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Effect of prior antiplatelet therapy on recurrence in patients with acute cerebral ischaemia: data from the triple antiplatelets for reducing dependency after ischaemic stroke (TARDIS) randomised trial
No full textBackground: Data regarding management of patients already on an antiplatelet when presenting with an ischaemic stroke or transient ischaemic attack (TIA) are limited. This secondary analysis of the triple antiplatelets for reducing dependency in ischaemic stroke (TARDIS) trial explored clinical outcomes across prior antiplatelet groups. Methods: TARDIS was an international prospective-randomised open-label blinded-endpoint trial assessing 30days of triple vs. guideline antiplatelet therapy in patients with acute ischaemic stroke or TIA. The number of pre-stroke/TIA antiplatelet agents was collected pre-randomisation. The primary outcome was the combined incidence of, and dependency from, any recurrent stroke (using the modified Rankin Scale) or TIA within 90days analysed using ordinal logistic regression with adjustment for prognostic factors. Baseline imaging features of brain frailty were adjudicated centrally by neuroimaging experts. Results: 1080/3096 (34.9%) participants were on an antiplatelet agent prior to their stroke/TIA and were older, more likely to be male, had more co-morbidities and dependency, and more baseline imaging features of brain frailty than those not on prior antiplatelets. They had a higher incidence of, and dependency from, recurrent stroke or TIA at day 90: 86 (8%) vs. 112 (5.6%), adjusted common OR 1.40, 95%CI 1.02–1.92, p = 0.036; the result was neutralised when adjusted for brain frailty. Randomisation to triple vs. guideline therapy did not influence this effect. Conclusions: Participants taking prior antiplatelets were frailer and had a higher incidence and severity of recurrent stroke or TIA at 90days compared with those not on prior antiplatelets prior to adjustment for brain frailty. Trial registration: ISRCTN47823388
‘clogged by masses of paperwork’: Britain’s Secret Intelligence Service (SIS/MI6), Whitehall and the early Cold War, 1949–1956
No full textThis article examines the work and organisation of Britain’s Secret Intelligence Service (SIS or MI6) in the early Cold War, broadening the study of the service beyond the 1949 cut-off date of the service’s authorised history. It shows that whilst efforts to reform the service for peacetime had started before the end of the Second World War, this process remained incomplete over a decade later. It also explores SIS’s relations with the rest of Whitehall, especially liaison with customers on the main Soviet target, and the financial aspects of the service’s work and the oversight of HM Treasury
Remittances as translocal collateral: How microfinance profitably sustains precarity in Cambodia
No full textIn this paper, we explore how commercialised microfinance institutions and banks leverage remittance-related information to assess and provide microfinance loans to households in Cambodia. We argue that (microfinance) debt regimes profitably sustain precarity in the Cambodian translocal context. Building from five studies undertaken between 2014 and 2022, we illustrate our argument through a two-pronged approach. First, we critically unpack the empirical realities of the relationship between migration, remittances, and debt repayment. We show that the lending strategies of microfinance institutions and banks take into account the remittances received by rural households from adult children who have moved to cities or overseas. It is the social obligations within the family to remit money home – or ‘filial debts’ – that are being collateralised. As the monetary expression of these social obligations, remittances serve as a form of what we call ‘translocal collateral’ which (re)constitutes connections among family members across space to mitigate repayment risks for the microfinance industry, often at the expense of the well-being of its borrowers. Second, we contend that these financial institutions’ lending practices – and the development programmes and policies that promote them – rely on translocal strategies of social reproduction that are unstable and fragile. Sudden interruptions in remittance flows can have significant ramifications for rural households, forcing them to deal not only with decreases in income but also looming debts to repay. This should serve as a call for caution among development practitioners and policymakers promoting the leveraging of remittances for financial inclusion
A Wireless Power Transfer System Based on Hybrid Self-switching of Coupled Inductors
