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This paper reflects on an Ethical Review Board's (ERB) established structure of practice throughout a student-led project. We use the research project as a means of exploring the three questions set by the Editors, Fox and Busher, regarding the role of ERBs throughout the research process. We gained full university-level ethical approval in October 2020. This project initially focused on collecting data from students, from a UK university. The participatory way we collaborated with both undergraduates and postgraduates illuminated their individual unique perspectives and successfully facilitated their agentive contributions. This required on-going simultaneous negotiation of predetermined ethical procedures through the ERB. We termed this iterative process 'circumnavigating the revolving door' as it summarised revisiting ethical approval in the light of requests from our student participants. The participants were also invited to be part of the analysis and dissemination phase of this research. Original data collected related to personalised experiences of learning during the on-going global pandemic. The philosophical approach adopted was through an adaptation of Photovoice. That is, with limited direction by the researchers, the participants were invited to construct images (photos or hand drawn pictures), with captions (written text or voice), to explore their own educative circumstances. With this in mind, this paper explores the students' participatory agency throughout this visual methods project through three lenses: namely, the appropriateness of ethical practices within a contextualised scenario (i.e., researching learning during lockdown in a higher educational institution); how the ethical process of an educational establishment supported the dynamic and iterative nature of participant-led research; and finally, how the original researchers' experiences can inform ethical regulations and policy, both nationally and internationally. The circumnavigation of the revolving door of participatory ethics has proved invaluable during this research. This iterative cycle was necessary to incorporate the students (or co-researchers) suggested contributions. One example includes gaining the ERB's approval, post full approval, for participants to audio record their own captions for a public facing website. From originally welcoming the students as participants, to facilitating them to become agentive co-researchers, it became increasingly important to provide them with opportunities to be actively involved in all parts of the research process. The reciprocal iterative relationship developed between co-researcher, researchers and the ERB served to strengthen the outcomes of the project.

BackgroundMyxomatous mitral valve disease (MMVD) is a common, acquired, and progressive canine heart disease. The presence of heart murmur and current cardiac biomarkers are useful in MMVD cases but are not sufficiently discriminatory for staging an individual patient.ObjectivesThis study aimed to conduct a preliminary assessment of canine serum and plasma expression profiles of 15 selected miRNA markers for accurate discrimination between MMVD patients and healthy controls. Additionally, we aim to evaluate the effectiveness of this method in differentiating between pre-clinical (stage B1/B2) and clinical (stage C/D) MMVD patients.AnimalsClient-owned dogs (n = 123) were recruited for the study. Following sample exclusions (n = 26), healthy controls (n = 50) and MMVD cases (n = 47) were analyzed.MethodsA multicenter, cross-sectional, prospective investigation was conducted. MicroRNA expression profiles were compared among dogs, and these profiles were used as input for predictive modeling. This approach aimed to distinguish between healthy controls and MMVD patients, as well as to achieve a more fine-grained differentiation between pre-clinical and clinical MMVD patients.ResultsPerformance metrics revealed a compelling ability of the method to differentiate healthy controls from dogs with MMVD (sensitivity 0.85; specificity 0.82; and accuracy 0.83). For the discrimination between the pre-clinical (n = 29) and clinical (n = 18) MMVD cases, the results were promising (sensitivity 0.61; specificity 0.79; and accuracy 0.73).Conclusion and clinical importanceThe use of miRNA expression profiles in combination with customized probabilistic predictive modeling shows good scope to devise a reliable diagnostic tool to distinguish healthy controls from MMVD cases (stages B1 to D). Investigation into the ability to discriminate between the pre-clinical and clinical MMVD cases using the same method yielded promising early results, which could be further enhanced with data from an increased study population.

Risk management has reduced vulnerability to floods and droughts globally1,2, yet their impacts are still increasing3. An improved understanding of the causes of changing impacts is therefore needed, but has been hampered by a lack of empirical data4,5. On the basis of a global dataset of 45 pairs of events that occurred within the same area, we show that risk management generally reduces the impacts of floods and droughts but faces difficulties in reducing the impacts of unprecedented events of a magnitude not previously experienced. If the second event was much more hazardous than the first, its impact was almost always higher. This is because management was not designed to deal with such extreme events: for example, they exceeded the design levels of levees and reservoirs. In two success stories, the impact of the second, more hazardous, event was lower, as a result of improved risk management governance and high investment in integrated management. The observed difficulty of managing unprecedented events is alarming, given that more extreme hydrological events are projected owing to climate change3.

