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Abstract Autism spectrum disorders (ASD) are complex, polygenic and heterogenous neurodevelopmental conditions. The severity of autism-associated variants is influenced by environmental factors, particularly social experiences during the critical neurodevelopmental period. While early behavioral interventions have shown efficacy in some children with autism, pharmacological support for core features — impairments in social interaction and communication, and stereotyped or restricted behaviors — is currently lacking. In this study, we examined how the social environment influences both wild-type (WT) and Shank3 knockout (KO) mice, a model reflecting core autism-like traits. Our findings revealed that chronic social isolation enhanced social interaction and olfactory neuron responses in WT animals. Furthermore, it restored impairments in social novelty preference and olfactory function, as well as self-grooming in Shank3 KO mice. Conversely, an enriched social environment heightened social interest toward novel conspecifics in WT mice, but elicited the opposite effect in Shank3 KO mice. Notably, Shank3 KO mice displayed distinct social responses when exposed to WT or Shank3 KO mice. These results offer novel insights that could favor the implementation of behavioral interventions and inclusive classroom programs for children with ASD.

Abstract Background Healthcare systems aim to enhance the health status and well-being of the individuals and populations they serve. To achieve this, measuring and evaluating the quality and safety of services provided and the outcomes achieved is essential. Like other countries, Romania faces challenges regarding the quality of care provided in its public hospitals. To address this, the Romanian Ministry of Health initiated reforms in 2022, including implementing a pay-for-performance model based on quality indicators. This paper presents a descriptive analysis of processes, methods, results and lessons learned from developing and piloting a set of Quality of Care indicators for Romanian public hospitals. Methods World Health Organization’s Athens Office on Quality of Care and Patient Safety assisted Romania in developing and piloting a set of quality-of-care indicators for public hospitals. The development phase included defining indicator domains, identifying potential indicators across these domains, and defining the final indicator set. The piloting phase involved selecting and recruiting piloting hospitals, developing data collection and validation methods and tools, training hospital staff, and collecting and analysing indicator data. Piloting ended with an evaluation workshop. Mixed, quantitative and qualitative methods were used, including literature reviews, stakeholder consultation workshops, survey instruments developed for this study, modified Delphi panels and consensus-building meetings. National stakeholders were actively involved throughout the process. Results Four priority domains were defined for quality-of-care indicators for Romanian public hospitals: patient safety, patient experience, healthcare workforce training and safety, and clinical effectiveness. 25 core indicators were selected across these domains. During the pilot, hospitals achieved an average completion rate of 90% for data submission, with all domains rated equally relevant during post-pilot evaluations. Lessons included the need for supportive legislation, improved internal auditing practices and enhanced staff training, refinement of indicator data collection methods and alignment of indicators with hospital-specific contexts. Conclusions This work presents a significant stride in improving Romanian public hospitals’ quality of care and patient safety. It underscores the importance of high-level commitment, stakeholder engagement, and robust data practices in driving successful quality improvement efforts. Emphasising the role of data-driven and patient-centric approaches in achieving optimal healthcare outcomes, lessons learned offer insights for the continuation of quality improvement work in Romania but also for healthcare systems elsewhere.

Abstract Background Tajikistan has embarked on health reforms to orient the health system towards primary health care (PHC). The health labour market analysis (HLMA) was initiated by the Ministry of Health with the World Health Organization (WHO) on policy questions related to the PHC workforce team. This article presents the results with focus on family doctors as a critical part of the PHC team, providing lessons for strengthening family medicine and PHC in the European Region and central Asia. Methods The HLMA framework was used to guide the analysis. The data for analysis were provided by the Ministry of Health and Social Protection of the Population of the Republic of Tajikistan. Descriptive means were used to analyse the data. A Technical Working Group guided the process. Results There has been an increase in the number of health workers in the country over the last 7 years. However, there is a huge shortage of family doctors when compared with norms, with decreasing family doctor densities over the last 7 years. Family doctors have the highest vacancy rates among specialists and also constitute the highest proportion of specialists who migrate. There is inequitable distribution of doctors across the regions. Overall number of enrolments and graduates in family medicine are declining. Although salaries in PHC are higher than in hospitals, the overall health workforce salaries are lower than the national average. While there have been efforts to retain and attract doctors to PHC in rural and remote regions, challenges exist. The attraction of doctors to narrow specialties may be leading to undermining PHC and family medicine. While the optimal skill-mix and availability of nurses provide an opportunity to strengthen multi-disciplinary teams at the PHC level, shortages and unequal distribution of doctors are affecting health services coverage and health indicators. Conclusions Application of the HLMA framework has helped identify the bottlenecks in the health labour market flows and the possible explanations for them. The policy considerations emerging out of the HLMA have contributed to improving evidence-based planning for retention and recruitment of the PHC workforce, improvements in medical and nursing education, and higher investments in the PHC workforce and particularly in family doctors. Implementation of the Action Plan will require political commitment, financial resources, strong inter-sectoral collaboration, stakeholder management, and cross-country learning of best practices. Through this process, Tajikistan has shown the way forward in implementing the Central Roadmap for health and well-being in Central Asia and the Framework for Action on the Health and Care Workforce in the WHO European Region.

The sparsity of post-translocation monitoring data for rehabilitated felids leaves a pressing gap in our current understanding of their integration into and use of novel landscapes. Remote monitoring tools such as GPS collars can provide crucial insights into animal movement behavior and habitat selection following translocation and assist in the decision-making process for rehabilitation and release sites. In January 2023, a young male ocelot was released on the Osa Peninsula, Costa Rica, after eight months of rehabilitation following a vehicle strike. Six months of post-translocation monitoring using a GPS and VHF-enabled collar revealed distinctive spatial patterns between the ocelot’s initial exploratory phase (~75 days) and subsequent residential period, as well as a selection for agricultural-forest matrix habitat over primary forest. We discuss the findings in terms of learning lessons for future post-release monitoring effects and provide insight into an individual’s patterns of habitat selection in an anthropogenically modified landscape.

Background A widely accepted set of imaging criteria or classification has not yet been adopted to evaluate response to treatment by percutaneous sclerotherapy for aneurysmal bone cyst (ABC). In this article, we described and illustrated the Royal Orthopaedic Hospital (ROH) scoring system which is a new, reproducible, and objective tool to evaluate the radiological response. We also reported our institutional experience in the efficacy of computed tomography (CT)-guided sclerotherapy for treating such lesions.

We present a genome assembly from an individual Zeus faber (the John Dory; Chordata; Actinopteri; Zeiformes; Zeidae). The genome sequence is 804.7 megabases in span. Most of the assembly is scaffolded into 22 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 16.72 kilobases in length.

Objective To conduct a head-to-head comparative analysis of cataract surgery patient education material generated by Chat Generative Pre-trained Transformer (ChatGPT-4) and Google Bard.Methods and analysis 98 frequently asked questions on cataract surgery in English were taken in November 2023 from 5 trustworthy online patient information resources. 59 of these were curated (20 augmented for clarity and 39 duplicates excluded) and categorised into 3 domains: condition (n=15), preparation for surgery (n=21) and recovery after surgery (n=23). They were formulated into input prompts with ‘prompt engineering’. Using the Patient Education Materials Assessment Tool-Printable (PEMAT-P) Auto-Scoring Form, four ophthalmologists independently graded ChatGPT-4 and Google Bard responses. The readability of responses was evaluated using a Flesch-Kincaid calculator. Responses were also subjectively examined for any inaccurate or harmful information.Results Google Bard had a higher mean overall Flesch-Kincaid Level (8.02) compared with ChatGPT-4 (5.75) (p0.10). None of the generated material contained dangerous information.Conclusion In comparison to Google Bard, ChatGPT-4 fared better overall, scoring higher on the PEMAT-P understandability scale and exhibiting more faithfulness to the prompt engineering instruction. Since input prompts might vary from real-world patient searches, follow-up studies with patient participation are required.

