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Metagenomic Insights into the Urban- Rural Variation of Antimicrobial Resistance and Pathogen Reservoirs in Untreated Wastewater from Central India
No full textIntroduction: Rapid and scalable surveillance of antimicrobial resistance (AMR) is urgently needed in resource-constrained countries where routine monitoring is limited. Wastewater-based metagenomics offers a potential solution for early detection and geographic mapping of AMR.Methods: We conducted a retrospective DNA shotgun metagenomic analysis of untreated wastewater collected across Nagpur, India (February–April 2021). A total of 422 grab samples were pooled into 138 composite samples from 10 urban zones and rural catchments. The bacterial microbiota and resistome were profiled, and urban–rural patterns were compared using diversity metrics and correlation analyses.Results: Across all samples, 871 bacterial genera were detected, dominated by Proteobacteria, with frequent presence of Pseudomonas, Acinetobacter, Aeromonas, Acidovorax and Bacteroides. Beta diversity revealed statistically significant but subtle urban–rural compositional shifts. Of 33 globally important pathogens examined, 13 were detected at generally low relative abundance (<1%). Vibrio cholerae appeared in one sample, while Aeromonas spp. were most prevalent. Seven pathogens occurred in ≥10% of samples, with Aeromonas, Citrobacter, and Enterobacter differing significantly between locations (p < 0.05). The resistome comprised 606 unique antimicrobial resistance genes (ARGs), dominated by drug/biocide efflux determinants, followed by macrolide-lincosamide-streptogramin B genes driven largely by 23S rRNA mutations. Carbapenemases (blaNDM, blaKPC) and colistin resistance (mcr) were detected at lower abundance. Correlation analyses linked Pseudomonas with mexEF/emhABC efflux and copBCDRS copper resistance operon, Acinetobacter with oxa and dfrA, and Aeromonas with ctx, tetA, sul1, dfrB/F, and gyrA/parC.Discussion: These findings show that wastewater metagenomics sensitively resolved clinically relevant pathogens and ARGs in an Indian urban–rural setting, capturing nuanced geographic structure. Integrating routine DNA metagenomics into One Health environmental surveillance could strengthen AMR early warning and guide interventions in resource-constrained contexts
High-Performance Heat-Powered Heat Pumps
Full text linkThis paper introduces a zero-carbon heating solution called High-Performance Heat-Powered Heat Pumps (HP 3), which combine the best attributes of hydrogen boilers and electric heat pumps. HP 3 systems allow us to continue using the existing gas infrastructure, offer higher efficiencies than hydrogen boilers, and avoid overwhelming the electricity grid. An HP 3 blends a heat engine and a heat pump into a single, fully integrated system sharing a common working fluid. This differentiates HP 3 systems from gas-engine-driven heat pumps (GEHP), where the integration between subsystems is limited to a mechanical shaft. A parametric analysis of a propane-based system is presented. The heat engine section has two main design variables: the working fluid's temperature (T max) and pressure (P high) after collecting high-grade heat from hydrogen combustion. Typical GEHPs achieve CoPs of around 1.8. The HP 3 concept achieves a CoP of 2.59 considering a T max of 650 • C, P high of 250 bar, and an ambient temperature of −9 • C. The paper presents a model for the expander's efficiency, which indicates that increasing the system's output makes it possible to achieve a higher expansion efficiency with a lower rotational speed. Results show that HP 3 is a promising concept for larger applications such as commercial buildings or district heating systems
Supporting mental well-being of healthcare workers using a mobile app: a mixed- methods feasibility study
Full text linkPoor mental well-being is common among healthcare workers, affecting individual health, patient safety, and organisational performance. Mobile app-based self-care interventions are promising due to their accessibility, low cost, and ease of use. This study aimed to assess the feasibility of a self-monitoring mobile app called MYARKEO, to improve mental well-being among healthcare workers and healthcare trainees in the United Kingdom (UK). The study evaluated recruitment and retention rates, variability of key outcomes to inform a future randomised controlled trial (RCT), intervention engagement, barriers and facilitators to engagement, and potential refinements to the mobile app. A mixed-method feasibility RCT was conducted with two groups: an intervention group using MYARKEO to monitor mental well-being over 6 weeks, and a non-intervention control