The Effect of Concussion Mechanism of Injury on Sleep Problems in Active Duty Service Members Following Deployment.

INTRODUCTION: Sleep disruption is pervasive in the military and is generally exacerbated during deployment, partially due to increases in operational tempo and exposure to stressors and/or trauma. In particular, sleep disruption is a commonly reported symptom following deployment-related traumatic brain injury (TBI), though less is known about the prevalence of sleep disturbance as a function of whether the TBI was induced by high-level blast (HLB) or direct impact to the head. TBI assessment, treatment, and prognosis are further complicated by comorbidity with posttraumatic stress disorder (PTSD), depression, and alcohol misuse. Here, we examine whether concussion mechanism of injury is associated with differences in the prevalence of self-reported sleep disturbance following deployment in a large sample of U.S. Marines while accounting for probable PTSD, depression, and alcohol misuse. MATERIALS AND METHODS: This was a retrospective cohort study of active duty enlisted Marines with a probable concussion (N = 5757) who completed the Post-Deployment Health Assessment between 2008 and 2012. Probable concussion was defined as endorsement of a potentially concussive event with corresponding loss or alteration of consciousness. The presence of concussion-related sleep problems was assessed with a dichotomous item. Probable PTSD, depression, and alcohol misuse were assessed using the Primary Care PTSD Screen, the Patient Health Questionnaire-2, and the Alcohol Use Identification Test-Concise, respectively. Logistic regression models investigated the effects of mechanism of injury (HLB vs. impact), PTSD, depression, and alcohol misuse on the presence of sleep problems, adjusting for sex and pay grade. The study was approved by the Naval Health Research Center Institutional Review Board. RESULTS: Approximately 41% of individuals with a probable deployment-related concussion reported sleep problems following the event; 79% of concussed individuals reporting both HLB and probable PTSD reported sleep problems. All main effects were significantly associated with sleep disturbance in adjusted models. PTSD showed the strongest association with sleep disturbance (adjusted odds ratio [AOR] = 2.84), followed by depression (AOR = 2.43), HLB exposure (AOR = 2.00), female sex (AOR = 1.63), alcohol misuse (AOR = 1.14), and pay grade (AOR = 1.10). A significant HLB × PTSD interaction emerged (AOR = 1.58), which suggests that sleep disturbance was elevated among those with both HLB-induced (vs. impact-induced) concussions and presence (vs. absence) of PTSD. No other significant interactions emerged. CONCLUSION: To our knowledge, this is the first study to examine the prevalence of concussion-related sleep complaints following deployment as a function of the mechanism of injury in individuals with and without probable PTSD and depression. Individuals with HLB-induced concussion were twice as likely to report sleep problems as those with an impact-induced concussion. Future work should examine these effects longitudinally with validated measures that assess greater precision of exposure and outcome assessment (e.g., blast intensity and type of sleep disturbance).

Hybrid effectiveness-implementation study of two novel spectrally engineered lighting interventions for shiftworkers on a high-security watchfloor.

Shiftwork leads to myriad negative health and safety outcomes. Lighting countermeasures can benefit shiftworkers via physiological effects of light (e.g. alerting, circadian adjustment), and short-wavelength light is the most potent for eliciting those responses; however, limited work indicates it may not be required for alerting. We developed similar-appearing light boxes (correlated color temperature: 3000-3375 K; photopic illuminance: 260-296 lux), enriched (SW+, melanopic EDI: 294 lux) or attenuated (SW-, melanopic EDI: 103 lux) in short-wavelength energy, and implemented them on a high-security watchfloor. Efficacy and feasibility of these two novel lighting interventions were assessed in personnel working 12-hour night shifts (n = 47) in this within-participants, crossover study. For each intervention condition, light boxes were arranged across the front of the watchfloor and illuminated the entire shift; blue-blocking glasses were worn post-shift and before sleep; and sleep masks were used while sleeping. Comparisons between baseline and intervention conditions included alertness, sleep, mood, quality of life (QOL), and implementation measures. On-shift alertness (Karolinska Sleepiness Scale) increased in SW- compared to baseline, while changes in SW+ were more limited. Under SW+, both mood and sleep improved. Psychomotor vigilance task performance did not vary by condition; however, perceived performance and QOL were higher, and reported caffeine consumption and sleep onset latency were lower, under SW-. For both interventions, satisfaction and comfort were high, and fewer symptoms and negative feelings were reported. The addition of spectrally engineered lights to this unique work environment improved sleep, alertness, and mood without compromising visual comfort and satisfaction. This paper is part of the Sleep and Circadian Rhythms: Management of Fatigue in Occupational Settings Collection.

