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Summary: Ten years ago, (black) stem rust – the most damaging of wheat (Triticum aestivum) rusts – re‐emerged in western Europe. Disease incidences have since increased in scale and frequency. Here, we investigated the likely underlying causes and used those to propose urgently needed mitigating actions. We report that the first large‐scale UK outbreak of the wheat stem rust fungus, Puccinia graminis f. sp. tritici (Pgt), in 2022 may have been caused by timely arrival of airborne urediniospores from southwest Europe. The drive towards later‐maturing wheat varieties in the UK may be exacerbating Pgt incidences, which could have disastrous consequences. Indeed, infection assays showed that two UK Pgt isolates from 2022 could infect over 96% of current UK wheat varieties. We determined that the temperature response data in current disease risk simulation models are outdated. Analysis of germination rates for three current UK Pgt isolates showed substantial variation in temperature response functions, suggesting that the accuracy of disease risk simulations would be substantially enhanced by incorporating data from prevailing Pgt isolates. As Pgt incidences continue to accelerate in western Europe, we advocate for urgent action to curtail Pgt losses and help safeguard future wheat production across the region. [ABSTRACT FROM AUTHOR]

Background: The sudden introduction of social distancing measures in response to the COVID-19 pandemic resulted in significant lifestyle changes for the UK population. People living with physical disabilities were deemed to be at greater risk of complications following COVID-19 infection and were subjected to stricter social distancing guidelines. But gaps remain in our understanding of how the COVID-19 pandemic and associated restrictions affected the ability to access support, health and wellbeing of people with physical disabilities. Such understanding is vital to ensure equitable future pandemic preparedness for people living with physical disabilities. Methods: We conducted qualitative semi-structured interviews with 31 people living in the UK between May 2020 and January 2022. All participants self-identified as having a physical disability that affected their mobility, sight, or hearing. We analysed the data using reflexive thematic analysis. Results: Six themes were identified that described the impact of the pandemic on ability to access support, health and wellbeing: (i) adaptations to healthcare provision led to difficulties in managing health and wellbeing; (ii) exacerbations of inequalities in access to public space due to social distancing guidelines; (iii) experiences of hostility from able-bodied people; (iv) loss of social lives and encounters; (v) difficulties maintaining distance from others and subsequent fear of infection and (vi) strategies to support wellbeing and coping when confined to the home. Conclusion: The COVID-19 pandemic exacerbated existing health and social inequalities experienced by disabled people. The disproportionate impact of the pandemic on service provision and social connections resulted in challenging circumstances for disabled people who faced unmet medical needs, deteriorating health, and at times, hostile public spaces. Disabled people's experiences need to be incorporated into future pandemic or health-related emergency planning to ensure equality of access to services and public spaces to ensure their health and wellbeing is supported and maintained. [ABSTRACT FROM AUTHOR]

Background and aims: Understanding the amounts of intensity-specific movement needed to attenuate the association between sedentary time and mortality may help to inform personalized prescription and behavioral counselling. Herein, we examined the joint associations of sedentary time and intensity-specific physical activity with all-cause and cardiovascular disease (CVD) mortality. Methods: Prospective cohort study including 73,729 adults from the UK Biobank who wore an Axivity AX3 accelerometer on their dominant wrist for at least 3 days, being one a weekend day, between June 2013 and December 2015. We considered the median tertile values of sedentary time and physical activity in each intensity band to determine the amount of physical activity needed to attenuate the association between sedentary time and mortality. Results: During a median of 6.9 years of follow-up (628,807 person-years), we documented 1521 deaths, including 388 from CVD. Physical activity of any intensity attenuated the detrimental association of sedentary time with mortality. Overall, at least a median of 6 min/day of vigorous physical activity, 30 min/day of MVPA, 64 min/day of moderate physical activity, or 163 min/day of light physical activity (mutually-adjusted for other intensities) attenuated the association between sedentary time and mortality. High sedentary time was associated with higher risk of CVD mortality only among participants with low MVPA (HR 1.96; 95% CI 1.23 to 3.14). Conclusions: Different amounts of each physical activity intensity may attenuate the association between high sedentary time and mortality. [ABSTRACT FROM AUTHOR]

Haplotype estimation, or phasing, has gained significant traction in large-scale projects due to its valuable contributions to population genetics, variant analysis, and the creation of reference panels for imputation and phasing of new samples. To scale with the growing number of samples, haplotype estimation methods designed for population scale rely on highly optimized statistical models to phase genotype data, and usually ignore read-level information. Statistical methods excel in resolving common variants, however, they still struggle at rare variants due to the lack of statistical information. In this study we introduce SAPPHIRE, a new method that leverages whole-genome sequencing data to enhance the precision of haplotype calls produced by statistical phasing. SAPPHIRE achieves this by refining haplotype estimates through the realignment of sequencing reads, particularly targeting low-confidence phase calls. Our findings demonstrate that SAPPHIRE significantly enhances the accuracy of haplotypes obtained from state of the art methods and also provides the subset of phase calls that are validated by sequencing reads. Finally, we show that our method scales to large data sets by its successful application to the extensive 3.6 Petabytes of sequencing data of the last UK Biobank 200,031 sample release. Author summary: Haplotype estimation, also known as phasing, is now applied to population scale projects, typically of hundreds of thousands of samples to millions of samples. Generally phasing relies on statistical methods as they provide very accurate results for common variations. However, for rare and very rare variants the lack of statistical power often results in poor phasing. The large amount of rare variations discovered with whole-genome sequencing as well as the number of samples makes it expensive to process. We have developed the SAPPHIRE method that leverages whole-genome sequencing data to verify and correct the phase at poorly phased variant loci. It does so by finding sequencing reads that contain both the poorly phased variant and an accurately phased common variant. SAPPHIRE scales with large data sets by specifically targeting variation where statistical phasing performed poorly, therefore it reduces the quantity of sequencing data to be processed and combines the advantages of both read-based and statistical approaches. We show the efficiency of SAPPHIRE by improving the estimated haplotypes for 200,031 samples in the UK Biobank. SAPPHIRE is free and available as open-source software. [ABSTRACT FROM AUTHOR]

The Multi‐Action Plan (MAP) model presents an idiosyncratic framework for human performance. MAP research has categorised four Performance Types (PTs; T1–T4) using self‐paced activities. Specifically, T1–4 present four distinct mental states experienced by athletes during performance, differing, among other aspects, in the level of effort and perceived control. However, transitions between PTs are yet to be empirically investigated. This study aimed to examine MAP in the hyperdynamic open‐skill combat context of judo. We explored how judoka experienced PTs and the transition processes between these mental states. Six British, high‐level judoka (n = 6; Mdnage = 19) were interviewed using a retrospective semi‐structured interview schedule. Interpretative phenomenological analysis indicated that judo presents a hyperdynamic difficult‐to‐predict performance context due to the opponent and fighting rhythm. Second, participants strongly related to T2 and T3 and less to T1 and T4. They also reported experiences 'between' T2 and T3. Lastly, participants reported common transition pathways (e.g., T2–T3), typical transition cues, and specific trainable strategies to optimise performance. Findings are discussed in relation to existing literature. Lastly, we present limitations, applied, and research considerations. Highlights: The Multi‐Action Plan model presents four distinct mental states experienced by athletes during performance, differing, among other aspects, in the level of effort and perceived control.The study findings indicate that judo presents a complex and dynamic performance environment, in which judoka (judo practitioners) mostly experience effortful and controlled mental states.Judoka experience specific transitions and respective self‐regulatory processes between mental states during a fight, which can lead to optimal (upregulation) or suboptimal (downregulation) performance. [ABSTRACT FROM AUTHOR]

Introduction: Oral semaglutide improves cardiovascular risk factors in people with type 2 diabetes (T2D) in clinical trials, though real-world evidence is limited. We aimed to determine the real-world impact of oral semaglutide on routinely collected clinical data in our practice. Methods: People with T2D initiated on oral semaglutide in secondary care diabetes clinics at two hospital sites in Wales (United Kingdom) were included. Data were collected on reasons for oral semaglutide initiation and changes in bodyweight, blood pressure, glycemic control, and lipid profiles over follow-up at 3–6 months, and at 6–12 months. Data were collected to determine the safety of oral semaglutide. Results: Seventy-six patients were included, with a median age 59.3 [51.4–67.6] years, and 38 (50.0%) patients were female. The most common reasons for oral semaglutide were need for weight loss and improved glycemia (69.8%), and improved glycemia alone (25.0%). Oral semaglutide associated with significantly reduced bodyweight (− 3.3 kg), body mass index (BMI) (– 0.9 kg/m2), glycated hemoglobin (HbA1c) (− 11 mmol/mol), and total cholesterol (− 0.4 mmol/l) by 3–6 months follow-up. At 6–12 months, there was a significant reduction in systolic blood pressure (− 7.0 mmHg), in addition to sustained reductions in other metabolic parameters. By 12 months, 18 (23.6%) patients had discontinued the drug, largely resulting from gastrointestinal disturbance, but there were no serious events in this cohort. Conclusions: Oral semaglutide was effective in improving cardiovascular risk factors in this real-world population living with T2D, and no serious events were identified related to oral semaglutide in this patient group. [ABSTRACT FROM AUTHOR]

