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The extreme rainfall alert (ERA) pilot was a response to the Pitt Review's recommendation that 'the Met Office and Environment Agency (EA) provide an early assessment of the costs, benefits and feasibility of techniques which can predict where rain will fall and where surface water flooding will occur'. In April 2009, the ERA became an operational service provided to the EA professional partners and Category 1 and 2 responders-organizations with legal responsibilities to respond to flooding. ERAs are intended as a first step towards warnings for surface water flooding (SWF). This article assesses the effectiveness of the ERA pilot at predicting SWF. ERAs relating to three case study areas and issued during the pilot were compared with reports of SWF, identified from the data available relating to all sources of flooding. While data were found to be lacking in quality and consistency, it is possible to provide an initial assessment of the effectiveness of the ERA pilot. The existing ERA rainfall thresholds do not relate directly to SWF in all areas. As the ERA service specifically intends to warn for rainfall likely to cause severe SWF in urban areas, it is impossible to draw strong conclusions without further investigating the magnitude of flooding which occurred both when an ERA was and was not issued. As SWF magnitude and extent data were extremely sparse, it is recommended that systematic collection of comprehensive data relating to flood events should be implemented nationally. This will facilitate more accurate investigations of the links between rainfall intensity and SWF, which it is vital to understand in order to provide the most effective surface water flood warnings possible. Copyright © 2011 Royal Meteorological Society [ABSTRACT FROM AUTHOR]

Flood risk consists of complex and dynamic problems, whose management calls for innovative ways of engaging with a wide range of local stakeholders, many of whom lack the technical expertise to engage with traditional flood risk management practices. Participatory approaches offer potential for involving these stakeholders in decision‐making, yet limited advice is available to users in choosing which techniques to employ and what they might expect them to deliver. Assessing the effectiveness of participatory approaches in local flood risk management is a critical step towards better understanding how community resilience is built. This article presents a framework for evaluating participatory approaches to flood risk management that covers four evaluation elements (context, process, substantive, and social outcomes). Practical success criteria are provided for evaluation, with references indicating where further advice and guidance can be sought. Criteria are tailored to the requirements of flood risk management, and aim to be sufficiently flexible for the framework to be easily transferable. [ABSTRACT FROM AUTHOR]

The family of pro-inflammatory and pro-angiogenic chemokines including Interleukin-8 (IL-8, aka CXCL8) and its homologues (CXCL1,2,3,5,6, and 7) exhibit promiscuous binding and activation of several G-protein-coupled receptors (i.e., CXCR2, CXCR1, and the atypical chemokine receptor (ACKR1)). A high proportion of their biological activity is attributed to CXCR2 activation, thus many CXCR2 inhibitors are in clinical trials for several chronic diseases. However, CXCR2 inhibition is often only investigated acutely in these trials or in Cxcr2 -/- mice grown in gnotobiotic conditions. Since humans do not live in germ-free environments, our first goal is to highlight novel retinal and systemic observations in Cxcr2 -/- mice grown in non-gnotobiotic conditions that suggest potential harmful consequences of long-term CXCR2 deficiency or blockade. Beyond confirmation of circulating blood/immune cell-related phenotypes, we report novel findings in Cxcr2 -/- mice including: (1) delayed dye transit to the retinal vasculature, (2) alterations in the density and distribution of retinal vessels, astrocytes and microglia, (3) decreased electroretinogram a- and b-wave amplitudes, (4) reduced visual acuity, and (5) increased polymorphonuclear cell accumulation in vascular lumina abutting venular walls in the retina and in vital non-ocular tissues (lung and liver). Furthermore, PheWAS of CXCR2 CXCR1, and ACKR1 gene variants using data from UK Biobank participants suggest clinical associations with both retinal and vascular disease phenotypes. We conclude that chronic CXCR2 deficiency in mice contributes to functional damage to the retina and that the long-term safety of CXCR1/2 inhibitors designed for chronic use in humans should be explored before clinical adoption to safeguard sight and overall vascular health., (© 2024. The Author(s).)