Abstract In the skin, Trypanosoma brucei colonises the subcutaneous white adipose tissue, and is proposed to be competent for forward transmission. The interaction between parasites, adipose tissue, and the local immune system is likely to drive the adipose tissue wasting and weight loss observed in cattle and humans infected with T. brucei. However, mechanistically, events leading to subcutaneous white adipose tissue wasting are not fully understood. Here, using several complementary approaches, including mass cytometry by time of flight, bulk and single cell transcriptomics, and in vivo genetic models, we show that T. brucei infection drives local expansion of several IL-17A-producing cells in the murine WAT, including TH17 and Vγ6+ cells. We also show that global IL-17 deficiency, or deletion of the adipocyte IL-17 receptor protect from infection-induced WAT wasting and weight loss. Unexpectedly, we find that abrogation of adipocyte IL-17 signalling results in a significant accumulation of Dpp4 + Pi16 + interstitial preadipocytes and increased extravascular parasites in the WAT, highlighting a critical role for IL-17 signalling in controlling preadipocyte fate, subcutaneous WAT dynamics, and local parasite burden. Taken together, our study highlights the central role of adipocyte IL-17 signalling in controlling WAT responses to infection, suggesting that adipocytes are critical coordinators of tissue dynamics and immune responses to T. brucei infection.

Background Due to the rapid advancement in information technology, changes to communication modalities are increasingly implemented in healthcare. One such modality is Computerised Provider Order Entry (CPOE) systems which replace paper, verbal or telephone orders with electronic booking of requests. We aimed to understand the uptake, and user acceptability, of CPOE in a large National Health Service hospital system.Methods This retrospective single-centre study investigates the longitudinal uptake of communications through the Prescribing, Information and Communication System (PICS). The development and configuration of PICS are led by the doctors, nurses and allied health professionals that use it and requests for CPOE driven by clinical need have been described.Records of every request (imaging, specialty review, procedure, laboratory) made through PICS were collected between October 2008 and July 2019 and resulting counts were presented. An estimate of the proportion of completed requests made through the system has been provided for three example requests. User surveys were completed.Results In the first 6 months of implementation, a total of 832 new request types (imaging types and specialty referrals) were added to the system. Subsequently, an average of 6.6 new request types were added monthly. In total, 8 035 132 orders were requested through PICS. In three example request types (imaging, endoscopy and full blood count), increases in the proportion of requests being made via PICS were seen. User feedback at 6 months reported improved communications using the electronic system.Conclusion CPOE was popular, rapidly adopted and diversified across specialties encompassing wide-ranging requests.

ObjectiveTo evaluate the extent to which the inter-institutional, inter-disciplinary mobilisation of data and skills in the Farr Institute contributed to establishing the emerging field of data science for health in the UK.Design and outcome measuresWe evaluated evidence of six domains characterising a new field of science:defining central scientific challenges,demonstrating how the central challenges might be solved,creating novel interactions among groups of scientists,training new types of experts,re-organising universities,demonstrating impacts in society.We carried out citation, network and time trend analyses of publications, and a narrative review of infrastructure, methods and tools.SettingFour UK centres in London, North England, Scotland and Wales (23 university partners), 2013-2018.Results1. The Farr Institute helped define a central scientific challenge publishing a research corpus, demonstrating insights from electronic health record (EHR) and administrative data at each stage of the translational cycle in 593 papers with at least one Farr Institute author affiliation on PubMed. 2. The Farr Institute offered some demonstrations of how these scientific challenges might be solved: it established the first four ISO27001 certified trusted research environments in the UK, and approved more than 1000 research users, published on 102 unique EHR and administrative data sources, although there was no clear evidence of an increase in novel, sustained record linkages. The Farr Institute established open platforms for the EHR phenotyping algorithms and validations (>70 diseases, CALIBER). Sample sizes showed some evidence of increase but remained less than 10% of the UK population in primary care-hospital care linked studies. 3.The Farr Institute created novel interactions among researchers: the co-author publication network expanded from 944 unique co-authors (based on 67 publications in the first 30 months) to 3839 unique co-authors (545 papers in the final 30 months). 4. Training expanded substantially with 3 new masters courses, training >400 people at masters, short-course and leadership level and 48 PhD students. 5. Universities reorganised with 4/5 Centres established 27 new faculty (tenured) positions, 3 new university institutes. 6. Emerging evidence of impacts included: > 3200 citations for the 10 most cited papers and Farr research informed eight practice-changing clinical guidelines and policies relevant to the health of millions of UK citizens.ConclusionThe Farr Institute played a major role in establishing and growing the field of data science for health in the UK, with some initial evidence of benefits for health and healthcare. The Farr Institute has now expanded into Health Data Research (HDR) UK but key challenges remain including, how to network such activities internationally.

