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Roles for endogenous aldehydes in haematopoietic ageing and immunity
Get PDFFormaldehyde is a fundamental driver of genomic instability. This has led to the evolution of a two-tiered defence system that engages metabolic detoxification (“tier-1” via ALDH2 and ADH5) and DNA repair pathways (“tier-2” via Fanconi’s anaemia repair (FA) and transcription coupled repair). Strikingly, ~540 million people of East Asian descent carry a variant in the ALDH2 allele (ALDH2*2), which impairs tier-1 protection. When these carriers also incur mutations in ADH5 or FA repair, they develop significant disease, characterised by leukaemia, bone marrow failure, developmental abnormality and shortening life span. Given this predisposition, the high prevalence of ALDH2*2 is surprising, suggesting this allele has evaded selection by conferring an underappreciated selective advantage, or that its effects become significant only over time. In this thesis, I explore whether ALDH2 deficiency may confer a selective advantage through enhancing humoral immunity. I compare the humoral immune response of Aldh2-/- mice to model antigens (HEL, OVA, BSA and HA), finding ALDH2-deficiency influenced humoral immunity in an antigen dependent manner, which may be significant in helping ALDH2*2 carriers to resist certain infections. I also investigate how tier-1 deficiency drives ageing in the blood. An existing model of tier-1 deficiency, Aldh2-/-Adh5-/-, shows features of accelerated ageing, including cell-fate bias and somatic mosaicism, but its extreme perinatal lethality prevents its use to study ageing as a time-dependent process. To address this, I use Vav1iCre to delete ALDH2 specifically in the blood of Adh5-/- mice. This rescued the peri-natal lethality, and revealed features of haematopoietic ageing, though without clonal haematopoiesis. Together, these models demonstrate that endogenous formaldehyde can drive instructional changes on stem cell fate, providing insight into how endogenous formaldehyde may act as a fundamental driver of ageing. This work has significant implications for understanding mechanisms of ageing and disease in the 540 million individuals with compromised tier-1 protection
B-field Orion Protostellar Survey (BOPS). IV. The Relative Orientation between Magnetic Fields and Density Structures in Young Protostellar Envelopes
Get PDFWe investigate the relative alignment between density structures and magnetic fields in eight young protostars from the Atacama Large Millimeter/submillimeter Array B-field Orion Protostellar Survey. Column density maps are derived from 870 μm dust continuum emission, and the Histogram of Relative Orientations method is applied to quantify the correlation between magnetic field orientations and density structures on envelope scales (∼103 au). We find that the relative alignment shows overall little evidence of systematic evolution with column density, suggesting that column density alone does not fully determine the alignment. The magnetization level also plays a crucial role, with weakly magnetized envelopes exhibiting predominantly parallel or random alignment, whereas strongly magnetized ones show perpendicular configurations even at moderate densities. These results reveal that density and magnetization jointly shape the morphology of protostellar envelopes and the coupling between gravity and magnetic fields during early stages of star formation
Threats and vulnerabilities in artificial intelligence and agentic AI models
Get PDFIntroduction: Adversarial robustness in artificial intelligence is commonly defined in terms of input-level perturbations applied to static models. This study reconceptualises adversarial vulnerability for artificial and agentic AI systems by extending the threat model to autonomy, self-governance, and closed-loop decision-making, where behaviour unfolds dynamically through feedback and control. Methods: We develop a system-level analytical framework that formalises adversarial risk across perceptual, cognitive, and executive layers. The analysis is grounded in a PRISMA-compliant systematic literature review, bibliometric mapping, and targeted empirical validation. Established adversarial results from vision benchmarks and recent large-language-model red-teaming studies are synthesised to contextualise the framework, rather than to introduce new benchmark performance claims. Results: The results demonstrate that no single defence mechanism provides robustness across all layers of agentic AI systems. Adversarial vulnerabilities propagate from perception to policy and actuation, with architectural similarity, domain shift, and feedback dynamics critically shaping transferability and failure modes. These effects have direct implications for safety-critical applications, including autonomous mobility, healthcare imaging, and biometric security. Discussion: By framing higher-order agentic adversarial threats as hypothesis-driven, system-level risks, this work shifts adversarial AI security from benchmark-centric evaluation to behavioural integrity and lifecycle resilience. The proposed framework defines a coherent research agenda for agentic AI security that integrates control-theoretic reasoning and governance-aware defence design, addressing limitations of classical adversarial machine-learning theory
