179566 research outputs found
Sort by
Neuroimmunometabolic alterations and severity of depressive symptoms in people with HIV:An exploratory diffusion-weighted MRS study
Get PDFDepression is associated with inflammation in the periphery and the central nervous system. People with HIV are at greater risk for depression, which may in part be driven by sustained neuroinflammation, although individuals with severe depression are often excluded from studies of HIV-related co-morbidities. In this exploratory study, we aimed to explore the neuroimaging signatures of severe and persistent depression among people with HIV. We enrolled N = 20 adults with HIV in Brighton, UK, of whom n = 11 had a Patient Health Questionnaire-9 (PHQ-9) score ⩾15 and a history of receiving antidepressant medication. We used diffusion-weighted magnetic resonance spectroscopy (DW-MRS), an emerging neuroimaging technique sensitive to neuroinflammation, to assess neurometabolite diffusion in the anterior cingulate cortex. Participants also underwent standard magnetic resonance spectroscopy (MRS) to assess neurometabolite concentrations in the anterior cingulate cortex, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess blood–brain barrier permeability in the whole brain and the thalamus. We observed a significant positive correlation between intracellular diffusion of creatine and depressive symptom severity (ρ = 0.46, p = 0.047). Increased creatine diffusion has previously been reported in conditions characterised by hypermetabolism and neuroinflammation, suggesting that worse depressive symptom severity in people with HIV may be correlated with neuroimmunometabolic alterations. Metabolite concentrations and blood–brain barrier permeability largely did not correlate with depressive symptom severity in this sample. In summary, we explored neuroimaging signatures of severe depression in people with HIV, including by applying diffusion-weighted magnetic resonance spectroscopy in this population. We report early evidence that worse depressive symptom severity in people with HIV may be correlated with neuroimmunometabolic dysfunction, evidenced by increased diffusion of creatine, likely reflecting hypermetabolism and neuroinflammation. Future research may aim to replicate these findings in larger and more diverse samples and compare the diffusion of neurometabolites between people with and without HIV living with severe depression
Looking inside the ‘black box’ of digital firm scaling:An ethnographically informed conceptualisation
Get PDFIn recent years there has been an upsurge of interest in firm scaling. Owing to the fact our conceptual and theoretical grasp of this phenomenon remains under-developed, this paper offers a novel conceptualisation of the scaling process based on an in-depth ethnographic study of a London-based digital Fintech. Scaling involves deliberately enacting and surmounting a series of managerial challenges such as human capital re-positioning, business model reconfiguration, customer acquisition and the acquisition of external growth capital. Our theoretical contribution views the micro-foundations of scaling as a distinctive relational process-based phenomenon. Under the conceptual framework posited, entrepreneurial human capital and successful scaling are inextricably interwoven. Entrepreneurial founders and managers are pivotal for orchestrating scaling and our conceptualisation builds upon the trigger point model of firm development, which reinforces the primacy of entrepreneurial agency for optimising growth triggers
The shared genetic architecture and evolution of human language and musical rhythm
Get PDFThis study aimed to test theoretical predictions over biological underpinnings of previously documented phenotypic correlations between human language-related and musical rhythm traits. Here, after identifying significant genetic correlations between rhythm, dyslexia and various language-related traits, we adapted multivariate methods to capture genetic signals common to genome-wide association studies of rhythm (N = 606,825) and dyslexia (N = 1,138,870). The results revealed 16 pleiotropic loci (P < 5 × 10 −8) jointly associated with rhythm impairment and dyslexia, and intricate shared genetic and neurobiological architectures. The joint genetic signal was enriched for foetal and adult brain cell-specific regulatory regions, highlighting complex cellular composition in their shared underpinnings. Local genetic correlation with a key white matter tract (the left superior longitudinal fasciculus-I) substantiated hypotheses about auditory–motor connectivity as a genetically influenced, evolutionarily relevant neural endophenotype common to rhythm and language processing. Overall, we provide empirical evidence of multiple aspects of shared biology linking language and musical rhythm, contributing novel insight into the evolutionary relationships between human musicality and linguistic communication traits.</p
On the economic feasibility of tidal range power plants
Get PDFThe potential energy associated with tides presents a sustainable energy resource that remains largely untapped. Uncertainties on the economic case of tidal range power plants are a known obstacle. Research on tidal range structures suggests energy yield may be maximized through operation strategy optimization, and that impacts can be mitigated through design optimization. While instructive, these perspectives alone are insufficient to support the feasibility of individual projects. We integrate operation optimization and hydrodynamic impact analyses within a cost evaluation framework for tidal range structures focusing on capital costs (CAPEX) and levelized cost of energy (LCOE). Once benchmarked against 11 historic proposal cost projections, we perform a redesign of 18 tidal power plants to deliver a comprehensive comparative basis across a diverse range of sites in the UK. Tidal power plant operation is simulated in regional shallow-water equation models, acknowledging tide variability. The cost evaluation framework demonstrates the impact of geospatial variations on key cost components. The redesign process indicates transformative implications in that equivalent and lower LCOE values can be achieved for designs at a substantially lower CAPEX. Given how the latter hinder development, we show how tidal range schemes could be far more economically feasible than commonly perceived.</p