Sleep, Immune Function, and Vaccinations in Military Personnel: Challenges and Future Directions.

The U.S. military invests substantial resources to vaccinate all personnel, including recruits, against operationally important infectious disease threats. However, research suggests that vaccine immune response and, therefore, vaccine effectiveness may be inadvertently reduced because of chronic and/or acute sleep deficiency experienced by recipients around the time of vaccination. Because sleep deficiency is expected and even necessary in deployed and training contexts, research investigations of the impacts of sleep and related physiological systems such as circadian rhythms on vaccine effectiveness in military settings are needed. Specifically, research should be aimed at understanding the effects of sleep deficiency, as well as vaccine administration schedules, on response to vaccination and clinical protection. Furthermore, knowledge gaps among military medical leadership on sleep, vaccines, and immune health should be assessed. This area of research may benefit the health and readiness of service members while also decreasing health care utilization and associated costs from illness.

Circadian, light, and sleep skills program: Efficacy of a brief educational intervention for improving sleep and psychological health at sea.

OBJECTIVES: Military service poses unique threats to sleep and circadian health, and the shipboard environment presents further challenges. Disrupted sleep and circadian rhythms are linked to myriad health and safety issues that compromise readiness, including negative psychological health outcomes. Thus, one advantage of mitigating sleep problems includes the possibility of also enhancing mental health. PROCEDURES: We evaluated the efficacy of the Circadian, Light, and Sleep Skills program for shipboard military personnel for improving sleep, and examined the impact of sleep on mental health in participating sailors. Questionnaires were administered to US sailors (N = 150) assigned to three ships (one control, two intervention) before the program (T1), immediately afterward (T2), and 2-4 months later, after a period at sea (T3). Outcomes included motivation to improve sleep; sleep and circadian knowledge; frequency of sleep-promoting behaviors; sleep quality (Pittsburgh Sleep Quality Index); and mental health symptoms. Satisfaction with specific program elements and perceived relevance were also examined. MAIN FINDINGS: Sleep and circadian knowledge, frequency of sleep-promoting behaviors, and sleep quality improved from T1 to T3 in the intervention versus control group. Sleep quality also mediated the effects of the underway (at sea) period on mental health. The intervention was well received, with high satisfaction and perceived relevance ratings. PRINCIPAL CONCLUSIONS: A brief 30-min intervention before an underway period improved sleep, circadian, and psychological health outcomes in shipboard sailors, even months later. Broader dissemination of this program may provide significant positive impact with minimal investment of resources.

The Development, Implementation, and Feasibility of a Circadian, Light, and Sleep Skills Program for Shipboard Military Personnel (CLASS-SM).

Service members face unique barriers to sufficient and high quality sleep. In the present study, a circadian, light, and sleep skills program for shipboard military personnel (CLASS-SM) was designed to encourage and inform strategies that support optimal sleep and circadian health in the context of those barriers. Phase 1 included program development and refinement via an iterative formative evaluation, including structured interviews with service members and feedback from veterans and experts, resulting in further tailoring to the population. In Phase 2, the highly tailored program was administered to shipboard personnel (n = 55), and acceptability indicators were measured. Sleep- and circadian-related knowledge (pre- and post-program) and the perceived relevance of, and satisfaction with, program content (post-program) were assessed. Before the intervention, most individuals were unaware that 7−9 h of sleep is recommended (72%) and had little understanding of the physiological effects of light; however, knowledge scores increased significantly post-program, from 51% to 88% correct (p < 0.0001). Reception was positive, with high reported satisfaction and relevance. Most individuals reported that they learned something new (89%), planned to use one or more learned strategies (100%), and intended to share learned information with others (85%); the physiological effects of light and circadian rhythms were the content areas most frequently reported as new and useful. The results demonstrate the need for, and feasibility of, the delivery of this program in operational environments.

