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The objectives of the study reported here were to document consumer attitudes, risk understanding, and behaviors with respect to sun safety and to define consumer preferences for protective shirt design and labeling. A sample of 1,508 adults was surveyed at the 2002 Farm Progress Show sun-safety exhibit. Results showed that people generally understood the long-term risk from exposure to ultraviolet radiation, but did not routinely use sun-protective clothing to avoid it. Design features preferred by consumers for sun-safe shirts were significantly related to demographic characteristics, including age, education, sex, occupation, and employment status. Overall, the sun-safe shirt design most preferred can be summarized as a casual-style, solid-color, knit shirt with a crew neck or collar. Over 80 percent of participants favored Ultraviolet Protective Factor labeling as well as other consumer labeling such as information on care, fiber content, colorfastness, and finishes applied to shirts. Industrial and educational implications are provided. [ABSTRACT FROM AUTHOR]

Focuses on the five reported cases of Cat Scratch Disease encephalitis in Broward and Palm Beach Counties in Florida on the year 1994. Identification of exposure to stray kittens as the only common link among affected children; Nature of treatments for the patients.

Background: Historically, percutaneous transcatheter left atrial appendage closure (LAAC) has been performed under general anesthesia (GA) with transesophageal echocardiographic images obtained by a noninvasive cardiologist and usually requires an overnight hospital stay. Alternatively, we present our single-center experience performing LAACs under deep sedation (DS), employing an echocardiographic technician instead of a noninvasive cardiologist, and expediting same-day discharge. Mid- to long-term outcomes were also evaluated with follow-up imaging at a 45-day visit., Objective: The purpose of this study was to demonstrate the safety, feasibility, and outcomes of our single-operator-technician LAAC approach., Methods: A total of 150 patients, with elevated CHA 2 DS 2 -VASc scores (a mean of 4 points), underwent transesophageal echocardiography-guided LAAC using the WATCHMAN FLX (Boston Scientific, Marlborough, MA) device under DS., Results: The mean age of patients was 78 years. Seventy-six (51%) were men. One hundred forty-seven patients (98%) had the LAAC device successfully implanted, and 145 (97%) were discharged on the same day. Nine patients (6%) required conversion from DS to GA. Only 5 patients (4%) had complications during the procedure. None of the patients died or had complications from DS. During the 45-day follow-up visit, one patient had a significant peridevice leak (maximum diameter ≥ 5 mm) and another patient had device-related thrombosis., Conclusion: Our novel single-operator-technician approach under DS is safe and feasible. Implementing protocols to simplify the traditional 2-operator approach under GA by using DS and an echocardiography technician as well as incorporating same-day discharge could make LAACs more widely available and potentially reduce procedural costs., Competing Interests: While the authors did not receive specific funding or sponsorship for this manuscript's publication, Drs Stone, Abdelrahim, Crossen, and Prasad were compensated for performing percutaneous left atrial appendage closures as electrophysiologists. The remaining authors declared no conflicts of interest., (© 2024 Heart Rhythm Society. Published by Elsevier Inc.)

Hydrologic reconstructions from North America are largely unknown for the Middle Miocene. Examination of fungal palynomorph assemblages coupled with traditional plant-based palynology permits delineation of local, as opposed to regional, climate signals and provides a baseline for study of ancient fungas. Here, the Fungi in a Warmer World project presents paleoecology and paleoclimatology of 351 fungal morphotypes from 3 sites in the United States: the Clarkia Konservat-Lagerstätte site (Idaho), the Alum Bluff site (Florida), and the Bouie River site (Mississippi). Of these, 83 fungi are identified as extant taxa and 41 are newly reported from the Miocene. Combining new plant-based paleoclimatic reconstructions with funga-based paleoclimate reconstructions, we demonstrate cooling and hydrologic changes from the Miocene climate optimum to the Serravallian. In the southeastern United States, this is comparable to that reconstructed with pollen and paleobotany alone. In the northwestern United States, cooling is greater than indicated by other reconstructions and hydrology shifts seasonally, from no dry season to a dry summer season. Our results demonstrate the utility of fossil fungi as paleoecologic and paleoclimatic proxies and that warmer than modern geological time intervals do not match the "wet gets wetter, dry gets drier" paradigm. Instead, both plants and fungi show an invigorated hydrological cycle across mid-latitude North America., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Jennifer M. K. O’Keefe et al.)

The amount of time available in a day is fixed, and consequently, sleep is often sacrificed for waking activities. For college students, daily activities, comprised of scheduled classes, work, study, social, and other extracurricular events, are major contributors to insufficient and poor-quality sleep. We investigated the impact of daily schedules on sleep-wake timing in 223 undergraduate students (age: 18-27 years, 37% females) from a United States university, who were monitored for ~30 days. Sleep-wake timing and daily recorded activities (attendance at academic, studying, exercise-based, and/or extracurricular activities) were captured by a twice-daily internet-based diary. Wrist-worn actigraphy was conducted to confirm sleep-wake timing. Linear mixed models were used to quantify associations between daily schedule and sleep-wake timing at between-person and within-person levels. Later scheduled start time predicted later sleep onset (between and within: p < .001), longer sleep duration on the previous night (within: p < .001), and later wake time (between and within: p < .001). Later schedule end time predicted later sleep onset (within: p < .001) and shorter sleep duration that night (within: p < .001). For every 1 hour that activities extended beyond 10 pm, sleep onset was delayed by 15 minutes at the within-person level and 40 minutes at the between-person level, and sleep duration was shortened by 6 and 23 minutes, respectively. Increased daily documented total activity time predicted earlier wake (between and within: p < .001), later sleep onset that night (within: p < .05), and shorter sleep duration (within: p < .001). These results indicate that daily schedules are an important factor in sleep timing and duration in college students. Clinical Trial: Multi-scale Modeling of Sleep Behaviors in Social Networks; URL: https://clinicaltrials.gov/study/NCT02846077; Registration:NCT02846077., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society.)

Internal circadian phase assessment is increasingly acknowledged as a critical clinical tool for the diagnosis, monitoring, and treatment of circadian rhythm sleep-wake disorders and for investigating circadian timing in other medical disorders. The widespread use of in-laboratory circadian phase assessments in routine practice has been limited, most likely because circadian phase assessment is not required by formal diagnostic nosologies, and is not generally covered by insurance. At-home assessment of salivary dim light melatonin onset (DLMO, a validated circadian phase marker) is an increasingly accepted approach to assess circadian phase. This approach may help meet the increased demand for assessments and has the advantages of lower cost and greater patient convenience. We reviewed the literature describing at-home salivary DLMO assessment methods and identified factors deemed to be important to successful implementation. Here, we provide specific protocol recommendations for conducting at-home salivary DLMO assessments to facilitate a standardized approach for clinical and research purposes. Key factors include control of lighting, sampling rate, and timing, and measures of patient compliance. We include findings from implementation of an optimization algorithm to determine the most efficient number and timing of samples in patients with Delayed Sleep-Wake Phase Disorder. We also provide recommendations for assay methods and interpretation. Providing definitive criteria for each factor, along with detailed instructions for protocol implementation, will enable more widespread adoption of at-home circadian phase assessments as a standardized clinical diagnostic, monitoring, and treatment tool., (© 2024 The Author(s). Journal of Pineal Research published by John Wiley & Sons Ltd.)

