Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults.

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Prevailing patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, international standard provides a SI-compliant way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, based on an expert scientific consensus and expressed in an easily measured quantity (melanopic equivalent daylight illuminance (melaponic EDI)) defined within this standard. The recommendations are supported by detailed analysis of the sensitivity of human circadian, neuroendocrine, and alerting responses to ocular light and provide a straightforward framework to inform lighting design and practice.

The spectral sensitivity of human circadian phase resetting and melatonin suppression to light changes dynamically with light duration.

Human circadian, neuroendocrine, and neurobehavioral responses to light are mediated primarily by melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs) but they also receive input from visual photoreceptors. Relative photoreceptor contributions are irradiance- and duration-dependent but results for long-duration light exposures are limited. We constructed irradiance-response curves and action spectra for melatonin suppression and circadian resetting responses in participants exposed to 6.5-h monochromatic 420, 460, 480, 507, 555, or 620 nm light exposures initiated near the onset of nocturnal melatonin secretion. Melatonin suppression and phase resetting action spectra were best fit by a single-opsin template with lambdamax at 481 and 483 nm, respectively. Linear combinations of melanopsin (ipRGC), short-wavelength (S) cone, and combined long- and medium-wavelength (L+M) cone functions were also fit and compared. For melatonin suppression, lambdamax was 441 nm in the first quarter of the 6.5-h exposure with a second peak at 550 nm, suggesting strong initial S and L+M cone contribution. This contribution decayed over time; lambdamax was 485 nm in the final quarter of light exposure, consistent with a predominant melanopsin contribution. Similarly, for circadian resetting, lambdamax ranged from 445 nm (all three functions) to 487 nm (L+M-cone and melanopsin functions only), suggesting significant S-cone contribution, consistent with recent model findings that the first few minutes of a light exposure drive the majority of the phase resetting response. These findings suggest a possible initial strong cone contribution in driving melatonin suppression and phase resetting, followed by a dominant melanopsin contribution over longer duration light exposures.

Effect on Patient Safety of a Resident Physician Schedule without 24-Hour Shifts.

BACKGROUND: The effects on patient safety of eliminating extended-duration work shifts for resident physicians remain controversial. METHODS: We conducted a multicenter, cluster-randomized, crossover trial comparing two schedules for pediatric resident physicians during their intensive care unit (ICU) rotations: extended-duration work schedules that included shifts of 24 hours or more (control schedules) and schedules that eliminated extended shifts and cycled resident physicians through day and night shifts of 16 hours or less (intervention schedules). The primary outcome was serious medical errors made by resident physicians, assessed by intensive surveillance, including direct observation and chart review. RESULTS: The characteristics of ICU patients during the two work schedules were similar, but resident physician workload, described as the mean (±SD) number of ICU patients per resident physician, was higher during the intervention schedules than during the control schedules (8.8±2.8 vs. 6.7±2.2). Resident physicians made more serious errors during the intervention schedules than during the control schedules (97.1 vs. 79.0 per 1000 patient-days; relative risk, 1.53; 95% confidence interval [CI], 1.37 to 1.72; P<0.001). The number of serious errors unitwide were likewise higher during the intervention schedules (181.3 vs. 131.5 per 1000 patient-days; relative risk, 1.56; 95% CI, 1.43 to 1.71). There was wide variability among sites, however; errors were lower during intervention schedules than during control schedules at one site, rates were similar during the two schedules at two sites, and rates were higher during intervention schedules than during control schedules at three sites. In a secondary analysis that was adjusted for the number of patients per resident physician as a potential confounder, intervention schedules were no longer associated with an increase in errors. CONCLUSIONS: Contrary to our hypothesis, resident physicians who were randomly assigned to schedules that eliminated extended shifts made more serious errors than resident physicians assigned to schedules with extended shifts, although the effect varied by site. The number of ICU patients cared for by each resident physician was higher during schedules that eliminated extended shifts. (Funded by the National Heart, Lung, and Blood Institute; ROSTERS ClinicalTrials.gov number, NCT02134847.).

Perception of Local COVID-19 Transmission and Use of Preventive Behaviors Among Adults with Recent SARS-CoV-2 Infection - Illinois and Michigan, June 1-July 31, 2022.

