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Risk factors for perioperative stroke, myocardial infarction, and death in patients undergoing carotid endarterectomy under local anesthesia: a systematic review and meta-analysis
Get PDFBackground: Patients with vascular disease undergoing surgery face increased
perioperative risks, and those scheduled for carotid endarterectomy (CEA)
represent a particularly vulnerable subgroup. This study aimed to (1) estimate
the prevalence and identify predictors of adverse postoperative outcomes in
patients undergoing carotid endarterectomy (CEA) under local/regional
anesthesia (LA), and (2) compare these outcomes with those of general
anesthesia (GA) where comparative data were available.
Methods: Following PRISMA and MOOSE guidelines, PubMed, Scopus, and Web
of Science were systematically searched for English-language studies published
up to January 2025. Pooled prevalence estimates were obtained using randomeffects
models. Meta-regression explored associations of demographic and
clinical variables with postoperative outcomes. In addition, pairwise randomeffects
meta-analyses were performed for studies reporting separate
outcomes for LA and GA. Effect sizes were expressed as odds ratios (OR) with
95% confidence intervals (CIs), and heterogeneity was quantified using the
I2 statistic.
Results: Of 267 records identified, 14 studies met eligibility criteria, including
22,302 patients undergoing CEA under LA. The pooled prevalence was 1% for
stroke (95% CI: 0.01–0.02) and 0.01% for both myocardial infarction and
death (95% CI: 0.00–0.01). Meta-regressions showed that male sex was
significantly associated with postoperative stroke (β = 0.010, p = 0.0002),
whereas older age predicted myocardial infarction (β = 0.006, p = 0.03). No
significant predictors of mortality were identified. In the comparative analysis,
LA was associated with a 52% lower risk of myocardial infarction and a 30%
lower risk of death compared with GA, while no significant difference
emerged for postoperative stroke. Conclusion: CEA performed under regional anesthesia is associated with low
rates of adverse postoperative events, with male sex and older age emerging as
relevant predictors for stroke and myocardial infarction, respectively.
Comparative evidence suggests potential advantages of LA over GA in reducing
myocardial infarction and mortality, while stroke risk appears similar between
anesthetic modalitie
A systematic review and equity analysis of school-based violence prevention interventions evaluated in randomised controlled trials
Get PDFBackground: Experiencing violence in school is a violation of a child’s rights and can increase school absence, affect academic achievement, employment prospects, and later-life health. Effective school-based violence prevention interventions are crucial, however, most are universally targeted. It is less clear if current interventions to prevent violence in schools ensure subgroups of children benefit equitably. Methods: We conducted a systematic review. We drew on professional networks and searched Medline, Cochrane Library, Embase, Global Health, PsycINFO, and Web of Science to identify systematic reviews (n = 29) which included randomised controlled trials (RCTs) of school-based violence prevention interventions. Reviews conducted searches until December 2023. We screened all included articles within the final review sample to identify all RCTs of universal school-based violence prevention interventions. We examined what sociodemographic characteristics were measured, assessed intervention effectiveness by subgroups, and applied criteria to assess equity. Results: Out of 160 articles of RCTs evaluating violence prevention interventions in schools, we identified 19 articles reporting on 16 trials that reported effects by the following subgroups: sex (n = 16), disability (n = 1), sexuality (n = 1), race/ethnicity (n = 1) and socioeconomic status (n = 1). Subgroup and moderation analysis found mixed results of intervention effectiveness by subgroups, with some evidence of heterogeneity. Conclusions: Most trials of school-based violence prevention interventions do not report whether they are effective for subgroups of minoritised children, or children at higher risk of experiencing violence, and therefore may not contribute to advancing health equity. Ensuring a commitment to equity in the design, delivery, and impact of school-based violence prevention is essential to achieving the Sustainable Development Goals. Review registration: PROSPERO: CRD42023463384
Detecting brick kiln infrastructure at scale: graph, foundation, and remote sensing models for satellite imagery data
