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Abstract Yield gap analysis is used to characterize the untapped production potential of cropping systems. With emerging large-n agronomic datasets and data science methods, pathways for narrowing yield gaps can be identified that provide actionable insights into where and how cropping systems can be sustainably intensified. Here we characterize the contributing factors to rice yield gaps across seven Indian states, with a case study region used to assess the power of intervention targeting. Primary yield constraints in the case study region were nitrogen and irrigation, but scenario analysis suggests modest average yield gains with universal adoption of higher nitrogen rates. When nitrogen limited fields are targeted for practice change (47% of the sample), yield gains are predicted to double. When nitrogen and irrigation co-limitations are targeted (20% of the sample), yield gains more than tripled. Results suggest that analytics-led strategies for crop intensification can generate transformative advances in productivity, profitability, and environmental outcomes.

Abstract Background There is a well-established cross-sectional association between income and health, but estimates of the causal effects of income vary substantially. Different definitions of income may lead to substantially different empirical results, yet research is often framed as investigating “the effect of income” as if it were a single, easily definable construct. Methods/Results The aim of this paper is to introduce a taxonomy for definitional and conceptual issues in studying individual- or household-level income for health research. We focus on (1) the definition of the income measure (earned and unearned; net, gross, and disposable; real and nominal; individual and household; relative and absolute income) and (2) the definition of the causal contrast (amount, functional form assumptions/transformations, direction, duration of change, and timing of exposure and follow-up). We illustrate the application of the taxonomy to four examples from the published literature. Conclusions Quantified estimates of causal effects of income on health and wellbeing have crucial relevance for policymakers to anticipate the consequences of policies targeting the social determinants of health. However, much prior evidence has been limited by lack of clarity in distinguishing between different causal questions. The present framework can help researchers explicitly and precisely articulate income-related exposures and causal questions.

Background: British soldiers undergoing jungle training in Belize typically experience a relatively low risk of developing cutaneous leishmaniasis. However, an uncharacteristically large outbreak of cutaneous leishmaniasis occurred in 2022. This study aimed to determine the cumulative incidence of the disease and highlight potential shortcomings in personal protective measures to mitigate exposure to sand fly vector bites. Methods: A retrospective analysis was conducted on medical records of cutaneous leishmaniasis cases between 2005 and 2022, as well as on questionnaire responses regarding personal protective measures administered to cutaneous leishmaniasis cases in 2022. Data were sourced from Defence Public Health Unit, Military Environmental Health Department and British Army Training Support Unit Belize. Results: Eighty-one confirmed clinical cutaneous leishmaniasis cases were recorded between 2005 and 2022, with a substantial peak (38 cases) in 2022. Most cases occurred during the wet season. Pre-2022, the median cumulative incidence per 8-week deployment was 0.90 % (Q1–Q3: 0.34 %–1.34 %), with an annual variation of 0.2 % to 2.0 %. In 2022, the cumulative incidence spiked to 4.22 %, associated with a risk ratio of 5.3 (95 % C.I.s, 3.41, 8.16), and rising to a cumulative incidence of 7.3 % in a single unit of 450 men (33 cases) in late 2022. These values are significantly higher than the median cumulative incidence of all previous years, and to published reports for other cutaneous leishmaniasis -endemic regions. Troop responses identified limitations in the supply of optimal equipment, and in sand fly bite and leishmaniasis risk avoidance information provided by the pre-deployment health education programme. Compliance with health education advise was also suboptimal, with irregular use of insect repellents, protective clothing / head netting, and insecticide-treated hammocks. Conclusions: The reasons behind the unusually high numbers of cutaneous leishmaniasis cases and cumulative incidence in 2022 remain unclear, emphasising the need to improve personal protective measures provision and implement a comprehensive health education programme for troops undergoing jungle training in Belize.

Abstract The lumped element network model has been proven to be an efficient tool for the interpretation of transformer Frequency Response Analysis. However, it is challenging to obtain parameters of the model if transformer design information is unavailable. In such a case, optimisation algorithms can be used for gray‐box model parameter estimation. A methodology is developed by the authors to establish a transformer network model without winding design data, and instead, end‐to‐end open circuit Frequency Response and other terminal test results are utilised; and Genetic Algorithm is applied to approximate the unknown parameters of the model. The modelling approach developed is independent of the unit number of the network model and therefore guarantees the accuracy of optimisation. Furthermore, it can deal with transformers with a complicated winding structure such as interleaved disc type winding. Two single windings, helical and interleaved disc type, and a single‐phase 144/13 kV 60 MVA transformer are used to demonstrate the method. FRA spectra produced by the best estimated gray‐box model and the corresponding white‐box model are compared. The main features in amplitude and phase spectra are well matched, with low values of Relative Standard Deviation, for both single windings and transformer. Estimated electrical parameters show a high consistency with reference values, which are calculated based on winding design data. This validates the methodology and gives confidence to apply grey‐box modelling for FRA interpretation.

With the widespread use of Generative AI in education, effectively utilizing and integrating it into teaching have become key focal points and challenges in education. Different subjects and target audiences require varied norms and strategies for implementing Generative AI, such as ChatGPT. These differences directly impact the educational integration of Generative AI in various educational contexts. To address these disparities and establish common ground, we propose the concept of ChatGPT literacy to bridge research gaps. In this study, we tailor the concept of ChatGPT literacy specifically for language teachers, aiming to delineate the essential competencies needed to proficiently and ethically use ChatGPT as a language learning and teaching tool. We propose a theoretical framework encompassing six fundamental constructs: benefits, limitations, prompts, evaluation (of ChatGPT responses), assessment (assisted by ChatGPT), and ethics, to comprehensively conceptualise and evaluate ChatGPT literacy. Drawing on both quantitative and qualitative survey data from 492 language teachers across 41 countries, we validate the proposed ChatGPT literacy framework by examining teachers' practices and challenges associated with ChatGPT usage. Our analysis of Likert-scale data, utilizing item and confirmatory techniques, confirms the effectiveness of the six-construct framework in defining ChatGPT literacy. In addition, we collected qualitative data through open questions and conducted thematic analysis, demonstrating that ChatGPT has been integrated throughout the instructional cycle, from material preparation to formative and summative assessment phases. These quantitative and qualitative findings have significant implications for a range of stakeholders, including language educators, learners, AI technology developers, and policymakers, providing valuable insights to inform decisions regarding ChatGPT integration in language education. Ultimately, our study equips relevant stakeholders with the necessary competencies to responsibly exploiting ChatGPT's potential in language and other subject areas.

The global increase in antibiotic resistances demands for additional efforts to identify novel antimicrobials such as bacteriocins. These antimicrobial peptides of bacterial origin are already used widely in food preservation and promising alternatives for antibiotics in animal feed and some clinical setting. Identification of novel antimicrobials is facilitated by appropriate high throughput screening (HTS) methods. Previously, we have described a rapid, simple and cost-efficient assay based on live biosensor bacteria for detection of antimicrobial compounds that act on membrane integrity using the ratiometric pH-dependent fluorescent protein pHluorin2 (pHin2). Here, we use these biosensors to develop an integrated pipeline for high-throughput identification of bacteriocin producers and their biosynthetic gene clusters. We extend the existing portfolio of biosensors by generating pHin2 expressing strains of Escherichia coli, Bacillus cereus, Staphylococcus epidermidis, and methicillin-resistant Staphylococcus aureus. These strains were characterized, and control experiments were performed to assess heterogeneity of these biosensors in response to known bacteriocins and develop a robust HTS system. To allow detection of compounds that inhibit target bacteria by inhibiting growth without disturbing membrane integrity, the HTS system was extended with a growth-dependent readout. Using this HTS system, we screened supernatants of a total of 395 strains of a collection of lactic acid bacteria. After two rounds of screening 19 strains of the collection were identified that produced antimicrobial activity against Listeria innocua and Listeria monocytogenes. Genomes of confirmed hits were sequenced and annotated. In silico analysis revealed that the identified strains encode between one and six biosynthetic gene clusters (BGCs) for bacteriocins. Our results suggest that pHin2 biosensors provides a flexible, cheap, fast, robust and easy to handle HTS system for identification of potential bacteriocins and their BGCs in large strain collections.

Background Electronic health records (EHRs) have the potential to be used to produce detailed disease burden estimates. In this study we created disease estimates using national EHR for three high burden conditions, compared estimates between linked and unlinked datasets and produced stratified estimates by age, sex, ethnicity, socio-economic deprivation and geographical region. Methods EHRs containing primary care (Clinical Practice Research Datalink), secondary care (Hospital Episode Statistics) and mortality records (Office for National Statistics) were used. We used existing disease phenotyping algorithms to identify cases of cancer (breast, lung, colorectal and prostate), type 1 and 2 diabetes, and lower back pain. We calculated age-standardised incidence of first cancer, point prevalence for diabetes, and primary care consultation prevalence for low back pain. Results 7.2 million people contributing 45.3 million person-years of active follow-up between 2000–2014 were included. CPRD-HES combined and CPRD-HES-ONS combined lung and bowel cancer incidence estimates by sex were similar to cancer registry estimates. Linked CPRD-HES estimates for combined Type 1 and Type 2 diabetes were consistently higher than those of CPRD alone, with the difference steadily increasing over time from 0.26% (2.99% for CPRD-HES vs. 2.73 for CPRD) in 2002 to 0.58% (6.17% vs. 5.59) in 2013. Low back pain prevalence was highest in the most deprived quintile and when compared to the least deprived quintile the difference in prevalence increased over time between 2000 and 2013, with the largest difference of 27% (558.70 per 10,000 people vs 438.20) in 2013. Conclusions We use national EHRs to produce estimates of burden of disease to produce detailed estimates by deprivation, ethnicity and geographical region. National EHRs have the potential to improve disease burden estimates at a local and global level and may serve as more automated, timely and precise inputs for policy making and global burden of disease estimation.