Get PDFThis paper proposes a wireless power transfer system based on hybrid self-switching of coupled inductor that not only realizes constant current (CC)/constant voltage (CV) output but also effectively copes with a variety of abnormal working conditions in the charging process by switching on the secondary side. First, the LCC-LCC/S self-switching composite topology is presented, and the CC/CV switching is achieved by utilizing a coupled inductor with a center tap based on the LCC compensation topology. The working principle of the CC/CV topology and the parameter calculation flow are analyzed in detail. Subsequently, the impedance, output characteristics, and switching characteristics of the constant current/constant voltage topology are simulated and analyzed. Additionally, the topology's stability under abnormal working conditions, such as the missing adjacency, load short-circuit, and load open-circuit, is analyzed. Finally, an experimental platform is constructed with the objective of verifying the feasibility and effectiveness of the proposed scheme. The experimental results demonstrate that the proposed charging system exhibits excellent constant current and constant voltage output characteristics without the need for additional inductor capacitance. The proposed system has a maximum output efficiency of 89.6%, a maximum current of 5.3A, and a maximum voltage of 23V, which fully meets the requirements of constant current and constant voltage wireless charging
Machine learning prediction of moderate‐to‐severe acute kidney injury after ICU admission and cardiac surgery with urine trace elements
Get PDFBackground: Acute kidney injury (AKI) is common and linked to poor outcomes, but early detection remains challenging. Previous research identified urinary trace elements (TE) as early AKI biomarkers in intensive care unit (ICU) or cardiac surgery patients. We aimed to explore whether urinary TE enhance machine learning (ML) models for AKI prediction. Methods: We constructed ML models using the ICU cohort. We filtered the variables and optimized hyperparameters before predicting Kidney Disease: Improving Global Outcomes stage 2–3 AKI using eight ML classifiers: light gradient boosting machine (LightGBM), random forest (RF), ML logistic regression, support vector machine, multilayer perceptron, eXtreme gradient boosting (XGBoost), Gaussian Naive Bayes and k-nearest neighbors. External validation was performed in the cardiac surgery cohort. Results: Among 149 ICU patients (median age 56.0 [interquartile range (IQR): 43.5–67.0], 63.1% male), 25 developed stage 2–3 AKI; among 144 cardiac surgery patients (median age 70.0 [IQR: 62.0–76.0], 72.9% male), 12 developed stage 2–3 AKI. Each ML in the internal validation had area under the curve (AUC) above.7, with XGBoost having the highest (.813); LightGBM had the second highest AUC (.799), highest G-mean (.567) and F1-score (.545). In external validation, RF had the highest AUC (.740), XGBoost had the highest G-mean (.289) and F1-score (.286). Age, strontium and boron were consistently ranked among the top five most important features in LightGBM, RF and XGBoost. Conclusion: ML models primarily based on urinary TE can identify AKI risk in both clinical groups (ICU and cardiac surgery), with LightGBM, RF and XGBoost serving as high-performance models for early prediction of stage 2–3 AKI
The incidence of aneuploidy and mosaicism in 2,045 genotyped cattle blastocysts
No full textChromosomal abnormalities are the most common cause of developmental arrest in mammalian embryos. They can be present consistently in all cells of the embryo or occur as admixtures of karyotypically distinct lineages (mosaics). The estimated incidence of mosaicism ranges from 14% to 82% in human embryo biopsies at the blastocyst stage. In cattle, mosaicism is not well described at a whole-genome level, with findings limited to sex chromosomes. Here, we conducted a retrospective analysis of published data spanning three studies from our laboratory to establish the incidence and nature of mosaicism in 2,045 bovine blastocysts genotyped using single nucleotide polymorphism-based approaches. We classified mosaic embryos as those where the inner cell mass and trophectoderm differed in ploidy and/or where embryos had a percentage of cells with aneuploidy ranging from 20% to 80%. We report an aneuploidy incidence of 15.2% (n = 311/2,045), with 25.6% of the aneuploid embryos (80/311) being mosaic. Mosaicism was particularly common (87.5%, n = 7/8) in embryos affected by multiple types of chromosomal errors and in embryos affected only by segmental aneuploidies (50.0%, n = 9/18). The chromosomal abnormalities with the highest incidence of mosaicism were segmental aneuploidies (48.1%, n = 13/27). Most errors leading to mosaicism had a paternal origin (44.9%, n = 22/49), followed by post-zygotic errors (37.3%, n = 19/51). Our results reveal an incidence of mosaicism in bovine embryos similar to that of human embryos. Additionally, we demonstrate that ploidy and mosaicism screening can be performed in embryos using the same single nucleotide polymorphism genotyping data obtained to calculate genomic estimated breeding values
Molecular Interactions of Fluoroquinolone Antibiotics with Lipid Membranes
