The effect of a dynamic lighting schedule on neurobehavioral performance during a 45-day simulated space mission.

Study Objectives: We previously reported that during a 45-day simulated space mission, a dynamic lighting schedule (DLS) improved circadian phase alignment and performance assessed once on selected days. This study aimed to evaluate how DLS affected performance on a 5-minute psychomotor vigilance task (PVT) administered multiple times per day on selected days. Methods: Sixteen crewmembers (37.4 ±â€…6.7 years; 5F) underwent six cycles of 2 × 8-hour/night followed by 5 × 5-hour/night sleep opportunities. During the DLS (n = 8), daytime white light exposure was blue-enriched (~6000 K; Level 1: 1079, Level 2: 76 melanopic equivalent daytime illuminance (melEDI) lux) and blue-depleted (~3000-4000 K; L1: 21, L2: 2 melEDI lux) 3 hours before bed. In the standard lighting schedule (SLS; n = 8), lighting remained constant (~4500K; L1: 284, L2 62 melEDI lux). Effects of lighting condition (DLS/SLS), sleep condition (5/8 hours), time into mission, and their interactions, and time awake on PVT performance were analyzed using generalized linear mixed models. Results: The DLS was associated with fewer attentional lapses (reaction time [RT] > 500 milliseconds) compared to SLS. Lapses, mean RT, and 10% fastest/slowest RTs were worse following 5 compared to 8 hours of sleep but not between lighting conditions. There was an effect of time into mission on RTs, likely due to sleep loss. Overall performance differed by time of day, with longer RTs at the beginning and end of the day. There were more lapses and slower RTs in the afternoon in the SLS compared to the DLS condition. Conclusions: Future missions should incorporate DLS to enhance circadian alignment and performance. This paper is part of the Sleep and Circadian Rhythms: Management of Fatigue in Occupational Settings Collection.

Time of Day and Sleep Deprivation Effects on Risky Decision Making.

Previous research has revealed that daily variations in human neurobehavioral functions are driven in part by the endogenous circadian system. The objective of this study was to explore whether there exists a circadian influence on performance regarding a risky decision-making task and to determine whether the performance changes with sleep deprivation (SD). Thirteen participants underwent a 39 h constant routine (CR) protocol, during which they remained awake in constant conditions and performed the BART (balloon analogue risk task) every two hours. The mean pumps (gains) (p < 0.001) and balloons popped (losses) (p = 0.003) exhibited variation during the CR. The reaction time (RT) also showed significant variation across the CR (p < 0.001), with slower mean RTs in the morning hours following SD. A greater risk propensity was observed around midday before SD and a lower risk propensity after 29.5 h of being awake. The sensitivity to punishment varied during the CR, but did not follow a predictable trend. Further research using real monetary incentives and neurophysiological measures is warranted to elucidate these findings.

Predicting neurobehavioral performance of resident physicians in a Randomized Order Safety Trial Evaluating Resident-Physician Schedules (ROSTERS).

OBJECTIVES: Mathematical models of human neurobehavioral performance that include the effects of acute and chronic sleep restriction can be key tools in assessment and comparison of work schedules, allowing quantitative predictions of performance when empirical assessment is impractical. METHODS: Using such a model, we tested the hypothesis that resident physicians working an extended duration work roster, including 24-28 hours of continuous duty and up to 88 hours per week averaged over 4weeks, would have worse predicted performance than resident physicians working a rapidly cycling work roster intervention designed to reduce the duration of extended shifts. The performance metric used was attentional failures (ie, Psychomotor Vigilance Task lapses). Model input was 169 actual work and sleep schedules. Outcomes were predicted hours per week during work hours spent at moderate (equivalent to 16-20 hours of continuous wakefulness) or high (equivalent to ≥20 hours of continuous wakefulness) performance impairment. RESULTS: The model predicted that resident physicians working an extended duration work roster would spend significantly more time at moderate impairment (p = .02, effect size=0.2) than those working a rapidly cycling work roster; this difference was most pronounced during the circadian night (p < .001). On both schedules, performance was predicted to decline from weeks 1 + 2 to weeks 3 + 4 (p < .001), but the rate of decline was significantly greater on extended duration work roster (p < .01). Predicted performance impairment was inversely related to prior sleep duration (p < .001). CONCLUSIONS: These findings demonstrate the utility of a mathematical model to evaluate the predicted performance profile of schedules for resident physicians and others who experience chronic sleep restriction and circadian misalignment.

A pilot study of light exposure as a countermeasure for menstrual phase-dependent neurobehavioral performance impairment in women.

