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The Future of the Biopsychosocial Model: Toward a Transdisciplinary Systems Science of Mental Health
No full textThe biopsychosocial model is perhaps the most widely accepted model of mental health. Yet, themodel is also surprisingly limited, failing to provide clear guidance for clinical research. In thispaper, we join recent efforts to chart a path forward for the biopsychosocial model, arguing thatthe success of this framework will hinge on our ability to engage in transdisciplinarycollaboration. We begin by showing that the biopsychosocial model is a systems model and thatcollaboration with researchers studying systems in other disciplines will, therefore, afford insightinto the nature, etiology, and treatment of mental disorders. We then illustrate how biological,psychological, social, and environmental systems all contribute to mental health and argue thatadvancing our understanding of mental health will, therefore, require collaborative integration ofwork from across domains of science. We conclude with three concrete steps that can help moveus toward a transdisciplinary systems science of mental health.</p
PremPath Final Report
No full textThe final report produced by the research team for the funders the National Institute for Health and Care Research Policy Research Programme (NIHR204242).</p
From reach to catchment-scale impacts: High-resolution hydrodynamic modelling of Nature-based solutions in the Cocker Catchment, UK
No full textStudy regionCocker River catchment (145 km²), Lake District, Cumbria, United Kingdom.Study focusThis study investigates the influence that Natural Flood Management (NFM) features have on flood behaviour at the catchment scale using a high-resolution, two-dimensional hydrodynamic modelling approach. A high-performance computing framework, based on the High-Performance Integrated hydrodynamic Modelling System (HiPIMS), was applied to simulate two events; 1) pre-NFM implementation - Storm Desmond flood in 2015, and 2) post-NFM implementation – High rainfall event in 2021. Leaky wooden barriers and other NFM features were explicitly represented using UAV-derived digital terrain data at 2 m and 4 m spatial resolutions.Hydrological insightsThe simulations indicate that the hydrological response to NFM within the Cocker catchment is strongly event dependent. Clearer flow attenuation and hydrograph smoothing were observed during the smaller 2021 event, while impacts during the extreme 2015 event were modest and spatially variable. Localised water retention within the Whinlatter sub-catchment translated into small but measurable downstream changes in flood levels, alongside indications that delayed flows may interact with contributions from other tributaries. These findings highlight the importance of event magnitude, spatial configuration, and flow timing when assessing the role of NFM in catchment-scale flood risk management.</p
Care and support needs of families in the first 9-months after PICU discharge: A multi-center, longitudinal, qualitative study
No full textNo description supplied</p
Electric youth: young people, energy infrastructures and power cuts
No full textNo description supplied</p
Hybrid closed-loop insulin delivery improves glycaemic control compared with sensor-augmented pump therapy: A meta-analysis of 'free-living' randomised trials in type 1 diabetes
No full textAIM: Although hybrid closed-loop systems (HCLS) and sensor-augmented pump (SAP) therapy are advanced diabetes management technologies for type 1 diabetes, their relative efficacy in optimising glycaemic control is not fully established. This meta-analysis evaluated the impact of HCLS versus SAP therapy on glucose regulation across multiple randomised controlled trials (RCTs) and randomised crossover trials (RCOs). The primary aim was to determine the efficacy of HCLS in improving glycaemic control, reducing glucose variability and enhancing time in range (TIR) compared with SAP therapy. METHODS: The review was prospectively registered with the International Prospective Register of Systematic Reviews as CRD42023488722. Data from 27 studies involving over 1000 participants were analysed. The studies included both RCTs and RCOs that compared HCLS with SAP therapy. Key metrics assessed were mean glucose levels, glucose variability (coefficient of variation and standard deviation), low blood glucose index (LBGI), high blood glucose index (HBGI), glycated haemoglobin (HbA1c) and TIR (3.9-10.0 mmol/L). Hyperglycaemia and hypoglycaemia outcomes were also evaluated. RESULTS: HCLS significantly reduced mean glucose levels by 2.0 mg/dL compared with SAP therapy. It also decreased glucose variability, including CV and SD, and reduced LBGI, HBGI and HbA1c. HCLS increased TIR by 8.8%. Regarding hyperglycaemia, HCLS reduced the time spent above 10 mmol/L by 7.8%, above 13.9 mmol/L by 3.63% and above 16.7 mmol/L by 0.88%. Hypoglycaemia outcomes showed modest improvements, with reductions in time below 3 mmol/L by 0.10% and below 3.9 mmol/L by 0.72%. CONCLUSIONS: Our findings support HCLS as a superior modality to SAP therapy in improving glycaemic control, particularly in paediatric populations. HCLS effectively reduces hyperglycaemia and increases TIR, with modest effects on hypoglycaemia. The clinical implications are significant, highlighting the advantages of HCLS in optimising glucose regulation and mitigating glycaemic variability. This technology offers improved glycaemic control and enhanced quality of life for people living with type 1 diabetes.</p
