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Background: Previous literature has highlighted the complexity of supporting an acutely unwell child and the unnecessary use of services by parents/carers. The Little Orange Book (LOB) was developed as an information resource for parents/carers of young children to assist in managing symptoms of childhood illness and to encourage the appropriate use of healthcare services., Objectives: This study aimed to understand parent/carer views and experiences using the Little Orange Book. Specifically, this study focused on barriers and facilitators to use, the impact on parents' behaviour and the views on improving the LOB., Methods: An explanatory sequential mixed-methods approach, including qualitative and quantitative components, was used to collect data regarding parent's experiences using the LOB. Parents and carers in the North-East of England were invited to participate in an online survey and a subset of these respondents took part in qualitative interviews. One-hundred-and-twenty-eight parents completed the online survey and 16 took part in interviews. Qualitative data were analysed using thematic analysis and quantitative data analysed using descriptive statistical analytical methods., Results: Three themes were identified within the data: Increasing parental empowerment in managing their child's health, Equality of Access to Health-based Literature and Barriers and Facilitators to using the Little Orange Book., Conclusions: The Little Orange Book was seen as a valuable form of information to support parents and carers in healthcare decisions. Further development should ensure inclusivity, widen access and view provision of the information as an opportunity for healthcare professionals to engage with parents., Competing Interests: No authors have competing interests, (Copyright: © 2025 Johnson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Evidence for Mobile Stroke Units (MSUs) demonstrates that onset to treatment times for intravenous thrombolysis can be reduced and access to mechanical thrombectomy might be improved. Despite growing use of MSUs internationally, to date there have been no studies in NHS England and NHS Wales exploring the acceptability of MSUs to clinicians, patient and public representatives and other key stakeholders, which are important when considering potential feasibility and implementation., Methods: This study used a mixed methods design with a cross-sectional survey and qualitative workshops and interviews between October 2023 to May 2024. Survey data were collected from clinicians involved in emergency stroke care. Qualitative data involved clinical and non-clinical professionals involved in stroke care alongside patient and public representatives with experience of stroke. Survey data were descriptively analysed while content analysis was used on open-ended questions. Qualitative data were thematically analysed, prior to triangulation using a convergent coding matrix., Results: The study results, drawn from 25 respondents to the survey and 21 participants in qualitative workshops, found that almost all participants had positive affective attitudes to the concept of MSUs. However, several key areas of concern were identified that need to be addressed prior to implementing MSUs. These concerns included how MSUs would be staffed; whether and how telemedicine could contribute; the types of economic impacts; extent to which triage systems could accurately identify stroke patients for MSUs to attend; where the base location and geographic coverage of MSUs should be, the impact of MSUs on equitable access to stroke care, and how to improve public awareness of MSUs., Conclusion: Whilst MSUs are mostly acceptable to key stakeholders, numerous areas of concern need to be addressed prior to MSU implementation. We recommend further research to address these issues prior to implementation in the NHS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Moseley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Evidence suggests that social prescribing might have a positive impact on identity, control, creativity and quality of life in people with dementia. While evidence on the benefits of social prescribing is accumulating, there is a sparsity of research on the experiences of social prescribers. This study aims to identify the challenges that social prescribers face when supporting people with dementia and their families and strategies to address these., Materials and Methods: A qualitative study involving 24 social prescribers from all regions in England. Semi-structured interviews investigated challenges and strategies that social prescribers experience in their own practice. Data were analysed through thematic analysis. Results on "Challenges" and the respective "Strategies" are presented in a chronological order that reflects the different stages of contact with and support for the client with dementia, from referral to discharge., Results and Discussion: This study identified unique barriers that social prescribers face when working with people with dementia, particularly around communication, motivation, engagement and overdependency. It identified person and system-level strategies that can be used to address these challenges. These include expanding opportunities for dementia training, offering in-person support, including social prescribing in annual dementia reviews, and increasing integration of services within Integrated Care Systems and collaborations between health care service providers and with the third sector. Improving delivery and effectiveness of services is crucial to ensure that social prescribing fulfils its ethos of personalised care approach for all, including people with dementia, as envisioned in the NHS long term plan., Competing Interests: Author Claudio Di Lorito currently serves as editor of Plos One. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2025 Di Lorito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Identifying processes that promote coral reef recovery and resilience is crucial as ocean warming becomes more frequent and severe. Sexual reproduction is essential for the replenishment of coral populations and maintenance of genetic diversity; however, the ability for corals to reproduce may be impaired by marine heatwaves that cause coral bleaching. In 2014 and 2015, the Hawaiian Islands experienced coral bleaching with differential bleaching susceptibility in the species Montipora capitata, a dominant reef-building coral in the region. We tested the hypothesis that coral bleaching resistance enhances reproductive capacity and offspring performance by examining the reproductive biology of colonies that bleached and recovered (B) and colonies that did not bleach (NB) in 2015 in the subsequent spawning seasons. The proportion of colonies that spawned was higher in 2016 than in 2017. Regardless of parental bleaching history, we found eggs with higher abnormality and bundles with fewer eggs in 2016 than 2017. While reproductive output was similar between B and NB colonies in 2016, survivorship of offspring that year were significantly influenced by the parental bleaching history (egg donor × sperm donor: B × B, B × NB, NB × B, and NB × NB). Offspring produced by NB egg donors had the highest survivorship, while offspring from previously bleached colonies had the lowest survivorship, highlighting the negative effects of bleaching on parental investment and offspring performance. While sexual reproduction continues in M. capitata post-bleaching, gametes are differentially impacted by recovery time following a bleaching event and by parental bleaching resistance. Our results demonstrate the importance of identifying bleaching resistant individuals during and after heating events. This study further highlights the significance of maternal effects through potential egg provisioning for offspring survivorship and provides a baseline for human-assisted intervention (i.e., selective breeding) to mitigate the effects of climate change on coral reefs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Lenz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Hog1 stress-activated protein kinase (SAPK) is a key mediator of stress resistance and virulence in Candida albicans. Hog1 activation via phosphorylation of the canonical TGY motif is mediated by the Pbs2 MAPKK, which itself is activated by the Ssk2 MAPKKK. Although this three-tiered SAPK signalling module is well characterised, it is unclear how Hog1 activation is regulated in response to different stresses. Functioning upstream of the Ssk2 MAPKKK is a two-component related signal transduction system comprising three sensor histidine kinases, a phosphotransfer protein Ypd1, and a response regulator Ssk1. Here, we report that Ssk1 is a master regulator of the Hog1 SAPK that promotes stress resistance and Hog1 phosphorylation in response to diverse stresses, except high osmotic stress. Notably, we find Ssk1 regulates Hog1 in a two-component independent manner by functioning to promote interactions between the Ssk2 and Pbs2 kinases. We propose this function of Ssk1 is important to maintain a basal level of Hog1 phosphorylation which is necessary for oxidative stress, but not osmotic stress, mediated Hog1 activation. We find that osmotic stress triggers robust Pbs2 phosphorylation which drives its dissociation from Ssk2. In contrast, Pbs2 is not robustly phosphorylated following oxidative stress and the Ssk1-mediated Ssk2-Pbs2 interaction remains intact. Instead, oxidative stress-stimulated increases in phosphorylated Hog1 is dependent on the inhibition of protein tyrosine phosphatases that negatively regulate Hog1 coupled with the Ssk1-mediated promotion of basal Hog1 activity. Furthermore, we find that inhibition of protein tyrosine phosphatases is linked to the hydrogen peroxide induced oxidation of these negative regulators in a mechanism that is partly dependent on thioredoxin. Taken together these data reveal stress contingent changes in Hog1 pathway architecture and regulation and uncover a novel mode of action of the Ssk1 response regulator in SAPK regulation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Day et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Severe and multiple disadvantage (SMD) is the combined effect of experiencing homelessness, substance use and repeat offending. People experiencing SMD have high burden of physical and mental health issues. Oral health is one of the most common health problems in people experiencing SMD which interacts with substance use, smoking, and unhealthy diet to create a cycle of harm and disadvantage. However, burden of these conditions is worsened by poor access to health services. This study aimed to identify pathways to improve engagement and access to health interventions, for oral health, substance and alcohol use, smoking and diet., Methods: Using a qualitative methodology, interviews/focus groups were conducted with: (a) people experiencing SMD in Newcastle Upon Tyne/Gateshead; and (b) frontline staff, volunteer workers, policy makers and commissioners from London, Plymouth and Newcastle Upon Tyne/Gateshead. Data was analysed iteratively using thematic analysis., Results: Twenty-eight people experiencing SMD (age range: 27-65 years; 21% females) and 78 service providers (age range: 28-72 years, 63% females) were