Purpose Despite the volume of accumulating knowledge from prospective Aboriginal cohort studies, longitudinal data describing developmental trajectories in health and well-being is limited. The linkage of child and carer cohorts from a historical cross-sectional survey with longitudinal health-service and social-service administrative data has created a unique and powerful data resource that underpins the Western Australian Aboriginal Child Health Survey (WAACHS) linked data study. This study aims to provide evidence-based information to Aboriginal communities across Western Australia, governments and non-government agencies on the heterogeneous life trajectories of Aboriginal children and families.Participants This study comprises data from a historical cross-sectional household study of 5289 Aboriginal children from the WAACHS (2000–2002) alongside their primary (N=2113) and other (N=1040) carers, and other householders. WAACHS data were linked with Western Australia (WA) government administrative datasets up to 2020 including health, education, child protection, police and justice system contacts. The study also includes two non-Aboriginal cohorts from WA, linked with the same administrative data sources allowing comparisons of outcomes across cohorts in addition to between-group comparisons within the Aboriginal population.Findings to date Linked data coverage rates are presented for all WAACHS participants. Child health outcomes for the WAACHS children (Cohort 1) are described from birth into adulthood along with other outcomes including child protection and juvenile justice involvement.Future plans Analysis of data from both the child and carer cohorts will seek to understand the contribution of individual, family (intergenerational) and community-level influences on Aboriginal children’s developmental and health pathways, identify key developmental transitions or turning points where interventions may be most effective in improving outcomes, and compare service pathways for Aboriginal and non-Aboriginal children. All research is guided by Aboriginal governance processes and study outputs will be produced with Aboriginal leadership to guide culturally appropriate policy and practice for improving health, education and social outcomes.

Introduction and Objective: Thoracic disc calcification is a radiological finding which may be incidental or diagnosed in patients presenting with myelopathy due to spinal cord compression. We performed a study to analyze the imaging patterns of calcified thoracic discs (CTDs). Patients and Methods: A retrospective review of the spinal and radiology database of a tertiary referral orthopedic hospital was conducted for the incidence of CTDs between 2007 and 2020. Patients’ demographics and radiological findings were recorded. The relationship between disc size, morphology, spinal cord compression, and management was assessed. Results: Fifty-one cases of CTDs were identified. The mean size of CTD was 806.2 mm3 (range: 144–2340). The most common level of disc calcification was T9–T10 (24%) in 12 patients. Thoracic disc calcifications in our series commonly involved disc “protrusion” in 67% (34 patients), followed by “mushroom” type in 31% (16 patients) and “extrusion” in 2% (1 patient). 37% (19 patients) had spinal cord compression with 12% (6 patients) undergoing surgical interventions. There was no statistically significant difference in the mean sizes of CTD between the groups with and without spinal cord compression (P = 0.566, independent sample t-test). Patients with “mushroom” type calcification were more likely to have surgical intervention (P = 0.01, Fisher’s exact test). Conclusion: Thoracic disc calcifications, while common, can still be underdiagnosed till late myelopathic deterioration. Care of the elderly physicians, spinal surgeons, and radiologists need to be aware of them to guide diagnosis and management. Our study demonstrates that disc morphology plays a vital role in myelopathic presentation and therefore determines the need for surgical intervention instead of the absolute size of disc calcification.

Abstract Under grid voltage sags, over current protection and exploiting the maximum capacity of the inverter are the two main goals of grid-connected PV inverters. To facilitate low-voltage ride-through (LVRT), it is imperative to ensure that inverter currents are sinusoidal and remain within permissible limits throughout the inverter operation. An improved LVRT control strategy for a two-stage three-phase grid-connected PV system is presented here to address these challenges. To provide over current limitation as well as to ensure maximum exploitation of the inverter capacity, a control strategy is proposed, and performance the strategy is evaluated based on the three generation scenarios on a 2-kW grid connected PV system. An active power curtailment (APC) loop is activated only in high power generation scenario to limit the current’s amplitude below the inverter’s rated current. The superior performance of the proposed strategy is established by comparison with two recent LVRT control strategies. The proposed method not only injects necessary active and reactive power but also minimizes overcurrent with increased exploitation of the inverter’s capacity under unbalanced grid voltage sag.

Abstract Background Indigenous adolescents access primary health care services at lower rates, despite their greater health needs and experience of disadvantage. This systematic review identifies the enablers and barriers to primary health care access for Indigenous adolescents to inform service and policy improvements. Methods We systematically searched databases for publications reporting enablers or barriers to primary health care access for Indigenous adolescents from the perspective of adolescents, their parents and health care providers, and included studies focused on Indigenous adolescents aged 10–24 years from Australia, Canada, New Zealand, and United States of America. Results were analyzed against the WHO Global standards for quality health-care services for adolescents. An additional ninth standard was added which focused on cultural safety. Results A total of 41 studies were included. More barriers were identified than enablers, and against the WHO Global standards most enablers and barriers related to supply factors – providers’ competencies, appropriate package of services, and cultural safety. Providers who built trust, respect, and relationships; appropriate package of service; and culturally safe environments and care were enablers to care reported by adolescents, and health care providers and parents. Embarrassment, shame, or fear; a lack of culturally appropriate services; and privacy and confidentiality were common barriers identified by both adolescent and health care providers and parents. Cultural safety was identified as a key issue among Indigenous adolescents. Enablers and barriers related to cultural safety included culturally appropriate services, culturally safe environment and care, traditional and cultural practices, cultural protocols, Indigenous health care providers, cultural training for health care providers, and colonization, intergenerational trauma, and racism. Nine recommendations were identified which aim to address the enablers and barriers associated with primary health care access for Indigenous adolescents. Conclusion This review provides important evidence to inform how services, organizations and governments can create accessible primary health care services that specifically meet the needs of Indigenous adolescents. We identify nine recommendations for improving the accessibility of primary health care services for Indigenous adolescents.

We present a genome assembly from a specimen of Bugula neritina (the ruby bryozoan; Bryozoa; Gymnolaemata; Cheilostomatida; Bugulidae). The genome sequence has total length of 216.00 megabases. Most of the assembly is scaffolded into 9 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 15.25 kilobases in length. Gene annotation of this assembly on Ensembl identified 20,264 protein-coding genes.

In response to the growing need for self-directed learning (SDL) skills in a rapidly changing world, research was conducted to map interventions that support SDL skills, aiming to find a model for supporting SDL skills in NEET-youth. SDL competencies support continuous personal development and coping with change. There is a significant number of young people in society who do not participate in working life, education, or training (NEET-youth) and are characterized by a low level of education. Little has been done to support SDL skills interventions for them; however, bringing young people back to the education path is a crucial issue. This raises important questions about which supportive approach and tools are most beneficial for developing SDL skills in NEET-youth, and how best to implement them. This literature review is based on the analysis of 25 articles. The results of the study showed that SDL interventions have not been used for NEET-youth, and therefore, the new model was created. In the case of NEET-youth the SDL intervention should be seen as a non-formal learning process that combines various activities that enable self-reflection and real-life experiences for acquiring new positive learning experiences.

