Search

Abstract Protein phosphatase 2A (PP2A) regulatory subunit B55α has been implicated in the transcriptional regulation of cardiac growth and fibrosis by suppressing HDAC5/MEF2 signalling in cardiomyocytes. We created and characterised two mouse models with global or cardiomyocyte-specific disruption of the gene encoding B55α (Ppp2r2a) to conduct the first detailed exploration of B55α in the heart. Global homozygous B55α knockout mice died in utero, while heterozygous mice had thinner left ventricular walls at 12 months, an effect more pronounced in males. At 10–12 weeks of age, cardiomyocyte-specific B55α knockout mice displayed normal cardiac morphology with increased left ventricular collagen deposition, identifying B55α as a negative regulator of cardiac fibrosis. Gene expression analyses demonstrated extensive remodelling of the cardiac transcriptome in male but not female mice, revealing a sexually dimorphic role for B55α in cardiac transcriptional regulation. These findings provide a basis for future work investigating B55α in cardiac stress settings.

Abstract Atrial fibrillation (AF) is a common arrhythmia encountered in acute and critical illness and is associated with poor short and long-term outcomes. Given the consequences of developing AF, research into prevention, prediction and treatment of this arrhythmia in the critically ill are of great potential benefit, however, study of AF in critically ill patients faces unique challenges, leading to a sparse evidence base to guide management in this population. Major obstacles to the study of AF in acute and critical illness include absence of a common definition, challenges in designing studies that capture complex etiology and assess causality, lack of a clear outcome set, difficulites in recruitment in acute environments with respect to timing, consent, and workflow, and failure to embed studies into clinical care platforms and capitalize on emerging technologies. Collaborative effort by researchers, clinicians, and stakeholders should be undertaken to address these challenges, both through interdisciplinary cooperation for the optimization of research efficiency and advocacy to advance the understanding of this common and complex arrhythmia, resulting in improved patient care and outcomes. The Symposium on Atrial Fibrillation in Acute and Critical Care was convened to address some of these challenges and propose potential solutions.

Bakery products are in great demand among Indonesians today. Therefore, small and medium enterprises (SMEs) of bakeries have an essential role in creating products that are guaranteed to be halal and safe, following regulations in Indonesia. This research aims to design a Halal Good Manufacturing Practice (HGMP) assessment model for “X” Bakery to improve product quality. HGMP integrates the criteria of Indonesia's Halal Assurance System, called Sistem Jaminan Produk Halal (SJPH), and Good Manufacturing Practices (GMP). The Quality Function Deployment (QFD) method evaluates company performance based on HGMP criteria and translates it into technical responses. The Pareto diagram determines the priority of HGMP criteria and technical responses. The identification results show 56 valid HGMP criteria for “X” Bakery, consisting of location and environment, buildings, facilities, employees, production, and storage. Implementing the assessment model at “X” Bakery resulted in 40 HGMP criteria that needed improvement and 12 technical responses that needed to be prioritized in meeting the HGMP criteria. This HGMP assessment model is hoped to help “X” Bakery improve the quality of halal, safe, high-quality products.

This study proposes an economic production quantity (EPQ) model that comprehensively addresses scrap items, imperfect quality items, rework processes, and shortages. The model incorporates various types of defective items, including scrap, imperfect quality, and rework able items, and implements immediate rework processes upon the completion of regular production. Shortages are treated as lost sales, enhancing the accuracy of inventory cost estimations. Numerical experiments demonstrate the opti­mal­ity of production lot sizes and underscore the impact of production and demand rate adjustments on overall inventory costs. Sensitivity analysis further elucidates the influence of imperfect quality items on inventory costs. This EPQ model offers a comprehensive approach to efficient and effective finished product inventory management by integrating consider­ations for scrap items, imperfect quality items, and rework processes. Addi­tionally, a furniture manufacturing company case is presented to illustrate the practical application of the proposed model.

Abstract Transdisciplinary co-produced health research and co-designed interventions have the capacity to improve research quality and the relevance, acceptability, and accessibility of healthcare. This approach also helps researchers to address power imbalances to share decision-making with service-users and the public. However, this growing methodology is currently difficult to appraise and develop as detailed sharing of practice is limited. The ‘CO-production of a Nature-based Intervention For children with ADHD study’ (CONIFAS) aimed to create a novel intervention with and for children with attention deficit hyperactivity disorder (ADHD) using co-production and co-design methodologies. This knowledge exchange paper will be of benefit to researchers with aspirations to undertake co-production, especially in the context of working with under-represented groups. Critical reflection on the use of co-production identified that every attempt was made to adequately resource the co-production, share power, value diversity, and develop trust. The team reflected that the re-conceptualisation of the role of the researcher in co-production can be challenging. Whilst the use of models of co-production provides a framework for study development, designing and running the specifics of the workshops, as well as how to effectively engage co-researchers in an equitable way, came from utilising clinical skills, networking, and creativity. These methods are particularly pertinent to involving neurodiverse children and their families who are under-represented in participatory research and in need of bespoke health interventions.

Objectives The caseload of family courts in England and Wales includes a growing share of domestic abuse cases. To increase knowledge about such cases, the research uses new administrative datasets and linkages. Trends between 2011-2021 are examined in the context of policy and operational changes. Method The complete set of family court cases is held in HM Courts & Tribunals Services (HMCTS) systems. Some family court data are collected by the Children and Families Court Advisory Support Service (Cafcass), insofar as courts refer the case to Cafcass. Using their new linkage, we conduct a descriptive analysis of domestic abuse cases in England and Wales over the ten years from 2011. This project is one of the first to gain approval from HMCTS to use their de-identified family court data. Results The data linkage allows to describe how court users approach domestic abuse matters, drawing distinctions between: emergency cases; lack of legal representation in court (litigants in person); repeat applications; presence of children in the household. Furthermore, the data show how courts respond through case management, timeliness of decisions and legal outcomes made. The policy context reveals how court users adapted to changes in eligibility for civil legal aid and to changes over how courts operated under lockdown measures. Conclusion Data linkage research is providing an evidence base at population level about court users in England and Wales who experience domestic abuse. This can help inform practice to support families, and policies to ease overburdened courts and avoid returns to court.

