Dampened circadian amplitude of EEG power in women after menopause.

Postmenopausal women are at high risk of developing sleep-wake disturbances. We previously reported dampened circadian rhythms of melatonin, alertness and sleep in postmenopausal compared with young women. The present study aims to further explore electroencephalography power spectral changes in the sleep of postmenopausal women. Eight healthy postmenopausal women were compared with 12 healthy, naturally ovulating, young women in their mid-follicular phase. Participants followed a regular 8-hr sleep schedule for ≥ 2 weeks prior to laboratory entry. The laboratory visit included an 8-hr baseline sleep period followed by an ultradian sleep-wake cycle procedure, consisting of alternating 1-hr wake periods and nap opportunities. Electroencephalography power spectral analysis was performed on non-rapid eye movement sleep obtained over a 48-hr period. The baseline nocturnal sleep of postmenopausal women comprised lower power within delta and sigma, and higher power within alpha bands compared with that of younger women. During nighttime naps of the ultradian sleep-wake cycle procedure, lower power within delta and sigma, and higher power within beta bands were observed in postmenopausal women. During the ultradian sleep-wake cycle procedure, postmenopausal women presented lower power of delta, theta and sigma (14-15 Hz), undetectable rhythms of delta and theta, and a dampened or undetectable rhythm of sigma (12-15 Hz) power compared with younger women. Our results support the hypothesis of a dampened circadian variation of sleep microstructure in healthy-sleeping postmenopausal women. Circadian changes with aging are potential mechanisms for increased susceptibility to develop sleep disturbances; however, further research is needed to clarify their clinical implications and contribution to insomnia.

Metabolic and cardiovascular consequences of shift work: The role of circadian disruption and sleep disturbances.

Shift work, defined as work occurring outside typical daytime working hours, is associated with an increased risk of various non-communicable diseases, including diabetes and cardiovascular disease. Disruption of the internal circadian timing system and concomitant sleep disturbances is thought to play a critical role in the development of these health problems. Indeed, controlled laboratory studies have shown that short-term circadian misalignment and sleep restriction independently impair physiological processes, including insulin sensitivity, energy expenditure, immune function, blood pressure and cardiac modulation by the autonomous nervous system. If allowed to persist, these acute effects may lead to the development of cardiometabolic diseases in the long term. Here, we discuss the evidence for the contributions of circadian disruption and associated sleep disturbances to the risk of metabolic and cardiovascular health problems in shift workers. Improving the understanding of the physiological mechanisms affected by circadian misalignment and sleep disturbance will contribute to the development and implementation of strategies that prevent or mitigate the cardiometabolic impact of shift work.

Alternatives to polysomnography (PSG): a validation of wrist actigraphy and a partial-PSG system.

The objective of this study was to assess the validity of a sleep/wake activity monitor, an energy expenditure activity monitor, and a partial-polysomnography system at measuring sleep and wake under identical conditions. Secondary aims were to evaluate the sleep/wake thresholds for each activity monitor and to compare the three devices. To achieve these aims, two nights of sleep were recorded simultaneously with polysomnography (PSG), two activity monitors, and a partial-PSG system in a sleep laboratory. Agreement with PSG was evaluated epoch by epoch and with summary measures including total sleep time (TST) and wake after sleep onset (WASO). All of the devices had high agreement rates for identifying sleep and wake, but the partial-PSG system was the best, with an agreement of 91.6% ± 5.1%. At their best thresholds, the sleep/wake monitor (medium threshold, 87.7% ± 7.6%) and the energy expenditure monitor (very low threshold, 86.8% ± 8.6%) had similarly high rates of agreement. The summary measures were similar to those determined by PSG, but the partial-PSG system provided the most consistent estimates. Although the partial-PSG system was the most accurate device, both activity monitors were also valid for sleep estimation, provided that appropriate thresholds were selected. Each device has advantages, so the primary consideration for researchers will be to determine which best suits a given research design.

Circadian Adaptation of Melatonin and Cortisol in Police Officers Working Rotating Shifts.