Introduction Pain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective.Methods and analysis The Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement.Ethics and dissemination The trial was approved by the London—Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist.Trial registration number ISRCTN87336549.

Abstract Background Antimicrobial resistance (AMR) is a growing global concern. AMR surveillance is a crucial component of the international response; however, passive surveillance of laboratory data is limited without corresponding patient-level clinical data. This study sought to examine the burden of AMR amongst medical inpatients in Rwanda, in the context of their clinical presentations and prior antibiotic exposures. Methods This cohort study was conducted over a 9-month period at a tertiary referral hospital in Kigali, Rwanda. We enrolled 122 adult medical inpatients with a history of fever and a positive microbiological culture result. Data were collected regarding the clinical and microbiological aspects of their admission. Results The most common diagnoses were urinary tract infection (n = 36, 30%), followed by pneumonia (n = 30, 25%) and bacteraemia (11 primary [9%] and 10 catheter-related [8%]). The most common pathogens were E. coli (n = 40, 33%) and Klebsiella pneumoniae (n = 36, 30%). The cohort were heavily antibiotic-exposed at the time of culture with 98% of patients (n = 119) having received an antibiotic prior to culture, with a median exposure of 3 days (IQR 2–4 days). Eighty patients (66%) were specifically prescribed ceftriaxone at the time of culture. Gram-negative organisms predominated (82% [100/122]) and exhibited high rates of resistance, with only 27% (21/77) being susceptible to ceftriaxone, 2.4% (2/82) susceptible to co-amoxiclav and 44% (8/18) susceptible to ciprofloxacin. Susceptibility amongst Gram-negatives was relatively preserved to amikacin (91%, 79/87) and imipenem (85%, 70/82). There were no cases of methicillin-resistant Staphylococcus aureus (0/12) or vancomycin-resistant enterococci (0/2). Discordant antibiotic therapy was significantly associated with in-hospital mortality (OR 6.87, 95%CI 1.80–45.1, p = 0.014). Conclusions This cohort highlights high rates of resistance amongst Gram-negative organisms in Rwanda, including the presence of carbapenem resistance. Nonetheless, the detailed prescribing data also highlight the challenges of using routine laboratory data to infer broader AMR prevalence. The significant exposure to empiric broad-spectrum antibiotic therapy prior to culturing introduces a selection bias and risks over-estimating the burden of resistant organisms. Broadening access to microbiological services and active surveillance outside of teaching hospitals are essential to support national and international efforts to curb the growth of AMR in low-resource settings.

Abstract Gene-edited mosquitoes lacking a gamma-interferon-inducible lysosomal thiol reductase-like protein, namely (mosGILT null ) have lower Plasmodium infection, which is linked to impaired ovarian development and immune activation. The transcriptome of mosGILT null Anopheles gambiae was therefore compared to wild type (WT) mosquitoes by RNA-sequencing to delineate mosGILT-dependent pathways. Compared to WT mosquitoes, mosGILT null A. gambiae demonstrated altered expression of genes related to oogenesis, 20-hydroxyecdysone synthesis, as well as immune-related genes. Serendipitously, the zero population growth gene, zpg, an essential regulator of germ cell development was found to be one of the most downregulated genes in mosGILT null mosquitoes. These results provide a crucial missing link between two previous studies on the role of zpg and mosGILT in ovarian development. This study further demonstrates that mosGILT has the potential to serve as a target for the biological control of mosquito vectors and to influence the Plasmodium life cycle within the vector.

Wheat (Triticum aestivum L.) yield in Indo-Gangetic plain of eastern India is much less than its actual potential. Apart from several yield deterministic factors, late sowing of wheat is one of the major reasons for sub-optimal wheat yield. The persistent yield gap poses a threat to future food security of this region with a vast population that is growing rapidly. In the present research, an attempt was made to quantify and classify the yield losses in wheat due to late sowing which is prevalent in this part of India. On-farm participatory agronomic trial was conducted at 1073 plots in 3 districts of eastern India, 2 from Uttar Pradesh and 1 from the state of Bihar. The trial was conducted during four consecutive winter season from 2016–17 to 2019–20. Following a split-plot design, main plots were categorized based on wheat sowing time and sub-plots were classified depending on the wheat varietal class. A sample survey of randomly selected 629 wheat farmers was conducted in 2017–18 wheat season in these 3 districts. Results from the agronomic trial showed that wheat yield decreased by 58 kg/ha for every one-day delay in sowing. Moreover, the yield of long-duration improved wheat variety (HD-2967) was statistically same (P=0.479) compared to the most preferred short-duration variety (PBW-373) in a very late-sown scenario (late December). Farmers’ survey data reconfirmed that the wheat yield has a very strong negative correlation with the sowing dates, but the yield decline was statistically insignificant until mid-November. Wheat yield in this part of India can be adequately boosted if sowing time of wheat advances and adoption of long-duration improved wheat varieties improves.

Abstract Background Immunosuppressive therapies have become a cornerstone of the management of severe COVID-19. The impact of these therapies on secondary infections and antimicrobial prescribing remains unclear. We sought to assess antimicrobial use and the incidence of bacterial and fungal infections in patients with severe COVID-19, and to explore their associations with receipt of immunosuppressive therapies. Methods Our retrospective cohort study included 715 hospitalised, adult patients with severe COVID-19 admitted to St George’s Hospital, London, UK, during the first UK pandemic wave (1st March–10th June 2020). Co-infections (occurring within 48 h of admission) and secondary infections (≥ 48 h) were defined as a positive microbiological culture with supporting clinical, radiological or laboratory data to suggest true infection. Cox regression models with time-dependent covariates were used to explore the association between immunosuppressant use and secondary infection. Results Microbiologically confirmed co-infection occurred in 4.2% (n = 30) and secondary infection in 9.3% (n = 66) of the cohort (n = 715) and were associated with in-hospital mortality (48% vs 35%, OR 1.8, 95%CI 1.1–2.7, p = 0.01). Respiratory (n = 41, 39%) and bloodstream infections (n = 38, 36%) predominated, with primarily Gram-negative pathogens. 606 (84.7%) patients received an antimicrobial, amounting to 742 days of therapy per 1000 patient-days (DOTs). In multivariable models, receipt of high-dose steroids (≥ 30 mg prednisolone or equivalent) or tocilizumab was significantly associated with increased antimicrobial consumption (+ 5.5 DOTs, 95%CI 3.4–7.7 days) but not secondary infection (HR 0.56, 95%CI 0.26–1.18). Conclusions Bacterial and fungal infections in severe COVID-19 were uncommon. Receipt of steroids or tocilizumab was independently associated with antimicrobial consumption despite its lack of association with secondary infection. These findings should galvanise efforts to promote antimicrobial stewardship in patients with COVID-19.

Abstract Purpose The COVID-19 pandemic increased psychiatric distress and impacts differed by family structure. We aimed to identify mechanisms contributing to these inequalities. Methods Survey data were from the UK Household Longitudinal Study. Psychiatric distress (GHQ-12) was measured in April 2020 (first UK lockdown; n = 10,516), and January 2021 (lockdown re-introduced following eased restrictions; n = 6,893). Pre-lockdown family structure comprised partner status and presence of children (

Objective To determine the socio-demographic profile of all students enrolled to study medicine in Aotearoa New Zealand (NZ).Design and setting Observational, cross-sectional study. Data were sought from the Universities of Auckland and Otago, the two NZ tertiary education institutions providing medical education, for the period 2016–2020 inclusive. These data are a subset of the larger project ‘Mirror on Society’ examining all regulated health professional enrolled students in NZ. Variables of interest: gender, citizenship, ethnicity, rural classification, socioeconomic deprivation, school type and school socioeconomic scores. NZ denominator population data (18–29 years) were sourced from the 2018 census.Participants 2858 students were enrolled to study medicine between 2016 and 2020 inclusive.Results There were more women (59.1%) enrolled to study medicine than men (40.9%) and the majority (96.5%) were in the 18–29 years age range. Māori students (rate ratio 0.92; 95% CI 0.84 to 1.0) and Pacific students (rate ratio 0.85; 95% CI 0.73 to 0.98) had lower overall rates of enrolment. For all ethnic groups, irrespective of rural or urban origin, enrolment rates had a nearly log-linear negative relationship with increasing socioeconomic deprivation. Enrolments were lower for students from rural areas compared with those from urban areas (rate ratio 0.53; 95% CI 0.46–0.61). Overall NZ’s medical students do not reflect the diverse communities they will serve, with under-representation of Māori and Pacific students and students who come from low socioeconomic and rural backgrounds.Conclusions To meaningfully address these issues, we suggest the following policy changes: universities commit and act to Indigenise institutional ways of knowing and being; selection policies are reviewed to ensure that communities in greatest need of doctors are prioritised for enrolment into medicine (specifically, the impact of low socioeconomic status should be factored into selection decisions); and the government fund more New Zealanders to study medicine.

