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Author: Steven W Lockley (92)


Feb
2018

A biophysical model of the key aspects of melatonin synthesis and excretion has been developed, which is able to predict experimental dynamics of melatonin in plasma and saliva, and of its urinary metabolite 6-sulfatoxymelatonin (aMT6s). This new model is coupled to an established model of arousal dynamics, which predicts sleep and circadian dynamics based on light exposure and times of wakefulness. The combined model thus predicts melatonin levels over the sleep-wake/dark-light cycle and enables prediction of melatonin-based circadian phase markers, such as dim light melatonin onset (DLMO) and aMT6s acrophase under conditions of normal sleep and circadian misalignment.

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Jan
2018

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 ambulatory (8-h sleep:16-h wake) and constant routine (CR) (constant wake, posture, nutrition and dim light) conditions from 20 healthy premenopausal women. Urinary 6-sulphatoxymelatonin (aMT6s; ng/h) and the bone resorption marker amino-terminal cross-linked collagen I telopeptide (NTx; bone collagen equivalents nM/h) were assayed and fit by cosinor models to determine significant 24-h rhythms and acrophase.

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Dec
2017

Extended duration (≥24 h) work shifts (EDWS) are associated with increased risk of motor vehicle crashes, and awareness of any impairment has important implications on legal accountability for any adverse driving outcome. The extent to which adverse driving events were preceded by pre-drive self -reported sleepiness was evaluated in medical residents after EDWS.
Sixteen resident physicians (10F;29.

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Dec
1969

While many studies have shown the benefits of later school starts, including better student attendance, higher test scores, and improved sleep duration, few have used starting times later than 9:00 a.m. Here we report on the implementation and impact of a 10 a.

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Dec
2017

Increased severity of problematic daytime behavior has been associated with poorer sleep quality in individuals with autism spectrum disorder. In this work, we investigate whether this relationship holds in a real-time setting, such that an individual's prior sleep can be used to predict their subsequent daytime behavior. We analyzed an extensive real-world dataset containing over 20,000 nightly sleep observations matched to subsequent challenging daytime behaviors (aggression, self-injury, tantrums, property destruction and a challenging behavior index) across 67 individuals with low-functioning autism living in two U.

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Dec
2017

The increasing scientific evidence that early school start times are harmful to the health and safety of teenagers has generated much recent debate about changing school start times policies for adolescent students. Although efforts to promote and implement such changes have proliferated in the United States in recent years, they have rarely been supported by law-based arguments and messages that leverage the existing legal infrastructure regulating public education and child welfare in the United States. Furthermore, the legal bases to support or resist such changes have not been explored in detail to date.

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Oct
2017

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 50,000 nights of care-giver sleep/wake logs were collected on school-days for 106 individuals with low functioning autism (87 boys, 14.

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Dec
2017

We aimed to identify the prevalence of circadian phase and phase angle abnormalities in patients with insomnia.
We conducted a cross-sectional, multicenter study at three sleep laboratories in the United States and Australia. Patients with insomnia and healthy control participants completed a sleep log for 7 days.

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Nov
2017

Night workers often experience high levels of sleepiness due to misalignment of the sleep-wake cycle from the circadian pacemaker, in addition to acute and chronic sleep loss. Exposure to light, in particular short wavelength light, can improve alertness and neurobehavioural performance. This randomised controlled trial examined the efficacy of blue-enriched polychromatic light to improve alertness and neurobehavioural performance in night workers.

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Jun
2017

The association of irregular sleep schedules with circadian timing and academic performance has not been systematically examined. We studied 61 undergraduates for 30 days using sleep diaries, and quantified sleep regularity using a novel metric, the sleep regularity index (SRI). In the most and least regular quintiles, circadian phase and light exposure were assessed using salivary dim-light melatonin onset (DLMO) and wrist-worn photometry, respectively.

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Aug
2017

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.

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Apr
2017

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.Twenty-six healthy individuals participated in a 9-day inpatient protocol that included assessment of dim light melatonin onset time (DLMO time) before and after exposure to a single 15-second (= 8) or 2-minute (= 12) pulse of bright light (9,500 lux; 4,100 K fluorescent) or control background dim light (<3 lux;= 6).