Background Australia does not have a national strategy for Aboriginal and Torres Strait Islander adolescent health and as a result, policy and programming actions are fragmented and may not be responsive to needs. Efforts to date have also rarely engaged Aboriginal and Torres Strait Islander people in co-designing solutions. The Roadmap Project aims to work in partnership with young people to define priority areas of health and well-being need and establish the corresponding developmentally appropriate, evidence-based actions.Methods and analysis All aspects of this project are governed by a group of Aboriginal and Torres Strait Islander young people. Needs, determinants and corresponding responses will be explored with Aboriginal and Torres Strait Islander adolescents (aged 10–24 years) across Australia through an online qualitative survey, interviews and focus group discussions. Parents, service providers and policy makers (stakeholders) will share their perspectives on needs and support required through interviews. Data generated will be co-analysed with the governance group and integrated with population health data, policy frameworks and evidence of effective programmes (established through reviews) to define responsive and effective actions for Aboriginal and Torres Strait Islander adolescent health and well-being.Ethics and dissemination Ethical approval for this study has been obtained from the Aboriginal Health Council of South Australia (Ref: 04-21-956), the Aboriginal Health and Medical Research Council of New South Wales (Ref: 1918/22), the Western Australian Aboriginal Health Ethics Committee (Ref: HREC1147), the Northern Territory Health and Menzies School of Health Research (Ref: 2022–4371), ACT Health Human Research Ethics Committee (Ref: 2022.ETH.00133), the St. Vincent’s Hospital, Victoria (Ref: HREC 129/22), University of Tasmania (Ref: 28020), Far North Queensland Human Research Ethics Committee (Ref: HREC/2023/QCH/89911) and Griffith University (Ref: 2023/135). Prospective adolescent participants will provide their own consent for the online survey (aged 13–24 years) and, interviews or focus group discussions (aged 15–24 years); with parental consent and adolescent assent required for younger adolescents (aged 10–14 years) participating in interviews.Study findings (priority needs and evidence-based responses) will be presented at a series of co-design workshops with adolescents and stakeholders from relevant sectors. We will also communicate findings through reports, multimedia clips and peer-reviewed publications as directed by the governance group.

Objectives Develop and validate short and rapid forms of the 36-item Menstrual Practice Needs Scale (MPNS-36).Design Item reduction prioritised content validity and was informed by cognitive interviews with schoolgirls in Bangladesh, performance of scale items in past research and stakeholder feedback. The original MPNS-36 was revalidated, and short and rapid forms tested in a cross-sectional survey. This was followed by further tests of dimensionality, internal consistency and validity in multiple cross-sectional surveys.Setting and participants Short form (MPNS-SF) and rapid form (MPNS-R) measures were developed in a survey of 313 menstruating girls (mean age=13.51) in Khulna, Bangladesh. They were further tested in the baseline survey of the Adolescent Menstrual Experiences and Health Cohort, in Khulna, Bangladesh (891 menstruating girls, mean age=12.40); and the dataset from the MPNS-36 development in Soroti, Uganda (538 menstruating girls, mean age=14.49).Results The 18-item short form reflects the six original subscales, with the four core subscales demonstrating good fit in all three samples (Khulna pilot: root mean square error of approximation (RMSEA)=0.064, 90% CI 0.043 to 0.084, Comparative Fit Index (CFI)=0.94, Tucker-Lewis Index (TLI)=0.92. Cohort baseline: RMSEA=0.050, 90% CI 0.039 to 0.062, CFI=0.96, TLI=0.95. Uganda: RMSEA=0.039, 90% CI 0.028 to 0.050, CFI=0.95, TLI=0.94). The 9-item rapid form captures diverse needs. A two-factor structure was the most appropriate but fell short of adequate fit (Khulna pilot: RMSEA=0.092, 90% CI 0.000 to 0.158, CFI=0.93, TLI=0.89). Hypothesised associations between the MPNS scores and other constructs were comparable between the MPNS-36 and MPNS-SF in all populations, and replicated, with attenuation, in the MPNS-R. Internal consistency remained acceptable.Conclusions The MPNS-SF offers a reliable and valid measure of adolescent girls’ menstrual hygiene experience while reducing participant burden, to support implementation and improve measurement in menstrual health research. The MPNS-R provides a brief measure with poorer structural validity, suited to short surveys and including menstrual health within broader research topics.

The rising demand for electrical energy, coupled with the running down of conventional energy sources, has prompted vast research into renewable energy sources (RES) for power generation. Wind and solar photovoltaic energies are among the most critical resources, despite their susceptibility to fluctuating climatic conditions. Power electronics have been helpful in the integration of renewable energy sources (RESs) with grid, and multilevel inverters (MLIs) have arisen as critical components for the effective utilization of energy from RES and the enhancement of power quality. This paper provides an extensive overview of the latest developments in MLI topologies and how they have been applied in different industries. Optimal MLI designs for various applications will be identified by a thorough investigation of performance parameters including component count, total harmonic distortion (THD), and overall efficiency. Additionally, the paper explores the role of MLIs in diverse sectors including RES, microgrids, and residential applications. By synthesizing insights from recent literature and performance evaluations, this review aims to provide valuable guidance for researchers and practitioners in selecting the most suitable MLI topology for specific applications.

The short-circuit (SC) immunity of power silicon carbide (SiC) MOSFETs is critical for high-reliability applications, where robust monitoring and protection strategies are essential to ensure system safety. Despite their superior voltage blocking capabilities and high energy efficiency, SiC MOSFETs exhibit greater sensitivity to SC-induced degradation compared to their silicon counterparts. This increased vulnerability necessitates the precise assessment of the key SC performance metrics, such as short-circuit withstand time (TSCWT), as well as a deeper understanding of the failure mechanisms. In this study, a comprehensive experimental methodology for evaluating the SC behavior of SiC MOSFETs is presented and validated using industrial references. The investigation further explores the concept of a Safe Operating Area (SOA) under SC conditions, highlighting the significant impact of quasi-simultaneous SC events on device lifetime. Additionally, an application case study demonstrates how these events can drastically reduce the device’s lifespan.

Biodiversity genomics research requires reliable organismal identification, which can be difficult based on morphology alone. DNA-based identification using DNA barcoding can provide confirmation of species identity and resolve taxonomic issues but is rarely used in studies generating reference genomes. Here, we describe the development and implementation of DNA barcoding for the Darwin Tree of Life Project (DToL), which aims to sequence and assemble high quality reference genomes for all eukaryotic species in Britain and Ireland. We present a standardised framework for DNA barcode sequencing and data interpretation that is then adapted for diverse organismal groups. DNA barcoding data from over 12,000 DToL specimens has identified up to 20% of samples requiring additional verification, with 2% of seed plants and 3.5% of animal specimens subsequently having their names changed. We also make recommendations for future developments using new sequencing approaches and streamlined bioinformatic approaches.