During the early stages of the COVID-19 pandemic, use of preventive behaviors was associated with perceived risk for contracting SARS-CoV-2 infection (1,2). Over time, perceived risk has declined along with waning COVID-19-related media coverage (3,4). The extent to which communities continue to be aware of local COVID-19 transmission levels and are implementing recommended preventive behaviors is unknown. During June 1-July 31, 2022, health departments in DuPage County, Illinois and metropolitan Detroit, Michigan surveyed a combined total of 4,934 adults who had received a positive test result for SARS-CoV-2 during the preceding 3 weeks. The association between awareness of local COVID-19 transmission and use of preventive behaviors and practices was assessed, both in response to perceived local COVID-19 transmission levels and specifically during the 2 weeks preceding SARS-CoV-2 testing. Both areas had experienced sustained high COVID-19 transmission during the study interval as categorized by CDC COVID-19 transmission levels.* Overall, 702 (14%) respondents perceived local COVID-19 transmission levels as high, 987 (20%) as substantial, 1,902 (39%) as moderate, and 581 (12%) as low; 789 (16%) reported they did not know. Adjusting for geographic area, age, gender identity, and combined race and ethnicity, respondents who perceived local COVID-19 transmission levels as high were more likely to report having made behavioral changes because of the level of COVID-19 transmission in their area, including wearing a mask in public, limiting travel, and avoiding crowded places or events. Continued monitoring of public perceptions of local COVID-19 levels and developing a better understanding of their influence on the use of preventive behaviors can guide COVID-19 communication strategies and policy making during and beyond the pandemic.

High dose melatonin increases sleep duration during nighttime and daytime sleep episodes in older adults.

Aging is associated with changes in sleep, and improving sleep may have important consequences for the health, cognition, and quality of life of older adults. Many prescription sleep aids increase the risk of nighttime falls, have adverse effects on next-day cognition, and are associated with increased mortality. Melatonin, a hormone secreted at night, increases sleep duration in young adults but only when administered during the day when endogenous levels are low. In a month-long cross-over study, we randomized 24 healthy older (age >55, mean 64.2 ± 6.3 years) participants to receive 2 weeks of placebo and 2 weeks of either a low (0.3 mg) or high (5.0 mg) dose of melatonin 30 min before lights out. Sleep was polysomnographically recorded and was scheduled during both the biological day and night using a forced desynchrony design. Although 0.3 mg melatonin had a trend towards increasing sleep efficiency (SE) overall, this was due to its effects on sleep during the biological day. In contrast, 5 mg melatonin significantly increased SE during both biological day and night, mainly by increasing the duration of Stage 2 non-rapid eye movement sleep and slightly shortening awakenings. Melatonin should be further explored as a sleep aid for older adults.

Dynamic lighting schedules to facilitate circadian adaptation to shifted timing of sleep and wake.

Circadian adaptation to shifted sleep/wake schedules may be facilitated by optimizing the timing, intensity and spectral characteristics of light exposure, which is the principal time cue for mammalian circadian pacemaker, and possibly by strategically timing nonphotic time cues such as exercise. Therefore, circadian phase resetting by light and exercise was assessed in 44 healthy participants (22 females, mean age [±SD] 36.2 ± 9.2 years), who completed 8-day inpatient experiments simulating night shiftwork, which included either an 8 h advance or 8 h delay in sleep/wake schedules. In the advance protocol (n = 18), schedules were shifted either gradually (1.6 h/day across 5 days) or abruptly (slam shift, 8 h in 1 day and maintained across 5 days). Both advance protocols included a dynamic lighting schedule (DLS) with 6.5 h exposure of blue-enriched white light (704 melanopic equivalent daylight illuminance [melEDI] lux) during the day and dimmer blue-depleted light (26 melEDI lux) for 2 h immediately before sleep on the shifted schedule. In the delay protocol (n = 26), schedules were only abruptly delayed but included four different lighting conditions: (1) 8 h continuous room-light control; (2) 8 h continuous blue-enriched light; (3) intermittent (7 × 15 min pulses/8 h) blue-enriched light; (4) 8 h continuous blue-enriched light plus moderate intensity exercise. In the room-light control, participants received dimmer white light for 30 min before bedtime, whereas in the other three delay protocols participants received dimmer blue-depleted light for 30 min before bedtime. Both the slam and gradual advance protocols induced similar shifts in circadian phase (3.28 h ± 0.37 vs. 2.88 h ± 0.31, respectively, p = .43) estimated by the change in the timing of timing of dim light melatonin onset. In the delay protocol, the continuous 8 h blue-enriched exposure induced significantly larger shifts than the room light control (-6.59 h ± 0.43 vs. -4.74 h ± 0.62, respectively, p = .02). The intermittent exposure induced ~60% of the shift (-3.90 h ± 0.62) compared with 8 h blue-enriched continuous light with only 25% of the exposure duration. The addition of exercise to the 8 h continuous blue-enriched light did not result in significantly larger phase shifts (-6.59 h ± 0.43 vs. -6.41 h ± 0.69, p = .80). Collectively, our results demonstrate that, when attempting to adapt to an 8 h overnight work shift, delay shifts are more successful, particularly when accompanied by a DLS with high-melanopic irradiance light stimulus during wake.