interviewed or included in focus groups. Data were organized into two overarching factors: barriers to accessing health interventions and improving access to health interventions. Barriers included: wider disadvantages of people experiencing SMD leading to low priority for support for oral health and associated health behaviours, psychosocial factors, waiting period and physical space. Factors that improved access to interventions included: positive relationships between service provider and person experiencing SMD, including a support worker, location of services and outreach services., Conclusions: The findings suggest the need for flexibility in offering services for oral health and related health behaviours for people experiencing SMD. Training health care providers and co-developing services with people with lived experience of SMD can help prevent (re)stigmatization. Systems-based approach to address factors on an environmental, organizational, inter-personal and individual level is needed. The results from this study could be extrapolated to other health intervention such as vaccinations and sexual and reproductive health., Competing Interests: The authors have declared that no competing interests exist. The funders had no role in the design of the study, in the collection, analysis, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results., (Copyright: © 2024 Jain et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The importance of maintaining data privacy and complying with regulatory requirements is highlighted especially when sharing omic data between different research centers. This challenge is even more pronounced in the scenario where a multi-center effort for collaborative omics studies is necessary. OmicSHIELD is introduced as an open-source tool aimed at overcoming these challenges by enabling privacy-protected federated analysis of sensitive omic data. In order to ensure this, multiple security mechanisms have been included in the software. This innovative tool is capable of managing a wide range of omic data analyses specifically tailored to biomedical research. These include genome and epigenome wide association studies and differential gene expression analyses. OmicSHIELD is designed to support both meta- and mega-analysis, so that it offers a wide range of capabilities for different analysis designs. We present a series of use cases illustrating some examples of how the software addresses real-world analyses of omic data., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Escriba-Montagut et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The impact of light exposure on mental health is increasingly recognised. Modifying inpatient evening light exposure may be a low-intensity intervention for mental disorders, but few randomised controlled trials (RCTs) exist. We report a large-scale pragmatic effectiveness RCT exploring whether individuals with acute psychiatric illnesses experience additional benefits from admission to an inpatient ward where changes in the evening light exposure are integrated into the therapeutic environment., Methods and Findings: From 10/25/2018 to 03/29/2019, and 10/01/2019 to 11/15/2019, all adults (≥18 years of age) admitted for acute inpatient psychiatric care in Trondheim, Norway, were randomly allocated to a ward with a blue-depleted evening light environment or a ward with a standard light environment. Baseline and outcome data for individuals who provided deferred informed consent were used. The primary outcome measure was the mean duration of admission in days per individual. Secondary outcomes were estimated mean differences in key clinical outcomes: Improvement during admission (The Clinical Global Impressions Scale-Improvement, CGI-I) and illness severity at discharge (CGI-S), aggressive behaviour during admission (Broset Violence Checklist, BVC), violent incidents (Staff Observation Aggression Scale-Revised, SOAS-R), side effects and patient satisfaction, probabilities of suicidality, need for supervision due to suicidality, and change from involuntary to voluntary admission. The Intent to Treat sample comprised 476 individuals (mean age 37 (standard deviation (SD) 13.3); 193 (41%) were male, 283 (59%) were female). There were no differences in the mean duration of admission (7.1 days for inpatients exposed to the blue-depleted evening light environment versus 6.7 days for patients exposed to the standard evening light environment; estimated mean difference: 0.4 days (95% confidence interval (CI) [-0.9, 1.9]; p = 0.523). Inpatients exposed to the blue-depleted evening light showed higher improvement during admission (CGI-I difference 0.28 (95% CI [0.02, 0.54]; p = 0.035), Number Needed to Treat for clinically meaningful improvement (NNT): 12); lower illness severity at discharge (CGI-S difference -0.18 (95% CI [-0.34, -0.02]; p = 0.029), NNT for mild severity at discharge: 7); and lower levels of aggressive behaviour (difference in BVC predicted serious events per 100 days: -2.98 (95% CI [-4.98, -0.99]; p = 0.003), NNT: 9). There were no differences in other secondary outcomes. The nature of this study meant it was impossible to blind patients or clinical staff to the lighting condition., Conclusions: Modifying the evening light environment in acute psychiatric hospitals according to chronobiological principles does not change duration of admissions but can have clinically significant benefits without increasing side effects, reducing patient satisfaction or requiring additional clinical staff., Trial Registration: Clinicaltrials.gov NCT03788993; 2018 (CRISTIN ID 602154)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kallestad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to potentially address a range of scientific questions. In this article, we describe the methods used to set up simulations to reproduce in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce experimental findings. Finally, we make data, code, and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This community-based model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Romani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The rapid development of vaccines to combat the spread of COVID-19, caused by the SARS-CoV-2 virus, is a great scientific achievement. Before the development of the COVID-19 vaccines, most studies capitalized on the available data that did not include pharmaceutical measures. Such studies focused on the impact of non-pharmaceutical measures such as social distancing, sanitation, use of face masks, and lockdowns to study the spread of COVID-19. In this study, we used the SIDARTHE-V model, an extension of the SIDARTHE model, which includes vaccination rollouts. We studied the impact of vaccination on the severity of the virus, specifically focusing on death rates, in African countries. The SIRDATHE-V model parameters were extracted by simultaneously fitting the COVID-19 cumulative data of deaths, recoveries, active cases, and full vaccinations reported by the governments of Ghana, Kenya, Mozambique, Nigeria, South Africa, Togo, and Zambia. Using South Africa as a case study, our analysis showed that the cumulative death rates declined drastically with the increased extent of vaccination drives. Whilst the infection rates sometimes increased with the arrival of new coronavirus variants, the death rates did not increase as they did before vaccination., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: The COVID-19 pandemic changed the way many industries work, including contact centres, with some employees working from home and new on-site restrictions/measures in place representing even greater challenges for employers around staff engagement and wellbeing. This study aimed to understand the interplay of individual, social, environmental and organisational factors influencing physical activity and sedentary behaviour in UK contact centre employees, how the pandemic impacted these factors, and their relevance for the future of hybrid working., Methods: Individual interviews (n = 33) were conducted with participants (staff working full and part time, on site and from home) from four UK contact centres. A topic guide based on the ecological model was developed to understand current barriers and facilitators to physical activity and (reducing) sedentary behaviour during and outside of working hours. Thematic analysis was carried out using a codebook and a deductive coding approach to identify themes., Results: Three key insights are provided. First, participants felt they were generally sitting more and moving less since the first UK-wide lockdown. Second, factors which negatively impacted on these behaviours were evident across all levels of the ecological model. These included individual and social barriers (e.g., lack of motivation and preferable physical activity options) as well as environmental and organisational barriers (e.g., poor home office setup, back-to-back virtual meetings). There were a mix of new and existing barriers (exacerbated by the pandemic) and several of these were linked to homeworking. Third, organisational support requirements (e.g., homeworking ergonomic support) and existing facilitators (such as the provision of informational support and flexible working arrangements) were identified., Conclusion: Solutions to reduce sedentary behaviours and increase physical activity in contact centres need to address barriers from the individual to the organisational level. Whilst the study was undertaken in the UK, the results are like to be applicable globally., Trial Registration: Clinical trial registration: The trial for the wider project has been registered on the ISRCTN database: http://www.isrctn.com/ISRCTN11580369., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Manner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Community-based sexual health services are recommended to increase sexually transmitted disease (STD) testing among men who have sex with men (MSM). Pilot study data from multiple sites found that MSM in Guangzhou who use public STD clinics were found to have different sociodemographic characteristics, lower community engagement, and increased social cohesion, compared to MSM who use MSM-led clinics., Competing Interests: The authors have declared no competing interests exist., (Copyright: © 2024 Huon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The ability of the attaching and effacing pathogens enterohaemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium to overcome colonisation resistance is reliant on a type 3 secretion system used to intimately attach to the colonic epithelium. This crucial virulence factor is encoded on a pathogenicity island known as the Locus of Enterocyte Effacement (LEE) but its expression is regulated by several core-genome encoded transcription factors. Here, we unveil that the core transcription factor PdhR, traditionally known as a regulator of central metabolism in response to cellular pyruvate levels, is a key activator of the LEE. Through genetic and molecular analyses, we demonstrate that PdhR directly binds to a specific motif within the LEE master regulatory region, thus activating type 3 secretion directly and enhancing host cell adhesion. Deletion of pdhR in EHEC significantly impacted the transcription of hundreds of genes, with pathogenesis and protein