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Abstract Background In England, the number of takeaway food outlets (‘takeaways’) has been increasing for over two decades. Takeaway management zones around schools are an effective way to restrict the growth of new takeaways but their impacts on population health have not been estimated. Methods To model the impact of takeaway management zones on health, we used estimates of change in and exposure to takeaways (across home, work, and commuting buffers) based on a previous evaluation suggesting that 50% of new outlets were prevented from opening because of management zones. Based on previous cross-sectional findings, we estimated changes in body mass index (BMI) from changes in takeaway exposure, from 2018 to 2040. We used PRIMEtime, a proportional multistate lifetable model, and BMI change to estimate the impact of the intervention, in a closed-cohort of adults (25–64 years), on incidence of 12 non-communicable diseases, obesity prevalence, quality-adjusted life years (QALYs), and healthcare costs saved by 2040 in six local authorities (LAs) across the rural–urban spectrum in England (Wandsworth, Manchester, Blackburn with Darwen, Sheffield, North Somerset, and Fenland). Results By 2031, compared to no intervention, reductions in outlet exposure ranged from 3 outlets/person in Fenland to 28 outlets/person in Manchester. This corresponded to mean per person reductions in BMI of 0.08 and 0.68 kg/m2, respectively. Relative to no intervention, obesity prevalence was estimated to be reduced in both sexes in all LAs, including by 2.3 percentage points (PP) (95% uncertainty interval:2.9PP, 1.7PP) to 1.5PP (95%UI:1.9PP, 1.1PP) in males living in Manchester and Wandsworth by 2040, respectively. Model estimates showed reductions in incidence of disease, including type II diabetes (e.g. 964 (95% UI: 1565, 870) fewer cases/100,000 population for males in Manchester)), cardiovascular diseases, asthma, certain cancers, and low back pain. Savings in healthcare costs (millions) ranged from £1.65 (95% UI: £1.17, £2.25)/100,000 population in North Somerset to £2.02 (95% UI: £1.39, £2.83)/100,000 population in Wandsworth. Gains in QALYs/100,000 person were broadly similar across LAs. Conclusions Takeaway management zones in England have the potential to meaningfully contribute towards reducing obesity prevalence and associated healthcare burden in the adult population, at the local level and across the rural–urban spectrum.

Abstract The increasing availability of ultrabright Light Sources is facilitating the study of smaller crystals at faster timescales but with an increased risk of severe X-ray damage, leading to developments in multi-crystal methods such as serial crystallography (SX). SX studies on crystals with small unit cells are challenging as very few reflections are recorded in a single data image, making it difficult to determine the orientation matrix for each crystal and thus preventing the combination of the data from all crystals for structure solution. We herein present a Small-Rotative Fixed-Target Serial Synchrotron Crystallography (SR-FT-SSX) methodology, in which rotation of the serial target through a small diffraction angle $$(\varphi )$$ ( φ ) at each crystal delivers high-quality data, facilitating ab initio unit cell determination and atomic-scale structure solution. The method is benchmarked using microcrystals of the small-molecule photoswitch sodium nitroprusside dihydrate, obtaining complete data to d min = 0.6 Å by combining just 66 partial datasets selected against rigorous quality criteria.

Abstract Variably Protease Sensitive Prionopathy (VPSPr) is a rare human prion disease that, like Creutzfeldt-Jakob disease (CJD), results in the deposition of abnormally folded prion protein aggregates in the brain and is ultimately fatal. Neuropathology and clinical features of VPSPr are heterogeneous. However, the key discriminating feature is the relative sensitivity of the pathological prion protein to proteinase digestion compared to that typically seen in other human prion cases. Three major fragments of 23, 17 and 7 kDa are characteristic of the disease following digestion with proteinase K. We recently reported the utility of the highly adaptive and reproducible ProteinSimple™ capillary electrophoresis (CE) system to perform protein separation of PK digested prion protein in CJD. Consequently, we explored capillary-based electrophoresis (CE) technology as a sensitive method to detect and characterize VPSPr in a cohort of 29 cases. The unique 7 kDa fragment has high intensity, particularly in cases with the codon 129 VV genotype, but can be missed by regular Western blotting due to the small size. However, this fragment is readily detected by CE in all cases. In addition, the flexibility of CE produced highly reproducible, semi-quantitative data for determining relative proteinase K sensitivity and epitope mapping of representative cases from each codon 129 genotype (VV, MV and MM).

