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Public health agencies need to be 'Kennedy ready'
No full textThe Secretary of the US Department of Health & Human Services, Robert Kennedy Jr is leading a political agenda against vaccination. This is undermining the delivery of life-saving vaccination programmes and provision of evidence-based information on the safety and effectiveness of vaccines for the public and health professionals. Inconsistent and conflicting messaging between health practitioners and government health agencies erodes trust in public health programmes, creating a vacuum which is often filled with mis/disinformation that presents severe consequences for families. Due to the transnational spread of diseases, we consider the implications of events in the US for routine childhood vaccination programmes in the UK. Public health agencies across the world need to be ‘Kennedy ready’; pragmatic steps must be taken to mitigate threats posed to vaccine confidence and the control of vaccine preventable diseases
Species diversity and risk factors of gastrointestinal nematodes in smallholder dairy calves in Kenya
No full textGastrointestinal nematodes (GIN) are of major concern in dairy farming, particularly in smallholder systems, because of their impact on the health of the calves and later on their productivity. These infections often occur as co-infections, which can complicate their prevention and treatment. The aim of this study was to conduct fecal egg counts (FEC), genetically identify GIN species, assess species diversity, and identify associated risk factors for GIN infections in dairy calves. Fecal samples were collected from 532 dairy calves across 289 small holder dairy farms. Species identification was achieved through deep amplicon sequencing of the Internal Transcribed Spacer-2 rDNA locus (ITS-2) of first-stage larvae (L1). The mean eggs per gram (EPG) was 62.0 ± 93.0. Most of the calves 64.2% had low-intensity infections (<50 EPG), 28.6% had medium-intensity infections (50-200 EPG), and 7.2% had high-intensity infections (>200 EPG). Next Generation Sequencing analysis identified nine GIN species, with Cooperia punctata (27.8%), Haemonchus placei (26.3%), and Haemonchus contortus (23.6%) being the most prevalent. Co-infections were common, accounting for 69.5% of all infections, with two (40.1%), three (26.9%), and four-species combinations (19.8%) predominating. Male calves showed a significant association with both increased FEC and smaller heart girth, while FEC decreased with age. H. placei and C. punctata were associated with increased FEC, whereas Ostertagia ostertagi (14.5%) and Trichostrongylus colubriformis (8.0%) were associated with decreased heart girth. Calves managed under pasture systems had higher odds of co-infection. This study reveals that GIN infections are highly prevalent in dairy calves, with co-infections being common, and that GIN burden is significantly influenced by calf age, sex, and management system. The Nemabiome tool offers a promising approach to assessing GIN burden and guiding the selection of anthelmintic protocols as part of sustainable farming strategies in tropical regions. </p
Prevalence of loss-of-function, gain-of-function and dominant-negative mechanisms across genetic disease phenotypes
Get PDFMolecular disease mechanisms caused by mutations in protein-coding regions are diverse, but they can be broadly categorised into loss-of-function, gain-of-function and dominant-negative effects. Accurately predicting these mechanisms is important, since therapeutic strategies can exploit these mechanisms. Computational predictors tend to perform less well at the identification of pathogenic gain-of-function and dominant-negative variants. Here, we develop a protein structure-based missense loss-of-function likelihood score that can separate recessive loss of function and dominant loss of function from alternative disease mechanisms. Using missense loss-of-function scores, we estimate the prevalence of molecular mechanisms across 2,837 phenotypes in 1,979 Mendelian disease genes, finding that dominant-negative and gain-of-function mechanisms account for 48% of phenotypes in dominant genes. Applying missense loss-of-function scores to genes with multiple phenotypes reveals widespread intragenic mechanistic heterogeneity, with 43% of dominant and 49% of mixed-inheritance genes harbouring both loss-of-function and non-loss-of-function mechanisms. Furthermore, we show that combining missense loss-of-function scores with phenotype semantic similarity enables the prioritisation of dominant-negative mechanisms in mixed-inheritance genes. Our structure-based approach, accessible via a Google Colab notebook, offers a scalable tool for predicting disease mechanisms and advancing personalised medicine
A novel protocol for a ‘Citizen Panel’ for diverse Public and Participant Involvement in the review and development of the process to access data in the UK Longitudinal Linkage Collaboration Trusted Research Environment
