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Pooled analysis of PCV13 efficacy from controlled human infection trials in Malawi and the UK
Get PDFWe conducted the first pooled analysis of two randomised controlled vaccine trials on experimental pneumococcal serotype 6B carriage, registered in Malawi (PACTR202008503507113) and the UK (ISRCTN45340436). This post-hoc exploratory study examined the sex-based differences in carriage, vaccine efficacy and vaccine-induced responses. PCV-13 reduced colonisation by 76% (p < 0.001) with non-significant interaction by sex (RR = 1.549, p = 0.413). Females showed a higher carriage rate than males (28% vs. 19%, p = 0.066). Baseline anti-6B Capsular Polysaccharide Immunoglobulin G (IgG) titres were higher in females, significantly in Malawi (2.62 µg/ml vs males 2.05 µg/ml, p = 0.015). Post-vaccination titres did not differ by sex. The pooled fold change in IgG pre-post vaccination, was higher in vaccinated females (5.47 vs 3.30, p = 0.053). This analysis demonstrates the utility and challenges of integrating CHIM data between diverse settings to evaluate vaccine efficacy, describe inter-setting differences, investigate biological and immunological factors influencing protection against pneumococcal carriage and ultimately inform future vaccine development strategies
Effect of psychotropic medications on suicide-related outcomes: a systematic review and meta-analysis of observational studies
Get PDFBackgroundPsychiatric disorders are associated with increased risk of suicide-related outcomes, and the impact of pharmacological treatments on these outcomes is uncertain. Although randomised controlled trials are the main approach to evaluate efficacy, they may not provide externally valid results for suicide prevention in psychiatric populations. Thus, we aimed to synthesise the evidence on the effect of psychotropic medications on suicide-related outcomes from observational studies.MethodsIn this systematic review and meta-analysis, we systematically searched Ovid (MEDLINE, Embase, APA PsychArticles, AMED, BIOSIS, Global Health, PsycINFO), and Web of Science Core Collection from database inception to 8 December 2025 for pharmacoepidemiological and other observational studies on suicide-related outcomes in people treated with the main types of psychotropic medications: antidepressants, antipsychotics, mood stabilisers (including antiepileptics), and medications for anxiety (anxiolytics), attention deficit and hyperactivity disorder (ADHD), and substance use disorder (SUD). We included primary studies involving adults with common psychiatric diagnoses (schizophrenia spectrum disorders, bipolar disorder, depressive disorders, and personality disorders), who were prescribed medication and a comparison sample with the same diagnosis without prescribed medication (between-individual studies) or the same individuals during a non-prescription period (within-individual studies). We excluded studies that did not report psychiatric diagnoses and from selected samples. Outcomes were suicide attempts/self-harm and suicide mortality. We pooled effect sizes as odds ratios (OR), hazard ratios (HR) or risk ratios (RR) using random-effects models and assessed study quality using NOS and QUIPS tools. Study protocol was registered with PROSPERO, CRD42024515794.FindingsOf 5653 records identified, 48 independent studies from 13 countries based on more than 6 million people (47% male) met inclusion criteria. Across the main diagnostic categories and 70 individual medications examined, associations with reducing risk of suicide mortality were found for second generation antipsychotics in schizophrenia spectrum disorders: clozapine (OR = 0.40; 0.36-0.60; I2 = 60%, moderate certainty), olanzapine (OR = 0.53; 0.39-0.71; I2 = 34%, high certainty), quetiapine (OR = 0.75; 0.58-0.96; I2 = 0%, high certainty), and zuclopenthixol (OR = 0.44; 0.30-0.63; I2 = 0%, high certainty). In schizophrenia, second generation antipsychotics were also associated with reduced risks of suicide attempts: olanzapine (OR = 0.76; 0.60-0.98; I2 = 84%, moderate certainty) and risperidone (OR = 0.61; 0.52-0.72; I2 = 57%, moderate certainty). In bipolar disorder, lithium (OR = 0.38; 0.28-0.50; I2 = 67%, moderate certainty) and valproic acid (OR = 0.66; 0.59-0.75; I2 = 0%, high certainty) were associated with lower suicide risks, and lithium was also associated with lower risks of suicide attempts (OR = 0.60; 0.44-0.82; I2 = 92%, moderate certainty). In depression, associations with lower risk of suicide mortality for selective serotonin reuptake inhibitors (SSRIs) (OR = 0.61; 0.47-0.81; I2 = 23%, high certainty) and tricyclic antidepressants (OR = 0.68; 0.59-0.78; I2 = 0%, high certainty) were found. Benzodiazepines were associated with higher risk of suicide mortality in most diagnostic categories, except depression. There was some evidence for publication bias for lithium in bipolar disorder and clozapine in schizophrenia spectrum