call nights (17.5% obtained no sleep). Alertness was significantly lower on mornings after on-call nights compared to regular shifts (p < .001). Naps between 9 am and 6 pm on the first day post-call were frequent (90.8%) and averaged 2.84 hours (95% CI 2.69-3.00 hours), but interns still slept 1.66 hours less per 24 hours (95% CI 1.56-1.76 hours) compared to regular shift days (p < .001). Sleep inertia significantly affected alertness in the 60 minutes after waking on-call. Conclusions Extended overnight shifts increase the likelihood of chronic sleep restriction in interns. Reduced levels of alertness after on-call nights need to be mitigated. A systematic comparison of sleep, alertness, and safety outcomes under current and past duty hour rules is encouraged.

Emily Carota Orne, wife of the late Martin T. Orne and his companion in research for almost 40 years, passed away on August 1, 2016, from amyotrophic lateral sclerosis.Emily Orne was born in Boston...

Sleep deprivation is associated with neurobehavioral deficits that include impairments in cognitive and psychomotor functions and alterations of mood. These effects appear to be due to instability of waking neurobiology resulting from sleep initiating systems when sleep drive is elevated. Attention, working memory, and divergent higher cognitive functions are particularly vulnerable to both total sleep deprivation and chronic partial sleep restriction. Few countermeasures to the neurobehavioral effects of sleep deprivation have been identified, and there is no substitute for sleep when it comes to stable wakefulness. Sleep duration is the best predictor of daily recovery of neurobehavioral functioning.

STUDY OBJECTIVES: Determine the effects of high versus moderate workload on sleep physiology and neurobehavioral measures, during sleep restriction (SR) and no sleep restriction (NSR) conditions. DESIGN: Ten-night experiment involving cognitive workload and SR manipulations. SETTING: Controlled laboratory environment. PARTICIPANTS: Sixty-three healthy adults (mean ± standard deviation: 33.2 ± 8.7 y; 29 females), age 22-50 y. INTERVENTIONS: Following three baseline 8 h time in bed (TIB) nights, subjects were randomized to one of four conditions: high cognitive workload (HW) + SR; moderate cognitive workload (MW) + SR; HW + NSR; or MW + NSR. SR entailed 5 consecutive nights at 4 h TIB; NSR entailed 5 consecutive nights at 8 h TIB. Subjects received three workload test sessions/day consisting of 15-min preworkload assessments, followed by a 60-min (MW) or 120-min (HW) workload manipulation comprised of visually based cognitive tasks, and concluding with 15-min of postworkload assessments. Experimental nights were followed by two 8-h TIB recovery sleep nights. Polysomnography was collected on baseline night 3, experimental nights 1, 4, and 5, and recovery night 1 using three channels (central, frontal, occipital [C3, Fz, O2]). MEASUREMENTS AND RESULTS: High workload, regardless of sleep duration, increased subjective fatigue and sleepiness (all P CONCLUSIONS: High cognitive workload delayed sleep onset, but it also promoted sleep homeostatic responses by increasing subjective fatigue and sleepiness, and producing a global sleep homeostatic response by reducing wake after sleep onset. When combined with sleep restriction, high workload increased local (occipital) sleep homeostasis, suggesting a use-dependent sleep response to visual work. We conclude that sleep restriction and cognitive workload interact to influence sleep homeostasis. CITATION: Goel N, Abe T, Braun ME, Dinges DF. Cognitive workload and sleep restriction interact to influence sleep homeostatic responses. SLEEP 2014;37(11):1745-1756. Language: en

BackgroundPatient safety and sleep experts advocate a protected sleep period for residents.ObjectiveWe examined whether interns scheduled for a protected sleep period during overnight call would have better end-of-rotation assessments of burnout, depression, and empathy scores compared with interns without protected sleep periods and whether the amount of sleep obtained during on call predicted end-of-rotation assessments.MethodsWe conducted a randomized, controlled trial with internal medicine interns at the Philadelphia Veterans Affairs Medical Center (PVAMC) and the Hospital of the University of Pennsylvania (HUP) in academic year 2009–2010. Four-week blocks were randomly assigned to either overnight call permitted under the 2003 duty hour standards or a protected sleep period from 12:30 am to 5:30 am. Participants wore wrist actigraphs. At the beginning and end of the rotations, they completed the Beck Depression Inventory (BDI-II), Maslach Burnout Inventory (MBI-HSS), and Interpersonal Reactivity Index (IRI).ResultsA total of 106 interns participated. There were no significant differences between groups in end-of-rotation BDI-II, MBI-HSS, or IRI scores at either location (P > .05). Amount of sleep while on call significantly predicted lower MBI-Emotional Exhaustion (P ConclusionsA protected sleep period produced few consistent improvements in depression, burnout, or empathy, although depression was already low at baseline. Possibly the amount of protected time was too small to affect these emotional states or sleep may not be directly related to these scores.