Get PDFBackgroundResearchers can apply to UK Longitudinal Linkage Collaboration (UK LLC) to access Longitudinal Population Study (LPS) data linked to health, non-health administrative and geo-environmental data. This paper describes the protocol for the "UK LLC Citizen Panel": a new method of incorporating a diverse public in decisions about the acceptability and suitability of the UK LLC data access process. The UK LLC Citizen Panel aims to embed public feedback and perceptions into UK LLC's data access process design and decision-making.MethodsThe UK LLC Citizen Panel will be created through a two-stage co-design process. Stage 1: UK LLC will identify and invite a public Steering Group to co-design the work of the Citizen Panel. The Steering Group will include public contributors from UK LLC's Public Involvement Programme and participant representatives from partner LPS. Stage 2: the UK LLC Citizen Panel will comprise participants of partner LPS and seldom-heard groups, primarily recruited via third sector organisations. The Panel will review the data access process during several online and in-person meetings. Findings will be analysed using thematic analysis and disseminated to UK LLC partner organisations, third sector organisations working with minority communities and young people under-represented in longitudinal studies, and networks of the Universities of Edinburgh and Bristol.DiscussionThe UK LLC Citizen Panel is a novel methodological approach that aims to consider a diverse public view of the use of a Trusted Research Environment to provide access to LPS data linked to health, non-health administrative and geo-environmental data. This diversity complements the existing public involvement in decision-making in all UK LLC data access and enables populations that are rarely heard in such decision-making to participate in and review the UK LLC data access process.<br/
The ghost of infections past: accounting for heterogeneity in individual infection history improves accuracy in epidemic forecasting
Get PDFVariation in infection history is an important but often underappreciated driver of individual variability in responses to infections. Such individual heterogeneity in immune responses, stemming from variable previous exposure to pathogens, subsequently influences epidemiological outcomes. By comparing research on innate immune priming in invertebrates, which lack adaptive immune memory but demonstrate enhanced responses to re-infections, to patterns seen in vertebrates, this Essay reveals broad implications for disease dynamics. Insights from mathematical modelling and experimental data highlight the critical need to integrate evolutionary disease ecology into public health initiatives to better predict and manage infectious diseases
Safety and efficacy of early medical abortion at home between 10+ 0 and 11+6 weeks: A Retrospective Review
Get PDFIntroduction Since 2020, legislation in Britain has allowed both mifepristone and misoprostol to be taken at home for early medical abortion (EMA). In England and Wales, legislation restricts this to 9+6 weeks, but in Scotland this is permitted up to 11+6 weeks. Data on the outcomes of EMA at home >10 weeks’ gestation is limited and so we aimed to establish the safety and efficacy of this in comparison with EMA in a hospital setting.Methods We conducted a retrospective review from our abortion service in Edinburgh, Scotland of outcomes of EMA at home versus hospital between 10+0 and 11+6 weeks' gestation over the 5-year period April 2020–March 2025. The primary outcome was complete abortion rate. Secondary outcomes were rates of incomplete abortion, ongoing pregnancy and serious complications.Results A total of 371 EMAs occurred at this gestation (n=258 home, n=113 hospital). Complete abortion rates were not statistically significantly different between groups: 251/258 (97%) (95% CI: 94% to 99%) at home and 110/113 (97%) (95% CI: 92% to 99%) in hospital. Neither incomplete abortion rates (home: 4/258, 1.6%; hospital: 3/113, 2.6%) nor ongoing pregnancy rates (home: 3/258, 1.2%; hospital: 0/113, 0%) were significantly different between groups. There was one case of haemorrhage requiring transfusion and three cases of infection receiving intravenous antibiotics, all in the at home group.Conclusions EMA at home between 10+0 and 11+6 weeks has the same high efficacy and safety as when conducted in hospital. Action is needed to extend EMA at home after 10 weeks' gestation to women across the rest of the UK and beyond
New openEHR technology and clinical collaboration in vital steps toward improved patient care and true interoperability: Scotland’s first digital ReSPECT emergency care plan
Get PDFObjectiveTo deploy a digital application of the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) across Health Boards. MethodsClinicians, patients and other regional stakeholders collaborated with the Scottish National Technology Service (NTS) defining requirements. Development was agile with user feedback. ResultsThe ReSPECT web application developed on Scotland’s National Digital Platform used an openEHR1 Clinical Data Repository. Plans can be viewed and edited across settings. Deployed in 2020, by July 2025, eight of fourteen HBs were onboarded and >5500 patients had digital ReSPECT plans.DiscussionopenEHR structures clinical data in a modular way, enabling other applications to use the same data layer. Close collaboration between technicians and users fulfilled the application’s requirements and solved problems together. ConclusionsCollaboration on the digital ReSPECT accelerated deployment, enabling more people’s wishes and clinical recommendations to be captured and shared across care settings and transitions. openEHR technology enables new data uses. <br/
Can we tackle the inverse care law in general practice?