As the adverse impacts of hydrological extremes increase in many regions of the world, a better understanding of the drivers of changes in risk and impacts is essential for effective flood and drought risk management and climate adaptation. However, there is currently a lack of comprehensive, empirical data about the processes, interactions, and feedbacks in complex human–water systems leading to flood and drought impacts. Here we present a benchmark dataset containing socio-hydrological data of paired events, i.e. two floods or two droughts that occurred in the same area. The 45 paired events occurred in 42 different study areas and cover a wide range of socio-economic and hydro-climatic conditions. The dataset is unique in covering both floods and droughts, in the number of cases assessed and in the quantity of socio-hydrological data. The benchmark dataset comprises (1) detailed review-style reports about the events and key processes between the two events of a pair; (2) the key data table containing variables that assess the indicators which characterize management shortcomings, hazard, exposure, vulnerability, and impacts of all events; and (3) a table of the indicators of change that indicate the differences between the first and second event of a pair. The advantages of the dataset are that it enables comparative analyses across all the paired events based on the indicators of change and allows for detailed context- and location-specific assessments based on the extensive data and reports of the individual study areas. The dataset can be used by the scientific community for exploratory data analyses, e.g. focused on causal links between risk management; changes in hazard, exposure and vulnerability; and flood or drought impacts. The data can also be used for the development, calibration, and validation of socio-hydrological models. The dataset is available to the public through the GFZ Data Services (Kreibich et al., 2023, https://doi.org/10.5880/GFZ.4.4.2023.001).

Background: Although X-rays are not recommended for routine diagnosis of osteoarthritis (OA), clinicians and patients often use or expect X-rays. We evaluated whether: (i) a radiographic diagnosis and explanation of knee OA influences patient beliefs about management, compared to a clinical diagnosis and explanation that does not involve X-rays; and (ii) showing the patient their X-ray images when explaining radiographic report findings influences beliefs, compared to not showing X-ray images. Methods and findings: This was a 3-arm randomised controlled trial conducted between May 23, 2024 and May 28, 2024 as a single exposure (no follow-up) online survey. A total of 617 people aged ≥45 years, with and without chronic knee pain, were recruited from the Australian-wide community. Participants were presented with a hypothetical scenario where their knee was painful for 6 months and they had made an appointment with a general practitioner (primary care physician). Participants were randomly allocated to one of 3 groups where they watched a 2-min video of the general practitioner providing them with either: (i) clinical explanation of knee OA (no X-rays); (ii) radiographic explanation (not showing X-ray images); or (iii) radiographic explanation (showing X-ray images). Primary comparisons were: (i) clinical explanation (no X-rays) versus radiographic explanation (showing X-ray images); and (ii) radiographic explanation (not showing X-ray images) versus radiographic explanation (showing X-ray images). Primary outcomes were perceived (i) necessity of joint replacement surgery; and (ii) helpfulness of exercise and physical activity, both measured on 11-point numeric rating scales (NRS) ranging 0 to 10. Compared to clinical explanation (no X-rays), those who received radiographic explanation (showing X-ray images) believed surgery was more necessary (mean 3.3 [standard deviation: 2.7] versus 4.5 [2.7], respectively; mean difference 1.1 [Bonferroni-adjusted 95% confidence interval: 0.5, 1.8]), but there were no differences in beliefs about the helpfulness of exercise and physical activity (mean 7.9 [standard deviation: 1.9] versus 7.5 [2.2], respectively; mean difference −0.4 [Bonferroni-adjusted 95% confidence interval: −0.9, 0.1]). There were no differences in beliefs between radiographic explanation with and without showing X-ray images (for beliefs about necessity of surgery: mean 4.5 [standard deviation: 2.7] versus 3.9 [2.6], respectively; mean difference 0.5 [Bonferroni-adjusted 95% confidence interval: −0.1, 1.2]; for beliefs about helpfulness of exercise and physical activity: mean 7.5 [standard deviation: 2.2] versus 7.7 [2.0], respectively; mean difference −0.2 [Bonferroni-adjusted 95% confidence interval: −0.7, 0.3]). Limitations of our study included the fact that participants were responding to a hypothetical scenario, and so findings may not necessarily translate to real-world clinical situations, and that it is unclear whether effects would impact subsequent OA management behaviours. Conclusions: An X-ray–based diagnosis and explanation of knee OA may have potentially undesirable effects on people's beliefs about management. Trial registration: ACTRN12624000622505. Author summary: Why was this study done?: Uptake of exercise and physical activity among people with osteoarthritis (OA) is low, and use of joint replacement surgery—recommended only for the minority of people with end-stage disease or whose symptoms cannot be managed adequately nonsurgically—is inappropriately high. Although radiographic imaging is not recommended for routine diagnosis of OA, many primary healthcare providers globally still rely on X-rays to diagnose OA. We aimed to provide, to our knowledge, the first empirical evidence from a randomised controlled trial to determine if use of X-rays to diagnose and explain OA influences people's beliefs about OA management. What did the researchers do and find?: This was a 3-arm randomised controlled trial involving 617 people who were presented with a hypothetical scenario (that their knee was painful and they had made an appointment with a general practitioner) before being randomly allocated to one of 3 groups where the general practitioner provides them with either: (i) clinical explanation of knee OA (no X-rays); (ii) radiographic explanation (not showing X-ray images); or (iii) radiographic explanation (showing X-ray images). We found that using X-rays increased participant beliefs that joint replacement surgery was necessary, but made no difference to beliefs about the helpfulness of exercise and physical activity. We also found that there were no differences in beliefs when explaining radiographic report findings with and without showing the X-ray images. What do these findings mean?: Our work provides, to our knowledge, the first causal evidence that using X-rays rather than a clinical approach to diagnose and explain knee OA can have potentially undesirable impacts on patient beliefs about knee OA. Changing clinical practice around use of X-rays will require a substantial shift in long-held beliefs and habits and our findings are a first step by showing use of X-rays to diagnose knee OA causally impacts patient beliefs. Although many outcomes met or exceeded our a priori minimal 1.0-unit difference immediately after watching the videos, it is unclear whether effects on patient beliefs would impact subsequent OA management behaviours. [ABSTRACT FROM AUTHOR]

