179566 research outputs found
Sort by
Estimation of respiratory syncytial virus-associated hospital admissions in five European countries using attribution analysis
Get PDFBackgroundRespiratory syncytial virus (RSV) can cause severe disease, notably among infants, older adults, and individuals with comorbidities. Non-systematic testing and differences in coding practices affect direct measures of the hospital disease burden. We aim to tackle this issue and estimate RSV-associated respiratory hospital admissions through time series modelling of hospital admissions.MethodsThe number of RSV hospital admissions in Denmark, England, Finland, the Netherlands, and Spain were estimated with attribution analyses, using age-specific respiratory tract infection (RTI) admissions combined with virological data, both from routinely collected healthcare data. Analyses covered the years 2016–2023.FindingsThe attributed incidence of RSV per 100,000 children 0–2 months ranged from 1715 in Denmark to 3842 in England. In older adults, substantial differences in the incidence of ICD-10 coded RSV hospitalisations were found, while the attributed RSV incidence was more comparable, ranging from approximately 100 per 100,000 in adults 65–74 years to 200 per 100,000 persons 75–84 years and 500 per 100,000 persons 85 years and older.InterpretationRSV-attributed time series exhibit a high degree of synchronicity between participating countries, suggesting that this method for attribution addresses the known issues with underdiagnosis and misclassification. In the older age groups, a substantial proportion of RTI hospitalisations is attributed to RSV, underscoring the relevance of RSV as a cause of severe respiratory infections
Genotype, phenotype, selection and more: improving the skeletal health of laying hens
Get PDF1. This review is a comprehensive exploration of the author’s work in improving skeletal health in laying hens, focusing on the insights from genetics on nutritional, and environmental factors. It discusses the importance of the large number of disciplines that have contributed to the efforts to tackle bone quality in laying hens, particularly the keel bone. 2. The transition from cages to non-cage environments has increased keel bone damage, despite improving overall skeletal health. It is a welfare paradox that improving the hen’s environment has often been accompanied by greater skeletal damage. 3. The role of genetics has been important in understanding and addressing bone health issues and will be a major factor in their improvement. This includes the identification of specific genes, like cystathionine-β-synthase, which has led to nutritional interventions using betaine supplementation to improve bone quality by targeting the one carbon pathway. 4. The role of the timing of puberty and its genetic control is an additional factor in bone health, and new methods of measuring bone density in live birds are now important to monitor potential issues and deliver genetic solutions. 5. The review emphasises a multi-faceted approach, combining genetics, nutrition, rearing practices, and housing design is required in order to improve skeletal health and enhance the welfare and sustainable performance in laying hens.</p
Anchors, archipelagos, and ports of departure:How resettlement shapes im/mobilities in Nyarugusu refugee camp, Tanzania
Get PDFThis article examines how the prospect of resettlement influences the migration plans and daily lives of encamped refugees. Using repeat surveys and interviews carried out with 77 refugee households in 2017-2023, we explore the consequences of the unfortunate ‘natural experiment’ of Nyarugusu refugee camp, where some Congolese refugees had substantial chances to be resettled while Burundian refugees were de facto barred from the opportunity. Participants depict resettlement as their favourite option in every single way; they are also acutely aware of their chance of being resettled and adjust their mobility plans accordingly. All feel stuck in the camp. Burundian refugees endure profound uncertainty and cast their hopes on moving to the ‘archipelago’ of refugee-hosting camps and cities in the region (yet rarely manage to do so). The possibility of resettlement anchors Congolese to the camp as they wait in a ‘port of departure’
Linking epidemiology and genomics of maternal smoking during pregnancy in utero and in aging: a population-based study using human foetuses and the UK Biobank cohort
Get PDFBackground Maternal smoking and foetal exposure to nicotine and other harmful chemicals in utero remains a serious public health issue with little knowledge about the underlying genetics and consequences of maternal smoking in aging individuals. Here, we investigated the epidemiology and genomic architecture of maternal smoking in a middle-aged population and compare the results to effects observed in the developing foetus.MethodsIn the current project, we included 351,562 participants from the UK Biobank (UKB) and estimated exposure to maternal smoking status during pregnancy through self-reporting from the UKB participants about the mother’s smoking status around their birth. In addition, we analysed 64 foetal liver transcriptomic expression datasets collected from women seeking elective pregnancy terminations. Foetal maternal smoking exposure was confirmed through measurement of foetal plasma cotinine levels.FindingsFoetal exposure to maternal smoking had a greater impact on males than females, with more differentially expressed genes in liver tissue (3,313 vs. 1,163) and a higher liver pathway activation. In the UKB, maternal smoking exposure was linked to an unhealthy lifestyle, lower education, and liver damage. In a genome-wide analysis in the UKB, we leveraged the shared genetic basis between affected offspring and their mothers and identified five genome-wide significant regions. We found a low heritability of the trait (~4%) and implicated several disease-related genes in a transcriptome-wide association study. Maternal smoking increased all-cause mortality risk (Hazard ratio and 95%CI: 1.10 [1.04; 1.16], P=4.04x10-4), which was attenuated in non-smoking males. Interpretation Although male foetuses are more affected than females by pregnancy maternal smoking, this effect was largely reduced in middle-aged individuals. Importantly, our results highlight