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STUDY OBJECTIVES: This single-arm, mixed-methods, pilot study examined the feasibility and preliminary efficacy of an adapted version of the transdiagnostic intervention for sleep and circadian dysfunction (TranS-C) on multidimensional sleep health (MDSH) in a sample of adults with excess weight and suboptimal sleep health. METHODS: Participants received up to eight, weekly, remotely delivered, tailored TranS-C sessions. At pre- and post-intervention, the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and 7 days of Fitbit data were used to evaluate changes in sleep dimensions (regularity, alertness, timing, satisfaction, duration, and efficiency) and the composite MDSH score. Study feasibility examined recruitment, data collection, and intervention engagement (completion of core TranS-C sessions). Acceptability of the intervention was assessed with semi-structured interviews, which were analyzed using thematic analysis. RESULTS: From 85 referrals, 11 individuals were eligible, and 10 completed the study. All intervention participants completed the measures needed to calculate their composite MDSH score and completed the core intervention sessions. Themes from interviews support the interventions remote delivery approach, applicability of the information provided, and impact on self-reported health. The intervention resulted in a large improvement in the mean composite MDSH score (Cohens d = 1.17). Small-to-large effects were also observed for individual sleep health dimensions except for timing. CONCLUSIONS: Adapted TranS-C is acceptable for adults with excess weight and suboptimal sleep health and may be effective at improving short-term MDSH. With changes to recruitment methods, a larger study is feasible. Limitations include the small sample size and the lack of a control condition.

Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (rg = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.

BACKGROUND: Train-the-trainer (TTT) is a promising method for implementing evidence-based psychological treatments (EBPTs) in community mental health centers (CMHCs). In TTT, expert trainers train locally embedded individuals (i.e., Generation 1 providers) to deliver an EBPT, who then train others (i.e., Generation 2 providers). The present study will evaluate implementation and effectiveness outcomes of an EBPT for sleep and circadian dysfunction-the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C)-delivered to CMHC patients with serious mental illness by Generation 2 providers (i.e., trained and supervised within CMHCs via TTT). Specifically, we will investigate whether adapting TranS-C to fit CMHC contexts improves Generation 2 (a) patient outcomes and (b) providers perceptions of fit. METHODS: TTT will be implemented in nine CMHCs in California, USA (N = 60 providers; N = 130 patients) via facilitation. CMHCs are cluster-randomized by county to Adapted TranS-C or Standard TranS-C. Within each CMHC, patients are randomized to immediate TranS-C or usual care followed by delayed treatment with TranS-C (UC-DT). Aim 1 will assess the effectiveness of TranS-C (combined Adapted and Standard), compared to UC-DT, on improvements in sleep and circadian problems, functional impairment, and psychiatric symptoms for Generation 2 patients. Aim 2 will evaluate whether Adapted TranS-C is superior to Standard TranS-C with respect to Generation 2 providers perceptions of fit. Aim 3 will evaluate whether Generation 2 providers perceived fit mediates the relation between TranS-C treatment condition and patient outcomes. Exploratory analyses will (1) evaluate whether the effectiveness of TranS-C for patient outcomes is moderated by generation, (2) compare Adapted and Standard TranS-C on patient perceptions of credibility/improvement and PhenX Toolkit outcomes (e.g., substance use, suicidality), and (3) evaluate other possible moderators. DISCUSSION: This trial has potential to (a) inform the process of embedding local trainers and supervisors to expand delivery of a promising transdiagnostic treatment for sleep and circadian dysfunction, (b) add to the growing body of TTT literature by evaluating TTT outcomes with a novel treatment and population, and (c) advance our understanding of providers perceptions of EBPT fit across TTT generations. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05805657 . Registered on April 10, 2023.

Background & aimsThere are limited data regarding fibrosis progression in biopsy-proven nonalcoholic fatty liver disease (NAFLD) in people with type 2 diabetes mellitus (T2DM) compared with people without T2DM. We assessed the time to fibrosis progression in people with T2DM compared with people without T2DM in a large, multicenter, study of people with NAFLD who had paired liver biopsies.MethodsThis study included 447 adult participants (64% were female) with NAFLD who had paired liver biopsies more than 1 year apart. Liver histology was systematically assessed by a central pathology committee blinded to clinical data. The primary outcome was the cumulative incidence of a ≥1-stage increase in fibrosis in participants with T2DM compared with participants without T2DM.ResultsThe mean (SD) age and body mass index (calculated as weight in kilograms divided by the square of the height in meters) were 50.9 (11.5) years and 34.7 (6.3), respectively. The median time between biopsies was 3.3 years (interquartile range, 1.8-6.1 years). Participants with T2DM had a significantly higher cumulative incidence of fibrosis progression at 4 years (24% vs 20%), 8 years (60% vs 50%), and 12 years (93% vs 76%) (P = .005). Using a multivariable Cox proportional hazards model adjusted for multiple confounders, T2DM remained an independent predictor of fibrosis progression (adjusted hazard ratio, 1.69; 95% CI, 1.17-2.43; P = .005). The cumulative incidence of fibrosis regression by ≥1 stage was similar in participants with T2DM compared with participants without T2DM (P = .24).ConclusionsIn this large, multicenter cohort study of well-characterized participants with NAFLD and paired liver biopsies, we found that fibrosis progressed faster in participants with T2DM compared with participants without T2DM. These data have important implications for clinical practice and trial design.

