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Introduction: The Chang'e-5 landing site is located to the East of Mons Rümker, in the mare unit Em4/P58 [1], one of the youngest mare basalt units on the Moon [2]. A total of 1731 g of soil samples were collected. Initial examination of these samples indicates that the Chang'e-5 basaltic fragments have several distinct textural types, low to intermediate Ti contents, formed ca. 2 billion years ago, were not linked directly to a KREEP reservoir, and originated from a mantle source with low water content [3-9]. These studies have tentatively linked the basaltic material to the Em4 unit, but it remains uncertain whether all of the samples came from a single basaltic unit. This study presents the results of petrological and geochemical investigations of a wide range of clasts, in order to address this uncertainty. Studied samples: We were allocated a 2 g scooped soil sample, CE5C0400, by the Chinese National Space Administration (CNSA) in July 2021. The average particle size is less than 5 microns. Fragments >1 mm picked out of a 1.5 g aliquot of CE5C0400 include 28 basaltic and 7 breccia clasts, 10 agglutinates, and ~200 glass beads >30 um. Results: The textures of the 28 basaltic fragments can be roughly divided into different grain size groups (coarsegrained, ophitic, subophitic, and fine-grained to aphanitic texture). The mineralogy and mineral chemistry of those fragments are very similar, consisting of minerals common in lunar basalts, such as chemically zoned pyroxene, plagioclase, olivine, and ilmenite, with small amounts of potassium-rich glass, potassium-feldspar, Ca-phosphates, and Zr-rich minerals. The pyroxene chemistry (Wo12-43, En3-38, Fs24-85 [coarse], Wo5-44, En0-37, Fs24-94 [ophitic], Wo11-44, En1-50, Fs23-88 [subophitic], Wo5-34, En0-38, Fs12-58 [fine], Wo9-47, En0-39, Fs32-92 [aphanitic]), plagioclase and pyroxene REE abundances, and Pb isotope systematics indicate that there is no distinct difference between different textural types. On the other hand, the chemical composition of some pyroxene grains from breccia and agglutinate clasts appears distinct from the basalt pyroxene compositions, with more Mg-rich and Ca-rich (En>45) compositions, akin to those observed in Apollo low Ti and high Ti lithologies, and some Ca-poor and Mg-rich compositions (Wo<5, En>80) more similar to those found in Mg-suite samples or KREEP basalts [10-12]. The impact glass bead compositions are consistent with having mainly originated from the same Em4 basaltic unit (mean 6 wt.% TiO2 [13]), although ~15% of the studied beads have more exotic compositons, ranging from low- to high-Ti abundances. Discussion: Mineral chemical compositions suggest that the basaltic fragments may represent a single basalt mantle source; we are testing the hypothesis that the textural variations could result from different cooling rates at various locations within a single basaltic flow. Based on the estimated cooling rates (~5 °C/hr for the majority of fragments [14-15]), the sampled fragments could represent only the upper part of the total thickness of the basaltic unit. Available chronology indicates that the sequence could have accumulated within a very short period of time, but determining a precise duration is limited by analytical uncertainties associated with the crystallization ages obtained [3,5]. The breccia and agglutinates lithic clasts, mineral fragments, and glass beads found in the CE5C0400 soil sample appear to be mainly derived from a single underlying basaltic unit, although a few rarer exotic components observed in breccias, agglutinates, and among glass beads may be linked to other types of mare basalts and non-mare lithologies. Acknowledgments: Sample CE5C0400 was provided by CNSA. This study was financially supported by CNSA (Grant Nos. D020204, D020206, and D020203) and the National Key R&D Program of China grant no. 2020YFE0202100. [ABSTRACT FROM AUTHOR]