Abstract Background Addressing persistent and pervasive health inequities is a global moral imperative, which has been highlighted and magnified by the societal and health impacts of the COVID-19 pandemic. Observational studies can aid our understanding of the impact of health and structural oppression based on the intersection of gender, race, ethnicity, age and other factors, as they frequently collect this data. However, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline, does not provide guidance related to reporting of health equity. The goal of this project is to develop a STROBE-Equity reporting guideline extension. Methods We assembled a diverse team across multiple domains, including gender, age, ethnicity, Indigenous background, disciplines, geographies, lived experience of health inequity and decision-making organizations. Using an inclusive, integrated knowledge translation approach, we will implement a five-phase plan which will include: (1) assessing the reporting of health equity in published observational studies, (2) seeking wide international feedback on items to improve reporting of health equity, (3) establishing consensus amongst knowledge users and researchers, (4) evaluating in partnership with Indigenous contributors the relevance to Indigenous peoples who have globally experienced the oppressive legacy of colonization, and (5) widely disseminating and seeking endorsement from relevant knowledge users. We will seek input from external collaborators using social media, mailing lists and other communication channels. Discussion Achieving global imperatives such as the Sustainable Development Goals (e.g., SDG 10 Reduced inequalities, SDG 3 Good health and wellbeing) requires advancing health equity in research. The implementation of the STROBE-Equity guidelines will enable a better awareness and understanding of health inequities through better reporting. We will broadly disseminate the reporting guideline with tools to enable adoption and use by journal editors, authors, and funding agencies, using diverse strategies tailored to specific audiences.

Abstract Background The UK Department for Work and Pensions (DWP) administers Universal Credit (UC) – the main UK benefit for people in- and out-of-work. UC is being rolled out nationally from 2013 to 2024. Citizens Advice (CA) is an independent charity that provides advice and support to people making a claim for UC. The aim of this study is to understand who is seeking advice from CA when making a UC claim and how the types of people seeking advice are changing as the rollout of UC continues. Methods Co-developed with Citizens Advice Newcastle and Citizens Advice Northumberland we performed longitudinal analysis of national data from Citizens Advice for England and Wales on the health (mental health and limiting long term conditions) and socio-demographic of 1,003,411 observations for people seeking advice with claiming UC over four financial years (2017/18 to 2020/21). We summarised population characteristics and estimated the differences between the four financial years using population-weighted t-tests. Findings were discussed with three people with lived experience of seeking advice to claim UC to help frame our interpretation and policy recommendations. Results When comparing 2017/18 to 2018/19, there was a significantly higher proportion of people with limiting long term conditions seeking advice with claiming UC than those without (+ 2.40%, 95%CI: 1.31-3.50%). However, as the rollout continued between 2018/29 and 2019/20 (-6.75%, 95%CI: -9.62%--3.88%) and between 2019/20 and 2020/21 (-2.09%, 95%CI: -2.54%--1.64%), there were significantly higher proportions of those without a limiting long term condition seeking advice than with. When comparing 2018/19 to 2019/20 and 2019/20 to 2020/21, there was a significant increase in the proportion of self-employed compared to unemployed people seeking advice with claiming UC (5.64%, 95%CI: 3.79-7.49%) and (2.26%, 95%CI: 1.29-3.23%) respectively. Conclusion As the rollout for UC continues, it is important to understand how changes in eligibility for UC may impact on those who need help with applying for UC. Ensuring that the advice process and application process is responsive to a range of people with different needs can help to reduce the likelihood that the process of claiming UC will exacerbate health inequalities.

With the steady increase in allergy prevalence worldwide, there is a strong need for novel diagnostic tools for precise, fast, and less invasive testing methods. Herein, a miniatured fluorescence-based biosensing system is developed for the rapid and quantitative detection of allergen-specific immunoglobulin-E. An antibody-based fluorescence assay in a microfluidic-patterned slide, combined with a custom-made portable fluorescence reader for image acquisition and user-friendly software for the data analysis, enables obtaining results for multiple allergens in just ~1 h with only 80 μL of blood serum. The multiplexed detection of common birch, timothy grass, cat epithelia, house dust mite, and dog epithelia shows quantitative IgE-mediated allergic responses to specific allergens in control serum samples with known total IgE concentration. The responses are verified with different control tests and measurements with a commercial fluorescence reader. These results open the door to point-of-care allergy screening for early diagnosis and broader access and for large-scale research in allergies.