Abstract Background and Aim Atrophic gastritis (AG) and gastric intestinal metaplasia (GIM) are early changes in the stepwise progression to gastric adenocarcinoma. There is heterogeneity in international guidelines regarding the endoscopic diagnosis and surveillance of AG and GIM. This study aims to determine the prevalence of GIM in an Australian center and assess the approach of Australian endoscopists for these two conditions. Methods We conducted a single‐center retrospective study of adult patients between January 2015 and December 2020 diagnosed with GIM on gastric biopsy following upper gastric endoscopy. A web‐based, 25‐question, investigator‐designed, multiple‐choice survey was distributed among all registered endoscopists in Australia. Results The overall prevalence of GIM within a single Australian center was 11.7% over 5 years. Of the 1026 patients identified, only 58.7% underwent mapping biopsies using the modified Sydney protocol. Among the cohort, 1.6% had low‐grade dysplasia, 0.9% had high‐grade dysplasia, and 1.8% had malignancy on initial gastroscopy. Two hundred and sixty‐seven (7.2%) endoscopists completed the survey, 44.2% indicated they would perform mapping for all patients, and 36% only for high‐risk patients. Only 1.5% (n = 4) of respondents were able to correctly identify all six endoscopic photos of GIM/AG. Conclusion This study demonstrates that in a large tertiary center, GIM is a prevalent endoscopic finding, but the associated rates of dysplasia and cancer were low. Additionally, among a small proportion of surveyed Australian endoscopists, there is notable variability in the endoscopic approach for AG and GIM and significant knowledge gaps. More training is required to increase the recognition of GIM and compliance with histological mapping.

Introduction Smoking cessation is an essential, but often overlooked aspect of diabetes management. Despite the need for tailored smoking cessation support for individuals with diabetes, evidence of effective interventions for this cohort is limited. Additionally, individuals with diabetes do not easily adopt such interventions, resulting in low uptake and abstinence rates. This protocol describes a study that aims to assess the feasibility and acceptability of a unique smoking cessation intervention, based on the best evidence, theory and the needs of individuals with diabetes, among patients and service providers, the diabetes nurse educators.Methods and analysis This is an open-label pragmatic randomised controlled trial. Between 80 and 100 individuals with type 1 or type 2 diabetes who smoke will be recruited from the diabetes outpatients at the main acute public hospital in Malta, starting in August 2023. Participants will be randomly assigned (1:1 ratio) to the intervention or control arm for 12 weeks. The experimental intervention will consist of three to four smoking cessation behavioural support sessions based on the 5As (Ask, Advise, Assess, Assist and Arrange) algorithm, and a 6-week supply of nicotine replacement therapy. The control intervention will consist of an active referral to the Maltese National Health Service’s one-to-one smoking cessation support service, which is based on motivational interviewing. The primary feasibility and acceptability outcomes include the recruitment and participation rates, resources used, problems identified by the nurses, the nurses’ perceived challenges and facilitators to implementation and the nurses’ and patients’ acceptability of the study intervention. Data analyses will be descriptive, with quantitative feasibility and acceptability outcomes reported with 95% confidence intervals.Ethics and dissemination Ethical clearance was obtained from the Faculty of Health Sciences Research Ethics Committee, University of Malta. The study results will be disseminated through conference presentations and a publication in a peer-reviewed journal.Trial registration number NCT05920096.

Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Introduction Improving the health of Indigenous adolescents is central to addressing the health inequities faced by Indigenous peoples. To achieve this, it is critical to understand what is needed from the perspectives of Indigenous adolescents themselves. There have been many qualitative studies that capture the perspectives of Indigenous young people, but synthesis of these has been limited to date.Methods and analysis This scoping review seeks to understand the specific health needs and priorities of Indigenous adolescents aged 10–24 years captured via qualitative studies conducted across Australia, Aotearoa New Zealand, Canada, the USA, Greenland and Sami populations (Norway and Sweden). A team of Indigenous and non-Indigenous researchers from these nations will systematically search PubMed (including the MEDLINE, PubMed Central and Bookshelf databases), CINAHL, Embase, Scopus, the Informit Indigenous and Health Collections, Google Scholar, Arctic Health, the Circumpolar Health Bibliographic Database, Native Health Database, iPortal and NZresearch.org, as well as specific websites and clearinghouses within each nation for qualitative studies. We will limit our search to articles published in any language during the preceding 5 years given that needs may have changed significantly over time. Two independent reviewers will identify relevant articles using a two-step process, with disagreements resolved by a third reviewer and the wider research group. Data will then be extracted from included articles using a standardised form, with descriptive synthesis focussing on key needs and priorities. This scoping review will be conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.Ethics and dissemination Ethics approval was not required for this review. Findings will be disseminated via a peer-reviewed journal article and will inform a broader international collaboration for Indigenous adolescent health to develop evidence-based actions and solutions.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

BackgroundThe prevalence of stunting among Indonesian children aged 5–12 years decreased from 30.7% in 2013 to 23.6% in 2018 but has remained among the highest rates worldwide. Furthermore, Indonesian children were shorter than the standard reported by the World Health Organization and experienced obesity. The Indonesian government has created many programs to reduce stunting in children under the age of 5 years. An early preventive strategy is necessary because stunting can manifest within the initial 1,000 days of life, including during pregnancy. Therefore, a newer perspective, such as that achieved by addressing stunting in adolescents, has been deemed useful, given that adolescents are in their pubertal stage and are undergoing lifestyle changes. This cohort study was designed to measure these factors comprehensively in stunted and non-stunted children as they pass through adolescence.MethodsFor the prospective cohort, 560 individuals will be recruited from DKI Jakarta, DI Yogyakarta, and East Java. The participants will be categorized into stunted and non-stunted groups, then undergo annual examinations in which key objectives, such as weight, height, and body mass index ,will be assessed for the growth profile; waist circumference, middle-upper arm circumference, hand-grip strength, body fat percentage, and food intake will be evaluated in a nutritional assessment; psychosocial and mental issues will be evaluated according to behavioral problems, symptoms of depression, quality of life, sleep patterns, anxiety disorders, and parenting style through the use of specific questionnaires; and pubertal stage will be assessed using a self-report questionnaire. Some cross-sectional data, such as cognitive performance, hair zinc levels, vitamin D levels, bone mineral density, and bone age, will also be included. All the outcomes will be analyzed in accordance with the variable types.DiscussionThis study provides a thorough dataset of Indonesian adolescents encompassing several elements, such as growth, nutrition, psychosocial wellbeing, mental health, and pubertal development, for both stunted and non-stunted individuals. The data acquired from this study can be used to formulate policies to prevent stunting through targeted interventions for adolescents. Finally, a better understanding of adolescent health could lead to improved strategies to decrease the number of stunted individuals in the next Indonesian generation.

Background Menstrual health is essential for gender equity and the well-being of women and girls. Qualitative research has described the burden of poor menstrual health on health and education; however, these impacts have not been quantified, curtailing investment. The Adolescent Menstrual Experiences and Health Cohort (AMEHC) Study aims to describe menstrual health and its trajectories across adolescence, and quantify the relationships between menstrual health and girls’ health and education in Khulna, Bangladesh.Methods and analysis AMEHC is a prospective longitudinal cohort of 2016 adolescent girls recruited at the commencement of class 6 (secondary school, mean age=12) across 101 schools selected through a proportional random sampling approach. Each year, the cohort will be asked to complete a survey capturing (1) girls’ menstrual health and experiences, (2) support for menstrual health, and (3) health and education outcomes. Survey questions were refined through qualitative research, cognitive interviews and pilot survey in the year preceding the cohort. Girls’ guardians will be surveyed at baseline and wave 2 to capture their perspectives and household demographics. Annual assessments will capture schools’ water, sanitation and hygiene, and support for menstruation and collect data on participants’ education, including school attendance and performance (in maths, literacy). Cohort enrolment and baseline survey commenced in February 2023. Follow-up waves are scheduled for 2024, 2025 and 2026, with plans for extension. A nested subcohort will follow 406 post-menarche girls at 2-month intervals throughout 2023 (May, August, October) to describe changes across menstrual periods. This protocol outlines a priori hypotheses regarding the impacts of menstrual health to be tested through the cohort.Ethics and dissemination AMEHC has ethical approval from the Alfred Hospital Ethics Committee (369/22) and BRAC James P Grant School of Public Health Institutional Review Board (IRB-06 July 22-024). Study materials and outputs will be available open access through peer-reviewed publication and study web pages.

