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Singlet-Triplet Gaps for Evaluating Thermally Activated Delayed Fluorescence: Which One is the (b)E_ST ?
Get PDFThe singlet–triplet energy gap (ΔEST) serves as a central screening parameter for new thermally activated delayed fluorescence (TADF) materials, and is a valuable indicator of eventual OLED performance. Surprisingly though,...</jats:p
Unsupervised learning of facial landmarks through self-attention and self-training
No full textFacial landmark detection serves a crucial role in analysing the shape and structure of human faces, particularly under varying expressions and poses. Traditionally, supervised methods dominate this area, but their reliance on extensive manually annotated facial datasets proves limiting. Unsupervised landmark discovery aims to address this, yet often struggles to identify meaningful, semantic facial features and may falter when encountering complex head poses, backgrounds, or significant viewpoint shifts. This thesis presents a groundbreaking self-training framework for unsupervised facial landmark detection. Rather than relying on indirect tasks like image generation, we introduce a self-attention mechanism to establish long-distance relationships between facial components within input data. This allows for improved performance and a greater capacity to handle complex facial scenarios. This thesis begin with generic keypoints and then iteratively refine them into distinctive facial landmarks. Pseudo-labels are generated via feature clustering, followed by contrastive learning to enhance feature distinctiveness for each pseudo-class. This approach consistently yields highly semantic facial landmarks adaptable to significant viewpoint changes and 3D head rotations. The proposed method sets new performance benchmarks across various challenging facial datasets
LAPAROSCOPIC HYSTERECTOMY IN ENGLAND: A DESCRIPTION OF RECENT PRACTICE AND CREATION AND VALIDATION OF PREDICTION MODELS FOR OUTCOMES
Get PDFAims and Methods This thesis uses a national database to investigate hysterectomy routes and to improve patient counselling for benign indications. A descriptive analysis examines changes in hysterectomy routes over time. Regression modelling examines regional variation in practice and develops and validates predictive models for conversion from laparoscopic to open hysterectomy and major complications in patients undergoing hysterectomy for benign disease. Results From 2011 to 2018, 261,309 patients underwent hysterectomy for benign non-prolapse indications and endometrial cancer. The proportion performed laparoscopically increased from 20.2% in 2011 to 48.2% in 2018. In 2018, regional variation in minimal access hysterectomy persisted when adjusted for primary diagnosis and age. The highest odds were in the South West, South East, and Northern and Yorkshire regions. Patients in the South West were twice as likely to undergo laparoscopic surgery compared to those in the West Midlands (AOR 2.10 95% CI 1.89;2.35) Between 2011 and 2018, 68,752 patients had a laparoscopic hysterectomy for benign indications and 4,153 (6.0%, 95% CI 5.9 to 6.2) were converted to open surgery. The discriminatory ability of the models were: Preoperative model C-statistic 0.65 (95% CI 0.64; 0.66) and operative model C-statistic 0.67 (95% CI 0.67; 0.68) From 2011 to 2018, 68,599 patients had a laparoscopic and 125, 971 patients had an abdominal hysterectomy for benign diagnoses. 4.4% patients undergoing laparoscopic Commented [KM1]: Not 68752 as per previous study as diagnostic criteria for diagnoses were refined slightly 7 hysterectomy and 4.9% of patients undergoing an abdominal hysterectomy had a major complication within 28-days of surgery. The discriminatory ability of the models were: laparoscopic C-statistic 0.61 (95% CI 0.60; 0.62) and abdominal C-statistic 0.67 (95% CI 0.65; 0.69) Conclusions Laparoscopic hysterectomy uptake has increased. The prediction models had acceptable discriminatory ability in predicting conversion and complications and can be used as a tool to improve pre-operative counselling. Further work is needed to improve the discriminatory ability of these models
Evolution of the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones.