Chronic inflammation contributes to the prevalence of cardiovascular disease in people living with HIV (PLWH). The immune mechanisms driving atherosclerosis progression in PLWH remain unclear. This study conducted comprehensive assessments of medium-sized coronary arteries and aorta from deceased PLWH and controls without HIV using DNA/RNA assays, spatial transcriptomics, and high-resolution mass spectrometry. Findings revealed more significant inflammation correlated with higher HIV copy numbers in late atheroma of PLWH. Enhanced CXCL12 and decreased ABCA1/ABCG1 expression in CD163+ macrophages were co-localized in coronaries of PLWH, suggesting a reduction in plasma lipoprotein clearance compared to controls. Spatial analyses identified potential therapeutic targets by revealing inflammatory changes in medium-sized arteries and the aorta. We examined the relationship between atherosclerotic phenotypes and inflammatory gene expression in Vanderbilts Biobank to study these findings in a larger clinical cohort. This established a significant association between ABCA1 and CXCL12 gene expressions with atherosclerosis, partly influenced by HIV.

Chronic systemic inflammation significantly increases myocardial infarction risk in people living with HIV (PLWH). Endothelial cell dysfunction disrupts vascular homeostasis regulation, increasing the risk of vasoconstriction, inflammation, and thrombosis, contributing to cardiovascular disease. We aimed to characterize endothelial cell (EC) chemokines, cytokine, and chemokine receptors of PLWH, hypothesizing that in our cohort, glucose intolerance contributes to their differential expression implicated in endothelial dysfunction. Using single-cell transcriptomic analysis, we phenotyped chemokine and cytokine receptor expression on arterial ECs, capillary ECs, venous ECs, and vascular smooth muscle cells (VSMCs) in subcutaneous adipose tissue of 59 PLWH with and without glucose intolerance. Our results show that arterial and capillary ECs express significantly higher interferon and tumor necrosis factor (TNF) receptors than venous ECs and VSMCs. Venous ECs exhibited more interleukin (IL)1R1 and ACKR1 receptors, and VSMCs showed significant IL6R expression than arterial and capillary ECs. When stratified by group, arterial ECs from PLWH with glucose intolerance expressed significantly higher IL1R1, IL6R, CXCL12, CCL14, and ICAM2 transcripts than arterial ECs from PLWH without diabetes. Of the different vascular cell types studied, arterial ECs as a proportion of all ECs in adipose tissue were positively correlated with plasma fasting blood glucose. In contrast, venous ECs and VSMCs were positively correlated with plasma IL6. To directly assess the effect of plasma from PLWH on endothelial function, we cultured human arterial ECs (HAECs) in plasma-conditioned media from PLWH and performed bulk RNA sequencing. Plasma from PLWH stimulated ECs with the upregulation of genes that enrich for the oxidative phosphorylation and the TNF-α via NFK-β pathways. In conclusion, ECs in PLWH show heterogeneous cytokine and chemokine receptor expression, and arterial ECs were the most influenced by glucose intolerance. Further research must explicate cytokine and chemokine roles in EC dysfunction and identify biomarkers for disease progression and therapeutic response., (© 2024 The Author(s). Journal of Cellular Physiology published by Wiley Periodicals LLC.)