Impact of accelerometer epoch summary measure on associations between physical activity and all-cause mortality in Whitehall II and UK Biobank
No full textAccelerometer data are commonly reduced into epoch summary measures (ESMs) for analysis, e.g. ENMO (Euclidean Norm Minus One), MAD (Mean Amplitude Deviation), MIMS (Monitor Independent Movement Summary) or Counts. We compared associations with all-cause mortality of the volume and intensity of physical activity when derived from those four measures in the Whitehall II and UK Biobank cohorts. Volume (Average Acceleration, AvAcc) and intensity (Intensity Gradient, IG) were derived from each ESM. Associations with mortality were estimated using Cox models. 3733 (25.1% female, median age 68.3 years) and 89,848 (56.4% female, 63.5 years) participants were included from Whitehall II and UK Biobank, respectively. Median (IQR) follow-up was 11.0 (10.7, 11.3) and 8.0 (7.5, 8.5) years, with 563 (15.1%) and 3656 (4.1%) deaths. Associations with mortality were largely consistent between ESMs with the lowest mortality risk for those high (above the median) in both AvAcc and IG (Whitehall: HR = 0.59-0.68; Biobank: 0.55-0.61, reference: low/low), and IG associated with lower mortality risk, irrespective of AvAcc. AvAcc was associated with lower mortality irrespective of IG in Biobank only. In conclusion, associations of AvAcc and IG with mortality are broadly consistent across common ESMs, supporting comparability of activity-health findings across studies using different ESMs.</p
A Decade of Exhibitions
No full textThis publication marks a decade of exhibitions at Attenborough Arts Centre, celebrating ten years of creativity, conversation and community. Since the opening of our purpose-built galleries in 2016, these spaces have become a vital home for contemporary art in Leicester, welcoming thousands of visitors and showcasing work by local, national and international artists.Gathering highlights from the past ten years, this collection offers a visual journey through a vibrant and diverse programme. With striking images and concise insights into each exhibition, it captures the breadth of artistic ideas and practices that have shaped our galleries.As we look back on a decade of innovation and collaboration, we also look ahead - celebrating how far we’ve come and imagining what the next ten years of creativity might bring.</p
1-Amino-but-3-enes scavenge formaldehyde and glyoxylic acid
No full textReactive carbonyl compounds are common pollutants and endogenous metabolites that are often toxic at high concentrations. Removal/detoxification of carbonyl compounds requires selective small molecule scavengers; however, few molecules suitable for this task have been fully characterised. Here, we report NMR-based kinetic and selectivity studies on representative 1-amino-but-3-enes, which are reported to be selective formaldehyde scavengers. Our experiments reveal that 1-amino-but-3-enes containing phenyl groups at position 1 react with formaldehyde via a 2-aza-Cope rearrangement. However, they also react with other carbonyl compounds, including the biologically relevant 1,2-dicarbonyl compound glyoxylic acid. The most efficient and promiscuous scavenging compound promoted the growth of Escherichia coli cells, while studies on cell lysate revealed potential for aldehyde sequestration. Overall, our analyses suggest that 1-amino-but-3-enes can be used to scavenge a variety of toxic carbonyl compounds and may be used in imaging and quantification studies, as well as for biomedical applications.</p
Discovery of Dimer-Dependent Aminoacrylamide Molecular Glues 2 for 14−3−3 Protein−Protein Interactions
No full textMolecular glues (MGs) offer a promising strategy for stabilizing protein–protein interactions (PPIs), particularly within the 14–3–3 protein family, which regulates diverse cellular processes and is implicated in many disease pathways. This study reports on the discovery of an aminoacrylamide MG (7) for 14–3–3 PPIs. Structure–activity relationship analysis using a fluorescence polarization (FP) assay revealed that both a basic amine and acrylamide moiety are essential for activity. However, further investigation using FP, mass spectrometry, and a thermal shift assay revealed that 7 has a cysteine-independent mode of action, distinguishing it from other covalent 14–3–3 MGs. Furthermore, its activity is reliant on 14–3–3 dimerization suggesting that it targets the 14–3–3 dimer interface. Aminoacrylamide 7 differentially affected interactions with ERα, LRRK2, and AHA2, suggesting that 14–3–3 dimerization plays an important role in 14–3–3 client recognition. These findings further validate the 14–3–3 dimer interface as a novel MG target and underscore the complexities of 14–3–3 molecular recognition and small-molecule modulation.</p