Melissa St. Hilaire

Harvard University | Harvard · Office of Technology Development

Circadian misalignment remains a distinct challenge for night shift workers. Variability in individual sleep-wake/light-dark patterns might contribute to individual differences in circadian alignment in night shift workers. In this simulation study, we compared the predicted phase shift from a mathematical model of the effect of light on the human...

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...

The circadian system regulates the timing of physiologic processes ranging from gene expression to drug metabolism. Even when healthy individuals maintain the same sleep‐wake and rest‐activity schedules, their endogenous circadian time can be up to 5 hours apart, suggesting that the same drug administered at the same local clock time in two patient...

We explored the predictive value of a neurobehavioral performance assessment under rested baseline conditions (evaluated at 8 hours awake following 8 hours of sleep) on neurobehavioral response to moderate sleep loss (evaluated at 20 hours awake two days later) in 151 healthy young participants (18–30 years). We defined each participant’s response-...

Study objectives: Women in the luteal phase of the menstrual cycle exhibit better cognitive performance overnight than women in the follicular phase, although the mechanism is unknown. Given the link between core body temperature (CBT) and performance, one potential mechanism is the thermoregulatory role of progesterone (P4), estradiol (E2), and t...

Light is the most effective environmental stimulus for shifting the mammalian circadian pacemaker. Numerous studies have been conducted across multiple species to delineate wavelength, intensity, duration, and timing contributions to the response of the circadian pacemaker to light. Recent studies have revealed a surprising sensitivity of the human...

Study Objectives We compared resident physician work hours and sleep in a multi-center clustered-randomized crossover clinical trial that randomized resident physicians to an Extended Duration Work Roster (EDWR) with extended-duration (≥24 hours) shifts or a Rapidly Cycling Work Roster (RCWR), in which scheduled shift lengths were limited to 16 or...

Introduction First year postgraduate (PGY1) resident physicians have impaired vigilance and more attentional failures working extended duration work rosters (EDWR) with 24+ hour extended-duration shifts compared to shifts scheduled to 16 or fewer hours. We examined the impact of a rapid cycling work roster (RCWR) intervention designed to limit cont...

Introduction Extended-duration work shifts (≥ 24 hours), the cornerstone of medical education, have been associated with reduced sleep first-year resident physicians in a single-site study. We compared more senior resident physician work hours and sleep habits in a multi-center clustered-randomized crossover clinical trial that randomized resident...

Introduction Mathematical models of neurobehavioral performance are a key tool in work schedule assessment, allowing quantitative predictions of performance, especially in cases where empirical assessment would be impractical. Models have recently been extended to predict accurately the effects of chronic sleep restriction on vigilant performance,...

Study Objectives The Accreditation Council for Graduate Medical Education (ACGME) recently reinstated extended-duration (24-28 hour) work shifts (EDWS) for postgraduate year 1 (PGY-1) resident physicians. This study examined the relationship between overnight sleep duration during EDWS and subsequent ‘post-call’ performance in PGY-1 resident physic...

Although evidence exists for a daily rhythm in bone metabolism, the contribution of factors such as melatonin levels, the light–dark cycle, and the sleep–wake cycle is difficult to differentiate given their highly correlated time courses. To examine these influences on bone resorption, we collected 48-h sequential urine samples under both ambulator...

Despite sleep disturbance being a common complaint in individuals with autism, specific sleep phenotypes and their relationship to adaptive functioning have yet to be identified. This study used cluster analysis to find distinct sleep patterns and relate them to independent measures of adaptive functioning in individuals with autism. Approximately...

Lay summary: We analyzed over 20,000 nights of sleep from 67 individuals with autism to investigate whether daytime behaviors can be predicted from prior sleep patterns. Better-than-chance accuracy was obtained for 81% of individuals, with measures of night-to-night variation in sleep timing and duration most relevant for accurate prediction. Our...

Key points: There is assumed to be a monotonic association between melatonin suppression and circadian phase resetting induced by light exposure. We tested the association between melatonin suppression and phase resetting in humans. Sixteen young healthy participants received nocturnal bright light (∼9500 lux) exposure of continuous or intermitten...

We compared the effects of bedroom-intensity light from a standard fluorescent and a blue- (i.e., short-wavelength) depleted LED source on melatonin suppression, alertness, and sleep. Sixteen healthy participants (8 females) completed a 4-day inpatient study. Participants were exposed to blue-depleted circadian-sensitive (C-LED) light and a standar...

Introduction It has recently been reported that providing resident physicians with 3- or 5-hour protected windows for sleep during an on-call night increases the amount of sleep obtained and improves next-day performance relative to an on-call night with no protected window, in contrast to earlier findings. These studies have not reported, however,...