An increased risk of cardiometabolic disease accompanies persistent systemic inflammation. Yet, the innate and adaptive immune system features in persons who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric and other immune phenotyping analyses, which limits our understanding of their relationship to disease states. Using well-characterized clinical cohorts, including participants with controlled HIV as a model for chronic inflammation and increased immune cell interactions, we show that circulating CD14 + monocytes complexed to CD3 + T cells are dynamic, biologically relevant, and increased in individuals with diabetes after adjusting for confounding factors. The complexes form functional immune synapses with increased expression of proinflammatory cytokines and greater glucose utilization. Furthermore, in persons with HIV, the CD3 + T-cell: CD14 + monocyte complexes had more HIV copies compared to matched CD14 + monocytes or CD4 + T cells alone. Our results demonstrate that circulating CD3 + T-cell:CD14 + monocyte pairs represent dynamic cellular interactions that may contribute to inflammation and cardiometabolic disease pathogenesis and may originate or be maintained, in part, by chronic viral infections. These findings provide a foundation for future studies investigating mechanisms linking T cellmonocyte cell-cell complexes to developing immune-mediated diseases, including HIV and diabetes., Competing Interests: Declaration of interests The authors have no competing interests.

Background: Final year medical students and postgraduate doctors regularly contend with feelings of under-preparedness when transitioning into new areas of clinical practice. This lack of confidence is most evident in the context of on-call work which frequently requires sound clinical prioritisation, rigorous decision making and the management of acutely unwell patients, often with reduced senior support and staffing. This has prompted the emergence of on-call simulation which seeks to enhance participant confidence in performing on-call tasks and facilitate the development of key clinical and non-technical skills. This narrative review examined the use of on-call simulation in medical student and newly qualified doctor cohorts, its effectiveness in achieving its stated outcomes and to identify novel areas for the development of existing models., Method: A search strategy was developed in conjunction with a specialist medical librarian. OVID Medline and Embase searches identified articles related to the use and design of on-call simulation in medical education with no restrictions placed upon date or language of publication. Key findings from articles were summarised to develop comprehensive themes for discussion., Results: Twenty Three unique publications were reviewed which unanimously reported that on-call simulation had a positive effect on self-reported participant confidence in performing on-call roles. Furthermore the value on-call simulation when used as an induction activity was also evident. However, there was limited evidence around improved patient and performance outcomes following simulation. It also remains resource intensive as an educational tool and there is a distinct absence of interprofessional education in current models., Conclusions: We concluded that on-call simulation must adopt an interprofessional educational approach, incorporating other clinical roles. Further studies are needed to characterise the impact on patient outcomes. It remains highly useful as a confidence-boosting induction activity, particularly in specialities where clinical exposure is limited. Virtual and tabletop simulation formats, could potentially address the resource burden of manikin-based models, particularly with ever growing demands on medical educators and the expansion of training posts., (© 2024. The Author(s).)

Aims: This systematic literature review (SLR) consolidated economic and healthcare resource utilization (HCRU) evidence for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to inform future economic evaluations., Materials and Methods: An electronic search was conducted in MEDLINE, Embase, and Cochrane databases from 2012-2022. Economic and HCRU studies in adults who underwent PET- or SPECT-MPI for coronary artery disease (CAD) diagnosis were eligible. A qualitative methodological assessment of existing economic evaluations, HCRU, and downstream cardiac outcomes was completed. Exploratory meta-analyses of clinical outcomes were performed., Results: The search yielded 13,439 results, with 71 records included. Economic evaluations and comparative clinical trials were limited in number and outcome types (HCRU, downstream cardiac outcomes, and diagnostic performance) assessed. No studies included all outcome types and only one economic evaluation linked diagnostic performance to HCRU. The meta-analyses of comparative studies demonstrated significantly higher rates of early- and late-invasive coronary angiography and revascularization for PET- compared to SPECT-MPI; however, the rate of repeat testing was lower with PET-MPI. The rate of acute myocardial infarction was lower, albeit non-significant with PET- vs. SPECT-MPI., Limitations and Conclusions: This SLR identified economic and HCRU evaluations following PET- and SPECT-MPI for CAD diagnosis and determined that existing studies do not capture all pertinent outcome parameters or link diagnostic performance to downstream HCRU and cardiac outcomes, thus, resulting in simplified assessments of CAD burden. A limitation of this work relates to heterogeneity in study designs, patient populations, and follow-up times of existing studies. Resultingly, it was challenging to pool data in meta-analyses. Overall, this work provides a foundation for the development of comprehensive economic models for PET- and SPECT-MPI in CAD diagnosis, which should link diagnostic outcomes to HCRU and downstream cardiac events to capture the full CAD scope.