group. Data were collected at baseline and post-intervention and included the Warwick-Edinburgh Mental Well-being Scale (WEMWBS), the Depression Anxiety and Stress Scale (DASS-21), and the mHealth App Usability Questionnaire (MAUQ). Qualitative data were collected through semi-structured interviews (n = 13) and analysed using thematic analysis. Forty-nine participants (32 workers, 17 trainees; aged 18–60+) were included in the trial, with a 20.5% dropout rate. Daily app usage averaged 64.5%. Participants frequently monitored mood, sleep, food, and exercise. Interviews identified themes of “Usefulness,” “Enablers of engagement,” “Barriers to engagement,” and “Suggested intervention improvements.” This study demonstrates the feasibility of using a mobile app to monitor and promote mental well-being among healthcare workers and trainees. While app engagement was promising, challenges were identified, highlighting the need for refinements to the app’s content, interface, and design for future trials
Scoping Review of the Socioeconomic Value of Working Equids, and the Impact of Educational Interventions Aimed at Improving Their Welfare
Full text linkWorking equids support millions of people globally, especially in low-income, lower-middle-income, and upper-middle-income countries. However, they commonly suffer from poor welfare and are typically overlooked in policy and funding decisions. This scoping review aimed to collate evidence on two topics related to working equid use in low- and middle-income countries: their socioeconomic value to their owners and the impact of educational interventions for owners/handlers aiming to improve equid welfare. Original research published from 2014 onwards was eligible for inclusion. This scoping review followed the JBI methodology and PRISMA-ScR framework. One search strategy encompassing both topics was applied to five databases (CAB Abstracts, MEDLINE, Embase, Web of Science, and IBSS) on 24.04.24. Key characteristics and findings of eligible studies were charted. In total, 3514 sources were independently screened by two reviewers. In total, 61 socioeconomic value studies (47 journal articles, 2 reports, and 12 conference contributions) and 23 educational intervention studies (11 journal articles and 12 conference contributions) were included. Working equids supported their owners’ livelihoods in wide-ranging ways and contributed to the United Nations’ Sustainable Development Goals. Educational interventions employed varied approaches, and most reported success. Multilevel initiatives and those developed through participatory engagement may be more likely to directly improve equid welfare in the long term. These aspects should be prioritised during intervention development. The included studies used inconsistent terminology and were of variable quality. This review highlights the importance of including working equids within policy and funding strategies and provides recommendations to increase the discoverability, quality, and impact of working equid research
A National Survey of Paediatric Turner Syndrome Services in the United Kingdom: Current Practice and Variability in Care
No full textBackground: Turner syndrome (TS) is a complex genetic condition requiring lifelong, multidisciplinary care. International consensus guidelines exist, but the organisation of paediatric TS services in the UK has not been systematically explored.Methods: A structured electronic survey was distributed to paediatric endocrinology centres across the UK with responses collected from June 2023 to February 2024. The survey collected information on service configuration, staffing, multidisciplinary team (MDT) composition, transition pathways, use of consensus guidelines, and engagement with patient registries and support societies.Results: Responses were received from 20 UK tertiary centres. Six out of 20 centres operated a dedicated TS clinic. MDTs were limited in most centres to paediatric endocrine consultants and nurse specialists, and shared care models for outreach patients were common. Transition practices varied, with 45% of centres using TS-specific pathways, 45% using general endocrine transition pathways, and 10% without a transition pathway. Awareness of international TS guidelines, the Turner Syndrome Support Society, and the i-TS registry was high, but active engagement varied.Conclusion: Significant variability exists in UK paediatric TS service models. Centres without dedicated clinics were generally smaller with fewer patients. Geographic challenges may exacerbate inequalities for outreach patients. While some centres offer best practice examples, improvements in MDT availability, transition planning, and registry engagement are needed to align more closely with international care recommendations