Aims: Genetic testing can be used to improve the safety and effectiveness of commonly prescribed medicines—a concept known as pharmacogenetics. This study aimed to quantify members of the UK public's preferences for a pharmacogenetic service to be delivered in primary care in the National Health Service. Methods: Members of the UK population were surveyed via an online panel company. Respondents completed 1 of 2 survey versions, asking respondents to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or pain. A conditional logit model was estimated, before the best functional form for the dataset was identified. Preference heterogeneity was identified via latent class analysis. Coefficients from the final selected models were used to estimate uptake in the context of different hypothetical pharmacogenetic services. Results: Responses from 1993 individuals were included in the analysis. There were no differences observed in preference between the 2 clinical scenarios. Conditional logit analysis, using maximum likelihood estimation, indicated that respondents preferred to have noninvasive tests and wanted their data to be shared between different healthcare organizations to guide future prescribing. There was a preference for regional over national data sharing initiatives, and respondents preferred to have access to their data. Predicted uptake varied considerably, ranging from 51% to >99%, depending on design of the service. Conclusion: This study identifies public preferences for a pharmacogenetic testing service and demonstrates how predicted uptake can be impacted by relatively minor adaptations. This highlights areas for prioritization during development of future pharmacogenetic services. [ABSTRACT FROM AUTHOR]

The area of land dedicated to growing maize for bioenergy in the United Kingdom is rapidly expanding. To understand how maize production influences soil carbon (C) dynamics, and whether this is influenced by soil type, we measured net ecosystem exchange (NEE) using the eddy covariance technique over the 2021 growing season. We combined the NEE data with C imports and exports to calculate the net ecosystem productivity (NEP) of two maize crops grown for bioenergy in the United Kingdom, one site on mineral soil and the other on lowland agricultural peat. Maize was similarly productive at both sites—gross primary productivity was 1107 g C m−2 at the site with mineral soil and 1407 g C m−2 at the peat site. However, total ecosystem respiration was considerably higher from the peat site (1198 g C m−2) compared with the mineral soil site (678 g C m−2). After accounting for the removal of C in harvested biomass, both sites were net C sources, but C losses were over two times greater from the peat site (NEP = 290 g C m−2) than the mineral site (NEP = 136 g C m−2). While annual crops may be needed to produce bioenergy in the short term, growing maize for bioenergy in the United Kingdom does not appear to be a viable option for C sequestration over the long term, as it leads to high carbon losses from agroecosystems, especially those on organic soils. Instead, growing perennial bioenergy crops on mineral soils with a low organic C content is a more appropriate option. [ABSTRACT FROM AUTHOR]

This research compares food insecurity for U.K. veterans and nonveterans using the United States Department of Agriculture (USDA) 10-item Adult Food Security Survey Module (AFSSM) for a sample of 1,492 participants. We find 1 in 10 veterans are living in a food-insecure household but that veteran status is not related to food insecurity. In addition, income and housing benefits are correlated with food insecurity for veterans and for nonveterans, but disability benefits are correlated with food insecurity among veterans only. Specifically, veterans with disability benefits averaged 1.12 (95% confidence interval, [0.42, 1.82]) more points (indicating more food insecurity) on the AFFSM than veterans without those benefits. These findings raise concerns that low-income disabled veterans with housing needs are a unique population at risk of living in food insecurity. Given the absence of research on food insecurity among U.K. veterans, it is necessity to study this population in greater detail and implement screening protocols where possible. [ABSTRACT FROM AUTHOR]

Background: While dietary salt intake has been linked with gastric cancer risk in Asian studies, findings from Western populations are sparse and limited to case—control studies. Our aim was to evaluate the frequency of adding salt to food at table in relation to gastric cancer risk among UK adults. Methods: We evaluated associations between the frequency of adding salt to food and the risk of gastric cancer in the UK Biobank (N = 471,144) using multivariable Cox regression. Frequency of adding salt to food was obtained from a touchscreen questionnaire completed at baseline (2006–2010). 24-h urinary sodium excretion was estimated using INTERSALT formulae. Cancer incidence was obtained by linkage to national cancer registries. Results: During a median follow-up period of 10.9 years, 640 gastric cancer cases were recorded. In multivariable models, the gastric cancer risk among participants reporting adding salt to food at table "always" compared to those who responded "never/rarely" was HR = 1.41 (95% CI: 1.04, 1.90). There was a positive linear association between estimated 24-h urinary sodium levels and the frequency of adding salt to food (p-trend <0.001). However, no significant association between estimated 24-h urinary sodium with gastric cancer was observed (HR = 1.19 (95% CI: 0.87, 1.61)). Conclusions: "Always adding salt to food" at table was associated with a higher gastric cancer risk in a large sample of UK adults. High frequency of adding salt to food at table can potentially serve as a useful indicator of salt intake for surveillance purposes and a basis for devising easy-to-understand public health messages. [ABSTRACT FROM AUTHOR]

Background: Despite its recognized importance, there is currently no reliable tool for surgical quality assurance (SQA) of gastrectomy in surgical oncology. The aim of this study was to develop an SQA tool for gastrectomy and to apply this tool within the ADDICT Trial in order to assess the extent and completeness of lymphadenectomy. Methods: The operative steps for D1+ and D2 gastrectomy have been previously described in the literature and ADDICT trial manual. Two researchers also performed fieldwork in the UK and Japan to document key operative steps through photographs and semi-structured interviews with expert surgeons. This provided the steps that were used as the framework for the SQA tool. Sixty-two photographic cases from the ADDICT Trial were rated by three independent surgeons. Generalizability (G) theory determined inter-rater reliability. D-studies examined the effect of varying the number of assessors and photographic series they rated. Chi-square assessed intra-rater reliability, comparing how the individual assessor's responses corresponded to their global rating for extent of lymphadenectomy. Results: The tool comprised 20 items, including 19 anatomical landmarks and a global rating score. Overall reliability had G-coefficient of 0.557. Internal consistency was measured with a Cronbach's alpha score of 0.869 and Chi-square confirmed intra-rater reliability for each assessor as < 0.05. Conclusions: A photographic surgical quality assurance tool is presented for gastrectomy. Using this tool, the assessor can reliably determine not only the quality but also the extent of the lymphadenectomy performed based on remaining anatomy rather than the excised specimen. [ABSTRACT FROM AUTHOR]

Considering the high prevalence and poor prognosis of cardiometabolic multimorbidity (CMM), identifying causal factors and actively implementing preventive measures is crucial. However, Mendelian randomization (MR), a key method for identifying the causal factors of CMM, requires knowledge of the effects of SNPs on CMM, which remain unknown. We first analyzed the genetic overlap of single cardiometabolic diseases (CMDs) using the latest genome‐wide association study (GWAS) for evidential support and comparison. We observed strong positive genetic correlations and shared loci among all CMDs. Further, GWAS and post‐GWAS analyses of CMM were performed in 407 949 European ancestry individuals from the UK Biobank. Eleven loci and 12 lead SNPs were identified. By comparison, we found these SNPs were a subset of SNPs associated with CMDs, including both shared and non‐shared SNPs. Then, the polygenic risk score model predicted the risk of CMM (C‐index = 0.62) and we identified candidate genes related to lipid metabolism and immune function. Finally, as an example, two‐sample MR analysis based on the GWAS revealed potential causal effects of total cholesterol, serum urate, body mass index, and smoking on CMM. These results provide a basis for future MR research and inspire future studies on the mechanism and prevention of CMM. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) are often underpowered due to small effect sizes of common single nucleotide polymorphisms (SNPs) on phenotypes and extreme multiple testing thresholds. The most common approach for increasing statistical power is to increase sample size. We propose an alternative strategy of redefining case-control outcomes into ordinal case-subthreshold-asymptomatic variables. While maintaining the clinical case threshold, we subdivide controls into two groups: individuals who are symptomatic but do not meet the clinical criteria for diagnosis (subthreshold) and individuals who are effectively asymptomatic. We conducted a simulation study to examine the impact of effect size, minor allele frequency, population prevalence, and the prevalence of the subthreshold group on statistical power to detect genetic associations in three scenarios: a standard case-control, an ordinal, and a case-asymptomatic control analysis. Our results suggest the ordinal model consistently provides the greatest statistical power while the case-control model the least. Power in the case-asymptomatic control model reflects the case-control or ordinal model depending on the population prevalence and size of the subthreshold category. We then analyzed a major depression phenotype from the UK Biobank to corroborate our simulation results. Overall, the ordinal model improves statistical power in GWAS consistent with increasing the sample size by approximately 10%. [ABSTRACT FROM AUTHOR]