Get PDFLevofloxacin is a broad-spectrum fluoroquinolone antibiotic in clinical use that targets DNA gyrase in the cytosol. It is used in systemic applications via oral or intravenous route, and its pharmacokinetics and access to its molecular targets are strongly influenced by interactions with cellular membranes. We used NMR and MD simulations to investigate the physical state of levofloxacin in solution and its interactions with lipid membranes, assessing the role of membrane charge and antibiotic concentration. Using zwitterionic DOPC and negatively charged DOPC/DOPG lipid membranes, we observe concentration-dependent self-association of levofloxacin in solution below its solubility limits and association with lipid membranes with a preference for negatively charged bilayers. Below the solubility limit, levofloxacin solutions that appear clear contain self-associated molecular assemblies in fast exchange equilibrium with a monomeric soluble population. In the presence of lipid membranes, this equilibrium is shifted in favor of a membrane-associated population with preference for negative lipids. MD simulations show levofloxacin condensation in solution and fractional membrane insertion, which suggest the presence of a molecular population embedded in the lipid bilayer, coexisting with self-associated levofloxacin molecular "droplets" in exchange with a solvated population
A partially pooled network scale-up method model: detailed estimation of child sexual exploitation material trafficking prevalence in Philippine municipalities
Get PDFEffective policy and intervention strategies to combat human trafficking for child sexual exploitation material (CSEM) production require accurate prevalence estimates. Traditional network scale-up method (NSUM) models often necessitate standalone surveys for each geographic region, escalating costs, and complexity. This study introduces a partially pooled NSUM model, using a hierarchical Bayesian framework that efficiently aggregates and utilizes data across multiple regions without increasing sample sizes. We developed this model for a novel national survey dataset from the Philippines and we demonstrate its ability to produce detailed municipal-level prevalence estimates of trafficking for CSEM production. Our results not only underscore the model’s precision in estimating hidden populations but also highlight its potential for broader application in other areas of social science and public health research, offering significant implications for resource allocation and intervention planning
The effects of prophylactic use of paracetamol on body temperature and blood pressure in elderly patients with acute stroke: Data from the PRECIOUS trial
Get PDFBackground and aims Prophylactic administration of paracetamol (acetaminophen) has been reported to reduce body temperature in the first day after stroke and to reduce blood pressure on the first day. We aimed to validate these findings in the randomised PRECIOUS trial and to assess the effect of paracetamol on body temperature in the first seven days after stroke. Patients and methods PRECIOUS was an international, 3*2 factorial, randomised, controlled, clinical trial assessing preventive treatment with paracetamol, metoclopramide, and ceftriaxone in patients aged 66 years or older with acute stroke and a score on the National Institutes of Health Stroke Scale (NIHSS) ≥ 6. Paracetamol was given in a dose of 4g daily for four days. Vital signs were recorded at 12 hours intervals up to seven days. The primary outcomes of this study were body temperature and systolic and diastolic blood pressure at 24 hours after randomisation, analysed with linear regression. The presence of a subfebrile temperature or fever at 24 hours was a secondary outcome. Results We used data from 1419 of 1493 patients included in PRECIOUS. Paracetamol reduced mean body temperature by 0.1°C (95% CI, 0.0–0.2) at 24 hours after randomisation but did not lower systolic or diastolic blood pressure. Paracetamol reduced the occurrence of subfebrile temperatures or fever at 24 hours from 15.8% to 8.3% (p<0.001). The effects of paracetamol on body temperature were consistent over the four days of treatment. Conclusion Prophylactic use of paracetamol resulted in a modest reduction in mean body temperature and almost halved the rate of subfebrile temperatures or fever at 24 hours after stroke, but had no effect on blood pressure
Human Decision-Making in Crowds in a Virtual Flood Scenario
Get PDFFlood evacuation outcomes are critically shaped by human behaviour, yet empirical data on individual decision-making remain scarce due to the dangers and logistical challenges of collecting data during real natural hazards. To address this gap, this study used Virtual Reality (VR) to examine how social cues, specifically crowd behaviour, interact with factors such as crowd size, clarity of the safe destination, and floodwater level to influence evacuation choices and delays. Four within-subjects VR experiments were conducted with 84 participants, systematically testing these variables in an immersive flood scenario. Results showed that crowd behaviour strongly determined both route choice and evacuation latency, often outweighing other factors. Participants tended to follow crowds into floodwater, demonstrating the influence of social information. However, this influence weakened when water levels were very high, indicating a threshold overrides social cues. Larger crowds and unclear destination information further increased reliance on social information and pre-movement times. These findings highlight the powerful role of social dynamics in emergency decision-making and underscore the need to integrate realistic human behaviour, particularly social influence, into flood risk models, public warnings, and evacuation planning to improve community resilience and safety
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