secretion emerging as the most affected functional categories. Furthermore, in vivo studies using C. rodentium, a murine model for EHEC infection, revealed that PdhR is essential for effective host colonization and maximal LEE expression within the host. Our findings provide new insights into the complex regulatory networks governing bacterial pathogenesis. This research highlights the intricate relationship between virulence and metabolic processes in attaching and effacing pathogens, demonstrating how core transcriptional regulators can be co-opted to control virulence factor expression in tandem with the cell's essential metabolic circuitry., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wale et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Citizens play a crucial role in attaining the United Nations 2030 sustainable development goals (SDGs). There is growing awareness of the importance of understanding citizen perspectives on environmental issues, in relation to developing and maintaining sustainable lifestyles, and in addressing perceived threats to protection and restoration of ecosystems and biodiversity. This analysis sought to understand people's attitudes towards environmental conservation, how they relate to perceived threats to the countryside, and to determine how attitudes and perceived threats vary demographically and between countries. A survey was administered to citizens (quota sampled on age, gender, education, and split between rural and urban residency) across five countries representative of differing biogeographical regions (N = 3,190): Czech Republic (n = 649) (Continental); Spain (Mediterranean) (n = 623); Sweden (Boreal) (n = 645); Switzerland (Alpine) (n = 641); United Kingdom (UK) (Atlantic) (n = 632). Attitudes were measured using the Environmental Attitudes Inventory (EAI-24) on 2 factors (utilization; preservation) and perceived threat to the countryside on 1-factor (15 items). Multigroup regression analysis indicated that preservationist attitudes were associated with greater perceived threat to the countryside in all five countries. Higher perceived threat was associated with activities linked to environmental degradation, socio-economic uncertainty and risks in agri-food supply chains in all countries. The "bad behaviour of visitors" was the greatest perceived threat in the Czech Republic, Switzerland and the UK, while "lack of young farmers taking over farming" was the greatest perceived threat in Spain and Sweden. To promote pro-environmental attitudes and obtain greater public support for policies and interventions targeting environmental conservation, communication about environmental threats is needed, together with threat mitigation measures. Raising peoples' awareness of threats to the countryside through targeted communications could promote pro-environment attitudes and potentially result in pro-environmental behaviours., 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., (Copyright: © 2024 Stewart-Knox et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We aimed to estimate the relative risk of mortality following a first positive SARS-CoV-2 test during the first, second, and third waves of the COVID-19pandemic in England by age, sex, and vaccination status, taking into account pre-existing health conditions and lifestyle factors., Methods: We conducted a retrospective cohort study of all individuals registered with the National Health Service (NHS) in England from 1 March 2020 to September 2022. Data for all individuals were obtained and linked including primary care records, hospital admission episodes, SARS-CoV-2 test results, vaccinations, and death registrations. We fitted Cox Proportional Hazards models with time dependent covariates for confirmed SARS-CoV-2 infection to model the risk of subsequent mortality., Results: The hazard ratio for death after testing positive for subsequent, compared with those not testing positive, amongst unvaccinated individuals, ranged from 11 to 89 by age and sex, in the first four weeks following a positive test in wave one and reduced to 14 to 50 in wave three. This hazard was further reduced amongst those who had three vaccines to between 1.4 and 7 in wave three., Conclusions: This study provides robust estimates of increased mortality risk among those who tested positive over the first three waves of the COVID-19 pandemic in England. The estimates show the impact of various factors affecting the risk of mortality from COVID-19. The results provide the first step towards estimating the magnitude and pattern of mortality displacement due to COVID-19, which is essential to understanding subsequent mortality rates in England., Competing Interests: PG declares consultancy payments made from OHID to UCL Consulting to support the preparation of this manuscript. All other authors have no declarations., (Copyright: © 2024 Bauer-Staeb et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context: LGBTQIA+ people worldwide experience discrimination, violence, and stigma that lead to poor health outcomes. Policy plays a crucial role in ensuring health equity and safety for LGBTQIA+ communities. Given Lancet Commissions' substantial impact on health policy across domains, we aimed to determine how LGBTQIA+ communities and their care needs are incorporated throughout Lancet Commission reports and recommendations., Methods: Using critical discourse analysis, we analyzed 102 Commissions for inclusion of and reference to LGBTQIA+ communities using 36 key terms. Three levels of analysis were conducted: 1) micro-level (overview of terminology use); 2) meso-level (visibility and placement of LGBTQIA+ references); and 3) macro-level (outlining characterizations and framing of references with consideration of broader social discourses)., Findings: 36 of 102 (35%) Commissions referenced LGBTQIA+ communities with 801 mentions in total. There were minimal (9/36) references made in the "Executive Summary," "Recommendations," and/or "Key Messages" sections of reports. LGBTQIA+ communities were most frequently discussed in reports related to HIV/AIDS and sexual and reproductive health. Few Commissions related to public health, or chronic conditions (9/60) referenced LGBTQIA+ communities. Some reports made non-specific or unexplained references; many discussed the LGBTQIA+ population without specific reference to sub-groups. LGBTQIA+ communities were often listed alongside other marginalized groups without rationale or a description of shared needs or experiences. We identified framings (legal, vulnerability, risk) and characterizations (as victims, as blameworthy, as a problem) of LGBTQIA+ communities that contribute to problematizing discourse., Conclusions: LGBTQIA+ people were rarely included in the Commissions, resulting in an inadvertent marginalization of their health needs. Policy initiatives must consider LGBTQIA+ groups from a strengths-based rather than problematizing perspective, integrating evidence-based approaches alongside community-based stakeholder engagement to mitigate inequities and promote inclusive care and policymaking., Competing Interests: These authors have no other conflicts to disclose., (Copyright: © 2024 Rosa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Frailty is characterised by a decline in physical, cognitive, energy, and health reserves and is linked to greater functional dependency and higher social care utilisation. However, the relationship between receiving care, or receiving insufficient care among older people with different frailty status and the risk of unplanned admission to hospital for any cause, or the risk of falls and fractures remains unclear., Methods and Findings: This study used information from 7,656 adults aged 60 and older participating in the English Longitudinal Study of Ageing (ELSA) waves 6-8. Care status was assessed through received care and self-reported unmet care needs, while frailty was measured using a frailty index. Competing-risk regression analysis was used (with death as a potential competing risk), adjusted for demographic and socioeconomic confounders. Around a quarter of the participants received care, of which approximately 60% received low levels of care, while the rest had high levels of care. Older people who received low and high levels of care had a higher risk of unplanned admission independent of frailty status. Unmet need for care was not significantly associated with an increased risk of unplanned admission compared to those receiving no care. Older people in receipt of care had an increased risk of hospitalisation due to falls but not fractures, compared to those who received no care after adjustment for covariates, including frailty status., Conclusions: Care receipt increases the risk of hospitalisation substantially, suggesting this is a group worthy of prevention intervention focus., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Maharani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The structured professional judgement (SPJ) approach was initially developed to support risk assessment and management decisions. The approach is now being adapted and applied to admission assessments for adult secure services. This systematic review aims to summarise the evidence for the effectiveness and acceptability of the SPJ approach in admission assessments of this kind. A comprehensive electronic search strategy was used to identify studies indexed in PubMed, PsycInfo, Medline and Cochrane Library (January 2007 -January 2024). Two search strategies included terms (and synonyms) for psychiatric patients (quantitative) or clinicians and clinicians' experiences (qualitative), structured professional judgement, admission, and secure services. Twelve quantitative articles (published 2007-2020) were identified. SPJ-informed guidance included were the DUNDRUM-1, DUNDRUM-2, DUNDRUM-3, DUNDRUM-4, and the HCR-20. While findings were variable, the overall pattern indicated that ratings suggestive of more problems were associated with increased likelihood of admission or movement to higher security levels. There is emerging evidence for the use of SPJ guidance to support admission decision-making. Specifically, it should be used as an adjunct to existing decision-making processes rather than as a replacement for those processes. Further research, both quantitative and qualitative, across a wider range of settings and populations is recommended., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bowden et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We evaluated by comparing the performance of three pneumatically-driven bioreactors in the production of L-asparaginase (L-ASNase), an enzyme used to treat leukaemia and lymphoma. A two-step screening process was conducted to detect Cunninghamella spp. strains producing L-ASNase. Cunninghamella echinulata DSM1905 produced the highest levels of L-ASNase during screening assays. Subsequently, fermentations were performed in bubble column (BCR), airlift (ALR), and hybrid fixed-bed airlift (FB-ALR) bioreactors to determine the best upstream bioprocess. Mycelial biomass production was higher in BCR than in ALR and FB-ALR (p ≤ 0.0322). The activity of L-ASNase produced in FB-ALR, in which the fungus grew as a consistent biofilm, was significantly higher (p ≤ 0.022) than that from ALR, which was higher than that of BCR (p = 