Abstract Background Neighbourhood exposure to takeaways can contribute negatively to diet and diet-related health outcomes. Urban planners within local authorities (LAs) in England can modify takeaway exposure through denying planning permission to new outlets in management zones around schools. LAs sometimes refer to these as takeaway “exclusion zones”. Understanding the long-term impacts of this intervention on the takeaway retail environment and health, an important policy question, requires methods to forecast future takeaway growth and subsequent population-level exposure to takeaways. In this paper we describe a novel two-stage method to achieve this. Methods We used historic data on locations of takeaways and a time-series auto-regressive integrated moving average (ARIMA) model, to forecast numbers of outlets within management zones to 2031, based on historical trends, in six LAs with different urban/rural characteristics across England. Forecast performance was evaluated based on root mean squared error (RMSE) and mean absolute scaled error (MASE) scores in time-series cross-validation. Using travel-to-work data from the 2011 UK census, we then translated these forecasts of the number of takeaways within management zones into population-level exposures across home, work and commuting domains. Results Our ARIMA models outperformed exponential smoothing equivalents according to RMSE and MASE. The model was able to forecast growth in the count of takeaways up to 2031 across all six LAs, with variable growth rates by RUC (min–max: 39.4-79.3%). Manchester (classified as a non-London urban with major conurbation LA) exhibited the highest forecast growth rate (79.3%, 95% CI 61.6, 96.9) and estimated population-level takeaway exposure within management zones, increasing by 65.5 outlets per capita to 148.2 (95% CI 133.6, 162.7) outlets. Overall, urban (vs. rural) LAs were forecast stronger growth and higher population exposures. Conclusions Our two-stage forecasting approach provides a novel way to estimate long-term future takeaway growth and population-level takeaway exposure. While Manchester exhibited the strongest growth, all six LAs were forecast marked growth that might be considered a risk to public health. Our methods can be used to model future growth in other types of retail outlets and in other areas.

In Kenya, influenza virus circulates year-round, raising questions about optimum strategies for vaccination. Given national interest in introducing influenza vaccination for young children 6–23 months of age, we modeled total influenza-associated illnesses (inclusive of hospitalizations, outpatient illnesses, and non‒medically attended illnesses) averted by multiple potential vaccination strategies: year-round versus seasonal-campaign vaccination, and vaccination starting in April (Southern Hemisphere influenza vaccine availability) versus October (Northern Hemisphere availability). We modeled average vaccine effectiveness of 50% and annual vaccination coverage of 60%. In the introduction year, year-round vaccination averted 6,410 total illnesses when introduced in October and 7,202 illnesses when introduced in April, whereas seasonal-campaign vaccination averted 10,236 (October) to 11,612 (April) illnesses. In the year after introduction, both strategies averted comparable numbers of illnesses (10,831–10,868 for year-round, 10,175–11,282 for campaign). Campaign-style vaccination would likely have a greater effect during initial pediatric influenza vaccine introduction in Kenya; however, either strategy could achieve similar longer-term effects.

Abstract We study the leading loop-level phenomenology of composite Higgs models via the effective field theory of a strongly interacting light Higgs and top quark (SILH+TQ). We systematically analyze the renormalization group evolution (RGE) of tree-generated operators in the SILH+TQ scenario, finding large mixings of flavor non-universal operators into those affecting electroweak precision observables. We show that these model-independent RG contributions are more important than typical estimates for finite parts. Flavor non-universal effects are completely captured by examining three options for the top mixing: fully composite q L 3 $$ {q}_L^3 $$ , equal compositeness, and fully composite t R . In the most phenomenologically viable case of a fully composite t R , we show that the strongest bound on the natural parameter space comes from next-to-leading log running of the 4-top operator O tt = t ¯ R γ μ t R t ¯ R γ μ t R $$ {\mathcal{O}}_{tt}=\left({\overline{t}}_R{\gamma}_{\mu }{t}_R\right)\left({\overline{t}}_R{\gamma}^{\mu }{t}_R\right) $$ into the Peskin-Takeuchi T parameter. In general, we find that this 2-loop effect allows existing electroweak precision data to give better constraints on 4-top operators than high-energy probes from top production at the LHC. Independent of the top mixing, we find that a future tera-Z machine such as FCC-ee has the potential to probe composite Higgs models up to a scale of m ∗ ≳ 25 TeV, and test the naturalness of the electroweak scale at the ≲ 10−4 level.

Malcolmia aegyptiaca (locally known as El Harra) and Matthiola livida (locally known as Chegara) are medicinal plants traditionally used to relieve pain and reduce inflammation. Little is known about the flavonoid content or the analgesie and anti-inflammatory properties of these plants.