Cardiovascular, respiratory, and related disorders (CVRDs) are the leading causes of adult death worldwide, and substantial inequalities in care of patients with CVRDs exist between countries of high income and countries of low and middle income. Based on current trends, the UN Sustainable Development Goal to reduce premature mortality due to CVRDs by a third by 2030 will be challenging for many countries of low and middle income. We did systematic literature reviews of effectiveness and cost-effectiveness to identify priority interventions. We summarise the key findings and present a costed essential package of interventions to reduce risk of and manage CVRDs. On a population level, we recommend tobacco taxation, bans on trans fats, and compulsory reduction of salt in manufactured food products. We suggest primary health services be strengthened through the establishment of locally endorsed guidelines and ensured availability of essential medications. The policy interventions and health service delivery package we suggest could serve as the cornerstone for the management of CVRDs, and afford substantial financial risk protection for vulnerable households. We estimate that full implementation of the essential package would cost an additional US$21 per person in the average low-income country and $24 in the average lower-middle-income country. The essential package we describe could be a starting place for low-income and middle-income countries developing universal health coverage packages. Interventions could be rolled out as disease burden demands and budgets allow. Our outlined interventions provide a pathway for countries attempting to convert the UN Sustainable Development Goal commitments into tangible action.

Intracellular pathogens construct their environmental niche, and influence disease susceptibility, by deploying factors that manipulate infected host cell gene expression. Theileria annulata is an important tick-borne parasite of cattle that causes tropical theileriosis. Excellent candidates for modulating host cell gene expression are DNA binding proteins bearing AT-hook motifs encoded within the TashAT gene cluster of the parasite genome. In this study, TashAT2 was transfected into bovine BoMac cells to generate three expressing and three non-expressing (opposite orientation) cell lines. RNA-Seq was conducted and differentially expressed (DE) genes identified. The resulting dataset was compared with genes differentially expressed between infected cells and non-infected cells, and DE genes between infected cell lines from susceptible Holstein vs tolerant Sahiwal cattle. Over 800 bovine genes displayed differential expression associated with TashAT2, 209 of which were also modulated by parasite infection. Network analysis showed enrichment of DE genes in pathways associated with cellular adhesion, oncogenesis and developmental regulation by mammalian AT-hook bearing high mobility group A (HMGA) proteins. Overlap of TashAT2 DE genes with Sahiwal vs Holstein DE genes revealed that a significant number of shared genes were associated with disease susceptibility. Altered protein levels encoded by one of these genes (GULP1) was strongly linked to expression of TashAT2 in BoMac cells and was demonstrated to be higher in infected Holstein leucocytes compared to Sahiwal. We conclude that TashAT2 operates as an HMGA analogue to differentially mould the epigenome of the infected cell and influence disease susceptibility.