Brexit will have implications on financial stability and the implementation of macroprudential policies. The United Kingdom (UK) will no longer be subject to the jurisdiction of the European Systemic Risk Board. This paper studies the welfare implications of this change of regime. By means of a dynamic stochastic general equilibrium model, I compare the pre‐Brexit scenario with the new one, in which the UK sets macroprudential policy independently. I find that, after Brexit, the UK is better off by setting its own macroprudential policy without taking into account Europe's welfare as a whole. [ABSTRACT FROM AUTHOR]

Background and purpose: Logopenic variant primary progressive aphasia (lvPPA) is a major variant presentation of Alzheimer's disease (AD) that signals the importance of communication dysfunction across AD phenotypes. A clinical staging system is lacking for the evolution of AD‐associated communication difficulties that could guide diagnosis and care planning. Our aim was to create a symptom‐based staging scheme for lvPPA, identifying functional milestones relevant to the broader AD spectrum. Methods: An international lvPPA caregiver cohort was surveyed on symptom development under an 'exploratory' survey (34 UK caregivers). Feedback from this survey informed the development of a 'consolidation' survey (27 UK, 10 Australian caregivers) in which caregivers were presented with six provisional clinical stages and feedback was analysed using a mixed‐methods approach. Results: Six clinical stages were endorsed. Early symptoms included word‐finding difficulty, with loss of message comprehension and speech intelligibility signalling later‐stage progression. Additionally, problems with hearing in noise, memory and route‐finding were prominent early non‐verbal symptoms. 'Milestone' symptoms were identified that anticipate daily‐life functional transitions and care needs. Conclusions: This work introduces a new symptom‐based staging scheme for lvPPA, and highlights milestone symptoms that could inform future clinical scales for anticipating and managing communication dysfunction across the AD spectrum. [ABSTRACT FROM AUTHOR]

Background and purpose: The eye is a well‐established model of brain structure and function, yet region‐specific structural correlations between the retina and the brain remain underexplored. Therefore, we aim to explore and describe the relationships between the retinal layer thicknesses and brain magnetic resonance image (MRI)‐derived phenotypes in UK Biobank. Methods: Participants with both quality‐controlled optical coherence tomography (OCT) and brain MRI were included in this study. Retinal sublayer thicknesses and total macular thickness were derived from OCT scans. Brain image‐derived phenotypes (IDPs) of 153 cortical and subcortical regions were processed from MRI scans. We utilized multivariable linear regression models to examine the association between retinal thickness and brain regional volumes. All analyses were corrected for multiple testing and adjusted for confounders. Results: Data from 6446 participants were included in this study. We identified significant associations between volumetric brain MRI measures of subregions in the occipital lobe (intracalcarine cortex), parietal lobe (postcentral gyrus), cerebellum (lobules VI, VIIb, VIIIa, VIIIb, and IX), and deep brain structures (thalamus, hippocampus, caudate, putamen, pallidum, and accumbens) and the thickness of the innermost retinal sublayers and total macular thickness (all p < 3.3 × 10−5). We did not observe statistically significant associations between brain IDPs and the thickness of the outer retinal sublayers. Conclusions: Thinner inner and total retinal thicknesses are associated with smaller volumes of specific brain regions. Notably, these relationships extend beyond anatomically established retina–brain connections. [ABSTRACT FROM AUTHOR]

Background and purpose: Treatment persistence is the continuation of therapy over time. It reflects a combination of treatment efficacy and tolerability. We aimed to describe real‐world rates of persistence on disease‐modifying therapies (DMTs) for people with multiple sclerosis (pwMS) and reasons for DMT discontinuation. Methods: Treatment data on 4366 consecutive people with relapse‐onset multiple sclerosis (MS) were pooled from 13 UK specialist centres during 2021. Inclusion criteria were exposure to at least one MS DMT and a complete history of DMT prescribing. PwMS in blinded clinical trials were excluded. Data collected included sex, age at MS onset, age at DMT initiation, DMT treatment dates, and reasons for stopping or switching DMT. For pwMS who had received immune reconstituting therapies (cladribine/alemtuzumab), discontinuation date was defined as starting an alternative DMT. Kaplan–Meier survival analyses were used to express DMT persistence. Results: In 6997 treatment events (1.6 per person with MS), median time spent on any single maintenance DMT was 4.3 years (95% confidence interval = 4.1–4.5 years). The commonest overall reasons for DMT discontinuation were adverse events (35.0%) and lack of efficacy (30.3%). After 10 years, 20% of people treated with alemtuzumab had received another subsequent DMT, compared to 82% of people treated with interferon or glatiramer acetate. Conclusions: Immune reconstituting DMTs may have the highest potential to offer a single treatment for relapsing MS. Comparative data on DMT persistence and reasons for discontinuation are valuable to inform treatment decisions and in personalizing treatment in MS. [ABSTRACT FROM AUTHOR]

Introduction: Thermoregulation refers to the ability to maintain a stable internal body temperature regardless of external conditions. In neonates, particularly preterm infants, thermoregulation is critical due to several factors. Objective: To assess the knowledge on thermoregulation among the mothers of under five children in selected hospitals, Dehradun (UK),To assess the practise of thermoregulation among the mothers of under five children in selected hospitals, Dehradun (UK),To assess the Effectiveness of planned teaching programme on knowledge and practice regarding thermoregulation among the mothers of under five children in selected hospitals, Dehradun (UK). Methodology-The researchers have used A Quasi Experimental Research Design (One group Pre-test and Post-test).Non Probability Purposive sampling technique was used.80 Mothers who fullfill the inclusion criteria were included in the study In the present study the below scales were used to collect the data. Structured Questionnaire and observational checklist was used to assess the Effectiveness of planned teaching programme on knowledge and practice regarding thermoregulation among the mothers of under five children in selected hospitals, Dehradun (UK). Conclusion: The planned teaching programme significantly improved the knowledge and practices of thermoregulation among mothers of under-five children. Educating mothers on thermoregulation techniques is crucial for reducing temperature-related health issues in children, thereby improving their overall health outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Vasa previa (VP), defined as unprotected fetal vessels traversing the membranes over the cervix, is associated with a high perinatal mortality when undiagnosed prenatally. Conversely, prenatal diagnosis with ultrasound and cesarean delivery before the membranes rupture is associated with excellent outcomes. However, controversy exists regarding screening for VP. In the UK, routine screening for VP is not recommended. The objective of this study was to report the incidence of VP and our experience in the detection of VP with a universal screening protocol at the time of the second‐trimester fetal anomaly scan with third‐trimester confirmation in an unselected population of pregnancies. Material and methods: We performed a single‐center historical cohort study of all pregnant women who underwent routine second‐trimester anomaly screening scans at West Middlesex University Hospital, London, UK, between 2012 and 2016. Over 5 years, every patient undergoing routine anomaly screening was evaluated for VP using a systematic protocol during their 20‐week anomaly scan. Suspected cases of VP were rescanned in the third trimester by specialist sonographers with an interest in VP. The primary outcomes were the incidence and detection of VP. Results: During the study period, 24 690 anatomy scans were performed. A total of 64 patients were identified as having potential VP at the second‐trimester anomaly screening scan, of which 19 were confirmed by the specialist sonographer in the third trimester and at delivery. The screen positive rate was 0.26% (95% confidence interval [CI] 0.20%–0.32%). VP at birth was found in 19/24690 births (1:1299 [95% CI: 1:832–1:2030] births). Universal screening for VP using our protocol had a sensitivity of 100% and a specificity of 99.78% (95% CI: 99.72%–99.84%). The false‐positive rate of the second‐trimester screen was 0.18% (95% CI: 0.13–0.24). There were no false positives or false negatives at delivery. Of the 19 patients with confirmed VP, 17 had scheduled cesarean deliveries, and two required emergency deliveries due to antepartum hemorrhage. One baby died, giving a perinatal mortality of 5%. Conclusions: VP complicates approximately 1:1300 pregnancies. Routine screening for VP yielded a 100% detection rate. We suggest the inclusion of structured VP assessment in standard fetal anomaly screening programs. [ABSTRACT FROM AUTHOR]

Introduction: Pregnant women with a fibrinogen level <2 g/L represent a high‐risk group that is associated with severe postpartum hemorrhage and other complications. Women who would qualify for fibrinogen therapy are not yet identified. Material and methods: A population‐based cross‐sectional study was conducted using the UK Obstetric Surveillance System between November 2017 and October 2018 in any UK hospital with a consultant‐led maternity unit. Any woman pregnant or immediately postpartum with a fibrinogen <2 g/L was included. Our aims were to determine the incidence of fibrinogen <2 g/L in pregnancy, and to describe its causes, management and outcomes. Results: Over the study period 124 women with fibrinogen <2 g/L were identified (1.7 per 10 000 maternities; 95% confidence interval 1.4–2.0 per 10 000 maternities). Less than 5% of cases of low fibrinogen were due to preexisting inherited dysfibrinogenemia or hypofibrinogenemia. Sixty percent of cases were due to postpartum hemorrhage caused by placental abruption, atony, or trauma. Amniotic fluid embolism and placental causes other than abruption (previa, accreta, retention) were associated with the highest estimated blood loss (median 4400 mL) and lowest levels of fibrinogen. Mortality was high with two maternal deaths due to massive postpartum hemorrhage, 27 stillbirths, and two neonatal deaths. Conclusions: Fibrinogen <2 g/L often, but not exclusively, affected women with postpartum hemorrhage due to placental abruption, atony, or trauma. Other more rare and catastrophic obstetrical events such as amniotic fluid embolism and placenta accreta also led to low levels of fibrinogen. Maternal and perinatal mortality was extremely high in our cohort. [ABSTRACT FROM AUTHOR]