Introduction Physical frailty is associated with increased mortality and poor quality of life (QoL) before and after liver transplantation (LT). Evidence is lacking on how to tailor exercise and behavioural techniques in this patient population.Methods and analysis Home-based EXercise and motivAtional programme before and after Liver Transplantation (EXALT) is a phase 2b, open-label, two-centre randomised controlled clinical trial designed to investigate whether a remotely monitored ‘home-based exercise and theory-based motivation support programme (HBEP)’ before and after LT improves QoL in LT recipients. Adult patients awaiting a primary LT will be assessed for eligibility at two LT centres (Birmingham, Royal Free London). Participants will be randomly assigned (1:1) to receive either an HBEP while on the LT waiting list through to 24 weeks after LT (Intervention) or a patient exercise advice leaflet (Control). Using a standard method of difference in means (two-sided significance level 0.05; power 0.90) and accounting for a 35% attrition/withdrawal rate, a minimum of 133 patients will be randomised to each treatment group. The primary outcome measure will be assessed using intention-to-treat analysis of the difference in the Physical Component Score of Short form-36 version 2.0 health-related QoL questionnaire between the groups at 24 weeks post-LT.Ethics and dissemination The protocol was approved by the South Central-Hampshire A National Research Ethics Committee. Recruitment into the EXALT trial started in May 2022 and is due to end in June 2024, with 217/266 patients randomised to date. The intervention follow-up is due to finish in May 2026. The findings of this trial will be disseminated through peer-reviewed publications, conferences and social media.Trial registration number ISRCTN13476586.

Abstract Background In the UK, tens of millions of working days are lost due to work‐related ill health every year, costing billions of pounds. The role of Occupational Health (OH) services is vital in helping workers to maintain employment when they encounter injury or illness. OH providers traditionally rely on a clinical workforce to deliver these services, particularly doctors and nurses with OH qualifications. However, the increasing demand for OH services is unlikely to be met in the future using this traditional model, due to the declining number of OH‐trained doctors and nurses in the UK. Multi‐disciplinary models of OH delivery, including a more varied range of healthcare and non‐healthcare professionals, could provide a way to meet this new demand for OH services. There is a need to identify collaborative models of OH service delivery and review their effectiveness on return‐to work outcomes. There is an existing pool of systematic review evidence evaluating workplace based, multi‐disciplinary OH interventions, but it is difficult to identify which aspects of the content and/or delivery of these interventions may be associated with improved work‐related outcomes. Objectives The aim of this evidence and gap map (EGM) was to provide an overview of the systematic review evidence that evaluates the effectiveness and cost‐effectiveness of multi‐disciplinary OH interventions intending to improve work‐related outcomes. Search Methods In June 2021 we searched a selection of bibliographic databases and other academic literature resources covering a range of relevant disciplines, including health care and business studies, to identify systematic review evidence from a variety of sectors of employment. We also searched Google Search and a selection of topically relevant websites and consulted with stakeholders to identify reports already known to them. Searches were updated in February 2023. Selection Criteria Systematic reviews needed to be about adults (16 years or over) in employment, who have had absence from work for any medical reason. Interventions needed to be multi‐disciplinary (including professionals from different backgrounds in clinical and non‐clinical professions) and designed to support employees and employers to manage health conditions in the workplace and/or to help employees with health conditions retain and/or return to work following medical absence. Effectiveness needed to be measured in terms of return to work, work retention or measures of absence, or economic evaluation outcomes. These criteria were applied to the title and abstract and full text of each systematic review independently by two reviewers, with disagreements resolved through discussion. We awarded each systematic review a rating of ‘High’, ‘Medium’ or ‘Low’ relevance to indicate the extent to which the populations, interventions and their contexts synthesised within the review were consistent with our research question. We also recorded the number of primary studies included within each of the ‘High’ and ‘Medium’ reviews that were relevant to research question using the same screening process applied at review level. Data Collection and Analysis Summary data for each eligible review was extracted. The quality of the systematic reviews, rated as ‘High’ or ‘Medium’ relevance following full text screening, was appraised using the AMSTAR‐2 quality appraisal tool. All data were extracted by one reviewer and checked by a second, with disagreements being settled through discussion. Summary data for all eligible systematic reviews were tabulated and described narratively. The data extracted from reviews of ‘High’ and ‘Medium’ relevance was imported into EPPI‐Mapper software to create an EGM. Stakeholder Involvement We worked alongside commissioners and policy makers from the Department of Health and Social Care (DHSC) and Department of Work and Pensions (DWP), OH personnel, and people with lived experience of accessing OH services themselves and/or supporting employees to access OH services. Individuals contributed to decision making at all stages of the project. This ensured our EGM reflects the needs of individuals who will use it. Main Results We identified 98 systematic reviews that contained relevant interventions, which involved a variety of professionals and workplaces, and which measured effectiveness in terms of return to work (RTW). Of these, we focused on the 30 reviews where the population and intervention characteristics within the systematic reviews were considered to be of high or medium relevance to our research questions. The 30 reviews were of varying quality, split evenly between High/Moderate quality and Low/Critically‐Low quality ratings. We did not identify any relevant systematic review evidence on any other work‐related outcome of interest. Interventions were heterogenous, both within and across included systematic reviews. The EGM is structured according to the health condition experienced by participants, and the effectiveness of the interventions being evaluated, as reported within the included systematic reviews. It is possible to view (i) the quality and quantity of systematic review evidence for a given health condition, (ii) how review authors assessed the effectiveness or cost‐effectiveness of the interventions evaluated. The EGM also details the primary studies relevant to our research aim included within each review. Authors’ Conclusions This EGM map highlights the array of systematic review evidence that exists in relation to the effectiveness or cost‐effectiveness of multi‐disciplinary, workplace‐based OH interventions in supporting RTW. This evidence will allow policy makers and commissioners of services to determine which OH interventions may be most useful for supporting different population groups in different contexts. OH professionals may find the content of the EGM useful in identifying systematic review evidence to support their practice. The EGM also identifies where systematic review evidence in this area is lacking, or where existing evidence is of poor quality. These may represent areas where it may be particularly useful to conduct further systematic reviews.

