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    Scoping Review of the Socioeconomic Value of Working Equids, and the Impact of Educational Interventions Aimed at Improving Their Welfare

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    Working 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

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    Background: 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

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    Background: 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

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    Tibetan 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

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    Background 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

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    Dissolving 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

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    This 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

    Literacies in the age of AI: Teaching and learning in the digital era

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    An innovative resource for understanding and teaching literacy in a digital and AI-powered worldLiteracies: Learning and Teaching in the Age of Digital Media and Artificial Intelligence responds to a critical need in contemporary education by redefining literacy in light of digital transformation and the rise of generative AI. Moving beyond traditional definitions of reading and writing, this innovative volume situates literacy as a complex, multimodal practice involving text, image, sound, space, and gesture. Through a compelling historical and theoretical account of literacy's evolution—spanning from oral traditions and early writing systems to today's AI-integrated learning environments—the text equips readers to navigate a shifting communicative landscape shaped by emerging technologies.Written by a team of leading educators and researchers, Literacies proposes a reflexive pedagogical framework that synthesizes didactic, authentic, functional, and critical approaches. Eight accessible yet detailed chapters explore how learners co-construct meaning within diverse social, cultural, and technological contexts. The authors critically address challenges such as algorithmic bias, fabricated content, and privacy while emphasizing the transformative potential of GenAI in education, including its role in assessment, inclusion, and personalized learning

    Recombinant factor VIIa versus placebo for spontaneous intracerebral haemorrhage within 2 h of symptom onset (FASTEST): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial

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    Background Recombinant factor VIIa has been shown to slow bleeding in patients with intracerebral haemorrhage (ICH), but no haemostatic agent has been shown to improve clinical outcomes. We aimed to evaluate the safety, clinical efficacy, and effect on growth of ICH and intraventricular haemorrhage (IVH) of recombinant factor VIIa in patients with acute spontaneous ICH who were most likely to benefit from treatment with this agent. Methods We conducted a multicentre, prospective, double-blind, randomised, placebo-controlled, adaptive, phase 3 trial (FASTEST) at 93 sites across the USA, Japan, Canada, Spain, Germany, and the UK. Adults aged 18–80 years with a spontaneous ICH of 2–60 mL, IVH in less than two-thirds of one lateral ventricle or in less than a third of both lateral ventricles, a Glasgow Coma Scale score of at least 8, no evidence of recent ischaemic stroke or myocardial infarction, no recent use of anticoagulation medication or other structural cause of ICH, and who had been treated with study medication within 2 h of stroke onset or last known well were eligible for inclusion. Patients were randomly assigned (1:1) by a simple randomisation scheme to either 80 μg/kg recombinant factor VIIa (intervention group) or an identical placebo (placebo group), administered intravenously over 2 min. All investigators and participants were masked to allocated group assignment. The primary outcome was functional outcome at 180 days, measured by modified Rankin Scale (mRS; score 0–2, 3, and 4–6) and analysed by intention to treat in all randomly assigned patients. The primary safety outcome was life-threatening thromboembolic events during the first 4 days, assessed in all randomly assigned participants. The secondary aim was change in ICH volume and ICH plus IVH volume between baseline and 24 h of treatment administration. We performed an ordinal logistic regression, adjusted for age, baseline ICH volume, baseline IVH volume, and pre-stroke mRS. Preplanned interim analyses, including adaptive sample size re-estimation and enrichment to a younger subgroup (aged ≤70 years), were also conducted. This trial is registered with ClinicalTrials.gov ( NCT03496883 ) and is closed to new participants. Findings Between Dec 3, 2021, and Oct 1, 2025, we screened 3288 patients, of whom 626 participants were randomly assigned and included in the intention-to-treat analyses: 298 (48%) in the placebo group and 328 (52%) in the intervention group. 216 (35%) participants were female and 410 (65%) were male, with a mean age of 61 years (SD 12). Mean time from stroke onset to administration of study drug was 100 min (SD 22). The trial met the prespecified stopping criteria for futility at the second interim analysis. There was no differential effect in the primary clinical outcome measure of mRS at 180 days between the intervention group and placebo group (adjusted common odds ratio 1·09 [95% CI 0·79–1·51]; p=0·61). Life-threatening thromboembolic complications within 4 days occurred in 15 (<5%) participants in the intervention group and in four (1%) in the placebo group (relative risk 3·41 [95% CI 1·14–10·15]; p=0·020). Compared with placebo, recombinant factor VIIa was associated with decreased growth of ICH (–3·7 mL [95% CI –5·4 to –1·9]) and of ICH plus IVH growth (–5·2 mL [–7·6 to –2·8]) between baseline and CT scan at 24 h. Interpretation Recombinant factor VIIa administered within 2 h of ICH onset slowed haematoma growth, but did not improve functional outcomes and showed a small increased risk of life-threatening thromboembolic complications. Further testing of recombinant factor VIIa in patients with the greatest risk of continued bleeding is ongoing. Funding National Institute of Neurological Diseases and Stroke, Japan Agency for Medical Research and Development, and Novo Nordisk

    Genome-wide profiling of lncRNAs in pediatric intracranial ependymomas identifies H19 as a novel pathogenic driver

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    BackgroundPediatric ependymomas (EPNs) frequently develop in the cerebellum and are treated with non-targeted therapies, partly due to limited understanding of their pathobiology. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis but remain mostly unexplored in pediatric EPNs. This study aimed to identify novel oncogenic drivers and prognostic biomarkers in posterior fossa (PF) EPN by profiling the genome-wide lncRNA expression landscape.MethodsWe used RNA sequencing data from 13 samples, three controls and ten PF EPNs, to profile the lncRNA expression landscape. Perturbation and functional assays in EPN cell lines were used to investigate putative oncogenic drivers, while large public datasets were used to explore associations with prognosis.ResultsWe identified several aberrantly expressed lncRNAs, including IGF2-AS, CD44-DT, and HOTAIRM1 and lncRNAs associated with poor prognosis such as DELEC1, H19, and CD44-AS1. We focused on H19 and IGF2-AS, which reside in the same imprinted locus together with IGF2, a gene encoding a growth factor. Knockdown of H19 reduced expression of cell cycle-related genes, decreased cell viability, and increased apoptosis and cell cycle arrest. In contrast, IGF2-AS knockdown upregulated H19 and the expression of cell cycle-related genes. Finally, public data showed that H19 is more abundant in the EPN PF subgroup A, and that methylation of its imprinting control region (ICR) correlates strongly with better prognosis in EPN PF subgroup B (PFB).ConclusionThese findings suggest that H19 plays an oncogenic role in EPN and that the methylation status of its ICR may serve as a prognostic biomarker in PFB

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