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Measuring for environmental impact:ethical and social challenges associated with addressing environmental harms related to health research
Get PDFHealth research is vital in advancing human well-being, but it is also a contributor to climate change and other environmental degradation. A growing bottom up advocacy movement is engaged in developing measures (often called ‘tools’) to help researchers better understand the ways in which they can mitigate these environmental harms. While limited evidence suggests benefits of using these tools, ethical and social challenges remain, including questions about whether tools will place undue burdens on researchers; whether tools will be effective in supporting large scale environmental harm mitigation; whether compliance based use of tools will remove opportunities to have wider discussions about what it means to conduct research in an environmentally sustainable way; and whether tools–which have been developed in high income countries–reinforce existing power imbalances between high and low resource settings and/or fail to address the needs of more marginalised research communities. We describe these issues. Our aim is not to discourage tool use, but to diagnose the ethical and social issues surrounding their adoption, and urge policymakers to reflect on them as the field evolves and these challenges become clearer, so that tools are implemented in a way that is effective and just
X-RAFT:Cross-Modal Non-rigid Registration of Blue and White Light Neurosurgical Hyperspectral Images
Get PDFIntegration of hyperspectral imaging into fluorescence-guided neurosurgery has the potential to improve surgical decision making by providing quantitative fluorescence measurements in real-time. Quantitative fluorescence requires paired spectral data in fluorescence (blue light) and reflectance (white light) mode. Blue and white image acquisition needs to be performed sequentially in a potentially dynamic surgical environment. A key component to the fluorescence quantification process is therefore the ability to find dense cross-modal image correspondences between two hyperspectral images taken under these drastically different lighting conditions. We address this challenge with the introduction of X-RAFT, a Recurrent All-Pairs Field Transforms (RAFT) optical flow model modified for cross-modal inputs. We propose using distinct image encoders for each modality pair, and fine-tune these in a self-supervised manner using flow-cycle-consistency on our neurosurgical hyperspectral data. We show an error reduction of 36.6% across our evaluation metrics when comparing to a naive baseline and 27.83% reduction compared to an existing cross-modal optical flow method (CrossRAFT). Our code and models are publicly available (https://github.com/charliebudd/x-raft-cross-modal-non-rigid-registration).</p
Immunophenotyping TCF1-expressing TILs:spatial profiling and prognostic value in operable non-small cell lung cancer
Get PDFBACKGROUND: The spatial distribution and functional heterogeneity of tumor-infiltrating lymphocytes (TILs) significantly impact patient outcomes in non-small cell lung cancer (NSCLC). While T cell factor 1 (TCF1) expressing TILs have emerged as key players in sustaining anti-tumor immunity, their subset characterization, localization, and clinical significance within the tumor microenvironment remain poorly defined.METHOD: We performed multiplex immunohistochemistry and immunofluorescence to characterize TCF1 + immune cell subsets, in 102 NSCLC tumors, separately analyzing the tumor center (TC) and invasive front (IF). We integrated this data with publicly available single-cell RNA-sequencing datasets and clinical outcome analyses. RESULTS: CD4 + T cells and CD79α + B cells, dominate the TCF1 + landscape, while CD8 + T cells constitute a minority of TCF1 + immune cells, particularly in the TC. We demonstrated the presence of tumor-infiltrating IgG +/IgA + plasma cells co-expressing TCF1. PD1 +TCF1 - cells were more frequent than PD1 +TCF1 + cells both in the TC and IF, reflecting that terminally differentiated exhausted TILs predominate within the tumor microenvironment. Survival analyses revealed significantly different prognostic impact of TILs including TCF1-expressing cells based on topography. Multivariate analysis showed that increased CD8 +TCF1 + cells (HR: 2.5; p=0.039) and increased TCF1 expression by cancer cells (HR: 2,7; p=0.041) in the TC and CD4 +TCF1 + cells (HR: 0.4; p=0.043) in the IF emerged as negative and positive independent prognostic markers for Disease-free survival (DFS), respectively. Integrating PD-L1 expression with TILs, PD-L1 immunopositivity was correlated with increased CD8 + and PD1 +TCF1 - cell infiltration and was associated with favorable DFS especially in the TC. CONCLUSIONS: Our findings support a more refined framework for TCF1 + TIL assessment and TCF1 expression across cellular populations in the tumor microenvironment, with implications for prognostication in operable NSCLC. </p
Exploring the barriers and facilitators to discussing social media in primary care for young adults with mental health concerns:a qualitative study
Get PDFBACKGROUND: Social media is a pervasive part of young peoples' lives and may influence their mental health. Primary care is often the first point of care when seeking help for mental health problems. However, little is known about how young adults with mental health problems experience and perceive primary care support for managing social media.AIM: To explore young adults' views on help-seeking for social media use in primary care in relation to mental health problems.DESIGN & SETTING: Qualitative interview study with 28 young adults aged 18-25 with self-reported mental health problems across England.METHOD: Semi-structured interviews were analysed thematically to identify barriers and facilitators to help-seeking. Themes were organised using the Theory of Planned Behaviour - attitudes, social norms and perceived behavioural control.RESULTS: Barriers for help-seeking included attitudes that social media was a secondary issue and low expectations of meaningful support; perceived negative attitudes and limited understanding of social media by primary care clinicians, communities and families; and constrained ability to seek help due to limited consultation time and uncertainty around how to seek help. Facilitators included clinicians offering practical strategies, raising the topic non-judgmentally, receiving training to better understand young people's digital lives, longer appointment times, and clearer information about support in primary care for social media-related concerns.CONCLUSION: Young adults with mental health concerns face multiple barriers to discussing social media in primary care, shaped by attitudes and structural challenges. Addressing these through clinician training, communication, and service adaptations may enhance engagement and support.</p