0.036). The specific activity of ALR and FB-ALR presented no differences (p = 0.073), but it was higher than that of BCR (p ≤ 0.032). In conclusion, C. echinulata DSM1905, grown under the biofilm phenotype, produced the highest levels of L-ASNase, and FB-ALR was the best upstream system for enzyme production., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ramos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Implicit statistical learning, whereby predictable relationships between stimuli are detected without conscious awareness, is important for language acquisition. However, while this process is putatively implicit, it is often assessed using measures that require explicit reflection and conscious decision making. Here, we conducted three experiments combining an artificial grammar learning paradigm with a serial reaction time (SRT-AGL) task, to measure statistical learning of adjacent and nonadjacent dependencies implicitly, without conscious decision making. Participants viewed an array of six visual stimuli and were presented with a sequence of three auditory (nonsense words, Expt. 1; names of familiar objects, Expt. 2) or visual (abstract shapes, Expt. 3) cues and were asked to click on the corresponding visual stimulus as quickly as possible. In each experiment, the final stimulus in the sequence was predictable based on items earlier in the sequence. Faster responses to this predictable final stimulus compared to unpredictable stimuli would provide evidence of implicit statistical learning, without requiring explicit decision making or conscious reflection. Despite previous positive results (Christiansen et al. 2009 and Misyak et al. 2010) we saw little evidence of implicit statistical learning in any of the experiments, suggesting that in this case, these SRT-AGL tasks were not an effective measure implicit statistical learning., Competing Interests: This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Jenkins et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Assisted sexual coral propagation, resulting in greater genet diversity via genetic recombination, has been hypothesized to lead to more adaptable and, hence, resilient restored populations compared to more common clonal techniques. Coral restoration efforts have resulted in substantial populations of 'Assisted sexual Recruits' (i.e., juvenile corals derived from assisted sexual reproduction; AR) of multiple species outplanted to reefs or held in in situ nurseries across many locations in the Caribbean. These AR populations provided context to evaluate their relative resilience compared to co-occurring coral populations during the 2023 marine heat wave of unprecedented duration and intensity that affected the entire Caribbean. Populations of six species of AR, most ranging in age from 1-4 years, were surveyed across five regions during the mass bleaching season in 2023 (Aug-Dec), alongside co-occurring groups of corals to compare prevalence of bleaching and related mortality. Comparison groups included conspecific adult colonies as available, but also the extant co-occurring coral assemblages in which conspecifics were rare or lacking, as well as small, propagated coral fragments. Assisted sexual recruits had significantly lower prevalence of bleaching impacts (overall pooled ~ 10%) than conspecific coral populations typically comprised of larger colonies (~ 60-100% depending on species). In addition, small corals derived from fragmentation (rather than sexual propagation) in two regions showed bleaching susceptibility intermediate between AR and wild adults. Overall, AR exhibited high bleaching resistance under heat stress exposure up to and exceeding Degree Heating Weeks of 20°C-weeks. As coral reefs throughout the globe are subject to increasingly frequent and intense marine heatwaves, restoration activities that include sexual reproduction and seeding can make an important contribution to sustain coral populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Miller et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Maternal nutrition is crucial for health in pregnancy and across the generations. Experiencing food insecurity during pregnancy is a driver of inequalities in maternal diet with potential maternal and infant health consequences. This systematic review explored associations between food insecurity in pregnancy and maternal and infant health outcomes., Methods and Findings: Searches included 8 databases (MEDLINE, Embase, Scopus, Web of Science, PsychInfo, ASSIA, SSPC in ProQuest, and CINAHL), grey literature, forwards and backwards citation chaining, and contacting authors. Studies in high-income countries (HICs) reporting data on food insecurity in pregnancy and maternal or infant health, from January 1, 2008 to November 21, 2023 were included. Screening, data extraction, and quality assessment were carried out independently in duplicate. Random effects meta-analysis was performed when data were suitable for pooling, otherwise narrative synthesis was conducted. The protocol was registered on PROSPERO (CRD42022311669), reported with PRISMA checklist (S1 File). Searches identified 24,223 results and 25 studies (n = 93,871 women) were included: 23 from North America and 2 from Europe. Meta-analysis showed that food insecurity was associated with high stress level (OR 4.07, 95% CI [1.22, 13.55], I2 96.40%), mood disorder (OR 2.53, 95% CI [1.46, 4.39], I2 55.62%), gestational diabetes (OR 1.64, 95% CI [1.37, 1.95], I2 0.00%), but not cesarean delivery (OR 1.42, 95% CI [0.78, 2.60], I2 56.35%), birth weight (MD -58.26 g, 95% CI [-128.02, 11.50], I2 38.41%), small-for-gestational-age (OR 1.20, 95%, CI [0.88, 1.63], I2 44.66%), large-for-gestational-age (OR 0.88, 95% CI [0.70, 1.12] I2 11.93%), preterm delivery (OR 1.18, 95% CI [0.98, 1.42], I2 0.00%), or neonatal intensive care (OR 2.01, 95% CI [0.85, 4.78], I2 70.48%). Narrative synthesis showed food insecurity was significantly associated with dental problems, depression, anxiety, and maternal serum concentration of perfluoro-octane sulfonate. There were no significant associations with other organohalogen chemicals, assisted delivery, postpartum haemorrhage, hospital admissions, length of stay, congenital anomalies, or neonatal morbidity. Mixed associations were reported for preeclampsia, hypertension, and community/resilience measures., Conclusions: Maternal food insecurity is associated with some adverse pregnancy outcomes, particularly mental health and gestational diabetes. Most included studies were conducted in North America, primarily the United States of America, highlighting a research gap across other contexts. Further research in other HICs is needed to understand these associations within varied contexts, such as those without embedded interventions in place, to help inform policy and care requirements., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tropilaelaps spp. are invasive mites that cause severe disease in Apis mellifera colonies. The UK has deployed an elaborate surveillance system that seeks to detect these mites early in any invasion to allow the best opportunity to eradicate any incursion. Effective field and laboratory protocols, capable of reliably detecting low numbers of mites, are key to the success of any intervention. Here we compared the efficacy of established field monitoring using brood removal with an uncapping fork, and brood 'bump' methods with novel methods for Tropilaelaps detection modified from Varroa monitoring schemes. In addition, we monitored the efficacy of the laboratory method for screening for mites in hive debris by floating mites in ethanol. Our results clearly indicated that novel methods such as uncapping infested brood with tweezers, catching mite drop using sticky traps and rolling adult bees in icing sugar were all significantly more likely to detect Tropilaelaps than existing methods such as using an uncapping fork on infested brood, or the brood 'bump' method. Existing laboratory protocols that sieved hive debris and then floated the mite containing layer failed to detect Tropilaelaps mites and new efficacious protocols were developed. Our results demonstrated that the national surveillance protocols for Tropilaelaps mite detection required modification to improve the early detection of this damaging invasive mite., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gill et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The prevalence of type 2 diabetes (DM) has been increasing globally, particularly among older adults who are more susceptible to DM-related complications. Elderly individuals with diabetes are at higher risk of developing hypoglycemia compared with younger diabetes patients. Hypoglycemia in elderly patients can result in serious consequences such as cognitive changes, increased risk of falls, heart and other vascular problems, and even high mortality rate., Objective: To assess prevalence, and factors associated with hypoglycemia events among geriatric outpatients with type 2 diabetes mellitus., Methods: The study was conducted at King Abdullah University Hospital (KAUH) at the outpatient diabetes clinic from October 1st, 2022 to August 1st, 2023. Variables such as socio-demographics, medication history, and comorbidities were obtained using electronic medical records. The prevalence of hypoglycemia was determined through patient interviews during their clinic visit. Patients were prospectively monitored for hospital admissions, emergency department visits, and mortality using electronic medical records over a three-month follow-up period. Logistic regression models were conducted to identify factors associated with hypoglycemia and hospital admissions/ emergency visits. Ethical Approval (Reference # 53/151/2022) was obtained on 19/9/2022., Results: Electronic medical charts of 640 patients who have type 2 diabetes mellitus and age ≥ 60 years were evaluated. The mean age ± SD was 67.19 (± 5.69) years. Hypoglycemia incidents with different severity levels were prevalent in 21.7% (n = 139) of the patients. Insulin administration was significantly associated with more hypoglycemic events compared to other antidiabetic medication. Patients with liver diseases had a significantly higher risk of hypoglycemia, with odds 7.43 times higher than patients without liver diseases. Patients with dyslipidemia also had a higher risk of hypoglycemia (odd ratio = 1.87). Regression analysis revealed that hypoglycemia and educational level were significant predictors for hospital admission and emergency department (ER) visits. Hypoglycemia was a positive predictor, meaning it increased the odds of these outcomes, while having a college degree or higher was associated with reduced odds of hospital admission and ER visits., Conclusion: Current study identified a considerable prevalence of hypoglycemia among older patients with type 2 diabetes, particularly, among those with concurrent liver diseases and dyslipidemia. Furthermore, hypoglycemia was associated with an increased rate of emergency department visits and hospital admissions by 2 folds in this population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Al-Azayzih et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Earthquake-triggered landslides show three important characteristics: they are often responsible for a considerable proportion of the damage sustained