Poor health is a key reason for early exit from the labour market. Few studies have explored how the health of local populations is related to occupational differences in employment outcomes among older people. Our study used data for England and Wales from the ONS Longitudinal Study linked with 2001 Census measures of the health of the older working age population at local authority level. We included 128,710 people aged 40-64y in 2001 who were in paid work in the previous five years. We investigated the associations of both occupation and area level with two employment outcomes ten years later (in 2011): i) in paid work or not; ii) economic activity (employed (reference), unemployed, retired, sick/disabled, other). People in elementary occupations were more likely to not be in paid work in 2011 compared to those in managerial occupations (RRR 1·55 [95%CI 1·47,1·64]). Compared to the healthiest third of local authority areas, being resident in the unhealthiest third was associated with greater likelihood of not being in paid employment ten years later (RRR 1·25 [95% CI 1·18,1·33]). While area level health was associated with employment outcomes for all major occupation groups, the gap between the healthiest and unhealthiest areas was most marked for skilled trades; process, plant and machine operatives; and elementary occupations. Occupational differences for the economic activity outcome were most marked for the sick/disabled category. Policies to improve the health of local populations may support retention and reduce occupational inequalities in employment rates of older workers., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite advances in HIV care and treatment in the U.S., disparities in outcomes along the HIV care continuum persist. The widespread replication of effective and sustainable interventions that prioritize the engagement of underserved populations has been identified as a promising path to ending the HIV epidemic in the U.S. Intervention dissemination products, however, rarely provide the comprehensive and accessible information needed to replicate interventions within community settings. To bridge the divide between research and community-based implementation, the Using Evidence-informed Interventions to Improve Health Outcomes among People Living with HIV (E2i) initiative-grounded in the HIV/AIDS Bureau Implementation Science Framework-created a suite of tools to promote the rapid replication of interventions focused on transgender women, Black men who have sex with men, behavioral health integration, and identifying and addressing trauma. The resulting dissemination products are detailed and digestible multimedia toolkits that follow adult learning theory principles and align with the Template for Intervention Description and Replication criteria for adapting non-pharmacological interventions. Each E2i toolkit consists of five components: implementation guides, narrative videos of site implementation, best practice demonstration videos, interactive learning modules, and recruitment posters and brochures. Over 2 years (2022-2024), the E2i toolkit webpages amassed 7703 unique users and 17,666 pageviews. These toolkits can serve as a blueprint for designing comprehensive and accessible dissemination products for replication of HIV interventions in care settings. Dissemination products that bridge the gap between intervention research and replication in community settings are a crucial missing tool for ending the HIV epidemic., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The transition to retirement is a significant turning point in life, which may lead to changes in food habits., Objective: To examine changes in red meat, fish, vegetables and fruit consumption during the retirement transition and whether these changes vary between sociodemographic groups., Methods: The data were from the Whitehall II study, a cohort of 10 308 British civil servants aged 35-55 years at study induction (1985-1988). Data collection has taken place every 2-3 years. Food consumption (n=2484-2491) was assessed with the Food Frequency Questionnaire in the periods before (max. 16 years) and after retirement (max. 16 years). Changes in preretirement and postretirement consumption were compared in the total cohort and subgroups by sex, marital status, preretirement occupation status and financial hardship using linear regression analyses with generalised estimating equations., Results: Weekly red meat consumption was stable before retirement but increased after retirement (p=0.02), especially among women, single and lower occupational status participants. Fish consumption increased during the follow-up and the increase was steeper before retirement than postretirement period (p=0.02). Vegetable and fruit consumption also increased during the entire follow-up, but more strongly during preretirement than postretirement period (p<0.001 for both)., Conclusion: The transition to retirement is accompanied by favourable (increase in fruit, vegetable and fish) and unfavourable (increase in red meat) dietary changes, varied to some extent by sex, marital status and preretirement occupational status. Our findings suggest that attention should be paid to this transitional phase to promote eating habits in accordance with the recommendations for retirement., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Coccidioidomycosis is a fungal disease affecting humans and other mammals, caused by environmental pathogens of the genus Coccidioides . Understanding the ecological factors that shape the distribution of Coccidioides in soils is important for minimizing the risk of human exposure, though this remains challenging due to the pathogen's highly variable spatial distribution. Here, we examined associations between the soil microbial community and Coccidioides immitis presence within the Carrizo Plain National Monument-a minimally disturbed grassland ecosystem, and the site of a longitudinal study examining the effects of rodents and their burrows on C. immitis presence in soils. Using internal transcribed spacer 2 (ITS2) and 16S sequencing to characterize the soil fungal and bacterial communities, we found over 30 fungal species, including several other members of the Onygenales order, that co-occurred with Coccidioides more frequently than expected by chance. Coccidioides -positive samples were significantly higher in microbial diversity than negative samples, an association partly driven by higher Coccidioides presence within rodent burrows compared to surface soils. Soil source ( i.e., rodent burrow versus surface soil) explained the largest amount of variation in bacterial and fungal community diversity and composition, with soils collected from rodent burrows having higher microbial diversity than those collected from adjacent surface soils. While prior evidence is mixed regarding associations between Coccidioides and microbial diversity, our study suggests that favorable microhabitats such as rodent burrows can lead to a positive association between soil diversity and Coccidioides presence, particularly in otherwise resource-limited natural environments.

Efforts to use transcriptomics for toxicity testing have classically relied on the assumption that chemicals consistently produce characteristic transcriptomic signatures that are reflective of their mechanism of action. However, the degree to which transcriptomic responses are conserved across different test methodologies has seldom been explored. With increasing regulatory demand for New Approach Methods (NAMs) that use alternatives to animal models and high-content approaches such as transcriptomics, this type of comparative analysis is needed. We examined whether common genes are dysregulated in Japanese quail (Coturnix japonica) liver following sublethal exposure to the flame retardant hexabromocyclododecane (HBCD), when life stage and test methodologies differ. The four exposure scenarios included one NAM: Study 1-early-life stage (ELS) exposure via a single egg injection, and three more traditional approaches; Study 2-adult exposure using a single oral gavage; Study 3-ELS exposure via maternal deposition after adults were exposed through their diet for 7 weeks; and Study 4-ELS exposure via maternal deposition and re-exposure of nestlings through their diet for 17 weeks. The total number of differentially expressed genes (DEGs) detected in each study was variable (Study 1, 550; Study 2, 192; Study 3, 1; Study 4, 3) with only 19 DEGs shared between Studies 1 and 2. Factors contributing to this lack of concordance are discussed and include differences in dose, but also quail strain, exposure route, sampling time, and HBCD stereoisomer composition. The results provide a detailed overview of the transcriptomic responses to HBCD at different life stages and routes of exposure in a model avian species and highlight certain challenges and limits of comparing transcriptomics across different test methodologies. Environ Toxicol Chem 2024;00:1-11. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

How populations adapt to their environment is a fundamental question in biology. Yet we know surprisingly little about this process, especially for endangered species such as non-human great apes. Chimpanzees, our closest living relatives, are particularly interesting because they inhabit diverse habitats, from rainforest to woodland-savannah. Whether genetic adaptation facilitates such habitat diversity remains unknown, despite having wide implications for evolutionary biology and conservation. Using 828 newly generated exomes from wild chimpanzees, we find evidence of fine-scale genetic adaptation to habitat. Notably, adaptation to malaria in forest chimpanzees is mediated by the same genes underlying adaptation to malaria in humans. This work demonstrates the power of non-invasive samples to reveal genetic adaptations in endangered populations and highlights the importance of adaptive genetic diversity for chimpanzees., Competing Interests: Competing interests: The authors declare no competing interests.