A deep learning approach for non-invasive Alzheimer’s monitoring using microwave radar data
No full textOver 50 million people globally suffer from Alzheimer’s disease (AD), emphasizing the need for efficient, early diagnostic tools. Traditional methods like Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) scans are expensive, bulky, and slow. Microwave-based techniques offer a cost-effective, non-invasive, and portable solution, diverging from conventional neuroimaging practices. This article introduces a deep learning approach for monitoring AD , using realistic numerical brain phantoms to simulate scattered signals via the CST Studio Suite. The obtained data is preprocessed using normalization, standardization, and outlier removal to ensure data integrity. Furthermore, we propose a novel data augmentation technique to enrich the dataset across various AD stages. Our deep learning approach combines Recursive Feature Elimination (RFE) with Principal Component Analysis (PCA) and Autoencoders (AE) for optimal feature selection. Convolution Neural Network (CNN) is combined with Gated Recurrent Unit (GRU), Bidirectional Long Short Term Memory (Bidirectional-LSTM), and Long Short-Term Memory (LSTM) to improve classification performance. The integration of RFE-PCA-AE significantly elevates performance, with the CNN+GRU model achieving an 87% accuracy rate, thus outperforming existing studies
A DSMC-CFD coupling method using surrogate modelling for low-speed rarefied gas flows
No full textA new Micro-Macro-Surrogate (MMS) hybrid method is presented that couples the Direct Simulation Monte Carlo (DSMC) method with Computational Fluid Dynamics (CFD) to simulate low-speed rarefied gas flows. The proposed MMS method incorporates surrogate modelling instead of direct coupling of DSMC data with the CFD, addressing the limitations CFD has in accurately modelling rarefied gas flows, the computational cost of DSMC for low-speed and multiscale flows, as well as the pitfalls of noise in conventional direct coupling approaches. The surrogate models, trained on the DSMC data using Bayesian inference, provide noise-free and accurate corrections to the CFD simulation enabling it to capture the non-continuum physics. The MMS hybrid approach is validated by simulating low-speed, steady-state, force-driven rarefied gas flows in a canonical 1D parallel-plate system, where corrections to the boundary conditions and stress tensor are considered and shows excellent agreement with DSMC benchmark results. A comparison with the typical domain decomposition DSMC-CFD hybrid method is also presented, to demonstrate the advantages of noise-avoidance in the proposed approach. The method also inherently captures the uncertainty arising from micro-model fluctuations, allowing for the quantification of noise-related uncertainty in the predictions. The proposed MMS method demonstrates the potential to enable multiscale simulations where CFD is inaccurate and DSMC is prohibitively expensive
Past Answers to Present Concerns. The Relevance of the Premodern Past for 21st Century Policy Planners: Comments on the State of the Field
No full textHow is history relevant to the present, or indeed the future? Governments around the world have used history to inform planning and decision-making in various fields for years, but more recently it has taken on a renewed importance as governments grapple with increasingly complex challenges arising from the impacts of climatic change. Yet identifying “lessons from the past” is not straightforward. Especially in the case of big questions about historical structures and social processes, establishing precise causal relationships is complex and interpretive, making consensus difficult among specialists. A second major challenge arises over the uses of history. Historical precedent can and does play a role in some contexts in helping formulate new strategies for addressing local environmental challenges. At the national level policy-makers and politicians often look to the past for inspiration, guidance, or justification. In both respects, the cases and examples chosen are often highly selective and tend to align with pre-existing assumptions. This article briefly reviews these challenges within the context of climate change and associated environmental and sustainability issues, comments on recent work in the field, and suggests some ways forward for historians
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/
Effectiveness of non-pharmaceutical interventions as implemented in the UK during the COVID-19 pandemic: a rapid review
Get PDFBackgroundAlthough non-pharmaceutical inventions (NPIs) were used globally to control the spread of COVID-19, their effectiveness remains uncertain. We aimed to assess the evidence on NPIs as implemented in the UK, to allow public health bodies to prepare for future pandemics.MethodsWe used rapid systematic methods (search date: January 2024) to identify, critically appraise and synthesise interventional, observational, and modelling studies reporting on NPI effectiveness in the UK. ResultsEighty-five modelling, nine observational, and three interventional studies were included. Modelling studies had multiple quality issues; six of the 12 non-modelling studies were high quality. The best available evidence was for test and release strategies for case contacts (moderate certainty), which was suggestive of a protective effect. Although evidence for school-related NPIs and universal lockdown was also suggestive of a protective effect, this evidence was considered low certainty. Evidence certainty for the remaining NPIs was very low or inconclusive.ConclusionThe validity and reliability of evidence on the effectiveness of NPIs as implemented in the UK during the COVID-19 pandemic is weak. To improve evidence generation and support decision-making during future pandemic or other public health emergencies, it is essential to build evaluation into the design of public health interventions.<br/
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!