Primary endometrial serous carcinoma, known for its aggressive nature and poor prognosis, shares similarities with breast and gastric cancers in terms of potential HER2 overexpression as a therapeutic target. Assessing HER expression is complicated by tumor heterogeneity and discrepancies between primary and metastatic sites. In this study, we retrospectively analyzed HER amplification and expression in 16 pairs of primary endometrial serous carcinoma resections and corresponding metastases. HER2 status was determined using immunohistochemistry (IHC), with criteria based on the percentage and intensity of tumor cell staining. Confirmatory techniques, such as dual in situ hybridization (DISH) and fluorescence in situ hybridization (FISH), were also employed. This study reports on the concordance rates and the presence and pattern of HER2 heterogeneity. Our results showed an 87.5% concordance rate in HER2 amplification status between primary and metastatic sites, with 33% of cases scored as 2+ being amplified. Heterogeneity was observed in 100% of amplified cases and 95% of non-amplified cases on in situ testing, with variations in heterogeneity patterns between techniques. In conclusion, our findings emphasize the importance of testing both primary and metastatic sites or recurrences, with a concordance rate of 87.5%. In addition, a review of the literature and combining the results showed a concordance rate of up to 68%. The presence and pattern of heterogeneity, particularly in cases of mosaic or clustered heterogeneity in the primary tumor, may serve as reliable indicators of concordance, predicting a non-amplified HER2 status in corresponding metastases.

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects women at various stages of life, presenting a wide range of symptoms and health implications. The term “Polycystic Ovary Syndrome” can be misleading, prompting many within the medical community and advocacy groups to advocate for a name change. Critics argue that this terminology can complicate understanding and awareness of the disease among patients. The primary concern is that PCOS emphasizes the ovarian aspect, fostering the misconception that PCOS is merely a gynecological disorder. In reality, PCOS impacts multiple organ systems, particularly metabolic health. Patients frequently experience insulin resistance, weight gain, irregular menstrual cycles, and hirsutism—symptoms that extend beyond ovarian dysfunction. In light of these issues, there is increasing support for renaming PCOS to better reflect its systemic implications and minimize confusion. The current name may hinder understanding and potentially lead to inadequate disease management. Alternative names have been proposed, including “Ovarian Dysmetabolic Syndrome,” which our team supports, as well as “Metabolic Reproductive Syndrome” and “Hyperandrogenic Persistent Ovulatory Dysfunction Syndrome.” These alternatives aim to highlight the hormonal imbalances and metabolic disturbances associated with the condition, fostering inclusivity and reducing stigma for all affected individuals. This narrative review provides a historical overview of PCOS, tracing its recognition from early descriptions to contemporary guidelines. We discuss the evolving understanding of its pathophysiology and the rationale behind the proposed name change. By adopting a new nomenclature, we can enhance understanding among healthcare professionals, increase inclusivity for affected women, reduce the stigma and anxiety linked to the diagnosis, and offer a more accurate representation of the condition’s complex pathophysiology.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Abstract Background Subacute ruminal acidosis (SARA) causes an increase in endotoxin, which can induce immune and inflammatory responses in the ruminal epithelium of dairy cows. In non-ruminants, epigallocatechin-3-gallate (EGCG), a major bioactive ingredient of green tea, is well-known to alleviate inflammation. Whether EGCG confers protection against SARA-induced inflammation and the underlying mechanisms are unknown. Results In vivo, eight ruminally cannulated Holstein cows in mid-lactation were randomly assigned to either a low-concentrate (40%) diet (CON) or a high-concentrate (60%) diet (HC) for 3 weeks to induce SARA (n = 4). Cows with SARA had greater serum concentrations of tumor necrosis factor (TNF)-α and interleukin-6, and epithelium had histological signs of damage. In vitro, immortalized bovine ruminal epithelial cells (BREC) were treated with lipopolysaccharide (LPS) to imitate the inflammatory damage caused by SARA. Our data revealed that BREC treated with 10 µg/mL LPS for 6 h successfully induce a robust inflammatory response as indicated by increased phosphorylation of IκBα and nuclear factor kappa-B (NF-κB) p65. Pre-treatment of BREC with 50 µmol/L EGCG for 6 h before LPS challenge promoted the degradation of NLR family pyrin domain containing 3 (NLRP3) inflammasome through activation of autophagy, which further repressed activation of NF-κB pathway targeting Toll-like receptor 4 (TLR4). Analyses also revealed that the ECGG upregulated tight junction (TJ) protein expression upon incubation with LPS. Conclusions Subacute ruminal acidosis causes ruminal epithelium injury and systemic inflammation in dairy cows. However, the anti-inflammatory effects of EGCG help preserve the integrity of the epithelial barrier through activating autophagy when BREC are exposed to LPS. Thus, EGCG could potentially serve as an effective therapeutic agent for SARA-associated inflammation. Graphical Abstract