BackgroundNon-communicable diseases (NCDs) account for some 90% of premature UK deaths, most being preventable. However, the systems driving NCDs are complex. This complexity can make NCD prevention strategies difficult to develop and implement. We therefore aimed to explore with key stakeholders the upstream policies needed to prevent NCDs and related inequalities. MethodsWe developed a theory-based co-production process and used a mixed methods approach to engage with policy- and decision-makers from across the United Kingdom in a series of 4 workshops, to better understand and respond to the complex systems in which they act. The first and fourth workshops (London) aimed to better understand the public health policy agenda and effective methods for co-production, communication and dissemination. In workshops 2 and 3 (Liverpool and Glasgow), we used nominal group techniques to identify policy issues and equitable prevention strategies, we prioritised emerging policy options for NCD prevention, using the MoSCoW approach. ResultsWe engaged with 43 diverse stakeholders. They identified ‘healthy environment’ as an important emerging area. Reducing NCDs and inequalities was identified as important, underpinned by a frustration relating to the evidence/policy gap. Evidence for NCD risk factor epidemiology was perceived as strong, the evidence underpinning the best NCD prevention policy interventions was considered patchier and more contested around the social, commercial and technological determinants of health. A comprehensive communications strategy was considered essential. The contribution of ‘elite actors’ (ministers, public sector leaders) was seen as key to the success of NCD prevention policies. ConclusionsNCDs are generated by complex adaptive systems. Early engagement of diverse stakeholders in a theory-based co-production process can provide valuable context and relevance. Subsequent partnership-working will then be essential to develop, disseminate and implement the most effective NCD prevention strategies.

Abstract Background Excessive sodium consumption is one of the leading dietary risk factors for non-communicable diseases, including cardiovascular disease (CVD), mediated by high blood pressure. Brazil has implemented voluntary sodium reduction targets with food industries since 2011. This study aimed to analyse the potential health and economic impact of these sodium reduction targets in Brazil from 2013 to 2032. Methods We developed a microsimulation of a close-to-reality synthetic population (IMPACT NCD-BR ) to evaluate the potential health benefits of setting voluntary upper limits for sodium content as part of the Brazilian government strategy. The model estimates CVD deaths and cases prevented or postponed, and disease treatment costs. Model inputs were informed by the 2013 National Health Survey, the 2008–2009 Household Budget Survey, and high-quality meta-analyses, assuming that all individuals were exposed to the policy proportionally to their sodium intake from processed food. Costs included costs of the National Health System on CVD treatment and informal care costs. The primary outcome measures of the model are cardiovascular disease cases and deaths prevented or postponed over 20 years (2013–2032), stratified by age and sex. Results The study found that the application of the Brazilian voluntary sodium targets for packaged foods between 2013 and 2032 could prevent or postpone approximately 110,000 CVD cases (95% uncertainty intervals (UI): 28,000 to 260,000) among men and 70,000 cases among women (95% UI: 16,000 to 170,000), and also prevent or postpone approximately 2600 CVD deaths (95% UI: − 1000 to 11,000), 55% in men. The policy could also produce a net cost saving of approximately US$ 220 million (95% UI: US$ 54 to 520 million) in medical costs to the Brazilian National Health System for the treatment of CHD and stroke and save approximately US$ 71 million (95% UI: US$ 17 to170 million) in informal costs. Conclusion Brazilian voluntary sodium targets could generate substantial health and economic impacts. The reduction in sodium intake that was likely achieved from the voluntary targets indicates that sodium reduction in Brazil must go further and faster to achieve the national and World Health Organization goals for sodium intake.

Background: Johne's disease, caused by Mycobacterium avium subspecies paratuberculosis (MAP), is a chronic enteritis that adversely affects welfare and productivity in cattle. Screening and subsequent removal of affected animals is a common approach for disease management, but efforts are hindered by low diagnostic sensitivity. Expression levels of small non‐coding RNA molecules involved in gene regulation (microRNAs), which may be altered during mycobacterial infection, may present an alternative diagnostic method. Methods: The expression levels of 24 microRNAs affected by mycobacterial infection were measured in sera from MAP‐positive (n = 66) and MAP‐negative cattle (n = 65). They were then used within a machine learning approach to build an optimal classifier for MAP diagnosis. Results: The method provided 72% accuracy, 73% sensitivity and 71% specificity on average, with an area under the curve of 78%. Limitations: Although control samples were collected from farms nominally MAP‐free, the low sensitivity of current diagnostics means some animals may have been misclassified. Conclusion: MicroRNA profiling combined with advanced predictive modelling enables rapid and accurate diagnosis of Johne's disease in cattle. [ABSTRACT FROM AUTHOR]