No full textBrick kilns are a major source of air pollution and forced labor in South Asia, yet large-scale monitoring remains limited by sparse and outdated ground data. We study brick kiln detection at scale using high-resolution satellite imagery and curate a multi-city zoom-20 resolution (0.149 m pixel−1 ) dataset comprising over 1.3 million image tiles across five regions in South and Central Asia. We propose ClimateGraph, a region-adaptive graphbased model that captures spatial and directional structure in kiln layouts, and evaluate it against established graph learning baselines. In parallel, we assess a remote sensing–based detection pipeline and benchmark it against recent foundation models for satellite imagery. Our results highlight complementary strengths across graph, foundation, and remote sensing approaches, providing practical guidance for scalable brick kiln monitoring from satellite imagery
Exploring the impact of patient-derived NMDAR NR1-specific IgG antibodies on the developing mouse striatum
Get PDFMaternal antibodies targeting neuronal proteins, such as the NMDA receptor (NMDAR) and its NR1 subunit, can cross the foetal blood-brain barrier and disrupt neurodevelopment. Previous studies suggest that these NR1-targeting antibodies may be elevated in mothers of children with neurodevelopmental disorders, and animal models have shown that exposure to them during gestation leads to developmental abnormalities that persist into adulthood. The central hypothesis of this thesis is that early exposure to maternal NR1-IgG antibodies disrupts the development of the striatum, leading to long-term structural and functional alterations in this critical brain region, which may underlie behavioural deficits. However, the specific mechanisms by which these antibodies impact the developing brain, particularly striatal circuits, remain poorly understood.To address this, a novel in utero model was developed to deliver patient-derived NR1-IgG antibodies directly into the mouse brain via intraventricular injections. Immunohistochemical analyses revealed that the embryonic lateral ganglionic eminence (LGE), a key progenitor region forstriatal development, exhibits high expression of the NMDAR NR1 subunit. Both polyclonal and monoclonal NR1-IgG antibodies were shown to bind to the LGE following in utero delivery, establishing a robust model for further investigation. Using this model, the impact of transient NR1-IgG exposure during the embryonic neurogenic period was examined. Analysis demonstrated reduced size of the primordial striatum, decreased proliferation of progenitor cells in the LGE, impaired neuronal migration, and an increase in microglial density and altered microglial morphology. In postnatal studies to examine the impact of transient NR1-IgG exposure, whole-cell patch-clamp electrophysiology and morphological reconstructions of striatal spiny projection neurons (SPNs) revealed immature intrinsic properties, simplified neuronal morphology, and altered synaptic function, including a reduced NMDA/AMPA ratio. Postnatal MRI scans corroborated these findings, showing reduced striatal volume. Additionally, an imbalance in the D1/D2-SPN ratio was observed, with fewer D2-SPNs. Increased microglial density and altered microglial morphology persisted postnatally, further implicating microglial involvement in the observed changes. Behaviourally, early motor reflexes were delayed and affected animals exhibited reduced anxiety-like behaviour in open-field tests and increased time on the accelerating rotarod, suggesting motor- and anxiety-related impairments. Treatment with the AMPAkine CX516 during the first postnatal week partially rescued the behavioural phenotype, indicating that enhancing glutamatergic signalling via alternative routes may mitigate some of the effects of NR1-IgG exposure.Overall, this thesis presents a novel experimental model to study the effects of maternal NR1-IgG antibody exposure on the developing striatum. The findings demonstrate that early exposure leads to significant embryonic and postnatal alterations in striatal development, which manifest as behavioural deficits. Importantly, the partial rescue of these phenotypes through AMPA receptor modulation highlights potential therapeutic avenuesfor addressing neurodevelopmental disorders associated with maternal antibodies
Pharmacological blood pressure-lowering for prevention of cardiovascular disease and death across the full spectrum of chronic kidney disease severity: an individual participant data meta-analysis of 46 randomised controlled trials