Health care workers experience high rates of burnout and psychiatric distress. A large health care system in the southwest United States developed a comprehensive mental health service model for employees. Services offered range from traditional benefits (eg, Employee Assistance Program), resiliency and well-being initiatives, and innovative technology solutions, to access to peer support services for professional practice issues. The latest innovation in services is a free, self-insured outpatient mental health clinic designed exclusively for health care workers and their dependents. In this article, the authors describe the development of expanded mental health programming for health care workers and discuss how this unique service model proactively reduces common barriers to the receipt of high-quality care. This approach to caring for the workforce may serve as a model for other health care organizations across the United States. By providing mental health support to employees, health care organizations are mitigating the risk of burnout and related consequences to the system., Competing Interests: K.B. and J.R. report funding from the Chao Foundation for salary support, and S.M.M. reports funding from the Chao Foundation for academic activities. B.L.W. reports stock/stock options in Mindbloom. B.L.W. is the C. James and Carole Walter Looke Presidential Distinguished Centennial at Houston Methodist. A.M. reports funding from the Houston Methodist Foundation for financial support for research personnel. A.M. is the John S. Dunn Foundation Distinguished Centennial Clinical Academic Scholar in Behavioral Health at Houston Methodist. J.H. reports funding for salary support from the Center for Performing Arts Medicine at Houston Methodist. J.R. reports a grant from the Constance M. and Byron F. Dyer Fellowship. N.V. reports a grant from the Constance M. and Byron F. Dyer Fellowship. The remaining authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Understanding species differences in sensitivity to toxicants is a critical issue in ecotoxicology. We recently established that double-crested cormorant (DCCO) embryos are more sensitive than Japanese quail (JQ) to the developmental effects of ethinylestradiol (EE2). We explored how this difference in sensitivity between species is reflected at a transcriptomic level. The EE2 was dissolved in dimethyl sulfoxide and injected into the air cell of eggs prior to incubation at nominal concentrations of 0, 3.33, and 33.3 µg/g egg weight. At midincubation (JQ 9 days; DCCO 16 days), livers were collected from five embryos/treatment group for RNA sequencing. Data were processed and analyzed using EcoOmicsAnalyst and ExpressAnalyst. The EE2 exposure dysregulated 238 and 1,987 genes in JQ and DCCO, respectively, with 78 genes in common between the two species. These included classic biomarkers of estrogen exposure such as vitellogenin and apovitellenin. We also report DCCO-specific dysregulation of Phase I/II enzyme-coding genes and species-specific transcriptional ontogeny of vitellogenin-2. Twelve Kyoto Encyclopedia of Genes and Genomes pathways and two EcoToxModules were dysregulated in common in both species including the peroxisome proliferator-activated receptor (PPAR) signaling pathway and fatty acid metabolism. Similar to previously reported differences at the organismal level, DCCO were more responsive to EE2 exposure than JQ at the gene expression level. Our description of differences in transcriptional responses to EE2 in early life stage birds may contribute to a better understanding of the molecular basis for species differences. Environ Toxicol Chem 2024;43:772-783. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

Issues in applied survey research, including minimizing respondent burden and ensuring measures' brevity for smartphone administration, have intensified efforts to create short measures. We conducted two studies on the psychometric properties of single-item satisfaction, love, conflict, and commitment measures. Study 1 was longitudinal, surveying college-age dating couples at three monthly waves ( n =121, 84, and 68 couples at the respective waves). Partners completed single- and multi-item measures of the four constructs, along with other variables, to examine test-retest reliability and convergent, concurrent, and predictive validity. Single-item measures of satisfaction, love, and commitment exhibited impressive psychometric qualities, but our single-item conflict measure performed somewhat less strongly. Study 2, a cross-sectional online survey ( n = 280), showed strong convergent validity of the single-item measures, including that of conflict., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To examine the association between high intakes of ultra-processed foods (UPF) and recurrence of depressive symptoms (DepS) in a Western non-Mediterranean country and its contribution to the overall diet-depression relationship., Methods: Analyses were carried out on British participants from the Whitehall II cohort. Present analyses were restricted to white participants N  = 4554 (74% men, mean age = 61; SD = 5.9). UPF consumption was estimated from a 127-item food frequency questionnaire using the NOVA classification, and cumulative average of UPF intakes (g/day) over 11 years of exposure (1991/1994-2002/2004) was computed. Recurrent DepS after measurement of UPF was defined as having two or more episodes of DepS (the Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16 or antidepressants use) during four phases of follow-up (2002/2004-2015/2016)., Results: Over the follow-up, 588 (12.9%) cases of recurrent DepS were observed. After adjusting for socio-demographic factors, health behaviours and health status, participants in top quintile of UPF intakes [mean 33% of total daily intakes in grams] had 31% higher odds of recurrent DepS (odds ratio 1.31; 95% CI 1.04-1.64) compared to participants in the four lowest quintiles of UPF [mean 18.1% of total daily intakes in grams]. Additional analyses showed that associations between adherence to several diet quality measures and recurrent DepS were partially attenuated (17-27%) by UPF intakes., Conclusion: In this British population, high intakes of ultra-processed foods were associated with increased odds of recurrent depressive symptoms and contributed to the overall diet quality-depressive symptoms association.