Charting the velocity of brain growth and development
No full textBrain charts have emerged as a highly useful approach for understanding brain development and aging on the basis of brain imaging and have shown substantial utility in describing typical and atypical brain development with respect to a given reference model. However, all existing models are fundamentally cross-sectional and cannot capture change over time at the individual level. We address this using velocity centiles, which directly map change over time and can be overlaid onto cross-sectionally derived population centiles. We demonstrate this by modelling rates of change for 24062 scans from 10795 healthy individuals with up to 8 longitudinal measurements across the lifespan. We provide a method to detect individual deviations from a stable trajectory, generalising the notion of thrive lines, which are used in pediatric medicine to declare failure to thrive. Using this approach, we predict transition from mild cognitive impairment to dementia more accurately than by using either time point alone, replicated across two datasets. Last, by taking into account multiple time points, we improve the sensitivity of velocity models for predicting the future trajectory of brain change. This highlights the value of predicting change over time and makes a fundamental step towards precision medicine.</p
Genotype-Phenotype Correlations in Recessive Dystrophic Epidermolysis Bullosa:A Systematic Review
Get PDFImportanceRecessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder with wide clinical heterogeneity, ranging from localized skin fragility to life-limiting systemic complications. Understanding genotype-phenotype correlations in COL7A1, the causative gene, is critical for clinical prognostication, genetic counseling, and the rational design of emerging molecular therapies.ObjectiveTo determine the frequency of genotypic and phenotypic subtypes, and to assess whether variant type or location can predict phenotypic severity and extracutaneous complications in patients with RDEB carrying homozygous variants.Evidence ReviewThis was a systematic review of all RDEB genotypes and phenotypes reported to the International Dystrophic Epidermolysis Bullosa Patient Registry (DEB Registry) and eligible studies published in English from May 1993 to September 2025. PubMed, Cochrane Library, and Web of Science were searched and eligible studies were reviewed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020) guidelines. Included studies reported bi-allelic COL7A1 variants and clinical phenotypes. Data from the DEB Registry were cross-checked to supplement the published cases. Descriptive statistics were used for data analyses, and Fisher exact and χ2 methods were used to test additional genotype-phenotype correlations in patients with RDEB carrying homozygous variants.Findings A total of 1802 patients with RDEB comprising 1002 pathogenic variants within COL7A1 were identified from 217 articles. Among the 706 patients with homozygous variants (mean [SD; range] age, 12.2 [13.0; 0-72] years), 533 (75.5%) had severe RDEB, most frequently associated with frameshift and nonsense variants (388 [72.8%] premature termination codons [PTCs]). In contrast, intermediate and milder subtypes were associated with missense or non-PTC variants. Variant location also influenced phenotype: homozygous variants affecting the noncollagenous 1 domain were associated with severe RDEB in 74 of 83 unique variants (89.2%). Extracutaneous involvement clustered in homozygous PTC carriers and was observed almost exclusively in severe RDEB, with occasional cases in the intermediate subtype and rare instances in the inversa, localized, and self-improving subtypes. Recurrent and population-specific variants suggested founder effects. Splice site and missense variants showed phenotypic variability, with augmented intelligence−based predictions correlating with severity.Conclusions and Relevance In this systematic review, the type and site of pathogenic variants in COL7A1 correlated with the severity of RDEB phenotype across different nationalities, races, and ethnicities. These findings may provide improved patient prognosis, genetic counseling, and personalized therapeutics
Defining key criteria for microhaplotype locus selection in forensic genetics:Progress and recommendations by the Microhaplotype Working Group
No full textThe Microhaplotype Working Group (MWG) has made significant progress in defining key criteria for identifying microhaplotype (MH) loci that will enhance forensic genetics. The growing number of publications on MHs reflects increasing interest in these markers and highlights the need for greater standardization in the field. This paper summarizes the group's achievements since its formation following forensic community discussions at the 29th ISFG Congress in 2022. In this paper, we focus on locus nomenclature, allele definitions for MHs, and the challenges of marker identification and characterization. With the progress achieved on the core published MH locus database, MicroHapDB (https://github.com/bioforensics/MicroHapDB), it is now possible to use unique names for all currently published MHs. The MWG has reached a consensus on the critical marker characteristics for selecting MH loci for forensic use, with the effective number of alleles (Ae) metric as the primary selection parameter. Criteria for excluding otherwise suitable