BACKGROUND. In humans, a single light exposure of 12 minutes and multiple-millisecond light exposures can shift the phase of the circadian pacemaker. We investigated the response of the human circadian pacemaker to a single 15-second or 2-minute light pulse administered during the biological night. METHODS. Twenty-six healthy individuals participat...

Study objectives: Intraindividual night-to-night sleep duration is often insufficient and variable. Here we report the effects of such chronic variable sleep deficiency on neurobehavioral performance and the ability of state-of-the-art models to predict these changes. Methods: Eight healthy males (mean age ± SD: 23.9 ± 2.4 years) studied at our...

Despite widely published speculation regarding a potential potency advantage of short-wavelength (blue-appearing) light for Seasonal Affective Disorder (SAD) treatment, there have been few systematic studies. Those comparing short-wavelength to broad-wavelength (white) light under actual clinical conditions suggest equivalent effectiveness. This mu...

Background: Sleep-wake disturbances are highly prevalent following traumatic brain injury (TBI), impeding rehabilitaion and quality of life. However, the mechanisms underlying these sleep disturnbances are unclear, and efficacious treatments are lacking. To investigate possible mechanisms underlying sleep disturbance in TBI, we examined characteri...

The risk of type 2 diabetes (T2D) is increased by abnormalities in sleep quantity, quality, circadian alignment, and melatonin regulation. A common genetic variant in a receptor for the circadian-regulated hormone melatonin (MTNR1B) is associated with increased fasting blood glucose and risk of T2D, but whether sleep or circadian disruption mediate...

Totally blind individuals are highly likely to suffer from Non-24-Hour Sleep-Wake Disorder due to a failure of light to reset the circadian pacemaker in the suprachiasmatic nuclei. In this outpatient case series, we investigated whether daily caffeine administration could entrain the circadian pacemaker in non-entrained blind patients to alleviate...

Melatonin is endogenously produced and released in humans during nighttime darkness and is suppressed by ocular light exposure. Exogenous melatonin is used to induce circadian phase shifts and sleep. The circadian phase-shifting ability of a stimulus (e.g., melatonin or light) relative to its timing may be displayed as a phase response curve (PRC)....

The photic resetting response of the human circadian pacemaker depends on the timing of exposure, and the direction and magnitude of the resulting shift is described by a Phase Response Curve (PRC). Previous PRCs in humans have utilized high intensity polychromatic white light. Given that the circadian photoreception system is maximally sensitive t...

In mammals, the pupillary light reflex is mediated by intrinsically photosensitive melanopsin-containing retinal ganglion cells that also receive input from rod-cone photoreceptors. To assess the relative contribution of melanopsin and rod-cone photoreceptors to the pupillary light reflex in humans, we compared pupillary light responses in normally...

There is currently no "gold standard" marker of cognitive performance impairment resulting from sleep loss. We utilized pattern recognition algorithms to determine which features of data collected under controlled laboratory conditions could most reliably identify cognitive performance impairment in response to sleep loss using data from only one t...

The phase resetting response of the human circadian pacemaker to light depends on the timing of exposure and is described by a phase response curve (PRC). The current study aimed to construct a PRC for a 1 h exposure to bright white light (∼8000 lux) and to compare this PRC to a <3 lux dim background light PRC. These data were also compared to a pr...

Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying brig...

Accurate determination of circadian phase is necessary for research and clinical purposes because of the influence of the master circadian pacemaker on multiple physiologic functions. Melatonin is presently the most accurate marker of the activity of the human circadian pacemaker. Current methods of analyzing the plasma melatonin rhythm can be grou...

The rhythm of plasma melatonin concentration is currently the most accurate marker of the endogenous human circadian pacemaker. A number of methods exist to estimate circadian phase and amplitude from the observed melatonin rhythm. However, almost all these methods are limited because they depend on the shape and amplitude of the melatonin pulse, w...

Mathematical models have become vital to the study of many biological processes in humans due to the complexity of the physiological mechanisms underlying these processes and systems. While our current mathematical representation of the human circadian pacemaker has proven useful in many experimental situations, it uses as input only a direct effec...

Mathematical models of neurobehavioral performance and alertness have both basic science and practical applications. These models can be especially useful in predicting the effect of different sleep-wake schedules on human neurobehavioral objective performance and subjective alertness under many conditions. Several relevant models currently exist i...

At an organism level, the mammalian circadian pacemaker is a two-dimensional system. For these two dimensions, phase (relative timing) and amplitude of the circadian pacemaker are commonly used. Both the phase and the amplitude (A) of the human circadian pacemaker can be observed within multiple physiological measures--including plasma cortisol, pl...