Background: Treatment for post-traumatic greater occipital neuralgia (GON) includes serial injections of steroid/anesthetic. While these injections can alleviate pain, effects can be transient, frequently lasting only 1 month. As a potential alternative, platelet-rich plasma (PRP) injections are an emerging biological treatment with beneficial effects in peripheral nerve disorders. We investigated the feasibility, safety, and effectiveness of a single PRP injection for post-traumatic GON in comparison to saline or steroid/anesthetic injection., Methods: In this pilot randomized, double-blinded, placebo-controlled trial, 32 adults with post-traumatic GON were allocated 1:1:1 to receive a single ultrasound-guided injection of (1) autologous PRP (2) steroid/anesthetic or (3) normal saline. Our primary outcome was feasibility (recruitment, attendance, retention) and safety (adverse events). Exploratory measures included headache intensity and frequency (daily headache diaries) and additional questionnaires (headache impact, and quality of life) assessed at pre-injection, 1 week, 1 month, and 3 months post-injection., Results: We screened 67 individuals, 55% were eligible and 95% of those participated. Over 80% of daily headache diaries were completed with 91% of participants completing the 3-month outcome questionnaires. No serious adverse events were reported. There were no significant differences between groups for headache intensity or frequency. Headache impact on function test-6 scores improved at 3 month in the PRP ( β  = -9.7, 95% CI [-15.6, -3.74], p  = 0.002) and saline ( β  = -6.7 [-12.7, -0.57], p  = 0.033) groups but not steroid/anesthetic group ( p  = 0.135)., Conclusion: PRP is a feasible and safe method for treating post-traumatic GON with comparable results to saline and steroid/anaesthetic. Further trials with larger sample sizes are required. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04051203., Competing Interests: CD reports research grants from the Canadian Institute of Health research, Hotchkiss brain institute, Province of Alberta, National Football League, Canadian Department of National Defense, Pfizer pharmaceuticals as well fees as an expert panelist from Teva Pharmaceuticals. The Arthrex Angel System was loaned to the team for the purpose of this study by Tribe Medical Group/Arthrex Inc. The Arthrex Angel PRP kits were also provided by Tribe Medical Group. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stone, Campbell, Tabor, Bonfield, Machan, Shan and Debert.)

Competing Interests: While the authors did not receive specific funding or sponsorship for this manuscript’s publication, Dr Arriola received compensation for successfully cannulating and closing the hepatic veins in his capacity as an interventional radiologist. Drs Prasad and Stone were also compensated for performing the percutaneous left atrial appendage closures as electrophysiologists. The remaining authors declared no conflict of interest.

Study Objectives: Sleep and affect are closely related. Whether modifiable cognitive factors moderate this association is unclear. This study examined whether Dysfunctional Beliefs and Attitudes about Sleep moderate the impact of sleep on next-day affect in young people., Methods: Four hundred and sixty-eight young people (205 adolescents, 54.1% female, M ± SD age =16.92 ± 0.87; 263 emerging adults, 71.9% female, M±SD age =21.29 ± 1.73) self-reported sleep and affect, and wore an actigraph for 7-28 days, providing >5000 daily observations. Linear mixed-effects models tested whether Dysfunctional Beliefs and Attitudes about Sleep moderated daily associations between self-reported and actigraphic sleep duration, sleep efficiency, and next-day affect on between- and within-person levels. Both valence (positive/negative) and arousal (high/low) dimensions of affect were examined. Covariates included age, sex, race/ethnicity, day of week, and previous-day affect., Results: Dysfunctional Beliefs and Attitudes about Sleep significantly moderated sleep and high arousal positive affect associations on between- but not within-person levels. Individuals with higher Dysfunctional Beliefs and Attitudes about Sleep (+1 SD) and lower average sleep duration (actigraphic: p = .020; self-reported: p = .047) and efficiency (actigraphic: p = .047) had significantly lower levels of high arousal positive affect. After adjusting for multiple comparisons, Dysfunctional Beliefs and Attitudes about Sleep did not moderate relationships between sleep duration and low arousal positive affect (p ≥ .340)., Conclusions: Young people with more unhelpful beliefs about sleep and shorter, or poorer, sleep may experience dampened levels of high arousal positive affect. DBAS may constitute a modifiable factor increasing affective vulnerability on a global but not day-to-day level. Intervention studies are needed to determine if changing Dysfunctional Beliefs and Attitudes about Sleep may reduce sleep-related affect disturbances in young people., Competing Interests: Declaration of conflict of interest None. All authors have approved the final article., (Copyright © 2023 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Study Objectives: Light is the main time cue for the human circadian system. Sleep and light are intrinsically linked; light exposure patterns can influence sleep patterns and sleep can influence light exposure patterns. However, metrics for quantifying light regularity are lacking, and the relationship between sleep and light regularity is underexplored. We developed new metrics for light regularity and demonstrated their utility in adolescents, across school term and vacation., Methods: Daily sleep/wake and light patterns were measured using wrist actigraphy in 75 adolescents (54% male, 17.17 ± 0.83 years) over 2 weeks of school term and a subsequent 2-week vacation. The Sleep Regularity Index (SRI) and social jetlag were computed for each 2-week block. Light regularity was assessed using (1) variation in mean daily light timing (MLiT); (2) variation in daily photoperiod; and (3) the Light Regularity Index (LRI). Associations between SRI and each light regularity metric were examined, and within-individual changes in metrics were examined between school and vacation., Results: Higher SRI was significantly associated with more regular LRI scores during both school and vacation. There were no significant associations of SRI with variation in MLiT or daily photoperiod. Compared to school term, all three light regularity metrics were less variable during the vacation., Conclusions: Light regularity is a multidimensional construct, which until now has not been formally defined. Irregular sleep patterns are associated with lower LRI, indicating that irregular sleepers also have irregular light inputs to the circadian system, which likely contributes to circadian disruption., (© Sleep Research Society 2023. Published by Oxford University Press on behalf of the Sleep Research Society.)