The rainbow trout gill cell line (RTgill-W1), via test guideline 249 of the Organisation for Economic Co-operation and Development, has been established as a promising New Approach Methodology, although to advance confidence in the method more case studies are needed that: 1) expand our understanding of applicability domains (chemicals with diverse properties); 2) increase methodological throughput (96-well format); and 3) demonstrate biological relevance (in vitro to in vivo comparisons; gill vs. other cells). Accordingly, the objective of our study was to characterize the cytotoxicity of 19 pesticides against RTgill-W1 cells, and also liver (RTL-W1) and gut epithelial (RTgutGC) cell lines, and then to compare the in vitro and in vivo data. Of the 19 pesticides tested, 11, 9, and 8 were cytotoxic to the RTgill-W1, RTL-W1, and RTgutGC cells, respectively. Six pesticides (carbaryl, chlorothalonil, chlorpyrifos, dimethenamid-P, metolachlor, and S-metolachlor) were cytotoxic to all three cell lines. Aminomethylphosphonic acid, chlorantraniliprole, dicamba, diquat, imazethapyr, and permethrin exhibited cell-line-specific toxicity. No cytotoxic responses were observed for three herbicides (atrazine, glyphosate, and metribuzin) and four insecticides (clothianidin, diazinon, imidacloprid, and thiamethoxam). When cytotoxicity was measured, there was a strong correlation (r s  = 0.9, p < 0.0001) between in vitro median effect concentration (EC50) values (based on predicted concentrations using the In Vitro Mass Balance Model Equilibrium Partitioning (IV-MBM EQP) Ver. 2.1) derived from RTgill-W1 and RTL-W1 cells with in vivo median lethal concentration (LC50) values from 96-h acute toxicity studies with trout. In all 28 cases, the in vitro EC50 was within 18-fold of the in vivo LC50. These data help increase our understanding of the ecotoxicological domains of applicability for in vitro studies using cultured rainbow trout cells, while also demonstrating that these assays performed well in a 96-well format and have promise to yield data of biological relevance. Environ Toxicol Chem 2024;00:1-13. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

The EcoToxChip project includes RNA-sequencing data from experiments involving model (Japanese quail, fathead minnow, African clawed frog) and ecological (double-crested cormorant, rainbow trout, northern leopard frog) species at multiple life stages (whole embryo and adult) exposed to eight chemicals of environmental concern known to perturb a wide range of biological systems (ethinyl estradiol, hexabromocyclododecane, lead, selenomethionine, 17β trenbolone, chlorpyrifos, fluoxetine, and benzo[a]pyrene). The objectives of this short communication were to (1) present and make available this RNA-sequencing database (i.e., 724 samples from 49 experiments) under the FAIR principles (FAIR data are data which meet principles of findability, accessibility, interoperability, and reusability), while also summarizing key meta-data attributes and (2) use ExpressAnalyst (including the Seq2Fun algorithm and EcoOmicsDB) to perform a comparative transcriptomics analysis of this database focusing on baseline and differential transcriptomic changes across species-life stage-chemical combinations. The database is available in NCBI GEO under accession number GSE239776. Across all species, the number of raw reads per sample ranged between 13 and 58 million, with 30% to 79% of clean reads mapped to the "vertebrate" subgroup database in EcoOmicsDB. Principal component analyses of the reads illustrated separation across the three taxonomic groups as well as some between tissue types. The most common differentially expressed gene was CYP1A1 followed by CTSE, FAM20CL, MYC, ST1S3, RIPK4, VTG1, and VIT2. The most common enriched pathways were metabolic pathways, biosynthesis of cofactors and biosynthesis of secondary metabolites, and chemical carcinogenesis, drug metabolism, and metabolism of xenobiotics by cytochrome P450. The RNA-sequencing database in the present study may be used by the research community for multiple purposes, including, for example, cross-species investigations, in-depth analyses of a particular test compound, and transcriptomic meta-analyses. Environ Toxicol Chem 2024;00:1-6. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

Purpose: Postoperative atrial fibrillation (POAF) has an incidence of 20-60% in cardiac surgery. The Society of Cardiovascular Anesthesiologists and the European Association of Cardiothoracic Anaesthesiology Practice Advisory have recommended postoperative beta blockers and amiodarone for the prevention of POAF. By employing quality improvement (QI) strategies, we sought to increase the use of these agents and to reduce the incidence of POAF among our patients undergoing cardiac surgery., Methods: This single-centre QI initiative followed the traditional Plan, Do, Study, Act (PDSA) cycle scientific methodology. A POAF risk score was developed to categorize all patients undergoing cardiac surgery as either normal or elevated risk. Risk stratification was incorporated into a preprinted prescribing guide, which recommended postoperative beta blockade for all patients and a postoperative amiodarone protocol for patients with elevated risk starting on postoperative day one (POD1). A longitudinal audit of all patients undergoing cardiac surgery was conducted over 11 months to track the use of prophylactic medications and the incidence of POAF., Results: Five hundred and sixty patients undergoing surgery were included in the QI initiative from 1 December 2020 to 1 November 2021. The baseline rate of POAF across all surgical subtypes was 39% (198/560). The use of prophylactic amiodarone in high-risk patients increased from 13% (1/8) at the start of the project to 41% (48/116) at the end of the audit period. The percentage of patients receiving a beta blocker on POD1 did fluctuate, but remained essentially unchanged throughout the audit (34.8% in December 2020 vs 46.7% in October 2021). After 11 months, the overall incidence of POAF was 29% (24.9% relative reduction). Notable reductions in the incidence of POAF were observed in more complex surgical subtypes by the end of the audit, including multiple valve replacement (89% vs 56%), aortic repair (50% vs 33%), and mitral valve surgery (45% vs 33%)., Conclusions: This single-centre QI intervention increased the use of prophylactic amiodarone by 28% for patients at elevated risk of POAF, with no change in the early postoperative initiation of beta blockers (46.7% of patients by POD1). There was a notable reduction in the incidence of POAF in patients at elevated risk undergoing surgery., (© 2023. The Author(s).)