during mountain region earthquakes, they are non-randomly distributed across space, and they continue to evolve in the years after the earthquake. Despite this, planning for future earthquakes rarely takes into consideration either landslides or their evolution with time. Here we couple a unique timeseries of mapped landslides between 2014-2020 across the area of Nepal impacted by the 2015 Mw 7.8 Gorkha earthquake and a numerical landslide runout model overlain with building locations to examine how the distributions of both evolving landslide hazard and exposure intersect to generate a dynamic threat to buildings. The threat from landslide runout is shown to change in predictable ways after the earthquake, becoming more pronounced at mid- and lower-hillslope positions and remaining in the landscape for multiple years. Using the positions of our mapped landslides as a starting point, we can identify a priori the locations of 78% of buildings that were subsequently impacted by landslide debris. We show that landslide exposure and hazard vary from negligible to high, in relative terms, over lateral distances of as little as 10s of m. Our findings hold important implications for guiding reconstruction and for taking steps to reduce the risks from future earthquakes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Arrell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: There is limited evidence on the effectiveness of parenting interventions to improve disruptive behaviour in children with intellectual developmental disabilities. This clinical trial evaluated whether an adapted group parenting intervention for preschool children with intellectual developmental disabilities who display challenging behaviour is superior to treatment as usual in England., Study Design: 261 children aged 30-59 months with moderate to severe intellectual developmental disabilities and challenging behaviour were randomised to either the intervention (Stepping Stones Triple P) and treatment as usual or treatment as usual alone. The primary outcome was the parent-rated Child Behaviour Checklist at 52 weeks after randomisation. A health economic evaluation was also completed., Results: We found no significant difference between arms on the primary outcome (mean difference -4.23; 95% CI: -9.99 to 1.53; p = 0.147). However, a subgroup analysis suggests the intervention was effective for participants randomised before the COVID-19 pandemic (mean difference -7.12; 95% CI: -13.44 to -0.81; p = 0.046). Furthermore, a complier average causal effects analysis (mean difference -11.53; 95% CI: -26.97 to 3.91; p = 0.143) suggests the intervention requires participants to receive a sufficient intervention dose. The intervention generated statistically significant cost savings (-£1,057.88; 95% CI -£3,218.6 to -£46.67) but the mean point estimate in Quality Adjusted Life Years was similar in both groups., Conclusion: This study did not find an effect of the intervention on reducing challenging behaviour, but this may have been influenced by problems with engagement. The intervention could be considered by services as an early intervention if families are supported to attend, especially given its low cost., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Royston et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia., Methods: We performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures., Results: Data from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, p<0.001), suggesting an improvement. In men, the -9-9 genotype was associated with lower arm fat (-9-9 2.39kg vs -9+9 2.72kg vs +9+9 2.76kg, p = 0.019)., Conclusion: In men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shrestha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Apnoea of prematurity (AOP) is a common complication among preterm infants (< 37 weeks gestation), globally. However, access to caffeine citrate (CC) that is a proven safe and effective treatment in high-income countries is largely unavailable in low- and-middle income countries, where most preterm infants are born. Therefore, the overall aim of this study was to describe the demand, policies, and supply factors affecting the availability and clinical use of CC in LMICs. A mixed methods approach was used to collect data from diverse settings in LMICs including Ethiopia, Kenya, Nigeria, South Africa, and India. Qualitative semi-structured interviews and focus group discussions were conducted with 107 different health care providers, and 21 policymakers and other stakeholders from industry. Additional data was collected using standard questionnaires. A thematic framework approach was used to analyze the qualitative data and descriptive statistics were used to summarize the quantitative data. The findings indicate that there is variation in in-country policies on the use of CC in the prevention and treatment of AOP and its availability across the LMICs. As a result, the knowledge and experience of using CC also varied with clinicians in Ethiopia having no experience of using it while those in India have greater knowledge and experience of using it. This, in turn, influenced the demand, and our findings show that only 29% of eligible preterm infants are receiving CC in these countries. There is an urgent need to address the multilevel barriers to accessing CC for managing AOP in Africa. These include cost, lack of national policies, and, therefore, lack of demand stemming from its clinical equivalency with aminophylline. Practical ways to reduce the cost of CC in LMICs could potentially increase its availability and use., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ekhaguere et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mechanistic investigation of host-microbe interactions in the human gut are hindered by difficulty of co-culturing microbes with intestinal epithelial cells. On one hand the gut bacteria are a mix of facultative, aerotolerant or obligate anaerobes, while the intestinal epithelium requires oxygen for growth and function. Thus, a coculture system that can recreate these contrasting oxygen requirements is critical step towards our understanding microbial-host interactions in the human gut. Here, we demonstrate Intestinal Organoid Physoxic Coculture (IOPC) system, a simple and cost-effective method for coculturing anaerobic intestinal bacteria with human intestinal organoids (HIOs). Using commensal anaerobes with varying degrees of oxygen tolerance, such as nano-aerobe Bacteroides thetaiotaomicron and strict anaerobe Blautia sp., we demonstrate that IOPC can successfully support 24-48 hours HIO-microbe coculture. The IOPC recapitulates the contrasting oxygen conditions across the intestinal epithelium seen in vivo. The IOPC cultured HIOs showed increased barrier integrity, and induced expression of immunomodulatory genes. A transcriptomic analysis suggests that HIOs from different donors show differences in the magnitude of their response to coculture with anaerobic bacteria. Thus, the IOPC system provides a robust coculture setup for investigating host-microbe interactions in complex, patient-derived intestinal tissues, that can facilitate the study of mechanisms underlying the role of the microbiome in health and disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fofanova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

China's poultry industry faces challenges in adopting and sustaining cage-free systems for poultry production. Effective interventions are crucial to support producers transitioning from cages to alternative systems or maintaining cage-free systems to improve animal welfare. However, little is known about how Chinese poultry producers perceive animal welfare in relation to cage-free systems and the importance of animal welfare in poultry production. Through a qualitative interview study with 30 Chinese farm owners, managers and senior managers from large-scale egg and broiler farms using cages and non-cage systems (collectively referred to as "producers"), this paper explores Chinese poultry producers' attitudes and perceptions regarding animal welfare and welfare in different poultry housing systems. Template analysis was used to analyse the data from semi-structured interviews, which generated themes related to the participants' awareness and understanding of the concept of animal welfare, the factors that impacted their choices of different housing systems, and the perceived priorities in poultry production. The responses revealed that the participating producers had a strong awareness and knowledge of animal welfare. However, the participants' understanding of the term is heterogeneous: generally, egg producers emphasised natural behaviours, whereas broiler producers prioritised health and productivity. Nevertheless, profitability, leadership, and organisational policies primarily influenced housing system choices rather than animal welfare values. Economic motives drove egg producers towards cage-free systems, prompted by consumers' and companies' demand for cage-free eggs committed to transitioning away from cages by 2025. In conclusion, tailored interventions for different poultry sectors within China are necessary. While animal welfare values matter, economic incentives seem more promising for steering the shift towards and maintaining cage-free poultry production., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This paper explores tool-using activities undertaken in and around the earliest known evidence of post-built structures in Britain. Microwear results associated with at least three structures identified at the Early Mesolithic site of Star Carr, North Yorkshire, are examined as a means of identifying activity zones associated with the diverse stone tools used to process a variety of materials (e.g. wood, bone, antler, plant, hide, meat, fish). With 341 lithic artefacts analysed, this research represents the first microwear study focused on the post-built structures at Star Carr. A combination of spatial and microwear data has provided different scales of interpretation: from individual tool use to patterns of activity across the three structures. Different types of tool use observed have aided interpretations of possible activity areas where objects were produced and materials were processed. Zones of activity within one of the structures suggest that the working of some materials was more spatially restricted than others; even where there are high densities of flint deposition, spatial patterns in tool-using activity were observed. From this, it is interpreted that social norms and behaviours influenced the spatial organisation of different spaces. Our results demonstrate the importance of combining microwear analysis with GIS to explore function and variability in the use of Mesolithic structures-providing new insights into their role as social spaces., Competing Interests: NO authors have competing interests, (Copyright: © 2024 Bates et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Evaluations of treatment efficacy in Duchenne muscular dystrophy (DMD), a rare genetic disease that results in progressive muscle wasting, require an understanding of the 'meaningfulness' of changes in functional measures. We estimated the minimal detectable change (MDC) for selected motor function measures in ambulatory DMD, i.e., the minimal degree of measured