Modeling and simulation of small molecules such as drugs and biological cofactors have been both a major focus of computational chemistry for decades and a growing need among computational biophysicists who seek to investigate the interaction of different types of ligands with biomolecules. Of particular interest in this regard are quantum mechanical (QM) calculations that are used to more accurately describe such small molecules, which can be of heterogeneous structures and chemistry, either in purely QM calculations or in hybrid QM/molecular mechanics (MM) simulations. QM programs are also used to develop MM force field parameters for small molecules to be used along with established force fields for biomolecules in classical simulations. With this growing need in mind, here we report a set of software tools developed and closely integrated within the broadly used molecular visualization/analysis program, VMD, that allow the user to construct, modify, and parametrize small molecules and prepare them for QM, hybrid QM/MM, or classical simulations. The tools also provide interactive analysis and visualization capabilities in an easy-to-use and integrated environment. In this paper, we briefly report on these tools and their major features and capabilities, along with examples of how they can facilitate molecular research in computational biophysics that might be otherwise prohibitively complex.

Computational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication and inheritance of genetic material. By creating a computational framework to model systems of replicating bacterial chromosomes as polymers at 10 bp resolution with Brownian dynamics, we investigate changes in chromosome organization during replication and extend the applicability of an existing whole-cell model (WCM) for a genetically minimal bacterium, JCVI-syn3A, to the entire cell-cycle. To achieve cell-scale chromosome structures that are realistic, we model the chromosome as a self-avoiding homopolymer with bending and torsional stiffnesses that capture the essential mechanical properties of dsDNA in Syn3A. In addition, the conformations of the circular DNA must avoid overlapping with ribosomes identitied in cryo-electron tomograms. While Syn3A lacks the complex regulatory systems known to orchestrate chromosome segregation in other bacteria, its minimized genome retains essential loop-extruding structural maintenance of chromosomes (SMC) protein complexes (SMC-scpAB) and topoisomerases. Through implementing the effects of these proteins in our simulations of replicating chromosomes, we find that they alone are sufficient for simultaneous chromosome segregation across all generations within nested theta structures. This supports previous studies suggesting loop-extrusion serves as a near-universal mechanism for chromosome organization within bacterial and eukaryotic cells. Furthermore, we analyze ribosome diffusion under the influence of the chromosome and calculate in silico chromosome contact maps that capture inter-daughter interactions. Finally, we present a methodology to map the polymer model of the chromosome to a Martini coarse-grained representation to prepare molecular dynamics models of entire Syn3A cells, which serves as an ultimate means of validation for cell states predicted by the WCM., Competing Interests: JES was employed by the company NVIDIA Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gilbert, Thornburg, Brier, Stevens, Grünewald, Stone, Marrink and Luthey-Schulten.)

This paper assesses and reports the experience of ten teams working to port, validate, and benchmark several High Performance Computing applications on a novel GPU-accelerated Arm testbed system. The testbed consists of eight NVIDIA Arm HPC Developer Kit systems, each one equipped with a server-class Arm CPU from Ampere Computing and two data center GPUs from NVIDIA Corp. The systems are connected together using InfiniBand interconnect. The selected applications and mini-apps are written using several programming languages and use multiple accelerator-based programming models for GPUs such as CUDA, OpenACC, and OpenMP offloading. Working on application porting requires a robust and easy-to-access programming environment, including a variety of compilers and optimized scientific libraries. The goal of this work is to evaluate platform readiness and assess the effort required from developers to deploy well-established scientific workloads on current and future generation Arm-based GPU-accelerated HPC systems. The reported case studies demonstrate that the current level of maturity and diversity of software and tools is already adequate for large-scale production deployments.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication transcription complex (RTC) is a multi-domain protein responsible for replicating and transcribing the viral mRNA inside a human cell. Attacking RTC function with pharmaceutical compounds is a pathway to treating COVID-19. Conventional tools, e.g., cryo-electron microscopy and all-atom molecular dynamics (AAMD), do not provide sufficiently high resolution or timescale to capture important dynamics of this molecular machine. Consequently, we develop an innovative workflow that bridges the gap between these resolutions, using mesoscale fluctuating finite element analysis (FFEA) continuum simulations and a hierarchy of AI-methods that continually learn and infer features for maintaining consistency between AAMD and FFEA simulations. We leverage a multi-site distributed workflow manager to orchestrate AI, FFEA, and AAMD jobs, providing optimal resource utilization across HPC centers. Our study provides unprecedented access to study the SARS-CoV-2 RTC machinery, while providing general capability for AI-enabled multi-resolution simulations at scale.

py-MCMD, an open-source Python software, provides a robust workflow layer that manages communication of relevant system information between the simulation engines NAMD and GOMC and generates coherent thermodynamic properties and trajectories for analysis. To validate the workflow and highlight its capabilities, hybrid Monte Carlo/molecular dynamics (MC/MD) simulations are performed for SPC/E water in the isobaric-isothermal ( NPT ) and grand canonical (GC) ensembles as well as with Gibbs ensemble Monte Carlo (GEMC). The hybrid MC/MD approach shows close agreement with reference MC simulations and has a computational efficiency that is 2 to 136 times greater than traditional Monte Carlo simulations. MC/MD simulations performed for water in a graphene slit pore illustrate significant gains in sampling efficiency when the coupled-decoupled configurational-bias MC (CD-CBMC) algorithm is used compared with simulations using a single unbiased random trial position. Simulations using CD-CBMC reach equilibrium with 25 times fewer cycles than simulations using a single unbiased random trial position, with a small increase in computational cost. In a more challenging application, hybrid grand canonical Monte Carlo/molecular dynamics (GCMC/MD) simulations are used to hydrate a buried binding pocket in bovine pancreatic trypsin inhibitor. Water occupancies produced by GCMC/MD simulations are in close agreement with crystallographically identified positions, and GCMC/MD simulations have a computational efficiency that is 5 times better than MD simulations. py-MCMD is available on GitHub at https://github.com/GOMC-WSU/py-MCMD.