Sleep-Scheduling Strategies in Hospital Shiftworkers.

INTRODUCTION: Shiftwork causes circadian disruption and results in impaired performance, sleep, and health. Often, individuals on non-standard shifts cannot modify work schedules. At-home sleep schedules are a potentially modifiable point of intervention, yet sleep-scheduling strategies remain relatively understudied. Specifically, the adoption of multiple strategies and the employment of strategies for not only night shifts, but also early starts on days, have yet to be formally examined to our knowledge. We studied how adoption of specific and/or multiple sleep-scheduling strategies for day and night shifts relates to measures of adaptation to shiftwork, self-reported on-shift sleepiness, and individual characteristics (eg, age, chronotype, education in circadian and sleep health). We hypothesized: 1) strategies would differ by shift type, 2) individuals would adopt multiple strategies, 3) strategies better aligned with circadian principles would relate to measures of adaptation, and 4) individual characteristics, such as having dependents, would relate to strategy selection. METHODS: A retrospective, online questionnaire (including items from the Survey of Shiftworkers and items related to sleep-scheduling strategies) was administered to both permanent and rotating hospital staff in four wards working 12-h day and/or night shifts (n=89). Additionally, reasons for strategy selection were explored. RESULTS: Level of adaptation varied by sleep-scheduling strategy, with the least adaptation for those utilizing the Incomplete Shifter strategies. For night shifts, Night Stay and Switch Sleeper-N strategies were related to lower mid-shift sleepiness. Many night workers reported using strategies that restricted sleep, and most reported using multiple strategies, both of which also related to lower adaptation. Domestic considerations were the most common rationale for strategy selection. Strategies varied by several individual characteristics, including chronotype, dependents, and level of sleep education. DISCUSSION: Future work should investigate sleep strategies and circadian interventions to help mitigate the effects of circadian and sleep disruption in hospital staff.

Chronotype and self-reported sleep, alertness, and mental health in U.S. sailors.

Service members are at risk for sleep and psychological conditions affecting their readiness. Chronotype ("morningness" or "eveningness") is strongly associated with sleep, health and performance. The objective of this study was to examine associations between validated measures of chronotype and sleep quality, daytime functioning, alertness, and symptoms of depression, anxiety, and post-traumatic stress disorder (PTSD) in US service members (n = 298). Although predominantly young males (who skew toward eveningness in civilian populations), these Sailors skewed toward morningness (35.6% morning, 51.3% intermediate). Eveningness was associated with symptoms of depression and post-traumatic stress disorder (PTSD) (P < 0.01), less time in bed (P < 0.05), more sleep disruption (P < 0.01), and poorer daytime functioning and alertness (P < 0.05). Evening types were less likely to consider sleep important for performance (P < 0.05). To maximize service member readiness, schedules should be aligned with endogenous rhythms, whenever possible, and evening chronotypes may benefit from targeted interventions. Chronotype should be examined alongside health and readiness in service members.

Naturalistic Intensities of Light at Night: A Review of the Potent Effects of Very Dim Light on Circadian Responses and Considerations for Translational Research.

In this review, we discuss the remarkable potency and potential applications of a form of light that is often overlooked in a circadian context: naturalistic levels of dim light at night (nLAN), equivalent to intensities produced by the moon and stars. It is often assumed that such low levels of light do not produce circadian responses typically associated with brighter light levels. A solid understanding of the impacts of very low light levels is complicated further by the broad use of the somewhat ambiguous term "dim light," which has been used to describe light levels ranging seven orders of magnitude. Here, we lay out the argument that nLAN exerts potent circadian effects on numerous mammalian species, and that given conservation of anatomy and function, the efficacy of light in this range in humans warrants further investigation. We also provide recommendations for the field of chronobiological research, including minimum requirements for the measurement and reporting of light, standardization of terminology (specifically as it pertains to "dim" light), and ideas for reconsidering old data and designing new studies.

A Qualitative Examination of Factors That Influence Sleep Among Shipboard Sailors.