Background Having a good start in life during pregnancy and infancy has been shown to be important for living both a healthy life and a longer life. Despite the introduction of many policies for the early-years age group, including voucher schemes, with the aim of improving nutrition, there is limited evidence of their impact on health. Objectives To assess the effectiveness of the Healthy Start voucher scheme on infant, child and maternal outcomes, and to capture the lived experiences of the Healthy Start voucher scheme for low-income women. Design This was a natural experiment study using existing data sets, linked to routinely collected health data sets, with a nested qualitative study of low-income women and an assessment of the health economics. Setting Representative sample of Scottish children and UK children. Participants Growing Up in Scotland cohort 2 (n = 2240), respondents to the 2015 Infant Feeding Study (n = 8067) and a sample of 40 participants in the qualitative study. Interventions The Health Start voucher, a means-tested scheme that provides vouchers worth £3.10 per week to spend on liquid milk, formula milk, fruit and vegetables. Main outcome measures Infant and child outcomes – breastfeeding initiation and duration; maternal outcomes – vitamin use pre and during pregnancy. Results The exposed group were women receiving the Healthy Start voucher (R), with two control groups: eligible and not claiming the Healthy Start voucher (E) and nearly eligible. There was no difference in vitamin use during pregnancy for either comparison (receiving the Healthy Start voucher, 82%; eligible and not claiming the Healthy Start voucher, 86%; p = 0.10 vs. receiving the Healthy Start voucher, 87%; nearly eligible, 88%; p = 0.43) in the Growing Up in Scotland cohort. Proportions were similar for the Infant Feeding Study cohort (receiving the Healthy Start voucher, 89%; eligible and not claiming the Healthy Start voucher, 86%; p = 0.01 vs. receiving the Healthy Start voucher, 89%; nearly eligible, 87%; p = 0.01); although results were statistically significantly different, these were small effect sizes. There was no difference for either comparison in breastfeeding initiation or breastfeeding duration in months in Growing Up in Scotland, but there was a negative effect of the Healthy Start voucher in the Infant Feeding Survey. This contrast between data sets indicates that results are inconclusive for breastfeeding. The qualitative study found that despite the low monetary value the women valued the Healthy Start voucher scheme. However, the broader lives of low-income women are crucial to understand the constraints to offer a healthy diet. Limitations Owing to the policy being in place, it was difficult to identify appropriate control groups using existing data sources, especially in the Infant Feeding Study. Conclusions As the Healthy Start voucher scheme attempts to influence health behaviour, this evaluation can inform other policies aiming to change behaviour and use voucher incentives. The null effect of Healthy Start vouchers on the primary outcomes may be due to the value of the vouchers being insufficient to change the broader lives of low-income women to offer a healthy diet. Future work The methods developed to undertake an economic evaluation alongside a natural experiment using existing data can be used to explore the cost-effectiveness of the Healthy Start voucher scheme. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 11, No. 11. See the NIHR Journals Library website for further project information. Plain language summary What was the problem? United Kingdom governments have introduced many policies to support infants and their families. Most of these policies have not been evaluated in terms of health outcomes. Therefore, there is limited evidence for policy-makers about whether or not the right policies are in place to make a difference to the health of young children and their families. What did we do? We investigated the impact of the Healthy Start voucher scheme (worth £3.10 per week to spend on milk, fruit and vegetables) on the health of low-income mothers, and their infants and young children, in particular vitamin use of mothers and breastfeeding of infants. What did we find? Using survey data, there were high rates of vitamin use during pregnancy, but fewer women taking vitamins before pregnancy. There was no effect of Healthy Start vouchers on taking vitamins before or during pregnancy. There was inconclusive evidence of the effect of Healthy Start vouchers on breastfeeding, indicating that use of the vouchers does not discourage breastfeeding in women with low incomes. From interviews with mothers, we found that they valued the Healthy Start vouchers and understood the aims of the policy. Healthy Start vouchers were not mentioned in decision-making around breastfeeding. Women’s choice to breast or formula feed was based on a range of other factors, such as support to breastfeed. They wanted to provide a healthy diet for their families, but owing to living on low incomes did not always manage it. What does this mean? Policy-makers still need more evidence about the effects of voucher schemes to improve the health of low-income mothers, and their infants and young children. The decision-makers require evidence to determine where to allocate limited resources. There is a need to improve support for low-income families to provide their families with a healthy diet. Scientific summary Background Having a good start in life during pregnancy and infancy has been shown to be important for living both a healthy life and a longer life. Health and well-being during the early years (which starts pre-conception) have a crucial impact on chronic disease and inequalities across the life course and from one generation to the next. There is a willingness of governments to invest in early years, as early investment in the life course has been shown to provide the highest rate of economic return. Despite the introduction of many policies designed to improve the circumstances during pregnancy and early life, there have been few outcome evaluations of these policies. Many of the evaluations are restricted to process evaluations of how the policy is implemented, rather than an evaluation of the outcomes for the mothers and their infants. The Healthy Start voucher (HSV) scheme was introduced in the United Kingdom (UK) in 2005/6. It is a means-tested voucher scheme for pregnant women and mothers with children under 4 years of age. If these women are in receipt of certain means-tested benefits then they are eligible for vouchers to be spent on milk, infant formula milk, fruit and vegetables. They also receive free vitamins. All mothers aged > 18 years are eligible for the scheme. Vouchers worth £3.10 per week are given to eligible women. These can be spent in neighbourhood shops and pharmacies. There are four main aims of the scheme: improve the nutrition of pregnant women, increase fruit and vegetable intake, initiate and maintain breastfeeding, and introduce foods in addition to milk as part of a progressively varied diet when infants are 6 months old. The effectiveness and cost-effectiveness of the HSV scheme have not yet been shown. Previous evaluations of outcomes comparing the HSV scheme with the Welfare Food Scheme (WFS) found that mothers eligible for the HSV scheme had higher daily intakes of iron, calcium, folate and vitamin C than mothers eligible for WFS. A mixed-methods study of practitioners and low-income mothers found that recipients valued the vouchers but that there were substantial barriers to access, including low levels of awareness of the HSV scheme among both mothers and practitioners, and uncertainty about the eligibility criteria among health professionals. A report on the operational aspects of the HSV scheme concluded that a comparative study is needed that extends previous analyses to the examination of outcomes and assessing the cost-effectiveness of the HSV scheme. There remains a need to determine the effectiveness on health outcomes and cost-effectiveness of the HSV scheme, using larger studies and investigating a wide range of outcomes with longer-term follow-up. Unless such schemes are rigorously evaluated there is a risk that resources will be wasted on ineffective interventions, or that opportunities to improve the design and administration of potentially valuable interventions are missed. Objectives The overall aim was to evaluate the HSV scheme in relation to the extent to which it improves the nutrition of pregnant women and the health outcomes of their infants. There were five objectives to investigate: the effectiveness of the HSV scheme in relation to vitamin use in pregnancy and breastfeeding initiation and duration the effectiveness of the HSV scheme in relation to infant and child weight and body size, child morbidity, infant and child feeding, and maternal health how findings differ between different populations (Scotland and England) to establish actual voucher usage and determine the reasons for uptake and non-uptake of the HSV to establish the cost-effectiveness of the HSV. Methods This evaluation of the HSV scheme had a focus on outcomes in pregnancy, early infancy and late infancy, with the potential to follow infants into adulthood through routinely collected data. It was a mixed-methods study, taking a natural experiment approach. It combined a quantitative evaluation with an integrated qualitative study to understand the lived experiences of low-income women. In addition to evaluating the health outcomes, we developed a framework to undertake an economic evaluation alongside a natural experiment using observational data. Exposure, controls and comparison groups The exposed group were those women eligible and claiming HSV, namely recipients (R). One reason the HSV scheme has not been evaluated on a large scale is the difficulty of identifying an appropriate comparison group. As the HSV is means tested it is not clear what an appropriate comparison group is; it is not appropriate to compare those who are eligible for HSV with those who do not meet the eligibility criteria as they are a very different group in terms of socioeconomic characteristics, with very different health behaviours and outcomes. We identified two comparison groups, the first being women who are eligible for HSV but do not claim the vouchers, namely eligible (E). The second comparison group was low-income women who just miss out on eligibility for HSV owing to not being eligible for the means-tested benefits owing to slightly increased income levels, namely nearly eligible (NE). With these exposure and control groups, there are three ways to compare these groups: recipients versus eligible but not claiming (group 1 vs. group 2) recipients versus nearly eligible (group 1 vs. group 3) all eligible versus nearly eligible (group 1 and 2 combined vs. group 3). Design The design used a multiple analytical approach in line with Medical Research Council guidance for the evaluation of natural experiments (NEs). There are three parts to this evaluation: secondary analysis of two existing data sets, including linking one to routinely collected health data (objectives 1, 2 and 3) qualitative interview study of mothers including a descriptive analysis of voucher usage (objective 4) establishing methods for cost-effectiveness analysis and conducting preliminary analysis (objective 5). Quantitative data sources and analysis For the quantitative analysis, we used two high-quality surveys representative of the Scottish population [Growing Up in Scotland (GUS); n = 2240] and the UK population [Infant Feeding Survey (IFS) 2010; n = 8067] to evaluate the HSV scheme. We examined potential improvement in vitamin use in pregnancy and breastfeeding initiation and duration, and other related health outcomes for low-income mothers and their children. We linked the GUS data to NHS routinely collected data to examine further health outcomes. We used propensity score matching on key characteristics to allow for the exposed and control groups to be more balanced on covariates. This method tries to mimic the characteristics of a randomised controlled trial. The propensity score is a balancing score, which means that it is conditional on the propensity score; the distribution of observed baseline covariates will be similar between treated and untreated subjects. This matching technique minimises selection bias and is better at getting to the causal effect than simple covariate adjustment in models. Qualitative interview study We carried out 40 in-depth, semistructured, face-to-face interviews, spread across each of the exposed and control groups. Key foci of the analysis were the processes involved in the take-up, non-take-up or discontinuation of the HSV scheme; the experience of using HSVs and how the vouchers are used. Framework for the cost-effectiveness analysis We developed and proposed methods and guidance for conducting economic evaluations in population health using observation data from NEs. Such evaluations are subject to the inherent biases that affect observational data. We reviewed and adapted current economic methods guidance and incorporated evidence from economic evaluations carried out in similar early years contexts. In addition, we used methods from previous studies that incorporated economics into NEs in education and microeconomics as well as health economic evaluations using observational data. Ethics Ethics approval was not required for the secondary analysis of existing data as there was no primary data collection. The linkage and release of the GUS data with the routinely collected data for research purposes was approved subject to Public Benefit and Privacy Panel for Health and Social Care project number 1516-0614. The qualitative study was reviewed and fully approved by the University of Glasgow, College of Social Science Ethics Committee in October 2015. This Committee complies with the Economic and Social Research Council’s research ethics framework. Results Impacts on child health For nearly all the outcomes across both GUS and IFS, apart from ever breastfeeding and breastfeeding duration in IFS, the results indicated there is no effect of HSV on the outcomes. For ever breastfed and duration of breastfeeding there are differences between propensity score results from GUS and IFS, with the IFS indicating a negative effect of HSV on breastfeeding. Ever breastfed: R 49%, E 53%, p = 0.255; R 58%, NE 62%, p = 0.189; all eligible (AE) 58%, NE 62%, p = 0.168, in GUS; R 57%, E 69%, p < 0.0001; R 53%, NE 70%, p < 0.0001; AE 60%, NE 74%, p < 0.0001, in IFS. Duration of breastfeeding in months (standard deviation): R 1.32 (2.1), E 1.46 (2.2), p = 0.374; R 1.73 (2.3), NE 1.88 (2.3), p = 0.315; AE 1.84 (2.4), NE 1.88 (2.3), p = 0.803, in GUS; R 1.37 (2.6), E 1.94 (3.0), p < 0.0001; R 1.23 (2.4), NE 2.09 (3.1), p < 0.0001; AE 1.53 (2.7), NE 2.51 (3.3), p < 0.0001, in IFS. For birthweight and low birthweight, the effect sizes and significance vary across the data sets and methods, indicating less confidence in the results of the HSV scheme on birthweight. For premature births and age at introduction of solid foods, there is more consistency across the data sets and evaluation methods, indicating some confidence in the results. Impacts on maternal health There was no difference in vitamin use during pregnancy for either comparison: R 82%, E 86%, p = 0.10; R 87%, NE 88%, p = 0.43; AE 87%, NE 88%, p = 0.43, in GUS. Proportions were similar for IFS: R 89%, E 86%, p = 0.01; R 89%, NE 87%, p = 0.01; AE 88%, NE 86%, p = 0.43. Although results were statistically significantly different, indicating increased vitamin use in the HSV groups, these are small effect sizes. We were able to examine further health outcomes, health behaviours and financial difficulties of the mothers in the GUS data set. For health during pregnancy, alcohol use and household managing financially, there was no effect of the HSV scheme across all the comparison groups. There were slight differences in mother’s current health as assessed by the Short Form questionnaire-12 items when the NE comparison group was used as the control. Short Form questionnaire-12 items physical health mean (standard deviation) R 52.26 (7.45), E 52.43 (6.84), p = 0.734; R 51.28 (8.36), NE 53.09 (6.87), p = 0.0002; AE 51.52 (8.13), NE 53.09 (6.87), p = 0.001. Short Form questionnaire-12 items mental health mean (standard deviation): R 51.11 (9.12), E 51.36 (8.74), p = 0.693; R 50.69 (9.23), NE 52.28 (8.36), p = 0.0045; AE 50.81 (9.19), NE 52.28 (8.3), p = 0.0083. There were large differences in smoking when the NE comparison group was used as the control: R 43%, E 34%, p = 0.419; R 37%, NE 24%, p < 0.0001; AE 35%, NE 24%, p < 0.0001 for current smoking status, and R 10.6, E 11.14, p = 0.581; R 10.9, NE 8.6, p = 0.00014; AE 10.9, NE 8.6, p = 0.0001 for numbers of cigarettes smoked per day. Understanding mother’s experiences The rich accounts given by the participants gave rise to four key themes: knowledge, awareness, take up and use of the HSV scheme; opinions of the HSV scheme; the effect of the HSV scheme on diet and feeding choices for their babies and children; and the broader lives of low-income women. The HSV scheme aims were well understood and the scheme was valued by participants. They thought that the eligibility criteria should be widened as they had had positive experiences and appreciated the scheme and the impact that the vouchers had on their lives. For some mothers, it supported them to provide a healthy diet and the opportunity to give their children a range of fruit and vegetables. For many other mothers, despite appropriate nutrition for children being important to them, there was evidence that some children still had poor diets. The HSVs were not mentioned in their decision-making around breastfeeding. Women’s choice to breast or formula feed was based on a range of other factors, such as support to breastfeed and assumptions and expectations of health professionals. The HSVs were incorporated into budgeting strategies and were seen as a good support in the context of the lives of low-income women. Methods for conducting a health economic analysis alongside a natural experiment Current guidance for economic evaluations focusses on randomised controlled trial designs and therefore does not address the specific challenges for natural experiment designs. Using such guidance can lead to suboptimal design, data collection and data analysis for NEs, leading to a bias in the estimated effectiveness and cost-effectiveness of the intervention or policy. We produced a framework to use when conducting an economic evaluation alongside a natural experiment. Conclusions Despite inconclusive findings of the impact of the HSV scheme on health, the HSV scheme attempts to influence health behaviour, and this evaluation can inform other policies aiming to change behaviours or use voucher incentives. There was a high use of vitamins during pregnancy in all groups, with indications of a small increase in vitamin use in the IFS group. Breastfeeding behaviour was similar in both recipients and nearly eligible groups, offering reassurance that the HSV scheme does not disincentivise breastfeeding, but results differed across GUS and IFS. The null effect of HSV on the primary outcomes may be due to the value of the vouchers being insufficient to make a large impact on the income for these women and children. There is a need to provide additional support for smoking cessation to the women eligible for HSVs. Implications for future research Future research should use the methods developed to undertake an economic evaluation alongside a natural experiment using existing data to explore the cost-effectiveness of the HSV scheme. We would also recommend further work to explore and identify other data sources or control groups to improve triangulation and strengthen the causal effects of this policy evaluation. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 13/164/10) and is published in full in Public Health Research; Vol. 11, No. 11. See the NIHR Funding and Awards website for further award information.