Background: During adolescence, sleep and circadian timing shift later, contributing to restricted sleep duration and irregular sleep-wake patterns. The association of these developmental changes in sleep and circadian timing with cognitive functioning, and consequently academic outcomes, has not been examined prospectively. The role of ambient light exposure in these developmental changes is also not well understood. Here, we describe the protocol for the Circadian Light in Adolescence, Sleep and School (CLASS) Study that will use a longitudinal design to examine the associations of sleep-wake timing, circadian timing and light exposure with academic performance and sleepiness during a critical stage of development. We also describe protocol adaptations to enable remote data collection when required during the COVID-19 pandemic., Methods: Approximately 220 healthy adolescents aged 12-13 years (school Year 7) will be recruited from the general community in Melbourne, Australia. Participants will be monitored at five 6 monthly time points over 2 years. Sleep and light exposure will be assessed for 2 weeks during the school term, every 6 months, along with self-report questionnaires of daytime sleepiness. Circadian phase will be measured via dim light melatonin onset once each year. Academic performance will be measured via national standardised testing (National Assessment Program-Literacy and Numeracy) and the Wechsler Individual Achievement Test-Australian and New Zealand Standardised Third Edition in school Years 7 and 9. Secondary outcomes, including symptoms of depression, anxiety and sleep disorders, will be measured via questionnaires., Discussion: The CLASS Study will enable a comprehensive longitudinal assessment of changes in sleep-wake timing, circadian phase, light exposure and academic performance across a key developmental stage in adolescence. Findings may inform policies and intervention strategies for secondary school-aged adolescents., Ethics and Dissemination: Ethical approval was obtained by the Monash University Human Research Ethics Committee and the Victorian Department of Education. Dissemination plans include scientific publications, scientific conferences, via stakeholders including schools and media., Study Dates: Recruitment occurred between October 2019 and September 2021, data collection from 2019 to 2023., Competing Interests: Competing interests: JES, MR, EC, AJH, SL, JW, MAC and BB have no conflicts to declare. AJKP was an investigator on projects supported by the CRC for Alertness, Safety and Productivity, and he has received research funding from Versalux and Delos. EBK reports (non-government, non-university): Travel support from World Conference of Chronobiology, Gordon Research Conference, Sleep Research Society, Santa Fe Institute, German Sleep Society (DGSM); Consulting/grant reviews income from Puerto Rice Science, Technology, and Research Trust, National Sleep Foundation, Sanofi-Genzyme; Family member owns Chronsulting. SWL has had a number of commercial interests in the last 2 years (2019–2021). His interests were reviewed and managed by Mass General Brigham in accordance with their conflict of interest policies. No interests are directly related to the research or topic reported in this paper but, in the interests of full disclosure, are outlined below. SWL has received consulting fees from the EyeJust, Rec Room, Six Senses, and Stantec; and has current consulting contracts with Akili Interactive; Apex 2100; Consumer Sleep Solutions; Hintsa Performance AG; KBR Wyle Services, Light Cognitive; Lighting Science Group Corporation/HealthE; Look Optic; Mental Workout/Timeshifter and View. He has received honoraria and travel or accommodation expenses from MIT, Roxbury Latin School, and University of Toronto, and travel or accommodation expenses (no honoraria) from Wiley; and royalties from Oxford University Press. He holds equity in iSleep Pty. He has received an unrestricted equipment gift from F. Lux Software LLC, and holds an investigator-initiated grant from F. Lux Software. He has a Clinical Research Support Agreement and a Clinical Trials Agreement with Vanda Pharmaceuticals. He is an unpaid Board Member of the Midwest Lighting Institute (non-profit). He was a Program Leader for the CRC for Alertness, Safety and Productivity, Australia, through an adjunct professor position at Monash University (2015–2019). He is currently a part-time faculty member at the University of Surrey. He has served as a paid expert in legal proceedings related to light, sleep and health. SMWR was a Program Leader for the CRC for Alertness, Safety and Productivity, Australia, and currently serves as the Chair of the Sleep Health Foundation. SMWR reports grants from Vanda Pharmaceuticals, Philips Respironics, Cephalon, Rio Tinto and Shell and receiving equipment support and consultancy fees through his institution from Vanda, Circadian Therapeutics, Optalert, Tyco Healthcare, Compumedics, Mental Health Professionals Network and Teva Pharmaceuticals, which are not related to this paper., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

ANARI is a new 3-D rendering API, an emerging Khronos standard that enables visualization applications to leverage the state-of-the-art rendering techniques across diverse hardware platforms and rendering engines. Visualization applications have historically embedded custom-written renderers to enable them to provide the necessary combination of features, performance, and visual fidelity required by their users. As computing power, rendering algorithms, dedicated rendering hardware acceleration operations, and associated low-level APIs have advanced, the effort and costs associated with maintaining renderers within visualization applications have risen dramatically. The rising cost and complexity associated with renderer development creates an undesirable barrier for visualization applications to be able to fully benefit from the latest rendering methods and hardware. ANARI directly addresses these challenges by providing a high-level, visualization-oriented API that abstracts low-level rendering algorithms and hardware acceleration details while providing easy and efficient access to diverse ANARI implementations, thereby enabling visualization applications to support the state-of-the-art rendering capabilities.

Background: Over the past 15 years, there has been substantial growth in web-based psychological interventions. We summarize evidence regarding the efficacy of web-based self-directed psychological interventions on depressive, anxiety and distress symptoms in people living with a chronic health condition., Method: We searched Medline, PsycINFO, CINAHL, EMBASE databases and Cochrane Database from 1990 to 1 May 2019. English language papers of randomized controlled trials (usual care or waitlist control) of web-based psychological interventions with a primary or secondary aim to reduce anxiety, depression or distress in adults with a chronic health condition were eligible. Results were assessed using narrative synthases and random-effects meta-analyses., Results: In total 70 eligible studies across 17 health conditions [most commonly: cancer (k = 20), chronic pain (k = 9), arthritis (k = 6) and multiple sclerosis (k = 5), diabetes (k = 4), fibromyalgia (k = 4)] were identified. Interventions were based on CBT principles in 46 (66%) studies and 42 (60%) included a facilitator. When combining all chronic health conditions, web-based interventions were more efficacious than control conditions in reducing symptoms of depression g = 0.30 (95% CI 0.22-0.39), anxiety g = 0.19 (95% CI 0.12-0.27), and distress g = 0.36 (95% CI 0.23-0.49)., Conclusion: Evidence regarding effectiveness for specific chronic health conditions was inconsistent. While self-guided online psychological interventions may help to reduce symptoms of anxiety, depression and distress in people with chronic health conditions in general, it is unclear if these interventions are effective for specific health conditions. More high-quality evidence is needed before definite conclusions can be made.

Study Objectives: The study aimed to, for the first time, (1) compare sleep, circadian phase, and alertness of intensive care unit (ICU) nurses working rotating shifts with those predicted by a model of arousal dynamics; and (2) investigate how different environmental constraints affect predictions and agreement with data., Methods: The model was used to simulate individual sleep-wake cycles, urinary 6-sulphatoxymelatonin (aMT6s) profiles, subjective sleepiness on the Karolinska Sleepiness Scale (KSS), and performance on a Psychomotor Vigilance Task (PVT) of 21 ICU nurses working day, evening, and night shifts. Combinations of individual shift schedules, forced wake time before/after work and lighting, were used as inputs to the model. Predictions were compared to empirical data. Simulations with self-reported sleep as an input were performed for comparison., Results: All input constraints produced similar prediction for KSS, with 56%-60% of KSS scores predicted within ±1 on a day and 48%-52% on a night shift. Accurate prediction of an individual's circadian phase required individualized light input. Combinations including light information predicted aMT6s acrophase within ±1 h of the study data for 65% and 35%-47% of nurses on diurnal and nocturnal schedules. Minute-by-minute sleep-wake state overlap between the model and the data was between 81 ± 6% and 87 ± 5% depending on choice of input constraint., Conclusions: The use of individualized environmental constraints in the model of arousal dynamics allowed for accurate prediction of alertness, circadian phase, and sleep for more than half of the nurses. Individual differences in physiological parameters will need to be accounted for in the future to further improve predictions., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society.)