Misalignment of behavior and circadian rhythms due to night work can impair sleep and waking function. While both simulated and field-based studies suggest that circadian adaptation to a nocturnal schedule is slow, the rates of adaptation in real-world shift-work conditions are still largely unknown. The aim of this study was to evaluate the extent of adaptation of 24-h rhythms with 6-sulfatoxymelatonin (aMT6s) and cortisol in police officers working rotating shifts, with a special attention to night shifts. A total of 76 police officers (20 women; aged 32 ± 5.4 years, mean ± SD) from the province of Quebec, Canada, participated in a field study during their 28- or 35-day work cycle. Urine samples were collected for ~32 h before a series of day, evening, and night shifts to assess circadian phase. Before day, evening, and night shifts, 60%-89% of officers were adapted to a day schedule based on aMT6 rhythms, and 71%-78% were adapted based on cortisol rhythms. To further quantify the rate of circadian adaptation to night shifts, initial and final phases were determined in a subset of 37 officers with suitable rhythms for both hormones before and after 3-8 consecutive shifts (median = 7). Data were analyzed with circular and linear mixed-effects models. After night shifts, 30% and 24% of officers were adapted to a night-oriented schedule for aMT6s and cortisol, respectively. Significantly larger phase-delay shifts (aMT6s: -7.3 ± 0.9 h; cortisol: -6.3 ± 0.8 h) were observed in police officers who adapted to night shifts than in non-adapted officers (aMT6s: 0.8 ± 0.9 h; cortisol: 0.2 ± 1.1 h). Consistent with prior research, our results from both urinary aMT6s and cortisol midpoints indicate that a large proportion of police officers remained in a state of circadian misalignment following a series of night shifts in dim-light working environments.

The circadian variation of sleep and alertness of postmenopausal women.

STUDY OBJECTIVES: Several factors may contribute to the high prevalence of sleep disturbances occurring in postmenopausal women. However, the contribution of the circadian timing system to their sleep disturbances remains unclear. In the present study, we aim to understand the impact of circadian factors on changes of sleep and alertness occurring after menopause. METHODS: Eight healthy postmenopausal women and 12 healthy young women in their mid-follicular phase participated in an ultradian sleep-wake cycle procedure (USW). This protocol consisted of alternating 60-min wake periods and nap opportunities for ≥ 48 h in controlled laboratory conditions. Core body temperature (CBT), salivary melatonin, self-reported alertness, and polysomnographically recorded sleep were measured across this procedure. RESULTS: In both groups, all measures displayed a circadian variation throughout the USW procedure. Compared to young women, postmenopausal women presented lower CBT values, more stage N1 and N2 sleep, and number of arousals. They also showed a reduced amplitude of the circadian variation of melatonin, total sleep time (TST), sleep onset latency (SOL), stage N3 sleep, and alertness levels. Postmenopausal women fell asleep faster and slept more during the biological day and presented higher alertness levels during the biological night than young women. CONCLUSION: These results support the hypothesis of a weakened circadian signal promoting sleep and wakefulness in older women. Aging processes including hormonal changes may be main contributors to the increased sleep-wake disturbances after menopause.

How Tired is Too Tired to Drive? A Systematic Review Assessing the Use of Prior Sleep Duration to Detect Driving Impairment.

Driver fatigue is a contributory factor in approximately 20% of vehicle crashes. While other causal factors (eg, drink-driving) have decreased in recent decades due to increased public education strategies and punitive measures, similar decreases have not been seen in fatigue-related crashes. Fatigued driving could be managed in a similar way to drink-driving, with an established point (ie, amount of prior sleep) after which drivers are "deemed impaired". This systematic review aimed to provide an evidence-base for the concept of deemed impairment and to identify how much prior sleep may be required to drive safely. Four online databases were searched (PubMed, Web of Science, Scopus, Embase). Eligibility requirements included a) measurement of prior sleep duration and b) driving performance indicators (eg, lane deviation) and/or outcomes (eg, crash likelihood). After screening 1940 unique records, a total of 61 studies were included. Included studies were categorised as having experimental/quasi-experimental (n = 21), naturalistic (n = 3), longitudinal (n = 1), case-control (n = 11), or cross-sectional (n = 25) designs. Findings suggest that after either 6 or 7 hours of prior sleep, a modest level of impairment is generally seen compared with after ≥ 8 hours of prior sleep (ie, well rested), depending on the test used. Crash likelihood appears to be ~30% greater after 6 or 7 hours of prior sleep, as compared to individuals who are well rested. After one night of either 4 or 5 hours of sleep, there are large decrements to driving performance and approximately double the likelihood of a crash when compared with well-rested individuals. When considering the scientific evidence, it appears that there is a notable decrease in driving performance (and associated increase in crash likelihood) when less than 5h prior sleep is obtained. This is a critical first step in establishing community standards regarding the amount of sleep required to drive safely.