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Dec
1969

To examine the prevalence of circadian misalignment in clinically diagnosed delayed sleep phase disorder (DSPD) and to compare mood and daytime functioning in those with and without a circadian basis for the disorder.
One hundred and eighty-two DSPD patients aged 16-64 years, engaged in regular employment or school, underwent sleep-wake monitoring in the home, followed by a sleep laboratory visit for assessment of salivary dim light melatonin onset (DLMO). Based on the DLMO assessments, patients were classified into two groups: circadian DSPD, defined as DLMO occurring at or after desired bedtime (DBT), or non-circadian DSPD, defined as DLMO occurring before DBT.

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Dec
1969

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.
Eight healthy males (mean age ± SD: 23.

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Dec
1969

Firefighters' schedules include extended shifts and long work weeks which cause sleep deficiency and circadian rhythm disruption. Many firefighters also suffer from undiagnosed sleep disorders, exacerbating fatigue. We tested the hypothesis that a workplace-based Sleep Health Program (SHP) incorporating sleep health education and sleep disorders screening would improve firefighter health and safety compared to standard practice.

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Oct
2016

While previous studies have demonstrated short-wavelength sensitivity to the acute alerting effects of light during the biological night, fewer studies have assessed the alerting effect of light during the daytime. This study assessed the wavelength-dependent sensitivity of the acute alerting effects of daytime light exposure following chronic sleep restriction in 60 young adults (29 men, 31 women; 22.5 ± 3.

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Oct
2016

The pineal gland produces the hormone melatonin, and its volume may influence melatonin levels. We describe an innovative method for estimating pineal volume in humans and present the association of pineal parenchyma volume with levels of the primary melatonin metabolite, 6-sulfatoxymelatonin. We selected a random sample of 122 older Icelandic men nested within the AGES-Reykjavik cohort and measured their total pineal volume, their parenchyma volume, and the extent of calcification and cysts.

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Oct
2016

An improvement to our current quantitative model of arousal state dynamics is presented that more accurately predicts sleep propensity as measured with sleep dynamics depending on circadian phase and prior wakefulness. A nonlinear relationship between the circadian variables within the dynamic circadian oscillator model is introduced to account for the skewed shape of the circadian rhythm of alertness that peaks just prior to the onset of the biological night (the "wake maintenance zone") and has a minimum toward the end of the biological night. The revised circadian drive thus provides a strong inhibitory input to the sleep-active neuronal population in the evening, counteracting the excitatory effects of the increased homeostatic sleep drive as originally proposed in the opponent process model of sleep-wake regulation.

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Jun
2016

Brain networks subserving alertness in humans interact with those for spatial attention orienting. We employed blue-enriched light to directly manipulate alertness in healthy volunteers. We show for the first time that prior exposure to higher, relative to lower, intensities of blue-enriched light speeds response times to left, but not right, hemifield visual stimuli, via an asymmetric effect on right-hemisphere parieto-occipital α-power.

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Jun
2016

The sleep electroencephalogram (EEG) is highly heritable in humans and yet little is known about the genetic basis of inter-individual differences in sleep architecture. The aim of this study was to identify associations between candidate circadian gene variants and the polysomnogram, recorded under highly controlled laboratory conditions during a baseline, overnight, 8 h sleep opportunity. A candidate gene approach was employed to analyze single-nucleotide polymorphisms from five circadian-related genes in a two-phase analysis of 84 healthy young adults (28 F; 23.

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May
2016

This study aimed to investigate sleep and circadian phase in the relationships between neurobehavioral performance and the number of consecutive shifts worked.
Thirty-four shift workers [20 men, mean age 31.8 (SD 10.

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Jun
2016

The objective of this study is to compare three methods of administering a sleep health program (SHP) in fire departments.
An SHP, comprising sleep health education and screening for common sleep disorders, was implemented in eight fire departments using three approaches: expert-led, train-the-trainer, and online. Participation rates, knowledge assessments, surveys, and focus group interviews were analyzed to assess the reach and effectiveness of the methodologies.

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May
2016

There is currently no questionnaire-based pre-screening tool available to detect non-24-hour sleep-wake rhythm disorder (N24HSWD) among blind patients. Our goal was to develop such a tool, derived from gold standard, objective hormonal measures of circadian entrainment status, for the detection of N24HSWD among those with visual impairment.
We evaluated the contribution of 40 variables in their ability to predict N24HSWD among 127 blind women, classified using urinary 6-sulfatoxymelatonin period, an objective marker of circadian entrainment status in this population.

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Dec
1969

The risk of type 2 diabetes (T2D) is increased by abnormalities in sleep quantity and 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 mediates this risk is unknown. We aimed to test if MTNR1B diabetes risk variant rs10830963 associates with measures of sleep or circadian physiology in intensive in-laboratory protocols (n = 58-96) or cross-sectional studies with sleep quantity and quality and timing measures from self-report (n = 4,307-10,332), actigraphy (n = 1,513), or polysomnography (n = 3,021).