Pasteurised donor human milk is recommended for very low birthweight infants who do not have access to their mother's milk. Although the use of donor milk continues to increase, little is known about the donation experiences of milk bank donors. We aimed to describe and compare enablers, barriers and patterns of human milk donation and identify factors predicting donation volume in a convenience sample of approved milk bank donors in the United Kingdom and the United States. A cross‐sectional online survey was conducted from August 2022 to December 2022. Approved milk bank donors (n = 556) from three milk banks in the United States (n = 369, Mothers' Milk Bank of Florida, Mother's Milk Bank of North Texas and Northwest Mothers Milk Bank) and one milk bank in the United Kingdom (n = 187, Hearts Milk Bank) completed the survey. A substantial portion of donors in both settings reported participating in other forms of milk exchange (51% of U.S. donors vs. 39% of UK donors, p = 0.009). Top donation barriers reported in both settings were completing the serological screening and having enough space to store collected milk. Most donors started donating when their infant was 3 months old or older and reported donating mature milk. The most common source of information related to milk banking in each setting was the internet (United Kingdom–70% vs. United States ‐ 63%, p = 0.112). Variables that predicted lifetime donation volume differed between the United States and the United Kingdom, highlighting the importance of setting‐specific milk banking research. Key messages: Milk bank donors in the United Kingdom and the United States reported primarily receiving milk banking information from the internet and not their health care provider.A substantial portion of human milk bank donors in the United Kingdom and the United States participate in other forms of milk exchange, including sharing with a peer.Participating in other forms of milk exchange did not predict lower milk bank donation volumes.Barriers to donation and predictors of donation volume differed between donors in the United Kingdom and the United States, suggesting setting‐specific research is warranted to improve the donation process globally. [ABSTRACT FROM AUTHOR]

Background: An imbalance in lipid metabolism has been linked to the development of AMD, but the causal relationship between AMD and plasma fatty acids (FAs) remains controversial. Using a two-sample Mendelian randomization (MR) approach, we sought to evaluate the impact of specific FA plasma levels on the risk of different AMD subtypes. Methods: We analysed genome-wide association data of circulating FAs from 115,006 European-descended individuals in the UK Biobank. These data were used in a two-sample MR framework to assess the potential role of circulating FAs in developing wet and dry AMD. Sensitivity analyses were conducted to ensure the robustness of our findings. Additional multivariable and locus-specific MR analyses were conducted to evaluate direct effects of FA on AMD subtypes, minimizing biases from lipoprotein-related traits and triglycerides. Results: Mendelian randomization revealed associations of omega-3 was associated with decreased wet (OR 0.78, 95%CI 0.66–0.92) and dry AMD (0.85, 0.74–0.97) risk, showed a protective effect on AMD. Notably, the omega-6 to omega-3 ratio showed potential causal effects on both wet (1.27, 1.03–1.56) and dry AMD (1.18, 1.02–1.37). Multivariable MR suggested that the causal relationship of omega-3, omega-6 to omega-3 ratio on wet AMD persists after conditioning on HDL, LDL and triglycerides, albeit with slightly diminished evidence strength. Locus-specific MR linked to omega-3(FADS1, 0.89, 0.82–0.98; FADS2, 0.88, 0.81–0.96) and omega-6 to omega-3 ratio (FADS1, 1.10, 1.02–1.20; FADS2, 1.11, 1.03–1.20) suggests causal effects of these factors on wet AMD. Conclusions: The associations between plasma FA concentrations and AMD, suggest potential causal role of omega-3, and the omega-6 to omega-3 ratio in wet AMD. These results underscore the impact of an imbalanced circulating omega-3 and omega-6 FA ratio on AMD pathophysiology from MR perspective. [ABSTRACT FROM AUTHOR]

Like other group-living species, humans often cooperate more with an in-group member than with out-group members and strangers. Greater in-group favoritism should imply that people also compete less with in-group members than with out-group members and strangers. However, in situations where people could invest to take other's resources and invest to protect against exploitation, we observed the opposite. Akin to what in other species is known as the "nasty neighbor effect," people invested more when facing an in-group rather than out-group member or stranger across 51 nations, in different communities in Kenya, and in representative samples from the United Kingdom. This "nasty neighbor" behavior is independent of in-group favoritism in trust and emerges when people perceive within-group resource scarcity. We discuss how to reconcile that humans exhibit nastiness and favoritism toward in-group members with existing theory on in-group favoritism. [ABSTRACT FROM AUTHOR]

Social prescribing (SP) is a promising intersectoral strategy of integrated and person-centered care that can improve individual health and well-being by going beyond medical treatment, potentially reducing overall disease burden on health system. SP addresses health and social determinants of health by linking patients to community responses, i.e. services and initiatives fostering social interaction, physical activity and creativity, among other health-promoting aspects, provided by local public, private, and non-profit entities. There is limited research on the implementation processes of SP beyond the UK, hindering improvement and scale-up. This study aims to identify enablers and barriers of implementation of an SP program conducted in Portugal. A participatory and qualitative approach was used to assess the implementation of an SP program in health units. Semi-structured interviews were conducted with family doctors, social workers and representatives of community partners who participated in SP implementation. The Consolidated Framework for Implementation Research was used to conduct thematic analysis. The main enablers of SP implementation included its recognition as an evolution towards a holistic model of health, the personal characteristics of professionals as being proactive, motivated, and concerned with social determinants of health, and the communication strategy used to engage the stakeholders. Perceived challenges included raising users' awareness of SP and ensuring intervention adherence. Lack of preparedness for intersectoral working processes, including insufficient communication channels, limited community responses and the need for a more systematic collection of data on activities adherence and progress were also highlighted as barriers to SP implementation. SP implementation seems simple, but the results show that in practice, we are facing a complex intervention with multiple stakeholders, diverse community responses and factors influencing project success. A deeper understanding of SP specificities, local context, enablers, and barriers is vital to develop strategies for improvement and successful implementation, ensuring scalability and sustainability. [ABSTRACT FROM AUTHOR]

Background: Colonoscopy is a valuable diagnostic tool but the procedure and the preparation for it cause anxiety and discomfort that impacts on patients' health-related quality of life (HRQoL). The 'disutility' of undergoing an invasive colonoscopy needs to be considered and accounted for in comprehensive cost-utility analyses that compare different diagnostic strategies, yet there is little empirical evidence that can be used in such studies. To fill this gap, we collected and analysed data on the effect of a colonoscopy examination on patients' HRQoL that can be used in economic evaluations. Methods: Patients scheduled to undergo a colonoscopy at a large NHS hospital were asked to complete the EuroQol EQ-5D-5 L instrument: (i) before the procedure, at the time of consent (T1), (ii) while undergoing bowel preparation (T2) and (iii) within 24 h after the procedure (T3). Complete responses were translated into preference-based HRQoL (utility) values using a UK-specific value set and were analysed using descriptive and inferential statistical analyses. Results: Two-hundred and seventy-one patients with gastrointestinal symptoms referred for a colonoscopy provided complete EQ-5D-5 L questionnaires at all three assessment points. At T1, the mean EQ-5D-5 L value was 0.76 (95%CI: 0.734–0.786). This value dropped to 0.727 at T2 (95%CI: 0.7–0.754, before increasing again to 0.794 (95%CI: 0.768–0.819) at T3. Both changes were statistically significant (p-value < 0.001). Conclusions: Preference-based HRQoL (utility) values reported by patients undergoing a colonoscopy dropped during bowel preparation and rose again shortly after the colonoscopy. This pattern was largely consistent across patients with different characteristics, symptoms and diagnoses. [ABSTRACT FROM AUTHOR]