Over the past 18 months, the need to perform atomic detail molecular dynamics simulations of the SARS-CoV-2 virion, its spike protein, and other structures related to the viral infection cycle has led biomedical researchers worldwide to urgently seek out all available biomolecular structure information, appropriate molecular modeling and simulation software, and the necessary computing resources to conduct their work. We describe our experiences from several COVID-19 research collaborations and the challenges they presented in terms of our molecular modeling software development and support efforts, our laboratory's local computing environment, and our scientists' use of non-traditional HPC hardware platforms such as public clouds for large scale parallel molecular dynamics simulations.

Objective : Irregular sleep-wake patterns are associated with poor health outcomes. However, factors that lead individuals to adopt more regular sleep-wake patterns are not well understood. This study aimed to (i) examine the relationship between sleep regularity and attitudes toward sleep in undergraduates; (ii) test an intervention to improve sleep regularity based on personalized feedback; and (iii) investigate whether changes in attitudes toward sleep associate with improved sleep regularity. Methods : Sleep-wake timing of 45 students (19.7 ± 1.8 years) was monitored daily over two weeks using an app-based diary. The least regular sleepers, calculated using the Sleep Regularity Index (SRI ≤ 81.4; N = 22), completed a four-week randomized control intervention (RCI) designed to improve sleep regularity. The Charlotte Attitudes Toward Sleep (CATS) scale was administered at baseline and post-RCI, with subscales measuring attitudes toward sleep as a time commitment (Time), and as a beneficial/enjoyable behavior (Benefits). Results : CATS Time was positively associated with SRI at baseline (r 2  = 0.16, p =.006) and during the four-week RCI (r 2  = 0.29, p =.01). CATS Benefits was not associated with SRI but was associated with sleep quality. There was no significant improvement in SRI during the intervention. The relationship between change in CATS Time and change in SRI (baseline vs. RCI) differed between intervention and control groups (r 2  = 0.27, p =.03). Conclusions : Attitudes toward sleep as a time commitment are associated with sleep regularity and should be considered as a target in future interventions aiming to improve sleep regularity.

During the COVID-19 pandemic, schools around the world rapidly transitioned from in-person to remote learning, providing an opportunity to examine the impact of in-person vs remote learning on sleep, circadian timing, and mood. We assessed sleep-wake timing using wrist actigraphy and sleep diaries over 1-2 weeks during in-person learning (n = 28) and remote learning (n = 58, where n = 27 were repeat assessments) in adolescents (age M ± SD = 12.79 ± 0.42 years). Circadian timing was measured under a single condition in each individual using salivary melatonin (Dim Light Melatonin Onset; DLMO). Online surveys assessed mood (PROMIS Pediatric Anxiety and Depressive Symptoms) and sleepiness (Epworth Sleepiness Scale - Child and Adolescent) in each condition. During remote (vs in-person) learning: (i) on school days, students went to sleep 26 minutes later and woke 49 minutes later, resulting in 22 minutes longer sleep duration (all P < .0001); (ii) DLMO time did not differ significantly between conditions, although participants woke at a later circadian phase (43 minutes, P = .03) during remote learning; and (iii) participants reported significantly lower sleepiness (P = .048) and lower anxiety symptoms (P = .006). Depressive symptoms did not differ between conditions. Changes in mood symptoms were not mediated by sleep. Although remote learning continued to have fixed school start times, removing morning commutes likely enabled adolescents to sleep longer, wake later, and to wake at a later circadian phase. These results indicate that remote learning, or later school start times, may extend sleep and improve some subjective symptoms in adolescents., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We develop a generalizable AI-driven workflow that leverages heterogeneous HPC resources to explore the time-dependent dynamics of molecular systems. We use this workflow to investigate the mechanisms of infectivity of the SARS-CoV-2 spike protein, the main viral infection machinery. Our workflow enables more efficient investigation of spike dynamics in a variety of complex environments, including within a complete SARS-CoV-2 viral envelope simulation, which contains 305 million atoms and shows strong scaling on ORNL Summit using NAMD. We present several novel scientific discoveries, including the elucidation of the spike's full glycan shield, the role of spike glycans in modulating the infectivity of the virus, and the characterization of the flexible interactions between the spike and the human ACE2 receptor. We also demonstrate how AI can accelerate conformational sampling across different systems and pave the way for the future application of such methods to additional studies in SARS-CoV-2 and other molecular systems., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Post-traumatic headaches (PTH) are a common sequelae of traumatic brain injury (TBI) and greatly impact patient function and quality of life. Post-traumatic greater occipital neuralgia (GON) is a type of post-traumatic headache. Conventional treatment includes steroid/anesthetic injections which typically alleviate pain but have a short duration of effect. Platelet-rich plasma (PRP) is an emerging biological treatment for numerous degenerative disorders, including peripheral nerve disorders. The primary aim of this pilot study is to evaluate whether a randomized control trial of PRP for the treatment of GON in patients with post-traumatic headaches is feasible in regard to recruitment, adherence, retention, and adherence and adverse events. Exploratory aims include improvement in pain, function, and quality of life in patients with post-traumatic GON receiving PRP compared to steroid/anesthetic and normal saline injections., Methods: Thirty adults (over 18 years of age) with post-traumatic GON will be randomized into one of three groups: (1) autologous PRP injection, (2) steroid/anesthetic injection (standard care), or (3) placebo injection with normal saline. Injections will be performed to the greater occipital nerve under ultrasound guidance by a trained physician. Daily headache intensity and frequency data will be collected pre-injection and for the duration of the study period. Feasibility will be defined as greater than 30% recruitment, 70% completion of intervention, 70% retention, and less than 2 minor adverse events. Exploratory outcomes will be explored using the Headache Impact Test-6 (HIT-6, a valid and reliable 6-item questionnaire for assessment of the impact of headaches across different diagnostic groups of headaches) and the quality of life in following brain injury questionnaire (QOILIBRI)., Discussion: This pilot study will be the first to evaluate the feasibility of PRP as a potential treatment of GON in patients with post-traumatic headache., Trial Registration: ClinicalTrials.gov - NCT04051203 (registered August 9, 2019).