The green vehicle routing problem (GVRP) has been a prominent topic in the literature on logistics and transportation, leading to extensive research and previous review studies covering various aspects. Operations research has seen the development of various exact and approximation approaches for different extensions of the GVRP. This paper presents an up-to-date and thorough review of GVRP literature spanning from 2016 to 2023, encompassing 458 papers. significant contribution lies in the updated solution approaches and algorithms applied to both single-objective and multi-objective GVRP. Notably, 92.58 % of the papers introduced a mathematical model for GVRP, with many researchers adopting mixed integer linear programming as the preferred modeling approach. The findings indicate that both metaheuristics and hybrid are the most employed solution approaches for addressing single-objective GVRP. Among hybrid approaches, the combination of metaheuristics-metaheuristics is particularly favored by GVRP researchers. Furthermore, large neighborhood search (LNS) and its variants (especially adaptive large neighborhood search) emerges as the most widely adopted algorithm in single-objective GVRP. These algorithms are proposed within both metaheuristic and hybrid approaches, where A-/LNS is often combined with other algorithms. Conversely, metaheuristics are predominant in addressing multi-objective GVRP, with NSGA-II being the most frequently proposed algorithm. Researchers frequently utilize GAMS and CPLEX as optimization modeling software and solvers. Furthermore, MATLAB is a commonly employed programming language for implementing proposed algorithms.

Abstract Background UNESCO biosphere reserves (BRs) have historically aimed to play a crucial role in contributing to sustainable development by bringing about win–win outcomes for both biodiversity and socio-economic development. However, recent studies show the need for a more thorough understanding of how conservation activities impact on and are affected by socio-economic development. Method We built this systematic review on a systematic map by Eales et al. [14] adding studies from further academic database and grey literature searches specifically designed for this systematic review. Because studies were not sufficiently homogeneous in their outcomes to warrant a valid meta-analysis, we used narrative synthesis to explore the studies’ findings. Results We assessed 10,053 titles and abstracts from database searches and Google Scholar. 343 articles were screened at full text and 16 studies were included in our review. Of the 16 studies, 3 were assessed as having overall high validity, 8 having moderate validity and 3 having low validity of evidence. 2 studies did not provide sufficient information for validity categorisation (unclear validity). Effects on economic living standards, reported in 11 studies, were in both desired and undesired directions, though most high validity studies reported no significant difference, and most others did not test for significance. Most studies reported that BR interventions were associated with positive impacts on material living standards. In general, studies reported good relations between local people and local enforcement/government following interventions in BRs. BR interventions may both reduce or cause social conflict, though the higher validity studies showed results in the desired direction. In one study, there was a positive impact on population family planning outcomes, when a reproductive health intervention was implemented with conservation efforts. There was no clear impact in either direction regarding education. Across two studies the overall message is positive for the subjective wellbeing of local people. Conclusions With 727 BRs worldwide, the BR model has been accepted and developed as an approach to facilitate the implementation of the UN's SDGs. However, our work shows that interventions implemented in UNESCO BRs can bring about impacts in quite diverse ways: positive, negative, unchanged, and may often present both positive and negative impacts in the same situation. This reconfirms that the expected win–win outcomes of UNESCO BR model in terms of biodiversity and socio-economic development should be more carefully considered. We suggest some main points for consideration, particularly when developing management mechanisms for UNESCO biosphere reserves and/or managing activities in biosphere reserves. We also highlight the need for further research to explore the socio-economic impacts of the UNESCO biosphere reserves in Southeast Asia, especially on the domains of freedom of choice and action, security and safety, and culture and spirituality. Moreover, it is vital to have research projects that measure long-term impacts of biosphere reserves, which have been lacking in previous work. Finally, the potential impact of external factors should be considered in programme and monitoring design.

Abstract Introduction We conducted a systematic review of qualitative evidence to improve understanding of the processes and outcomes of redress and reconciliation following a life‐changing event from the perspectives of individuals experiencing the event and their families. Methods We searched six bibliographic databases for primary qualitative evidence exploring the views of individuals who have experienced a life‐changing event, and/or their family or carers, of redress or reconciliation processes. This was supplemented with targeted database searches, forward and backward citation chasing and searches of Google Scholar and relevant websites. Title and abstract and full‐text screening were undertaken independently by two reviewers. Data extraction and quality appraisal were conducted by one reviewer and checked by a second. We used a best‐fit framework synthesis approach, drawing upon procedural and restorative justice concepts. Findings Fifty‐three studies (61 papers) were eligible for inclusion. Forty‐one studies (47 papers) were included in the synthesis, from which we identified four themes. Three themes ‘Transparency’, ‘Person‐centered’ and ‘Trustworthy’ represent the procedural elements required to support a fair and objective process. The fourth, ‘Restorative justice’ encapsulates how a fair process feels to those who have experienced a life‐changing event. This theme highlights the importance of an empathic relationship between the different parties involved in the redress‐reconciliation process and the significance of being able to engage in meaningful action. Conclusion Our findings highlight the procedural aspects and context of redress‐reconciliation processes required to ensure that the process and outcomes are experienced as fair. These criteria may be applied to the processes used to investigate both recent and historical patient safety events. Public Contribution One member of the public affiliated with the Exeter Policy Research Programme Evidence Review Facility helped develop the review protocol. Two people with experience of medically life‐changing events provided insight which corroborated our findings and identified important limitations of the evidence included in this review.