Disturbance of the Circadian System in Shift Work and Its Health Impact.

The various non-standard schedules required of shift workers force abrupt changes in the timing of sleep and light-dark exposure. These changes result in disturbances of the endogenous circadian system and its misalignment with the environment. Simulated night-shift experiments and field-based studies with shift workers both indicate that the circadian system is resistant to adaptation from a day- to a night-oriented schedule, as determined by a lack of substantial phase shifts over multiple days in centrally controlled rhythms, such as those of melatonin and cortisol. There is evidence that disruption of the circadian system caused by night-shift work results not only in a misalignment between the circadian system and the external light-dark cycle, but also in a state of internal desynchronization between various levels of the circadian system. This is the case between rhythms controlled by the central circadian pacemaker and clock genes expression in tissues such as peripheral blood mononuclear cells, hair follicle cells, and oral mucosa cells. The disruptive effects of atypical work schedules extend beyond the expression profile of canonical circadian clock genes and affects other transcripts of the human genome. In general, after several days of living at night, most rhythmic transcripts in the human genome remain adjusted to a day-oriented schedule, with dampened group amplitudes. In contrast to circadian clock genes and rhythmic transcripts, metabolomics studies revealed that most metabolites shift by several hours when working nights, thus leading to their misalignment with the circadian system. Altogether, these circadian and sleep-wake disturbances emphasize the all-encompassing impact of night-shift work, and can contribute to the increased risk of various medical conditions. Here, we review the latest scientific evidence regarding the effects of atypical work schedules on the circadian system, sleep and alertness of shift-working populations, and discuss their potential clinical impacts.

Timing of Sleep in the Break Between Two Consecutive Night-Shifts: The Effect of Different Strategies on Daytime Sleep and Night-Time Neurobehavioural Function.

OBJECTIVE: The aim of this study was to examine whether the timing of sleep in the break between consecutive night-shifts affects the quantity and quality of sleep obtained during the daytime and/or neurobehavioural function and self-perceived capacity during the night-time. METHODS: Participants (n = 12, all male, aged 22.9±5.2 y) completed three randomised, counterbalanced conditions in a sleep laboratory, consisting of two consecutive 12-hour night-shifts (18:00-06:00) with 7 hours in bed in the break between shifts. The three conditions differed only in the timing of the sleep opportunities - immediate (07:00-14:00), delayed (10:00-17:00), split (07:00-10:30 and 13:30-17:00). Neurobehavioural function (attention, memory, throughput) and self-perceived capacity (sleepiness, alertness, fatigue, mood) were assessed at 2-hour intervals during the night-shifts. RESULTS: Condition did not affect total sleep time (p = 0.465), but it did affect sleep onset latency (p < 0.001; W = 0.780; large effect), wake after sleep onset (p = 0.018; W = 0.333; moderate effect) and the amount of Stage N3 sleep (p < 0.001; η2=0.510; small effect). Compared to the immediate and delayed sleep conditions, the split sleep condition had less wake after sleep onset and more Stage N3 sleep; and compared to the delayed condition, the split sleep condition had longer latency to sleep onset. There was no effect of condition on measures of neurobehavioural function or self-perceived capacity during the second night-shift. CONCLUSION: None of the three sleep strategies examined here - immediate, delayed or split - are clearly superior or inferior to the others in terms of the capacity to sleep during the daytime or to work at night. Therefore, those who work consecutive night-shifts should employ the strategy that best suits their personal preferences and/or circumstances.

Effects of Shift Work on the Eating Behavior of Police Officers on Patrol.