Background: Liver disease and dementia are both highly prevalent and share common pathological mechanisms. We aimed to investigate the associations between metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of all-cause and cause-specific dementia. Methods: We conducted a prospective study with 403,506 participants from the UK Biobank. Outcomes included all-cause dementia, Alzheimer's disease, and vascular dementia. Multivariable Cox proportional hazards models were used for analyses. Results: 155,068 (38.4%) participants had MAFLD, and 111,938 (27.7%) had MASLD at baseline. During a median follow-up of 13.7 years, 5,732 participants developed dementia (2,355 Alzheimer's disease and 1,274 vascular dementia). MAFLD was associated with an increased risk of vascular dementia (HR 1.32 [95% CI 1.18–1.48]) but a reduced risk of Alzheimer's disease (0.92 [0.84–1.0]). Differing risks emerged among MAFLD subtypes, with the diabetes subtype increasing risk of all-cause dementia (1.8 [1.65–1.96]), vascular dementia (2.95 [2.53–3.45]) and Alzheimer's disease (1.46 [1.26–1.69]), the lean metabolic disorder subtype only increasing vascular dementia risk (2.01 [1.25–3.22]), whereas the overweight/obesity subtype decreasing risk of Alzheimer's disease (0.83 [0.75–0.91]) and all-cause dementia (0.9 [0.84–0.95]). MASLD was associated with an increased risk of vascular dementia (1.24 [1.1–1.39]) but not Alzheimer's disease (1.0 [0.91–1.09]). The effect of MAFLD on vascular dementia was consistent regardless of MASLD presence, whereas associations with Alzheimer's disease were only present in those without MASLD (0.78 [0.67–0.91]). Conclusions: MAFLD and MASLD are associated with an increased risk of vascular dementia, with subtype-specific variations observed in dementia risks. Further research is needed to refine MAFLD and SLD subtyping and explore the underlying mechanisms contributing to dementia risk. [ABSTRACT FROM AUTHOR]

In this study, we aimed to compare imaging-based features of brain function, measured by resting-state fMRI (rsfMRI), with individual characteristics such as age, gender, and total intracranial volume to predict behavioral measures. We developed a machine learning framework based on rsfMRI features in a dataset of 20,000 healthy individuals from the UK Biobank, focusing on temporal complexity and functional connectivity measures. Our analysis across four behavioral phenotypes revealed that both temporal complexity and functional connectivity measures provide comparable predictive performance. However, individual characteristics consistently outperformed rsfMRI features in predictive accuracy, particularly in analyses involving smaller sample sizes. Integrating rsfMRI features with demographic data sometimes enhanced predictive outcomes. The efficacy of different predictive modeling techniques and the choice of brain parcellation atlas were also examined, showing no significant influence on the results. To summarize, while individual characteristics are superior to rsfMRI in predicting behavioral phenotypes, rsfMRI still conveys additional predictive value in the context of machine learning, such as investigating the role of specific brain regions in behavioral phenotypes. Individual characteristics tend to over-perform fMRI-based metrics in the prediction of behavioral measures. However, the combination of both metrics can increase predictive accuracy, suggesting that fMRI-based metrics can successfully complement individual characteristics, mainly in large datasets. [ABSTRACT FROM AUTHOR]

Dairy production in the UK has undergone substantial restructuring over the last few decades. Farming intensification has led to a reduction in the total numbers of farms and animals, while the average herd size per holding has increased. These ever-changing circumstances have important implications for the health and welfare of dairy cows, as well as the overall business performance of farms. For decision-making in dairy farming, it is essential to understand the underlying causes of the inefficiencies and their relative impact. The investigation of yield gaps regarding dairy cattle has been focused on specific causes. However, in addition to the risk of overestimating the impact of a specific ailment, this approach does not allow understanding of the relative contribution to the total, nor does it allow understanding of how well-described that gap is in terms of underlying causes. Using the English and Welsh dairy sectors as an example, this work estimates the Loss Gap–composed of yield losses and health expenditure ‐ using a benchmarking approach and scenario analysis. The Loss Gap was estimated by comparing the current performance of dairy herds as a baseline with that of scenarios where assumptions were made about the milk production of cows, production costs, market prices, mortality, and expenditure related to health events. A deterministic model was developed, consisting of an enterprise budget, in which the cow was the unit, with milking herd and young stock treated separately. When constraining milk production, the model estimated an annual Loss Gap of £148 to £227 million for the whole sector. The reduction in costs of veterinary services and medicines, alongside herd replacement costs, were important contributors to the estimate with some variation between the scenarios. Milk price had a substantial impact in the estimate, with revenue from milk yield representing more than 30% of the Loss Gap, when milk price was benchmarked against that of the top performing farms. This framework provides the boundaries for understanding the relative burden from specific causes in English and Welsh dairy cattle, ensuring that the sum of the estimated losses due to particular problem does not exceed the losses from all-causes, health or non-health related. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has had enormous implications for the world of work. However, there has been relatively little focus on the employment and workforce challenges of the virus in relation to workforce health, beyond the immediate management of the spread of the disease. There is an important gap in understanding the ongoing workforce issues created by the significant incidence of Long COVID in the population. Aim: This paper examines the effects of Long COVID on employment and workers' mental health to contribute to understanding of work-limiting health conditions and to offer policy implications for COVID-19 and similar health conditions on employment and the workforce. Methods: A large national panel study for the UK is used to estimate the likelihood of exiting employment as well as on changes in working hours and general mental health and happiness of those who remain in work. The sample includes individuals 16 years and older who were in employment in January/February 2020 and followed during the pandemic 2020–2021. Long COVID is self-reported in the data. Informed by conceptual consideration of employment protection in the UK, two groups of individuals with Long COVID are defined based on the duration of symptoms. Group 1 has Long COVID 5–28 weeks after an infection with COVID-19, which is up to the maximum length of Statutory Sick Pay in the UK. Group 2 has symptoms for 29+ weeks, which is beyond the statutory entitlement to sickness pay. Panel regression models are fitted both with fixed-effects and random-effects. Individual and job characteristics are used as controls Those with no COVID-19 symptoms are the reference group. Results: In between-person comparison, Group 2 is at higher risk of exiting employment compared to those with no COVID-19 symptoms. Between-person estimates of mental health and well-being show negative effects of Long COVID for both groups but these are greatest in Group 2. Within-person estimates suggest that factors associated with earnings mediate the negative Long COVID effects on mental health in Group 1 and that Group 2 adapts to working with Long COVID. Group 1 is at risk of working zero hours (i.e. being on sick leave) but neither Group 1 nor Group 2 have a higher probability of working fewer hours compared to those with no COVID-19 symptoms. The negative impact of Long COVID on working hours stems primarily from working zero hours (sickness leave) rather than working fewer hours, suggesting a lack of accommodation by employers of Long COVID at work. Policy implications: The extension of Statutory Sickness Pay and greater flexibility to manage partial (returns to) work would help preserve employment and mental health. Those with Long COVID for 12 months are likely to meet the definition of disability and so have a right to receive reasonable workplace adjustments. [ABSTRACT FROM AUTHOR]

People on low-incomes in the UK develop multiple long-term health conditions over 10 years earlier than affluent individuals. Financial diaries -new to public health- are used to explore the lived experiences of financially-vulnerable individuals, diagnosed with at least one long-term condition, living in two inner-city London Boroughs. Findings show that the health status of these individuals is a key barrier to work opportunities, undermining their income. Their precarious and uncertain financial situation, sometimes combined with housing issues, increased stress and anxiety which, in turn, contributed to further deteriorate participants' health. Long-term health conditions limited the strategies to overcome moments of financial crisis and diarists frequently used credit to cope. Restrictions to access reliable services and timely support were connected to the progression of multiple long-term conditions. Models that integrate healthcare, public health, welfare and financial support are needed to slow down the progression from one to many long-term health conditions. [ABSTRACT FROM AUTHOR]

The recent rise in artificial intelligence systems, such as ChatGPT, poses a fundamental problem for the educational sector. In universities and schools, many forms of assessment, such as coursework, are completed without invigilation. Therefore, students could hand in work as their own which is in fact completed by AI. Since the COVID pandemic, the sector has additionally accelerated its reliance on unsupervised 'take home exams'. If students cheat using AI and this is undetected, the integrity of the way in which students are assessed is threatened. We report a rigorous, blind study in which we injected 100% AI written submissions into the examinations system in five undergraduate modules, across all years of study, for a BSc degree in Psychology at a reputable UK university. We found that 94% of our AI submissions were undetected. The grades awarded to our AI submissions were on average half a grade boundary higher than that achieved by real students. Across modules there was an 83.4% chance that the AI submissions on a module would outperform a random selection of the same number of real student submissions. [ABSTRACT FROM AUTHOR]

Probabilistic projections from the UK Climate Projections 2018 are presented for four global warming levels (GWLs) at 1.5, 2, 3, and 4°C above the 1850–1900 baseline. Our results show how uncertainties associated with climate models and four representative concentration pathways (RCP) emission scenarios translate to UK regional scale changes in maximum temperature and precipitation, with data also available for minimum and mean temperatures, humidity and surface net downward shortwave radiation flux. We compare weighting the likelihood of RCPs based on (hypothetical) policy decisions, against our baseline assumption that each RCP is equally likely. Differences between weighted and unweighted GWL distributions are small, particularly in relation to the full breadth of uncertainties that are incorporated into the probabilistic projections. Finally we quantify the relative importance of scenario, model and internal variability on regional projected GWLs and show that uncertainty associated with an uncertain climate response to forcings dominates at all GWLs. Plain Language Summary: Global warming levels define the global averaged increase in temperature since the pre‐industrial period. This study looks at what the regional climate in the UK could be like in the future. We estimate how temperature and precipitation in the UK might change under four different global warming levels (GWLs) (1.5, 2, 3, and 4°C above pre‐industrial times). We account for a wide range of outcomes from both climate models and future emissions scenarios. Assuming that the range of future emissions scenarios are equally likely, the center of the ranges of years that we could reach GWLs of 1.5, 2, 3, and 4°C are 2032, 2050, 2072, and 2078 respectively. The largest influence of future climate on these range estimates comes from our understanding of how the Earth actually responds to changes in greenhouse gases. Even if we knew the exact quantity of greenhouse gas emissions we would emit in the future, we still wouldn't be able to predict the exact changes in UK climate with perfect accuracy because our understanding of the regional climate response to these emissions requires further investigation. Key Points: Probabilistic climate projections from the UK are presented for four global warming levels (GWLs) across four representative concentration pathways (RCP)We show how uncertainty associated with climate models and future emission scenarios translate to UK regional scale changesUncertainty associated with an uncertain climate response to forcings dominates at all GWLs [ABSTRACT FROM AUTHOR]