The instructors of four biology-related courses at a Canadian university integrated Labster virtual labs in their courses as a pre-lab activity, lecture substitute, or to provide lab experience in courses with no on-site labs. The instructors used a backward design approach to align the labs with the learning objectives of their courses and to connect the labs with their course assessments. A study was conducted to examine students' perceptions of the usefulness of the virtual labs in terms of content knowledge and lab skills. At the end of each course, the instructors administered an anonymous survey in their classes. In total, 370 students participated. Across all four courses, survey results showed that at least 77% of the students found that virtual lab simulations helped them understand course concepts. At least 74% of the students navigated the virtual labs with no issues and 58% of the students found the simulations to be of high quality.

Introduction The European Alliance for Sport and Mental Health (EASMH) is a partnership of scientific institutions, charity associations and sport organizations, funded by EU-Erasmus+. It aimed at developing good clinical practice in psychiatric rehabilitation through sport-based interventions as an integration of pharmacological and psychological therapies. Within the framework of the EASMH projects, several actions have been promoted including an assessment of the dissemination of sport-based interventions, a training course for specialized coaches and the implementation of pilot actions in four European Countries. Objectives To briefly describe EASMH pilot actions performed in Finland, Italy, Romania and United Kingdom, where trained coaches delivered sport-based interventions to patients with severe mental disorders. Methods After completing pilot actions, charity associations and sport organizations belonging to EASMH network described general and specific aims, sport activities, composition of staff, timing and tools for assessing the outcomes. Results In Italy, “Crazy for Rugby”, including adolescents and young patients, and “Not only headshots”, a football project for adults with severe mental disorders were performed. In UK, a football-based activity called “Imagine Your Goal” and a walking-football program for participants aged more than 40 were delivered. In Romania, two courses including gymnastics, yoga and pilates called “Get fit!” were provided. Different team sport-based activities were implemented in Finland, where “Multiple Sport Group” and “Rehabilitating Sports” aimed at increasing patients’ autonomy. Assessment of psychopathological, social, cognitive and sport/fitness outcomes confirmed the overall beneficial effects of sport on mental health. Conclusions Pilot actions represent the final step of EASMH project, which showed improvement of mental health outcomes by also delivering sport-based rehabilitation to patients with severe mental disorders. Institutions and stakeholders are now called to promote the implementation of such initiatives on a broader scale. Disclosure of Interest None Declared

Background: Studies have found that women with gynaecological conditions and symptoms do not feel listened to by primary care clinicians (PCCs). Less understood is whether PCCs perceive that there are challenges around listening to and interacting with this patient group. Aim: To understand PCCs’ perspectives on the challenges of listening to and interacting with women patients with gynaecological conditions and symptoms. Design & setting: Systematic review of English-language studies. Method: We searched ASSIA (Applied Social Sciences Index and Abstracts), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Embase, HMIC (Healthcare Management Information Consortium), and MEDLINE from inception to July 2023. We also conducted forward and backward citation searches of included studies. Identified records were screened independently by two reviewers. Data extraction was undertaken by one reviewer and checked by a second. Quality appraisal used the Wallace checklist. 'Best-fit' framework synthesis was used to synthesise findings around themes that explored the challenges of patient–clinician interaction. Results: We identified 25 relevant articles. Perceived challenges associated with listening to and interacting with patients with gynaecological conditions and symptoms were identified at four ‘levels’: individual clinician level factors; structural and organisational factors; community and external factors; and factors related to gynaecological conditions. Interpretive analysis identified specific challenges relating to sociocultural factors affecting the consultation experience; the need for further education, training, or guidance for clinicians; factors affecting referral decisions; and factors related to service structure and organisation. Conclusion: PCCs acknowledge that empathy, respect, and attentive listening are important when interacting with women patients with gynaecological conditions and symptoms. However, these ideals are impeded by several factors.

Abstract The influence of aging on intestinal stem cells and their niche can explain underlying causes for perturbation in their function observed during aging. Molecular mechanisms for such a decrease in the functionality of intestinal stem cells during aging remain largely undetermined. Using transcriptome-wide approaches, our study demonstrates that aging intestinal stem cells strongly upregulate antigen presenting pathway genes and over-express secretory lineage marker genes resulting in lineage skewed differentiation into the secretory lineage and strong upregulation of MHC class II antigens in the aged intestinal epithelium. Mechanistically, we identified an increase in proinflammatory cells in the lamina propria as the main source of elevated interferon gamma (IFNγ) in the aged intestine, that leads to the induction of Stat1 activity in intestinal stem cells thus priming the aberrant differentiation and elevated antigen presentation in epithelial cells. Of note, systemic inhibition of IFNγ-signaling completely reverses these aging phenotypes and reinstalls regenerative capacity of the aged intestinal epithelium.

Abstract Detection and differentiation of brown fat in humans poses several challenges, as this tissue is sparse and often mixed with white adipose tissue. Non-invasive detection of beige fat represents an even greater challenge as this tissue is structurally and functionally more like white fat than brown fat. Here we used positron emission tomography with 18F-fluorodeoxyglucose, computed tomography, xenon-enhanced computed tomography, and dynamic contrast-enhanced ultrasound, to non-invasively detect functional and structural changes associated with the browning process of inguinal white fat, induced in mice by chronic stimulation with the β3-adrenergic receptor agonist CL-316243. These studies reveal a very heterogeneous increase in baseline tissue radiodensity and xenon-enhanced radiodensity, indicative of both an increase in adipocytes water and protein content as well as tissue perfusion, mostly in regions that showed enhanced norepinephrine-stimulated perfusion before CL-316243 treatment. No statistically significant increase in 18F-fluorodeoxyglucose uptake or norepinephrine-stimulated tissue perfusion were observed in the mice after the CL-316243 treatment. The increase in tissue-water content and perfusion, along with the negligible increase in the tissue glucose uptake and norepinephrine-stimulated perfusion deserve more attention, especially considering the potential metabolic role that this tissue may play in whole body metabolism.

