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Spatial myopia, financial hubs and the “Golden Triangle”:Tracing the uneven landscape of exogenous equity investments in the UK
No full textThe entrepreneurial finance literature has hitherto largely neglected the role of non-indigenous equity finance across different territorial jurisdictions. Invoking the concept of spatial myopia, this paper examines the role played by this specialist form of finance within different locations and how a firm’s relative geographic location within a national economy plays a fundamental determinant shaping their ability to obtain this form of specialist equity funding. In particular, this study explores the spatial dynamics of international equity investments, with a specific focus on the UK’s six major financial EE hubs. By integrating firm-level data from Crunchbase with city-level economic indicators, the analysis employs a multilevel mixed-effects probit regression model to assess the probability of firms attracting international investors. Our findings reveal that the famous "Golden Triangle" of London, Cambridge, and Oxford remain dominant in terms of attracting international equity investments. Spatial myopia significantly influences investment patterns, with increased distance from the Golden Triangle correlating with reduced probabilities of securing international equity finance. However, no distinct advantages are observable for early and late-stage ventures within the triumvirate compared to the other financial hubs. We conclude that overcoming myopic decision making in international equity investors is a non-trivial policy objective to address
Maternal ethnicity, severe perinatal mental illness and involuntary admission:mother and baby unit service evaluation
No full textAIMS AND METHOD: To investigate associations between maternal ethnicity and involuntary mother and baby unit (MBU) admission, adjusting for potential confounding variables. Data from electronic records in a Scottish MBU (July 2012 to January 2024) were analysed with logistic regression.RESULTS: A total of 450 first admissions were analysed. The proportion of patients from Black, Asian, Mixed or other ethnic minorities who were admitted involuntarily ( n = 8/48, 38%) was twice that of White British patients ( n = 66/364, 18%) with White not British patients showing an intermediate proportion ( n = 12/38, 32%). In the unadjusted model, being of Black, Asian, Mixed or other minority ethnicity was associated with involuntary admission (odds ratio 2.7, 95% CI 1.4-5.2; P = 0.002), as was being of White not British ethnicity (odds ratio 2.1, 95% CI 1.0-4.3; P = 0.04997). Association were attenuated after adjustment for potential confounders, including psychosis. CLINICAL IMPLICATIONS: We identified racial inequalities in a perinatal mental health setting. The drivers of these differences are likely multifactorial.</p
Genome-Wide Aggregated Trans-Effects Analysis Implicates Deficient Type III Interferon Signaling as a Key Cause of Inflammatory Bowel Disease
No full textBACKGROUND: Genome-wide association studies of inflammatory bowel disease have identified hundreds of common genetic variants that are associated with inflammatory bowel disease, but few promising therapeutic targets. The "omnigenic" sparse effector hypothesis postulates that the polygenic effects of common SNPs on a typical complex trait are mediated by trans-effects that coalesce on the expression of a sparse set of core genes. The objective of this study was to identify core genes for inflammatory bowel disease.METHODS: Using summary statistics from studies of transcript levels in whole blood or proteins in plasma, we constructed genome-wide aggregated trans-effects (GATE) scores for predicted gene expression in the UK Biobank cohort and tested these scores for association with inflammatory bowel disease (7949 cases, 452 790 noncases).RESULTS: Inflammatory bowel disease was inversely associated with GATE scores for 5 interferon-stimulated genes-IFIT1, IFI44, HERC5, MX1, IFI44L-regulated by the same trans-expression quantitative trait locus, and with the GATE score for IFNL1. For 6 other genes, GATE score associations with inflammatory bowel disease were supported by other criteria: reported associations with nearby genetic variants, perturbation in experimental models, association with measured protein levels, or drug effects.CONCLUSIONS: These results implicate down-regulation of Type III interferon signaling as a core pathway in the etiology of inflammatory bowel disease, supported by reports of monogenic inflammatory bowel disease caused by rare loss-of-function variants and by perturbation in experimental models of colitis. Deficient Type III interferon signaling may be amenable to therapeutic intervention.</p
Co-developing resources for better public understanding of Longitudinal Population Study Data and the Law
No full textIntroductionThe legal basis for using participants' data in Longitudinal Population Studies (LPS) is complex. Laws of particular relevance are (1) UK data protection legislation, including Data Protection Act 2018 and UK General Data Protection Regulation (UK-GDPR); (2) common law duty of confidentiality; (3) Digital Economy Act (DEA) 2017; (4) Section 251 of the National Health Service Act 2006; and (5) Health Service (Control of Patient Information) Regulations 2002.ObjectiveTo develop transparency materials for LPS participants to raise awareness and understanding of key laws, legal principles and their rights.MethodsPublic contributors from UK Longitudinal Linkage Collaboration (UK LLC), Health Data Research UK (HDR UK) and DATAMIND provided input to benchmark current public understanding of laws and legal principles relevant to research. Based on this involvement, we worked with the UK LLC Public Advisory Group (PAG) and external organisations to produce a series of infographics. These were available in written English, audio, British Sign Language (BSL) and additional languages, to reach as wide an audience as possible.ResultsInput from 56 public contributors informed the work by suggesting low levels of awareness of the laws and legal principles. The DEA was the least well-known, with 11% of people aware of this legislation and the most well-known was UK-GDPR, with 88% awareness. We developed key messages for LPS participants on what they should be aware of as individuals, including what they should expect from their LPS. The information is available to the public and LPS participants as a series of infographics (https://ukllc.ac.uk/lps-data-and-the-law).ConclusionOur series of transparency materials support LPS participants to understand the legal basis for study data use, and their rights. General awareness of the laws and legal principles involved in the use of longitudinal data is low and we recommend data providers should raise awareness in clear and accessible ways.<br/