Maintaining human alertness and behavioral capability under conditions of sleep loss and circadian misalignment requires fatigue management technologies due to: (i) dynamic nonlinear modulation of performance capability by the interaction of sleep homeostatic drive and circadian regulation; (ii) large differences among people in neurobehavioral vulnerability to sleep loss; (iii) error in subjective estimates of fatigue on performance; and (iv) to inform people of the need for recovery sleep. Two promising areas of technology have emerged for managing fatigue risk in safety-sensitive occupations. The first involves preventing fatigue by optimizing work schedules using biomathematical models of performance changes associated with sleep homeostatic and circadian dynamics. Increasingly these mathematical models account for individual differences to achieve a more accurate estimate of the timing and magnitude of fatigue effects on individuals. The second area involves technologies for detecting transient fatigue from drowsiness. The Psychomotor Vigilance Test (PVT), which has been extensively validated to be sensitive to deficits in attention from sleep loss and circadian misalignment, is an example in this category. Two shorter-duration versions of the PVT recently have been developed for evaluating whether operators have sufficient behavioral alertness prior to or during work. Another example is online tracking the percent of slow eyelid closures (PERCLOS), which has been shown to reflect momentary fluctuations of vigilance. Technologies for predicting and detecting sleepiness/fatigue have the potential to predict and prevent operator errors and accidents in safety-sensitive occupations, as well as physiological and mental diseases due to inadequate sleep and circadian misalignment.

The success of interplanetary human spaceflight will depend on many factors, including the behavioral activity levels, sleep, and circadian timing of crews exposed to prolonged microgravity and confinement. To address the effects of the latter, we used a high-fidelity ground simulation of a Mars mission to objectively track sleep–wake dynamics in a multinational crew of six during 520 d of confined isolation. Measurements included continuous recordings of wrist actigraphy and light exposure (4.396 million min) and weekly computer-based neurobehavioral assessments ( n = 888) to identify changes in the crew's activity levels, sleep quantity and quality, sleep–wake periodicity, vigilance performance, and workload throughout the record-long 17 mo of mission confinement. Actigraphy revealed that crew sedentariness increased across the mission as evident in decreased waking movement (i.e., hypokinesis) and increased sleep and rest times. Light exposure decreased during the mission. The majority of crewmembers also experienced one or more disturbances of sleep quality, vigilance deficits, or altered sleep–wake periodicity and timing, suggesting inadequate circadian entrainment. The results point to the need to identify markers of differential vulnerability to hypokinesis and sleep–wake changes during the prolonged isolation of exploration spaceflight and the need to ensure maintenance of circadian entrainment, sleep quantity and quality, and optimal activity levels during exploration missions. Therefore, successful adaptation to such missions will require crew to transit in spacecraft and live in surface habitats that instantiate aspects of Earth's geophysical signals (appropriately timed light exposure, food intake, exercise) required for temporal organization and maintenance of human behavior.

Apnea-hypopnea index (AHI) is the primary measure used to confirm a diagnosis of obstructive sleep apnea (OSA). However, there may be significant night-to-night variability (NNV) in AHI, limiting the value of AHI in clinical decision-making related to OSA management. We examined short-term NNV in AHI and its predictors during home portable monitoring (PM).Single center prospective observational study of patients (n = 84) with newly diagnosed OSA by polysomnography (PSG) AHI ≥ 5/h. All participants underwent 2 to 8 consecutive nights of PM.Participants (n = 84) were middle-aged (47 ± 8.3 y, mean ± standard deviation; SD), including 28 women, with mean AHI on baseline PSG (AHIPSG) of 30.1 ± 31.8. Mean AHI on PM (AHIPM) was 27.4 ± 23.7. Intraclass correlation coefficient (ICC) for AHIPM in the entire sample was 0.73 (95% CI 0.66-0.8), indicating that 27% of the variability in AHIPM was due to intra-individual factors. Mild severity of OSA, defined by AHIPSG 5-15/h, was associated with higher NNV (likelihood ratio, -0.4 ± 0.14; p = 0.006) and absence of comorbidity showed a trend towards higher NNV (-0.54 ± 0.27, p = 0.05) on AHIPM.The intraindividual short-term NNV in AHIPM is higher in mild versus moderately severe OSA, even in the home setting, where first-night effect is not expected. Larger studies of NNV focused on patients with mild OSA are needed to identify characteristics that predict need and timing for repeated diagnostic testing and treatment.A commentary on this article appears in this issue on page 787.

Suicide is a major public health problem and the 10th leading cause of death in the United States. The identification of modifiable risk factors is essential for reducing the prevalence of suicide. Recently, it has been shown that insomnia and nightmares significantly increase the risk for suicidal ideation, attempted suicide, and death by suicide. While both forms of sleep disturbance may independently confer risk, and potentially be modifiable risk factors, it is also possible that simply being awake at night represents a specific vulnerability for suicide. The present analysis evaluates the frequency of completed suicide per hour while taking into account the percentage of individuals awake at each hour.Archival analyses were conducted estimating the time of fatal injury using the National Violent Death Reporting System for 2003-2010 and the proportion of the American population awake per hour across the 24-hour day using the American Time Use Survey.The mean ± SD incident rate from 06:00-23:59 was 2.2% ± 0.7%, while the mean ± SD incident rate from 00:00-05:59 was 10.3% ± 4.9%. The maximum incident rate was from 02:00-02:59 (16.3%). Hour-by-hour observed values differed from those that would be expected by chance (P.001), and when 6-hour blocks were examined, the observed frequency at night was 3.6 times higher than would be expected by chance (P.001).Being awake at night confers greater risk for suicide than being awake at other times of the day, suggesting that disturbances of sleep or circadian neurobiology may potentiate suicide risk.