Abstract Epithelial-to-mesenchymal transitions (EMTs) of both endocardium and epicardium guide atrioventricular heart valve formation, but the cellular complexity and small scale of this tissue have restricted analyses. To circumvent these issues, we analyzed over 50,000 murine single-cell transcriptomes from embryonic day (E)7.75 hearts to E12.5 atrioventricular canals. We delineate mesenchymal and endocardial bifurcation during endocardial EMT, identify a distinct, transdifferentiating epicardial population during epicardial EMT, and reveal the activation of epithelial-mesenchymal plasticity during both processes. In Sox9-deficient valves, we observe increased epithelial-mesenchymal plasticity, indicating a role for SOX9 in promoting endothelial and mesenchymal cell fate decisions. Lastly, we deconvolve cell interactions guiding the initiation and progression of cardiac valve EMTs. Overall, these data reveal mechanisms of emergence of mesenchyme from endocardium or epicardium at single-cell resolution and will serve as an atlas of EMT initiation and progression with broad implications in regenerative medicine and cancer biology.

Distribution activities are closely related to the objective function of minimizing fuel consumption, which is affected by distance and product load in transportation. This indicates the need for optimization to improve company performance. Therefore, this study aims to develop a new Hybrid Spotted Hyena Optimizer (HSHO) algorithm, to minimize the total transportation and fuel costs. This was provided by applying the Large Rank Value (LRV) procedure to convert hyena positions to travel sequences. This also proposed a Flip and Swap rule in each iteration to improve the algorithm's performance. Furthermore, a mathematical model was developed for the Fuel Consumption Capacitated Vehicle Routing Problem (FCCVRP) by considering the load and FC (fuel consumption) rates between the nodes. This indicated that several population variations, iterations, and several nodes were used to investigate the effectiveness of the HSHO algorithm. The results showed increased population parameters, and HSHO iterations reduced the FCCVRP total transportation costs. Furthermore, decreasing the fuel consumption rate between nodes affected reduced fuel consumption. In addition, the proposed HSHO produced a more optimal total transportation cost than the state-of-the-art algorithm.?

This article investigates the integrated approach of the Simultaneous Impor­tance-Performance Analysis (SIPA) model and the modified Kano model to evaluate and prioritize service attributes for telecommunication companies in Indonesia. The study is based on the demographic profiles and usage patterns of 74 respondents. The results demonstrate that the SIPA and Kano models can provide valuable insights for identifying priority areas and effective strategies for improving service quality. Specifically, the SIPA model helps to compare competitor performance and identify important service attributes. In contrast, the modified Kano model facilitates a dynamic cycle of service attribute evaluation to inform managerial strate­gies. This article contributes by highlighting the potential of the proposed ap­proach to offer valuable insights to telecommunication companies seeking to enhance their service offerings and remain competitive in a con­stantly evolving market.

Objectives We aimed to map the systematic review evidence available to inform the optimal prescribing of statins and antihypertensive medication.Design Systematic umbrella review and evidence and gap map (EGM).Data sources Eight bibliographic databases (Cochrane Database of Systematic Reviews, CINAHL, EMBASE, Health Management Information Consortium, MEDLINE ALL, PsycINFO, Conference Proceedings Citation Index—Science and Science Citation Index) were searched from 2010 to 11 August 2020. Update searches conducted in MEDLINE ALL 2 August 2022. We searched relevant websites and conducted backwards citation chasing.Eligibility criteria for selecting studies We sought systematic reviews of quantitative or qualitative research where adults 16 years+ were currently receiving, or being considered for, a prescription of statin or antihypertensive medication. Eligibility criteria were applied to the title and abstract and full text of each article independently by two reviewers.Data extraction and synthesis Quality appraisal was completed by one reviewer and checked by a second. Review characteristics were tabulated and incorporated into an EGM based on a patient care pathway. Patients with lived experience provided feedback on our research questions and EGM.Results Eighty reviews were included within the EGM. The highest quantity of evidence focused on evaluating interventions to promote patient adherence to antihypertensive medication. Key gaps included a lack of reviews synthesising evidence on experiences of specific interventions to promote patient adherence or improve prescribing practice. The evidence was predominantly of low quality, limiting confidence in the findings from individual reviews.Conclusions This EGM provides an interactive, accessible format for policy developers, service commissioners and clinicians to view the systematic review evidence available relevant to optimising the prescribing of statin and antihypertensive medication. To address the paucity of high-quality research, future reviews should be conducted and reported according to existing guidelines and address the evidence gaps identified above.

Abstract Background Opportunities for social connection between generations have diminished over the last few decades around the world as a result of changes in the way that we live and work. The COVID‐19 pandemic has exacerbated loneliness for many with young and old being kept apart for safety. The Public Health England prevention concordat for better mental health (Office for Health Improvement and Disparities) aims to bring a prevention‐focused approach to improving public mental health. The concordat promotes evidence‐based planning and commissioning to increase the impact on reducing health inequalities using sustainable and cost‐effective interventions that impact on the wider determinants of mental health and wellbeing for children and young people and older people. Intergenerational activities could provide an opportunity to support both populations. In 2023, we produced an evidence and gap map to illustrate the amount and variety of research on intergenerational interventions and the gaps in research that still exist in this area. The review conducted here is based on the evidence in that map. Objectives This systematic review examines the impact of intergenerational interventions on the wellbeing and mental health of older people and identifies areas for future research as well as key messages for service commissioners. Search Methods We searched an evidence and gap map published in 2022 (comprehensive searches conducted July 2021 and updated June 2023) to identify randomised controlled trials of intergenerational interventions that report mental health and wellbeing outcomes for older people. Selection Criteria Randomised controlled trials of intergenerational interventions that involved unrelated younger and older people with at least one skipped generation between them and reported mental health or wellbeing outcomes for older people were included in this review. Data Collection and Analysis We used standard methodological procedures expected by The Campbell Collaboration. We conducted data extraction and Cochrane risk of bias assessments in EPPI reviewer. Where data allowed meta‐analyses were conducted in STATA. Main Results This review includes 14 trials from six different countries. The trials had some important methodological weaknesses. Interventions were mainly delivered in‐person and often in groups. They included visiting programmes, school volunteering programmes, music‐based interventions and task‐oriented interventions such as activities set in a multigenerational park, reminiscing activities, aggression management programmes, learning a language, making local environmental changes and in‐school project work. Intergenerational interventions showed a small positive trend towards improving self‐esteem (effect size [ES]: 0.33, 95% confidence interval [CI]: −0.35, 1.01) and depression (ES: 0.19, 95% CI: −0.23, 0.60) for older people participating. However, due to the small study sizes and low number of studies available, we cannot be confident about any effects. The results for other mental health and wellbeing outcomes are reported but due to little overlap in similar assessments across the studies, we could not combine them to assess the strength of evidence. There were no data about social isolation, spiritual health or sense of community. There are no long‐term studies and no data on equity. We still know very little about what works and how or why. Whilst some interventions do use theories and logic to inform their development others do not. More exploration of this is needed. Authors’ Conclusions Commissioners and intervention developers should ensure interventions provide sufficient theoretical evidence for the logic behind the proposed intervention and should improve their consideration of equity within the interventions Research on intergenerational interventions need more consistent and agreed measures for reporting outcomes including community outcomes (core outcome sets). More understanding is needed on how best to measure ‘community’ outcomes. Research on intergenerational interventions should measure outcomes for BOTH the older and younger population engaged in the intervention—these may or may not be the same outcomes reflected in both populations. Further research is needed on the long‐term impact of interventions on outcomes (whether participants need to keep being involved in an ‘intervention’ to continue to benefit) and sustainability of interventions beyond the initial funding of the research project. Supporting this our stakeholders highlighted that interventions that are initiated for research and then end (usually within a year) are not helpful.