Unanticipated daytime melatonin secretion on a simulated night shift schedule generates a distinctive 24-h melatonin rhythm with antiphasic daytime and nighttime peaks.

The daily rhythm of plasma melatonin concentrations is typically unimodal, with one broad peak during the circadian night and near-undetectable levels during the circadian day. Light at night acutely suppresses melatonin secretion and phase shifts its endogenous circadian rhythm. In contrast, exposure to darkness during the circadian day has not generally been reported to increase circulating melatonin concentrations acutely. Here, in a highly-controlled simulated night shift protocol with 12-h inverted behavioral/environmental cycles, we unexpectedly found that circulating melatonin levels were significantly increased during daytime sleep (p < .0001). This resulted in a secondary melatonin peak during the circadian day in addition to the primary peak during the circadian night, when sleep occurred during the circadian day following an overnight shift. This distinctive diurnal melatonin rhythm with antiphasic peaks could not be readily anticipated from the behavioral/environmental factors in the protocol (e.g., light exposure, posture, diet, activity) or from current mathematical model simulations of circadian pacemaker output. The observation, therefore, challenges our current understanding of underlying physiological mechanisms that regulate melatonin secretion. Interestingly, the increase in melatonin concentration observed during daytime sleep was positively correlated with the change in timing of melatonin nighttime peak (p = .002), but not with the degree of light-induced melatonin suppression during nighttime wakefulness (p = .92). Both the increase in daytime melatonin concentrations and the change in the timing of the nighttime peak became larger after repeated exposure to simulated night shifts (p = .002 and p = .006, respectively). Furthermore, we found that melatonin secretion during daytime sleep was positively associated with an increase in 24-h glucose and insulin levels during the night shift protocol (p = .014 and p = .027, respectively). Future studies are needed to elucidate the key factor(s) driving the unexpected daytime melatonin secretion and the melatonin rhythm with antiphasic peaks during shifted sleep/wake schedules, the underlying mechanisms of their relationship with glucose metabolism, and the relevance for diabetes risk among shift workers.

Effects of dynamic lighting on circadian phase, self-reported sleep and performance during a 45-day space analog mission with chronic variable sleep deficiency.