Mental health disorders among Sudanese medical students amid the 2023 conflict: prevalence, predictors, and implications
Get PDFBackground: The ongoing military conflict in Sudan since 2023 has disrupted both medical education and the healthcare system, likely adversely affecting the mental health of medical students. Purpose: This study investigates the prevalence of anxiety, depression, post-traumatic stress disorder (PTSD) and possible predictive factors in Sudanese medical students during the April 2023 military conflict. Cross-sectional: Studies were included among the faces of Sudanese medical students in conflict-affected regions. Participants completed an online questionnaire covering demographics, education, coping strategies, and mental health using the Hospital Anxiety and Depression Scale (HADS) and Posttraumatic Stress Checklist (PCL-5). Results: In our large sample of 4185 medical students, very high rates of anxiety (61.98%), depression (65.5%), and PTSD (36.7%) were reported. Medical students without plans for continuation of education exhibited significantly higher levels of anxiety and depression compared to their counterparts (p < 0.001). An increased age is associated with higher levels of anxiety (estimate: 0.14, 95%CI: 0.08 to 0.19), depression (estimate: 0.11, 95%CI: 0.06 to 0.16), and PTSD (estimate: 0.35, 95%CI: 0.16 to 0.55). Males exhibit significantly lower levels of anxiety (estimate: −2.1, 95%CI: −2.4 to −1.8), depression (estimate: −0.59, 95%CI:-0.86 to −0.33), and PTSD (estimate: −6.1, 95%CI:-7.2 to −4.9) compared to females. Perceived below-average financial status before conflict significantly increases anxiety (estimate: 0.69, 95%CI: 0.19 to 1.2), depression (estimate: 0.82, 95%CI: 0.38 to 1.3), and PTSD (estimate: 3.2, 95%CI: 1.3 to 5.0). Experiences of sexual abuse, physical abuse, death of a family member, and financial damage are strongly associated with increased anxiety, depression, and PTSD. Attending public medical school is associated with lower anxiety (estimate: −0.74, 95%CI: −1.0 to −0.45), depression (estimate: −0.76, 95%CI: −1.0 to −0.51), and TSD (estimate: −1.6, 95%CI: −2.6 to −0.54) compared to private school attendance. Conclusion: Our study found high rates of mental health conditions and distress among Sudanese medical students during the ongoing conflict. Associated factors include demographic factors, personal economic stability, coping strategies, and trauma. Urgent interventions are vital to target the factors mentioned above. Prioritising students’ mental well-being is critical for their resilience and to support their contributions to post-conflict nation-building efforts
Statistical shape modeling in cardiovascular disease: a narrative review
Get PDFCardiovascular diseases (CVDs) remain a leading cause of mortality worldwide. We explore the application of statistical shape modeling (SSM) as a powerful tool in cardiac anatomy assessment, facilitating innovative approaches to diagnosis and treatment. SSM uses advanced mathematical and statistical techniques to understand the geometric properties of anatomical structures across populations. By identifying significant shape parameters, it captures and quantifies subtle variations that may elude traditional approaches. We discuss its evolution, from landmark-based methods to point distribution models for establishing the point-to-point correspondence crucial for accurate shape analysis. We delve into the statistical techniques used to measure shape variability, with a focus on principal component analysis for dimensionality reduction. Key evaluation metrics in the assessment of model performance, such as compactness, generalization and specificity, are reviewed. The clinical utility of SSM across the spectrum of CVDs is examined, covering diagnosis, risk stratification, treatment optimization, follow-up and research applications. Future directions, including the development of multi-label models, integration of deep learning approaches, and spatio-temporal SSM to capture dynamic changes in cardiac geometry, are considered. Through this narrative review, we aim to underscore SSM’s promise as a powerful tool in combating CVDs and advancing personalized medicine, ultimately improving patient outcomes
Vegetarian diets and cancer risk: pooled analysis of 1.8 million women and men in nine prospective studies on three continents