There is large interindividual variability in circadian timing, which is underestimated by mathematical models of the circadian clock. Interindividual differences in timing have traditionally been modeled by changing the intrinsic circadian period, but recent findings reveal an additional potential source of variability: large interindividual differences in light sensitivity. Using an established model of the human circadian clock with real-world light recordings, we investigated whether changes in light sensitivity parameters or intrinsic circadian period could capture variability in circadian timing between and within individuals. Healthy participants ( n = 12, aged 18-26 years) underwent continuous light monitoring for 3 weeks (Actiwatch Spectrum). Salivary dim-light melatonin onset (DLMO) was measured each week. Using the recorded light patterns, a sensitivity analysis for predicted DLMO times was performed, varying 3 model parameters within physiological ranges: (1) a parameter determining the steepness of the dose-response curve to light ( p ), (2) a parameter determining the shape of the phase-response curve to light ( K ), and (3) the intrinsic circadian period ( tau ). These parameters were then fitted to obtain optimal predictions of the three DLMO times for each individual. The sensitivity analysis showed that the range of variation in the average predicted DLMO times across participants was 0.65 h for p , 4.28 h for K , and 3.26 h for tau . The default model predicted the DLMO times with a mean absolute error of 1.02 h, whereas fitting all 3 parameters reduced the mean absolute error to 0.28 h. Fitting the parameters independently, we found mean absolute errors of 0.83 h for p , 0.53 h for K , and 0.42 h for tau . Fitting p and K together reduced the mean absolute error to 0.44 h. Light sensitivity parameters captured similar variability in phase compared with intrinsic circadian period, indicating they are viable targets for individualizing circadian phase predictions. Future prospective work is needed that uses measures of light sensitivity to validate this approach.

We develop a generalizable AI-driven workflow that leverages heterogeneous HPC resources to explore the time-dependent dynamics of molecular systems. We use this workflow to investigate the mechanisms of infectivity of the SARS-CoV-2 spike protein, the main viral infection machinery. Our workflow enables more efficient investigation of spike dynamics in a variety of complex environments, including within a complete SARS-CoV-2 viral envelope simulation, which contains 305 million atoms and shows strong scaling on ORNL Summit using NAMD. We present several novel scientific discoveries, including the elucidation of the spike's full glycan shield, the role of spike glycans in modulating the infectivity of the virus, and the characterization of the flexible interactions between the spike and the human ACE2 receptor. We also demonstrate how AI can accelerate conformational sampling across different systems and pave the way for the future application of such methods to additional studies in SARS-CoV-2 and other molecular systems.

Enveloped viruses, such as SARS-CoV-2, infect cells via fusion of their envelope with the host membrane. By employing molecular simulations to characterize viral envelopes, researchers can gain insights into key determinants of infection. Here, the Frontera supercomputer is leveraged for large-scale modeling and analysis of authentic viral envelopes, whose lipid compositions are complex and realistic. Visual Molecular Dynamics (VMD) with support for MPI is employed, overcoming previous computational limitations and enabling investigation into virus biology at an unprecedented scale. The techniques applied here to an authentic HIV-1 envelope at two levels of spatial resolution (29 million particles and 280 million atoms) are broadly applicable to the study of other viruses. The authors are actively employing these techniques to develop and characterize an authentic SARS-CoV-2 envelope. A general framework for carrying out scalable analysis of simulation trajectories on Frontera is presented, expanding the utility of the machine in humanity's ongoing fight against infectious diseases.

NAMDis a molecular dynamics program designed for high-performance simulations of very large biological objects on CPU- and GPU-based architectures. NAMD offers scalable performance on petascale parallel supercomputers consisting of hundreds of thousands of cores, as well as on inexpensive commodity clusters commonly found in academic environments. It is written in C++ and leans on Charm++ parallel objects for optimal performance on low-latency architectures. NAMD is a versatile, multipurpose code that gathers state-of-the-art algorithms to carry out simulations in apt thermodynamic ensembles, using the widely popular CHARMM, AMBER, OPLS, and GROMOS biomolecular force fields. Here, we review the main features of NAMD that allow both equilibrium and enhanced-sampling molecular dynamics simulations with numerical efficiency. We describe the underlying concepts utilized by NAMD and their implementation, most notably for handling long-range electrostatics; controlling the temperature, pressure, and pH; applying external potentials on tailored grids; leveraging massively parallel resources in multiple-copy simulations; and hybrid quantum-mechanical/molecular-mechanical descriptions. We detail the variety of options offered by NAMD for enhanced-sampling simulations aimed at determining free-energy differences of either alchemical or geometrical transformations and outline their applicability to specific problems. Last, we discuss the roadmap for the development of NAMD and our current efforts toward achieving optimal performance on GPU-based architectures, for pushing back the limitations that have prevented biologically realistic billion-atom objects to be fruitfully simulated, and for making large-scale simulations less expensive and easier to set up, run, and analyze. NAMD is distributed free of charge with its source code at www.ks.uiuc.edu.

Conversion of sunlight into chemical energy, namely photosynthesis, is the primary energy source of life on Earth. A visualization depicting this process, based on multiscale computational models from electronic to cell scales, is presented in the form of an excerpt from the fulldome show Birth of Planet Earth . This accessible visual narrative shows a lay audience, including children, how the energy of sunlight is captured, converted, and stored through a chain of proteins to power living cells. The visualization is the result of a multi-year collaboration among biophysicists, visualization scientists, and artists, which, in turn, is based on a decade-long experimental-computational collaboration on structural and functional modeling that produced an atomic detail description of a bacterial bioenergetic organelle, the chromatophore. Software advancements necessitated by this project have led to significant performance and feature advances, including hardware-accelerated cinematic ray tracing and instanced visualizations for efficient cell-scale modeling. The energy conversion steps depicted feature an integration of function from electronic to cell levels, spanning nearly 12 orders of magnitude in time scales. This atomic detail description uniquely enables a modern retelling of one of humanity's earliest stories-the interplay between light and life., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest.