Spaceflight exposes crewmembers to circadian misalignment and sleep loss, which impair cognition and increase the risk of errors and accidents. We compared the effects of an experimental dynamic lighting schedule (DLS) with a standard static lighting schedule (SLS) on circadian phase, self-reported sleep and cognition during a 45-day simulated space mission. Sixteen participants (mean age [±SD] 37.4 ± 6.7 years; 5 F; n = 8/lighting condition) were studied in four-person teams at the NASA Human Exploration Research Analog. Participants were scheduled to sleep 8 h/night on two weekend nights, 5 h/night on five weekday nights, repeated for six 7-day cycles, with scheduled waketime fixed at 7:00 a.m. Compared to the SLS where illuminance and spectrum remained constant during wake (~4000K), DLS increased the illuminance and short-wavelength (blue) content of white light (~6000K) approximately threefold in the main workspace (Level 1), until 3 h before bedtime when illuminance was reduced by ~96% and the blue content also reduced throughout (~4000K × 2 h, ~3000K × 1 h) until bedtime. The average (±SE) urinary 6-sulphatoxymelatonin (aMT6s) acrophase time was significantly later in the SLS (6.22 ± 0.34 h) compared to the DLS (4.76 ± 0.53 h) and more variable in SLS compared to DLS (37.2 ± 3.6 min vs. 28.2 ± 2.4 min, respectively, p = .04). Compared to DLS, self-reported sleep was more frequently misaligned relative to circadian phase in SLS RR: 6.75, 95% CI 1.55-29.36, p = .01), but neither self-reported sleep duration nor latency to sleep was different between lighting conditions. Accuracy in the abstract matching and matrix reasoning tests were significantly better in DLS compared to SLS (false discovery rate-adjusted p ≤ .04). Overall, DLS alleviated the drift in circadian phase typically observed in space analog studies and reduced the prevalence of self-reported sleep episodes occurring at an adverse circadian phase. Our results support incorporating DLS in future missions, which may facilitate appropriate circadian alignment and reduce the risk of sleep disruption.

Exploratory assessment of pineal gland volume, composition, and urinary 6-sulfatoxymelatonin levels on prostate cancer risk.

INTRODUCTION: Melatonin levels are partially driven by the parenchyma volume of the pineal gland. Low urinary levels of 6-sulfatoxymelatonin have been associated with increased risk of advanced prostate cancer, but the relationship between pineal gland volume and composition and prostate cancer risk has not been examined. MATERIALS AND METHODS: We utilized data from 864 men from the AGES-Reykjavik Study with complete pineal gland volumes and urinary 6-sulfatoxymelatonin measurements. Pineal parenchyma, calcification, and cyst volumes were calculated from brain magnetic resonance imaging. Levels of 6-sulfatoxymelatonin were assayed from prediagnostic urine samples. We calculated Pearson correlation coefficients between parenchyma volume and urinary 6-sulfatoxymelatonin levels. We used Cox proportional hazards regression to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) comparing prostate cancer risk across parenchyma volume tertiles and across categories factoring in parenchyma volume, gland composition, and urinary 6-sulfatoxymelatonin level. RESULTS: Parenchyma volume was moderately correlated with urinary 6-sulfatoxymelatonin level (r = .24; p < .01). There was no statistically significant association between parenchyma volume tertile and prostate cancer risk. Men with high parenchyma volume, pineal cysts and calcifications, and low urinary 6-sulfatoxymelatonin levels had almost twice the risk of total prostate cancer as men with low parenchyma volume, no pineal calcifications or cysts, and low urinary 6-sulfatoxymelatonin levels (HR: 1.98; 95% CI: 1.02, 3.84; p: .04). CONCLUSIONS: Although parenchyma volume is not associated with prostate cancer risk, pineal gland composition and other circadian dynamics may influence risk for prostate cancer. Additional studies are needed to examine the interplay of pineal gland volume, composition, and melatonin levels on prostate cancer risk.

Mental Health and Substance Use Among Adults with Disabilities During the COVID-19 Pandemic - United States, February-March 2021.

Adults with disabilities, a group including >25% of U.S. adults (1), experience higher levels of mental health and substance use conditions and lower treatment rates than do adults without disabilities* (2,3). Survey data collected during April-September 2020 revealed elevated adverse mental health symptoms among adults with disabilities (4) compared with the general adult population (5). Despite disproportionate risk for infection with SARS-CoV-2, the virus that causes COVID-19, and COVID-19-associated hospitalization and mortality among some adults with disabilities (6), information about mental health and substance use in this population during the pandemic is limited. To identify factors associated with adverse mental health symptoms and substance use among adults with disabilities, the COVID-19 Outbreak Public Evaluation (COPE) Initiative† administered nonprobability-based Internet surveys to 5,256 U.S. adults during February-March 2021 (response rate = 62.1%). Among 5,119 respondents who completed a two-item disability screener, nearly one third (1,648; 32.2%) screened as adults with disabilities. These adults more frequently experienced symptoms of anxiety or depression (56.6% versus 28.7%, respectively), new or increased substance use (38.8% versus 17.5%), and suicidal ideation (30.6% versus 8.3%) than did adults without disabilities. Among all adults who had received a diagnosis of mental health or substance use conditions, adults with disabilities more frequently (42.6% versus 35.3%; p <0.001) reported that the pandemic made it harder for them to access related care or medication. Enhanced mental health and substance use screening among adults with disabilities and improved access to medical services are critical during public health emergencies such as the COVID-19 pandemic.