IntroductionThe chronic inflammatory skin disease Hidradenitis suppurativa (HS) is strongly associated with Crohn’s Disease (CD). HS and CD share clinical similarities and similar inflammatory pathways are upregulated in both conditions. Increased prevalence of inflammatory disease in industrialised nations has been linked to the Western diet. However, gut microbiota composition and diet interaction have not been compared in HS and CD.MethodsHere we compared the fecal microbiota (16S rRNA gene amplicon sequencing) and habitual diet of previously reported subjects with HS (n = 55), patients with CD (n = 102) and controls (n = 95).Results and discussionPatients with HS consumed a Western diet similar to patients with CD. Meanwhile, habitual diet in HS and CD was significantly different to controls. Previously, we detected differences in microbiota composition among patients with HS from that of controls. We now show that 40% of patients with HS had a microbiota configuration similar to that of CD, characterised by the enrichment of pathogenic genera (Enterococcus, Veillonella and Escherichia_Shigella) and the depletion of putatively beneficial genera (Faecalibacterium). The remaining 60% of patients with HS harboured a normal microbiota similar to that of controls. Antibiotics, which are commonly used to treat HS, were identified as a co-varying with differences in microbiota composition. We examined the levels of several inflammatory markers highlighting that growth-arrest specific 6 (Gas6), which has anti-inflammatory potential, were significantly lower in the 40% of patients with HS who had a CD microbiota configuration. Levels of the pro-inflammatory cytokine IL-12, which is a modulator of intestinal inflammation in CD, were negatively correlated with the abundance of health-associated genera in patients with HS. In conclusion, the fecal microbiota may help identify patients with HS who are at greater risk for development of CD.

Background and purpose: High-dose dual antibiotic-loaded bone cement (ALBC) may reduce the risk of revision after total hip and knee replacements. The aim of our study therefore was to determine the risk of re-revision following first time aseptic hip or knee revision using single versus dual ALBC. Patients and methods: Patients from the Dutch Arthroplasty Register treated from 2007 to 2018 with first time cemented aseptic hip (n = 2,529) or knee revisions (n = 7,124) were incorporated into 2 datasets. The primary endpoint of this observational cohort study was subsequent all-cause re-revision. Multivariable Cox proportional hazard and competing risk was analyzed for both groups. Results: There was no difference in re-revision rate (any reason) with single versus dual ALBC (hazard ratio 1.06, 95% confidence interval [CI] 0.83–1.35 for hip and 0.93, CI 0.80–1.07 for knee revisions). The 10-year crude cumulative re-revision rate also showed no differences for single versus dual ALBC use. The crude cumulative 7-year THA re-revision and 9-year TKA re-revision rates did not show any difference in implant survival for common cement types used. Conclusion: We could not confirm the potential benefit of using dual ALBC compared with single ALBC for aseptic hip and knee revisions.

Abstract The UK net‐zero target requires the integration of significant renewable energy resources into the electrical grid. This, together with the projected growth in electricity demand imposes practical challenges on the power transfer capability of existing transmission feeders. For environmental and planning reasons, construction of new overhead lines is problematic, and where possible upgrading of existing substations and lines is preferred. This paper investigates the feasibility of transforming an existing three‐phase (3Φ) double‐circuit 400 kV line into a six‐phase (6Φ) feeder for a simulated future GB scenario. Results indicate a 6Φ feeder, operating at a ‘phase‐adjacent phase’ voltage of 400 kV can effectively solve the constraints of boundaries in transmission networks. When considering the various operating contingencies, associated with an important UK network boundary and its expected near‐future winter‐peak power transfer requirements, the thermal overload issues are mitigated by transforming a feeder from 3Φ to 6Φ. The paper demonstrates upgrading to 6Φ technology is a potential solution to certain future boundary constraints and in these cases avoids the need to build new underground or overhead AC/DC lines.

Abstract Background Labeling a patient “non-compliant” is a form of dehumanization that can deprive the patient of positive human qualities and/or agency in the mind of a physician. The term “non-compliant” is frequently used in medical record documentation and has been shown to compromise care, particularly for marginalized communities. There is limited literature on the impact of the label on medical trainees. We aimed to explore how internal medicine residents and fellows (trainees) perceive the term “non-compliant patient” and its impact on their practice after interacting with a simulated refugee patient who has not followed a physician’s recommendations. Methods Kolb’s experiential learning cycle guided the design of the educational session which was part of a required communication skills curriculum for trainees. A scenario was created to simulate a refugee patient who had not adhered to their treatment plan and could potentially be labeled as “non-compliant.” Trainees participated in the 3-h session consisting of a remote simulated patient encounter immediately followed by a virtual structured debrief session that was recorded and transcribed. Thematic analysis of debrief transcripts was conducted starting with the use of provisional codes from the literature on the doctor-patient relationship and de/humanization. Results In group debrief sessions, trainees reflected upon the standardized patient case and chose to also discuss similar cases they had experienced in clinical practice. Trainees indicated that the term “non-compliant patient” served as a biasing function and described how this bias negatively impacted the doctor-patient relationship. Trainees described how marginalized communities might be more susceptible to the negative connotation associated with the term “non-compliant patient.” For some trainees, the term triggered further investigation of underlying barriers to care and exploration of the social determinants of health. Conclusions The use of the phrase “non-compliant patient,” though common in medical practice, may lead to patient dehumanization among trainees. A simulated refugee patient encounter followed by a facilitated group debrief allowed participants to verbalize and reflect on the meaning and possible impact of the label.

Societal Impact Statement The coronavirus pandemic has reminded us that green spaces provide sanctuary and comfort, as well as opportunities for release and relief, during difficult times. However, to ensure continuing viability, botanical gardens can do more to address important societal concerns, especially around the environment. Sustaining relevance through action, especially local action, while also thinking beyond botanical science, and making creative use of electronic outreach will help botanic gardens to flourish. Summary This paper is a personal reflection on high‐level issues relevant to future of botanic gardens and similar organisations, based on the personal experiences of the author at the Field Museum in Chicago, the Royal Botanic Gardens, Kew, in London, the Yale School of Forestry and Environmental Studies (now the Yale School of the Environment) in New Haven, Connecticut, and the Oak Spring Garden Foundation in northern Virginia. Botanic gardens have the inherent advantage that passages of nature, especially in cities, are vital for individual and social well‐being. But this natural advantage needs to be supplemented by actions that take into account a changing world and that respond in meaningful ways to the concerns of supporters and stakeholders. I emphasise five principles that are important now and for the future: (1) Sustaining relevance is key; (2) science is not enough; (3) actions speak louder than words; (4) local action is disproportionately important; and (5) electronic outreach is not optional. Leadership from outstanding individuals is also vital. Finding, encouraging and developing energetic people who are open minded, determined to make a difference and willing to embrace change is vital for institutional success.