Recent studies indicate that the timing of food intake can significantly affect metabolism and weight management. Workers operating at atypical times of the 24-h day are at risk of disturbed feeding patterns. Given the increased risk of weight gain, obesity and metabolic syndrome in shift working populations, further research is required to understand whether their eating behavior could contribute to these increased metabolic risks. The objective of this study was to characterize the dietary patterns of police officers across different types of shifts in their natural environments. Thirty-one police officers (six women; aged 32.1 ± 5.4 years, mean ± SD) from the province of Quebec, Canada, participated in a 28- to 35-day study, comprising 9- to 12-h morning, evening, and night shifts alternating with rest days. Sleep and work patterns were recorded with actigraphy and diaries. For at least 24 h during each type of work day and rest day, participants logged nutrient intake by timestamped photographs on smartphones. Macronutrient composition and caloric content were estimated by registered dieticians using the Nutrition Data System for Research database. Data were analyzed with linear mixed effects models and circular ANOVA. More calories were consumed relative to individual metabolic requirements on rest days than both evening- and night-shift days (p = 0.001), largely sourced from increased fat (p = 0.004) and carbohydrate (trend, p = 0.064) intake. Regardless, the proportions of calories from carbohydrates, fat, and protein did not differ significantly between days. More calories were consumed during the night, between 2300 h and 0600 h, on night-shift days than any other days (p < 0.001). Caloric intake occurred significantly later for night-shift days (2308 h ± 0114 h, circular mean ± SD) than for rest days (1525 h ± 0029 h; p < 0.01) and was dispersed across a longer eating window (13.9 h ± 3.1 h vs. 11.3 h ± 1.8 h, mean ± SD). As macronutrient proportions were similar and caloric intake was lower, the finding of later meals times on night-shift days versus rest days is consistent with emerging hypotheses that implicate the biological timing of food intake-rather than its quantity or composition-as the differentiating dietary factor in shift worker health.

Do split sleep/wake schedules reduce or increase sleepiness for continuous operations?

This study compared the impact of split and consolidated sleep/wake schedules on subjective sleepiness during the biological day and biological night. This was achieved using a between-group design involving two forced desynchrony protocols: consolidated sleep/wake and split sleep/wake. Both protocols included 7×28-h days with 9.33h in bed and 18.67h of wake each day. While the consolidated sleep/wake protocol had 1×9.33-h sleep opportunity and 1×18.67-h wake period each day, the split sleep/wake protocol had 2×4.67-h sleep opportunities and 2×9.33-h wake periods each day. For both protocols, subjective sleepiness was measured using the Karolinska Sleepiness Scale every 2.5h during wake. A total of 29 healthy adult males participated, with 13 in the consolidated sleep/wake group (mean age=22.5 yrs) and 16 in the split sleep/wake group (mean age=22.6 yrs). On average, subjective sleepiness during wake periods of the split condition was significantly higher than that during the first half of wake periods of the consolidated condition, but was similar to the level during the second half. These findings were observed for wake periods that occurred during both the biological day and biological night. Previous data have shown that cognitive impairment at night is lower for split schedules than consolidated schedules, but the current data indicate that feelings of sleepiness are greater for split schedules than consolidated schedules for at least half of the time awake. Thus, it should be explained to people operating split sleep/wake schedules that although they may perform well, they are likely to feel sleepy.

Using interstimulus interval to maximise sensitivity of the Psychomotor Vigilance Test to fatigue.

There is some evidence that short interstimulus intervals (ISIs) on the Psychomotor Vigilance Test (PVT) are associated with longer and more varied reaction times (RTs). Preparation processes may impede RT following short ISIs, resulting in additional unexplained variance. The aims of this study were to investigate whether there is an effect of ISI on RT and errors within the PVT, and whether such an effect changes with three elements of fatigue: time of day, prior wake and time on task. Twelve male participants completed 49 PVTs across 7× 28h periods of forced desynchrony. For analysis, RTs, reciprocal reaction times (1/RT), false starts and lapse responses within each 10min session were assigned to a 1-s ISI group, a 2-min time of task group, a 2.5-h PW level and a 60° phase of the circadian rhythm of core body temperature (as a measure of time of day). Responses following short ISIs (2-5s) were significantly slower and more varied than responses following longer ISIs (5-10s). The likelihood of a lapse was also higher for short ISIs, while the probability of a false start increased as a function of ISI. These effects were independent of the influences of time of day, prior wake and time on task. Hence, mixed model ANOVAs comprising only long ISIs (5-10s) contained stronger effect sizes for fatigue than a model of all ISIs (2-10s). Including an ISI variable in a model improved the model fit and explained more variance associated with fatigue. Short ISIs resulted in long RTs both in the presence and absence of fatigue, possibly due to preparation processes or ISI conditioning. Hence, omitting short ISI trials from RT means or including an ISI variable in analysis can reduce unwanted variance in PVT data, improving the sensitivity of the PVT to fatigue.