STUDY OBJECTIVES: Several studies have shown that patients with short sleep duration show a poor response to cognitive behavioral therapy for insomnia (CBT-I), but such studies have not included patients with comorbid conditions. The current study was conducted to determine whether pretreatment sleep duration moderates the response of patients with major depression and insomnia disorders to a combined CBT-I and antidepressant medication treatment. METHODS: This study comprised a secondary analysis of a larger randomized trial that tested combined CBT-I/antidepressant medication treatment of patients with major depression and insomnia. Participants (n = 99; 70 women; Mage = 47.712.4 years) completed pretreatment polysomnography and then were randomly assigned to a 12-week treatment with antidepressant medication combined with CBT-I or a sham therapy. Short and longer sleepers were defined using total sleep time cutoffs of < 5, < 6, and < 7 hours for short sleep. Insomnia and depression remission ascertained respectively from the Insomnia Severity Index and Hamilton Rating Scale for Depression were used to compare treatment responses of short and longer sleepers defined by the cutoffs mentioned. RESULTS: Logistic regression analyses showed that statistically significant results were obtained only when the cutoff of < 5 hours of sleep was used to define short sleep. Both the CBT-I recipients with < 5 hours of sleep (odds ratio = 0.053; 95% confidence interval = 0.006-0.499) and the sham-therapy group with ≥ 5 hours of sleep (odds ratio = 0.149; 95% confidence interval = 0.045-0.493) were significantly less likely to achieve insomnia remission than were CBT-I recipients with ≥ 5 hours of sleep. The shorter sleeping CBT-I group (odds ratio = 0.118; 95% confidence interval = 0.020-0.714) and longer sleeping sham-therapy group (odds ratio = 0.321; 95% confidence interval = 0.105-0.983) were also less likely to achieve insomnia and/or depression remission than was the longer sleeping CBT-I group with ≥ 5 hours of sleep. CONCLUSIONS: Sleeping < 5 hours may dispose comorbid major depression/insomnia patients to a poor response to combined CBT-I/medication treatments for their insomnia and depression. Future studies to replicate these findings and explore mechanisms of treatment response seem warranted. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Treatment of Insomnia and Depression (TRIAD); URL: https://clinicaltrials.gov/ct2/show/results/NCT00767624; Identifier: NCT00767624. CITATION: Edinger JD, Smith ED, Buysse DJ, et al. Objective sleep duration and response to combined pharmacotherapy and cognitive behavioral insomnia therapy among patients with comorbid depression and insomnia: a report from the TRIAD study. J Clin Sleep Med. 2023;19(6):1111-1120.

Innovative solutions are required to make long-duration space missions feasible. Crew performance and health is paramount to the success of anticipated Moon and Mars missions. Metabolic reduction via a quasi-torpor state is a possible mitigation strategy that can reduce consumable payload, which is necessary given the lack of available resupply options, and to reduce psychological stress, which is a risk for such lengthy missions. Even in lunar or cis-lunar missions, a quasi-torpor state could be implemented as an emergency countermeasure for critical situations where life support becomes limited. However, to date no studies have tested a quasi-torpor state in humans, and the impacts of intentional prolonged metabolic reduction on physiological and psychological parameters are unknown. To this end, we planned a three-phase study to provide proof-in-principle of the tolerability, feasibility, and side effects of a non-intravenous alpha-2-adrenergic receptor agonist for moderate sedation. This was accomplished by 1) determining the dosing and metabolic effects for different non-intravenous routes of alpha-2-adrenergic receptor agonist drugs; 2) assessing the degree of metabolic reduction and side effects during a 24-h quasi-torpor protocol; and 3) evaluating participant performance and total metabolic reduction achieved over a 5-day quasi-torpor protocol. We also aim to determine how skeletal muscle health and performance are affected by this quasi-torpor state. Quasi-torpor induced changes in skeletal muscle health and performance, as well as impacts on cognition and psychological stress, also have implications for terrestrial situations that result in prolonged confinement (e.g., austere environments such as submarine or remote scientific or military deployment and protracted critical illness). The findings of this three-phase study will be immediately applicable as a rescue strategy for emergencies during current or upcoming space missions. They will also identify key physiological and practical questions that need to be addressed for future deployment in long-duration space missions. This paper reviews the relevant literature that informed our rationale and approaches for this three-phase study.

The main directions of mining and industrial wastes’ utilization are the production of building materials, their use in the construction industry without additional processing, and also the production of metals from metal-containing raw materials. It should be noted that current waste is preferable for the production of building materials, since they preserve the primary physical and mechanical properties and chemical composition and, moreover, can reach the consumer bypassing all other steps that are mandatory for waste consolidated (transportation, storage, etc.). For the production of building materials, not less than 30% of overburden and refinement tailings are suitable, almost all metallurgical and fuel slags, waste products of fertilizers and building materials. Even larger amounts of waste can be used for various laying and burial works (construction of road bases and dams, filling of worked out areas, leveling of the relief).

Abstract Tick-borne bacteria of the genera Ehrlichia and Anaplasma cause several emerging human infectious diseases worldwide. In this study, we conduct an extensive survey for Ehrlichia and Anaplasma infections in the rainforests of the Amazon biome of French Guiana. Through molecular genetics and metagenomics reconstruction, we observe a high indigenous biodiversity of infections circulating among humans, wildlife, and ticks inhabiting these ecosystems. Molecular typing identifies these infections as highly endemic, with a majority of new strains and putative species specific to French Guiana. They are detected in unusual rainforest wild animals, suggesting they have distinctive sylvatic transmission cycles. They also present potential health hazards, as revealed by the detection of Candidatus Anaplasma sparouinense in human red blood cells and that of a new close relative of the human pathogen Ehrlichia ewingii, Candidatus Ehrlichia cajennense, in the tick species that most frequently bite humans in South America. The genome assembly of three new putative species obtained from human, sloth, and tick metagenomes further reveals the presence of major homologs of Ehrlichia and Anaplasma virulence factors. These observations converge to classify health hazards associated with Ehrlichia and Anaplasma infections in the Amazon biome as distinct from those in the Northern Hemisphere.