Background: Myxomatous mitral valve disease (MMVD) is a common, acquired, and progressive canine heart disease. The presence of heart murmur and current cardiac biomarkers are useful in MMVD cases but are not sufficiently discriminatory for staging an individual patient. Objectives: This study aimed to conduct a preliminary assessment of canine serum and plasma expression profiles of 15 selected miRNA markers for accurate discrimination between MMVD patients and healthy controls. Additionally, we aim to evaluate the effectiveness of this method in differentiating between pre-clinical (stage B1/B2) and clinical (stage C/D) MMVD patients. Animals: Client-owned dogs (n = 123) were recruited for the study. Following sample exclusions (n = 26), healthy controls (n = 50) and MMVD cases (n = 47) were analyzed. Methods: A multicenter, cross-sectional, prospective investigation was conducted. MicroRNA expression profiles were compared among dogs, and these profiles were used as input for predictive modeling. This approach aimed to distinguish between healthy controls and MMVD patients, as well as to achieve a more fine-grained differentiation between pre-clinical and clinical MMVD patients. Results: Performance metrics revealed a compelling ability of the method to differentiate healthy controls from dogs with MMVD (sensitivity 0.85; specificity 0.82; and accuracy 0.83). For the discrimination between the pre-clinical (n = 29) and clinical (n = 18) MMVD cases, the results were promising (sensitivity 0.61; specificity 0.79; and accuracy 0.73). Conclusion and clinical importance: The use of miRNA expression profiles in combination with customized probabilistic predictive modeling shows good scope to devise a reliable diagnostic tool to distinguish healthy controls from MMVD cases (stages B1 to D). Investigation into the ability to discriminate between the pre-clinical and clinical MMVD cases using the same method yielded promising early results, which could be further enhanced with data from an increased study population. [ABSTRACT FROM AUTHOR]

Background Adverse pregnancy outcomes (APOs) (hypertensive disorders of pregnancy [HDP], preterm delivery [PTD], or low birth weight [LBW]) are associated adverse maternal and offspring cardiovascular outcomes. Therefore, we sought to describe nationwide temporal trends in the burden of each APO (HDP, PTD, LBW) from 2007 to 2019 to inform strategies to optimize maternal and offspring health outcomes. Methods and Results We performed a serial cross‐sectional analysis of APO subtypes (HDP, PTD, LBW) from 2007 to 2019. We included maternal data from all live births that occurred in the United States using the National Center for Health Statistics Natality Files. We quantified age‐standardized and age‐specific rates of APOs per 1000 live births and their respective mean annual percentage change. All analyses were stratified by self‐report of maternal race and ethnicity. Among 51 685 525 live births included, 15% were to non‐Hispanic Black individuals, 24% Hispanic individuals, and 6% Asian individuals. Between 2007 and 2019, age standardized HDP rates approximately doubled, from 38.4 (38.2–38.6) to 77.8 (77.5–78.1) per 1000 live births. A significant inflection point was observed in 2014, with an acceleration in the rate of increase of HDP from 2007 to 2014 (+4.1% per year [3.6–4.7]) to 2014 to 2019 (+9.1% per year [8.1–10.1]). Rates of PTD and LBW increased significantly when co‐occurring in the same pregnancy with HDP. Absolute rates of APOs were higher in non‐Hispanic Black individuals and in older age groups. However, similar relative increases were seen across all age,racial and ethnic groups. Conclusions In aggregate, APOs now complicate nearly 1 in 5 live births. Incidence of HDP has increased significantly between 2007 and 2019 and contributed to the reversal of favorable trends in PTD and LBW. Similar patterns were observed in all age groups, suggesting that increasing maternal age at pregnancy does not account for these trends. Black–White disparities persisted throughout the study period.