The Unfolded Protein Response (UPR) is a retrograde, ER-to-nucleus, signalling pathway which is conserved across kingdoms. In plants, it contributes to development, reproduction, immunity and tolerance to abiotic stress. This RNA sequencing (RNA-seq) dataset was produced from 14-day-old Arabidopsis thaliana seedlings challenged by tunicamycin (Tm), an antibiotic inhibiting Asn-linked glycosylation in the endoplasmic reticulum (ER), causing an ER stress and eventually activating the UPR. Wild-type (WT) and a double mutant deficient for two main actors of the UPR (INOSITOL-REQUIRING ENZYME 1A and INOSITOL-REQUIRING ENZYME 1B) were used as genetic backgrounds in our experimental setup, allowing to distinguish among differentially-expressed genes (DEGs) which ones are dependent on or independent on IRE1s. Also, shoots and roots were harvested separately to determine organ-specific transcriptomic responses to Tm. Library and sequencing were performed using DNBseq™ technology by the Beijing Genomics Institute. Reads were mapped and quantified against the Arabidopsis genome. Differentially-expressed genes were identified using Rflomics upon filtering and normalization by the Trimmed Mean of M-value (TMM) method. While the genotype effect was weak under mock conditions (with a total of 182 DEGs in shoots and 195 DEGs in roots), the tunicamycin effect on each genotype was characterized by several hundred of DEGs in both shoots and roots. Among these genes, 872 and 563 genes were statistically up- and down-regulated in the shoot tissues of the double mutant when compared to those of WT, respectively. In roots of Tm-challenged seedlings, 425 and 439 genes were significantly up- and down-regulated in mutants with respect to WT. We believe that our dataset could be reused for investigating any biological questions linked to ER homeostasis and its role in plant physiology.

Introduction: We report a rare case of an aggressive large-cell neuroendocrine lung tumour, which presented with ocular metastasis. Case Presentation: A 70-year-old lady presented with a 4-week history of left eye pain and photophobia. Ocular examination revealed left-sided episcleritis and she was treated with topical lubricants and steroids. However, she re-presented 6 months later with recurrent left eye symptoms and was found to have an iris stroma amelanotic lesion, posterior synechiae, 360-degrees rubeosis iridis, raised intraocular pressure, and trace vitreous inflammation. Ultrasound biomicroscopy revealed a left thickened iris with an associated ciliary body lesion. Sarcoid-related ocular inflammation was suspected, but a computed tomography (CT) scan of the lung revealed an incidental right upper lobe lesion. Histology from a transcorneal iris biopsy showed a high-grade neuroendocrine carcinoma, and the diagnosis of metastatic lung large-cell neuroendocrine carcinoma was confirmed via high-resolution CT scan, positron emission tomography scan, and CT-guided lung biopsy. She was given multiple courses of different chemotherapy regimens along with palliative radiotherapy. However, the tumour and its metastases continued to progress and she passed away 4 years after her initial presentation. Conclusion: Ocular metastatic large-cell neuroendocrine carcinoma is rare, and the first presentation with ocular metastasis is even rarer. This case highlights the importance of early detection of ocular metastases in order to hasten oncological treatment. A low threshold for systemic investigations and ophthalmology referral in cases of unexplained, refractory ocular symptomatology is essential, given the heterogeneous presentation, rarity, and poor prognosis of these tumours, even with maximal treatment.

Abstract Background Knowledge management (KM) emerged as a strategy to promote evidence-informed decision-making. This scoping review aims to map existing KM tools and mechanisms used to promote evidence-informed health decision-making in the WHO European Region and identify knowledge gaps. Methods Following the Joanna Briggs Institute (JBI) guidance for conducting scoping reviews, we searched Medline, PubMed, EMBASE, the Cochrane library, and Open Grey. We conducted a descriptive analysis of the general characteristics of the included papers and conducted narrative analysis of the included studies and categorized studies according to KM type and phase. Results Out of 9541 citations identified, we included 141 studies. The KM tools mostly assessed are evidence networks, surveillance tools, observatories, data platforms and registries, with most examining KM tools in high-income countries of the WHO European region. Findings suggest that KM tools can identify health problems, inform health planning and resource allocation, increase the use of evidence by policymakers and stimulate policy discussion. Conclusion Policymakers and funding agencies are called to support capacity-building activities, and future studies to strengthen KM in the WHO European region particularly in Eastern Europe and Central Asia. An updated over-arching strategy to coordinate KM activities in the WHO European region will be useful in these efforts.

Objective The purpose of this study was to analyze quantitative values of normal and abnormal marrow on T1-weighted images of spine, to propose a ratio for T1 values of abnormal to normal vertebrae, and to assess whether this ratio could be helpful in predicting presence of neoplastic lesions in the spine.

Abstract Digital technologies change the healthcare environment, with several studies suggesting barriers and facilitators to using digital interventions by healthcare professionals (HPs). We consolidated the evidence from existing systematic reviews mentioning barriers and facilitators for the use of digital health technologies by HP. Electronic searches were performed in five databases (Cochrane Database of Systematic Reviews, Embase®, Epistemonikos, MEDLINE®, and Scopus) from inception to March 2023. We included reviews that reported barriers or facilitators factors to use technology solutions among HP. We performed data abstraction, methodological assessment, and certainty of the evidence appraisal by at least two authors. Overall, we included 108 reviews involving physicians, pharmacists, and nurses were included. High-quality evidence suggested that infrastructure and technical barriers (Relative Frequency Occurrence [RFO] 6.4% [95% CI 2.9–14.1]), psychological and personal issues (RFO 5.3% [95% CI 2.2–12.7]), and concerns of increasing working hours or workload (RFO 3.9% [95% CI 1.5–10.1]) were common concerns reported by HPs. Likewise, high-quality evidence supports that training/educational programs, multisector incentives, and the perception of technology effectiveness facilitate the adoption of digital technologies by HPs (RFO 3.8% [95% CI 1.8–7.9]). Our findings showed that infrastructure and technical issues, psychological barriers, and workload-related concerns are relevant barriers to comprehensively and holistically adopting digital health technologies by HPs. Conversely, deploying training, evaluating HP’s perception of usefulness and willingness to use, and multi-stakeholders incentives are vital enablers to enhance the HP adoption of digital interventions.

This paper examines the status of the development of national digital health information systems (HIS) in Commonwealth of Independent States (CIS) member states. Data for research were collected using a questionnaire adapted from the questionnaire of the WHO’s Third Global Survey on eHealth. The results showed that the digital transformation of HIS was occurring in all seven CIS member states (participating in the study), which were financed by different resources. Laws and regulations on electronic medical records (EMR) use were present in almost all participating CIS member states. Various international standards and classifications were used to support development and the interoperability of digital health information system (d-HIS), including International Classification of Diseases (ICD), Digital Imaging and Communications in Medicine (DICOM), ISO 18308, Logical Observation Identifiers, Names, and Codes (LOINC), Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), and ISO TC 215. Several CIS member states had adopted a national information security strategy for the safe processing of both personal data and medical confidential information. The digital transformation of healthcare and the Empowerment through Digital Health initiative are taking place in all CIS member states, which are at different stages of introducing electronic medical and health records.