LD score regression (LDSC) is a method to estimate narrow-sense heritability from genome-wide association study (GWAS) summary statistics alone, making it a fast and popular approach. In this work, we present interaction-LD score (i-LDSC) regression: an extension of the original LDSC framework that accounts for interactions between genetic variants. By studying a wide range of generative models in simulations, and by re-analyzing 25 well-studied quantitative phenotypes from 349,468 individuals in the UK Biobank and up to 159,095 individuals in BioBank Japan, we show that the inclusion of a cis-interaction score (i.e. interactions between a focal variant and proximal variants) recovers genetic variance that is not captured by LDSC. For each of the 25 traits analyzed in the UK Biobank and BioBank Japan, i-LDSC detects additional variation contributed by genetic interactions. The i-LDSC software and its application to these biobanks represent a step towards resolving further genetic contributions of sources of non-additive genetic effects to complex trait variation. [ABSTRACT FROM AUTHOR]

Background: Frailty is a clinical state that increases susceptibility to minor stressor events. The risk of frailty is higher in chronic conditions, such as Chronic Obstructive Pulmonary Disease (COPD). Recent studies on COPD have shown that patients living with frailty have an increased risk of mortality. The presence of cardiovascular diseases or conditions are common in COPD and may increase the risk of death. Methods: This protocol describes a European prospective cohort study of community-based people, in a stable condition with diagnosis of COPD (as defined by GOLD guidelines) across hospitals in Italy and UK. Frailty prevalence will be assessed using the Clinical Frailty Scale. At 1- and 2-year follow up, primary outcome will be the impact of frailty on the number of cardiovascular events; secondary outcomes: the influence of frailty on cardiovascular mortality, all-cause mortality, and deaths due to COPD. For the primary outcome a zero-inflated Poisson regression will compare the number of cardiovascular events at 1 year. Secondary outcomes will be analysed using the time to mortality. Discussion: This multicentre study will assess the association between frailty and cardiovascular events and mortality in population with COPD. Data collection is prospective and includes routine clinical data. This research will have important implications for the management of patients with COPD to improve their quality of care, and potentially prognosis. Trial registration number: NCT05922202 (www.clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Background: Dental caries remains a significant problem in England, affecting 11% of 3-year-olds and 23% of 5-year-olds. While current approaches have been extensively investigated, their ability to (1) control pain and infection; (2) prevent hospital admissions, and (3) be implemented within the National Health Service (NHS) contractual arrangements, remains unsatisfactory. Silver diamine fluoride (SDF) is an alternative, non-invasive approach that has proven efficacy in arresting caries progression in primary teeth, principally from studies conducted outside of Europe. Its use in primary dental care in the UK is limited, despite the acknowledged need. The clinical and cost-effectiveness of SDF has not been compared to usual care in the UK. Before a pragmatic randomised controlled trial (RCT) can be conducted to compare SDF to usual care for caries management in young children, there are several uncertainties that require investigation. This study aims to establish whether such an RCT is feasible. Methods: This mixed-method parallel design study is a feasibility study with an embedded process evaluation, to compare SDF with usual treatment in primary dental care in the UK. It will be individually randomised, with 13 dentists and therapists, in 8 different dental primary care sites with a sample size of 80 child participants aged 1–8 years old. The aim will be to recruit ten participants per site with equal arm allocation. Follow-up will be for 1 year. The study will inform whether an RCT is feasible by resolving several key uncertainties. The acceptability and implementation of SDF and the research processes will be explored. Patient and Public Involvement and Engagement representatives will be involved throughout recruitment and retention strategies, participant documentation, analysis, engagement and dissemination. Discussion: The ability to conduct an RCT will be evaluated. If feasible, this RCT has the potential to evaluate the effectiveness of a non-invasive approach for the management of untreated caries in young children. A feasibility study also offers the opportunity to consider factors associated with the implementation of SDF at an early stage through a process evaluation that will inform the definitive trial and an implementation strategy for SDF by identifying relevant barriers and facilitators. Trial registration: ClinicalTrials.gov identifier: NCT06092151. Date: 19/10/2023. [ABSTRACT FROM AUTHOR]

Background: Fibromyalgia is a common reason for referral to a rheumatologist and is a centralised pain state with symptoms beginning in adolescence/early adulthood and manifests as pain throughout the body, fatigue and cognitive dysfunction. Whilst there is considerable evidence on effective treatments, diagnosis and management are complex. There is almost no evidence on how to organise health services to deliver recommended therapies. The aim of the current study was to understand patient preferences for different features of healthcare services for fibromyalgia. Methodology: We use the Discrete Choice Experiment Method (DCE), a choice-based survey that quantifies preferences for attributes of goods, services or policy interventions, to elicit preferences in relation to alternative models of care for people with fibromyalgia. In this study, attributes describe different models of care for fibromyalgia. We based attributes and levels on earlier phases of the PACFiND project and a literature review on fibromyalgia models of care. The final analysis sample consisted of 518 respondents who completed the survey in full. Results: The final analysis sample consisted of 518 respondents ((patients living in the UK, over 18 years old, with a diagnosis of fibromyalgia), who completed the survey in full. The model of care most preferred is one characterised by earlier diagnosis and ongoing management by a Rheumatologist, via Face-to-face or Phone/video call appointments, with a stronger preference for the latter mode of support. The most preferred treatment was Medication, followed by Physical Therapy, with the least preferred being Talking Therapy. Relative to a Waiting Time for treatment of 6 months, respondents would prefer a lower Waiting Time of 3 months and dislike waiting 12 months for treatment. Respondents showed willingness to receive Ongoing Help and Advice by a Nurse Practitioner or a GP, instead of a Specialist Rheumatologist, provided they were compensated by other changes in the model of care. Conclusion: This study has found that, although respondents express a preference for specialist care, provided by a Rheumatologist, they may be willing to trade-off this preference against other features within a model of care. This willingness to accept a different skill-mix (e.g., appointments with a GP or a Nurse Practitioner) has important implications for practice and policy, as this is a more feasible option in settings where the availability of specialist care is highly constrained. [ABSTRACT FROM AUTHOR]

Background: Achilles tendon rupture (ATR) account for 10.7% of all tendon and ligament injuries and causes lasting muscular deficits and have a profound impact on patients' quality of life. The incidence, characteristics and management of ATR in the United Kingdom (UK) is poorly understood. This investigation aims to understand the incidence of ATR in the UK. Methods: Prospective data collection of ATR incidence from a United Kingdom Emergency department. Retrospective review of management protocols and immobilisation duration from electronic medical records. Results: ATR incidence is 8 per 100,000 people per annum. Participants were predominately male (79.2%) and primarily reported a sporting mechanism of injury (65.2%). Mean immobilisation duration was 63.1 days. 97.1% were non-surgically managed post ATR. 46.2% of participants had experienced a previous ATR or Achilles tendinopathy prior to their current ATR. Conclusion: The incidence of ATR found was 8. cases per 100,000 people per annum. Most ATR were managed non-surgically in this cohort. The majority of ruptures occurred during sporting activity. Almost one quarter (23.3%) of individuals report Achilles pain prior to ATR. [ABSTRACT FROM AUTHOR]

Introduction: Recruitment of care home staff to research studies is recognised as challenging. This was further exacerbated by the COVID-19 pandemic and the associated negative media portrayal of care home workers. Social media use has surged since the onset of COVID-19 lockdowns, offering a plausible approach to understanding the barriers to care home research recruitment and gaining insight into public perceptions of care home workers. Aim: To utilise comments from two Facebook recruitment posts to: 1) gain an understanding of potential barriers to recruitment of healthcare workers (HCWs) in UK care homes, and 2) explore public sentiment towards care home research and care homes in the context of the COVID-19 pandemic. Methods: This cross-sectional study analysed comments from two Facebook posts (available June-October 2021) advertising a separate study on psychological support for care staff during the pandemic. This study was situated within a larger investigation into the mental health and wellbeing of care home staff and employed both qualitative analysis and quantitative methods (word count and correlations between words used and between posts). Results: Three themes were identified from the qualitative analysis: support, mistrust and blame. There was a greater use of words associated with support and negative emotive words in post 2. Post 2 comments featured significantly more choice words and first-person singular pronouns than post 1 which indicated a resentful sentiment from those who advocate freedom of choice and control. Discussion of mistrust towards researchers was most prominent in post 1 indicating the importance of relationship building between researchers and HCWs in UK care homes. With attribution to blame, there was a larger range of negative emotion words than positive emotion words. Discussion and conclusion: Taken together our findings offer novel insights into why recruitment to care home research during the pandemic including the use of social media might be problematic. Social media is a useful tool for recruitment but should not be considered as a one-time input. Researchers should pro-actively engage with the study population from the start using co-design with resident and public groups to support recruitment and ensure these populations are accurately represented within research. [ABSTRACT FROM AUTHOR]