disorders, leading to more papers reporting lower risks of suicide-related outcomes. The risk of bias in included studies was low in 47 studies, moderate in one study, and certainty of evidence was moderate.InterpretationThere is evidence of varying effects of psychotropic medication on the risk of suicide-related outcomes across different psychiatric disorders. The appropriate use of prescribed medications in people with high risks of suicide-related outcomes is an important suicide prevention strategy. Findings are not causal, and limitations include the observational nature of included studies, risk of residual confounding, high heterogeneity for some outcomes, and moderate quality of the evidence.FundingUniversity of Oxford (Hill Foundation), NIHR Oxford Health Biomedical Research Centre, Wellcome Trust
Trends in the incidence of cancers of the breast and female genital tract in Harare, Zimbabwe 1990–2019
Get PDFTrends in age standardised incidence rates (ASRs) in the black (African) female population of Harare are reported for five cancers—of the breast and genital tract (cervix and corpus uteri, ovary and vulva) over a 30‐year period. The incidence of cervix cancer is very high (ASR of 73.7 per 105) and has increased at a rate of 1% annually over the period, although remaining stable in the most recent 15 years; the increase involves mainly women born between 1950 and 1970. Breast cancer rates are less than half those of cervix, but the increase has been more dramatic—3% annually—although this seems to involve only women aged over 40. The incidence of ovarian cancer has been constant over the 30 years; there was a small increase in the incidence of cancer of the corpus uteri (1.5% annually) and a more marked one for vulvar cancer (5.6% annually), for which the incidence is relatively high, by global standards. Concurrent with the increasing incidence of cancers of the breast and corpus uteri are notable trends of population risk factors such as rising obesity rates and declining fertility. The elevated burden of cervix and vulvar cancers aligns with patterns observed in populations with high HPV prevalence, though population‐specific data remain limited. The results confirm that cancers associated with increasingly affluent lifestyles (breast and corpus uteri) are increasing, although the incidence of cancer of the cervix—an eminently preventable cancer—remains persistently high and is clearly a priority for cancer control
Chemically Doped Conductive Polymers for Wearable Health Monitoring
Get PDFChemically doped conductive polymers are a class of “synthetic metals” that combine metal‐level electrical conductivity with intrinsic mechanical flexibility, and they are emerging as core materials for wearable health‐monitoring technologies. This review systematically summarizes recent advances in the field, focusing on chemical doping strategies—including small‐molecule dopants, ionic liquids, and polymeric dopants—that effectively overcome the intrinsic conductivity limitations of conductive polymers while simultaneously improving mechanical compliance and environmental stability. Enabled by these material innovations, high‐performance flexible sensors based on piezoresistive and chemiresistive mechanisms have been developed, allowing in situ, high‐fidelity monitoring of physiological signals such as electrocardiography, electromyography, and joint motion, as well as environmental hazards including toxic gases and ultraviolet radiation. From a fabrication perspective, printed electronics and fiber‐spinning technologies provide scalable and low‐cost routes for producing flexible devices and electronic textiles. Furthermore, through flexible hybrid electronics, sensing elements have been successfully integrated with wireless communication and power supply modules to form complete wearable systems. Although challenges remain in long‐term stability, reproducibility, and large‐scale manufacturing, the integration of doping engineering with artificial intelligence and self‐powered technologies is accelerating the evolution of chemically doped conductive polymers toward multimodal sensing, intelligent data analysis, and personalized health management, highlighting their substantial potential
Grief cinema: loss, mourning, repair: Bureau of Environmental Imaging and Memory Analysis