INTRODUCTION: Sleep disturbance is prevalent among service members; however, little is known about factors that compromise sleep in unique operational environments, such as naval ships. Given the importance of sleep to health and performance, it is critical to identify both causes and potential solutions to this serious issue. The objective of this qualitative study was to elucidate the barriers to sleep and the strategies service members use to improve their sleep and combat fatigue while living and working aboard ships (i.e., underway). METHODS AND MATERIALS: Interviews were conducted with 22 active duty service members assigned to sea duty. The semi-structured interview guide assessed the experiences of service members sleeping in shipboard environments. Interview transcripts were analyzed using applied thematic content analysis by two independent coders. RESULTS: Participants were largely male (77.8%) and enlisted (88.9%). The most common barrier to obtaining sufficient sleep was stress, followed by rotating schedules, and environmental factors (e.g., noise and light). Additionally, many participants reported prioritizing other activities over sleep when off duty. Many participants did not report using any specific strategies to improve their sleep while underway. Among those who did, most described mitigating environmental barriers (e.g., noise-cancelling headphones or sleep masks). However, some participants also acknowledged these strategies are not always feasible, either attributable to cost or because sailors must be able to respond to alarms or commands. Notably, few sailors reported using stress mitigation or relaxation strategies to help sleep. Ingesting caffeine was the only strategy sailors reported using to alert themselves while fatigued. CONCLUSIONS: Service members reported many unique barriers to sleep in the shipboard environment, yet many did not report the use of strategies to mitigate them. Further, few used alerting techniques when fatigued. This at-risk population could benefit from targeted educational interventions on sleep-promoting behaviors, prioritization of sleep, and fatigue mitigation.

Implementation of interventions designed to promote healthy sleep and circadian rhythms in shiftworkers.

Shiftwork is a significant risk factor for a host of negative health and safety outcomes, which have been at least partly attributed to disturbances of the circadian timing system. As a result, an entire sub-field of chronobiology has been devoted to developing and evaluating countermeasures for circadian misalignment, sleep disruption, fatigue, and other issues associated with shiftwork. Much of this research takes place under highly controlled laboratory conditions due to the necessity of accurately characterizing individual rhythms, both for intervention design and assessment of efficacy. Applied studies of interventions for shiftworkers are, by their nature, more complicated, often demonstrating less consistent findings. While this, in part, reflects execution under less rigorously controlled conditions, it may also stem from variability in implementation approaches. A systematic review of published studies (through May 2017) of interventions designed to enhance circadian health in shiftworkers was conducted to determine the frequency and quality of the assessment of implementation as well as barriers and enablers to implementation. A search of PubMed, PsychINFO, Web of Science, and CINAHL databases yielded a total of 5368 unique references. After a title and abstract screen, 323 proceeded to full-text review; 68 of those met final criteria for data extraction. Implementation was assessed to some degree in 60.3% of those 68 articles. Where it was assessed, the mean quality score on a scale from 1 to 5 (1 = very little, 3 = moderate, 5 = very in-depth) was 2.56. One or more enablers were identified in just 17 of the 68 studies (25.0%), and barriers in just 18 (26.5%). Implementation of these interventions is a critical but seldom-acknowledged component of their uptake and effectiveness, and we highly recommend that future shiftworker intervention research make an effort to incorporate formalized assessments of implementation and/or hybrid effectiveness-implementation approaches.

Studying the Health and Performance of Shipboard Sailors: An Evidence Map.