Background: Preconception health has the potential to improve parental, pregnancy and infant outcomes. This scoping review aims to (1) provide an overview of the strategies, policies, guidelines, frameworks, and recommendations available in the UK and Ireland that address preconception health and care, identifying common approaches and health-influencing factors that are targeted; and (2) conduct an audit to explore the awareness and use of resources found in the scoping review amongst healthcare professionals, to validate and contextualise findings relevant to Northern Ireland. Methods: Grey literature resources were identified through Google Advanced Search, NICE, OpenAire, ProQuest and relevant public health and government websites. Resources were included if published, reviewed, or updated between January 2011 and May 2022. Data were extracted into Excel and coded using NVivo. The review design included the involvement of the "Healthy Reproductive Years" Patient and Public Involvement and Engagement advisory panel. Results: The searches identified 273 resources, and a subsequent audit with healthcare professionals in Northern Ireland revealed five additional preconception health-related resources. A wide range of resource types were identified, and preconception health was often not the only focus of the resources reviewed. Resources proposed approaches to improve preconception health and care, such as the need for improved awareness and access to care, preconceptual counselling, multidisciplinary collaborations, and the adoption of a life-course approach. Many behavioural (e.g., folic acid intake, smoking), biomedical (e.g., mental and physical health conditions), and environmental and social (e.g., deprivation) factors were identified and addressed in the resources reviewed. In particular, pre-existing physical health conditions were frequently mentioned, with fewer resources addressing psychological factors and mental health. Overall, there was a greater focus on women's, rather than men's, behaviours. Conclusions: This scoping review synthesised existing resources available in the UK and Ireland to identify a wide range of common approaches and factors that influence preconception health and care. Efforts are needed to implement the identified resources (e.g., strategies, guidelines) to support people of childbearing age to access preconception care and optimise their preconception health. [ABSTRACT FROM AUTHOR]

Background: Dietary changes are necessary to improve population health and meet environmental sustainability targets. Here we analyse the impact of promotional activities implemented in UK supermarkets on purchases of healthier and more sustainable foods. Methods: Three natural experiments examined the impact of promotional activities on sales of a) no-added-sugar (NAS) plant-based milk (in 199 stores), b) products promoted during 'Veganuary' (in 96 stores), and c) seasonal fruit (in 100 non-randomised intervention and 100 matched control stores). Data were provided on store-level product sales, in units sold and monetary value (£), aggregated weekly. Predominant socioeconomic position (SEP) of the store population was provided by the retailer. Analyses used interrupted time series and multivariable hierarchical mixed-effects models. Results: Sales of both promoted and total NAS plant-based milks increased significantly during the promotional period (Promoted:+126 units, 95%CI: 105–148; Overall:+307 units, 95%CI: 264–349). The increase was greater in stores with predominately low SEP shoppers. During Veganuary, sales increased significantly for plant-based foods on promotion (+60 units, 95%CI: 37–84), but not for sales of plant-based foods overall (dairy alternatives: -1131 units, 95%CI: -5821–3559; meat alternatives: 1403 units, 95%CI: -749–3554). There was no evidence of a change in weekly sales of promoted seasonal fruit products (assessed via ratio change in units sold: 0.01, 95%CI: 0.00–0.02), and overall fruit category sales slightly decreased in intervention stores relative to control (ratio change in units sold: -0.01, 95%CI: -0.01–0.00). Conclusion: During promotional campaigns there was evidence that sales of plant-based products increased, but not seasonal fruits. There was no evidence for any sustained change beyond the intervention period. [ABSTRACT FROM AUTHOR]

Background: Experiencing childbirth as traumatic is common and can have long-lasting negative consequences for women's mental health. However, fostering a sense of social identity has been shown to protect psychological wellbeing and mental health during life transitions, such as entering parenthood. This study therefore investigated the relationship between traumatic childbirth and first-time mothers' social identity and their psychological wellbeing, and more specifically whether strength of identity as a first-time mother protected psychological wellbeing following traumatic childbirth. Method: Women over the age of 18 who were living in the UK and had given birth to their first child in the past nine months were recruited to the study from clinical and community settings. They completed digital self-report questionnaires about their birth experience, social identity, mental health, and psychological wellbeing. Women who perceived themselves to have had a traumatic birth (the trauma group; N = 84) were compared to women who did not perceive themselves to have had a traumatic birth (the control group, N = 39). T-tests and chi square tests assessed preliminary group differences before multivariate analyses of covariance controlled for covariates. Post-hoc tests identified the direction of differences. Multiple regression and moderation analyses analysed interaction effects. Results: The trauma group had significantly lower psychological wellbeing (mean = 41.5, 95% CI [39.4–43.7], p =.008, partial η2 = 0.059), compared to the control group (mean = 48.4, 95% CI [45.3–51.5]), but the two groups did not differ in the strength of their first-time mother identity, which was high across both groups. Strength of identity did not moderate the relationship between traumatic childbirth and psychological wellbeing. Giving birth by caesarean section independently reduced the strength of the first-time mother identity (p =.017, partial η2 = 0.049). All analyses controlled for emotional and practical support, perceptions of healthcare staff, and mode of birth. Conclusions: Having a traumatic birth was associated with lower psychological wellbeing, and the strength of first-time mother identity does not appear to moderate this relationship. Factors such as mode of birth may be more important. Further research, including longitudinal designs, is needed to understand the relationship between these constructs and identify more effective ways of protecting first-time mothers' mental health. [ABSTRACT FROM AUTHOR]

Background: Disease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial. Methods: This randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the "Trials within Cohorts" (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19–9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment. Discussion: The RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients' quality of life will be obtained. Trial registration: Clinicaltrials.gov, NCT04875325. Registered on May 6, 2021. [ABSTRACT FROM AUTHOR]

Background: Findings from studies assessing Long Covid in children and young people (CYP) need to be assessed in light of their methodological limitations. For example, if non-response and/or attrition over time systematically differ by sub-groups of CYP, findings could be biased and any generalisation limited. The present study aimed to (i) construct survey weights for the Children and young people with Long Covid (CLoCk) study, and (ii) apply them to published CLoCk findings showing the prevalence of shortness of breath and tiredness increased over time from baseline to 12-months post-baseline in both SARS-CoV-2 Positive and Negative CYP. Methods: Logistic regression models were fitted to compute the probability of (i) Responding given envisioned to take part, (ii) Responding timely given responded, and (iii) (Re)infection given timely response. Response, timely response and (re)infection weights were generated as the reciprocal of the corresponding probability, with an overall 'envisioned population' survey weight derived as the product of these weights. Survey weights were trimmed, and an interactive tool developed to re-calibrate target population survey weights to the general population using data from the 2021 UK Census. Results: Flexible survey weights for the CLoCk study were successfully developed. In the illustrative example, re-weighted results (when accounting for selection in response, attrition, and (re)infection) were consistent with published findings. Conclusions: Flexible survey weights to address potential bias and selection issues were created for and used in the CLoCk study. Previously reported prospective findings from CLoCk are generalisable to the wider population of CYP in England. This study highlights the importance of considering selection into a sample and attrition over time when considering generalisability of findings. [ABSTRACT FROM AUTHOR]

Background: Stigma, lack of trust in authorities, and poor knowledge can prevent health-seeking behaviour, worsen physical and mental health, and undermine efforts to control transmission during disease outbreaks. These factors are particularly salient with diseases such as mpox, for which 96% of cases in the 2022–2023 UK outbreak were identified among gay, bisexual, queer and men who have sex with men (MSM). This study explored stigma and health-seeking behaviour in Liverpool through the lens of the recent mpox outbreak. Methods: Primary sources of data were interviews with national and regional key informants involved in the mpox response, and participatory workshops with priority populations. Workshop recruitment targeted Grindr users (geosocial dating/hookup app) and at risk MSM; immigrant, black and ethnic minority MSM; and male sex workers in Liverpool. Data were analysed using a deductive framework approach, building on the Health Stigma and Discrimination Framework. Results: Key informant interviews (n = 11) and five workshops (n = 15) were conducted. There were prevalent reports of anticipated and experienced stigma due to mpox public health messaging alongside high demand and uptake of the mpox vaccine and regular attendance at sexual health clinics. Respondents believed the limited impact of stigma on health-seeking behaviour was due to actions by the LGBTQ + community, the third sector, and local sexual health clinics. Key informants from the LGBTQ + community and primary healthcare felt their collective action to tackle mpox was undermined by central public health authorities citing under-resourcing; a reliance on goodwill; poor communication; and tokenistic engagement. Mpox communication was further challenged by a lack of evidence on disease transmission and risk. This challenge was exacerbated by the impact of the COVID-19 pandemic on the scientific community, public perceptions of infectious disease, and trust in public health authorities. Conclusions: The LGBTQ + community and local sexual health clinics took crucial actions to counter stigma and support health seeking behaviour during the 2022–2023 UK mpox outbreak. Lessons from rights based and inclusive community-led approaches during outbreaks should be heeded in the UK, working towards more meaningful and timely collaboration between affected communities, primary healthcare, and regional and national public health authorities. [ABSTRACT FROM AUTHOR]