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Feb
2016

Sleep deficiency is a major public health problem. There are limited human data on whether sleep duration or disruption are risk factors for prostate cancer.
We prospectively followed 32,141 men in the Health Professionals Follow-Up Study who reported their typical sleep duration in 1987, 2000, and 2008.

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Dec
2015

Non-24-hour sleep-wake rhythm disorder (N24SWD) is a cyclic debilitating circadian rhythm sleep disorder characterized by an inability to sleep on a 24-hour schedule. Individuals isolated from a 24-hour light-dark cycle exhibit sleep-wake cycles different from 24 hours. Relatively rare in sighted patients, it may be associated with delayed sleep-wake rhythm disorder or psychiatric disorders.

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Oct
2015

Most totally blind people have non-24-hour sleep-wake disorder (non-24), a rare circadian rhythm disorder caused by an inability of light to reset their circadian pacemaker. In two consecutive placebo-controlled trials (SET and RESET), we assessed safety and efficacy (in terms of circadian entrainment and maintenance) of once-daily tasimelteon, a novel dual-melatonin receptor agonist.
We undertook the placebo-controlled, randomised, double-masked trials in 27 US and six German clinical research centres and sleep centres.

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Oct
2015

The study examined the relationship between the circadian rhythm of 6-sulphatoxymelatonin (aMT6s) and ocular measures of sleepiness and neurobehavioral performance in shift workers undergoing a simulated night shift.
Twenty-two shift workers (mean age 33.4, SD 11.

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Dec
1969

Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M) aged 22.

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Jun
2015

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 symptoms of non-24-hour sleep-wake disorder.
Three totally blind males (63.

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Mar
2015

Heart attacks and motor vehicle crashes are the leading causes of death in US firefighters. Given that sleep disorders are an independent risk factor for both of these, we examined the prevalence of common sleep disorders in a national sample of firefighters and their association with adverse health and safety outcomes.
Firefighters (n = 6,933) from 66 US fire departments were assessed for common sleep disorders using validated screening tools, as available.

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Dec
1969

Although there is evidence that significant sleep problems are common in children with autism spectrum disorder (ASD) and that poor sleep exacerbates problematic daytime behavior, such relationships have received very little attention in both research and clinical practice. Treatment guidelines to help manage challenging behaviors in ASD fail to mention sleep at all, or they present a very limited account. Moreover, limited attention is given to children with low-functioning autism, those individuals who often experience the most severe sleep disruption and behavioral problems.

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Jul
2015

Various aspects of immune response exhibit 24-h variations suggesting that infection susceptibility and treatment efficacy may vary by time of day. Whether these 24-h variations are endogenous or evoked by changes in environmental or behavioral conditions is not known. We assessed the endogenous circadian control and environmental and behavioral influences on ex-vivo lipopolysaccharide stimulation of whole blood in thirteen healthy participants under 48h of baseline conditions with standard sleep-wake schedules and 40-50h of constant environmental and behavioral (constant routine; CR) conditions.

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Jan
2015

Circadian genes may be involved in regulating cancer-related pathways, including cell proliferation, DNA damage response, and apoptosis. We aimed to assess the role of genetic variation in core circadian rhythm genes with the risk of fatal prostate cancer and first morning void urinary 6-sulfatoxymelatonin levels.
We used unconditional logistic regression to evaluate the association of 96 single-nucleotide polymorphisms (SNPs) across 12 circadian-related genes with fatal prostate cancer in the AGES-Reykjavik cohort (n = 24 cases), the Health Professionals Follow-Up Study (HPFS) (n = 40 cases), and the Physicians' Health Study (PHS) (n = 105 cases).

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Feb
2015

Melatonin has anticarcinogenic properties in experimental models. We undertook a case-cohort study of 928 Icelandic men without prostate cancer (PCa) nested within the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort to investigate the prospective association between first morning-void urinary 6-sulfatoxymelatonin (aMT6s) levels and the subsequent risk for PCa, under the hypothesis that men with lower aMT6s levels have an increased risk for advanced PCa. We used weighted Cox proportional hazards models to assess the association between first morning-void aMT6s levels and PCa risk, adjusting for potential confounders.