INTRODUCTION: It is estimated that sailors who are assigned to surface ships and submarines are deployed for more than 1 year across their careers and they spend 15% to 23% of their time away from home. Research suggests that shipboard sailors experience rates of behavioral health issues similar to those with ground combat experiences. Despite the rigorous operational tempo and the unique shipboard environment experienced by these service members, little military health research has examined the health outcomes of sailors serving aboard ships. The objectives of this study were to develop an evidence map of the peer-reviewed literature to (1) identify potential threats to the health and readiness of shipboard sailors, (2) identify health and performance issues experienced by this population, and (3) identify gaps in the current peer-reviewed published literature on shipboard health and performance. MATERIALS AND METHODS: A systematic review of the existing peer-reviewed literature pertaining to the health, experiences, and performance of shipboard service members was conducted. Comprehensive search terms were used to identify articles published between January 2000 and April 2018. Identified articles were subject to a two-level review process. Study characteristics for all articles selected for final review were extracted, and articles were categorized into 13 content areas that were selected a priori. Findings are presented in an evidence map. RESULTS: The initial literature search yielded 8,858 unique articles, 90 of which were eligible for full review. Most articles primarily examined active duty sailors from the U.S. or other foreign militaries (88.9%). A total of 60 articles (67.8%) included information about the type of ship studied; the most frequently examined were submarines (29.5%) and aircraft carriers (27.9%). Most of the included studies used cross-sectional (63.3%) or longitudinal (24.4%) designs. Only 7.8% (n = 7) of articles described interventions. The most commonly examined focal areas included physical health issues, such as viral infections and injuries (56.7%), and health behaviors, such as substance use/misuse (40.0%). Other frequently addressed content areas were occupational stress (38.9%), interpersonal issues (32.2%), ship conditions (30.0%), and mental health (28.9%). Most articles (73.3%) addressed more than one content area. There was a high degree of variation in the measurement tools used; self-report surveys were the most common (48.9%), followed by objective physical, biological, or cognitive measures (32.2%) and medical and personnel record reviews (31.1%). CONCLUSIONS: The evidence map identified various gaps in the research pertaining to the health and performance of shipboard sailors. These gaps included a lack of research on the risk factors for common health and performance issues experienced by sailors and on the relationship between stressors of shipboard life and sailors' health, performance, and readiness. The results of this evidence map should be used to inform the development, implementation, and evaluation of interventions to improve the shipboard environment and/or the preventive health behaviors used by sailors while underway or deployed.

A Hybrid Effectiveness-Implementation Study of a Multi-Component Lighting Intervention for Hospital Shift Workers.

Simple lighting solutions may mitigate the harmful effects of shiftwork. This hybrid effectiveness-implementation study evaluated a multi-component lighting intervention in hospital nurses that included 6500 K architectural lighting in the nurses' station plus optional behavioral components (a lightbox, blueblocker glasses, eyemasks) with instruction about appropriately timed usage. Selective improvements from baseline were observed in on-shift performance, sleep quality, and caffeine consumption in day workers (all p < 0.05); off-shift sleepiness scores improved for night workers (p < 0.05). Further, self-reported measures of quality of life improved for both groups (p < 0.05). Preliminary implementation data from interviews and questionnaires suggest perceived benefits and high acceptability of the intervention.

Circadian rhythm bifurcation induces flexible phase resetting by reducing circadian amplitude.

Shift-work and jet-lag-related disorders are caused by the limited flexibility of the suprachiasmatic nucleus (SCN), a master circadian clock in the hypothalamus, to adjust to new light-dark (LD) cycles. Recent findings confirmed here establish that behavioral jet lag after simulated time-zone travel is virtually eliminated following bifurcated circadian entrainment under a novel and atypical 24-h light:dark:light:dark (LDLD) cycle. To investigate the mechanisms of this fast resetting, we examined the oscillatory stability of the SCN and peripheral tissues in LDLD-bifurcated mice employing the dissection procedure as a perturbing resetting stimulus. SCN, lung, liver, and adrenal tissue were extracted at times throughout the day from female and male PER2::Luciferase knock-in mice entrained to either LDLD or a normal LD cycle. Except for adrenals, the phase of the cultured explants was more strongly set by dissection under LDLD than under normal LD. Acute bioluminescence levels of SCN explants indicate that the rhythm amplitude of PER2 is reduced and phase is altered in LDLD. Real-time quantitative PCR suggests that amplitude and rhythmicity of canonical clock genes in the lung, liver, and kidney are also significantly reduced in LDLD in vivo. Furthermore, spatiotemporal patterns of PER2 peak time in cultured SCN were altered in LDLD. These results suggest that altered gene expression patterns in the SCN caused by bifurcation likely result in fast resetting of behavior and cultured explants, consistent with previously reported mathematical models. Thus, non-invasive, simple light manipulations can make circadian rhythms more adaptable to abrupt shifts in the environmental LD cycle.

Circadian Profile of an Emergency Medicine Department: Scheduling Practices and Their Effects on Sleep and Performance.