BackgroundPediatric metabolic-associated fatty liver disease (MAFLD) is a global health problem, with lifestyle modification as its major therapeutic strategy. Rigorous characterization of dietary content on MAFLD in children is lacking. We hypothesized an objectively measured healthier diet would positively modulate MAFLD.MethodsDiet was assessed using the Nutrition Data System for Research in children enrolled from 10 tertiary clinical centers to determine the Healthy Eating Index (HEI, 0-100) and individual food components.ResultsIn all, 119 children were included (13.3 ± 2.7 y), 80 (67%) male, 67 (18%) White, and 90 (76%) Hispanic, with an average body mass index Z-score of 2.2 ± 0.5. Diet was classified as low HEI < 47.94 (n = 39), mid HEI ≥ 47.94 and < 58.89 (n = 41), or high HEI ≥ 58.89 (n=39). Children with high HEI (healthier diet) had lower body weight (p = 0.005) and more favorable lipids. Mean serum triglycerides for low, mid, and high HEI were 163, 148, and 120 mg/dL, respectively; p = 0.04 mid versus high, p = 0.01 low versus high. Mean HDL was 38, 41 and 43 mg/dL; p = 0.02 low vs high. Less severe steatosis was noted with added sugar ≤ 10% of calories (p = 0.03). Higher lobular inflammation is associated with a higher percentage of calories from fat (OR (95% CI) = 0.95 (0.91-1.00), p = 0.04).ConclusionsIn children with MAFLD, high HEI is associated with lower body weight and more favorable lipids, while added sugar and fat intake has individual histologic features. Differential consumption of major dietary components may modify both metabolic risk factors and histologic liver injury, highlighting the importance of objective diet assessments in children with MAFLD.

Specific sleep characteristics have been associated with cognitive decline, Alzheimers disease, and related dementias; however, studies examining the association between multidimensional sleep (a more comprehensive integration of sleep parameters) and cognitive decline are lacking. Among 2,811 older men without dementia, those with none, 1-2, and 3-5 poor self-reported sleep health dimensions had an adjusted 10-year change score of global cognition (3MS) of 2.9, 4.0 and 3.5 points (p-trend = 0.05), and in executive function (Trails B) completion time of 36.7, 42.7, and 46.7 seconds (p-trend

PURPOSE: We examined whether interindividual differences in naturalistic sleep patterns correlate with any deviations from typical brain aging. METHODS: Our sample consisted of 251 participants without current psychiatric diagnoses (9-25 years; mean [standard deviation] = 17.4 ± 4.52 yr; 58% female) drawn from the Neuroimaging and Pediatric Sleep Databank. Participants completed a T1-weighted structural magnetic resonance imaging scan and 5-7 days of wrist actigraphy to assess naturalistic sleep patterns (duration, timing, continuity, and regularity). We estimated brain age from extracted structural magnetic resonance imaging indices and calculated brain age gap (estimated brain age-chronological age). Robust regressions tested cross-sectional associations between brain age gap and sleep patterns. Exploratory models investigated moderating effects of age and biological gender and, in a subset of the sample, links between sleep, brain age gap, and depression severity (Patient-Reported Outcomes Measurement Information System Depression). RESULTS: Later sleep timing (midsleep) was associated with more advanced brain aging (larger brain age gap), β = 0.1575, puncorr = .0042, pfdr = .0167. Exploratory models suggested that this effect may be driven by males, although the interaction of gender and brain age gap did not survive multiple comparison correction (β = 0.2459, puncorr = .0336, pfdr = .1061). Sleep duration, continuity, and regularity were not significantly associated with brain age gap. Age did not moderate any brain age gap-sleep relationships. In this psychiatrically healthy sample, depression severity was also not associated with brain age gap or sleep. DISCUSSION: Later midsleep may be one behavioral cause or correlate of more advanced brain aging, particularly among males. Future studies should examine whether advanced brain aging and individual differences in sleep precede the onset of suboptimal cognitive-emotional outcomes in adolescents.

BackgroundSerious mental illness (SMI) can have devastating consequences. Unfortunately, many patients with SMI do not receive evidence-based psychological treatment (EBPTs) in routine practice settings. One barrier is poor "fit" between EBPTs and contexts in which they are implemented. The present study will evaluate implementation and effectiveness outcomes of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) implemented in community mental health centers (CMHCs). TranS-C was designed to target a range of SMI diagnoses by addressing a probable mechanism and predictor of SMI: sleep and circadian problems. We will investigate whether adapting TranS-C to fit CMHC contexts improves providers' perceptions of fit and patient outcomes.MethodsTranS-C will be implemented in at least ten counties in California, USA (N = 96 providers; N = 576 clients), via facilitation. CMHC sites are cluster-randomized by county to Adapted TranS-C or Standard TranS-C. Within each county, patients are randomized to immediate TranS-C or usual care followed by delayed treatment with TranS-C (UC-DT). Aim 1 will compare TranS-C (combined Adapted and Standard) with UC-DT on improvements in sleep and circadian problems, functional impairment, and psychiatric symptoms. Sleep and circadian problems will also be tested as a mediator between treatment condition (combined TranS-C versus UC-DT) and functional impairment/psychiatric symptoms. Aim 2 will evaluate whether Adapted TranS-C is superior to Standard TranS-C with respect to provider perceptions of fit. Aim 3 will evaluate whether the relation between TranS-C treatment condition (Adapted versus Standard) and patient outcomes is mediated by better provider perceptions of fit in the Adapted condition. Exploratory analyses will (1) compare Adapted versus Standard TranS-C on patient perceptions of credibility/improvement and select PhenX Toolkit outcomes and (2) evaluate possible moderators.DiscussionThis trial has the potential to (a) expand support for TranS-C, a promising transdiagnostic treatment delivered to patients with SMI in CMHCs; (b) take steps toward addressing challenges faced by providers in delivering EBPTs (i.e., high caseloads, complex patients, poor fit); and (c) advance evidence on causal strategies (i.e., adapting treatments to fit context) in implementation science.Trial registrationClinicaltrials.gov NCT04154631. Registered on 6 November 2019. https://clinicaltrials.gov/ct2/show/NCT04154631.