Abstract One of the greatest challenges for widespread utilization of solar energy is the low conversion efficiency, motivating the needs of developing more innovative approaches to improve the design of solar energy conversion equipment. Solar cell is the fundamental component of a photovoltaic (PV) system. Solar cell’s precise modelling and estimation of its parameters are of paramount importance for the simulation, design, and control of PV system to achieve optimal performances. It is nontrivial to estimate the unknown parameters of solar cell due to the nonlinearity and multimodality of search space. Conventional optimization methods tend to suffer from numerous drawbacks such as a tendency to be trapped in some local optima when solving this challenging problem. This paper aims to investigate the performance of eight state-of-the-art metaheuristic algorithms (MAs) to solve the solar cell parameter estimation problem on four case studies constituting of four different types of PV systems: R.T.C. France solar cell, LSM20 PV module, Solarex MSX-60 PV module, and SS2018P PV module. These four cell/modules are built using different technologies. The simulation results clearly indicate that the Coot-Bird Optimization technique obtains the minimum RMSE values of 1.0264E-05 and 1.8694E−03 for the R.T.C. France solar cell and the LSM20 PV module, respectively, while the wild horse optimizer outperforms in the case of the Solarex MSX-60 and SS2018 PV modules and gives the lowest value of RMSE as 2.6961E−03 and 4.7571E−05, respectively. Furthermore, the performances of all eight selected MAs are assessed by employing two non-parametric tests known as Friedman ranking and Wilcoxon rank-sum test. A full description is also provided, enabling the readers to understand the capability of each selected MA in improving the solar cell modelling that can enhance its energy conversion efficiency. Referring to the results obtained, some thoughts and suggestions for further improvements are provided in the conclusion section.

Introduction A unilateral or bilateral pars interarticularis defect (spondylolysis) is a leading cause of axial back pain in adolescent athletes. Currently, a spectrum of imaging modalities is used for assessment of pars interarticularis defects. Objectives The aim of this study is to compare the accuracy of chemical shift sequence (magnetic resonance imaging [MRI]) technique to conventional MRI sequences in the detection of pars defects. Patients and Methods Conventional T1, T2, and short tau inversion recovery sagittal and axial, as well as “in-” and “out-” phase chemical shift sagittal MRI sequences of 70 consecutive patients referred for low back pain were reviewed. Demographic details, clinical indication, and presence/diagnosis of pars defects using a 5-point Likert scale on both conventional and chemical shift MRI sequences. Spearman's correlation was used for statistical analysis. Intraclass correlation coefficient analysis was evaluated to assess the intraclass reliability between observers. Data were analyzed using DATAtab web-based statistics software (2022). Results A total of 70 patients with an average age of 54.34 years with a female predominance were included. There were 11 pars defects in the cohort. Both in and out phases of chemical shift imaging were able to identify pars defect and intact pars. However, out phase was relatively better in delineating pars defects, while the in phase was superior in identifying an intact pars, though this was not statistically significant. There was good intra- and interobserver reliabilities. Conclusion Chemical shift MRI sequence is a quicker, complementary technique to assess and analyze pars interarticularis confidently than conventionally utilized MRI sequences in patients being evaluated for axial back pain.

Introduction Cryoablation is the destruction of living tissue by the application of extreme freezing temperature. There has been an increase in the use of cryoablation in the management of musculoskeletal lesions, in particular fibromatosis. Aim This study aimed to measure the average and relative increase in size of the cryoablation ice ball after the first (10 minutes) and second freeze cycles (20 minutes) to accurately predict the size of the ice ball between first and second freezes to help prevent any unwanted damage of the nearby skin and neurovascular structures. This is especially important when ablating in relatively small body parts such as in the appendicular skeleton. Material and Methods Eight patients treated with cryoablation over a 12-month period for fibromatosis were, included in the study. The size and volume of the ice ball were measured during the first and second cycle of cryoablation. Results The average patient age of the cohort was 35.6 years old (min 28 and max 43). There was female predominance in the study (3:2, F:M). There was a significant increase (26%) in the linear dimensions and almost doubling in the volume of the ice ball between freeze cycles (p-value = 0.0037 for dimensions and p-value = 0.0002 for volumes). Conclusion This pilot study is a preliminary attempt to predict the eventual size of the ice ball during cryoablation procedures when treating cases of fibromatosis. This should help in planning cryoablation to ensure decrease morbidity by preventing injury to adjacent critical structures (neurovascular bundle and skin).

We present a genome assembly from an individual Zeus faber (the John Dory; Chordata; Actinopteri; Zeiformes; Zeidae). The genome sequence is 804.7 megabases in span. Most of the assembly is scaffolded into 22 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 16.72 kilobases in length.

Introduction Premature onset of type 2 diabetes and excess mortality are critical issues internationally, particularly in Indigenous populations. There is an urgent need for developmentally appropriate and culturally safe models of care. We describe the methods for the codesign, implementation and evaluation of enhanced models of care with Aboriginal and Torres Strait Islander youth living with type 2 diabetes across Northern Australia.Methods and analysis Our mixed-methods approach is informed by the principles of codesign. Across eight sites in four regions, the project brings together the lived experience of Aboriginal and Torres Strait Islander young people (aged 10–25) with type 2 diabetes, their families and communities, and health professionals providing diabetes care through a structured yet flexible codesign process. Participants will help identify and collaborate in the development of a range of multifaceted improvements to current models of care. These may include addressing needs identified in our formative work such as the development of screening and management guidelines, referral pathways, peer support networks, diabetes information resources and training for health professionals in youth type 2 diabetes management. The codesign process will adopt a range of methods including qualitative interviews, focus group discussions, art-based methods and healthcare systems assessments. A developmental evaluation approach will be used to create and refine the components and principles of enhanced models of care. We anticipate that this codesign study will produce new theoretical insights and practice frameworks, resources and approaches for age-appropriate, culturally safe models of care.Ethics and dissemination The study design was developed in collaboration with Aboriginal and Torres Strait Islander and non-Indigenous researchers, health professionals and health service managers and has received ethical approval across all sites. A range of outputs will be produced to disseminate findings to participants, other stakeholders and the scholarly community using creative and traditional formats.

Adolescent birth rates in Lao People's Democratic Republic (PDR) remain the highest in Southeast Asia. There is growing recognition that adolescent pregnancy in Lao PDR is occurring within and outside marriage, but there is a lack of robust qualitative evidence to understand girls' pathways to adolescent pregnancy and contributing factors, especially outside of union (cohabitation or marriage). This study aimed to improve understanding of pathways to adolescent pregnancy in Lao PDR among girls who experienced pregnancy at age 18 or below. We conducted participatory timeline interviews with 57 girls from urban, peri-urban, and rural communities in Vientiane Capital, Vientiane Province, and Luang Namtha, and follow-up interviews with a subset of 20 girls. We identified six pathways to pregnancy, including pathways outside (n = 23) and within union (n = 34). Outside-union pathways diverged according to the nature of sex preceding pregnancy (consensual/pressured, or forced), and pregnancy intention (unplanned, partner-led, or planned). Within-union pathways diverged according to the nature of the relationship before union (romantic or no romantic relationship/arranged union), who initiated the union (couple/girl, parent/partner, or pressured), and pregnancy intention. Factors contributing to girls' pregnancy included barriers to sexual and reproductive health (SRH) information and services; partner's control over reproductive decision-making; male sexual entitlement and alcohol use driving pressured/forced sex; cultural acceptance of child marriage and early union; and attitudes and norms regarding sex and pregnancy outside of union. Our findings support strengthening comprehensive sexuality education, including a focus on addressing myths about contraception, building girls' and boys' communication skills, engaging in respectful relationships, and addressing harmful gender norms. Our findings also highlight the need to improve girls' access to adolescent-responsive SRH services, address harmful substance use, challenge sociocultural barriers to young people accessing SRH information and services, and respond to sociocultural and financial drivers of child marriage/early union that contribute to adolescent pregnancy.