BACKGROUND: Shiftwork causes circadian disruption and is the primary reason for attrition from Emergency Medicine. OBJECTIVES: We aimed to develop concrete recommendations to mitigate negative effects of shiftwork based on measures of work, sleep, alertness, and performance in emergency physicians. METHODS: Thirty-one Emergency Medicine residents were surveyed retrospectively about sleep and alertness on different shifts. Additionally, the sleep, performance, and alertness of 22 Emergency Medicine resident and attending physicians was tracked continuously over 4 weeks via sleep logs, actigraphy, real-time reported sleepiness, and performance on a vigilance task. Schedules were analyzed for circadian disruption. Physicians also predicted their sleep schedules, which were compared with actual schedules; participants tracked extensions of shifts, schedule changes, and shifts in other hospitals. RESULTS: Daily rhythms were apparent in real-time performance and alertness data, with peaks at around 4 pm. Sleep difficulty was highest, sleep shortest, and alertness and performance lowest for night shifts. Emergency Medicine residents tended to cluster multiple night shifts in a row, despite evidence of accumulating sleep debt over consecutive shifts. There were many shifts that caused high circadian disruption, which could be avoided by simple amendments to scheduling practices. CONCLUSIONS: Circadian principles should be applied as suggested by the American College of Emergency Physicians. Chronotype should be considered in scheduling. Night shifts, particularly, should not be extended. Clustering all night shifts in a row should probably be discouraged. The additional vulnerabilities for night shift could be mitigated by adopting napping mid- or post night shift and by providing pay differentials.

Reported light in the sleep environment: enhancement of the sleep diary.

BACKGROUND: Light is the primary synchronizing cue for the circadian timing system, capable of exerting robust physiological effects, even with very dim and/or brief photic exposure. Mammals, including humans, are particularly susceptible to light at night. As such, measures of light in the sleeping environment are critical for evaluating sleep health. Sleep diaries provide inexpensive measures of sleep, but do not typically include light information. METHODS: Four questions probing visual perception of light in the bedtime and waking environments were added to the Consensus Sleep Diary for Morning administration. As part of a lighting intervention study, 18 hospital Labor and Delivery Department personnel completed the sleep diary for 1 week in each of two experimental conditions while wearing Actiwatch devices equipped with photosensors. Diary responses were evaluated against photosensor values from the beginning and end of each rest interval (n=194 rest intervals), as well as against sleep measures, utilizing linear mixed models. RESULTS: Responses to light questions were related to actual light measures at bedtime, controlling for shift type and experimental condition. In addition, subjective light information at bedtime and waking was related to both objective and subjective sleep parameters, with data generally indicating poorer sleep with light in the sleeping environment. CONCLUSION: Questions addressing perception of light in the sleeping environment may provide a crude yet affordable metric of relative photic intensity. Further, as responses relate to sleep outcomes, subjective light information may yield valuable insights regarding mechanisms and outcomes of clinical significance in sleep and circadian research.

Enhanced Circadian Entrainment in Mice and Its Utility under Human Shiftwork Schedules.

The circadian system is generally considered to be incapable of adjusting to rapid changes in sleep/work demands. In shiftworkers this leads to chronic circadian disruption and sleep loss, which together predict underperformance at work and negative health consequences. Two distinct experimental protocols have been proposed to increase circadian flexibility in rodents using dim light at night: rhythm bifurcation and T-cycle (i.e., day length) entrainment. Successful translation of such protocols to human shiftworkers could facilitate alignment of internal time with external demands. To assess entrainment flexibility following bifurcation and exposure to T-cycles, mice in Study 1 were repeatedly phase-shifted. Mice from experimental conditions rapidly phase-shifted their activity, while control mice showed expected transient misalignment. In Study 2 and 3, mice followed a several weeks-long intervention designed to model a modified DuPont or Continental shiftwork schedule, respectively. For both schedules, bifurcation and nocturnal dim lighting reduced circadian misalignment. Together, these studies demonstrate proof of concept that mammalian circadian systems can be rendered sufficiently flexible to adapt to multiple, rapidly changing shiftwork schedules. Flexible adaptation to exotic light-dark cycles likely relies on entrainment mechanisms that are distinct from traditional entrainment.

Extraordinary behavioral entrainment following circadian rhythm bifurcation in mice.