Get PDFThe inverse care law (ICL), as described by Julian Tudor Hart in his seminal 1971 Lancet article, is the observation that ‘The availability of good medical care tends to vary inversely with the need for it in the population served.’ 1 Tudor Hart’s main target was the threat of marketisation in health care, made clear in the second (less quoted) part of the ICL: ‘This inverse care law operates more completely where medical care is most exposed to market forces, and less so where such exposure is reduced.’Whether or not you agree with Tudor Hart’s thesis on market forces, it is clear that the distribution of general practice resources is not targeted to areas of greatest need. A 2022 report from The Health Foundation found that there were fewer GPs, despite higher health needs, in the most socioeconomically disadvantaged areas of England.2 We conducted a similar analysis of the general practice workforce in Scotland and found that, not only were there fewer GPs in the most deprived areas, but there were also fewer non-GP clinical staff (for example, practice nurses) and fewer non-clinical staff.3In our systematic scoping review, we found that, since Scottish devolution in 1999, a range of policies and interventions have sought to address health inequalities in general practice, with varying success and sustainability;4 only 2 of the 20 interventions — community links workers and financial advisers — have been rolled out nationally, though sustainability is uncertain. In this editorial, we discuss a range of developments to improve the volume and quality of general practice in the most socioeconomically deprived areas, and what more can be done.<br/
Governing antimicrobial resistance in Norwegian livestock farming to 2050: a participatory strategy development approach
Get PDFAntimicrobial resistance (AMR) is a wicked problem with long-term and unpredictable impacts on human and animal health. Understanding how to govern AMR long-term, amidst evolving social, political, economic, technological and environmental changes which will impact livestock production, animal health and AMR risks is therefore critical. The study used scenario planning as a methodology for envisioning plausible future challenges and thus identify possible strategic responses. The national context for this research was Norway, a stable, high-income country which has achieved low antibiotic use and low AMR prevalence in livestock farming through nearly 30 years of concerted industry and state actions. Working with Norwegian agricultural, animal and public health stakeholders, the scenario approach was motivated by the question of how to maintain existing governance capabilities and outcomes in an uncertain future. This is the first scenario planning study to explore stakeholder perceptions about important change drivers and strategies to manage uncertainties for AMR governance in the Norwegian livestock industry. Participants identified three critical drivers of change (state resource prioritisation of agriculture, trust in institutions, global geopolitical conditions) that would influence the development of Norwegian livestock farming, and public and private animal health and AMR governance capacity. The main threats were identified as erosion of trust impacting a culture of organisational collaboration on animal health, loss of capacity and solidarity in the context of declining farmers and veterinarians, and the tensions this produces between winners and losers. This was the basis for identifying several actions including the development of strong local networks of farmers, integrating veterinary and farm advisory services, utilising Ai and data technology to improve national animal health monitoring, and the need for sustaining the institutional and economic structures that are pre-conditions for work on AMR and animal health. These results highlight the importance of attending to these broader structural and institutional conditions that facilitate or hinder the adoption of biosecurity, antibiotic stewardship and preventive veterinary health measures as industry stakeholders and public authorities in Europe continue to grapple with AMR and antibiotic use in livestock farming
Single-site ruthenium catalyst supported on zeolite for CO<sub>2</sub> hydrogenation to methyl formate
Get PDFTechnologies for the transformation of atmospheric CO2 to useful chemicals, such as formic acid (FA), are essential to combatting excessive fossil fuel use and will need to be implemented on large scale. However, hydrogenation of CO2 to (base-free) FA is challenging for heterogeneous catalysts, due to the requirement for low temperatures enforced by the entropically unfavorable reaction of gases. By coupling CO2 hydrogenation to esterification, methyl formate (MF) can be prepared as a promising alternative platform chemical. Herein, a robust, heterogeneous single-metal-site catalyst was prepared and shown to achieve methanol hydrocarboxylation rates superior to nanoparticle catalysts (up to 18.3 ± 0.6 mmol hour−1 g−cat1) while maintaining very high selectivity to MF (≥95%). Characterization reveals isolated, monodisperse Ru-nitrosyl complexes bound to three O-atoms of the zeolite framework, and the robust catalyst formed achieves a cumulative turnover number of more than 3500 over eight cycles. This work pushes the boundaries of supported single-site catalysts in CO2 utilization.</p
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