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Training a high-performance retinal foundation model with half-the-data and 400 times less compute
No full textMedical artificial intelligence is limited by available training datasets. Foundation models like RETFound from Moorfields Eye Hospital (MEH) can be adapted with small downstream datasets and thus alleviate this issue. RETFound-MEH used 900,000 training images. Recently, "data-efficient" DERETFound achieved comparable performance with 150,000 images. Both require very substantial compute resources for training and use. We propose RETFound-Green trained on only 75,000 publicly available images with 400 times less compute using a novel Token Reconstruction objective. RETFound-MEH and DERETFound training costs are estimated at 14,000, respectively. RETFound-Green cost less than $100, with equally reduced environmental impact. RETFound-Green can be downloaded 14 times faster, computes vector embeddings 2.7 times faster which then require 2.6 times less storage space. On a variety of downstream tasks from geographically diverse datasets, RETFound-Green achieves more than twice as many statistically significant wins than the next best model.</p
Podcasts as pedagogy in higher education:A scoping review to map and advance the field
No full textPodcasts are now one of the most ubiquitous forms of digital engagement and entertainment. Their increasing global impact also extends to higher education (HE), where they serve a variety of pedagogical purposes despite limited conceptual clarity. This paper reports on a scoping review exploring the concept and role of podcasts in HE teaching and learning. Based on a review of 91 publications, the paper maps definitions, taxonomies and pedagogical uses of podcasts, leading to a working definition of the concept ‘educational podcasts’. This conceptualisation seeks to capture the many types of pedagogical work for which podcasts are used in contemporary HE, which are explored in an adapted taxonomy based on the scoping review. The paper then points to four key areas for future research. Together, the paper thinks productively and creatively toward further development in researching and teaching of, with and through podcasts
The brain neurovascular epigenome and its association with dementia
No full textCerebral small vessel disease (SVD) is frequently comorbid with Alzheimer's disease (AD), and brain endothelial cells (BECs) express genes associated with AD genetic risk. However, the epigenome of neurovascular cells and its intersection with genetic risk remain unexplored. Here, we generated gene regulomes for human BECs, mural cells, and other brain cell types and showed that AD heritability is primarily immune related, with a modest BEC enrichment. On the other hand, SVD heritability is enriched across the neurovascular unit, including astrocytes. Enhancer-to-gene interactomes implicated disease-distinct putative risk genes associated with amyloid and phospholipid processes in AD and senescence-associated pathways in SVD. Motifs for putative partners of lineage-determining transcription factors (TFs) in microglia and BECs were enriched for AD and SVD variants linked to disease-associated genes. In silico screening of compounds implicated vitamin D receptor agonists, mammalian target of rapamycin (mTOR), histone deacetylase (HDAC), and vascular endothelial growth factor receptor (VEGFR) inhibitors for AD. Our findings highlight regulatory mechanisms and therapeutic targets within the neurovascular system.</p
Light therapy for bipolar disorders:Clinical recommendations from the international society for bipolar disorders (ISBD) Chronobiology and Chronotherapy Task Force
No full textThe International Society for Bipolar Disorders (ISBD) Chronobiology and Chronotherapy Task Force conducted a comprehensive review to deliver concise evidence-based recommendations on the use of bright light therapy (BLT) for bipolar disorder (BD). Adjunctive BLT is likely an efficacious acute treatment for bipolar depression as implicated by higher quality evidence. The position of maintenance BLT for relapse prevention awaits further investigation. Protocols of effective BLT in BD are similar to parameters indicated for treatment of seasonal and non-seasonal major depressive disorder. Anti-manic prophylaxis (especially for BD-I) and clinical monitoring are recommended with initiation of and ongoing light treatment. Administer BLT daily, preferably in the morning or at mid-day. If mornings are prohibitive, then mid-day exposure, implemented to avoid excessively early wake times, is an acceptable alternative. Informed by the literature, target 30 min/day of BLT exposure. Patients wary of emergent hypomania or partial responders, can initiate 15 min/day and increase by 15 min each week to full response (or 30-60 min/day by the fourth week). Consider patient centred outcome assessments to evaluate mood response, safety and side effects. Clinical improvement is typically observed within 1-2 weeks, with response/remission expected by 4-6 weeks. Integration of BLT with other chronotherapeutic strategies may enhance long-term efficacy.</p
Spatial imaginaries underpin community objections to shale gas exploration in the UK
No full textSpatial imaginaries refer to collective understandings of socio-spatial relations that encompass three types: imaginaries about specific places in the world, generic types of space (e.g. a rural village), and transformations to space (e.g. industrialisation). The concept has been applied in diverse fields, notably city and regional planning, yet significant gaps remain in terms of understanding interdependencies between types of spatial imaginary at multiple scales, and of the fairness and justice implications of contested imaginaries, particularly in contexts of low carbon energy transitions. To address these gaps, we draw on qualitative data from 45 interviews with residents in two UK communities—Great Altcar and Woodsetts— to analyse arguments about proposals for local shale gas exploration. We highlight three key findings. First, objections are underpinned by the three types of spatial imaginary, which are used relationally to contest local proposals. We demonstrate the distinction, consistencies and contradictions across the types of spatial imaginaries in practice. Second, the spatial imaginaries create particular sets of ‘othering’, in terms of where residents believe fracking should or should not occur, which build upon distinctions between city and countryside, locals and ‘outsiders’, the north and south of England, and internationally between Great Britain and other countries. Finally, concerns with fairness and justice underpin how spatial imaginaries are used to object to local fracking proposals. By recognising community-level concerns with energy infrastructure projects, in the form of diverse spatial imaginaries at multiple scales, we can move toward more inclusive approaches to sustainable energy transitions.</p