The mammalian circadian timing system uses light to synchronize endogenously generated rhythms with the environmental day. Entrainment to schedules that deviate significantly from 24 h (T24) has been viewed as unlikely because the circadian pacemaker appears capable only of small, incremental responses to brief light exposures. Challenging this view, we demonstrate that simple manipulations of light alone induce extreme plasticity in the circadian system of mice. Firstly, exposure to dim nocturnal illumination (<0.1 lux), rather than completely dark nights, permits expression of an altered circadian waveform wherein mice in light/dark/light/dark (LDLD) cycles "bifurcate" their rhythms into two rest and activity intervals per 24 h. Secondly, this bifurcated state enables mice to adopt stable activity rhythms under 15 or 30 h days (LDLD T15/T30), well beyond conventional limits of entrainment. Continuation of dim light is unnecessary for T15/30 behavioral entrainment following bifurcation. Finally, neither dim light alone nor a shortened night is sufficient for the extraordinary entrainment observed under bifurcation. Thus, we demonstrate in a non-pharmacological, non-genetic manipulation that the circadian system is far more flexible than previously thought. These findings challenge the current conception of entrainment and its underlying principles, and reveal new potential targets for circadian interventions.

Rapid Adjustment of Circadian Clocks to Simulated Travel to Time Zones across the Globe.

Daily rhythms in mammalian physiology and behavior are generated by a central pacemaker located in the hypothalamic suprachiasmatic nuclei (SCN), the timing of which is set by light from the environment. When the ambient light-dark cycle is shifted, as occurs with travel across time zones, the SCN and its output rhythms must reset or re-entrain their phases to match the new schedule-a sluggish process requiring about 1 day per hour shift. Using a global assay of circadian resetting to 6 equidistant time-zone meridians, we document this characteristically slow and distance-dependent resetting of Syrian hamsters under typical laboratory lighting conditions, which mimic summer day lengths. The circadian pacemaker, however, is additionally entrainable with respect to its waveform (i.e., the shape of the 24-h oscillation) allowing for tracking of seasonally varying day lengths. We here demonstrate an unprecedented, light exposure-based acceleration in phase resetting following 2 manipulations of circadian waveform. Adaptation of circadian waveforms to long winter nights (8 h light, 16 h dark) doubled the shift response in the first 3 days after the shift. Moreover, a bifurcated waveform induced by exposure to a novel 24-h light-dark-light-dark cycle permitted nearly instant resetting to phase shifts from 4 to 12 h in magnitude, representing a 71% reduction in the mismatch between the activity rhythm and the new photocycle. Thus, a marked enhancement of phase shifting can be induced via nonpharmacological, noninvasive manipulation of the circadian pacemaker waveform in a model species for mammalian circadian rhythmicity. Given the evidence of conserved flexibility in the human pacemaker waveform, these findings raise the promise of flexible resetting applicable to circadian disruption in shift workers, frequent time-zone travelers, and any individual forced to adjust to challenging schedules.

Understanding suffering: Utermohlen's self-portraits and Alzheimer's disease.

Human suffering is a universal experience simply defined as, or associated with, physical or psychological pain and distress. Faculty seeks ways to help its students understand and ease their patients' suffering. The author uses Alzheimer's disease as an exemplar of suffering and describes a creative teaching strategy using 9 self-portraits that chronicle American-born artist William Utermohlen's deterioration from the disease.

Changing the waveform of circadian rhythms: considerations for shift-work.

Circadian disruption in shift-work is common and has deleterious effects on health and performance. Current efforts to mitigate these harms reasonably focus on the phase of the circadian pacemaker, which unfortunately in humans, shifts slowly and often incompletely. Temporal reorganization of rhythmic waveform (i.e., the shape of its 24 h oscillation), rather than phase, however, may better match performance demands of shift-workers and can be quickly and feasibly implemented in animals. In fact, a bifurcated pacemaker waveform may permit stable entrainment of a bimodal sleep/wake rhythm promoting alertness in both night and daylight hours. Although bifurcation has yet to be formally assessed in humans, evidence of conserved properties of circadian organization and plasticity predict its occurrence: humans respond to conventional manipulations of waveform (e.g., photoperiodism); behaviorally, the sleep/wake rhythm is adaptable; and finally, the human circadian system likely derives from the same multiple cellular oscillators that permit waveform flexibility in the rodent pacemaker. In short, investigation into untried manipulations of waveform in humans to facilitate adjustment to challenging schedules is justified.