Get PDFT cells contribute to immune protection and pathogenesis in tuberculosis, but measurements of polyclonal responses have failed to resolve correlates of outcome. We report the temporal evaluation of the human in vivo clonal repertoire of Mycobacterium tuberculosis (Mtb)-reactive T cell responses, by T cell receptor (TCR) sequencing at the site of the tuberculin skin test, as a model for a standardised antigenic challenge. Initial non-selective recruitment of T cells is followed by enrichment of Mtb-reactive clones arising from oligoclonal T cell proliferation. We introduce a modular computational pipeline, Metaclonotypist, to sensitively cluster distinct TCRs with shared epitope specificity, which we apply here to establish a catalogue of public Mtb-reactive HLA-restricted T cell metaclones. Although most in vivo Mtb-reactive T cells are private, 10 metaclones were sufficient to identify Mtb-T cell reactivity across our study population (N≥128), indicating striking population level immunodominance of specific TCR-peptide interactions that may inform patient stratification and vaccine development
THE ROLE OF THE LAMININ-332-ACTIN-CHOLESTEROL AXIS IN SKIN CONDITIONS WITH ALTERED LIPID PROFILES
Get PDFThe skin serves a critical barrier function, which is compromised in several conditions, leading to increased water loss and dry skin. Recent studies indicate that laminin-332, a basement membrane extracellular matrix protein, contributes to barrier maintenance by regulating lipid metabolism and transport. In this project, an nTERT keratinocyte cell line with knockdown of the laminin α3 subunit of laminin-332 was used to investigate the molecular mechanisms underlying this regulation. Analysis of proteins involved in intracellular cholesterol and lipid transport revealed that NPC2 and Myo5b levels decreased, whereas NPC1 increased, upon laminin α3 loss. Detailed phenotypic characterization further suggested that laminin α3 acts as a master regulator of keratinocytes and is crucial for E-cadherin–mediated cell-cell junctions. These findings were supported by transcriptomic, proteomic, and lipidomic analyses of shC and shLAMA3 nTERT keratinocytes, which demonstrated dysregulation of ECM, developmental, and actin-regulating proteins. Unexpectedly, a cluster of mitochondrial proteins was also downregulated in shLAMA3 cells, revealing a novel association between laminin α3 and mitochondrial function. Laminin α3 loss was found to induce generalized, context-dependent mitochondrial dysfunction. Finally, analyses of patient skin samples confirmed the relevance of these findings: subjects with dry skin exhibited higher levels of NPC2, NPC1, and E-cadherin. Overall, this project identifies several novel functions of laminin α3 in skin metabolism and provides insights relevant to conditions characterized by laminin α3 deficiency, as well as skin ageing, which is also associated with reduced laminin α3 levels
The utilisation and cost of social care after hip fracture: a prospective observational cohort study.
Get PDFBACKGROUND: The cost of medical care associated with hip fracture has been reported but the cost of social care is less well understood. Social care costs include formal residential and home care and home adaptations, but also informal care from family and friends. This study investigated the utilisation and cost of care beyond acute hospital stays following hip fracture. METHODS: A multi-centre, prospective observational study of patients ≥60 years with a hip fracture in the United Kingdom (UK), with 120-day follow-up. Marginal costs were calculated, with scenario analysis projecting the cost to the UK hip fracture population. A two-part model was used to calculate the incremental mean cost attributable to complications following surgery. RESULTS: Amongst 16 679 patients with a hip fracture, the mean cost of social care was £15 525 (95% CI: 14 991-16 059) per person. Mean cost per person for the change in residential requirements was £1656 (95% CI: 1568-1743); formal and informal home care £12 849 (95% CI: 12 448-13 250); and home adaptations £1021 (95% CI: 976-1067). The projected national cost of social care in the first 120 days following all hip fractures in the UK was £1.25 billion. Incremental mean cost of social care for patients who developed a surgery-specific or general complication were £1264 (95% CI: 58-2469) and £1418 (95% CI: 792-2043) per person, respectively. CONCLUSION: Social care represents a substantial and often under-recognised component of the economic burden following hip fracture. Formal and informal care were major cost drivers after discharge from hospital and may rival or exceed the cost of acute hospital care
A rare heterozygous IGFI variant causing postnatal growth failure and offering novel insights into IGF-I physiology
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