Abstract Rickettsia, a genus of obligate intracellular bacteria, includes species that cause significant human diseases. This study challenges previous claims that the Leucine‐973 residue in the RNA polymerase beta subunit is the primary determinant of rifampin resistance in Rickettsia. We investigated a previously untested Rickettsia species, R. lusitaniae, from the Transitional group and found it susceptible to rifampin, despite possessing the Leu‐973 residue. Interestingly, we observed the conservation of this residue in several rifampin‐susceptible species across most Rickettsia phylogenetic groups. Comparative genomics revealed potential alternative resistance mechanisms, including additional amino acid variants that could hinder rifampin binding and genes that could facilitate rifampin detoxification through efflux pumps. Importantly, the evolutionary history of Rickettsia genomes indicates that the emergence of natural rifampin resistance is phylogenetically constrained within the genus, originating from ancient genetic features shared among a unique set of closely related Rickettsia species. Phylogenetic patterns appear to be the most reliable predictors of natural rifampin resistance, which is confined to a distinct monophyletic subclade known as Massiliae. The distinctive features of the RNA polymerase beta subunit in certain untested Rickettsia species suggest that R. raoultii, R. amblyommatis, R. gravesii, and R. kotlanii may also be naturally rifampin‐resistant species.

Aim: Investigate long-term outcome in paediatric submersion-related cardiac arrests (CA). Methods: Children (age one day-17 years) were included if admitted to the Erasmus MC Sophia Children’s Hospital, after drowning with CA, between 2002 and 2019. Primary outcome was survival with favourable neurological outcome, defined as a Paediatric Cerebral Performance Category (PCPC) score of 1–3 at longest available follow-up. Secondary outcome were age-appropriate neuropsychological assessments at longest available follow-up. Results: Upon hospital admission, 99 children were included (median age at time of CA 3.2 years [IQR 2.0–5.9] and 65% males). Forty children died in-hospital (no return of circulation (45%) or withdrawal of life sustaining therapies (55%)) and 4 children deceased after hospital discharge due to complications following the drowning-incident. Among survivors, with a median follow-up of 2.3 years [IQR 0.2–5.5], 47 children had favourable neurological outcome (i.e. PCPC 1–3) and 8 children unfavourable (unfavourable outcome group total n = 52, i.e. PCPC 4–5 or deceased). Twenty-six (47%) children participated in a neuropsychological assessment (median follow-up 4.0 years [IQR 2.3–8.7]). Compared with normative test data, participants obtained worse general (p = 0.008) and performance (p = 0.003) intelligence scores, processing speed (p = 0.002) and visual motor integration scores (p = 0.0012). Conclusions: Although overall outcome in survivors was favourable at longest available follow-up, significant deficits in neuropsychological assessments were found. This study underlines the need for a standardized long term follow-up program as standard of care in paediatric drowning with CA.

Abstract Since the discovery of natural malaria vector populations infected by the endosymbiont bacterium Wolbachia, a renewed interest has arisen for using this bacterium as an alternative for malaria control. Among naturally infected mosquitoes, Anopheles moucheti, a major malaria mosquito in Central Africa, exhibits one of the highest prevalences of Wolbachia infection. To better understand whether this maternally inherited bacterium could be used for malaria control, we investigated Wolbachia influence in An. moucheti populations naturally infected by the malaria parasite Plasmodium falciparum. To this end, we collected mosquitoes in a village from Cameroon, Central Africa, where this mosquito is the main malaria vector. We found that the prevalence of Wolbachia bacterium was almost fixed in the studied mosquito population, and was higher than previously recorded. We also quantified Wolbachia in whole mosquitoes and dissected abdomens, confirming that the bacterium is also elsewhere than in the abdomen, but at lower density. Finally, we analyzed the association of Wolbachia presence and density on P. falciparum infection. Wolbachia density was slightly higher in mosquitoes infected with the malaria parasite than in uninfected mosquitoes. However, we observed no correlation between the P. falciparum and Wolbachia densities. In conclusion, our study indicates that naturally occurring Wolbachia infection is not associated to P. falciparum development within An. moucheti mosquitoes.

Long-term outcome studies after pediatric cardiac arrest (CA) are few. They require a CA registry and dedicated outcome teams. Learning about the long-term outcomes is very important for developing prognostication guidelines, improving post-cardiac care, counseling caregivers about the future of their child, and creating opportunities for therapeutic intervention studies to improve outcomes.Few PICUs worldwide provide a multidisciplinary follow-up program as routine practice at an outpatient clinic with standardized measurements, using validated instruments including neuropsychological assessments by psychologists. The primary goal of such a follow-up program should be to provide excellent care to children and their caregivers, thereby resulting in a high attendance. Pediatric psychologists, neurologists and pediatricians/pediatric intensivists should ideally be involved to screen for delayed development and psychosocial problems and offer appropriate care at the same time. Preferably, outcomes should consist of evaluation of morbidity (physical and neuropsychological), functional health and Health Related Quality Of Life (QoL) of the patient and their caregivers.