Background: Nursing deficits are growing, and healthcare providers in developed countries must address the challenges of ethically building a sustainable workforce without a continued excessive reliance on overseas recruitment. To secure this, a focus on long-term retention of international recruits is paramount. Objective: To explore the migration motivations and experiences of initial integration for internationally recruited nurses within the healthcare system (England). Design: A mixed methods survey. Setting(s) and participants: 655 internationally recruited nurses who had recently commenced work in England completed the survey. Methods: qualitative and quantitative data was gathered to explore internationally recruited nurses’ demographics and professional backgrounds, migration motivations, application processes, arrival and settlement and initial experiences of integration into the workforce alongside their support and future aspirations. Results: The quantitative results revealed a population of international nurses that were highly educated and vastly experienced, with career development and desires to improve quality of life being the primary motivations for migration. Participants indicated a perception of being well supported during initial application and arrival stage, however, did experience some degree of challenge during workplace integration involving fluctuating levels of support and appointments into positions that did not match their years of experience and previous qualifications. This data was reinforced further detailed by the qualitative feedback that illuminated the difficulties nurses can face during initial arrival and integration and the apparent impact on mental well-being. Conclusion: This paper, contextualised with an international literature base verifying the experiences of internationally recruited nurses, argues that it is the consistent responsibility of employers in developed countries to protect the experiences of international recruits. This can be done by investing in solutions as a key retention strategy.

Introduction: Aircraft-assisted suicide is a rare but serious event, with immediate consequences for the pilot, crew, and passengers. The overt linkage between mental illness and suicidal behaviour is well-known, however, the infrequency of these events in the context of aviation, coupled with poor record-keeping and reluctance to disclose, likely disguises the true extent of mental illness among pilots. One critical research gap in Canada has been the lack of investigation of crashes linked to suicide or a mental disorder. Research on aircraft-assisted suicide will address the key issues of pilots’ reluctance to disclose, report, and seek mental health services. Our study investigates the frequency of aircraft-assisted suicide in Canada, reviews current medical standards, and discusses preventative interventions to manage future risk. Materials and methods: Our study examined investigations and reports conducted by the Transport Safety Board to explore the frequency of aircraft-assisted suicide over a ten year period. Results: Aircraft-assisted suicides in Canada are rare, however, mentally ill pilots involved in fatal crashes are likely underestimated. Our study highlights key barriers in aviators’ disclosure of mental health symptoms, an ineffective screening process, and a consequence-based system that deters pilots from their duty to report. Discussion: our investigative analysis addresses key limitations in screening of mentally ill pilots, explores current medical standards and aeromedical exams, infrequency of fitness assessments, and demonstrates the critical need for continuous evaluation of pilots in this safety-sensitive occupation. Conclusion: The current paper addresses the need for continuous evaluation of pilot’s mental health and a more rigorous screening process to accurately identify suicide risk in pilots and prevent aircraft-assisted suicide.

Indonesia is currently entering a new normal era; this requires people to adapt to the clean-living habit in accordance with health standards in order to carry out normal activities. At the same time, online transportation services have reopened for activity. The service quality provided by online ride-hailing companies (i.e., ojek) such as Gojek, Grab, and Maxim must now consider matters relating to user safety. This study proposes Multi Criteria Decision Making (MCDM) as a method for assessing the service quality of online transportation service providers and uses the Pandemic-SERVQUAL 4.0 model. Pandemi-SERVQUAL 4.0 model adds two new criteria, namely "pandemic" and "industry 4.0". The addition of two new criteria that are more relevant to the current circumstances will increase the accuracy of the research. This study aims to propose the integration of Interval Valued Intuitionistic Fuzzy Analytical Hierarchy Process (IVIF-AHP) to determine the criteria weight and Interval Valued Intuitionistic Fuzzy Weighted Aggregated Sum-Product Assessment (IVIF-WASPAS) to assess the service quality of several online transportation service providers based on the obtained criteria weights. From the results of the service quality assessment using the integration of IVIF-AHP and IVIF-WASPAS, the ranking of online transportation service providers during the new normal era were Grab-car, Go-car, and Maxim-car.