Get PDFIn 2125, Eve works for the Bureau of Environmental Imaging and Memory Analysis (BEIMA), an intergovernmental institution established in the aftermath of an unnamed ecological catastrophe. The Bureau is responsible for capturing ecological underthoughts—dreams, thoughts, and feelings unconsciously generated by Nature. Drawing on ecofeminist critique, Black hauntologies, and critical fabulation, BEIMA proposes ecological remembrance as a procedural labour essential to the protection of Nature. Central to the Bureau is a method called conditional apparition, which seeks to enable re-encounters with near-extinct species through creative staging, including dance, installation, film, and written accounts. Conditional Apparition operates as a representational strategy through which endangered and disappeared species are reactivated in cultural memory. Eve is an exhausted but dedicated bureaucrat in the Special Office of the Haunted, Cinema of Ecological Grief Division. To work in this office, one must be sufficiently haunted by ecological grief—the irreparable sorrow felt in response to devastated species, places, and landscapes. Eve’s responsibility is to inventory and perform memories pressed upon her by snowdrop plants, beluga whales, and river dolphins. Her work at the Bureau thus involves archival research at the Institute of Hydrobiology, Chinese Academy of Sciences, where the last living Baiji dolphin died in 2002 and efforts to protect the Yangtze finless porpoise have continued. Eve draws on the fieldnotes of an anonymous woman researcher who conducted fieldwork there in 2023. In lieu of repairing Eve’s estranged relationship with her father, who worked for the Department of Air and Sea, Eve delves into her archive to escape childhood. This dissertation offers a glimpse into life at the Bureau through an assemblage of official documents, family histories, diaries, reports, and dream journals, treating ecological grief as a condition through which ecological remembrance and more-than-human care may flourish
HDL Regulates TGFβ-receptor lipid raft partitioning, restoring contractile features of cholesterol-loaded vascular smooth muscle cells
Get PDFMany cells identified as macrophage-like in human and mouse atherosclerotic plaques are thought to be of vascular smooth muscle cell (VSMC) origin. We identified cholesterol-mediated down-regulation of TGFβ signaling in vitro in human (h)VSMCs by localization of TGFβ receptors in membrane lipid rafts, which was reversed by high-density lipoprotein (HDL)-mediated cholesterol efflux. This restored VSMC contractile marker (Acta2) and suppressed macrophage marker (CD68) expression by promoting TGFβ enhancement of Mir145 expression. In vivo, administration of ApoA1 (which forms HDL) to atherosclerotic mice also promoted VSMC Acta2 expression and reduced CD68 expression. Because macrophage-like VSMCs are thought to have adverse properties, our studies not only show mechanistically how cholesterol causes their transition, but also suggest that efflux-competent HDL particles may have a therapeutic role by restoring a more favorable phenotypic state of VSMCs in atherosclerotic plaques
Three-year risk prediction of aortic stenosis using routine medical records: derivation and validation in 919 954 individuals from two cohorts
Get PDFAims: All-cause mortality ranges between 33% and 42% for individuals with untreated moderate to severe aortic stenosis (AS). Transcatheter aortic valve replacement makes this a treatable condition, if identified early. Machine learning-based tools show great promise to predict cardiovascular outcomes. Methods and results: We developed and validated a machine learning model for 3-year prediction of AS risk (ASrisk) using serum biomarkers and vital sign measurements. We then evaluated the tool’s capacity to identify diagnoses of AS sequelae, echocardiographic outcomes in individuals not diagnosed with AS, as well as enrichment and 3-year aortic valve area reduction in individuals with high ASrisk. Among 919 954 participants, 429 996 were from the Mount Sinai Data Warehouse (MSDW) [2179 (0.5%) AS cases] and 489 958 were from the UK Biobank [5066 (1%) AS cases]. Odds ratio (OR) of AS sequelae increased quantitatively with ascending deciles of ASrisk [OR 1.63 (95% CI 1.60–1.67) in MSDW]. Increasing ASrisk by 1 SD resulted in higher odds of echocardiographic findings in undiagnosed individuals [OR 1.88 (95% CI 1.71–2.06) for Doppler velocity index, OR 2.50 (95% CI 2.36–2.64) for aortic valve area, and OR 2.61 (95% CI 1.89–2.71) for mean gradient]. Three years after risk assessment, individuals with ASrisk > 0.95 show an 11-fold enrichment for AS diagnosis in both cohorts and an average reduction in aortic valve area of 0.42 cm2. Conclusion: ASrisk can predict risk of AS 3 years ahead of diagnosis in the general population
The epidemiology of acute febrile illness in rural South and Southeast Asian primary care, and evaluation of selected interventions to improve its management