No full textBackground: Owing to safety concerns, individuals with chronic kidney disease (CKD), particularly those at more advanced stages, have been systematically underrepresented in randomised controlled trials (RCTs) of blood pressure (BP)-lowering treatment, leading to a persistent paucity of evidence for cardiovascular risk management in this high-risk group. We sought to investigate the effect of BP-lowering treatment on the risk of major cardiovascular disease and death across the full spectrum of CKD stages, and by key clinical subgroups.Methods: We conducted a one-stage individual participant data meta-analysis of RCTs in which participants were randomised to a BP-lowering therapy—single or multiple agents or an intensive regimen—versus a comparator (placebo, active agent, or a less intensive regimen). RCTs with at least 1000 person-years of follow-up per arm, with baseline BP and creatinine measurements, and time-to-event outcomes were eligible; those with unclear randomisation procedures or restricted to heart failure or acute care settings were excluded. Participants with a documented history of heart failure or extreme creatinine values were excluded. The primary outcome was major cardiovascular events, defined as a composite of fatal or non-fatal stroke, ischaemic heart disease, or hospitalisation for, or death from, heart failure. Relative treatment effects were estimated using a stratified Cox proportional hazards model. Heterogeneity of treatment effects was evaluated across prespecified subgroups defined by CKD status, CKD stage (1–5), diabetes, proteinuria, and baseline BP. Stratified network meta-analysis was performed to examine whether treatment effects differed by defined subgroups within each of five principal antihypertensive drug classes.Findings: A total of 285,124 participants from 46 randomised trials met the eligibility criteria; 41.5% were women, 20.7% had CKD at baseline, and 22.8% had type 2 diabetes. During a median follow up of 4.4 years (IQR 3.2–5.1), a 5 mm Hg achieved reduction in systolic BP reduced the risk of major cardiovascular disease by approximately 10% in individuals both with and without CKD (with CKD: HR 0.91 [95% CI 0.87–0.94]; without CKD: HR 0.90 [0.88–0.93], Pinteraction >0.99 ). Furthermore, these observed relative risk reductions were consistent across all CKD stages, including severe stages 4–5 (Pinteraction > 0.99). Similar treatment effects were observed by proteinuria status and across BP categories, down to <120/70 mm Hg. However, the relative treatment effect in individuals with CKD was notably attenuated among those with coexisting diabetes (HR 0.96 [95% 72 CI 0.90–1.02]) compared with those without (HR 0.88 [95% CI 0.84–0.93]; Pinteraction = 0.04). The stratified analysis within each drug class showed that the class-specific effects of antihypertensive agents versus placebo on cardiovascular disease risk remained unchanged across the investigated subgroups.Interpretation: In the context of cardiovascular risk reduction, the relative benefit of BP lowering in patients with CKD is comparable to that in individuals without CKD, with consistent efficacy across all CKD stages, BP thresholds, and proteinuria status. Notably, however, this relative benefit is attenuated in patients with CKD and concomitant diabetes, underscoring the requirement for adapted therapeutic strategies in this high-risk subgroup. Moreover, the class-specific effects of principal antihypertensives in CKD mirror those observed in the broader population, independent of CKD 82 stage or proteinuria status. Funding: British Heart Foundatio
The Great Filter – Is it just a matter of time?
Get PDFThe discussion on the second day of the symposium centred on the Great Filter, a concept proposed by Robin Hanson as a way to reframe the analysis of the Fermi Paradox. It asserts that there must be a least one Great Filter – an evolutionary step that is extremely improbable – somewhere along a chain which starts from a lifeless Earth-like planet, followed by the sequential development of simple, complex, intelligent/technological life, and culminating in an explosive phase of readily-detectable galactic colonization. Some 25 years on from Hanson’s proposal, we examine the Great Filter’s continuing usefulness as a concept and current thinking on whether any such filter lies in our past (Early Great Filter), or is waiting in our future (Late Great Filter), and what this means for us and our search for life in the Univers
Nicholas of Lyra's literal and moral postillae on the Book of Esther
Get PDFNicholas of Lyra (c. 1270-1349) wrote two commentaries on the entire Bible: one according to the literal, the other according to the spiritual (what he called the 'moral') sense of scripture. In keeping with tradition, the Franciscan declares that the literal sense is the foundation for any other sense; what he meant by literal and moral senses and what relationship exists between them are questions which have no clear answer. Nicholas's exegesis is also remarkable for an unprecedented use of Jewish sources in his literal commentary. Most of the scholarly engagement with Nicholas's work centres around this first commentary, and explores Nicholas's attitude toward his Jewish sources. I am interested in understanding the relationship between the two commentaries. Did Nicholas's unprecedented use of Jewish sources in his literal commentary lead to any serious innovations in his spiritual commentary? In what sense is the literal a 'foundation' for the moral?