Abstract Background Adolescent pregnancy has significant health and socio-economic consequences for women, their families and communities. Efforts to prevent too-early pregnancy rely on accurate information about adolescents' knowledge, behaviours and access to family planning, however available data are limited in some settings. Demographic and Health Survey (DHS) reports are recognised as providing nationally representative data that are accessible to policymakers and programmers. This paper reviews DHS reports for low and lower middle income countries in East Asia and the Pacific to determine what information regarding adolescent fertility and family planning is available, and summarises key findings. Methods The most recent DHS reports were sought for the 33 low and lower middle income countries in the East Asia and Pacific region as defined by UNICEF and World Bank. Age-disaggregated data for all indicators relevant to fertility and current use, knowledge and access to family planning information and services were sought to identify accessible information. Reported data were analysed using an Excel database to determine outcomes for adolescents and compare with adult women. Results DHS reports were available for eleven countries: Cambodia, Indonesia, Marshall Islands, Nauru, Papua New Guinea, Philippines, Samoa, Solomon Islands, Timor-Leste, Tuvalu and Vietnam. Twenty seven of 40 relevant DHS indicators reported outcomes for adolescent women aged 15-19 years. There were limited data for unmarried adolescents. A significant proportion of women commence sexual activity and childbearing during adolescence in the context of low contraceptive prevalence and high unmet need for contraception. Adolescent women have lower use of contraception, poorer knowledge of family planning and less access to information and services than adult women. Conclusion DHS reports provide useful and accessible data, however, they are limited by the failure to report data for unmarried adolescents and report age-disaggregated data for some indicators. Further research is required to better understand the barriers that both married and unmarried adolescents face accessing reproductive health information and services, and their information and service delivery preferences.

Abstract There are strong links between heritage and the environment yet, heritage is not fully included in existing ecosystem‐based frameworks. Different understandings of heritage values exist, and heritage values are not yet related to key value categories in environmental values research. To address this gap and facilitate a common values‐based approach, we develop a novel framework that links heritage and environmental values. First, we expand the understanding of heritage values by linking heritage to key environmental value categories. We then use the Life Framework of Values to show how heritage features in the different ways in which people relate to the world. The resulting heritage values framework is operationalised by applying it to six case examples drawn from participatory research on the governance of European coastal and maritime heritage. We found that the environment was not only considered to be a setting for heritage but was itself valued as heritage in different ways; that heritage is not extrinsic to the environment but is also a way in which people see meaning in the environment; and that multiple value frames and types were involved in shaping this perspective. The results highlight important discrepancies between stakeholders' perspectives and existing management approaches. Applying the framework shows the ways in which heritage and nature are entwined by providing a structure for elucidating what can be valued as heritage, what values can inform heritage values and how heritage values feature in human–nature relations. Read the free Plain Language Summary for this article on the Journal blog.

Medicines can be taken by various routes of administration. These can impact the effects and perceptions of medicines. The literature about individuals' preferences for and perceptions of the different routes of administration is sparse, but indicates a potential influence of culture. Our aim was to determine: (i) any association between one's culture and one's preferred route of medicine administration and (ii) individual perceptions of pain, efficacy, speed of action and acceptability when medicines are swallowed or placed in the mouth, under the tongue, in the nose, eye, ear, lungs, rectum, vagina, on the skin, or areinjected.A cross-sectional, questionnaire-based survey of adults was conducted in 21 countries and regions of the world, namely, Tunisia, Ghana, Nigeria, Turkey, Ethiopia, Lebanon, Malta, Brazil, Great Britain, United States, India, Serbia, Romania, Portugal, France, Netherlands, Japan, South Korea, Hong Kong, mainland China and Estonia, using the Inglehart–Welzel cultural map to ensure coverage across all cultures. Participants scored the pain/discomfort, efficacy, speed of onset and acceptability of the different routes of medicine administration and stated their preferred route. Demographic information was collected.A total of 4435 participants took part in the survey. Overall, the oral route was the most preferred route, followed by injection, while the rectal route was the least preferred. While the oral route was the most preferred in all cultures, the percentage of participants selecting this route varied, from 98% in Protestant Europe to 50% in the African-Islamic culture. A multinomial logistic regression model revealed a number of predictors for the preferred route. Injections were favoured in the Baltic, South Asia, Latin America and African-Islamic cultures while dermal administration was favoured in Catholic Europe, Baltic and Latin America cultures. A marked association was found between culture and the preference for, and perceptions of the different routes by which medicines are taken. This applied to even the least favoured routes (vaginal and rectal). Only women were asked about the vaginal route, and our data shows that the vaginal route was slightly more popular than the rectal one.

Summary: Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2−8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27–2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32–0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69–3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26–0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3–2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.

In multilevel inverters (MLI), output voltage waveform consists of dominant low order harmonics, which needs to be minimized. Simultaneously, good control over the fundamental voltage for desirable operation is needed. In this paper, an atom search optimization (ASO) based selective harmonic elimination (SHE) method is proposed for a variable dc bus based reduced component count (RCC) MLI. ASO is a population-based metaheuristic algorithm, which mathematically models the motion of atoms in nature to accurately determine the optimum firing angle of the switches by solving SHE fitness function. The proposed ASO SHE method outperforms recent metaheuristics based SHE methods such as bee algorithm, imperialistic colonial algorithm (ICA), firefly, particle swarm optimization (PSO), and teaching learning-based optimization (TLBO) in solving SHE problem for 11-level multilevel inverter. Detailed simulation case studies are presented to effectively demonstrate the performance of the proposed ASO SHE method on a stand-alone photovoltaic (PV) based RCC MLI subjected to sudden changes in irradiance, load and dc-link capacitor voltage. The experimental results on a PV based variable dc bus multilevel inverter validate the excellent performance of ASO SHE method in minimizing the total harmonic distortion (THD) and dominant order harmonics under sudden change in operating conditions.

Background Vertebral insufficiency fractures in the elderly are associated with increased morbidity and mortality. Early diagnosis is essential to direct patient-specific rehabilitation. Aims We hypothesize that in patients with vertebral insufficiency fractures, there is atrophy of the psoas and paraspinal muscles with alteration in the cross-sectional area (CSA) of the muscles. Materials and Methods Magnetic resonance imaging (MRI) studies for 100 consecutive patients, older than 60 years presenting with lower back pain, were included in the study. For each MRI study, the CSA of the psoas and paraspinal muscles (multifidus) at the level of L4/5-disc space was measured to calculate the cross-sectional area ratio (CSAR) by two readers. One reader repeated the measurements after an interval of 2 weeks. We divided the patients (n = 100) into various groups based on the number of vertebral fractures. Results In total, 77 patients with vertebral body fractures (48 with one, 16 with two and 13 with more than two fractures) were identified with a mean age of 73 (range 60–92) years. The ratio of multifidus CSA to psoas CSA was calculated with mean values of each group (1–4) as 2.56, 1.89, 2.09 and 2.16, respectively. There was statistically significance difference of the CSAR between the cohorts (p-value = 0.0115). Conclusion Vertebral insufficiency fractures in the elderly are associated not only with atrophy of psoas and the multifidus group of muscles as evident by the CSA values, but they also affect the CSAR depending on the number of fractures. This finding may help to direct targeted patient-specific physiotherapy rehabilitation and interventions to prevent further such fractures.