Polypharmacy and potentially inappropriate prescribing in people with type 2 diabetes:An analysis of the Scottish Diabetes Research Network national diabetes cohort
No full textAIMS: This study assesses national trends and, socio-demographic and clinical factors associated with polypharmacy and potentially in appropriate prescribing among people with type 2 diabetes in Scotland from 2012 to 2022.METHODS: Retrospective cohort study using nationwide data from the Scottish Care Information - Diabetes database. Individuals aged ≥40 years with type 2 diabetes were included. Medication counts were based on unique medications dispensed per calendar year. Potentially inappropriate medications were based on the 2023 Beers criteria and applied to people aged over 65 years. A Poisson mixed-effects model with individual-level random intercepts assessed the relationship between the number of drug classes dispensed and year, gender, age group and socio-economic status, Elixhauser comorbidity index and the hospital frailty risk score.RESULTS: 387,338 people were included. The median number of medications dispensed per person was 9 (interquartile range 5-13). Adjusted medication counts were modestly higher in older people (rate ratio [RR] 1.06, 95% confidence interval [CI] 1.06-1.06 at age 80+ compared to 40-59), higher in women (1.14, 1.13-1.14), in more deprived areas (1.24, 1.23-1.24 in the most deprived vs. the most affluent quintile) and in those with higher comorbidity (1.12, 1.12-1.13 in 4+ vs. 0 comorbidities) but not with high frailty risk (1.00, 1.00-1.00). People over 65 were dispensed a median of 2 (IQR 1-3) potentially inappropriate medications. Potentially inappropriate medication showed a stronger association with comorbidity (1.24, 1.23-1.25) and a positive association with high frailty risk (1.24, 1.23-1.25).CONCLUSIONS: The degree of polypharmacy highlights the need for regular formal medication reviews in this population.</p
DoggifAI: A transformer based approach for antibody caninisation
No full textAntibody translation across species offers a compelling strategy to extend the vast and expensive investments in human therapeutic antibodies to veterinary oncology, with applications in both veterinary medicine and comparative oncology. While precise, low-immunogenic treatments are essential for canine cancer care, traditional species conversion methods rely on ad hoc bioinformatics modifications. These methods often implicitly decouple the framework (FR) and complementarity-determining regions (CDRs), ignoring how structural changes in FRs can affect the conformation and function of CDRs. This can compromise binding specificity and require costly high-throughput in vitro screening. To address this, we present DoggifAI, a transformer model that translates non-canine antibody sequences into canine ones by generating species-appropriate framework regions (FRs) based on desired CDRs. This allows the model to better preserve structural compatibility between FRs and CDRs. The model is pretrained in a T5-style text-to-text denoising task on a large multispecies antibody dataset, which allows further finetuning on a much smaller species-specific dataset. DoggifAI generates highly canine-like antibodies and shows promising results in preserving binding specificity. To support further progress in this field, we also release a curated dataset of over 430,000 unique canine antibody chain sequences, significantly expanding the public sequence repertoire
Effectiveness and cost-effectiveness of a peer-delivered, relational, harm reduction intervention to improve mental health, quality of life, and related outcomes, for people experiencing homelessness and substance use problems:protocol for the 'SHARPS' cluster randomised controlled trial
No full textBACKGROUND: Those experiencing homelessness and problem substance use find it challenging to access the healthcare and treatment they need. The Supporting Harm Reduction through Peer Support (SHARPS) feasibility study demonstrated that Peer Navigators can help these individuals to improve their service engagement, increase access to opioid substitution therapy, and lead to reductions in drug use and risky injection practices. Specifically, participants indicated that the lived experience of Peer Navigators was particularly helpful by enabling the development of trusting relationships. A cluster randomised controlled trial (cRCT) will now assess the effectiveness and cost-effectiveness of a Peer Navigator intervention with this population.METHODS: A two-arm, pragmatic, cRCT will be conducted with embedded cost-effectiveness and mixed methods process evaluations. Individuals will be recruited who are as follows: over the age of 18 years; experiencing/at risk of homelessness and self-report problem substance use; and attending The Salvation Army (TSA) homelessness services across 20 included clusters (towns/cities). Each cluster will be randomised (1:1) to either the intervention or control arm using covariate-constrained allocation based on area-level characteristics. The target sample size is 550 participants in total. A co-produced peer-delivered harm reduction, relational intervention lasting 12 months will be delivered to those in the