candidate MHs include genome location, length limitations, close physical linkage with forensic STRs, and sequence complexity considerations. Specifically, MHs in Long and Short Interspersed Nuclear Elements (LINEs and SINEs) and Long Terminal Repeats (LTRs) should be avoided, along with loci longer than ∼250 base pairs (bp). Finally, loci containing Indels or low complexity sequence patterns near their allele-defining SNPs should be excluded. MHs less than roughly 100 bp are potentially useful for typing degraded samples while those up to 250 bp are broadly useful and generally more informative if they include a higher average number of informative SNPs. The potential development of specialized MH panels for applications such as mixture deconvolution or biogeographic ancestry estimation is discussed. Considering these parameters, the MWG has identified 1148 loci theoretically suitable for forensic applications. The assembly of a final panel will maximize Ae while ensuring marker independence and loci with flanking sequence suitable for robust primer designs. This work serves as a foundation for the future selection of a core set of MH loci for forensic applications and development of recommendations for their implementation in forensic casework.</p
Turning pain into purpose:a qualitative investigation into the psycho-social impacts associated with ectopic pregnancy loss among women in the United Kingdom
Get PDFDespite the profound effects ectopic pregnancy has been demonstrated to have on women’s mental health, this type of pregnancy loss has received little attention compared to other forms. Ectopic pregnancies are the leading cause of maternal death in early pregnancy and often require urgent medical intervention, which overshadows the psycho-social impacts associated with pregnancy loss. We aimed to undertake a detailed investigation into women’s experiences and associated psychosocial impacts of ectopic pregnancy. Using a qualitative research design, semi-structured interviews (N = 20) were conducted with women who suffered an ectopic pregnancy. The interviews were subject to a Grounded Theory Analysis. Four interconnected themes emerged: ‘Waiting for the Inevitable’, ‘End of the Agony’, ‘Fighting through Perceived Loneliness’, and ‘Restorative Empowerment’. Together, these themes form the theory ‘Turning Pain into Purpose’. This theory suggests, although ectopic pregnancy loss is deeply painful, the challenges encountered can foster personal growth, transforming suffering into a source of empowerment and, ultimately, purpose. Whilst ectopic pregnancies represent a life-threatening condition with profound mental health impacts, this research emphasizses the potential for resilience and healing. It underscores the need for compassionate, tailored care and mental health support, along with increased societal awareness. By listening to women’s voices and understanding their complex experiences, healthcare systems can improve care and support, fostering better outcomes and effecting lasting positive change. When women reach out and form networks of support, they can end the psycho-emotional agony whilst also recovering from the physical agony of the ectopic pregnancy
Young Person and Parent Experience of an Intensive Outreach Programme for Eating Disorders—A Reflexive Thematic Analysis
No full textBackgroundIntensive Outreach Programmes (IOP) for eating disorders (ED) were established to reduce the need for inpatient admissions by providing intensive support to families of young people at high risk of hospitalisation, thereby facilitating ongoing community treatment and decreasing the use of inpatient services. This study investigates patient and carer experiences of treatment in IOP with the aim of identifying perceived benefits, challenges, and changes during treatment and generating recommendations for enhancing outreach services.MethodsNine adolescent patients and 13 caregivers participated in individual semi-structured interviews at 1-month post-discharge from the IOP. Open-ended questions guided the discussions, which were recorded and transcribed verbatim. Data were analysed using the 6-stages of reflexive thematic analysis.ResultsThe analysis generated three key themes: (1) From Despair to Direction (2) Rock Bottom (3) No Quick Fix. Various shared insights were reported, such as beginning during an acute crisis and viewing IOP as a catalyst to change. Parents reflected on feeling supported by professionals to take a more assertive role during treatment and young people reflecting on the firm but necessary boundaries that shaped and supported their engagement with the treatment.DiscussionFamilies recognised prompt structured support, collaboration, individualised approaches as key facilitators for change. Recommendations include enhancing communication between ED services and families, ensuring flexibility in appointments, and maintaining a structured, patient-centred approach to optimise the efficacy of intensive outreach interventions for young people with ED
Multi-centennial internal variability in the North Atlantic could drive additional warming over Europe
No full textEurope has experienced abnormal warming over the recent decades. Model-based studies highlight that multi-centennial internal variability of the North Atlantic can strongly affect European temperatures. However, the limited availability of high-resolution proxy records has hindered observational assessment of the existence and amplitude of such variability in the real climate system. Here, we compile annual-to-decadal proxy-based Holocene reconstructions, instrumental observations, and climate model simulations to demonstrate the existence of this multi-centennial variability mode and quantify its amplitude. We show that this mode is closely tied to the internal variability of the Atlantic Meridional Overturning Circulation. Its temporal evolution explains part of the observed 20th century variability, and a shift towards a positive phase in the late 1990s can explain the recent amplified warming over Europe. When its amplitude is constrained by observations, this internal variability may enhance anthropogenic warming in Northern Europe by up to 30% over 2000–2035