Health Care Access and Use Among Adults with Diabetes During the COVID-19 Pandemic - United States, February-March 2021.

Diabetes affects approximately one in 10 persons in the United States† and is a risk factor for severe COVID-19 (1), especially when a patient's diabetes is not well managed (2). The extent to which the COVID-19 pandemic has affected diabetes care and management, and whether this varies across age groups, is currently unknown. To evaluate access to and use of health care, as well as experiences, attitudes, and behaviors about COVID-19 prevention and vaccination, a nonprobability, Internet-based survey was administered to 5,261 U.S. adults aged ≥18 years during February-March 2021. Among respondents, 760 (14%) adults who reported having diabetes currently managed with medication were included in the analysis. Younger adults (aged 18-29 years) with diabetes were more likely to report having missed medical care during the past 3 months (87%; 79) than were those aged 30-59 years (63%; 372) or ≥60 years (26%; 309) (p<0.001). Overall, 44% of younger adults reported difficulty accessing diabetes medications. Younger adults with diabetes also reported lower intention to receive COVID-19 vaccination (66%) compared with adults aged ≥60 years§ (85%; p = 0.001). During the COVID-19 pandemic, efforts to enhance access to diabetes care for adults with diabetes and deliver public health messages emphasizing the importance of diabetes management and COVID-19 prevention, including vaccination, are warranted, especially in younger adults.

Mental Health Among Parents of Children Aged <18 Years and Unpaid Caregivers of Adults During the COVID-19 Pandemic - United States, December 2020 and February-⁠March 2021.

Early during the COVID-19 pandemic, nearly two thirds of unpaid caregivers of adults reported adverse mental or behavioral health symptoms, compared with approximately one third of noncaregivers† (1). In addition, 27% of parents of children aged <18 years reported that their mental health had worsened during the pandemic (2). To examine mental health during the COVID-19 pandemic among U.S. adults on the basis of their classification as having a parenting role (i.e., unpaid persons caring for children and adolescents aged <18 years, referred to as children in this report) or being an unpaid caregiver of adults (i.e., persons caring for adults aged ≥18 years),§ CDC analyzed data from cross-sectional surveys that were administered during December 2020 and February-March 2021 for The COVID-19 Outbreak Public Evaluation (COPE) Initiative.¶ Respondents were categorized as parents only, caregivers of adults only, parents-caregivers (persons in both roles), or nonparents/noncaregivers (persons in neither role). Adjusted odds ratios (aORs) for any adverse mental health symptoms, particularly suicidal ideation, were higher among all respondents who were parents, caregivers of adults, or both compared with respondents who were nonparents/noncaregivers and were highest among persons in both roles (parents-caregivers) (any adverse mental health symptoms: aOR = 5.1, 95% confidence interval [CI] = 4.1-6.2; serious suicidal ideation: aOR = 8.2, 95% CI = 6.5-10.4). These findings highlight that parents and caregivers, especially those balancing roles both as parents and caregivers, experienced higher levels of adverse mental health symptoms during the COVID-19 pandemic than adults without these responsibilities. Caregivers who had someone to rely on for support had lower odds of experiencing any adverse mental health symptoms. Additional measures are needed to improve mental health among parents, caregivers, and parents-caregivers.

Sleep difficulties, incident dementia and all-cause mortality among older adults across 8 years: Findings from the National Health and Aging Trends Study.