These are question not yet addressed by scholars of his work, but answers to these questions would provide insights into the development of the senses of scripture, and a more complete picture of Nicholas himself as a Franciscan exegete. I am using Nicholas's literal and moral commentaries on the book of Esther to explore the relationship between the two commentaries. Esther is an interesting context in which to explore these questions because Nicholas was the first Christian exegete to write a literal commentary on this book, which had traditionally been allegorised to contrast Jews and Christians.
I will argue that the content and methods of Jewish sources are used by Nicholas in his innovative literal commentary as part of an effort to provide the literal sense of Esther with a religious and spiritual value in its own right, a value rooted in the perceived historical truth of the events. This theological attitude toward history increased the importance of the literal/historical sense of Esther, which no longer needed to be allegorised to have significance for Christians. This same theological and historiographical interest shapes Nicholas's moral commentary also. He does provide an allegory for the book of Esther, but his allegory has its value in being historical, rather than doctrinal. Ultimately, I believe Nicholas is best understood as a Church historian, with a deeply theological understanding of history. My study contributes to our understanding of later medieval Christian Hebraism, Franciscan historiography, and changing perceptions of the fourfold senses method
First host record of stylopization of a worker ant, Ectatomma edentatum (Formicidae: Ectatomminae), by a Myrmecolacidae (Strepsiptera)
Get PDFStrepsipterans of the family Myrmecolacidae are endoparasitoid insects of ants distributed worldwide, except in the Palearctic and Antarctic regions. Despite this, knowledge about their host ants and the effects of this parasitism on their biology remains scarce. To fill this gap in Brazil, we used yellow pan traps in a fragment of Atlantic Forest in search of stylopized ants (i.e., parasitized by Strepsiptera). The present study records for the first time the observation of a stylopized worker ant of the species Ectatomma edentatum in Brazil and details the general behavior of stylopized ants. Furthermore, we discuss the potential of yellow pan traps as a collection method of stylopized ants and compare their functionality to previously employed methods
The future of transfusion and transplant microbiology safety: can new molecular technologies improve the safety of blood and transplant?
Get PDFClinical trial number: Not applicable
Social, environmental and policy contexts affecting the feasibility and acceptability of improving household flooring for better health in rural Kenya
Get PDFBackground: Homes with unimproved floors (earth, sand, or clay) are associated with increased risks of soil-transmitted parasites and enteric infections, leading to higher morbidity and reduced quality of life. This study explored the enablers and barriers to adopting improved flooring (sealed, washable, and durable) in three culturally diverse regions of Kenya - Narok, Bungoma, and Kwale - to mitigate disease burdens. Methods: Between August 2021 and July 2022, we conducted 24 focus group discussions with homeowners, stratified by age, gender, and floor type. Additionally, 28 key informant interviews with local government officials, microfinance representatives, and masonry trainers in Kwale and Bungoma provided contextual insights. Transcribed data underwent thematic analysis. Results: In the study areas, most homes were constructed by residents themselves using traditional techniques and locally sourced materials. Despite awareness of the health risks, unimproved floors remained widespread. In Bungoma and Kwale, financial constraints and competing household priorities were primary barriers to flooring improvements, while in Narok, cultural identity contributed strongly to the rejection of changes in traditional houses. Key enablers included perceived health benefits and social status, while feasibility depended on the affordability and availability of materials and skilled labour. Strengthening the role of local artisans and leveraging their social influence were seen as effective strategies to shift perceptions on cost and feasibility. Improved collaboration between health and built-environment sectors could enhance community trust and support environmental disease management. Conclusion: Communities in Kwale and Bungoma were more receptive to improved flooring, while cultural practices and preferences in Narok posed significant adoption challenges. For receptive communities, affordable flooring technologies are critical to overcoming financial barriers, while behaviour change initiatives should address cultural and perceptual concerns. However, clinical evidence on locally generated health benefits is needed to support policy decisions and budget allocations for flooring interventions