The catalytic chaperone tapasin assists peptide loading onto MHC-I molecules for antigen presentation and immune recognition. Here, the authors present crystal structures that provide insights into the molecular mechanism of tapasin-mediated peptide exchange.

Chronic pain is a substantial health burden and options for treating chronic pain remain minimally effective. Ketogenic diets are emerging as well-tolerated, effective therapeutic strategies in preclinical models of chronic pain, especially diabetic neuropathy. We tested whether a ketogenic diet is antinociceptive through ketone oxidation and related activation of ATP-gated potassium (KATP) channels in mice. We demonstrate that consumption of a ketogenic diet for one week reduced evoked nocifensive behaviors (licking, biting, lifting) following intraplantar injection of different noxious stimuli (methylglyoxal, cinnamaldehyde, capsaicin, or Yoda1) in mice. A ketogenic diet also decreased the expression of p-ERK, an indicator of neuronal activation in the spinal cord, following peripheral administration of these stimuli. Using a genetic mouse model with deficient ketone oxidation in peripheral sensory neurons, we demonstrate that protection against methylglyoxal-induced nociception by a ketogenic diet partially depends on ketone oxidation by peripheral neurons. Injection of tolbutamide, a KATP channel antagonist, prevented ketogenic diet-mediated antinociception following intraplantar capsaicin injection. Tolbutamide also restored the expression of spinal activation markers in ketogenic diet-fed, capsaicin-injected mice. Moreover, activation of KATP channels with the KATP channel agonist diazoxide reduced pain-like behaviors in capsaicin-injected, chow-fed mice, similar to the effects observed with a ketogenic diet. Diazoxide also reduced the number of p-ERK+ cells in capsaicin-injected mice. These data support a mechanism that includes neuronal ketone oxidation and activation of KATP channels to provide ketogenic diet-related analgesia. This study also identifies KATP channels as a new target to mimic the antinociceptive effects of a ketogenic diet.

Shirley Shackleton said that after her husband Greg was killed in Timor-Leste in October 1975, for seven weeks she became a campaigner for justice for the journalists murdered in Balibo, then after Indonesia invaded in December 1975 she became a campaigner for justice for all the East Timorese too. Shackleton saw the Australian government treatment of the killings as a litmus test of Australian East Timor policy. She continued to pressure the government for a Federal Police investigation of those responsible for the deaths, culminating with Australian politicians and diplomats being put in the dock and scrutinised under oath in a Coronial Inquiry in 2007.

IntroductionConservation agriculture (CA) is gaining attention in the South Asia as an environmentally benign and sustainable food production system. The knowledge of the soil bacterial community composition along with other soil properties is essential for evaluating the CA-based management practices for achieving the soil environment sustainability and climate resilience in the rice-wheat-greengram system. The long-term effects of CA-based tillage-cum-crop establishment (TCE) methods on earthworm population, soil parameters as well as microbial diversity have not been well studied.MethodsSeven treatments (or scenarios) were laid down with the various tillage (wet, dry, or zero-tillage), establishment method (direct-or drill-seeding or transplantation) and residue management practices (mixed with the soil or kept on the soil surface). The soil samples were collected after 7 years of experimentation and analyzed for the soil quality and bacterial diversity to examine the effect of tillage-cum-crop establishment methods.Results and DiscussionEarthworm population (3.6 times), soil organic carbon (11.94%), macro (NPK) (14.50–23.57%) and micronutrients (Mn, and Cu) (13.25 and 29.57%) contents were appreciably higher under CA-based TCE methods than tillage-intensive farming practices. Significantly higher number of OTUs (1,192 ± 50) and Chao1 (1415.65 ± 14.34) values were observed in partial CA-based production system (p ≤ 0.05). Forty-two (42) bacterial phyla were identified across the scenarios, and Proteobacteria, Actinobacteria, and Firmicutes were the most dominant in all the scenarios. The CA-based scenarios harbor a high abundance of Proteobacteria (2–13%), whereas the conventional tillage-based scenarios were dominated by the bacterial phyla Acidobacteria and Chloroflexi and found statistically differed among the scenarios (p ≤ 0.05). Composition of the major phyla, i.e., Proteobacteria, Actinobacteria, and Firmicutes were associated differently with either CA or farmers-based tillage management practices. Overall, the present study indicates the importance of CA-based tillage-cum-crop establishment methods in shaping the bacterial diversity, earthworms population, soil organic carbon, and plant nutrient availability, which are crucial for sustainable agricultural production and resilience in agro-ecosystem.

Introduction Housing-related factors can be predictors of health, including of diabetes outcomes. We analysed the association between subsidised housing residency and diabetes mortality among a large cohort of low-income adults in Brazil.Research design and methods A cohort of 9 961 271 low-income adults, observed from January 2010 to December 2015, was created from Brazilian administrative records of social programmes and death certificates. We analysed the association between subsidised housing residency and time to diabetes mortality using a Cox model with inverse probability of treatment weighting and regression adjustment. We assessed inequalities in this association by groups of municipality Human Development Index. Diabetes mortality included diabetes both as the underlying or a contributory cause of death.Results At baseline, the mean age of the cohort was 40.3 years (SD 15.6 years), with a majority of women (58.4%). During 29 238 920 person-years of follow-up, there were 18 775 deaths with diabetes as the underlying or a contributory cause. 340 683 participants (3.4% of the cohort) received subsidised housing. Subsidised housing residents had a higher hazard of diabetes mortality compared with non-residents (HR 1.17; 95% CI 1.05 to 1.31). The magnitude of this association was more pronounced among participants living in municipalities with lower Human Development Index (HR 1.30; 95% CI 1.04 to 1.62).Conclusions Subsidised housing residents had a greater risk of diabetes mortality, particularly those living in low socioeconomic status municipalities. This finding suggests the need to intensify diabetes prevention and control actions and prompt treatment of the diabetes complications among subsidised housing residents, particularly among those living in low socioeconomic status municipalities.

IntroductionPlace-based public health evaluations are increasingly making use of natural experiments. This scoping review aimed to provide an overview of the design and use of natural experiment evaluations (NEEs), and an assessment of the plausibility of the as-if randomization assumption.MethodsA systematic search of three bibliographic databases (Pubmed, Web of Science and Ovid-Medline) was conducted in January 2020 to capture publications that reported a natural experiment of a place-based public health intervention or outcome. For each, study design elements were extracted. An additional evaluation of as-if randomization was conducted by 12 of this paper's authors who evaluated the same set of 20 randomly selected studies and assessed ‘as-if ' randomization for each.Results366 NEE studies of place-based public health interventions were identified. The most commonly used NEE approach was a Difference-in-Differences study design (25%), followed by before-after studies (23%) and regression analysis studies. 42% of NEEs had likely or probable as-if randomization of exposure (the intervention), while for 25% this was implausible. An inter-rater agreement exercise indicated poor reliability of as-if randomization assignment. Only about half of NEEs reported some form of sensitivity or falsification analysis to support inferences.ConclusionNEEs are conducted using many different designs and statistical methods and encompass various definitions of a natural experiment, while it is questionable whether all evaluations reported as natural experiments should be considered as such. The likelihood of as-if randomization should be specifically reported, and primary analyses should be supported by sensitivity analyses and/or falsification tests. Transparent reporting of NEE designs and evaluation methods will contribute to the optimum use of place-based NEEs.

Snow accumulation rates in Antarctica can now be reconstructed from nitrate isotopes in snow and ice. This independent technique offers scientists a new tool for studying how Antarctic climate changed in the past and how it may change in the future.

Abstract The number of mass spectrometry (MS)-based proteomics datasets in the public domain keeps increasing, particularly those generated by Data Independent Acquisition (DIA) approaches such as SWATH-MS. Unlike Data Dependent Acquisition datasets, the re-use of DIA datasets has been rather limited to date, despite its high potential, due to the technical challenges involved. We introduce a (re-)analysis pipeline for public SWATH-MS datasets which includes a combination of metadata annotation protocols, automated workflows for MS data analysis, statistical analysis, and the integration of the results into the Expression Atlas resource. Automation is orchestrated with Nextflow, using containerised open analysis software tools, rendering the pipeline readily available and reproducible. To demonstrate its utility, we reanalysed 10 public DIA datasets from the PRIDE database, comprising 1,278 SWATH-MS runs. The robustness of the analysis was evaluated, and the results compared to those obtained in the original publications. The final expression values were integrated into Expression Atlas, making SWATH-MS experiments more widely available and combining them with expression data originating from other proteomics and transcriptomics datasets.