Abstract Background Stakeholder engagement is being increasingly recognised as an important way to achieving impact in public health. The WorkHORSE (Working Health Outcomes Research Simulation Environment) project was designed to continuously engage with stakeholders to inform the development of an open access modelling tool to enable commissioners to quantify the potential cost-effectiveness and equity of the NHS Health Check Programme. An objective of the project was to evaluate the involvement of stakeholders in co-producing the WorkHORSE computer modelling tool and examine how they perceived their involvement in the model building process and ultimately contributed to the strengthening and relevance of the modelling tool. Methods We identified stakeholders using our extensive networks and snowballing techniques. Iterative development of the decision support modelling tool was informed through engaging with stakeholders during four workshops. We used detailed scripts facilitating open discussion and opportunities for stakeholders to provide additional feedback subsequently. At the end of each workshop, stakeholders and the research team completed questionnaires to explore their views and experiences throughout the process. Results 30 stakeholders participated, of which 15 attended two or more workshops. They spanned local (NHS commissioners, GPs, local authorities and academics), third sector and national organisations including Public Health England. Stakeholders felt valued, and commended the involvement of practitioners in the iterative process. Major reasons for attending included: being able to influence development, and having insight and understanding of what the tool could include, and how it would work in practice. Researchers saw the process as an opportunity for developing a common language and trust in the end product, and ensuring the support tool was transparent. The workshops acted as a reality check ensuring model scenarios and outputs were relevant and fit for purpose. Conclusions Computational modellers rarely consult with end users when developing tools to inform decision-making. The added value of co-production (continuing collaboration and iteration with stakeholders) enabled modellers to produce a “real-world” operational tool. Likewise, stakeholders had increased confidence in the decision support tool’s development and applicability in practice.

Abstract Background Canine hemorrhagic gastroenteritis (also canine gastrointestinal hemorrhagic syndrome) is commonly associated with Clostridium perfringens, although in some cases the etiology remains unclear. This report describes a fatal acute hemorrhagic and necrotizing gastroenteropathy in a dog associated with Clostridium sordellii, a bacterial species never before identified as the etiological agent of hemorrhagic and necrotizing gastroenteropathy in dogs. Case presentation A fully vaccinated, eight-year-old, female neutered Labrador presented with a history of vomiting without diarrhea. Clinical examination revealed pink mucous membranes, adequate hydration, normothermia, and normocardia. The dog was discovered deceased the following day. Post-mortem examination showed moderate amounts of dark red, non-clotted fluid within the stomach that extended into the jejunum. Discoloration was noted in the gastric mucosa, liver, lungs, and kidneys, with small petechial hemorrhages present in the endocardium over the right heart base and thymic remnants. Histological analysis demonstrated that the gastric fundic mucosa, the pyloric region, small intestine, and large intestine exhibited superficial coagulative necrosis and were lined with a layer of short Gram-positive rods. Anaerobic culture of the gastric content revealed C. sordellii as the dominant bacterial species and neither Salmonella spp., Campylobacter spp., C. perfringens, nor C. difficile were isolated. Unexpectedly, whole genome sequencing of the C. sordellii isolate showed that it lacked the main plasmid-encoded virulence factors typical of the species, indicating that the genetic determinants of pathogenicity of this strain must be chromosomally encoded. Further phylogenetic analysis revealed it to be genetically similar to C. sordellii isolates associated with gastroenteric disease in livestock, indicating that the infection may have been acquired from the environment. Conclusions This case demonstrates that C. sordellii can associate with a canine hemorrhagic and necrotizing gastroenteropathy in the absence of C. perfringens and illustrates the benefits of using bacterial whole genome sequencing to support pathological investigations in veterinary diagnostics. These data also update the molecular phylogeny of C. sordellii, indicating a possible pathogenic clade in the environment that is distinct from currently identified clades.

Abstract Background The NHS Health Check Programme is a risk-reduction programme offered to all adults in England aged 40–74 years. Previous studies mainly focused on patient perspectives and programme delivery; however, delivery varies, and costs are substantial. We were therefore working with key stakeholders to develop and co-produce an NHS Health Check Programme modelling tool (workHORSE) for commissioners to quantify local effectiveness, cost-effectiveness, and equity. Here we report on Workshop 1, which specifically aimed to facilitate engagement with stakeholders; develop a shared understanding of current Health Check implementation; identify what is working well, less well, and future hopes; and explore features to include in the tool. Methods This qualitative study identified key stakeholders across the UK via networking and snowball techniques. The stakeholders spanned local organisations (NHS commissioners, GPs, and academics), third sector and national organisations (Public Health England and The National Institute for Health and Care Excellence). We used the validated Hovmand “group model building” approach to engage stakeholders in a series of pre-piloted, structured, small group exercises. We then used Framework Analysis to analyse responses. Results Fifteen stakeholders participated in workshop 1. Stakeholders identified continued financial and political support for the NHS Health Check Programme. However, many stakeholders highlighted issues concerning lack of data on processes and outcomes, variability in quality of delivery, and suboptimal public engagement. Stakeholders’ hopes included maximising coverage, uptake, and referrals, and producing additional evidence on population health, equity, and economic impacts. Key model suggestions focused on developing good-practice template scenarios, analysis of broader prevention activities at local level, accessible local data, broader economic perspectives, and fit-for-purpose outputs. Conclusions A shared understanding of current implementations of the NHS Health Check Programme was developed. Stakeholders demonstrated their commitment to the NHS Health Check Programme whilst highlighting the perceived requirements for enhancing the service and discussed how the modelling tool could be instrumental in this process. These suggestions for improvement informed subsequent workshops and model development.