In Europe, the heterogeneous features of crop systems with majority of small to medium sized agricultural holdings, and diversity of crop rotations, require high-resolution information to estimate cropland Net Ecosystem Exchange (NEE) and its two main components of Gross Ecosystem Exchange (GEE) and the Ecosystem Respiration (RECO). In this context, this paper presents an assimilation of high-resolution Sentinel-2 indices with eddy covariance measurements at selected European cropland flux sites in a new modified version of Vegetation Photosynthesis Respiration Model (VPRM). VRPM is a data-driven model simulating CO2 fluxes previously applied using satellite-derived vegetation indices from the Moderate Resolution Imaging Spectroradiometer (MODIS). This study proposes a modification of the VPRM by including an explicit soil moisture stress function to the GEE and changing the equation of RECO. It also compares the model results driven by S2 indices instead of MODIS. The parameters of the VPRM model are calibrated using eddy-covariance data. All possible parameters optimization scenarios include the use of the initial version vs. the proposed modified VPRM, S2, or MODIS vegetation indices, and finally the choice of calibrating a single set of parameters against observations from all crop types, a set of parameters per crop type, or one set of parameters per site. Then, we focus the analysis on the improvement of the model with distinct parameters for different crop types vs. parameters optimized without distinction of crop types. Our main findings are: (1) the superiority of S2 vegetation indices over MODIS for cropland CO2 fluxes simulations, leading to a root mean squared error (RMSE) for NEE of less than 3.5 μmolm-2s-1 with S2 compared to 5 μmolm-2s-1 with MODIS (2) better performances of the modified VPRM version leading to a significant improvement of RECO, and (3) better performances when the parameters are optimized per crop-type instead of for all crop types lumped together, with lower RMSE and Akaike information criterion (AIC), despite a larger number of parameters. Associated with the availability of crop-type land cover maps, the use of S2 data and crop-type modified VPRM parameterization presented in this study, provide a step forward for upscaling cropland carbon fluxes at European scale.

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications.

Study objectivesTo identify actigraphy sleep health profiles in older men (Osteoporotic Fractures in Men Study; N = 2640) and women (Study of Osteoporotic Fractures; N = 2430), and to determine whether profile predicts mortality.MethodsWe applied a novel and flexible clustering approach (Multiple Coalesced Generalized Hyperbolic mixture modeling) to identify sleep health profiles based on actigraphy midpoint timing, midpoint variability, sleep interval length, maintenance, and napping/inactivity. Adjusted Cox models were used to determine whether profile predicts time to all-cause mortality.ResultsWe identified similar profiles in men and women: High Sleep Propensity [HSP] (20% of women; 39% of men; high napping and high maintenance); Adequate Sleep [AS] (74% of women; 31% of men; typical actigraphy levels); and Inadequate Sleep [IS] (6% of women; 30% of men; low maintenance and late/variable midpoint). In women, IS was associated with increased mortality risk (Hazard Ratio [HR] = 1.59 for IS vs. AS; 1.75 for IS vs. HSP). In men, AS and IS were associated with increased mortality risk (1.19 for IS vs. HSP; 1.22 for AS vs. HSP).ConclusionsThese findings suggest several considerations for sleep-related interventions in older adults. Low maintenance with late/variable midpoint is associated with increased mortality risk and may constitute a specific target for sleep health interventions. High napping/inactivity co-occurs with high sleep maintenance in some older adults. Although high napping/inactivity is typically considered a risk factor for deleterious health outcomes, our findings suggest that it may not increase risk when it occurs in combination with high sleep maintenance.

Abstract Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (rg = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.

Abstract Background Studies show conflicting results on neonatal outcomes following embryo biopsy for PGT, primarily due to small sample sizes and/or heterogeneity in the timing of embryo biopsy (day 3; EBD3 or day 5/6; EBD5) and type of embryo transfer. Even fewer data exist on the impact on children’s health beyond the neonatal period. This study aimed to explore outcomes in children born after EBD3 or EBD5 followed by fresh (FRESH) or frozen-thawed embryo transfer (FET). Methods This single-centre cohort study compared birth data of 630 children after EBD3, of 222 EBD5 and of 1532 after non-biopsied embryo transfers performed between 2014 and 2018. Follow-up data on growth were available for 426, 131 and 662 children, respectively. Results Embryo biopsy, either at EBD3 or EBD5 in FET and FRESH cycles did not negatively affect anthropometry at birth, infancy or childhood compared to outcomes in non-biopsied FET and FRESH cycles. While there was no adverse effect of the timing of embryo biopsy (EBD3 versus EBD5), children born after EBD3 followed by FET had larger sizes at birth, but not thereafter, than children born after EBD3 followed by FRESH. Reassuringly, weight and height gain, proportions of major congenital malformations, developmental problems, hospital admissions and surgical interventions were similar between comparison groups. Conclusion Our study indicated that neither EBD3 nor EBD5 followed by FRESH or FET had a negative impact on anthropometry and on health outcomes up to 2 years of age.