Background: Hürthle cell carcinoma (HCC) is an unusual and aggressive variant of the follicular type of differentiated thyroid cancer (DTC), accounting for less than 3% of DTCs but posing the highest risk of metastasis. Brain metastases are uncommonly reported in the literature but pose a poor prognosis. The low rate of brain metastases from HCC coupled with ambiguous treatment protocols for the extracranial disease complicate successful disease management and definitive treatment strategy. The authors present the case of a patient with HCC metastasis to the skull base, cortex, and spine with recent tibial metastasis., Observations: Despite the presence of metastasis to the cortex, skull base, and spine, the patient responded very well to radiation therapy, sellar mass resection, and cervical spine decompression and fixation and has made a remarkable recovery., Lessons: The authors' multidisciplinary approach to the patient's care, including a diverse team of specialists from oncology, neurosurgery, orthopedic surgery, radiology, endocrinology, and collaboration with clinical trial researchers, was fundamental to her successful outcome, demonstrating the utility of intersecting specialties in successful outcomes in neuro-oncological patient care.

Initiating end-of-life conversations can be daunting for clinicians and overwhelming for patients and families. This leads to delays in communicating prognosis and preparing for the inevitable in old age, often generating potentially harmful overtreatment and poor-quality deaths. We aimed to develop an electronic resource, called Communicating Health Alternatives Tool (CHAT) that was compatible with hospital medical records software to facilitate preparation for shared decision-making across health settings with older adults deemed to be in the last year of life. The project used mixed methods including: literature review, user-directed specifications, web-based interface development with authentication and authorization; clinician and consumer co-design, iterative consultation for user testing; and ongoing developer integration of user feedback. An internet-based conversation guide to facilitate clinician-led advance care planning was co-developed covering screening for short-term risk of death, patient values and preferences, and treatment choices for chronic kidney disease and dementia. Printed summary of such discussion could be used to begin the process in hospital or community health services. Clinicians, patients, and caregivers agreed with its ease of use and were generally accepting of its contents and format. CHAT is available to health services for implementation in effectiveness trials to determine whether the interaction and documentation leads to formal decision-making, goal-concordant care, and subsequent reduction of unwanted treatments at the end of life., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Diffuse midline glioma (DMG) is a pediatric cancer that originates in the midline structures of the brain. Prognosis of DMG patients remains poor due to the infiltrative nature of these tumors and the protection they receive from systemically delivered therapeutics via an intact blood-brain barrier (BBB), making treatment difficult. While the cell of origin remains disputed, it is believed to reside in the ventral pons. Recent research has pointed toward epigenetic dysregulation inducing an OPC-like transcriptomic signature in DMG cells. This epigenetic dysregulation is typically caused by a mutation (K27M) in one of two histone genes- H3F3A or HIST1H3B -and can lead to a differentiation block that increases these cells oncogenic potential. Standard treatment with radiation is not sufficient at overcoming the aggressivity of this cancer and only confers a survival benefit of a few months, and thus, discovery of new therapeutics is of utmost importance. In this review, we discuss the cell of origin of DMGs, as well as the underlying molecular mechanisms that contribute to their aggressivity and resistance to treatment. Additionally, we outline the current standard of care for DMG patients and the potential future therapeutics for this cancer that are currently being tested in preclinical and clinical trials., Competing Interests: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

The increasing workforce participation at higher ages may impact social insurance systems, however, this has hardly been studied at all. We studied associations between sociodemographic factors and prior sickness absence and disability pension, with having paid work and sickness absence after age 65, and if such associations changed over time. We used longitudinal register data regarding three cohorts of all residents in Sweden who turned 65 in 2000, 2005, or 2010 (N = 50,000, 68,000, and 99,000, respectively). Although employment rates when aged 66-71 increased between the cohorts, associations of sociodemographic factors with paid work and sickness absence, when aged 66-71 did not. Both sickness absence and disability pension when aged 60-64 were negatively associated with working past 65. Sickness absence when aged 60-64 was positively associated and disability pension was negatively associated with sickness absence after 65. Possibilities to remain in paid work with different health conditions need to be strengthened to avoid inequalities when raising the retirement age.

Pending antibiotic susceptibility results, vancomycin is often used for bloodstream infections (BSIs) to ensure treatment of methicillin-resistant Staphylococcus aureus (MRSA). As rapid discrimination of methicillin-susceptible S. aureus (MSSA) from MRSA in BSIs could decrease vancomycin use and allow early optimization of beta-lactam therapy, this study evaluated the impact of the use of rapid molecular testing for MSSA and MRSA coupled with an antimicrobial stewardship program (ASP) intervention. Between January and July 2020, the Cepheid Xpert MRSA/SA blood culture assay was performed on blood cultures with Gram-positive cocci in clusters that were identified as S. aureus using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The ASP team member then consulted with the treating physician. The time to optimal therapy (TTOT) and clinical outcomes, including length of hospital stay (LOS), were compared between the intervention ( n  = 29) and historical ( n  = 27) cohorts. TTOT was defined as the time from the first blood culture draw to the use of appropriately dosed antistaphylococcal beta-lactam monotherapy without vancomycin. Molecular testing significantly reduced the median time to MSSA and MRSA discrimination to 7.8 h, compared to 24.3 h with culture-based methods ( P <  0.001). Compared to the control group, the median TTOT in the ASP intervention group was significantly shorter ( P =  0.041) at 38.0 h (versus 50.1 h). Rapid discrimination between MRSA and MSSA using molecular testing, paired with an ASP intervention, significantly reduced the TTOT in patients with MSSA BSIs. IMPORTANCE Our research shows that time to optimal antibiotic treatment for serious bloodstream infections can be improved with rapid molecular sensitivity testing and feedback to prescribers. This can be implemented in laboratories without full microbiology services or training to improve patient outcomes by improving antimicrobial use.