Previously, we have shown that bulk microtubule (MT) movement correlates with neurite elongation, and blocking either dynein activity or MT assembly inhibits both processes. However, whether the contributions of MT dynamics and dynein activity to neurite elongation are separate or interdependent is unclear. Here, we investigated the underlying mechanism by testing the roles of dynein and MT assembly in neurite elongation of Aplysia and chick neurites using time-lapse imaging, fluorescent speckle microscopy, super-resolution imaging and biophysical analysis. Pharmacologically inhibiting either dynein activity or MT assembly reduced neurite elongation rates as well as bulk and individual MT anterograde translocation. Simultaneously suppressing both processes did not have additive effects, suggesting a shared mechanism of action. Single-molecule switching nanoscopy revealed that inhibition of MT assembly decreased the association of dynein with MTs. Finally, inhibiting MT assembly prevented the rise in tension induced by dynein inhibition. Taken together, our results suggest that MT assembly is required for dynein-driven MT translocation and neurite outgrowth., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Light is a variable of key interest in circadian rhythms research, commonly measured using wrist-worn sensors. The GENEActiv Original is a cost-effective and practical option for assessing light in ambulatory settings. With increasing research on health and well-being incorporating sleep and circadian factors, the validity of wearable devices for assessing light environments needs to be evaluated. In this study, we tested the accuracy of the GENEActiv Original devices ( n = 10) for recording light under a range of ecologically relevant lighting conditions, including LED, fluorescent, infrared, and outdoor lighting. The GENEActiv output had a strong linear relationship with photopic illuminance. However, the devices consistently under-reported photopic illuminance, especially below 100 lux. Accuracy below 100 lux depended on the light source, with lower accuracy and higher variability under fluorescent lighting. The device's accuracy was also tested using light sources of varying spectral composition, which indicated that the device tends to under-report photopic illuminance for green light sources and over-report for red light sources. Furthermore, measures of photopic illuminance were impacted by infrared light exposure. We conclude that the GENEActiv Original is suitable for mapping light patterns within an individual context, and can reasonably differentiate indoor vs. outdoor lighting, though the accuracy is variable at low light conditions. Given the human circadian system's high sensitivity to light levels below 100 lux, if using the GENEActiv Original, we recommend also collecting light source data to better understand the impact on the circadian system, especially where participants spend prolonged periods in dim lighting., Competing Interests: Conflicts of InterestJES and EMM have no relevant financial conflicts of interest to report. ERFC is currently funded by an Innovation Connections Grant from the Australian Government, Department of Industry, Innovation and Science. SWC and AJKP are both investigators on projects funded by the Alertness Safety and Productivity CRC., (© 2020 by the authors.)

Background: Long-term data on the safety and efficacy of left atrial appendage closure (LAAC) for stroke prevention in patients with nonvalvular atrial fibrillation remain limited., Objectives: The purpose of this study was to evaluate 4.5- to 5-year data in 2 U.S. Food and Drug Association LAAC mandated registries (CAP [Continued Access to PROTECT-AF] and CAP2 [Continued Access to PREVAIL]) for safety and efficacy., Methods: Two registries of patients implanted with LAAC devices provide the largest source of follow-up data. Both accompanied their respective randomized clinical trials, PROTECT-AF (Watchman Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the WATCHMAN LAA Closure Device In Patients with Atrial Fibrillation versus Long Term Warfarin Therapy), which used the same endpoints (primary efficacy of composite of stroke, systemic embolism, cardiovascular/unexplained death, and safety)., Results: CAP included 566 patients with an average follow-up of 50.1 months (2,293 patient-years), and CAP2 included 578 patients with an average follow-up of 50.3 months (2,227 patient-years). CAP2 patients were significantly older and had higher CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) scores (4.51 vs. 3.88; p < 0.001). Procedural success was similar in both (94%). The primary composite endpoint occurred at a rate of 3.05 per 100 patient-years in CAP and 4.80 per 100 patient-years in CAP2; events contributing to this endpoint were most commonly cardiovascular/unexplained death (1.69 per 100 patient-years for CAP and 2.92 per 100 patient-years for CAP2). Hemorrhagic stroke was significantly less than ischemic stroke (0.17 per 100 patient-years in CAP and 0.09 per 100 patient-years in CAP2), and total stroke rates were significantly less than predicted by CHA 2 DS 2 -VASc score (78% reduction with CAP, 69% reduction with CAP2)., Conclusions: These registries, which contain the longest and largest follow-up data of patients with the Watchman device, support LAAC as a safe and effective therapy for long-term anticoagulation in patients with nonvalvular atrial fibrillation, and document the lowest rate of hemorrhagic stroke identified in this population., (Copyright © 2019. Published by Elsevier Inc.)

We report a 100-million atom-scale model of an entire cell organelle, a photosynthetic chromatophore vesicle from a purple bacterium, that reveals the cascade of energy conversion steps culminating in the generation of ATP from sunlight. Molecular dynamics simulations of this vesicle elucidate how the integral membrane complexes influence local curvature to tune photoexcitation of pigments. Brownian dynamics of small molecules within the chromatophore probe the mechanisms of directional charge transport under various pH and salinity conditions. Reproducing phenotypic properties from atomistic details, a kinetic model evinces that low-light adaptations of the bacterium emerge as a spontaneous outcome of optimizing the balance between the chromatophore's structural integrity and robust energy conversion. Parallels are drawn with the more universal mitochondrial bioenergetic machinery, from whence molecular-scale insights into the mechanism of cellular aging are inferred. Together, our integrative method and spectroscopic experiments pave the way to first-principles modeling of whole living cells., (Published by Elsevier Inc.)

Compartmentalization is a central theme in biology. Cells are composed of numerous membrane-enclosed structures, evolved to facilitate specific biochemical processes; viruses act as containers of genetic material, optimized to drive infection. Molecular dynamics simulations provide a mechanism to study biomolecular containers and the influence they exert on their environments; however, trajectory analysis software generally lacks knowledge of container interior versus exterior. Further, many relevant container analyses involve large-scale particle tracking endeavors, which may become computationally prohibitive with increasing system size. Here, a novel method based on 3-D ray casting is presented, which rapidly classifies the space surrounding biomolecular containers of arbitrary shape, enabling fast determination of the identities and counts of particles (e.g., solvent molecules) found inside and outside. The method is broadly applicable to the study of containers and enables high-performance characterization of properties such as solvent density, small-molecule transport, transbilayer lipid diffusion, and topology of protein cavities. The method is implemented in VMD, a widely used simulation analysis tool that supports personal computers, clouds, and parallel supercomputers, including ORNL's Summit and Titan and NCSA's Blue Waters, where the method can be employed to efficiently analyze trajectories encompassing millions of particles. The ability to rapidly characterize the spatial relationships of particles relative to a biomolecular container over many trajectory frames, irrespective of large particle counts, enables analysis of containers on a scale that was previously unfeasible, at a level of accuracy that was previously unattainable.