change needed to be confident that true underlying change has occurred rather than transient variation or measurement error. MDC estimates were compared across multiple data sources, representing >1000 DMD patients in clinical trials and real-world clinical practice settings. Included patients were ambulatory, aged ≥4 to <18 years and receiving steroids. Minimal clinically important differences (MCIDs) for worsening were also estimated. Estimated MDC thresholds for >80% confidence in true change were 2.8 units for the North Star Ambulatory Assessment (NSAA) total score, 1.3 seconds for the 4-stair climb (4SC) completion time, 0.36 stairs/second for 4SC velocity and 36.3 meters for the 6-minute walk distance (6MWD). MDC estimates were similar across clinical trial and real-world data sources, and tended to be slightly larger than MCIDs for these measures. The identified thresholds can be used to inform endpoint definitions, or as benchmarks for monitoring individual changes in motor function in ambulatory DMD., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: Francesco Muntoni is a member of the Rare Disease Scientific Advisory Group for Pfizer and of Dyne Therapeutics SAB, and has participated to SAB meetings for PTC, Sarepta, Santhera, Wave Therapeutics. UCL and Great Ormond Street Hospital are recipient of grants from Pfizer, Italfarmaco, Wave, Santhera, Sarepta regarding clinical trials. James Signorovitch co-founded the collaborative Trajectory Analysis Project (cTAP) and is an employee of Analysis Group, Inc., a consulting firm that received funding from the membership of cTAP to conduct this study. Gautam Sajeev, Nicolae Done, and Henry Lane are employees of Analysis Group, Inc., a consulting firm that received funding from the membership of cTAP to conduct this study. Ibrahima Dieye and Zhiwen Yao were employees of Analysis Group, Inc. at the time this study was conducted. Nathalie Goemans has served on clinical steering committees and/or as a consultant and received compensation from Eli Lilly, Italfarmaco, PTC Therapeutics, and BioMarin Pharmaceutical; has served as site investigator for GlaxoSmithKline, Prosensa, BioMarin Pharmaceutical, Italfarmaco, Roche, and Eli Lilly. Craig McDonald has served as a consultant for PTC Therapeutics, BioMarin Pharmaceutical, Sarepta Therapeutics, Eli Lilly, Pfizer Inc, Santhera Pharmaceuticals, Cardero Therapeutics, Inc, Catabasis Pharmaceuticals, Capricor Therapeutics, Astellas Pharma (Mitobridge), and FibroGen, Inc; serves on external advisory boards related to DMD for PTC Therapeutics, Sarepta Therapeutics, Santhera Pharmaceuticals, and Capricor Therapeutics; and reports grants from US Department of Education/National Institute on Disability and Rehabilitation Research, the National Institute on Disability, Independent Living, and Rehabilitation Research, US NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH/National Institute of Neurologic Disorders and Stroke, US Department of Defense, and Parent Project Muscular Dystrophy US. Eugenio Mercuri has served on clinical steering committees and/or as a consultant for Eli Lilly, Italfarmaco, PTC Therapeutics, Sarepta, Santhera, and Pfizer; has served as PI for GlaxoSmithKline, Prosensa, BioMarin Pharmaceutical, Italfarmaco, Roche, PTC, Pfizer, Sarepta, Santhera, Wave, NS and Eli Lilly. EM reports personal fees as consultant, PI or member on advisory board form BIOGEN S.R.L. outside the submitted work; EM reports personal fees consultant, PI or member on advisory board from ROCHE; EM reports personal fees consultant, PI or member on advisory board form AVEXIS outside the submitted work; EM reports personal fees consultant, PI or member on advisory board from SCHOLAR ROCK outside the submitted work; EM is part of an institution that receives funding from Biogen for a SMA disease registry (ISMAR). Erik H. Niks is a member of the European Reference Network for Rare Neuromuscular Diseases (ERN EURO‐NMD). EN report grants from Duchenne Parent Project, ZonMW and AFM, consultancies for BioMarin and Summit, and worked as local investigator of clinical trials of BioMarin, GSK, Lilly, Santhera, Givinostat, and Roche outside the submitted work. E.H.N. reports ad hoc consultancies for WAVE, Santhera, Regenxbio, and PTC, and he worked as investigator of clinical trials of Italfarmaco, NS Pharma, Reveragen, Roche, WAVE, and Sarepta outside the submitted work. Brenda Wong has participated in advisory committee meetings for Prosensa and Biomarin and has received compensation for consultancy services for Gilead Sciences, Pfizer, GSK, RegenXBio, and PepGen. Krista Vandenborne has received grants from NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institute of Neurologic Disorders and Stroke, Parent Project Muscular Dystrophy, and the Muscular Dystrophy Association. She has also received funding from ltalfarmaco SpA, Sarepta Therapeutics, Summit Therapeutics plc, Catabasis Pharmaceuticals, Pfizer Inc, ldera Pharmaceuticals, Bristol-Myers Squibb, and Eli Lilly through grant awards to the University of Florida. Volker Straub has participated in advisory boards for Audentes Therapeutics, Biogen, Exonics Therapeutics, Italfarmaco S.p.A., Roche, Sanofi Genzyme, Sarepta Therapeutics, Summit Therapeutics, UCB, and Wave Therapeutics. He has research collaborations with Ultragenyx and Sanofi Genzyme. Imelda JM de Groot has no disclosures. Cuixia Tian has participated as the site principal investigator for trials sponsored by PTC Therapeutics, Eli Lilly, GSK, Prosensa/Biomarin, Bristol Myers Squibb, Roche, Pfizer. Santhera, Sarepta, Fibrogen, Capricor, Pfizer, Avexis, and Catabasis. Adnan Manzur has no disclosures. Susan J. Ward co-founded and manages the collaborative Trajectory Analysis Project and has received funding from the membership of cTAP to facilitate this study. Laurent Servais is member of the SAB or has performed consultancy for Sarepta, Dynacure, Santhera, Avexis, Biogen, Cytokinetics and Roche, Audentes Therapeutics and Affinia Therapeutics; LS has given lectures and has served as a consultant for Roche, Biogen, Avexis, and Cytokinetics. LS is the project leader of the newborn screening in Southern Belgium funded by Avexis, Roche, and Biogen.]. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Muntoni et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Keel bone fractures (KBF) are prevalent in commercial laying hens and are considered one of the greatest welfare concerns in the egg-production industry. While clear associations exist between KBF and animal mobility, suggesting that KBF impair mobility, the effect of mobility on KBF remains unclear. We combined data from three studies that assessed keel bone fracture severity through radiographs and monitored hens' transitions between different zones of a multi-tier aviary system (the three tiers, a littered floor, and a winter garden) the week prior to radiograph. For each hen, we extracted two daily movement behaviours: the vertical distance travelled and the mean number of zones crossed within one transition; and two daily space-use behaviours: the time spent in the top tier and the unevenness of time spent across zones. We used hierarchical Bayesian continuous time dynamic modelling to estimate how a change in a behaviour predicted a later change in keel bone fracture severity, and vice versa. Increased fracture severity did not predict later changes in space-use behaviours, but it did predict changes in movement behaviours. Specifically, increased fracture severity led to decreased vertical travelled distance and a tendency to cross more zones within one transition, suggesting impaired mobility in hens with increased fracture severity. In contrast, we found no evidence that movement or space-use behaviours predict later change in fracture severity, challenging previous literature suggesting that vertical locomotion through jumping and flying may exacerbate keel bone fractures in complex three-dimensional systems due to increased risk of collisions. However, similar efforts accounting for the location of fractures on the keel could unveil the potential influence of movement and space-use behaviours in the formation and change (healing or worsening) of KBF and increase our ability to mitigate their effects., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Montalcini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

AXL+ Siglec-6+ dendritic cells (ASDC) are novel myeloid DCs which can be subdivided into CD11c+ and CD123+ expressing subsets. We showed for the first time that these two ASDC subsets are present in inflamed human anogenital tissues where HIV transmission occurs. Their presence in inflamed tissues was supported by single cell RNA analysis of public databases of such tissues including psoriasis diseased skin and colorectal cancer. Almost all previous studies have examined ASDCs as a combined population. Our data revealed that the two ASDC subsets differ markedly in their functions when compared with each other and to pDCs. Relative to their cell functions, both subsets of blood ASDCs but not pDCs expressed co-stimulatory and maturation markers which were more prevalent on CD11c+ ASDCs, thus inducing more T cell proliferation and activation than their CD123+ counterparts. There was also a significant polarisation of naïve T cells by both ASDC subsets toward Th2, Th9, Th22, Th17 and Treg but less toward a Th1 phenotype. Furthermore, we investigated the expression of chemokine receptors that facilitate ASDCs and pDCs migration from blood to inflamed tissues, their HIV binding receptors, and their interactions with HIV and CD4 T cells. For HIV infection, within 2 hours of HIV exposure, CD11c+ ASDCs showed a trend in more viral transfer to T cells than CD123+ ASDCs and pDCs for first phase transfer. However, for second phase transfer, CD123+ ASDCs showed a trend in transferring more HIV than CD11c+ ASDCs and there was no viral transfer from pDCs. As anogenital inflammation is a prerequisite for HIV transmission, strategies to inhibit ASDC recruitment into inflamed tissues and their ability to transmit HIV to CD4 T cells should be considered., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Warner van Dijk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The growing deprescribing field is challenged by a lack of consensus around evidence and knowledge gaps. The objective of this overview of systematic reviews was to summarize the review evidence for deprescribing interventions in older adults., Methods: 11 databases were searched from 1st January 2005 to 16th March 2023 to identify systematic reviews. We summarized and synthesized the results in two steps. Step 1 summarized results reported by the included reviews (including meta-analyses). Step 2 involved a narrative synthesis of review results by outcome. Outcomes included medication-related outcomes (e.g., medication reduction, medication appropriateness) or twelve other outcomes (e.g., mortality, adverse events). We summarized outcomes according to subgroups (patient characteristics, intervention type and setting) when direct comparisons were available within the reviews. The quality of included reviews was assessed using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2)., Results: We retrieved 3,228 unique citations and assessed 135 full-text articles for eligibility. Forty-eight reviews (encompassing 17 