Study Objectives: Sleep duration and difficulties have been shown to associate with cognitive function. This study examined how changes in sleep and in cognitive function are associated during retirement transition., Methods: The study population consisted of 2980 Whitehall II study participants, who retired during the follow-up, whose sleep was queried, and cognitive function measured (inductive reasoning and verbal memory) before and after retirement (follow-up 16 years). Using the last information on sleep before and the first after retirement, participants were categorized into constantly without (59%), increasing (13%), decreasing (11%), and constantly with (18%) sleep difficulties; and constantly short (26%), increasing (19%), decreasing (8.5%), and constantly mid-range (47%) sleep duration. Change in cognitive function during retirement transition was examined by sleep change groups using linear regression analyses with generalized estimating equations., Results: More pronounced decline in inductive reasoning during retirement transition was observed among participants with increasing sleep difficulties (-1.96, 95% CI -2.52 to -1.41) compared to those constantly without sleep difficulties (-1.25, 95% CI -1.52 to -0.98) and constantly with sleep difficulties (-1.26, 95% CI -1.75 to -0.92). Decreasing sleep difficulties (-0.64, 95% CI -0.86 to -0.43) were associated with a more pronounced decline in verbal memory when compared to constantly without sleep difficulties (-0.42, 95% CI -0.52 to -0.32) in post-retirement period. No statistically significant differences across sleep duration groups in cognitive function were observed., Conclusions: Increasing and decreasing sleep difficulties may be associated with accelerated decline in cognitive function during retirement transition and post-retirement., (© Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society.)

Background: Inequalities between different areas in the United Kingdom (UK) according to health and employment outcomes are well-documented. Yet it is unclear which health indicator is most closely linked to labour market outcomes, and whether associations are restricted to the older population., Methods: We used the Office for National Statistics (ONS) Longitudinal Study (LS) to analyse which measures of health-in-a-place were cross-sectionally associated with three employment outcomes in 2011: not being in paid work, working hours (part-time, full-time), and economic inactivity (unemployed, retired, sick/disabled, other). Seven health indicators from local-authority census and vital records data were chosen to represent the older working age population (self-rated health 50-74y, long-term illness 50-74y, Age-specific mortality rate 50-74y, avoidable mortality, life expectancy at birth and 65 years, disability-free life expectancy at 50 years, and healthy life expectancy at 50 years). An additional two health indicators (life expectancy at birth and infant mortality rate) were included as test indicators to determine if associations were limited to the health of older people in a place. These nine health indicators were then linked with the LS sample aged 16-74y with data on employment outcomes and pertinent demographic and individual health information. Interactions by gender and age category (16-49y vs. 50-74y) were also tested., Findings: For all health-in-a-place measures, LS members aged 16-74 who resided in the tertile of local authorities with the 'unhealthiest' older population, had higher odds of not being in paid work, including all four types of economic inactivity. The strongest associations were seen for the health-in-a-place measures that were self-reported, long-term illness (Odds Ratio 1.60 [95% Confidence Intervals 1.52, 1.67]) and self-rated health (1.60 [1.52, 1.68]). Within each measure, associations were slightly stronger for men than women and for the 16-49y versus 50-74y LS sample. In models adjusted for individual self-rated health and gender and age category interactions, health-in-a-place gradients were apparent across all economic inactivity's. However, these same gradients were only apparent for women in part-time work and men in full-time work., Conclusion: Improving health of older populations may lead to wider economic benefits for all., (© 2022. The Author(s).)

Transcriptomics dose-response analysis (TDRA) has emerged as a promising approach for integrating toxicogenomics data into a risk assessment context; however, variability and uncertainty associated with experimental design are not well understood. Here, we evaluated n = 55 RNA-seq profiles derived from Japanese quail liver tissue following exposure to chlorpyrifos (0, 0.04, 0.1, 0.2, 0.4, 1, 2, 4, 10, 20, and 40 μg/g; n = 5 replicates per group) via egg injection. The full dataset was subsampled 637 times to generate smaller datasets with different dose ranges and spacing (designs A-E) and number of replicates ( n = 2-5). TDRA of the 637 datasets revealed substantial variability in the gene and pathway benchmark doses, but relative stability in overall transcriptomic point-of-departure (tPOD) values when tPODs were calculated with the "pathway" and "mode" methods. Further, we found that tPOD values were more dependent on the dose range and spacing than on the number of replicates, suggesting that optimal experimental designs should use fewer replicates ( n = 2 or 3) and more dose groups to reduce uncertainty in the results. Finally, tPOD values ranged by over ten times for all surveyed experimental designs and tPOD types, suggesting that tPODs should be interpreted as order-of-magnitude estimates.

Competing Interests: The 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.