Abstract Aim To explore factors that influence registered nurses' intention to stay working in the healthcare sector. Design A systematic review and narrative synthesis. Methods CINAHL, Medline and Cochrane library databases were searched from Jan 2010 to Jan 2022 inclusive and research selected using a structured criterion, quality appraisal and data extraction and synthesis were guided by Campbell's Synthesis Without Meta‐analysis. Results Thirty‐four studies identified that nurses stay if they have job satisfaction and/or if they are committed to their organizations. The factors permeating these constructs weigh differently through generations and while not an infallible explanation, demonstrate stark differences in workplace needs by age, which influence the intention to stay, job satisfaction, organizational commitment and ultimately nurse turnover. Public Contribution Environmental, relational and individual factors have bearing on improving nurse satisfaction and commitment. Understanding why nurses stay through a generational behavioural and career stage lens can bolster safeguarding nurse retention.

Palm oil is a commodity whose demand continues to increase, requiring proper risk management in the supply chain. This study aims to develop a hybrid method that integrates probability impact matrix, analytical network process, and house of risk to mitigate strategies in the palm oil supply chain. The Probability Impact Matrix (PIM) method is used to map the priority risk agents and determine the occurrence value of the risk agents, and Analytical Network Process (ANP) is used to determine the severity value of the risk event. Furthermore, the House of Risk (HOR) is proposed to determine the priority of the mitigation strategy. The proposed method was applied in a case study on the palm oil supply chain in Indonesia. The research results show that ten priority risk agents and 6 mitigation strategies were obtained based on the proposed method to overcome risk agents in palm oil supply chain

Abstract Background There is some evidence to suggest that animal-assisted interventions can have beneficial impact for residents in long-term care, but the focus of the evidence has largely been on behavioural and psychosocial measured outcomes. Animals, either as companion animals or in the form of pet/animal-assisted therapy, may provide benefits in the form of social contact, as well as opportunities for sensory experiences and meaningful engagement not picked up by outcome tools. This review aimed to create a state-of-knowledge synthesis, bringing together qualitative and quantitative findings, on the impact of animal-human interaction on care home residents and care home staff. Methods Fourteen databases were searched from inception to July 2020. Forward and backward citation chasing of included articles was conducted. Screening was undertaken independently by a team of reviewers. Thematic synthesis and meta-analysis were used to synthesise the qualitative and quantitative data. Results Thirty-four studies, published in 40 articles (20 qualitative and 20 quantitative) were included. Five themes relating to resident wellbeing were identified in the qualitative evidence synthesis. These were animals as ‘living beings’, reminiscence and storytelling, caring (as ‘doing’ and ‘feeling’), respite (from loneliness, institutionalisation, and illness), and sensory engagement. A sixth theme related to staff perceptions and wellbeing, and a seventh to animal health and wellbeing. Maintaining identity was identified as an overarching theme. The majority of randomised trials had small sample sizes and were rated as low quality, mostly showing no evidence of beneficial effect. There was, however, limited evidence of a positive effect of pet/animal interaction on outcomes of loneliness, anxiety and depression, supporting the themes of respite and sensory engagement. Conclusions The presence of animals can significantly impact the health and wellbeing of some care home residents. Residents had meaningful relationships with animals and derived pleasure and comfort from them. Interacting with animals offered residents a way to maintain a sense of self in the care homes, and with support, residents with dementia could also express their identities. Facilitating residents to interact with animals as part of person-centred care may also help residents to feel ‘at home’ in the care home. Trial registration PROSPERO registration no: CRD42017058201.

**Background:** Endometrial cancer (EC) represents a substantial economic burden for patients in the United States. Patients with advanced or recurrent EC have a much poorer prognosis than patients with early-stage EC. Data on healthcare resource utilization (HCRU) and costs for patients with advanced or recurrent EC specifically are lacking. **Objectives:** To describe HCRU and costs associated with first-line (1L) therapy for commercially insured patients with advanced or recurrent EC in the United States. **Methods:** This was a retrospective cohort study of adult patients with advanced or recurrent EC using the MarketScan® database. Treatment characteristics, HCRU, and costs were assessed from the first claim in the patient record for 1L therapy for advanced or recurrent EC (index) until initiation of a new anti-cancer therapy, disenrollment from the database, or the end of data availability. Baseline demographics were determined during the 12 months before the patient’s index date. **Results:** A total of 7932 patients were eligible for inclusion. Overall, mean age at index was 61 years, most patients (77.3%) had received prior surgery for EC, and the most common 1L regimen was carboplatin/paclitaxel (59.1%). During the observation period, most patients had at least one healthcare visit (all-cause, 99.9%; EC-related, 82.8%), most commonly outpatient visits (all-cause, 91.4%; EC-related, 68.7%). The highest mean (SD) costs (US dollars) were for inpatient hospitalization for both all-cause and EC-related events ($8396 \[$15,130\] and $9436 \[$16,784\], respectively). Total costs were higher for patients with a diagnosis of metastasis at baseline than for those without a diagnosis of metastasis. **Discussion:** For patients with advanced or recurrent EC in the United States, 1L therapy is associated with considerable HCRU and economic burden. They are particularly high for patients with metastatic disease. **Conclusions:** This study highlights the need for new cost-effective treatments for patients with newly diagnosed advanced or recurrent EC.

**Background:** Patients with advanced or recurrent endometrial cancer (EC) typically have limited treatment options and poor long-term survival outcomes following first-line therapy. Real-world treatment patterns and survival outcomes data are limited for patients in this setting. **Objectives:** The objective of this retrospective study was to describe real-world demographics, clinical characteristics, treatment patterns, and overall survival among patients in the United States with primary advanced or recurrent EC who initiated at least 1 line of therapy (LOT). **Methods:** Patients with a diagnosis of primary advanced or recurrent EC in a real-world database from January 1, 2013, to July 31, 2021, were included. The date for inclusion was the date of EC diagnosis documentation; patients were indexed for treatment patterns and outcomes at the start of the first LOT and at the start of each subsequent LOT they initiated. Data were stratified by subgroups of patients who had mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) tumors. **Results:** A total of 1961 patients who received at least 1 LOT were included. Most patients in this cohort, and the dMMR/MSI-H subgroup, received a platinum combination as first-line treatment, with carboplatin-paclitaxel being the most common regimen. Only 53% of patients who received first-line treatment subsequently received second-line therapy. Of the patients who received at least 1 LOT, use of immunotherapy in the second-line setting was more common in the dMMR/MSI-H subgroup. Median overall survival ranged from 14.1 to 31.8 months across the 5 most frequently used first-line treatment regimens in the ≥1 LOT cohort and became shorter with each subsequent LOT. **Discussion:** The use of platinum-based chemotherapy for first-line treatment of advanced or recurrent EC predominates in the real-world setting, despite the poor long-term survival outcomes associated with most of these regimens. **Conclusions:** Patients with recurrent/advanced EC have a poor prognosis, highlighting the need for therapies with more durable benefits.