BACKGROUND: Effective and equitable strategies to prevent youth suicidal thoughts and behaviors (STB) are an urgent public health priority. Adolescent sleep disturbances are robustly linked to STB but are rarely addressed in preventive interventions or among Black and/or Hispanic/Latinx youth for whom STB risk is increasing disproportionately. This paper describes an application of health equity-informed implementation science models and frameworks to adapt and evaluate the evidence-based Transdiagnostic Sleep and Circadian (TSC) intervention for primary care implementation with adolescents of minoritized backgrounds with depression and STB risk. METHODS: This multiphase study protocol uses the Assessment, Decision, Adaptation, Production, Topical Experts-Integration, Training, Testing (ADAPT-ITT) model to adapt and evaluate TSC for primary care implementation with adolescents who are depressed, at risk for STB, and of primarily Black and/or Hispanic/Latinx backgrounds. We integrate the Consolidated Framework for Implementation Research (CFIR) in an initial qualitative inquiry of adolescent, caregiver, and clinician perceptions of TSC. Subsequent ADAPT-ITT phases include systematically and iteratively testing adaptations based on the qualitative inquiry, with ongoing key informant input, and then evaluating the adapted TSC for feasibility, acceptability, and efficacy in a pilot randomized trial. ANTICIPATED RESULTS: Based on youth depression and sleep health disparities research, we expect that TSC adaptations will be needed to enhance intervention content for adolescents with depression, STB risk, and primarily Black and/or Hispanic/Latinx backgrounds. We also anticipate adaptations will be needed to align TSC delivery methods with primary care implementation. CONCLUSIONS: Adapting evidence-based interventions with end-users and contexts in mind can help ensure that intervention strategies and delivery methods are acceptable to, and feasible with, health disparate populations. Although TSC has shown effectiveness for adolescents with sleep disturbances, we expect that additional multiphase research is necessary to optimize TSC for primary care delivery with Black and/or Hispanic/Latinx adolescents with depression and STB risk.

IntroductionDisturbed sleep is a common feature of psychotic disorders that is also present in the clinical high risk (CHR) state. Evidence suggests a potential role of sleep disturbance in symptom progression, yet the interrelationship between sleep and CHR symptoms remains to be determined. To address this knowledge gap, we examined the association between disturbed sleep and CHR symptoms over time.MethodsData were obtained from the North American Prodrome Longitudinal Study (NAPLS)-3 consortium, including 688 CHR individuals and 94 controls (mean age 18.25, 46% female) for whom sleep was tracked prospectively for 8 months. We used Cox regression analyses to investigate whether sleep disturbances predicted conversion to psychosis up to >2 years later. With regressions and cross-lagged panel models, we analyzed longitudinal and bidirectional associations between sleep (the Pittsburgh Sleep Quality Index in conjunction with additional sleep items) and CHR symptoms. We also investigated the independent contribution of individual sleep characteristics on CHR symptom domains separately and explored whether cognitive impairments, stress, depression, and psychotropic medication affected the associations.ResultsDisturbed sleep at baseline did not predict conversion to psychosis. However, sleep disturbance was strongly correlated with heightened CHR symptoms over time. Depression accounted for half of the association between sleep and symptoms. Importantly, sleep was a significant predictor of CHR symptoms but not vice versa, although bidirectional effect sizes were similar.DiscussionThe critical role of sleep disturbance in CHR symptom changes suggests that sleep may be a promising intervention target to moderate outcome in the CHR state.

Study objectivesStructural brain maturation and sleep are complex processes that exhibit significant changes over adolescence and are linked to many physical and mental health outcomes. We investigated whether sleep-gray matter relationships are developmentally invariant (i.e. stable across age) or developmentally specific (i.e. only present during discrete time windows) from late childhood through young adulthood.MethodsWe constructed the Neuroimaging and Pediatric Sleep Databank from eight research studies conducted at the University of Pittsburgh (2009-2020). Participants completed a T1-weighted structural MRI scan (sMRI) and 5-7 days of wrist actigraphy to assess naturalistic sleep. The final analytic sample consisted of 225 participants without current psychiatric diagnoses (9-25 years). We extracted cortical thickness and subcortical volumes from sMRI. Sleep patterns (duration, timing, continuity, regularity) were estimated from wrist actigraphy. Using regularized regression, we examined cross-sectional associations between sMRI measures and sleep patterns, as well as the effects of age, sex, and their interaction with sMRI measures on sleep.ResultsShorter sleep duration, later sleep timing, and poorer sleep continuity were associated with thinner cortex and altered subcortical volumes in diverse brain regions across adolescence. In a discrete subset of regions (e.g. posterior cingulate), thinner cortex was associated with these sleep patterns from late childhood through early-to-mid adolescence but not in late adolescence and young adulthood.ConclusionsIn childhood and adolescence, developmentally invariant and developmentally specific associations exist between sleep patterns and gray matter structure, across brain regions linked to sensory, cognitive, and emotional processes. Sleep intervention during specific developmental periods could potentially promote healthier neurodevelopmental outcomes.

Abstract Background Train-the-trainer (TTT) is a promising method for implementing evidence-based psychological treatments (EBPTs) in community mental health centers (CMHCs). In TTT, expert trainers train locally embedded individuals (i.e., Generation 1 providers) to deliver an EBPT, who then train others (i.e., Generation 2 providers). The present study will evaluate implementation and effectiveness outcomes of an EBPT for sleep and circadian dysfunction—the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C)—delivered to CMHC patients with serious mental illness by Generation 2 providers (i.e., trained and supervised within CMHCs via TTT). Specifically, we will investigate whether adapting TranS-C to fit CMHC contexts improves Generation 2 (a) patient outcomes and (b) providers’ perceptions of fit. Methods TTT will be implemented in nine CMHCs in California, USA (N = 60 providers; N = 130 patients) via facilitation. CMHCs are cluster-randomized by county to Adapted TranS-C or Standard TranS-C. Within each CMHC, patients are randomized to immediate TranS-C or usual care followed by delayed treatment with TranS-C (UC-DT). Aim 1 will assess the effectiveness of TranS-C (combined Adapted and Standard), compared to UC-DT, on improvements in sleep and circadian problems, functional impairment, and psychiatric symptoms for Generation 2 patients. Aim 2 will evaluate whether Adapted TranS-C is superior to Standard TranS-C with respect to Generation 2 providers’ perceptions of fit. Aim 3 will evaluate whether Generation 2 providers’ perceived fit mediates the relation between TranS-C treatment condition and patient outcomes. Exploratory analyses will (1) evaluate whether the effectiveness of TranS-C for patient outcomes is moderated by generation, (2) compare Adapted and Standard TranS-C on patient perceptions of credibility/improvement and PhenX Toolkit outcomes (e.g., substance use, suicidality), and (3) evaluate other possible moderators. Discussion This trial has potential to (a) inform the process of embedding local trainers and supervisors to expand delivery of a promising transdiagnostic treatment for sleep and circadian dysfunction, (b) add to the growing body of TTT literature by evaluating TTT outcomes with a novel treatment and population, and (c) advance our understanding of providers’ perceptions of EBPT “fit” across TTT generations. Trial registration ClinicalTrials.gov identifier NCT05805657 . Registered on April 10, 2023.