Introduction: Cardiovascular diseases (CVDs) are the number one cause of death globally, impacting on public and private sectors. Current traditional interventions to prevent CVDs are mainly provided in healthcare centres and even when they are effective, they are not enough to reduce the rising prevalence; therefore, additional strategies are needed. Evidence suggests that health interventions in the workplace supply numerous benefits improving cardiovascular risk factor profiles in individuals. Hence, the aim of this systematic review and meta-analysis is to collate the evidence from randomised controlled trials, cluster randomised trials and quasi-experimental studies of workplace interventions to determine their effectiveness in terms of improving cardiovascular risk factors and preventing CVDs., Methods and Analysis: EMBASE, PsycINFO, PubMed, the Cochrane Central Register of Controlled Trials, LILACS, Scopus, Web of Science, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov and ProQuest Dissertations & Theses Global will be searched to include articles on workplace interventions in adults for CVDs events, cardiometabolic risk factors or behavioural risk factors. The study selection, data extraction, risk of bias and the assessment of the quality of the body of evidence will be conducted by two reviewers working in parallel and disagreements will be resolved by consensus or consultations with a third reviewer. Data synthesis will be done by meta-analysis using random-effects models when possible, otherwise the vote counting method will be applied. Statistical heterogeneity will be assessed by a χ 2 test and I 2 statistics. The quality of the body of evidence for each outcome will be assessed by applying the Grading of Recommendations, Assessment, Development and Evaluation approach., Ethics and Dissemination: Ethical approval is not required for this systematic review protocol. The results of the systematic review will be published in a peer-reviewed journal and will be publicly available., Prospero Registration Number: CRD42021276161., Competing Interests: Competing interests: None declared., (© 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.)

Early-life stage (ELS) avian toxicity tests have been proposed as a more ethical alternative to traditional standardized tests with adult birds. At the same time, 'omics approaches are gaining traction in the field of avian toxicology, but little has been done to characterize the metabolome and transcriptome at different life stages. The present study uses 'omics data from toxicity tests of 8 environmental chemicals in ELS and adult Japanese quail (Coturnix japonica) to address this data gap. Previous analyses of these data focused on responses to each of the individual chemicals. Here, we consider data from all studies to describe variation in the metabolome and transcriptome between life stages and across independent experiments, irrespective of chemical treatment. Of the 230 metabolites detected in liver, 163 were shared between the two life stages. However, many of the targeted bile acids that were present in the adult liver were absent from ELS samples. For the transcriptome, >90% of the 18,364 detected transcripts were common to both life stages. Based on the 213 genes solely detected in ELS liver, the neuroactive ligand-receptor interaction pathway was significantly enriched. Multivariate and hierarchical clustering analyses revealed that variability among independent experiments was higher for the adult than the ELS studies at both the metabolomic and transcriptomic levels. Our results indicate concordance of the two approaches, with less variation between independent experiments in the ELS metabolome and transcriptome than in adults, lending support for the use of ELS as an alternative toxicity testing strategy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Sedation is an essential component of treatment for some patients admitted to the ICU, but it carries a risk of sedation-related delirium. Sedation-related delirium is associated with higher mortality and increased length of stay, but pharmacologic treatments for delirium can lead to oversedation or other adverse effects. Therefore, nonpharmacologic treatments are recommended in the literature; however, these recommendations are quite general and do not provide structured interventions. To establish a structured nonpharmacologic intervention that could improve indications of delirium after sedation, we combined evidence-based interventions including recordings of sensory-rich stories told by the patient's family and patient-specific music into our novel positive stimulation for medically sedated patients (PSMSP) protocol. The positive listening stimulation playlist organized by a board-certified music therapist (MT-BC) within the PSMSP protocol can be used in carefully monitored sessions with the MT-BC potentially to decrease agitation and stabilize arousal, as well as being played by nursing staff throughout the patient's recovery from sedation. Further controlled studies will be necessary, but the PSMSP protocol has the potential to reduce agitation and increase arousal during listening, as highlighted by the case of a patient recovering from sedation during treatment for COVID-19 pneumonia. It is important for the entire critical care team to be aware of nonpharmacologic treatments like PSMSP that are available for delirium mitigation so that, where applicable, these therapies can be incorporated into the patient's treatment regimen., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The context of child prosthetics is a complex and important area for research and innovation. Yet, like many areas of paediatric medical technology development, there are several barriers to innovating specifically for the unique needs of children (i.e., a relatively small patient population or 'market'). As such, much child prosthetics technology is developed from the downsizing of adult prosthetics, leading to suboptimal outcomes for children and young people. Since 2016, the Starworks Child Prosthetics Research Network has been exploring this space, bringing children and their families together with key opinion leaders from the NHS, clinical Academia and leading National Research Centres with capabilities in child prosthetics with the aim of increasing research across the system. Above all else, Starworks is centred on the needs of children and their families, ensuring they have an equal voice in driving the ongoing research agenda. This article will share key learnings from the creation and development of the Starworks Network that may be applicable and/or adaptable across a wider paediatric medical technology research and innovation landscape. In particular it will discuss how it addressed three key aims of; (1) Addressing child-specific issues; (2) Building a sustainable network; and (3) Fostering impactful innovation.