OBJECTIVE: To examine effects of menstrual phase and nighttime light exposure on subjective sleepiness and auditory Psychomotor Vigilance Task performance. METHODS: Twenty-nine premenopausal women (12 =Follicular; 17 =Luteal) completed a 6.5-hour nighttime monochromatic light exposure with varying wavelengths (420-620 nm) and irradiances (1.03-14.12 µW/cm2). Subjective sleepiness, reaction time, and attentional lapses were compared between menstrual phases in women with minimal (<33%) or substantial (≥33%) light-induced melatonin suppression. RESULTS: When melatonin was not suppressed, women in the follicular phase had significantly worse reaction time (mean difference=145.1 ms, 95% CI 51.8-238.3, p < .001, Cohen's D=1.9) and lapses (mean difference=12.9 lapses, 95% CI 4.37-21.41, p < .001, Cohen's D=1.7) compared to women in the luteal phase. When melatonin was suppressed, women in the follicular phase had significantly better reaction time (mean difference=152.1 ms, 95% CI 43.88-260.3, p < .001, Cohen's D=1.7) and lapses (mean difference=12.3 lapses, 95% CI 1.14-25.6, p < .01, Cohen's D=1.6) compared to when melatonin was not suppressed, such that their performance was not different (p > .9) from women in the luteal phase. Subjective sleepiness did not differ by menstrual phase (mean difference=0.6, p > .08) or melatonin suppression (mean difference=0.2, p > .4). CONCLUSIONS: Nighttime light exposure sufficient to suppress melatonin can also mitigate neurobehavioral performance deficits associated with the follicular phase. Despite the relatively small sample size, these data suggest that nighttime light may be a valuable strategy to help reduce errors and accidents in female shift workers.

Age-related changes in circadian regulation of the human plasma lipidome.

Aging alters the amplitude and phase of centrally regulated circadian rhythms. Here we evaluate whether peripheral circadian rhythmicity in the plasma lipidome is altered by aging through retrospective lipidomics analysis on plasma samples collected in 24 healthy individuals (9 females; mean ± SD age: 40.9 ± 18.2 years) including 12 younger (4 females, 23.5 ± 3.9 years) and 12 middle-aged older, (5 females, 58.3 ± 4.2 years) individuals every 3 h throughout a 27-h constant routine (CR) protocol, which allows separating evoked changes from endogenously generated oscillations in physiology. Cosinor regression shows circadian rhythmicity in 25% of lipids in both groups. On average, the older group has a ~14% lower amplitude and a ~2.1 h earlier acrophase of the lipid circadian rhythms (both, p ≤ 0.001). Additionally, more rhythmic circadian lipids have a significant linear component in addition to the sinusoidal across the 27-h CR in the older group (44/56) compared to the younger group (18/58, p < 0.0001). Results from individual-level data are consistent with group-average results. Results indicate that prevalence of endogenous circadian rhythms of the human plasma lipidome is preserved with healthy aging into middle-age, but significant changes in rhythmicity include a reduction in amplitude, earlier acrophase, and an altered temporal relationship between central and lipid rhythms.

Supplementation of ambient lighting with a task lamp improves daytime alertness and cognitive performance in sleep-restricted individuals.

STUDY OBJECTIVES: We examined the impact of adding a single-high-melanopic-illuminance task lamp in an otherwise low-melanopic-illuminance environment on alertness, neurobehavioral performance, learning, and mood during an 8-h simulated workday. METHODS: Sixteen healthy young adults [mean(±SD) age = 24.2 ± 2.9, 8F] participated in a 3-day inpatient study with two 8-h simulated workdays and were randomized to either ambient fluorescent room light (~30 melanopic EDI lux, 50 lux), or room light supplemented with a light emitting diode task lamp (~250 melanopic EDI lux, 210 lux) in a cross-over design. Alertness, mood, and cognitive performance were assessed throughout the light exposure and compared between conditions using linear mixed models. RESULTS: The primary outcome measure of percentage correct responses on the addition task was significantly improved relative to baseline in the supplemented condition (3.15% ± 1.18%), compared to the ambient conditions (0.93% ± 1.1%; FDR-adj q = 0.005). Additionally, reaction time and attentional failures on the psychomotor vigilance tasks were significantly improved with exposure to supplemented compared to ambient lighting (all, FDR-adj q ≤ 0.030). Furthermore, subjective measures of sleepiness, alertness, happiness, health, mood, and motivation were also significantly better in the supplemented, compared to ambient conditions (all, FDR-adj q ≤ 0.036). There was no difference in mood disturbance, affect, declarative memory, or motor learning between the conditions (all, FDR-adj q ≥ 0.308). CONCLUSIONS: Our results show that supplementing ambient lighting with a high-melanopic-illuminance task lamp can improve daytime alertness and cognition. Therefore, high-melanopic-illuminance task lighting may be effective when incorporated into existing suboptimal lighting environments. CLINICAL TRIALS: NCT04745312. Effect of Lighting Supplementation on Daytime Cognition. https://clinicaltrials.gov/ct2/show/NCT04745312.