Get PDFAcute febrile illness (AFI) accounts for a major proportion of presentations in primary care, particularly in tropical low-income and middle-income countries (LMICs). The paradigm that tropical AFI is primarily attributable to malaria is no longer valid in South and Southeast Asia, yet there is precious little high-quality contemporary evidence on its epidemiology, especially in the rural, resource-constrained, and under-studied areas containing most of the regional population. Clinical and health policy decision-making is, thus, hampered leading to larger-scale problems such as antimicrobial over-prescription and development of resistance, and hospital overcrowding from poorly-targeted referrals. Viewing this pressing but neglected problem through a pragmatic, multi-disciplinary lens, this thesis aims to lay the foundations for the development of interventions to improve primary care management of AFI in rural South and Southeast Asia at both individual patient and population levels. Beginning with two multi-national prospective studies embedded in the South and Southeast Asian Community-based Trials Network Rural Febrile Illness project, it details the baseline contextual and epidemiological realities confronting health workers and policymakers in Bangladesh, Cambodia, Laos, Myanmar, and Thailand daily, which have thus far been poorly researched. The first showed that while there were considerable differences between these sites, all relied on primary health centres and village health/malaria workers as the main providers of primary healthcare. The key results from the second, an observational study, were that in the 82,760 patients enrolled by these two provider groups the most frequent diagnoses were upper respiratory tract infection (URTI, 61.0%) and fever of unclear source (30.7%). This study also showed that targeting of antibiotic prescriptions and identification of patients with potentially severe illness could be improved, although mortality was very low (0.01%). Building on the results, a variety of research methodologies based on real-world data were used to generate evidence on potential interventions, starting with one commonly used in high-income settings (pulse oximetry), followed by one for which the need is well-established but data for its development is lacking (a multiplex rapid diagnostic test for AFI). With regard to pulse oximetry, a systematic review concluded that it may assist clinicians in diagnosing and managing paediatric pneumonia, but for the greatest impact on patient outcomes should be implemented as part of a health systems approach. For the latter, the most important finding from a priority-setting Delphi survey was that it should be able to diagnose dengue and enteric fever at a minimum in adults and children. Health economic modelling studies showed that both these interventions were likely to be cost-effective in the settings which they were evaluated. The culminating work describes the development of a novel algorithmic electronic clinical decision support tool which integrates epidemiological and clinical data to guide diagnosis and management, and the methodology for its evaluation via a cluster-randomised trial in Cambodia. The generalisability of the knowledge gained from this thesis to other tropical LMICs, as well as the barriers to its application and implementation, are also discussed, along with potential solutions
Rapid all-optical loading of trapped ions using a miniaturized atom source
No full textWe characterise an efficient optically-heated neutral atom source for ion trapping. We observe loading rates of up to 24(3) s−1 with heating powers below 85 mW, and demonstrate loading of a single ion in under 30 s with 41.4(4) mW of optical power in a room-temperature ion trap system with an ionisation probability of 1.50(5) × 10−5 . We calibrate a thermal model for the source’s internal temperature by imaging the fluorescence of a collimated flux of neutral calcium that effuses from the source at various optical heating powers. We show that the thermal performance of this source is mainly limited by radiative losses. We explore the effect of second-stage photo-ionisation laser power on the loading rate, and identify a path beyond the loading rates reported in this study. We predict that this source is also well-suited to a wide range of metals used in ion trapping
Medium-Range Structural Order in Amorphous Arsenic
Get PDFMedium-range order (MRO) is a key structural feature of amorphous materials, but its origin and nature remain elusive. Here, we reveal the MRO in amorphous arsenic (a-As) using advanced atomistic simulations, based on machine-learned potentials derived using automated workflows. Our simulations accurately reproduce the experimental structure factor of a-As, especially the first sharp diffraction peak (FSDP), which is a signature of MRO. We compare and contrast the structure of a-As with that of its lighter homologue, red amorphous phosphorus (a-P): we find that a-As has a more uniform dihedral-angle distribution, and so we confirm that its structure can be thought of as a 3-fold coordinated continuous random network in first approximation, in contrast to the more molecular-cluster-like structure of a-P. The pressure-dependent structural behaviors of a-As and a-P differ as well, and the origin of the FSDP is closely correlated with the size and spatial distribution of voids in the amorphous networks. Our work provides fundamental insights into MRO in an amorphous elemental system, and more widely it illustrates the usefulness of automation for machine-learning-driven atomistic simulations