BackgroundKnowledge of factors that influence the outcome of infection are crucial for determining the risk of severe disease and requires the characterisation of pathogen-host interactions that have evolved to confer variable susceptibility to infection. Cattle infected by Theileria annulata show a wide range in disease severity. Native (Bos indicus) Sahiwal cattle are tolerant to infection, whereas exotic (Bos taurus) Holstein cattle are susceptible to acute disease.Methodology/principal findingsWe used RNA-seq to assess whether Theileria infected cell lines from Sahiwal cattle display a different transcriptome profile compared to Holstein and screened for altered expression of parasite factors that could generate differences in host cell gene expression. Significant differences (Conclusions/significanceWe conclude that divergent pathogen-host molecular interactions that influence chromatin architecture of the infected cell are a major determinant in the generation of gene expression differences linked to disease susceptibility.

BackgroundThere is uncertainty around the health impact and economic costs of the recent slowing of the historical decline in cardiovascular disease (CVD) incidence and the future impact on dementia and disability.MethodsPreviously validated IMPACT Better Ageing Markov model for England and Wales, integrating English Longitudinal Study of Ageing (ELSA) data for 17,906 ELSA participants followed from 1998 to 2012, linked to NHS Hospital Episode Statistics. Counterfactual design comparing two scenarios: Scenario 1. CVD Plateau-age-specific CVD incidence remains at 2011 levels, thus continuing recent trends. Scenario 2. CVD Fall-age-specific CVD incidence goes on declining, following longer-term trends. The main outcome measures were age-related healthcare costs, social care costs, opportunity costs of informal care, and quality adjusted life years (valued at £60,000 per QALY).FindingsThe total 10 year cumulative incremental net monetary cost associated with a persistent plateauing of CVD would be approximately £54 billion (95% uncertainty interval £14.3-£96.2 billion), made up of some £13 billion (£8.8-£16.7 billion) healthcare costs, £1.5 billion (-£0.9-£4.0 billion) social care costs, £8 billion (£3.4-£12.8 billion) informal care and £32 billion (£0.3-£67.6 billion) value of lost QALYs.InterpretationAfter previous, dramatic falls, CVD incidence has recently plateaued. That slowdown could substantially increase health and social care costs over the next ten years. Healthcare costs are likely to increase more than social care costs in absolute terms, but social care costs will increase more in relative terms. Given the links between COVID-19 and cardiovascular health, effective cardiovascular prevention policies need to be revitalised urgently.

Denmark has experienced a remarkable reduction in CVD mortality over recent decades. The scale of the health contribution from the Danish regulation on industrially produced trans fatty acid (ITFA) has therefore long been of interest. Thus the objective was to determine health and equity benefits of the Danish regulation on ITFA content in Danish food, by quantifying the relative contributions of changes in ITFA intake, other risk factors and treatments on coronary heart disease (CHD) mortality decline from 1991 to 2007 in Denmark, stratified by socioeconomic group. To evaluate the effects of the ITFA ban (Danish Order no. 160 of March 2003) the Danish IMPACTSEC model was extended to quantify reductions in CHD deaths attributable to changes in ITFA (%E) intake between 1991-2007. Population counts were obtained from the Danish Central Office of Civil Registration, financial income from Statistics Denmark and ITFA intake from Dan-MONICA III (1991) and DANSDA (2005-2008). Participants were adults aged 25-84 years living in Denmark in 1991 and 2007, stratified by socioeconomic quintiles. The main outcome measure was CHD deaths prevented or postponed (DPP). Mean energy intake from ITFA was decimated between 1991 and 2007, falling from 1.1%E to 0.1%E in men and from 1·0%E to 0·1%E in women. Approximately 1,191 (95% CI 989-1,409) fewer CHD deaths were attributable to the ITFA reduction, representing some 11% of the overall 11,100 mortality fall observed in the period. The greatest attributable mortality falls were seen in the most deprived quintiles. Adding ITFA data to the original IMPACTsec model improved the overall model fit from 64% to 73%. In conclusion: Denmark's mandatory elimination of ITFA accounted for approximately 11% of the substantial reduction in CHD deaths observed between 1991 and 2007. The most deprived groups benefited the most, thus reducing inequalities. Adopting the Danish ITFA regulatory approach elsewhere could substantially reduce CHD mortality while improving health equity.