Violence and abuse towards staff by patients and the public in general practice since COVID-19
Full text linkBackground: General practice (family medicine) experiences more violence and abuse by patients and the public than other healthcare settings. There is limited research on such experiences amongst non-clinical staff, and no direct comparisons between staff groups in general practice. Aims: To explore•The extent of violence and abuse from patients or the public towards general practice staff between 2020 and 2023;•Staff correlates and environmental correlates for violence and abuse; •Potential impacts of violence and abuse regarding staff feeling of safety and support at work.Design and Setting: An online survey of general practice staff was conducted across England between 11/7/23 and 30/11/23.Methods: Questions covered demographics, physical violence and threats, verbal abuse, harassment, and inappropriate sexual behaviours experienced or witnessed between 2020 and 2023. It asked whether participants felt safe and supported at work. Results: Participants (N=1,152, 44% clinical, 56% non-clinical) were aged 21-75 years (mean=47.3 years, SD=11.1). Overall, 93.7% reported violence and abuse, with 92.3% reporting verbal abuse, 47.7% reporting physical violence or threats, 60.5% reporting feeling harassed, and 23.7% reporting inappropriate sexual behaviours. Additionally, 21% of staff felt unsafe but only 57.1% felt supported at work. Non-clinical, younger or less experienced staff and those in urban and deprived areas experience more violence and abuse. Those experiencing it more frequently felt less safe and supported.Conclusions: Violence and abuse from patients and the public towards general practice staff may be prevalent and increased since the COVID-19 pandemic. Those at greater risk require more organisational support
Comprehensive profiling of antibiotic resistance, virulence genes, and mobile genetic elements in the gut microbiome of Tibetan antelopes
Full text linkTibetan antelopes, native to high-altitude plateau regions, play an important role in the local ecosystem. Their gut harbors antimicrobial-resistant microbes, including potential pathogens. To explore this, we analyzed 33,925 metagenome-assembled genomes (MAGs), including 7,318 from 68 Tibetan antelopes sequenced in our laboratory. We first profiled the composition of antibiotic resistance genes (ARGs) and then examined their associations with virulence factor genes (VFGs). In total, 2,968 ARGs were identified, conferring resistance to 23 antibiotic classes, with elfamycin resistance being most prevalent. Two ARGs were located on phage-derived sequences, though their phage taxonomy could not be resolved. ARGs were significantly correlated with VFGs, particularly genes linked to adherence and effector delivery systems. Given potential dissemination risks, we further assessed associations between ARGs and mobile genetic elements (MGEs), finding that insertion elements accounted for the largest number of ARG-MGE links. Comparative analysis with other plateau animals and humans revealed seven ARGs uniquely present in Tibetan antelopes. In summary, this study provides the first comprehensive overview of ARG composition in Tibetan antelope gut microbiomes, establishing a baseline for future hypothesis-driven studies and antimicrobial resistance surveillance in wildlife. IMPORTANCE: Investigating the drug resistance of Tibetan antelope (Pantholops hodgsonii) gut microbiota serves as a critical biological indicator for assessing the impact of human activities (particularly antibiotic contamination) on the fragile ecosystem of the Qinghai-Tibet Plateau. This study untangles the invasion of antibiotic resistance genes (ARGs) into remote conservation areas, suggesting that Tibetan antelopes may act as potential vectors for ARG dissemination across plateau environments. Such findings not only highlight threats to wildlife health but also provide an ecological warning regarding the pervasive environmental risks posed by the global antimicrobial resistance crisis in natural ecosystems
Systematic identification of familial hypercholesterolaemia: An updated systematic review and meta-analysis