BackgroundHIV remains a persistent health problem in the United States, especially among women. Approved in 2012, HIV pre-exposure prophylaxis (PrEP) is a daily pill or bimonthly injection that can be taken by individuals at increased risk of contracting HIV to reduce their risk of new infection. Women who are at risk of HIV face numerous barriers to HIV services and information, underscoring the critical need for strategies to increase awareness of evidence-based HIV prevention methods, such as HIV PrEP, among women. ObjectiveWe aimed to identify historical trends in the use of Twitter hashtags specific to women and HIV PrEP and explore content about women and PrEP shared through Twitter. MethodsThis was a qualitative descriptive study using a purposive sample of tweets containing hashtags related to women and HIV PrEP from 2009 to 2022. Tweets were collected via Twitter’s API. Each Twitter user profile, tweet, and related links were coded using content analysis, guided by the framework of the Health Belief Model (HBM) to generate results. We used a factor analysis to identify salient clusters of tweets. ResultsA total of 1256 tweets from 396 unique users were relevant to our study focus of content about PrEP specifically for women (1256/2908, 43.2% of eligible tweets). We found that this sample of tweets was posted mostly by organizations. The 2 largest groups of individual users were activists and advocates (61/396, 15.4%) and personal users (54/396, 13.6%). Among individual users, most were female (100/166, 60%) and American (256/396, 64.6%). The earliest relevant tweet in our sample was posted in mid-2014 and the number of tweets significantly decreased after 2018. We found that 61% (496/820) of relevant tweets contained links to informational websites intended to provide guidance and resources or promote access to PrEP. Most tweets specifically targeted people of color, including through the use of imagery and symbolism. In addition to inclusive imagery, our factor analysis indicated that more than a third of tweets were intended to share information and promote PrEP to people of color. Less than half of tweets contained any HBM concepts, and only a few contained cues to action. Lastly, while our sample included only tweets relevant to women, we found that the tweets directed to lesbian, gay, bisexual, transgender, queer (LGBTQ) audiences received the highest levels of audience engagement. ConclusionsThese findings point to several areas for improvement in future social media campaigns directed at women about PrEP. First, future posts would benefit from including more theoretical constructs, such as self-efficacy and cues to action. Second, organizations posting on Twitter should continue to broaden their audience and followers to reach more people. Lastly, tweets should leverage the momentum and strategies used by the LGBTQ community to reach broader audiences and destigmatize PrEP use across all communities.

Flaviviruses continue to emerge as global health threats. There are currently no Food and Drug Administration (FDA) approved antiviral treatments for flaviviral infections. Therefore, there is a pressing need to identify host and viral factors that can be targeted for effective therapeutic intervention. Type I interferon (IFN-I) production in response to microbial products is one of the host's first line of defense against invading pathogens. Cytidine/uridine monophosphate kinase 2 (CMPK2) is a type I interferon-stimulated gene (ISG) that exerts antiviral effects. However, the molecular mechanism by which CMPK2 inhibits viral replication is unclear. Here, we report that CMPK2 expression restricts Zika virus (ZIKV) replication by specifically inhibiting viral translation and that IFN-I- induced CMPK2 contributes significantly to the overall antiviral response against ZIKV. We demonstrate that expression of CMPK2 results in a significant decrease in the replication of other pathogenic flaviviruses including dengue virus (DENV-2), Kunjin virus (KUNV) and yellow fever virus (YFV). Importantly, we determine that the N-terminal domain (NTD) of CMPK2, which lacks kinase activity, is sufficient to restrict viral translation. Thus, its kinase function is not required for CMPK2's antiviral activity. Furthermore, we identify seven conserved cysteine residues within the NTD as critical for CMPK2 antiviral activity. Thus, these residues may form an unknown functional site in the NTD of CMPK2 contributing to its antiviral function. Finally, we show that mitochondrial localization of CMPK2 is required for its antiviral effects. Given its broad antiviral activity against flaviviruses, CMPK2 is a promising potential pan-flavivirus inhibitor.

BackgroundEvidence indicates that older people with biological and social vulnerabilities are at high risk of short- and long-term consequences related to the COVID-19 pandemic. However, studies have also highlighted that the crisis may present opportunities for personal growth if older individuals are met with appropriate resources and support.ObjectiveThe aim of this study was to explore the perceptions of older people regarding how individual, social, and environmental factors have supported or hindered their well-being and health during COVID-19.MethodsWe analyzed data collected between April–May and October–November 2021 from the Well-being, Interventions and Support during Epidemics (WISE) study, a qualitative investigation of community-dwellers based in Ireland and aged 65 years or over. Participants (n = 57) completed written submissions, narrative interviews and/or go-along interviews detailing their experiences during the pandemic. Framework analysis was carried out in NVivo 12 to identify determinants, linkages, and explanations within Bronfenbrenner’s socio-ecological model.ResultsThe mean age of participants was 74.9 years, 53% were female, 45% lived alone, and 86% lived in areas with high urban influence. Our findings highlight the heterogeneous effect of COVID-19 across diverse older individuals who held distinct concerns, capabilities, and roles in society before and during the pandemic. Multi-scalar contextual characteristics such as individual’s living arrangements, neighborhood social and built environments, as well as social expectations about aging and help seeking, had an influential role in participants’ well-being and available supports. We identified mixed views regarding public health restrictions, but a consensus emerged questioning the suitability of one-size-fits-all approaches based on chronological age.ConclusionsOur results suggest that some negative pandemic consequences could have been avoided by increasing collaboration with older people and with the provision of clearer communications. The interdependencies identified between individual characteristics and socio-ecological factors that influenced participants’ availability of supports and development of adaptive strategies represent areas of opportunity for the development of age-friendly interventions during and beyond public health crises.

Objectives To provide a sociodemographic profile of students enrolled in their first year of a health professional pre-registration programme offered within New Zealand (NZ) tertiary institutions.Design Observational, cross-sectional study. Data were sought from NZ tertiary education institutions for all eligible students accepted into the first ‘professional’ year of a health professional programme for the 5-year period 2016–2020 inclusive. Variables of interest: gender, citizenship, ethnicity, rural classification, socioeconomic deprivation, school type and school socioeconomic scores. Analyses were carried out using the R statistics software.Setting Aotearoa NZ.Participants All students (domestic and international) accepted into the first ‘professional’ year of a health professional programme leading to registration under the Health Practitioners Competence Assurance Act 2003.Results NZ’s health workforce pre-registration students do not reflect the diverse communities they will serve in several important dimensions. There is a systematic under-representation of students who identify as Māori and Pacific, and students who come from low socioeconomic and rural backgrounds. The enrolment rate for Māori students is about 99 per 100 000 eligible population and for some Pacific ethnic groups is lower still, compared with 152 per 100 000 for NZ European students. The unadjusted rate ratio for enrolment for both Māori students and Pacific students versus ‘NZ European and Other’ students is approximately 0.7.Conclusions We recommend that: (1) there should be a nationally coordinated system for collecting and reporting on the sociodemographic characteristics of the health workforce pre-registration; (2) mechanisms be developed to allow the agencies that fund tertiary education to base their funding decisions directly on the projected health workforce needs of the health system and (3) tertiary education funding decisions be based on Te Tiriti o Waitangi (the foundational constitutional agreement between the Indigenous people, Māori and the British Crown signed in 1840) and have a strong pro-equity focus.

Introduction The 2001 Primary Health Care Strategy provided significant new government funding for primary care (general practice and related services) via capitation funding formulas. However, there remain important unanswered questions about how capitation funding formulas should be redesigned to ensure equitable and sustainable service provision to all population groups. Aim To compare levels of chronic illness, utilisation, and unmet need in patients categorised as ‘high-need’ with those categorised as non-‘high-need’ using the definitions that are used in the current funding context, in order to inform primary care funding formula design. Methods Respondents of the New Zealand Health Survey (2018–19) were categorised into ‘high-need’ and non-‘high-need’, as defined in current funding formulas. We analysed: (i) presence, and number, of chronic diseases; (ii) self-reported primary care utilisation (previous 12 months); and (iii) self-reported unmet need for primary care (previous 12 months). Analyses used integrated survey weights to account for survey design. Results In total, 29% of respondents were ‘high-need’, of whom 50.2% reported one or more chronic conditions (vs 47.8% of non-‘high-need’ respondents). ‘High-need’ respondents were more likely than non-‘high-need’ respondents to: report three or more chronic conditions (14.4% vs 13.7%); visit a general practitioner more often (seven or more visits per year: 9.9% vs 6.6%); and report barriers to care. Discussion There is an urgent need for further quantification of the funding requirements of general practices serving high proportions of ‘high-need’ patients in order to ensure their viability, sustainability and the provision of quality of care.