Background: Schools are high-risk settings for infectious disease transmission. Wastewater monitoring for infectious diseases has been used to identify and mitigate outbreaks in many near-source settings during the COVID-19 pandemic, including universities and hospitals but less is known about the technology when applied for school health protection. This study aimed to implement a wastewater surveillance system to detect SARS-CoV-2 and other public health markers from wastewater in schools in England., Methods: A total of 855 wastewater samples were collected from 16 schools (10 primary, 5 secondary and 1 post-16 and further education) over 10 months of school term time. Wastewater was analysed for SARS-CoV-2 genomic copies of N1 and E genes by RT-qPCR. A subset of wastewater samples was sent for genomic sequencing, enabling determination of the presence of SARS-CoV-2 and emergence of variant(s) contributing to COVID-19 infections within schools. In total, >280 microbial pathogens and >1200 AMR genes were screened using RT-qPCR and metagenomics to consider the utility of these additional targets to further inform on health threats within the schools., Results: We report on wastewater-based surveillance for COVID-19 within English primary, secondary and further education schools over a full academic year (October 2020 to July 2021). The highest positivity rate (80.4%) was observed in the week commencing 30th November 2020 during the emergence of the Alpha variant, indicating most schools contained people who were shedding the virus. There was high SARS-CoV-2 amplicon concentration (up to 9.2x106 GC/L) detected over the summer term (8th June - 6th July 2021) during Delta variant prevalence. The summer increase of SARS-CoV-2 in school wastewater was reflected in age-specific clinical COVID-19 cases. Alpha variant and Delta variant were identified in the wastewater by sequencing of samples collected from December to March and June to July, respectively. Lead/lag analysis between SARS-CoV-2 concentrations in school and WWTP data sets show a maximum correlation between the two-time series when school data are lagged by two weeks. Furthermore, wastewater sample enrichment coupled with metagenomic sequencing and rapid informatics enabled the detection of other clinically relevant viral and bacterial pathogens and AMR., Conclusions: Passive wastewater monitoring surveillance in schools can identify cases of COVID-19. Samples can be sequenced to monitor for emerging and current variants of concern at the resolution of school catchments. Wastewater based monitoring for SARS-CoV-2 is a useful tool for SARS-CoV-2 passive surveillance and could be applied for case identification and containment, and mitigation in schools and other congregate settings with high risks of transmission. Wastewater monitoring enables public health authorities to develop targeted prevention and education programmes for hygiene measures within undertested communities across a broad range of use cases., Competing Interests: Department of Health and Social Care - NHS test and trace, Funded cost of sample collection, analysis and reporting. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Hassard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Persons with HIV (PWH) on long-term antiretroviral therapy (ART) have a higher incidence and prevalence of cardiometabolic diseases attributed, in part, to persistent inflammation despite viral suppression. In addition to traditional risk factors, immune responses to co-infections such as cytomegalovirus (CMV) may play an unappreciated role in cardiometabolic comorbidities and offer new potential therapeutic targets in a subgroup of individuals. We assessed the relationship of CX3CR1 + , GPR56 + , and CD57 +/- T cells (termed CGC + ) with comorbid conditions in a cohort of 134 PWH co-infected with CMV on long-term ART. We found that PWH with cardiometabolic diseases (non-alcoholic fatty liver disease, calcified coronary arteries, or diabetes) had higher circulating CGC + CD4 + T cells compared to metabolically healthy PWH. The traditional risk factor most correlated with CGC + CD4 + T cell frequency was fasting blood glucose, as well as starch/sucrose metabolites. While unstimulated CGC + CD4 + T cells, like other memory T cells, depend on oxidative phosphorylation for energy, they exhibited higher expression of carnitine palmitoyl transferase 1A compared to other CD4 + T cell subsets, suggesting a potentially greater capacity for fatty acid β-oxidation. Lastly, we show that CMV-specific T cells against multiple viral epitopes are predominantly CGC + . Together, this study suggests that among PWH, CGC + CD4 + T cells are frequently CMV-specific and are associated with diabetes, coronary arterial calcium, and non-alcoholic fatty liver disease. Future studies should assess whether anti-CMV therapies could reduce cardiometabolic disease risk in some individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wanjalla, Gabriel, Fuseini, Bailin, Mashayekhi, Simmons, Warren, Glass, Oakes, Gangula, Wilfong, Priest, Temu, Newell, Pakala, Kalams, Gianella, Smith, Harrison, Mallal and Koethe.)