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Jun
2014

Light is the major environmental time cue that synchronizes the endogenous central circadian pacemaker, located in the suprachiasmatic nuclei of the hypothalamus, and is detected exclusively by the eyes primarily via specialized non-rod, non-cone ganglion cell photoreceptors. Consequently, most blind people with no perception of light (NPL) have either nonentrained or abnormally phased circadian rhythms due to this inability to detect light. Conversely, most visually impaired participants with some degree of light perception (LP) exhibit normal entrainment, emphasizing the functional separation of visual and "nonvisual" photoreception.

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Jun
2014

Breast cancer is the leading cause of cancer death among women worldwide, and there is only a limited explanation of why. Risk is highest in the most industrialized countries but also is rising rapidly in the developing world. Known risk factors account for only a portion of the incidence in the high-risk populations, and there has been considerable speculation and many false leads on other possibly major determinants of risk, such as dietary fat.

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Feb
2014

Previous studies have demonstrated short-wavelength sensitivity for the acute alerting response to nocturnal light exposure. We assessed daytime spectral sensitivity in alertness, performance, and waking electroencephalogram (EEG).
Between-subjects (n = 8 per group).

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Jan
2014

Despite the high prevalence of insomnia, daytime consequences of the disorder are poorly characterized. This study aimed to identify neurobehavioral impairments associated with insomnia, and to investigate relationships between these impairments and subjective ratings of sleep and daytime dysfunction.
Cross-sectional, multicenter study.

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Dec
2013

The current study characterized the temporal dynamics of ocular indicators of sleepiness during extended sleep restriction. Ten male participants (mean age ± SD = 23.3 ± 1.

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Jan
2014

Light is a potent stimulus for regulating circadian, hormonal, and behavioral systems. In addition, light therapy is effective for certain affective disorders, sleep problems, and circadian rhythm disruption. These biological and behavioral effects of light are influenced by a distinct photoreceptor in the eye, melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), in addition to conventional rods and cones.

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May
2014

Fatigue is a common, persistent complaint following traumatic brain injury (TBI). Effective treatment is not well established.
.

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Sep
2013

The American Medical Association House of Delegates in June of 2012 adopted a policy statement on nighttime lighting and human health. This major policy statement summarizes the scientific evidence that nighttime electric light can disrupt circadian rhythms in humans and documents the rapidly advancing understanding from basic science of how disruption of circadian rhythmicity affects aspects of physiology with direct links to human health, such as cell cycle regulation, DNA damage response, and metabolism. The human evidence is also accumulating, with the strongest epidemiologic support for a link of circadian disruption from light at night to breast cancer.

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Sep
2013

Shiftwork has been implicated as a risk factor for prostate cancer. Results from prior studies have been mixed but generally support an association between circadian disruption and prostate cancer. Our aim was to investigate the relationship between shiftwork and prostate-specific antigen (PSA) test obtained as part of the National Health and Nutrition Examination Survey (NHANES) study.

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Dec
2013

Light regulates multiple non-image-forming (or nonvisual) circadian, neuroendocrine, and neurobehavioral functions, via outputs from intrinsically photosensitive retinal ganglion cells (ipRGCs). Exposure to light directly enhances alertness and performance, so light is an important regulator of wakefulness and cognition. The roles of rods, cones, and ipRGCs in the impact of light on cognitive brain functions remain unclear, however.

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May
2013

Although positive associations have consistently been reported between sleep disruption and breast cancer, less is known about its potential role in prostate cancer.
Within the prospective AGES-Reykjavik cohort study, we followed 2,102 men recruited in 2002-2006 until the end of 2009. Participants answered questions on sleep disruption.

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Apr
2013

Although impairment of daytime functioning is a symptom of many sleep disorders, there are limited data on their nature for some patient groups. The role of the circadian system on impaired functioning, specifically the wake maintenance zone (WMZ)-a ∼3-h window of reduced sleep propensity that occurs shortly before the onset of melatonin synthesis-has received little attention. The study examined the influence of the WMZ on neurobehavioral performance under normal conditions and following sleep deprivation.

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Feb
2013

To evaluate the sensitivity and specificity of a portable single-channel (intra-nasal pressure) sleep apnea device (ApneaLink) in both the laboratory and at home for assessment of sleep apnea risk in comparison with standard polysomnography (PSG).
Fifty-five participants underwent simultaneous recordings of standard PSG and ApneaLink in the laboratory. Of these, 38 participants also used the ApneaLink device in their own homes for one night.

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Jan
2013

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 to short-wavelength visible light, the aim of the current study was to construct a PRC to blue (480 nm) light and compare it to a 10,000 lux white light PRC constructed previously using a similar protocol.

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