Practical alternatives to gold-standard measures of circadian timing in shift workers are needed. We assessed the feasibility of applying a limit-cycle oscillator model of the human circadian pacemaker to estimate circadian phase in 25 nursing and medical staff in a field setting during a transition from day/evening shifts (diurnal schedule) to 3-5 consecutive night shifts (night schedule). Ambulatory measurements of light and activity recorded with wrist actigraphs were used as inputs into the model. Model estimations were compared to urinary 6-sulphatoxymelatonin (aMT6s) acrophase measured on the diurnal schedule and last consecutive night shift. The model predicted aMT6s acrophase with an absolute mean error of 0.69 h on the diurnal schedule (SD = 0.94 h, 80% within ±1 hour), and 0.95 h on the night schedule (SD = 1.24 h, 68% within ±1 hour). The aMT6s phase shift from diurnal to night schedule was predicted to within ±1 hour in 56% of individuals. Our findings indicate the model can be generalized to a shift work setting, although prediction of inter-individual variability in circadian phase shift during night shifts was limited. This study provides the basis for further adaptation and validation of models for predicting circadian phase in rotating shift workers.

A neural network model was previously developed to predict melatonin rhythms accurately from blue light and skin temperature recordings in individuals on a fixed sleep schedule. This study aimed to test the generalizability of the model to other sleep schedules, including rotating shift work. Ambulatory wrist blue light irradiance and skin temperature data were collected in 16 healthy individuals on fixed and habitual sleep schedules, and 28 rotating shift workers. Artificial neural network models were trained to predict the circadian rhythm of (i) salivary melatonin on a fixed sleep schedule; (ii) urinary aMT6s on both fixed and habitual sleep schedules, including shift workers on a diurnal schedule; and (iii) urinary aMT6s in rotating shift workers on a night shift schedule. To determine predicted circadian phase, center of gravity of the fitted bimodal skewed baseline cosine curve was used for melatonin, and acrophase of the cosine curve for aMT6s. On a fixed sleep schedule, the model predicted melatonin phase to within ± 1 hour in 67% and ± 1.5 hours in 100% of participants, with mean absolute error of 41 ± 32 minutes. On diurnal schedules, including shift workers, the model predicted aMT6s acrophase to within ± 1 hour in 66% and ± 2 hours in 87% of participants, with mean absolute error of 63 ± 67 minutes. On night shift schedules, the model predicted aMT6s acrophase to within ± 1 hour in 42% and ± 2 hours in 53% of participants, with mean absolute error of 143 ± 155 minutes. Prediction accuracy was similar when using either 1 (wrist) or 11 skin temperature sensor inputs. These findings demonstrate that the model can predict circadian timing to within ± 2 hours for the vast majority of individuals on diurnal schedules, using blue light and a single temperature sensor. However, this approach did not generalize to night shift conditions.

We aimed to characterize objective and subjective sleepiness and driving events during short work commutes and examine the impact of circadian and homeostatic factors across different shift types in a shift worker population. Thirty-three nurses were monitored for 2 weeks over day (07:00-15:30), evening (13:00-21:30), and night shifts (21:00-07:30). Sleep was measured via daily sleep logs and wrist actigraphy. Driving logs were completed for each work commute, reporting driving events and a predrive Karolinska Sleepiness Scale (KSS). Ocular data from a subset of participants (n = 11) assessed objective sleepiness using infrared oculography during commutes. Circadian phase was assessed at three time points via urinary 6-sulphatoxymelatonin (aMT6s) collected over 24-48 hours. Subjective and objective sleepiness and sleep-related and hazardous driving events significantly increased following night shift compared with preshift. There were significant shift differences with KSS, sleep-related and inattention-related events highest during the postnight shift commute, compared with day and evening shifts. Sleep-related events were highest following the first night shift, while inattention-related events were most frequent after consecutive night shifts. KSS, sleep-related and hazardous events were increased during drives following ≥16 hours of wakefulness. KSS and sleep-related events increased during drives within ±3 hours of aMT6s acrophase. An interaction between homeostatic and circadian processes was observed, with KSS and sleep-related events highest within ±3 hours of acrophase, when wakefulness was ≥16 hours. In naturalistic conditions, subjective and objective sleepiness and driving events are increased following night shifts, even during short (~30 minutes) commutes and exacerbated by an interaction between circadian phase and duration of wakefulness., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Shift work is associated with impaired alertness and performance due to sleep loss and circadian misalignment. This study examined sleep between shift types (day, evening, night), and alertness and performance during day and night shifts in 52 intensive care workers. Sleep and wake duration between shifts were evaluated using wrist actigraphs and diaries. Subjective sleepiness (Karolinska Sleepiness Scale, KSS) and Psychomotor Vigilance Test (PVT) performance were examined during day shift, and on the first and subsequent night shifts (3 rd , 4 th or 5 th ). Circadian phase was assessed using urinary 6-sulphatoxymelatonin rhythms. Sleep was most restricted between consecutive night shifts (5.74 ± 1.30 h), consecutive day shifts (5.83 ± 0.92 h) and between evening and day shifts (5.20 ± 0.90 h). KSS and PVT mean reaction times were higher at the end of the first and subsequent night shift compared to day shift, with KSS highest at the end of the first night. On nights, working during the circadian acrophase of the urinary melatonin rhythm led to poorer outcomes on the KSS and PVT. In rotating shift workers, early day shifts can be associated with similar sleep restriction to night shifts, particularly when scheduled immediately following an evening shift. Alertness and performance remain most impaired during night shifts given the lack of circadian adaptation to night work. Although healthcare workers perceive themselves to be less alert on the first night shift compared to subsequent night shifts, objective performance is equally impaired on subsequent nights.

NAMD (NAnoscale Molecular Dynamics) is a parallel molecular dynamics application that has been used to make breakthroughs in understanding the structure and dynamics of large biomolecular complexes, such as viruses like HIV and various types of influenza. State-of-the-art biomolecular simulations often require integration of billions of timesteps, computing all interatomic forces for each femtosecond timestep. Molecular dynamics simulation of large biomolecular systems and long-timescale biological phenomena requires tremendous computing power. NAMD harnesses the power of thousands of heterogeneous processors to meet this demand. In this paper, we present algorithm improvements and performance optimizations that enable NAMD to achieve high performance on the IBM Newell platform (with POWER9 processors and NVIDIA Volta V100 GPUs) which underpins the Oak Ridge National Laboratory's Summit and Lawrence Livermore National Laboratory's Sierra supercomputers. The Top-500 supercomputers June 2018 list shows Summit at the number one spot with 187 Petaflop/s peak performance and Sierra third with 119 Petaflop/s. Optimizations for NAMD on Summit include: data layout changes for GPU acceleration and CPU vectorization, improving GPU offload efficiency, increasing performance with PAMI support in Charm++, improving efficiency of FFT calculations, improving load balancing, enabling better CPU vectorization and cache performance, and providing an alternative thermostat through stochastic velocity rescaling. We also present performance scaling results on early Newell systems.