Full text linkBackground and aims Familial hypercholesterolaemia (FH) is an inherited lipid disorder characterised by raised LDL-C and increased risk of premature atherosclerotic cardiovascular disease. Despite effective treatments, FH remains substantially underdiagnosed. Electronic health records (EHRs) enable systematic case-finding, but evidence on their effectiveness remains limited. This review aimed to evaluate EHR-based strategies for FH identification. Methods Seven databases and grey literature were systematically searched for relevant studies. Eligible studies reported on systematic EHR-based case-finding in adults (≥18 years). Meta-analysis of FH prevalence was conducted using random-effects modelling. Risk of bias was assessed using ROBINS-I; evidence certainty with GRADE. Results Of 831 citations screened, 12 eligible studies were included, including three from a prior review. Case-finding approaches included traditional diagnostic criteria (Simon–Broome, DLCN, MEDPED), hybrid models, and machine-learning algorithms (FAMCAT, FIND FH, TARB-Ex). FH prevalence estimates varied: 1.2% (95% CI 0.0%–3.0%; p= 0.06) in general population studies, 41% (95% CI 2%–90%; p =0.02) in high-risk CVD populations, and 15% (95% CI 2%–34%; p= 0.00) in genetically confirmed cohorts. Novel algorithmic approaches such as FAMCAT 2 and incorporating EHR-genomic data models demonstrated superior performance to traditional criteria. Secondary outcomes were inconsistently reported, though cholesterol levels at diagnosis were consistently higher in probable/confirmed FH, and markedly elevated in genetically confirmed cohorts. Certainty of evidence was moderate due to heterogeneity, non-randomised design, and potential publication bias. Conclusions Algorithmic/genomics augmented EHR-based methods can enhance FH identification, but evidence remains limited. Standardised, scalable approaches validated in diverse populations are required to inform equitable FH screening and policy development
Optimisation of Backing Layer Formulations via Rational Polymer Selection to Improve the Insertion of Dissolving Microneedles Into Skin
Full text linkDissolving microneedles (MNs) hold promise as a versatile drug delivery platform, particularly suited to the delivery of complex molecules across the skin. Dissolving MNs are commonly manufactured using an accessible and reproducible two-step casting process. The selection of different polymers for both the needle and backing layer increases the adaptability of this platform. Previously, work has focused on the needle layer formulation and how the formulation will affect drug delivery. Less well understood is the role of the backing layer on insertion and, subsequently, drug delivery. Therefore, the aim of this work was to evaluate changes to the backing layer formulation on MN insertion and understand the relationships between material properties. The needle layer was formulated with polyvinylpyrrolidone-co-vinyl acetate, with and without insulin, a model protein therapeutic. A range of polymers was used to formulate the backing layer, including sodium carboxymethylcellulose (Na-CMC), poly(vinyl alcohol) (PVA), and polystyrene (PS). MNs manufactured with a PVA backing layer demonstrated an improved insertion profile (efficiency and depth). Permeation studies supported that the PVA backing layer offered an overall advantage in insulin delivery, with a cumulative recovery of 17.6% of the total insulin loading. This work demonstrates the importance of the backing layer formulation in MN arrays. Changing the backing layer formulation impacted both the insertion of MNs and subsequent drug delivery. Moving forward, the properties of polymers selected for use in MN backing layers should be thoroughly explored and rationally selected depending on the intended application
Reconceptualizing Exiting and Career Development in Sex Work: Work Like Any Other
No full textThis book explores ‘exiting’ programs for sex workers, which are behavioural change interventions that support people to stop selling sex. This book examines questions about how we should conceptualise and respond to ‘exiting’ and, by centring sex workers’ voices, it provides evidence of the impact of these programs. It examines sex work ‘exiting’, not as something sex workers need to stop doing, but as part of sex work careers. Drawing on interviews and a global program review to establish best practice, this book challenges the idea of sex work as something a person is ‘in’ or ‘out’ of. It also explores sex workers’ resistance to this area of programming to highlight the power and politics of ‘exiting’. Using a labour framing and seeing sex work as career, this book repositions ‘exiting’ as career development and sheds new light on everyday working circumstances, popular discourses, policies and programs and grassroots struggles for change. As a co-collaboration incorporating knowledge from researchers and lived experience experts, this book is a unique addition that challenges the dominant abolitionist, anti-sex work framings and is of interest to academics, policy makers, sex worker support organisations and non-government organisations globally
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