The efficacy of objective and subjective predictors of driving performance during sleep restriction and circadian misalignment.

Fatigue is a significant contributor to motor-vehicle accidents and fatalities. Shift workers are particularly susceptible to fatigue-related risks as they are often sleep-restricted and required to commute around the clock. Simple assays of performance could provide useful indications of risk in fatigue management, but their effectiveness may be influenced by changes in their sensitivity to sleep loss across the day. The aim of this study was to evaluate the sensitivity of several neurobehavioral and subjective tasks to sleep restriction (SR) at different circadian phases and their efficacy as predictors of performance during a simulated driving task. Thirty-two volunteers (M±SD; 22.8±2.9 years) were time-isolated for 13-days and participated in one of two 14-h forced desynchrony protocols with sleep opportunities equivalent to 8h/24h (control) or 4h/24h (SR). At regular intervals during wake periods, participants completed a simulated driving task, several neurobehavioral tasks, including the psychomotor vigilance task (PVT), and subjective ratings, including a self-assessment measure of ability to perform. Scores transformed into standardized units relative to baseline were folded into circadian phase bins based on core body temperature. Sleep dose and circadian phase effect sizes were derived via mixed models analyses. Predictors of driving were identified with regressions. Performance was most sensitive to sleep restriction around the circadian nadir. The effects of sleep restriction around the circadian nadir were larger for simulated driving and neurobehavioral tasks than for subjective ratings. Tasks did not significantly predict driving performance during the control condition or around the acrophase during the SR condition. The PVT and self-assessed ability were the best predictors of simulated driving across circadian phases during SR. These results show that simple performance measures and self-monitoring explain a large proportion of the variance in driving when fatigue-risk is high.

Are two halves better than one whole? A comparison of the amount and quality of sleep obtained by healthy adult males living on split and consolidated sleep-wake schedules.

The aim of this study was to compare the quantity/quality of sleep obtained by people living on split and consolidated sleep-wake schedules. The study had a between-groups design, with 13 participants in a consolidated condition (all males, mean age of 22.5yr) and 16 participants in a split condition (all males, mean age of 22.6yr). Both conditions employed forced desynchrony protocols with the activity:rest ratio set at 2:1, but the consolidated condition had one sleep-wake cycle every 28h (9.33+18.67), while the split condition had one sleep-wake cycle every 14h (4.67+9.33). Sleep was assessed using polysomnography. Participants in the split and consolidated conditions obtained 4.0h of sleep per 14h and 7.6h of sleep per 28h, respectively. Some differences between the groups indicated that sleep quality was lower in the split condition than the consolidated condition: the split sleeps had longer sleep onset latency (9.7 vs. 4.3min), more arousals (7.4 vs. 5.7 per hour in bed), and a greater percentage of stage 1 sleep (4.1% vs. 3.1%), than the consolidated sleeps. Other differences between the groups indicated that sleep quality was higher in the split condition than the consolidated condition: the split sleeps had a lower percentage of wake after sleep onset sleep (11.7% vs. 17.6%), and a greater percentage of slow wave sleep (30.2% vs. 23.8%), than the consolidated sleeps. These results indicate that the split schedule was not particularly harmful, and may have actually been beneficial, to sleep. Split work-rest schedules can be socially disruptive, but their use may be warranted in work settings where shiftworkers are separated from their normal family/social lives (e.g., fly-in fly-out mining) or where the need for family/social time is secondary to the task (e.g., emergency response to natural disasters).

Is it on? An algorithm for discerning wrist-accelerometer non-wear times from sleep/wake activity.

The accuracy of sleep/wake estimates derived with actigraphy is often dependent on researchers being able to discern non-wear times from sleep or quiescent wakefulness when confronted by discrepancies in a sleep log. Without knowing when an accelerometer is being worn, non-wear could be inferred from periods of inactivity unlikely to occur while in bed. Data collected in our laboratory suggest that more than 50% of inactive periods during time in bed are <8 min in duration. This duration may be an appropriate minimum threshold for routine non-wear classification during self-reported wake. Higher thresholds could be chosen to derive non-wear definitions for self-reported bedtimes depending on the desired level of certainty. To determine non-wear at thresholds of 75%, 95% and 99%, for example, would require periods of inactivity lasting ≥18 min, ≥53 min and ≥85 min, respectively.

No first night shift effect observed following a nocturnal main sleep and a prophylactic 1-h afternoon nap.