Introduction: Cardiovascular diseases (CVDs) are the number one cause of death, and there is evidence that work exposures could be associated with their development. This study aimed to systematically review observational studies of adults exposed to job strain, effort-reward imbalance, long working hours, job insecurity, shift work, and occupational noise, and assess the association of those work exposures with CVDs., Methods: The Navigation Guide framework was applied. The population were adults of working age (18-65), and cohort and case-control studies were included. The work exposures were job strain, effort-reward imbalance, long working hours, job insecurity, shift work, and occupational noise. The outcomes were cerebrovascular diseases, ischaemic heart disease, and hypertensive diseases. The selection, data extraction, risk of bias assessment, and quality assessment were carried out by two reviewers independently and disagreements were solved by a third reviewer or by consensus. The synthesis of the results was done by applying the 'vote counting based on direction' method, and the results were summarized in an effect direction plot. The strength of the evidence for every risk factor and CVD was defined by consensus., Results: A total of 17 643 papers were initially identified in the literature search, but after applying the filters by title and abstract, and full text, 86 studies were finally included. From the included studies, sufficient evidence was found of the harmfulness of job strain for cerebrovascular disease and ischemic heart disease. Furthermore, there was sufficient evidence of the harmfulness of shift work for ischemic heart disease. Evidence of no relationship was found between long working hours and shift work with ischaemic heart disease and hypertensive disease, respectively. The other associations of work exposures and CVDs had limited or inadequate evidence of harmfulness., Conclusions: In this comprehensive review, there was sufficient evidence of a harmful relationship between job strain, shift work, and CVDs. For the other work exposures, more high-quality studies are needed. In order to improve current prevention strategies for CVDs, the findings of this review imply that job strain and shift work are work exposures that constitute additional risk factors that could be approached as targets for worksite interventions., Systematic Review Registration: PROSPERO CRD42020179972., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Aim: . This study aimed to pilot test, assess usability and utility of, and identify barriers to implementation for the Profile of Preschool Communication (PPC) - a new data collection tool designed to support outcome monitoring in preschool speech-language programs and practice-based research., Methods: . This pilot study was conducted with three sites in the Ontario Preschool Speech and Language (PSL) program. Twenty-three speech-language pathologists used the PPC for all outcome monitoring assessments for 2-3-months and provided feedback about their experience using it in practice. Then, 18 of the 23 speech-language pathologists completed online surveys to rate usability and utility, and report their perceived implementation barriers and facilitators., Results: . Speech-language pathologists reported difficulties completing some sections of the PPC, most notably obtaining data related to maternal education and family history of mental health concerns. Usability and utility were generally rated favorably with some items rated as neutral. Barriers to implementation included the paper format, completion time, requirement to ask personal questions, and the perception by some that data were useful for outcome monitoring but not practice. Facilitators included ease of use, an improvement over the existing tool, and the collection of data to support service planning., Conclusions: . The PPC shows potential as an outcome monitoring data collection tool in preschool speech-language pathology programs. Findings will be of interest to researchers engaged in practice-based research and those interested in engaging end users to develop clinically meaningful tools., (Copyright © 2022. Published by Elsevier Inc.)

Health expectancies are an indicator of healthy ageing that reflect quantity and quality of life. Using limiting long term illness and mortality prevalence, we calculate disability-free life expectancy for small areas in England and Wales between 1991 and 2011 for males and females aged 50-74, the life stage when people may be changing their occupation from main career to retirement or alternative work activities. We find that inequalities in disability-free life expectancy are deeply entrenched, including former coalfield and ex-industrial areas and that areas of persistent (dis-) advantage, worsening or improving deprivation have health change in line with deprivation change. A mixed health picture for rural and coastal areas requires further investigation as do the demographic processes which underpin these area level health differences., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Knowledge on the population history of endangered species is critical for conservation, but whole-genome data on chimpanzees ( Pan troglodytes ) is geographically sparse. Here, we produced the first non-invasive geolocalized catalog of genomic diversity by capturing chromosome 21 from 828 non-invasive samples collected at 48 sampling sites across Africa. The four recognized subspecies show clear genetic differentiation correlating with known barriers, while previously undescribed genetic exchange suggests that these have been permeable on a local scale. We obtained a detailed reconstruction of population stratification and fine-scale patterns of isolation, migration, and connectivity, including a comprehensive picture of admixture with bonobos ( Pan paniscus ). Unlike humans, chimpanzees did not experience extended episodes of long-distance migrations, which might have limited cultural transmission. Finally, based on local rare variation, we implement a fine-grained geolocalization approach demonstrating improved precision in determining the origin of confiscated chimpanzees., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

The health care delivery system in the United States, structured to provide single-disease care, presents unique challenges for patients with complex physical and psychiatric comorbidities. Patients in these populations are often referred to multiple specialty clinics, encounter little continuity of care or collaboration among their providers, incur high health care costs, and experience poor treatment outcomes. Given these barriers, questions remain about the extent to which siloed and fragmented care, as opposed to the complex nature of the illnesses themselves, contribute to poor outcomes. If given the opportunity to receive well-integrated, consistent, and personalized care, can patients with historically difficult-to-treat comorbid medical and mental illnesses make progress? This article describes an innovative model of care called functional rehabilitation that is designed to address existing barriers in treatment. The functional rehabilitation program seeks to disrupt the escalating effects of interacting comorbidities by offering highly collaborative treatment from a small team of clinicians, personalized interventions using a shared decision-making framework, multipronged treatment options, colocation in a large hospital system, and significant 1:1 time with patients. The article includes a case example with longitudinal outcome data that illustrates how progress can be made with appropriate programmatic supports. Future research should examine the cost-effectiveness of this model of care., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study designed a pilot elective course to augment geriatric education in undergraduate and medical students, and secondarily to investigate an alternative individual cognitive stimulation therapy (iCST) platform., Methods: Student participants (SPs) were recruited over five semesters to create and deliver iCST sessions to geriatric participants (GPs) for 10 weeks. Likert scale survey items and open-ended questions were used to evaluate the success of the SPs. Pre- and post-Saint Louis University Mental Status (SLUMS) exam and Quality of Life in Alzheimer's disease (QOL-AD) scores were obtained and a paired t-test determined whether the novel iCST model significantly improved GPs' cognition and/or quality of life., Results: Thirty SPs and 10 GPs successfully completed the pilot course and iCST intervention. Ninety-three percent of all SPs rated the course positively and 100% felt the course was relevant to their future careers. The iCST model also yielded positive results, including a 3.8-point increase in quality of life for the GP, as measured by the QOL-AD ( p = .01). SLUMS scores increased by 1.3-points, although failing to reach statistical significance ( p = .25)., Conclusions: This pilot has shown success in exposing students to geriatric-specific education and introducing an alternative iCST platform.