that the overall 10% increased mortality due to pregnancy maternal smoking was greatly attenuated in non-smokers. This study demonstrates the importance of campaigns promoting offspring smoking prevention in families where the parent/s smoke. FundingFunding for this project was provided by the University of Aberdeen, the Science Initiative Panel of the Institute of Medical Science, the UK Medical Research Council, the Seventh Framework Programme of the European Union under Grant Agreement 212885 (REEF) and by NHS Grampian Endowments grants.Key wordssmoking, epidemiology, genetics, transcriptomics, survival Research in contextEvidence before this studyMaternal smoking during pregnancy has been linked to many health issues for the offspring. However, we previously had limited knowledge about which in-utero processes are influenced by maternal smoking and how they translate to diminished health later in life.Added value of this studyHere, we linked data from foetal liver tissues to markers of health and disease in middle aged individuals using high-throughput data. We show that males, especially over 16 weeks of gestation, respond most strongly to maternal smoking in-utero. This apparent sex difference in disease risk and mortality persists throughout life, at least into middle age. We are also the first to report genetic variations associated with maternal smoking by leveraging the shared genetics between affected offspring and their mothers. Implications of all the available evidenceOur results indicate that smoking cessation or, ideally, prevention of smoking initiation in men is crucial to counter the increased mortality due to perinatal maternal smoking. In addition, several genes were identified which increase the propensity for maternal smoking, which highlighted relevant and potentially targetable pathways. These findings can therefore offer ways to decrease the societal burden of maternal smoking in our aging society.<br/
uniGasFoam: a particle-based OpenFOAM solver for multiscale rarefied gas flows
Get PDFThis paper presents uniGasFoam, an open-source particle-based solver for multiscale rarefied gas flow simulations, which has been developed within the well-established Open-FOAM framework, and is an extension of the direct simulation Monte Carlo (DSMC) solver dsmcFoam+. The developed solver addresses the coupling challenges inherent in hybrid continuum-particle methods, originating from the disparate nature of finite-volume (FV) solvers found in computational fluid dynamics (CFD) software and DSMC particle solvers. This is achieved by employing alternative stochastic particle methods, resembling DSMC, to tackle the continuum limit. The uniGasFoam particle-particle coupling produces a nu-merical implementation that is simpler and more robust, faster in many steady-state flows, and more scalable for transient flows compared to conventional continuum-particle coupling. The presented framework is unified and generic, and can couple DSMC with stochastic par-ticle (SP) and unified stochastic particle (USP) methods, or be employed for pure DSMC, SP, and USP gas simulations. To enhance user experience, reduce required computational resources and minimise user error, advanced adaptive algorithms such as transient adaptive sub-cells, non-uniform cell weighting, and adaptive global time stepping have been integrated into uniGasFoam. In this paper, the hybrid USP-DSMC module of uniGasFoam is rigorously validated through multiple benchmark cases, consistently showing excellent agreement with pure DSMC, hybrid CFD-DSMC, and literature results. Notably, uniGasFoam achieves sig-nificant computational gains compared to pure dsmcFoam+ simulations, rendering it a robust computational tool well-suited for addressing multiscale rarefied gas flows of engineering im-portance
Cellular activity of CQWW nullomer-derived peptides
Get PDFAnalysis of observed protein sequences across all species within the UniProtKB/Swiss-Prot data set reveals CQWW as the shortest absent stretch of amino acids. While DNA can be found encoding the CQWW sequence, it has never been observed to be translated or included in manually curated sets of proteins, existing only in predicted, tentative sequences and in a single mature antibody sequence. We have synthesized this “nullomer” peptide, along with 13 derivatives, reversed, truncated, stereoisomers, and alanine-scanning peptides, conjugated to polyarginine stretches to increase cellular uptake. We observed their impact against a healthy neuronal line and six patient-derived glioblastoma cell lines spanning three clinical subtypes. Results reveal IC 50 values averaging 4.9 μM for inhibition of cell survival across tested oncogenic cell lines. High-content phenotypic analysis of cellular features and reverse-phase protein arrays failed to discern a clear mode of action for the nullomer peptide but suggests mitochondrial impairment through the inhibition of GSK3 and isoforms, supported by observations of reduced mitochondrial stain intensities. With a recent increase in interest in nullomer peptides, we see the results in this study as a starting point for further investigation into this potentially therapeutic peptide class.</p
Synthesising a corpus of Gaelic traditional narrative with cross-lingual text expansion
Get PDFAdvances in large language modelling have disproportionately benefited high-resource languages due to their vastly greater training data reserves. This paper proposes a novel cross-lingual text expansion (XLTE) technique using multilingual large language models (MLLMs) to mitigate data sparsity in low-resource languages (LRLs). We apply XLTE to the domain of traditional Scottish Gaelic storytelling, aiming to generate coherent, long-form narrative texts by leveraging MLLMs’ cross-lingual capabilities. The effectiveness of this technique is demonstrated using GPT-4o, with supervised fine-tuning (SFT) providing a reduction in perplexity and decreased neologism over baseline models. Despite these improvements, qualitative analyses reveal stylistic divergences between synthesised and genuine data. Nevertheless, XLTE offers a promising, scalable method for synthesising training sets in other languages and domains, opening avenues for further improvements in low-resource language modelling
Endothelin antagonism: a new era for resistant hypertension?