Background: Culex pipiens L. is a principal vector of zoonotic arboviruses in Europe, acting in both an amplification role in enzootic transmission between avian hosts and as a bridge vector between avian hosts and mammals. The species consists of two forms which are indistinguishable using morphological methods but possess varying ecological and physiological traits that influence their vector capacity. In this study we validate methods that can be used to extract trace DNA from single pupal exuviae of Cx. pipiens for use in molecular speciation of samples. These DNA extraction methods are compared using measurement of the total yield and successful identification using a real-time polymerase chain reaction (PCR) assay. Results: Genomic DNA was initially extracted from colony-derived individuals using an ethanol precipitation method, two commercially available DNA extraction kits: DNeasy® Blood & Tissue Kit (Qiagen, UK) and Wizard® SV Genomic DNA Purification System (Promega, UK) and a direct real-time PCR method. Time elapsed between eclosion and processing of pupae significantly influenced Cx. pipiens form identification as nucleic acid concentration and PCR amplification success decreased with increased time elapsed. Real-time PCR amplification success, however, was not shown to vary significantly between the three extraction methods, with all methods successfully identifying all samples, but the direct real-time PCR method achieved a lesser amplification success rate of 70% (n = 20 for each treatment). More variable results were produced when field-derived exuviae were used, with no significant difference in real-time PCR amplification success found across the four methods and a lower overall rate of successful identification of 55–80%. Conclusions: This study shows that both colony and field derived Cx. pipiens pupal exuviae can be a useful non-invasive source of trace DNA permitting accurate biotype differentiation for at least twenty-four hours post-eclosion. The significance and utility of this technique in ecological and behavioural studies of Cx. pipiens is discussed and recommendations made for use according to experimental scenario. [ABSTRACT FROM AUTHOR]

Background: Computer gaming has recently been suggested to be associated with benefits for cognition, but its impact on incident dementia remains uncertain. We aimed to investigate the observational associations of playing computer games with incident dementia, cognitive functions, and brain structural measures, and further explore the genetic associations between computer gaming and dementia. Methods: We included 471,346 White British participants without dementia at baseline based on the UK Biobank, and followed them until November 2022. We estimated the risk of dementia using Cox proportional hazard models, and assessed the changes of cognitive functions and brain structural measures using logistic regression models and linear regression models. Mendelian randomization (MR) analyses were performed to examine the association between genetically determined computer gaming and dementia. Results: High frequency of playing computer games was associated with decreased risk of incident dementia (HR, 0.81 [95% CI: 0.69, 0.94]). Individuals with high frequency of playing computer games had better performance in prospective memory (OR, 1.46 [1.26, 1.70]), reaction time (beta, -0.195 [-0.243, -0.147]), fluid intelligence (0.334 [0.286, 0.382]), numeric memory (0.107 [0.047, 0.166]), incorrect pairs matching (-0.253 [-0.302, -0.203]), and high volume of gray matter in hippocampus (0.078 [0.023, 0.134]). Genetically determined high frequency of playing computer games was associated with a low risk of dementia (OR, 0.37 [0.15, 0.91]). Conclusions: Computer gaming was associated with a decreased risk of dementia, favorable cognitive function, and better brain structure, suggesting that computer gaming could modulate cognitive function and may be a promising target for dementia prevention. [ABSTRACT FROM AUTHOR]

Background: The practice of palliative sedation continues to raise ethical questions among people, which in turn leads to its varied acceptance and practice across regions. As part of the Palliative Sedation European Union (EU) project, the aim of the present study was to determine the perceptions of palliative care experts regarding the practice of palliative sedation in eight European countries (The Netherlands, Belgium, Germany, UK, Italy, Spain, Hungary, and Romania). Methods: A specifically designed survey, including questions on the most frequently used medications for palliative sedation, their availability per countries and settings, and the barriers and facilitators to the appropriate practice of palliative sedation was sent to expert clinicians involved and knowledgeable in palliative care in the indicated countries. A purposive sampling strategy was used to select at least 18 participating clinicians per consortium country. Descriptive statistical analysis was conducted on the survey data. Results: Of the 208 expert clinicians invited to participate, 124 participants completed the survey. Midazolam was perceived to be the most frequently used benzodiazepine in all eight countries. 86% and 89% of expert clinicians in Germany and Italy, respectively, perceived midazolam was used "almost always", while in Hungary and Romania only about 50% or less of the respondents perceived this. Levomepromazine was the neuroleptic most frequently perceived to be used for palliative sedation in the Netherlands, Spain, Germany, and the United Kingdom. Between 38- 86% of all eight countries´ expert clinicians believed that opioid medications were "almost always" used during palliative sedation. The perceived use of IV hydration and artificial nutrition "almost always" was generally low, while the country where both IV hydration and artificial nutrition were considered to be "very often" given by a third of the expert clinicians, was in Hungary, with 36% and 27%, respectively. Conclusions: Our study provides insight about the differences in the perceived practice of medication during palliative sedation between eight European countries. In countries where palliative care services have been established longer perceptions regarding medication use during palliative sedation were more in line with the recommended European guidelines than in Central and Eastern European countries like Romania and Hungary. [ABSTRACT FROM AUTHOR]

This study describes a method that combines synthetic aperture radar (SAR) data with shallow-water modeling to estimate flood hazards at a local level. The method uses particle filtering to integrate flood probability maps derived from SAR imagery with simulated flood maps for various flood return periods within specific river sub-catchments. We tested this method in a section of the Severn River basin in the UK. Our research involves 11 SAR flood observations from ENVISAT ASAR images, an ensemble of 15 particles representing various pre-computed flood scenarios, and 4 masks of spatial units corresponding to different river segmentations. Empirical results yield maps of maximum flood extent with associated return periods, reflecting the local characteristics of the river. The results are validated through a quantitative comparison approach, demonstrating that our method improves the accuracy of flood extent and scenario estimation. This provides spatially distributed return periods in sub-catchments, making flood hazard monitoring effective at a local scale. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials show improved progression‐free survival (PFS) and overall survival (OS) in first‐line metastatic renal cell carcinoma (mRCC) patients with immunotherapy containing systemic anti‐cancer therapies (SACT). However, in the favourable international metastatic renal cell cancer database consortium (IMDC) group there is no trial evidence for OS benefit despite clear PFS improvement when comparing anti‐VEGF tyrosine kinase inhibitor (TKI) monotherapy and (immunotherapy and TKI) IO/TKI combinations. Objective: To assess the impact of first‐line SACT choice on the clinical outcomes of PFS and OS in mRCC. To evaluate this impact of initial SACT for allcomers and the favourable IMDC group. Methods: A multicentre retrospective review of patients who started SACT for mRCC (01/01/2018–30/06/2021) at 17 UK NHS trusts. Patient demographics and IMDC group were analysed. Survival data were compared using Kaplan–Meier curves, and the statistical significance of differences in outcome between the groups was assessed with the log‐rank test. Univariable and multivariable Cox proportional hazard modelling estimate the hazard ratios (HRs) for survival outcomes associated with IMDC and treatment subtype. Results: One thousand three hundred and nineteen patients were identified with a median age of 64. 294 (22.3%), 695 (52.7%) and 321 (24.3%) were IMDC group favourable, intermediate and poor, respectively. 311 (23.6%), 197 (14.9%) and 778 (59%) patients received checkpoint inhibitor and anti‐CTLA4 monoclonal antibody (IO/IO), IO/TKI and TKI first‐line SACT across all IMDC groups. Significant PFS improvement favouring IO/TKI versus TKI was demonstrated in allcomers HR = 0.61. In the favourable risk group, Log rank testing demonstrated a significant benefit for IO/TKI over TKI for PFS (HR = 0.60, 95% CI [0.39, 0.91]) and OS (HR = 0.42, 95% CI [0.18, 0.99]). Conclusion: In this real‐world evidence cohort, we have shown OS and PFS benefit with IO/TKI versus TKI in the favourable IMDC risk group. This has not been previously reported from trial outcomes and would support use of front‐line IO/TKI in mRCC favourable risk patients. [ABSTRACT FROM AUTHOR]