Objectives The caseload of family courts in England and Wales includes a growing share of domestic abuse cases. To increase knowledge about such cases, the research uses new administrative datasets and linkages to describe trends between 2011-2021 and to supplement the information already available from family court national statistics. Method The complete set of family court cases is held in HM Courts & Tribunals Services (HMCTS) systems. Some family court data are collected by the Children and Families Court Advisory Support Service (Cafcass), insofar as courts refer the case to Cafcass. By using their new linkage, we can conduct a descriptive analysis of domestic abuse cases in England and Wales over the ten years since 2011. This project is one of the first to gain approval from HMCTS to use their family court data. Access to de-identified versions of all datasets is through the SAIL Databank trusted research environment. Results The data linkage builds a more complete picture of the individuals involved, exploring their age group, gender and ethnicity. The new datasets allow to describe how court users approach domestic abuse matters and to draw distinctions between different types of cases: emergency situations; individuals being unrepresented in court (litigants in person); repeat applications; requests for different types of legal measures against the domestic abuse; and presence of children in the household. Furthermore, the data show how courts respond through case management, timeliness of decisions and legal outcomes made. We explore how different types of individuals and cases are associated with legal outcomes, and how the added understanding at population-level can focus and support discussions about the use of family courts to address domestic abuse. Conclusion Data linkage research is providing an evidence base at population level about court users in England and Wales who experience domestic abuse. This can help inform practice to support those families and policies to ease overburdened courts who see the same families and domestic abuse issues return to court.

Abstract Background Methods for the long-term in situ transduction of the unperturbed murine intestinal epithelium have not been developed in past research. Such a method could speed up functional studies and screens to identify genetic factors influencing intestinal epithelium biology. Here, we developed an efficient method achieving this long-sought goal. Results We used ultrasound-guided microinjections to transduce the embryonic endoderm at day 8 (E8.0) in utero. The injection procedure can be completed in 20 min and had a 100% survival rate. By injecting a small volume (0.1–0.2 μl) of concentrated virus, single shRNA constructs as well as lentiviral libraries can successfully be transduced. The new method stably and reproducibly targets adult intestinal epithelium, as well as other endoderm-derived organs such as the lungs, pancreas, liver, stomach, and bladder. Postnatal analysis of young adult mice indicates that single transduced cells at E8.0 gave rise to crypt fields that were comprised of 20–30 neighbouring crypts per crypt-field at 90 days after birth. Lentiviral targeting of Apc Min/+ mutant and wildtype mice revealed that heterozygous loss of Apc function suppresses the developmental normal growth pattern of intestinal crypt fields. This suppression of crypt field sizes did not involve a reduction of the crypt number per field, indicating that heterozygous Apc loss impaired the growth of individual crypts within the fields. Lentiviral-mediated shRNA knockdown of p53 led to an approximately 20% increase of individual crypts per field in both Apc +/+ and Apc Min/+ mice, associating with an increase in crypt size in Apc Min/+ mice but a slight reduction in crypt size in Apc +/+ mice. Overall, p53 knockdown rescued the reduction in crypt field size in Apc-mutant mice but had no effect on crypt field size in wildtype mice. Conclusions This study develops a novel technique enabling robust and reproducible in vivo targeting of intestinal stem cells in situ in the unperturbed intestinal epithelium across different regions of the intestine. In vivo somatic gene editing and genetic screening of lentiviral libraries has the potential to speed up discoveries and mechanistic understanding of genetic pathways controlling the biology of the intestinal epithelium during development and postnatal life. The here developed method enables such approaches.

The authors identify Nuclear receptor subfamily 6 group A member 1 (Nr6a1) as a master regulator of elongation, segmentation, patterning and lineage allocation specifically within the trunk region of the mouse, acting downstream of the major signals known to control vertebral column formation.

Abstract Brown adipose tissue (BAT) is a fat tissue specialized in heat production (non-shivering thermogenesis) and used by mammals to defend core body temperature when exposed to cold. Several studies have shown that during non-shivering thermogenesis the increase in BAT oxygen demand is met by a local and specific increase in tissue’s blood flow. While the vasculature of BAT has been extensively studied postmortem in rodents using histology, optical and CT imaging techniques, vasculature changes during stimulation of non-shivering thermogenesis have never been directly detected in vivo. Here, by using computed tomography (CT) angiography with gold nanoparticles we investigate, non-invasively, changes in BAT vasculature during adrenergic stimulation of non-shivering thermogenesis by norepinephrine, a vasoconstrictor known to mediate brown fat heat production, and by CL 316,243, a specific β3-adrenergic agonist also known to elicit BAT thermogenesis in rodents. We found that while CL 316,243 causes local vasodilation in BAT, with little impact on the rest of the vasculature throughout the body, norepinephrine leads to local vasodilation in addition to peripheral vasoconstriction. As a result, a significantly greater relative increase in BAT perfusion is observed following the injection of NE compared to CL. This study demonstrates the use of in vivo CT angiography as an effective tool in assessing vascular reactivity in BAT both qualitatively and quantitatively in preclinical studies.

Abstract This is the protocol for a Campbell systematic review. The objectives are as follows: This systematic review will examine the impact of intergenerational interventions on the mental health and wellbeing of older people and will identify areas for future research as well as key messages for service commissioners.