Get PDFHypertension, defined as a blood pressure (BP) above which treatment provides more benefit than harm, is the leading cause of morbidity and mortality worldwide and is strongly associated with the development of a range of diseases, including cerebrovascular, chronic kidney, and coronary disease. Between 1990 and 2019 the global prevalence of hypertension doubled and it is now estimated to affect ~1 in 4 adults worldwide.1 Despite an extensive therapeutic armamentarium, only 1 in 5 individuals with hypertension achieves adequate BP control..2 The reasons for this are multifactorial and include therapeutic inertia partly as a consequence of physicians doubting the accuracy of office BP measures,3 and poor medication adherence.4 However, there is a particularly high-risk group of patients with treatment-resistant hypertension (TRH) who, despite lifestyle measures and adherence to maximally tolerated doses of three or more different classes of antihypertensive including a diuretic, continue to have uncontrolled BP
The cultural legacy of historical ethnic violence:The impact on access to finance and innovation
Get PDFUsing the case of the pogroms that took place in the historical region of the 'Pale of Settlement' in Eastern Europe, this paper analyzes the cultural legacy of ethnic violence and its long-term economic impact on access to finance and on corporate innovation. We find that firms in regions with a higher historical intensity of ethnic persecution face greater financial constraints, relying more on internal finance and experiencing reduced access to external finance. These financial limitations are linked to sluggish innovation activities among present-day firms. We propose that a mechanism of financial antipathy, rooted in a persistent anti-market culture fostered by historical ethnic animosity, explains these effects and reflects a long-term degradation of local social capital. Our results are supported by causal evidence using instrumental variables based on the precursors of historical inter-ethnic violence. The animosity and discrimination against the minority group appear to transfer to the broader economic activities in which that group was involved, creating lasting economic consequences for the majority population – consequences that continue to affect financial development and innovation to the present day.</p
Magnetic recording fidelity of basalts through 3D nanotomography
Get PDFVolcanic basalt samples originating from two historic eruptions, that is, the 1991 C.E. Hekla, Iceland, and 1944 C.E. Vesuvius, Italy, have been studied to determine the 3D tomographic and spatial distributions of their constituent (titano)magnetite minerals using SEM-FIB slice-and-view. Determining the morphology is key to quantifying the magnetic recording fidelity of a rock, as grain morphology is a primary control of the magnetic (domain) state of a grain, which in turn determines magnetic recording fidelity. Smaller grains are magnetically uniform and are termed single domain (SD). A surface morphology resolution of 2 nm was achieved and the smallest grains that were resolved with 21 nm in diameter; a total of 971 particles were analyzed. We determined a median equivalent-volume spherical diameter of 70 nm for the Hekla sample, and 135 nm for the Vesuvius sample. The particles had nearest-neighbor distances of 184 and 355 nm, indicate the majority of grains were free from magnetostatic interactions. In both samples there was a roughly even split between oblate and prolate grains. This number of oblate grains is much higher than traditionally assumed, and will have implications for many paleomagnetic methods which assume prolate grains, for example, anisotropy of magnetic susceptibility analysis. Numerical micromagnetic analysis of the grain-morphologies, predict that 64% of the Hekla grains have SD ground-states (6% by volume), but only 26% of the Vesuvius grains have SD ground-states (1% by volume). Both samples are predicted to be excellent paleomagnetic recorders, with median relaxation times far larger than the length of the Universe
Access Repository Dashboard
Do you manage Edinburgh Research Explorer? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!