Sleep difficulties have been implicated in the development and progression of dementia and in all-cause mortality. This study examines the relationship between sleep difficulties, incident dementia and all-cause mortality over 8 years of follow-up among a nationally representative sample of older (≥65 years) adults in the United States. We used data collected from the National Health and Aging Trends Study (NHATS) from 2011 to 2018, a prospective cohort study of Medicare beneficiaries. At baseline, the NHATS sample comprised 6,376 older adults who were representative of 32 million older adults. Respondents reported routine difficulty initiating sleep or difficulty falling back asleep "most nights" or "every night" in each study year. In each year, dementia was determined by either self-reported diagnosis or performance on immediate and delayed recall word and clock drawing tests, whereas all-cause mortality was determined by proxy. We conducted Cox proportional hazards modelling, adjusting for age, sex, marital status and chronic conditions. In models predicting all-cause mortality, we also controlled for dementia. Among respondents at baseline, 19% were 65-75 years of age, 71% identified as non-Hispanic white and 59% were female. Difficulty initiating sleep (hazard ratio [HR], 1.49; 95% confidence interval [CI],1.25-1.77), difficulty falling back asleep (HR, = 1.39; 95% CI,1.14-1.70) and concurrent sleep difficulties (HR, 1.58; 95% CI, 1.25-1.99) were associated with greater risk of dementia. Difficulty initiating sleep (HR, 1.44; 95% CI,1.20-1.72), difficulty falling back asleep (HR, 1.56; 95% CI,1.29-1.89), and concurrent sleep difficulties (HR, 1.80; 95% CI, 1.44-2.24) were associated with greater risk of all-cause mortality. Our findings demonstrate that reported difficulties are prospectively associated with an increased risk of dementia and all-cause mortality among older people.

Interhemispheric sleep depth coherence predicts driving safety in sleep apnea.

Obstructive sleep apnea is associated with increased risk of car crashes; however, conventional measures of sleep apnea severity do not clearly identify those individuals who are at greatest risk. Here we tested whether, among individuals with sleep apnea, those with reduced interhemispheric sleep depth coherence, measured by correlation between right and left hemisphere odds ratio product, are at greater risk. The sample was derived from the Sleep Heart Health Study, a prospective observational cohort study, and included 1,378 adults with sleep apnea. The occurrence of a car crash was ascertained by a questionnaire administered 2 years after the sleep study, which asked about the occurrence of crashes during the year prior to questionnaire administration. We computed the sleep depth coherence from electroencephalograms recorded during baseline sleep studies and after 5 years. The weighted kappa coefficient and Bangdiwala's B were 0.34 and 0.59, respectively, indicating a fair to moderate stability over a 5-year interval. Multivariate logistic regression, adjusted for age, sex, race, body mass index and miles driven per year, was used to assess the risk of a car crash. Compared to the lowest quartile of sleep depth coherence (<0.86), individuals in the highest quartile (>0.93) had a 62% (95% confidence interval, 22%-81%) lower risk of an accident. Further adjustments for usual sleep duration and sleepiness did not meaningfully alter these findings. Higher interhemispheric sleep depth coherence is associated with significantly lower risk of motor vehicle crashes in individuals with sleep apnea. This suggests that high interhemispheric sleep depth coherence may be a marker of resistance to sleep apnea-related adverse neurocognitive outcomes.

Endogenous circadian regulation and phase resetting of clinical metabolic biomarkers.

Shiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40 hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8 hours sleep at night, four meals during a 16 hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n = 16 males, mean age ± SD = 23.4 ± 2.3 years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near-identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n = 25, 14 females, 36.3 ± 8.9 years) across four protocols; two with abrupt 8 hour delay shifts and exposure to either blue-enriched or standard white light; and either an abrupt or gradual 8 hour advance (1.6 hours/day over 5 days) both with exposure to blue-enriched white light. In the delay protocols, the cholesterol rhythm shifted later by -3.7 hours and -4.2 hours, respectively, compared to -6.6 hours and -4.7 hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1 hours) but not the gradual (+2.1 hours) protocol, compared to +3.1 hours and +2.8 hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.

Robust stability of melatonin circadian phase, sleep metrics, and chronotype across months in young adults living in real-world settings.