Abstract Background Machine learning tools such as random forests provide important opportunities for modeling large, complex modern data generated in medicine. Unfortunately, when it comes to understanding why machine learning models are predictive, applied research continues to rely on ‘out of bag’ (OOB) variable importance metrics (VIMPs) that are known to have considerable shortcomings within the statistics community. After explaining the limitations of OOB VIMPs – including bias towards correlated features and limited interpretability – we describe a modern approach called ‘knockoff VIMPs’ and explain its advantages. Methods We first evaluate current VIMP practices through an in-depth literature review of 50 recent random forest manuscripts. Next, we recommend organized and interpretable strategies for analysis with knockoff VIMPs, including computing them for groups of features and considering multiple model performance metrics. To demonstrate methods, we develop a random forest to predict 5-year incident stroke in the Sleep Heart Health Study and compare results based on OOB and knockoff VIMPs. Results Nearly all papers in the literature review contained substantial limitations in their use of VIMPs. In our demonstration, using OOB VIMPs for individual variables suggested two highly correlated lung function variables (forced expiratory volume, forced vital capacity) as the best predictors of incident stroke, followed by age and height. Using an organized analytic approach that considered knockoff VIMPs of both groups of features and individual features, the largest contributions to model sensitivity were medications (especially cardiovascular) and measured medical risk factors, while the largest contributions to model specificity were age, diastolic blood pressure, self-reported medical risk factors, polysomnography features, and pack-years of smoking. Thus, we reach very different conclusions about stroke risk factors using OOB VIMPs versus knockoff VIMPs. Conclusions The near-ubiquitous reliance on OOB VIMPs may provide misleading results for researchers who use such methods to guide their research. Given the rapid pace of scientific inquiry using machine learning, it is essential to bring modern knockoff VIMPs that are interpretable and unbiased into widespread applied practice to steer researchers using random forest machine learning toward more meaningful results.

IntroductionIdentifying intervention methods that target sleep characteristics involved in memory processing is a priority for the field of cognitive aging. Older adults with greater sleep efficiency and non-rapid eye movement slow-wave activity (SWA) (0.5–4 Hz electroencephalographic activity) tend to exhibit better memory and cognitive abilities. Paradoxically, long total sleep times are consistently associated with poorer cognition in older adults. Thus, maximizing sleep efficiency and SWA may be a priority relative to increasing mere total sleep time. As clinical behavioral sleep treatments do not consistently enhance SWA, and propensity for SWA increases with time spent awake, we examined with a proof-of concept pilot intervention whether a greater dose of time-in-bed (TiB) restriction (75% of habitual TiB) would increase both sleep efficiency and SWA in older adults with difficulties staying asleep without impairing memory performance.MethodsParticipants were adults ages 55–80 with diary-reported sleep efficiency < 90% and wake after sleep onset (WASO) >20 min. Sleep diary, actigraphy, polysomnography (PSG), and paired associate memory acquisition and retention were assessed before and after a week-long TiB restriction intervention (n = 30). TiB was restricted to 75% of diary-reported habitual TiB. A comparison group of n = 5 participants repeated assessments while following their usual sleep schedule to obtain preliminary estimates of effect sizes associated with repeated testing.ResultsSubjective and objective sleep measures robustly improved in the TiB restriction group for sleep quality, sleep depth, sleep efficiency and WASO, at the expense of TiB and time spent in N1 and N2 sleep. As hypothesized, SWA increased robustly with TiB restriction across the 0.5–4 Hz range, as well as subjective sleep depth, subjective and objective WASO. Despite increases in sleepiness ratings, no impairments were found in memory acquisition or retention.ConclusionA TiB restriction dose equivalent to 75% of habitual TiB robustly increased sleep continuity and SWA in older adults with sleep maintenance difficulties, without impairing memory performance. These findings may inform long-term behavioral SWA enhancement interventions aimed at improving memory performance and risk for cognitive impairments.