Neurobehavioural impairment on the first night shift is often greater than on subsequent night shifts due to extended wakefulness. The aim of the study was to determine whether a 1-h afternoon nap prior to the first night shift is sufficient to produce neurobehavioural performance at levels comparable to the second night shift. Twelve male volunteers (mean age 22.9 years) participated in a laboratory protocol that simulated two 12-h night shifts. A nap preceded the first shift and a 7-h daytime sleep was scheduled between shifts. Neurobehavioural performance and subjective sleepiness measured across each night did not significantly differ between first and second shifts.

The effects of a split sleep-wake schedule on neurobehavioural performance and predictions of performance under conditions of forced desynchrony.

Extended wakefulness, sleep loss, and circadian misalignment are factors associated with an increased accident risk in shiftwork. Splitting shifts into multiple shorter periods per day may mitigate these risks by alleviating prior wake. However, the effect of splitting the sleep-wake schedule on the homeostatic and circadian contributions to neurobehavioural performance and subjective assessments of one's ability to perform are not known. Twenty-nine male participants lived in a time isolation laboratory for 13 d, assigned to one of two 28-h forced desynchrony (FD) schedules. Depending on the assigned schedule, participants were provided the same total time in bed (TIB) each FD cycle, either consolidated into a single period (9.33 h TIB) or split into two equal halves (2 × 4.67 h TIB). Neurobehavioural performance was regularly assessed with a psychomotor vigilance task (PVT) and subjectively-assessed ability was measured with a prediction of performance on a visual analogue scale. Polysomnography was used to assess sleep, and core body temperature was recorded to assess circadian phase. On average, participants obtained the same amount of sleep in both schedules, but those in the split schedule obtained more slow wave sleep (SWS) on FD days. Mixed-effects ANOVAs indicated no overall difference between the standard and split schedules in neurobehavioural performance or predictions of performance. Main effects of circadian phase and prior wake were present for both schedules, such that performance and subjective ratings of ability were best around the circadian acrophase, worst around the nadir, and declined with increasing prior wake. There was a schedule by circadian phase interaction for all neurobehavioural performance metrics such that performance was better in the split schedule than the standard schedule around the nadir. There was no such interaction for predictions of performance. Performance during the standard schedule was significantly better than the split schedule at 2 h of prior wake, but declined at a steeper rate such that the schedules converged by 4.5-7 h of prior wake. Overall, the results indicate that when the total opportunity for sleep per day is satisfactory, a split sleep-wake schedule is not detrimental to sleep or performance. Indeed, though not reflected in subjective assessments of performance capacity, splitting the schedule may be of some benefit, given its reduction of neurobehavioural impairment at night and its association with increased SWS. Therefore, for some industries that require operations to be sustained around the clock, implementing a split work-rest schedule may be of assistance.

Simulated driving under the influence of extended wake, time of day and sleep restriction.

Around a fifth of all road accidents can be attributed to fatigued drivers. Previous studies indicate that driving performance is influenced by time of day and decreases with sustained wakefulness. However, these influences occur naturally in unison, confounding their effects. Typically, when people drive at a poor time of day and with extended wake, their sleep is also restricted. Hence, the aim of the current study was to determine the independent effects of prior wake and time of day on driving performance under conditions of sleep restriction. The driving performance of fourteen male participants (21.8 ± 3.8 years, mean ± SD) was assessed during a 10 min simulated driving task with speed/lane mean, variability and violations (speeding and crashes) measured. Participants were tested at 2.5h intervals after waking, across 7 × 28 h days with a sleep:wake ratio of 1:5. By forced desynchrony each driving session occurred at 9 doses of prior wake and within 6 divisions of the circadian cycle based on core body temperature. A mixed models ANOVA revealed significant main effects of circadian phase, prior wake and sleep debt on lane violations. In addition, three significant two-way interactions (circadian phase × prior wake, prior wake × sleep debt, sleep debt × circadian phase) and one three-way interaction (circadian × prior wake × sleep debt) were identified. The presence of the large interaction effects shows that the influence of each factor is largely dependent on the magnitude of the other factors. For example, the presence of the time of day influence on driving performance is dependent on the length of prior wake or the presence of sleep debt. The findings suggest that people are able to undertake a low-difficulty simulated drive safely, at least for a short period, during their circadian nadir provided that they have had sufficient sleep and have not been awake too long.