Abstract Background Summer learning loss has been the subject of longstanding concern among researchers, the public and policy makers. The aim of the current research was to investigate inequality changes in children’s mental health and cognitive ability across the summer holidays. Methods We conducted linear and logistic regression analysis of mental health (borderline-abnormal total difficulty and prosocial scores on the strengths and difficulties questionnaire (SDQ)) and verbal cognitive ability (reading, verbal reasoning or vocabulary) at ages 7, 11 and 14, comparing UK Millennium Cohort Study members who were interviewed before and after the school summer holidays. Inequalities were assessed by including interaction terms in the outcome models between a discrete binary variable with values representing time periods and maternal academic qualifications. Coefficients of the interaction terms were interpreted as changes from the pre- to post-holiday period in the extent of inequality in the outcome between participants whose mothers had high or low educational qualifications. Separate models were fitted for each age group and outcome. We used inverse probability weights to allow for differences in the characteristics of cohort members assessed before and after the summer holidays. Results Mental health (borderline/abnormal SDQ total and prosocial scores) at ages 7 and 14 worsened and verbal cognitive ability scores at age 7 were lower among those surveyed after the summer holidays. Mental health inequalities were larger after the holidays at age 7 ([OR = 1.4; 95%CI (0.6, 3.2) and 14: [OR = 1.5; 95%CI (0.7, 3.2)], but changed little at age 11 (OR = 0.9; 95%CI (0.4, 2.6)]. There were differences in pro-social behaviours among those surveyed before/after the school holidays at age 14 [OR = 1.2; 95%CI (0.5, 3.5)] but not at age 7 or 11. There was little change in inequalities in verbal cognitive ability scores over the school holidays [Age 7: b = 1.3; 95%CI (− 3.3, 6.0); Age 11: b = − 0.7; 95%CI (− 4.3, 2.8); Age 14: b = − 0.3; 95%CI (− 1.0, 0.4)]. Conclusion We found inequalities in mental health and cognitive ability according to maternal education, and some evidence or worsening mental health and mental health inequalities across school summer holidays. We found little evidence of widening inequalities in verbal cognitive ability. Widespread school closures during the COVID-19 restrictions have prompted concerns that prolonged closures may widen health and educational inequalities. Management of school closures should focus on preventing or mitigating inequalities that may arise from differences in the support for mental health and learning provided during closures by schools serving more or less disadvantaged children.

We analyse stellar streams in action-angle coordinates combined with recent local direct acceleration measurements to provide joint constraints on the potential of our galaxy. Our stream analysis uses the Kullback–Leibler divergence with a likelihood analysis based on the two-point correlation function. We provide joint constraints from pulsar accelerations and stellar streams for local and global parameters that describe the potential of the Milky Way (MW). Our goal is to build an “acceleration ladder,” where direct acceleration measurements that are currently limited in dynamic range are combined with indirect techniques that can access a much larger volume of the MW. To constrain the MW potential with stellar streams, we consider the Palomar 5, Orphan, Nyx, Helmi, and GD1 streams. Of the potential models that we have considered here, the preferred potential for the streams is a two-component Staeckel potential. We also compare the vertical accelerations from stellar streams and pulsar timing, defining the function $f(z)={\alpha }_{1\mathrm{pulsar}}z-\tfrac{\partial {\rm{\Phi }}}{\partial z}$ , where Φ is the MW potential determined from stellar streams and α _1 pulsar z is the vertical acceleration determined from pulsar timing observations. Our analysis indicates that the Oort limit determined from streams is consistently (regardless of the choice of potential) lower than that determined from pulsar timing observations. The calibration we have derived here may be used to correct the estimate of the acceleration from stellar streams.

The BLOOM study (co-Benefits of Largescale Organic farming On huMan health) aims to determine if a government-implemented agroecology programme reduces pesticide exposure and improves dietary diversity in agricultural households. To achieve this aim, a community-based, cluster-randomised controlled evaluation of the Andhra Pradesh Community-managed Natural Farming (APCNF) programme will be conducted in 80 clusters (40 intervention and 40 control) across four districts of Andhra Pradesh state in south India. Approximately 34 households per cluster will be randomly selected for screening and enrolment into the evaluation at baseline. The two primary outcomes, measured 12 months post-baseline assessment, are urinary pesticide metabolites in a 15% random subsample of participants and dietary diversity in all participants. Both primary outcomes will be measured in (1) adult men ≥18 years old, (2) adult women ≥18 years old, and (3) children

This dataset provides detailed information on rice production practices being applied by farmers during 2018 rainy season in India. Data was collected through computer-assisted personal interview of farmers using the digital platform Open Data Kit (ODK). The dataset, n = 8355, covers eight Indian states, viz., Andhra Pradesh, Bihar, Chhattisgarh, Haryana, Odisha, Punjab, Uttar Pradesh and West Bengal. Sampling frames were constructed separately for each district within states and farmers were selected randomly. The survey was deployed in 49 districts with a maximum of 210 interviews per district. The digital survey form was available on mobile phones of trained enumerators and was designed to minimize data entry errors.Each survey captured approximately 225 variables around rice production practices of farmers’ largest plot starting with land preparation, establishment method, crop variety and planting time through to crop yield. Detailed modules captured fertilizer application, irrigation, weed management, biotic and abiotic stresses. Additional information was gathered on household demographics and marketing. Geo-points were recorded for each surveyed plot with an accuracy of

Integration of Responsible Research and Innovation (RRI) principles into a research project is key to ensure outputs are ethically acceptable and socially desirable. However, translating RRI principles into practice is challenging as there are no recipes that fit all projects. Drawing on interviews and case studies with researchers, external partners and support staff associated with two linked programmes of research addressing trustworthy autonomous systems and the ethical use of personal data, this reflective paper provides a bottom-up perspective on RRI as it is understood and “done” within the focussed, often relatively short, research projects that largely comprise the research programmes. Existing RRI frameworks and tools were found to provide useful resources for use in supported RRI activities. However, effective use is dependant on facilitation by experienced staff, and time pressure and timing within a project can limit the application of RRI. Research institutions and funding bodies could provide more practical and sustained support for RRI practice – throughout the research lifespan - including incentives for RRI and clearer RRI/RI roles and career pathways, helping to develop an embedded community of RRI practice throughout the digital research community and beyond.

Introduction: Physician engagement is crucial for furthering patient safety and quality improvement within healthcare organizations. Medical Safety Huddles, which are physician-specific huddles, is a novel way to engage physicians with patient safety and may reduce adverse events experienced by patients. We plan to conduct a multi-center quality improvement (QI) initiative to implement and evaluate Medical Safety Huddles. The primary objective is to determine the impact of the huddles on adverse events experienced by patients. Secondary objectives include assessing the impact of the huddles on patient safety culture and physician engagement, and a process evaluation to assess the fidelity of implementation. Methods: This stepped wedge cluster randomized study will be conducted at four academic inpatient hospitals over 19 months. Each site will adapt Medical Safety Huddles to its own practice context to best engage physicians. We will review randomly selected patient charts for adverse events. Generalized linear mixed effects regression will be used to estimate the overall intervention effect on adverse events. Process measures such as physician attendance rates and number of safety issues raised per huddle will be tracked to monitor implementation adherence. Conclusion: Medical Safety Huddles may help healthcare organizations and medical leaders to better engage physicians with patient safety. The project results will assess the fidelity of implementation and determine the impact of Medical Safety Huddles on patient safety.

Abstract New Caledonia was, until recently, considered an old continental island harbouring a rich biota with outstanding Gondwanan relicts. However, deep marine sedimentation and tectonic evidence suggest complete submergence of the island during the latest Cretaceous to the Paleocene. Molecular phylogenies provide evidence for some deeply-diverging clades that may predate the Eocene and abundant post-Oligocene colonisation events. Extinction and colonization biases, as well as survival of some groups in refuges on neighbouring paleo-islands, may have obscured biogeographic trends over long time scales. Fossil data are therefore crucial for understanding the history of the New Caledonian biota, but occurrences are sparse and have received only limited attention. Here we describe five exceptional fossil assemblages that provide important new insights into New Caledonia’s terrestrial paleobiota from three key time intervals: prior to the submersion of the island, following re-emergence, and prior to Pleistocene climatic shifts. These will be of major importance for elucidating changes in New Caledonia’s floristic composition over time.

Objectives Hospital-acquired pressure injuries (PIs) are a source of morbidity and mortality, and many are potentially preventable.Design This study prospectively evaluated the prevalence and the associated factors of PIs in adult critical care patients admitted to intensive care units (ICU) in the UK.Setting This service evaluation was part of a larger, international, single-day point prevalence study of PIs in adult ICU patients. Training was provided to healthcare givers using an electronic platform to ensure standardised recognition and staging of PIs across all sites.Participants The characteristics of the ICUs were recorded before the survey; deidentified patient data were collected using a case report form and uploaded onto a secure online platform.Primary and secondary outcome measures Factors associated with ICU-acquired PIs in the UK were analysed descriptively and using mixed multiple logistic regression analysis.Results Data from 1312 adult patients admitted to 94 UK ICUs were collected. The proportion of individuals with at least one PI was 16% (211 out of 1312 patients), of whom 8.8% (n=115/1312) acquired one or more PIs in the ICU and 7.3% (n=96/1312) prior to ICU admission. The total number of PIs was 311, of which 148 (47.6%) were acquired in the ICU. The location of majority of these PIs was the sacral area, followed by the heels. Braden score and prior length of ICU stay were associated with PI development.Conclusions The prevalence and the stage of severity of PIs were generally low in adult critically ill patients admitted to participating UK ICUs during the study period. However, PIs are a problem in an important minority of patients. Lower Braden score and longer length of ICU stay were associated with the development of injuries; most ICUs assess risk using tools which do not account for this.Trial registration number NCT03270345.