Clinical testing of children in schools is challenging, with economic implications limiting its frequent use as a monitoring tool of the risks assumed by children and staff during the COVID-19 pandemic. Here, a wastewater-based epidemiology approach has been used to monitor 16 schools (10 primary, 5 secondary and 1 post-16 and further education) in England. A total of 296 samples over 9 weeks have been analysed for N1 and E genes using qPCR methods. Of the samples returned, 47.3% were positive for one or both genes with a detection frequency in line with the respective local community. WBE offers a low cost, non-invasive approach for supplementing clinical testing and can provide longitudinal insights that are impractical with traditional clinical testing., Competing Interests: The authors have declared that no competing interests exist.

Background The General Medical Council (GMC) requires all newly qualified doctors to be competent in certain surgical skills, including the provision of basic wound closure. Yet there is a profound lack of undergraduate competence in, and exposure to, basic surgical skills such as wound closure. The Surgical Skills Day (SSD) aimed to provide medical students with additional skills training. Methods Student self-assessment and instructors' assessment forms were completed prior to and following a workshop on basic wound closure skills. Paired t-tests was used to statistically compare the two pre and post-instruction data sets. Results A total of 46 students attended the SSD; 29 consented to the skills assessment. 100% (n = 29) self-reported improved competency in at least one of the skills following tuition (p < 0.001). Instructors' assessment agreed that 100% (n = 29) of students improved in at least one of the skills assessed (p < 0.001). 100% of the attendees agreed that additional practical surgical skills should be incorporated into the undergraduate curriculum. 64% (n = 21) of students also confirmed that they were more likely to pursue a career in surgery following the SSD. Conclusion Current clinical teaching in basic suturing is unsuitable for long term retention. SSDs can improve skills acquisition and elevate student confidence. This data builds on our previous work by documenting the high efficacy in skills acquisition as a result of SSD tuition. We recommend that SSDs be integrated into medical school curricula in order to address shortcomings in current undergraduate programmes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Lee et al.)

Introduction:  Medical students across the United Kingdom (UK) report poor satisfaction with surgical teaching. The Surgical Skills Day (SSD) begins to address this by exposing medical students to surgery through an easily accessible one-day practical workshop. This study shows how the SSD encourages undergraduate engagement in surgery., Method:  Feedback forms were emailed to attendees of the SSD and their anonymised responses were used to evaluate the SSD., Results:  A total of 144 students attended the SSD across three years and the feedback response rate was 74% (n = 107). Key findings were that 100% of respondents (n = 107) would like the SSD to be an annual event, 79% (n = 83) were more inclined to pursue a surgical career following the event, and 97% (n = 103) would like to see practical surgical skills incorporated into the curriculum. The SSD was able to engage undergraduates with surgery through mentorship, practical skills, specialty exposure, and teaching of the General Medical Council (GMC) mandated skills., Conclusions:  Undergraduate surgical teaching in the UK is insufficient. The student-led annual SSD showed improved engagement in practical surgical skills and increased enthusiasm for a surgical career. In light of this, the authors feel the SSD or similar event should be integrated into the UK medical school curriculum., Competing Interests: The authors have declared that no competing interests exist.