ObjectiveTo determine if the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) improves functional impairment, psychiatric symptoms, and sleep and circadian functioning.MethodAdults diagnosed with serious mental illness (SMI) and sleep and circadian dysfunction (N = 121) were randomly allocated to TranS-C plus usual care (TranS-C + UC; n = 61; 8 individual weekly sessions) or 6 months of Usual Care followed by Delayed Treatment with TranS-C (UC-DT; n = 60). Schizophrenia (45%) and anxiety disorders (47%) were common. Blind assessments were conducted pre-treatment, post-treatment, and 6 months later (6FU). The latter two were the post-randomization points of interest. The location was Alameda County Behavioral Health Care Services (ACBHCS), a Community Mental Health Center (CMHC) in California.ResultsFor the primary outcomes, relative to UC-DT, TranS-C + UC was associated with reduction in functional impairment (b = -3.18, p = 0.025, d = -0.58), general psychiatric symptoms (b = -5.88, p = 0.001, d = -0.64), sleep disturbance (b = -5.55, p < .0001, d = -0.96), and sleep-related impairment (b = -9.14, p < .0001, d = -0.81) from pre-treatment to post-treatment. These effects were maintained to 6-month follow-up (6FU; d = -0.42 to -0.82), except functional impairment (d = -0.37). For the secondary outcomes, relative to UC-DT, TranS-C + UC was associated with improvement in sleep efficiency and on the Sleep Health Composite score from pre-treatment to 6FU. TranS-C + UC was also associated with reduced total wake time and wake time variability from pre-treatment to post-treatment, as well as reduced hallucinations and delusions, bedtime variability, and actigraphy measured waking activity count variability from pre-treatment to 6FU.ConclusionsA novel transdiagnostic treatment, delivered within a CMHC setting, improves selected measures of functioning, symptoms of comorbid disorders, and sleep and circadian outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Abstract Hydras are freshwater cnidarians widely used as a biological model to study different questions such as senescence or phenotypic plasticity but also tumoral development. The spontaneous tumors found in these organisms have been so far described in two female lab strains domesticated years ago (Hydra oligactis and Pelmatohydra robusta) and the extent to which these tumors can be representative of tumors within the diversity of wild hydras is completely unknown. In this study, we examined individuals isolated from recently sampled wild strains of different sex and geographical origin, which have developed outgrowths looking like tumors. These tumefactions have common features with the tumors previously described in lab strains: are composed of an accumulation of abnormal cells, resulting in a similar enlargement of the tissue layers. However, we also found diversity within these new types of tumors. Indeed, not only females, but also males seem prone to form these tumors. Finally, the microbiota associated to these tumors is different from the one involved in the previous lineages exhibiting tumors. We found that tumorous individuals hosted yet undescribed Chlamydiales vacuoles. This study brings new insights into the understanding of tumor susceptibility and diversity in brown hydras from different origins.

Abstract Night shift work is associated with poor cardiometabolic outcomes, even post-retirement. However, the characteristics of cardiometabolic function in retired night shift workers (RNSW) compared to retired day workers (RDW) are not well-understood. Rigorous characterization of cardiometabolic dysfunction in RNSW and RDW will inform targeted risk stratification for RNSW. This observational study evaluated whether RNSW (n = 71) had poorer cardiometabolic function than RDW (n = 83). We conducted a multimodal assessment of cardiometabolic function including metabolic syndrome prevalence, brachial artery flow-mediated dilation, and carotid intima-media thickness. Main analyses tested overall group differences. Sex-stratified follow-up analyses tested group differences separately in men and women. RNSW had 2.6-times higher odds of metabolic syndrome prevalence than RDW in unadjusted analyses (95% CI [1.1,6.3]); this association was not significant when adjusting for age, race and education. RNSW and RDW (Mage = 68.4; 55% female) did not differ in percent flow-mediated dilation or carotid intima-media thickness. In sex-stratified analyses, women RNSW had 3.3-times higher odds of having high body mass index than women RDW (95% CI [1.2,10.4]). Men RNSW had 3.9-times higher odds of having high triglycerides than men RDW (95% CI [1.1,14.2]). No other group differences were observed. We found mixed evidence that night shift work exposure was associated with cardiometabolic dysfunction in retirement, possibly in a sex-specific manner.

Abstract Background Serious mental illness (SMI) can have devastating consequences. Unfortunately, many patients with SMI do not receive evidence-based psychological treatment (EBPTs) in routine practice settings. One barrier is poor “fit” between EBPTs and contexts in which they are implemented. The present study will evaluate implementation and effectiveness outcomes of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) implemented in community mental health centers (CMHCs). TranS-C was designed to target a range of SMI diagnoses by addressing a probable mechanism and predictor of SMI: sleep and circadian problems. We will investigate whether adapting TranS-C to fit CMHC contexts improves providers’ perceptions of fit and patient outcomes. Methods TranS-C will be implemented in at least ten counties in California, USA (N = 96 providers; N = 576 clients), via facilitation. CMHC sites are cluster-randomized by county to Adapted TranS-C or Standard TranS-C. Within each county, patients are randomized to immediate TranS-C or usual care followed by delayed treatment with TranS-C (UC-DT). Aim 1 will compare TranS-C (combined Adapted and Standard) with UC-DT on improvements in sleep and circadian problems, functional impairment, and psychiatric symptoms. Sleep and circadian problems will also be tested as a mediator between treatment condition (combined TranS-C versus UC-DT) and functional impairment/psychiatric symptoms. Aim 2 will evaluate whether Adapted TranS-C is superior to Standard TranS-C with respect to provider perceptions of fit. Aim 3 will evaluate whether the relation between TranS-C treatment condition (Adapted versus Standard) and patient outcomes is mediated by better provider perceptions of fit in the Adapted condition. Exploratory analyses will (1) compare Adapted versus Standard TranS-C on patient perceptions of credibility/improvement and select PhenX Toolkit outcomes and (2) evaluate possible moderators. Discussion This trial has the potential to (a) expand support for TranS-C, a promising transdiagnostic treatment delivered to patients with SMI in CMHCs; (b) take steps toward addressing challenges faced by providers in delivering EBPTs (i.e., high caseloads, complex patients, poor fit); and (c) advance evidence on causal strategies (i.e., adapting treatments to fit context) in implementation science. Trial registration Clinicaltrials.gov NCT04154631. Registered on 6 November 2019. https://clinicaltrials.gov/ct2/show/NCT04154631