meta-analyses) were included. Thirty-one of the 48 reviews had a general deprescribing focus, 16 focused on specific medication classes or therapeutic categories and one included both. Twelve of 17 reviews meta-analyzed medication-related outcomes (33 outcomes: 25 favored the intervention, 7 found no difference, 1 favored the comparison). The narrative synthesis indicated that most interventions resulted in some evidence of medication reduction while for other outcomes we found primarily no evidence of an effect. Results were mixed for adverse events and few reviews reported adverse drug withdrawal events. Limited information was available for people with dementia, frailty and multimorbidity. All but one review scored low or critically low on quality assessment., Conclusion: Deprescribing interventions likely resulted in medication reduction but evidence on other outcomes, in particular relating to adverse events, or in vulnerable subgroups or settings was limited. Future research should focus on designing studies powered to examine harms, patient-reported outcomes, and effects on vulnerable subgroups., Systematic Review Registration: PROSPERO CRD42020178860., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chua et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Double burden of malnutrition (DBM) has been recognized by the World Health Organisation (WHO) as an emerging Global Syndemic characterized by the simultaneous occurrence of both undernutrition and overnutrition. Women of the reproductive age group (15 to 49 years) are disproportionately affected by DBM and are at high risk of continuing the intergenerational cycle of malnutrition. This study aims to assess the changing trends and determinants of DBM among women of the reproductive age group in India., Materials and Methods: We used data from three rounds of National Family Health Surveys (NFHS-3,4,5) conducted in years 2005-06, 2015-16, and 2019-2021. Descriptive statistics and Poisson regression analysis were done using weights with log link function., Results: The prevalence of anaemia, underweight and overweight/obesity was 57.2%, 18.6% and 24% respectively. The combined burden of underweight and anaemia has declined by 46% (21.6% to 11.7%), whereas the combined burden of overweight/obesity and anaemia has increased by 130% (5.4% to 12.4%) in the past 15 years. The prevalence of DBM, which includes both underweight and overweight/obesity with anaemia was 24.1% in 2021, a decline of 11% in 15 years. Women who were younger, rural, less educated, poor and middle class, and women living in the eastern, western and southern regions of India had higher risk for being underweight with anaemia and lower risk for developing overweight/obesity with anaemia., Conclusion: The significant decrease in underweight yet enormous increase in overweight/obesity over the past 15 years with the persistence of anaemia in both ends of the nutritional spectrum is characteristic of the new nutritional reality emphasizing the need to address malnutrition in all its forms. It is critical to consider geography and a population specific, double-duty targeted intervention to holistically address the risk factors associated with DBM and accomplish India's commitment to the global agenda of Sustainable Development Goals-2030., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Prithishkumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this study, we characterize the exopolymer produced by Halomonas sp. strain TGOS-10 -one of the organisms found enriched in sea surface oil slicks during the Deepwater Horizon oil spill. The polymer was produced during the early stationary phase of growth in Zobell's 2216 marine medium amended with glucose. Chemical and proton NMR analysis showed it to be a relatively monodisperse, high-molecular-mass (6,440,000 g/mol) glycoprotein composed largely of protein (46.6% of total dry weight of polymer). The monosaccharide composition of the polymer is typical to that of other marine bacterial exopolymers which are generally rich in hexoses, with the notable exception that it contained mannose (commonly found in yeast) as a major monosaccharide. The polymer was found to act as an oil dispersant based on its ability to effectively emulsify pure and complex oils into stable oil emulsions-a function we suspect to be conferred by the high protein content and high ratio of total hydrophobic nonpolar to polar amino acids (52.7:11.2) of the polymer. The polymer's chemical composition, which is akin to that of other marine exopolymers also having a high protein-to-carbohydrate (P/C) content, and which have been shown to effect the rapid and non-ionic aggregation of marine gels, appears indicative of effecting marine oil snow (MOS) formation. We previously reported the strain capable of utilising aromatic hydrocarbons when supplied as single carbon sources. However, here we did not detect biodegradation of these chemicals within a complex (surrogate Macondo) oil, suggesting that the observed enrichment of this organism during the Deepwater Horizon spill may be explained by factors related to substrate availability and competition within the complex and dynamic microbial communities that were continuously evolving during that spill., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nikolova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Social prescribing is an approach that enables the referral of patients to non-clinical support and places a focus on holistic care. This study explored views of community pharmacists regarding social prescribing in pharmacies., Study Design: A qualitative phenomenological approach was used., Methods: A convenience sample of eleven community pharmacists from Northern England were recruited via social media (Twitter, Facebook) and took part in a semi-structured, one-to-one qualitative interviews that asked about their knowledge of social prescribing, the advantages of community pharmacist involvement and any barriers they predicted to its implementation. Interviews were transcribed verbatim and thematically analysed., Results: The sample included largely male pharmacists (63.3%) with less than five years' experience (45.5%) and included pharmacists working as employees (63.6%), locums (27.3%) and owners (9%) in both chain (36%) and independent stores (54.5%). The main findings indicate an enthusiasm for but limited understanding of social prescribing. Factors which appeared to influence involvement were training requirements and time available to complete an additional service in busy pharmacies. Opportunities centred on the broader pharmacy team's role to optimise health outcomes., Conclusions: The findings indicate pharmacists may be an underused resource due to a poor understanding of the full scale and scope of social prescribing beyond health promotion, lifestyle interventions. Further work is needed to explore the transferability of the findings to the broader pharmacy workforce to understand how social prescribing can be positioned within pharmacy practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rathbone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Childhood, adolescent and young adult (CAYA) cancer survivors are vulnerable to adverse late-effects. For CAYA cancer survivors, tobacco smoking is the most important preventable cause of ill-health and early death. Yet, effective strategies to support smoking cessation in this group are lacking. The PRISM study aims to undertake multi-method formative research to explore the need for, and if appropriate, inform the future development of an evidence-based and theory-informed tobacco smoking cessation intervention for CAYA cancer survivors., Materials and Methods: PRISM involves three phases of: 1) an environmental scan using multiple strategies to identify and examine a) smoking cessation interventions for CAYA cancer survivors that are published in the international literature and b) current smoking cessation services in England that may be available to, or tailorable to, CAYA cancer survivors; 2) a qualitative study involving semi-structured interviews with CAYA cancer survivors (aged 16-29 years and who are current or recent ex-smokers and/or current vapers) to explore their views and experiences of smoking, smoking cessation and vaping; and 3) stakeholder workshops with survivors, healthcare professionals and other stakeholders to consider the potential for a smoking cessation intervention for CAYA cancer survivors and what such an intervention would need to target and change. Findings will be disseminated to patient groups, healthcare professionals and researchers, through conference presentations, journal papers, plain English summaries and social media., Discussion: PRISM will explore current delivery of, perceived need for, and barriers and facilitators to, smoking cessation advice and support to CAYA cancer survivors from the perspective of both survivors and healthcare professionals. A key strength of PRISM is the user involvement throughout the study and the additional exploration of survivors' views on vaping, a behaviour which often co-occurs with smoking. PRISM is the first step in the development of a person-centred, evidence- and theory-based smoking cessation intervention for CAYA cancer survivors who smoke, which if effective, will reduce morbidity and mortality in the CAYA cancer survivor population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Brown et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: It is unclear what biopsychosocial factors influence the impact of NAFLD on health-related quality of life (HRQoL), and if these factors are equally important predictors between different nationalities., Methods: HRQoL (CLDQ) was measured in both Southern European (Spain, n = 513) and Northern European (United Kingdom -UK-, n = 224) cohorts of patients with NAFLD in this cross-sectional study. For each cohort, participant data were recorded on histological grade of steatohepatitis, stage of fibrosis and biopsychosocial variables. Regression analysis was used to explore which of these variables predicted HRQoL. Moderated mediation models were conducted using SPSS PROCESS v3.5 macro., Results: Participants with severe fibrosis reported more fatigue, systemic symptoms and worry, and lower HRQoL than those with none/mild fibrosis, regardless of place of origin. In addition, body mass index (BMI) and gender were found to be significant predictors of HRQoL in both Spanish and UK participants. Female gender was associated with worse emotional function, higher BMI and more fatigue, which predicted lower participants' HRQoL. UK participants showed more systemic symptoms and worry than Spanish participants, regardless of liver severity. The negative effects of gender on HRQoL through emotional function, BMI and fatigue were reported to a greater degree in UK than in Spanish participants., Conclusions: UK participants showed a greater impairment in HRQoL as compared to Spanish participants. Higher fibrosis stage predicted lower HRQoL, mainly in the Spanish cohort. Factors such as female gender or higher BMI contributed to the impact on HRQoL in both cohorts of patients and should be considered in future multinational intervention studies in NAFLD., Competing Interests: The authors have read the journal’s policy and have the following potential competing