Get PDFBACKGROUND: Vegetarian diets might influence cancer risk. METHODS: We studied 1,645,555 meat eaters, 57,016 poultry eaters, 42,910 pescatarians, 63,147 vegetarians and 8849 vegans in 9 cohorts (UK, US, Taiwan, India). After a median 16 years follow-up, incident cancers were: 4504 mouth and pharynx, 1308 oesophagus (squamous cell), 2105 oesophagus (adenocarcinoma), 3578 stomach, 30,528 colorectum, 2970 liver, 8030 pancreas, 3077 lung (never smokers), 61,368 breast, 11,220 endometrium, 8076 ovary, 45,946 prostate, 7193 kidney, 6869 bladder, 11,651 non-Hodgkin lymphoma, 4658 multiple myeloma and 7306 leukaemia. Multivariable Cox regression was used to estimate cohort-specific hazard ratios (HRs) and 95% confidence intervals (CIs), and the results were combined using meta-analysis. RESULTS: Compared to meat eaters, poultry eaters had lower risk of prostate cancer (0.93, 0.88-0.98), pescatarians had lower risks of colorectal (0.85, 0.77-0.93), breast (0.93, 0.88-0.98) and kidney cancer (0.73, 0.58-0.93), vegetarians had lower risks of cancers of the pancreas (0.79, 0.65-0.97), breast (0.91, 0.86-0.97), prostate (0.88, 0.79-0.97), kidney (0.72, 0.57-0.92) and multiple myeloma (0.69, 0.51-0.93) but higher risk of squamous cell carcinoma of the oesophagus (1.93, 1.30-2.87), and vegans had higher risk of colorectal cancer (1.40, 1.12-1.75). CONCLUSIONS: Vegetarian diets might influence risk for several cancers. The generalisability should be considered cautiously
From millimeters to microns: a hybrid strategy for reconfigurable liquid‐crystal patterning
Get PDFProgrammable patterning of nematic liquid crystals (LCs) enables spatially encoded optical functionality, but existing approaches often face trade-offs between patterned area, feature fidelity, dimensionality, and device integration. Many methods rely on surface alignment, electrode patterning, or global illumination, limiting local addressability, depth control, or scalability. Field-assisted polymerization of reactive mesogens offers a means to capture designed LC director configurations as permanent, structurally encoded profiles. Here, we report a hybrid strategy combining wide-field one-photon polymerization (1PP) for rapid, large-area templating with two-photon polymerization direct laser writing (2PP-DLW) for localized, maskless microstructuring with depth control. This decoupling of patterned area from feature fidelity allows multiple, spatially co-located director profiles to be encoded within a single glass cell, enabling voltage-selective visibility and reconfigurable optical responses. Local 2PP-DLW features define confinement boundaries and deterministic defect nucleation and guidance, while 1PP establishes the global architecture with high throughput. Because patterning is encoded in the polymer rather than electrode geometry, complex profiles can be realized using uniform electrodes. In a nematic Pi-cell, this approach enables controlled defect channeling, programmable topological transitions, and multistate optical patterns, offering a scalable route to high-fidelity reconfigurable LC micro-optics
Secondary Epigraphy in the Pyramid Complex of Senwosret III Part I
No full textThe archaeological exploration led by the Metropolitan Museum of Art team in the pyramid precinct of Senwosret III at Dahshur, Egypt, has now continued for more than three decades. Added figural and textual epigraphy, also known as ‘secondary epigraphy’, or ‘graffiti’, constitutes a significant trace of the post-Middle Kingdom activities, and has an important role in a comprehensive cultural biographical approach to the study of this archaeological site. This is the first volume of its systematic edition, focused on the North Chapel and the Pyramid Temple of Senwosret III
Academic impact and research data utilisation of the Clinical Practice Research Datalink: scientometric analyses
No full textSince its establishment in the late 1980s, the UK Clinical Practice Research Datalink (CPRD) has become one of the most widely utilised data resources in both national and international research. Its value lies in the richness, scale and quality of its routinely collected primary care data, as well as the availability of numerous linkable datasets. This study provides comprehensive scientometric analyses of CPRD-related research output, impact, and data usage from 1988 to 2024. A total of 3,779 peer-reviewed publications were identified, and for 98.78% of them, enriched bibliometric metadata were retrieved through Scopus and Web of Science. The UK emerged as the leading contributing country, with the United States and Canada ranking second and third. ‘McGill University’ was the most frequently affiliated institution, followed by the ‘University of Manchester’ and the ‘University of Oxford’, with seven UK universities among the top ten. The three journals most frequently publishing CPRD-based research overall, and since 2020, were ‘BMJ Open’, ‘Pharmacoepidemiology and Drug Safety’ and ‘British Journal of General Practice’. Analyses of primary care data sources utilisation revealed that overall, 86.35% of manuscripts used CPRD GOLD exclusively, 8.39% used both CPRD GOLD and CPRD Aurum, and 4.76% used CPRD Aurum alone, although recent years showed an increased use of CPRD Aurum. Between 2016 and 2024, most articles (80.26%) were associated with CPRD research applications that referenced linked or CPRD algorithm-derived datasets. The three most frequently used were ‘Hospital Episode Statistics’ (69.77%), ‘Small Area Linkages’ (62.27%) and ‘Office for National Statistics’ mortality data (53.28%)