Appropriate synchronization of the timing of behaviors with the circadian clock and adequate sleep are both important for almost every physiological process. The timing of the circadian clock relative to social (ie, local) clock time and the timing of sleep can vary greatly among individuals. Whether the timing of these processes is stable within an individual is not well-understood. We examined the stability of circadian-controlled melatonin timing, sleep timing, and their interaction across ~ 100 days in 15 students at a single university. At three time points ~ 35-days apart, circadian timing was determined from the dim-light melatonin onset (DLMO). Sleep behaviors (timing and duration) and chronotype (ie, mid-sleep time on free days corrected for sleep loss on school/work days) were determined via actigraphy and analyzed in ~ 1-month bins. Melatonin timing was stable, with an almost perfect relationship strength as determined via intraclass correlation coefficients ([ICC]=0.85); average DLMO timing across all participants only changed from the first month by 21 minutes in month 2 and 5 minutes in month 3. Sleep behaviors also demonstrated high stability, with ICC relationship strengths ranging from substantial to almost perfect (ICCs = 0.65-0.85). Average DLMO was significantly associated with average chronotype (r2  = 0.53, P <.01), with chronotype displaying substantial stability across months (ICC = 0.61). These findings of a robust stability in melatonin timing and sleep behaviors in young adults living in real-world settings holds promise for a better understanding of the reliability of previous cross-sectional reports and for the future individualized strategies to combat circadian-associated disease and impaired safety (ie, "chronomedicine").

A classification approach to estimating human circadian phase under circadian alignment from actigraphy and photometry data.

The time of dim light melatonin onset (DLMO) is the gold standard for circadian phase assessment in humans, but collection of samples for DLMO is time and resource-intensive. Numerous studies have attempted to estimate circadian phase from actigraphy data, but most of these studies have involved individuals on controlled and stable sleep-wake schedules, with mean errors reported between 0.5 and 1 hour. We found that such algorithms are less successful in estimating DLMO in a population of college students with more irregular schedules: Mean errors in estimating the time of DLMO are approximately 1.5-1.6 hours. We reframed the problem as a classification problem and estimated whether an individual's current phase was before or after DLMO. Using a neural network, we found high classification accuracy of about 90%, which decreased the mean error in DLMO estimation-identifying the time at which the switch in classification occurs-to approximately 1.3 hours. To test whether this classification approach was valid when activity and circadian rhythms are decoupled, we applied the same neural network to data from inpatient forced desynchrony studies in which participants are scheduled to sleep and wake at all circadian phases (rather than their habitual schedules). In participants on forced desynchrony protocols, overall classification accuracy dropped to 55%-65% with a range of 20%-80% for a given day; this accuracy was highly dependent upon the phase angle (ie, time) between DLMO and sleep onset, with the highest accuracy at phase angles associated with nighttime sleep. Circadian patterns in activity, therefore, should be included when developing and testing actigraphy-based approaches to circadian phase estimation. Our novel algorithm may be a promising approach for estimating the onset of melatonin in some conditions and could be generalized to other hormones.

Early public adherence with and support for stay-at-home COVID-19 mitigation strategies despite adverse life impact: a transnational cross-sectional survey study in the United States and Australia.

BACKGROUND: Governments worldwide recommended unprecedented measures to contain the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As pressure mounted to scale back measures, understanding public priorities was critical. We assessed initial public adherence with and support for stay-at-home orders in nations and cities with different SARS-CoV-2 infection and COVID-19 death rates. METHODS: Cross-sectional surveys were administered to representative samples of adults aged ≥18 years from regions with different SARS-CoV-2 prevalences from April 2-8, 2020. Regions included two nations [the United States (US-high prevalence) and Australia (AU-low prevalence)] and two US cities [New York City (NY-high prevalence) and Los Angeles (LA-low prevalence)]. Regional SARS-CoV-2 and COVID-19 prevalence (cumulative SARS-CoV-2 infections, COVID-19 deaths) as of April 8, 2020: US (363,321, 10,845), AU (5956, 45), NY (81,803, 4571), LA (7530, 198). Of 8718 eligible potential respondents, 5573 (response rate, 63.9%) completed surveys. Median age was 47 years (range, 18-89); 3039 (54.5%) were female. RESULTS: Of 5573 total respondents, 4560 (81.8%) reported adherence with recommended quarantine or stay-at-home policies (range of samples, 75.5-88.2%). Additionally, 29.1% of respondents screened positive for anxiety or depression symptoms (range of samples, 28.6-32.0%), with higher prevalences among those of younger age, female gender, and those in quarantine or staying at home most of the time versus those who did not report these behaviours. Despite elevated prevalences of adverse mental health symptoms and significant life disruptions, 5022 respondents (90.1%) supported government-imposed stay-at-home orders (range of samples, 88.9-93.1%). Of these, 90.8% believed orders should last at least three more weeks or until public health or government officials recommended, with support spanning the political spectrum. CONCLUSIONS: Public adherence with COVID-19 mitigation policies was highly prevalent, in both highly-affected (US, NY) and minimally-affected regions (AU, LA). Despite disruption of respondents' lives, the vast majority supported continuation of extended stay-at-home orders. Despite common support, these two countries diverged in stringent mitigation implementation, which may have contributed to subsequent outcomes. These results reveal the importance of surveillance of public support for and adherence with such policies during the COVID-19 pandemic and for future infectious disease outbreaks.