intervention arm. Usual care will be social care via TSA Support Workers delivered within homelessness services. The co-primary outcomes will be mental health and quality of life, with harmful substance use, risk taking behaviours, social functioning, physical health, social outcomes, housing status, therapeutic alliance/accessibility, service utilisation, and relational empathy chosen as secondary outcomes. Data collection points are baseline, 6 and 12 months, for all measures. The primary timepoint of interest is 12 months after baseline measurement. Economic outcomes will be incremental cost per quality-adjusted life year (QALY) and per year in full capability (YFC) gained with the intervention versus standard homelessness service care, inclusive of costs to the NHS, local government and criminal justice, and the third-sector host organisation. The EQ-5D-5L and ICECAP-A will be used to calculate QALYs and YFC respectively. We will also conduct a cost-consequence analysis.DISCUSSION: The results of this trial will be used to inform whether the SHARPS intervention has a positive impact on those experiencing homelessness and problem substance use and if it is cost-effective to roll it out across social care services.TRIAL REGISTRATION: ISRCTN11094645 (https://doi.org/10.1186/ISRCTN11094645, registered April 5, 2024).</p
Experiences and perspectives on traditional and faith healers' involvement in the care of people with severe mental health conditions in ethiopia:a scoping review
No full textBACKGROUND: Traditional and faith healers (TFHs) play a prominent role in the care of people with severe mental health conditions (MHCs) in many countries. Consequently, there have been calls for closer collaboration between TFHs and mental health care practitioners. This scoping review aimed to map the literature on the experiences of, and perspectives on, traditional and faith healing for people with severe MHCs in Ethiopia.METHODS: The review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews. Pubmed, Embase, CINAHL, Scopus, Web of Science, and PsycINFO databases were searched from the earliest available records to May 2024. Online student MSc/PhD theses and catalogued Ethiopian publications up to 2015 were also searched. Studies were included if they were in English and of any study design using primary data collection. Narrative synthesis was chosen for data synthesis.RESULTS: Of the 3,824 records identified, 31 were included. There were 17 qualitative, 12 quantitative, and two mixed methods studies, conducted in most regions in Ethiopia but with more focus on urban than rural settings. Findings were synthesised under the following themes: perceived causes of MHCs; pathways to care and help-seeking preferences; identification and intervention methods used by TFHs; experience of treatment, satisfaction with care, gaps, and barriers; and collaboration between TFHs and mental health practitioners. People with severe MHCs commonly accessed TFHs first and alongside biomedical care. A substantial range of healers was identified but they were not accessible or acceptable to all communities equally. TFH interventions were diverse and some of their practices were reported to be harmful. However, there were few in-depth studies of TFH care processes. Furthermore, there was little evidence about the experience of care from the perspective of people with severe MHCs. Efforts toward collaboration emphasised the need to develop relationships within which differences could be negotiated.CONCLUSION: Although much is known about the place of TFHs within care pathways for people with MHCs in Ethiopia, there are evidence gaps in relation to the perspectives of people with MHCs and rich contextual understanding of healing processes, both of which are needed for meaningful collaboration to occur.</p
Methylome-wide association studies and epigenetic biomarker development for 133 mass spectrometry-assessed circulating proteins in 14,671 Generation Scotland participants
Get PDFBACKGROUND: DNA methylation (DNAm) can regulate gene expression, and its genome-wide patterns (epigenetic scores or EpiScores) can act as biomarkers for complex traits. The relative stability of methylation profiles may enable better assessment of chronic exposures compared to single time-point protein measures. We present the first large-scale epigenetic study of the highly-abundant serum proteome measured via ultra-high throughput mass spectrometry in 14,671 samples from the Generation Scotland cohort. We further demonstrate the first large-scale comparison of protein EpiScores and their respective proteins as predictors of incident cardiovascular disease.RESULTS: Marginal epigenome-wide association models, adjusting for age, sex, measurement batch, estimated white cell proportions, BMI, smoking and methylation principal components, reveal 15,855 significant CpG – protein associations across 125 of 133 proteins P Bonferroni < 2.71 × 10 -10. Bayesian epigenome-wide association studies of the same 133 proteins reveal 697 CpG-Protein associations (posterior inclusion probability > 0.95). 112 protein EpiScores correlate significantly with their respective protein in a holdout test-set. Of these, sixteen associate significantly with incident all-cause cardiovascular disease (N events=191) compared to one measured protein. CONCLUSIONS: We highlight a complex interplay between the blood-based methylome and proteome. Importantly, we show that protein EpiScores correlate with measured proteins and demonstrate that the, as-yet understudied, high-abundance proteome may yield clinically relevant biomarkers. The protein EpiScores demonstrate more significant associations with cardiovascular disease than directly measured proteins, suggesting their potential as clinical biomarkers for monitoring or predicting disease risk. We suggest that biomarker development could be enhanced by the consideration of protein EpiScores alongside measured proteins.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-025-03892-0.</p
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