Balini Balasubramaniam,1 Yu Jeat Chong,2 Matthew Azzopardi,3 Abison Logeswaran,4 Alastair K Denniston1 1Ophthalmology Department, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK; 2Birmingham & Midland Eye Centre, Birmingham, B18 7QH, UK; 3Ophthalmology Department, Royal London Hospital, Barts Health NHS Trust, London, E1 1BB, UK; 4Moorfields Eye Hospital NHS Foundation Trust, London, UKCorrespondence: Yu Jeat Chong, Birmingham & Midland Eye Centre, Dudley Road, Birmingham, B18 7QH, UK, Email yu.chong.2@city.ac.ukAbstract: Non-infectious uveitis represents a heterogenous group of immune-mediated ocular diseases, which can be associated with underlying systemic disease. While the initial choice of treatment of non-infectious uveitis depends on a number of factors such as anatomical location and degree of inflammation, topical therapies often remain the initial choice of non-invasive therapy. In this narrative review, we aim to describe the literature on non-infectious uveitis, with specific focus on the current perspective on topical anti-inflammatory therapy.Keywords: non-infectious uveitis, topical anti-inflammatory therapy, topical corticosteroids, topical non-steroid anti-inflammatory drugs, topical cycloplegics

An enhanced version of the moth flame optimization algorithm is proposed in this paper for rapid and precise parameter extraction of solar cells. The proposed OBLVMFO algorithm’s novelty lies primarily in the improved search strategies, where two modifications are proposed to maintain a proper balance between exploration and exploitation. Firstly, an opposition-based learning mechanism is employed to initialize the search population for the purpose of enhancing the global search. Secondly, Lévy flight distribution is used to prevent the stagnation of solutions in local minima. The implementation of intelligent rules such as OBL and Lévy flight distribution significantly improves the performance of the standard MFO. The developed OBLVMFO performed adequately and is reliable in terms of RMSE compared to other methodologies such as MFO, ALO, SCA, MRFO, and WOA. The best optimized value of RMSE achieved by OBLVMFO is 6.060E−04, 1.3600E−05, and 7.0001E−06 for STE 4/100 (polycrystalline), LSM 20 (monocrystalline), and SS2018P (polycrystalline) PV modules, respectively. The experiments performed on the benchmark test function revealed that the OBLVMFO has a 61% faster convergence speed than the standard version of MFO, which improves solution accuracy. In addition to this, two non-parametric tests: Friedman ranking and Wilcoxon rank sum are performed for the validation.

Key Clinical Message Iliac artery‐enteric fistula is a rare cause of lower GI bleeding and can cause life‐threatening consequences. A high degree of clinical suspicion is needed in patients with previous aortic surgery to allow early multidisciplinary intervention. Abstract This case study discusses the staged management of a 78‐year‐old patient presenting with life‐threatening lower gastrointestinal (GI) bleeding secondary to an aortoiliac graft‐enteric fistula (GEF) into the sigmoid colon on the background of an adenocarcinoma and diverticular disease. The patient had an aorto bi‐iliac synthetic dacron graft repair of an abdominal aortic aneurysm (AAA) some 20 years ago. Here, we present a case of successful endovascular treatment of massive hemorrhage as a bridge to definitive second‐stage dacron graft explant and autologous vein reconstruction with a simultaneous anterior resection.

IntroductionVariation in stage at diagnosis of childhood cancers (CC) may explain differences in survival rates observed across geographical regions. The BENCHISTA project aims to understand these differences and to encourage the application of the Toronto Staging Guidelines (TG) by Population-Based Cancer Registries (PBCRs) to the most common solid paediatric cancers.MethodsPBCRs within and outside Europe were invited to participate and identify all cases of Neuroblastoma, Wilms Tumour, Medulloblastoma, Ewing Sarcoma, Rhabdomyosarcoma and Osteosarcoma diagnosed in a consecutive three-year period (2014-2017) and apply TG at diagnosis. Other non-stage prognostic factors, treatment, progression/recurrence, and cause of death information were collected as optional variables. A minimum of three-year follow-up was required. To standardise TG application by PBCRs, on-line workshops led by six tumour-specific clinical experts were held. To understand the role of data availability and quality, a survey focused on data collection/sharing processes and a quality assurance exercise were generated. To support data harmonization and query resolution a dedicated email and a question-and-answers bank were created.Results67 PBCRs from 28 countries participated and provided a maximally de-personalized, patient-level dataset. For 26 PBCRs, data format and ethical approval obtained by the two sponsoring institutions (UCL and INT) was sufficient for data sharing. 41 participating PBCRs required a Data Transfer Agreement (DTA) to comply with data protection regulations. Due to heterogeneity found in legal aspects, 18 months were spent on finalizing the DTA. The data collection survey was answered by 68 respondents from 63 PBCRs; 44% of them confirmed the ability to re-consult a clinician in cases where stage ascertainment was difficult/uncertain. Of the total participating PBCRs, 75% completed the staging quality assurance exercise, with a median correct answer proportion of 92% [range: 70% (rhabdomyosarcoma) to 100% (Wilms tumour)].ConclusionDifferences in interpretation and processes required to harmonize general data protection regulations across countries were encountered causing delays in data transfer. Despite challenges, the BENCHISTA Project has established a large collaboration between PBCRs and clinicians to collect detailed and standardised TG at a population-level enhancing the understanding of the reasons for variation in overall survival rates for CC, stimulate research and improve national/regional child health plans.

Summary: Systematic reviews have quantified the effectiveness, feasibility, acceptability, and cost-effectiveness of digital health technologies (DHTs) used by health-care workers. We aimed to collate available evidence on technologies’ effect on health-care workers’ competencies and performance. We searched the Cochrane Database of Systematic Reviews, Embase, MEDLINE, Epistemonikos, and Scopus for reviews published from database inception to March 1, 2023. Studies assessing the effects of DHTs on the organisational, socioeconomic, clinical, and epidemiological levels within the workplace, and on health-care workers’ performance parameters, were included. Data were extracted and clustered into 25 domains using vote counting based on the direction of effect. The relative frequency of occurrence (RFO) of each domain was estimated using R software. AMSTAR-2 tool was used to appraise the quality of reporting, and the Confidence in the Evidence from Reviews of Qualitative research approach developed by Grading of Recommendations Assessment, Development and Evaluation was used to analyse the certainty of evidence among included studies. The 12 794 screened reviews generated 132 eligible records for assessment. Top-ranked RFO identifiers showed associations of DHT with the enhancement of health-care workers’ performance (10·9% [95% CI 5·3–22·5]), improvement of clinical practice and management (9·8% [3·9–24·2]), and improvement of care delivery and access to care (9·2% [4·1–20·9]). Our overview found that DHTs positively influence the daily practice of health-care workers in various medical specialties. However, poor reporting in crucial domains is widely prevalent in reviews of DHT, hindering our findings’ generalisability and interpretation. Likewise, most of the included reviews reported substantially more data from high-income countries. Improving the reporting of future studies and focusing on low-income and middle-income countries might elucidate and answer current knowledge gaps.