Desynchronizing the sleep---wake cycle from circadian timing to assess their separate contributions to physiology and behaviour and to estimate intrinsic circadian period.

Circadian clocks drive cyclic variations in many aspects of physiology, but some daily variations are evoked by periodic changes in the environment or sleep-wake state and associated behaviors, such as changes in posture, light levels, fasting or eating, rest or activity and social interactions; thus, it is often important to quantify the relative contributions of these factors. Yet, circadian rhythms and these evoked effects cannot be separated under typical 24-h day conditions, because circadian phase and the length of time awake or asleep co-vary. Nathaniel Kleitman's forced desynchrony (FD) protocol was designed to assess endogenous circadian rhythmicity and to separate circadian from evoked components of daily rhythms in multiple parameters. Under FD protocol conditions, light intensity is kept low to minimize its impact on the circadian pacemaker, and participants have sleep-wake state and associated behaviors scheduled to an imposed non-24-h cycle. The period of this imposed cycle, Τ, is chosen so that the circadian pacemaker cannot entrain to it and therefore continues to oscillate at its intrinsic period (τ, ~24.15 h), ensuring circadian components are separated from evoked components of daily rhythms. Here we provide detailed instructions and troubleshooting techniques on how to design, implement and analyze the data from an FD protocol. We provide two procedures: one with general guidance for designing an FD study and another with more precise instructions for replicating one of our previous FD studies. We discuss estimating circadian parameters and quantifying the separate contributions of circadian rhythmicity and the sleep-wake cycle, including statistical analysis procedures and an R package for conducting the non-orthogonal spectral analysis method that enables an accurate estimation of period, amplitude and phase.

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.

Measuring Urinary 6-Sulphatoxymelatonin in Humans.

The pineal melatonin rhythm provides a robust reference signal for the timing of the endogenous human circadian system. The rhythm in the major urinary metabolite of melatonin, 6-sulphatoxymelatonin (aMT6s), is highly correlated with plasma melatonin and provides a noninvasive method to measure circadian phase, particularly in field-based studies. In this chapter, we describe the protocol for collecting urinary aMT6s and the method used to calculate the acrophase, or peak, time as a circadian phase marker.

Measuring Dim Light Melatonin Onset in Humans.

The pineal melatonin rhythm provides a robust reference signal for the timing of the endogenous human circadian system. Dim light melatonin onset (DLMO) time is considered a gold-standard marker of the central circadian clock when measured from plasma or saliva. In this chapter, we describe the appropriate conditions for collecting plasma and salivary melatonin and the threshold method to calculate the DLMO.

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.

Modeling (circadian).

In this chapter, we will discuss mathematical models of the master circadian rhythm in the suprachiasmatic nucleus of the hypothalamus with a particular emphasis on models that incorporate the effect of light on circadian phase resetting and melatonin suppression. We will show that limit cycle oscillators provide a better representation of the salient properties of the human circadian system than a sinusoid. We will then discuss how the phototransduction of light to the SCN has been incorporated in various models. Finally, we will introduce different theoretical and practical applications of these models and highlight areas for future model development.

Impact of Upgraded Lighting on Falls in Care Home Residents.

OBJECTIVES: Falls in care home residents have major health and economic implications. Given the impact of lighting on visual acuity, alertness, and sleep and their potential influence on falls, we aimed to assess the impact of upgraded lighting on the rate of falls in long-term care home residents. DESIGN: An observational study of 2 pairs of care homes (4 sites total). One site from each pair was selected for solid-state lighting upgrade, and the other site served as a control. SETTING AND PARTICIPANTS: Two pairs of care homes with 758 residents (126,479 resident-days; mean age (±SD) 81.0 ± 11.7 years; 57% female; 31% with dementia). METHODS: One "experimental" site from each pair had solid-state lighting installed throughout the facility that changed in intensity and spectrum to increase short-wavelength (blue light) exposure during the day (6 am-6 pm) and decrease it overnight (6 pm-6 am). The control sites retained standard lighting with no change in intensity or spectrum throughout the day. The number of falls aggregated from medical records were assessed over an approximately 24-month interval. The primary comparison between the sites was the rate of falls per 1000 resident-days. RESULTS: Before the lighting upgrade, the rate of falls was similar between experimental and control sites [6.94 vs 6.62 falls per 1000 resident-days, respectively; rate ratio (RR) 1.05; 95% CI 0.70-1.58; P = .82]. Following the upgrade, falls were reduced by 43% at experimental sites compared with control sites (4.82 vs 8.44 falls per 1000 resident-days, respectively; RR 0.57; 95% CI 0.39-0.84; P = .004). CONCLUSIONS AND IMPLICATIONS: Upgrading ambient lighting to incorporate higher intensity blue-enriched white light during the daytime and lower intensity overnight represents an effective, passive, low-cost, low-burden addition to current preventive strategies to reduce fall risk in long-term care settings.