Nymphaea “Eldorado” flower extract targets serpine 1 to attenuate inflammatory and antioxidant crosstalk in zebrafish
No full textChronic inflammation and oxidative stress are pivotal drivers of pathological conditions, necessitating safer plant-derived therapeutic alternatives. This study elucidates the anti-inflammatory and antioxidant mechanisms of Nymphaea “Eldorado” flower water extract (NEWE) in a zebrafish (Danio rerio) model of copper sulfate (CuSO4)-induced inflammation. NEWE (25–100 μg/mL) attenuates CuSO4-triggered neutrophil migration and oxidative stress by downregulating proinflammatory genes (il1b, ptgs2a/b) and reducing reactive oxygen species (ROS) production. Transcriptomic profiling identified 339 differentially expressed genes (DEGs), enriched in cytokine signaling and redox regulation, with serpine1, stat3, and mmp9 emerging as key regulatory hubs. Widely targeted metabolomics revealed 891 bioactive compounds, including flavonoids and phenylpropanoids, with network pharmacology predicting multi-target interactions involving inflammatory and oxidative stress pathways. Molecular docking confirmed binding affinities between protocatechuic acid, L-pyroglutamic acid, and Serpine1’s active site, indicating direct interference with inflammation modulation. Collectively, these results establish NEWE as a polypharmacological agent that disrupts inflammation-oxidative stress crosstalk primarily through Serpine1-mediated pathways, offering a molecular foundation for plant-derived interventions against chronic inflammatory diseases
Baseline Characteristics of the TOPaZ Study: Randomised Trial of Teriparatide and Zoledronic Acid Compared with Standard Care in Adults with Osteogenesis Imperfecta
No full textIntroductionOsteogenesis imperfecta (OI) is a rare disorder causing multiple fractures throughout life. No treatment has been shown to reduce the risk of fractures in OI. Here, we present the baseline characteristics of participants in the Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid (TOPaZ) trial. The aim of the trial is to determine whether teriparatide and zoledronic acid are superior to standard care in reducing the risk of clinical fractures.MethodsWe summarised data on the baseline characteristics of TOPaZ participants, including demographics, genetic diagnosis, clinical features, bone density measurements, previous treatments, and fracture history.ResultsWe recruited 350 adults with a clinical diagnosis of OI in 27 European referral centres between June 2017 and October 2022. Overall, 266 (76.2%) had type I OI, 55 (15.8%) had type IV, and 19 (5.4%) had type III. The type was unknown in 9 (2.6%). Blue sclera were noted in 80.8%, and 35.8% had dentinogenesis imperfecta. Bisphosphonates had been administered to 28.1% in the 2 years prior to enrolment. Pathogenic variants in COL1A1 or COL1A2 were found in 87.6%. Fractures occurring in the 2 years prior to enrolment were not associated with bone density.ConclusionsThe TOPaZ population represents a unique cohort with which to study the genetic epidemiology and outcome of OI in relation to bone density and biochemical markers of bone turnover. When the trial reports, it will also provide new insights into the effect of an anabolic therapy, followed by antiresorptive treatment in the management of OI
Governance of the private health sector in Georgia:A situation analysis using WHO’s Progression Pathway for Governance of Mixed Health Systems
Get PDFSince 2013, Georgia has aimed to achieve universal health coverage by progressively expanding publicly funded benefits. However, with 85% of hospital beds and most primary care clinics, outpatient facilities and pharmacies under private ownership, strong governance is essential to align profit-driven incentives with policy goals. This study examines governance in Georgia, analysing sectoral strategies, regulations, purchasing mechanisms, and public–private dialogue. It is based on a literature review, document analysis, interviews with state authorities, private sector representatives and local experts, and a validation workshop. Although a strategic framework for the health system exists, it lacks sufficient detail to inform private sector investment and resource allocation. Regulatory and purchasing gaps contribute to imbalances in provider distribution and risks to care affordability, quality and appropriateness. Weak institutional mechanisms for inclusive policy dialogue have hindered effective collaboration between stakeholders and failed to address conflicts of interest. To enhance governance, strategic planning must be supported by detailed implementation plans with full budgetary integration. Strengthening the capacity of the state purchaser is crucial to creating the right incentives and holding providers accountable. Transparent and inclusive policy processes are also needed to enhance the design of reforms, facilitate implementation and protect the public interest
Progression pathway for governance of mixed health systems
Get PDFThe Progression Pathway for Governance of Mixed Health Systems aims to guide countries in governing mixed health systems to achieve universal health coverage (UHC). While the private sector's role in health offers benefits, it also poses challenges to equity, access, and financial sustainability if not properly governed. WHA Resolution 63.27 urges governments to gather strategic intelligence to assess the private sector's impact, identify engagement strategies, and develop regulatory frameworks for universal access and people-centered primary care. A collaborative "steering" approach to governance is recommended. The Progression Pathway has been designed to support the work of government agencies in three ways: 1. Identify the governance arrangements and capacities needed to deliver better health outcomes that will work in their context. 2. Take stock of existing governance arrangements and capacities, their strengths and weaknesses and identify the priority areas for improvement. 3. Help define strategies and specific actions for strengthening governance arrangements focused on building the capacity to make and implement health policies in the private sector to improve healthcare access, quality, and cost-effectiveness. It offers multiple entry points to work on health systems governance, such as informing the development or review of national health strategies. It can also serve as a reference tool for donors and international agencies supporting health system reform in a country
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