interests: The Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) consortium is funded by the Innovative Medicines Initiative (IMI2) Program of the EU which receives funding from the European Federation of Pharmaceutical Industries and Associations (EFPIA). There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Funuyet-Salas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Micronutrient deficiencies are prevalent in West Africa, particularly among women of reproductive age (WRA) and young children. Bouillon is a promising food fortification vehicle due to its widespread consumption. This study aims to evaluate the impact of multiple micronutrient-fortified bouillon cubes, compared to control bouillon cubes (fortified with iodine only), on micronutrient status and hemoglobin concentrations among lactating and non-lactating WRA and young children in northern Ghana., Methods: This randomized, controlled doubly-masked trial will be conducted in the Kumbungu and Tolon districts in the Northern Region of Ghana, where prior data indicate multiple micronutrient deficiencies are common. Participants will be: 1) non-pregnant non-lactating WRA (15-49 y), 2) children 2-5 y, and 3) non-pregnant lactating women 4-18 months postpartum. Eligible participants will be randomly assigned to receive household rations of one of two types of bouillon cubes: 1) a multiple micronutrient-fortified bouillon cube containing vitamin A, folic acid, vitamin B12, iron, zinc, and iodine, or 2) a control cube containing iodine only. Each participant's household will receive a ration of bouillon cubes every 2 weeks, and households will be advised to prepare meals as usual, using the study-provided cubes. The trial duration will be 9 months for non-pregnant non-lactating WRA and children, and 3 months for lactating women. The primary outcomes will be changes in biomarkers of micronutrient status and hemoglobin among WRA and children and milk micronutrient concentrations among lactating women. Secondary outcomes will include change in prevalence of micronutrient deficiency and anemia; dietary intake of bouillon and micronutrients; inflammation, malaria, and morbidity symptoms; and child growth and development., Discussion: Evidence from this study will inform discussions about bouillon fortification in Ghana and West Africa., Trial Registration: The trial was registered on ClinicalTrials.gov (NCT05178407) and the Pan-African Clinical Trial Registry (PACTR202206868437931). This manuscript reflects protocol version 4 (August 29, 2022)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Engle-Stone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Women at increased risk of developing pre-eclampsia are advised to take a daily low-dose of aspirin from 12 weeks of pregnancy to reduce their risks. Despite the well-established prophylactic effect of aspirin, adherence to this therapy is low. This systematic review aimed to summarise evidence on the barriers and facilitators of adherence to low-dose aspirin to inform intervention development to support decision making and persistence with aspirin use for pre-eclampsia prevention., Materials and Methods: A systematic review and meta-synthesis of qualitative research was co-produced by representatives from charities, and public, clinical and academic members. Eight electronic databases (MEDLINE, PsycINFO, CINAHL, Web of Science, Scopus, EMBASE, Prospero, OpenGrey), archives of charities and professional organisations were searched (between October and November 2023 and re-run in August 2023) using predefined search terms. Studies containing qualitative components related to barriers and facilitators of adherence to low-dose aspirin during pregnancy were included. Quality assessment was performed using the Critical Appraisal Skills Programme checklist for qualitative research. A combination of the COM-B framework with phases of adherence process as defined by international taxonomy was used as the coding framework. Co-production activities were facilitated by use of 'Zoom' and 'Linoit'., Results: From a total of 3377 papers identified through our searches, five published studies and one dissertation met our inclusion criteria. Studies were published from 2019 to 2022 covering research conducted in the USA, Canada, UK, Netherlands and Australia. Barriers and facilitators to adherence were mapped to six categories of the COM-B for three phases of adherence: initiation, implementation, and discontinuation. The discontinuation phase of adherence was only mentioned by one author. Four key themes were identified relating to pregnancy: 'Insufficient knowledge', 'Necessity concerns balance', 'Access to medicine', 'Social influences', and 'Lack of Habit'., Conclusions: The COM-B framework allowed for detailed mapping of key factors shaping different phases of adherence in behavioural change terms and now provides a solid foundation for the development of a behavioural intervention. Although potential intervention elements could be suggested based on the results of this synthesis, additional co-production work is needed to define elements and plan for the delivery of the future intervention., Trial Registration: PROSPERO CRD42022359718. https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42022359718., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Vinogradov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Poverty impacts negatively on children's health and future life chances. Access to the UK's National Health Service (NHS) is based on clinical need rather than the ability to pay but horizontal inequities in access exist. Children North East, a charity supporting children experiencing poverty, are working with partners to reduce the impacts of poverty on NHS access. This collaborative study aimed to understand barriers to healthcare access faced by families living on low incomes to validate and support further development of a Poverty Proofing© healthcare tool. Twenty-four parents and eight Voluntary Community Social Enterprise sector staff participated in qualitative interviews or focus groups. Data were analysed thematically, and three main themes were identified as impacting access to healthcare: hidden costs, securing appointments and developing relationships with healthcare providers. We conclude that low-income families experience both financial and other barriers to accessing NHS healthcare and that these barriers are exacerbated for low-income families living in remote/rural areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bidmead et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: People experiencing homelessness co-occurring with substance use or offending ('severe and multiple disadvantage' SMD) often have high levels of poor oral health and related health behaviours (particularly, substance use, smoking, poor diet). This systematic review aimed to assess the effectiveness and cost-effectiveness of interventions in adults experiencing SMD to improve oral health and related health behaviours., Methods and Findings: From inception to February 2023, five bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, and Scopus) and grey literature were searched. Two researchers independently screened the search results. Randomized controlled trials (RCTs), comparative studies and economic evaluations were included that reported outcomes on oral health and the related health behaviours. Risk of bias was assessed and results narratively synthesized. Meta-analyses were performed where appropriate. This review was registered with PROSPERO (reg. no: CRD42020202416). Thirty-eight studies were included (published between 1991 and 2023) with 34 studies reporting about effectiveness. Most studies reported on substance use (n = 30). Interventions with a combination of housing support with substance use and mental health support such as contingent work therapy appeared to show some reduction in substance use in SMD groups. However, meta-analyses showed no statistically significant results. Most studies had short periods of follow-up and high attrition rates. Only one study reported on oral health; none reported on diet. Three RCTs reported on smoking, of which one comprising nicotine replacement with contingency management showed improved smoking abstinence at 4 weeks compared to control. Five studies with economic evaluations provided some evidence that interventions such as Housing First and enhanced support could be cost-effective in reducing substance use., Conclusion: This review found that services such as housing combined with other healthcare services could be effective in improving health behaviours, particularly substance use, among SMD groups. Gaps in evidence also remain on oral health improvement, smoking, and diet. High quality studies on effectiveness with adequate power and retention are needed to address these significant health challenges in SMD populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 McGowan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The COVID-19 pandemic caused far-reaching societal changes, including significant educational impacts affecting over 1.6 billion pupils and 100 million education practitioners globally. Senior school leaders were at the forefront and were exposed to particularly high demands during a period of "crisis leadership". This occupation were already reporting high work-related stress and large numbers leaving the profession preceding COVID-19. This cross-sectional descriptive study through the international COVID-Health Literacy network aimed to examine the well-being and work-related stress of senior school leaders (n = 323) in Wales (n = 172) and Northern Ireland (n = 151) during COVID-19 (2021-2022). Findings suggest that senior school leaders reported high workloads (54.22±11.30 hours/week), low well-being (65.2% n = 202, mean WHO-5 40.85±21.57), depressive symptoms (WHO-5 34.8% n = 108) and high work-related stress (PSS-10: 29.91±4.92). High exhaustion (BAT: high/very high 89.0% n = 285) and specific psychosomatic complaints (experiencing muscle pain 48.2% n = 151) were also reported, and females had statistically higher outcomes in these areas. School leaders were engaging in self-endangering working behaviours; 74.7% (n = 239) gave up leisure activities in favour of work and 63.4% (n = 202) sacrificed sufficient sleep, which was statistically higher for females. These findings are concerning given that the UK is currently experiencing a "crisis" in educational leadership against a backdrop of pandemic-related pressures. Senior leaders' high attrition rates further exacerbate this, proving costly to educational systems and placing additional financial and other pressures on educational settings and policy response. This has implications for senior leaders and pupil-level outcomes including health, well-being and educational attainment, requiring urgent tailored and targeted support from the education and health sectors. This is particularly pertinent for Wales and Northern Ireland as devolved nations in the UK, who are both implementing or contemplating major education system level reforms, including new statutory national curricula, requiring significant leadership, engagement and ownership from the education profession., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Marchant et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)