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.

Circadian lipid and hepatic protein rhythms shift with a phase response curve different than melatonin.

While studies suggest that light and feeding patterns can reset circadian rhythms in various metabolites, whether these shifts follow a predictable pattern is unknown. We describe the first phase response curves (PRC) for lipids and hepatic proteins in response to combined light and food stimuli. The timing of plasma rhythms was assessed by constant routine before and after exposure to a combined 6.5-hour blue light exposure and standard meal schedule, which was systematically varied by ~20° between in0000dividuals. We find that the rhythms shift according to a PRC, with generally greater shifts for lipids and liver proteins than for melatonin. PRC timing varies relative to the stimulus, with albumin and triglyceride PRCs peaking at a time similar to melatonin whereas the cholesterol and high-density lipoprotein PRCs are offset by ~12 h. These data have important implications for treating circadian misalignment in shiftworkers who consume meals and are exposed to light around the clock.

Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients.

STUDY OBJECTIVES: To determine whether there was evidence of circadian or sleep-regulatory dysfunction in sighted individuals with non-24-hour sleep-wake rhythm disorder. METHODS: Three sighted individuals with signs and/or symptoms of non-24-hour sleep-wake rhythm disorder were studied. Thirty-five- to 332-day laboratory and home-based assessments of sleep-wake and circadian timing, endogenous circadian period, photic input to the circadian pacemaker, and/or circadian and sleep-wake-dependent regulation of sleep were conducted. RESULTS: No evidence of circadian dysfunction was found in these individuals. Instead, sleep-wake timing appeared to dissociate from the circadian timing system, and/or self-selected sleep-wake and associated light/dark timing shifted the circadian pacemaker later, rather than the circadian pacemaker determining sleep-wake timing. CONCLUSIONS: These findings suggest that the etiology of this disorder may be light- and/or behaviorally induced in some sighted people, which has implications for the successful treatment of this disorder. CITATION: Emens JS, St Hilaire MA, Klerman EB, et al. Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients. J Clin Sleep Med. 2022;18(2):453-459.

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.

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.

Extended Work Shifts and Neurobehavioral Performance in Resident-Physicians.

OBJECTIVES: Extended-duration work rosters (EDWRs) with shifts of 24+ hours impair performance compared with rapid cycling work rosters (RCWRs) that limit shifts to 16 hours in postgraduate year (PGY) 1 resident-physicians. We examined the impact of a RCWR on PGY 2 and PGY 3 resident-physicians. METHODS: Data from 294 resident-physicians were analyzed from a multicenter clinical trial of 6 US PICUs. Resident-physicians worked 4-week EDWRs with shifts of 24+ hours every third or fourth shift, or an RCWR in which most shifts were ≤16 consecutive hours. Participants completed a daily sleep and work log and the 10-minute Psychomotor Vigilance Task and Karolinska Sleepiness Scale 2 to 5 times per shift approximately once per week as operational demands allowed. RESULTS: Overall, the mean (± SE) number of attentional failures was significantly higher (P =.01) on the EDWR (6.8 ± 1.0) compared with RCWR (2.9 ± 0.7). Reaction time and subjective alertness were also significantly higher, by ∼18% and ∼9%, respectively (both P <.0001). These differences were sustained across the 4-week rotation. Moreover, attentional failures were associated with resident-physician-related serious medical errors (SMEs) (P =.04). Although a higher rate of SMEs was observed under the RCWR, after adjusting for workload, RCWR had a protective effect on the rate of SMEs (rate ratio 0.48 [95% confidence interval: 0.30-0.77]). CONCLUSIONS: Performance impairment due to EDWR is improved by limiting shift duration. These data and their correlation with SME rates highlight the impairment of neurobehavioral performance due to extended-duration shifts and have important implications for patient safety.