Chronic sleep curtailment, even without extended (>16-h) wakefulness, degrades human vigilance performance.

Millions of individuals routinely remain awake for more than 18 h daily, which causes performance decrements. It is unknown if these functional impairments are the result of that extended wakefulness or from the associated shortened sleep durations. We therefore examined changes in objective reaction time performance and subjective alertness in a 32-d inpatient protocol in which participants were scheduled to wakefulness durations below 16 h while on a 20-h "day," with randomization into standard sleep:wake ratio (1:2) or chronic sleep restriction (CSR) ratio (1:3.3) conditions. This protocol allowed determination of the contribution of sleep deficiency independent of extended wakefulness, since individual episodes of wakefulness in the CSR condition were only 15.33 h in duration (less than the usual 16 h of wakefulness in a 24-h day) and sleep episodes were 4.67 h in duration each cycle. We found that chronic short sleep duration, even without extended wakefulness, doubled neurobehavioral reaction time performance and increased lapses of attention fivefold, yet did not uniformly decrease self-reported alertness. Further, these impairments in neurobehavioral performance were worsened during the circadian night and were not recovered during the circadian day, indicating that the deleterious effect from the homeostatic buildup of CSR is expressed even during the circadian promotion of daytime arousal. These findings reveal a fundamental aspect of human biology: Chronic insufficient sleep duration equivalent to 5.6 h of sleep opportunity per 24 h impairs neurobehavioral performance and self-assessment of alertness, even without extended wakefulness.

Estimated Sleep Duration Before and During the COVID-19 Pandemic in Major Metropolitan Areas on Different Continents: Observational Study of Smartphone App Data.

BACKGROUND: Amid the COVID-19 pandemic, public health policies to curb the spread of SARS-CoV-2 and its associated disease, COVID-19, have resulted in significant alterations to daily routines (eg, work-from-home policies) that may have enabled longer sleep duration among the general population. OBJECTIVE: We aimed to examine changes in estimated sleep duration in 5 major metropolitan areas before and after the start of the COVID-19 pandemic. METHODS: We conducted a prospective observational study using estimated sleep duration data obtained from a smartphone app. The data were obtained from regular users of the smartphone app before and after the World Health Organization declared COVID-19 a pandemic in March 2020. We compared within-subject estimated sleep duration before and during the COVID-19 pandemic using generalized linear mixed models. RESULTS: Among the 2,871,037 observations, 957,022 (33.3%) were from users in London; 549,151 (19.1%) were from users in Los Angeles; 846,527 (29.5%) were from users in New York City; 251,113 (8.7%) were from users in Seoul; and 267,224 (9.3%) were from users in Stockholm. The average age of the users in the sample was 35 years (SE 11 years). Prior to the COVID-19 pandemic, people residing in Seoul had the shortest estimated sleep duration (mean 6 hours 28 minutes, SE 11.6 minutes) and those residing in Stockholm had the longest estimated sleep duration (mean 7 hours 34 minutes, SE 9.9 minutes). The onset of the COVID-19 pandemic was associated with a 13.7 minute increase in estimated sleep duration when comparing March 2019 and March 2020 (95% CI 13.1-14.3, P<.001) and an increase of 22.3 minutes when comparing April 2019 and April 2020 (95% CI 21.5-23.1, P<.001). CONCLUSIONS: The average estimated sleep duration increased sharply in the months after the onset of the COVID-19 pandemic. This finding suggests that the implementation of COVID-19 mitigation strategies has provided people worldwide with increased opportunities to sleep, which may enhance the response of the immune system to viral pathogens.