Our study explored the phytochemical composition and biological properties of sprouted and unsprouted quinoa seed extracts (red, black, and yellow varieties). We observed distinct differences in primary metabolites between sprouted and unsprouted seeds, particularly in carbohydrates, fats, and proteins. Sprouted seeds exhibited increased levels of simple soluble sugars, amino acids, and fatty acids. Additionally, sprouted seeds showed higher quantities of polyphenols and flavonoids, with the black variety displaying the most. However, antioxidant activity did not directly correlate with phenol and flavonoid content, with unsprouted seeds demonstrating superior performance. Conversely, unsprouted seed extracts displayed greater anti-inflammatory efficacy, attributed to saponin loss during germination. Specifically, the best carbohydrate value was found in sprouted red seeds at 21.55±1.07 mg/g of plant material, the highest protein content was in sprouted red seeds at 4.6±0.28 mg/g, and the best lipid content was in sprouted black seeds at 2.97±0.13 mg/g. The highest polyphenol content was in sprouted black seeds at 10.74±0.6 mg E GA/g Ex, while the highest flavonoid content was also in sprouted black seeds. The most effective antioxidant activity in the DPPH test was observed in non-sprouted black seeds with an IC50 of 0.06±0.01 mg/ml. The highest hemolysis inhibition was found in sprouted red seeds at 49.04% at 0.8 mg/ml, and the greatest anti-inflammatory activity was in non-sprouted yellow seeds at 1.6±0.07 mg E Dc/mg Ex.

Abstract Population-representative estimates of SARS-CoV-2 infection prevalence and antibody levels in specific geographic areas at different time points are needed to optimise policy responses. However, even population-wide surveys are potentially impacted by biases arising from differences in participation rates across key groups. Here, we used spatio-temporal regression and post-stratification models to UK’s national COVID-19 Infection Survey (CIS) to obtain representative estimates of PCR positivity (6,496,052 tests) and antibody prevalence (1,941,333 tests) for different regions, ages and ethnicities (7-December-2020 to 4-May-2022). Not accounting for vaccination status through post-stratification led to small underestimation of PCR positivity, but more substantial overestimations of antibody levels in the population (up to 21 percentage points), particularly in groups with low vaccine uptake in the general population. There was marked variation in the relative contribution of different areas and age-groups to each wave. Future analyses of infectious disease surveys should take into account major drivers of outcomes of interest that may also influence participation, with vaccination being an important factor to consider.

Abstract Background Vagus nerve stimulation (VNS) is an established therapy for treating a variety of chronic diseases, such as epilepsy, depression, obesity, and for stroke rehabilitation. However, lack of precision and side-effects have hindered its efficacy and extension to new conditions. Achieving a better understanding of the relationship between VNS parameters and neural and physiological responses is therefore necessary to enable the design of personalized dosing procedures and improve precision and efficacy of VNS therapies. Methods We used biomarkers from recorded evoked fiber activity and short-term physiological responses (throat muscle, cardiac and respiratory activity) to understand the response to a wide range of VNS parameters in anaesthetised pigs. Using signal processing, Gaussian processes (GP) and parametric regression models we analyse the relationship between VNS parameters and neural and physiological responses. Results Firstly, we illustrate how considering multiple stimulation parameters in VNS dosing can improve the efficacy and precision of VNS therapies. Secondly, we describe the relationship between different VNS parameters and the evoked fiber activity and show how spatially selective electrodes can be used to improve fiber recruitment. Thirdly, we provide a detailed exploration of the relationship between the activations of neural fiber types and different physiological effects. Finally, based on these results, we discuss how recordings of evoked fiber activity can help design VNS dosing procedures that optimize short-term physiological effects safely and efficiently. Conclusion Understanding of evoked fiber activity during VNS provide powerful biomarkers that could improve the precision, safety and efficacy of VNS therapies.

Abstract Background The literature for assessing online and offline shopping behaviours that are linked to intelligent robotic goods and services is inadequate. In this study, we applied the Theory of Planned Behaviour model for guidance regarding how consumer behaviour affects their purchase intentions for intelligent robotic goods and services. Methods Data from 408 respondents were gathered through an online questionnaire binned into Online and Overall Shoppers, and analysed using SPSS, AMOS, and Covariance-Based Structural Equation Modelling software to evaluate the appropriateness of the measurements and to confirm data reliability, convergence, divergence, and validity. These tools were also used to track and test hypothesized relationships between the variables and model constructs used in this study. Results and conclusions The overarching outcomes from the data analyses indicated the Ease of Usage, Brand Perception, and Product Pricing variables causally impacted the TPB model constructs, namely Attitude, Subjective Norms, and Perceived Behaviour Control for the two populations tested with respect to their intention to purchase intelligent robotic goods and services. The reliability measurements for Ease of Usage, Brand Perception, and Product Pricing are discussed. The results are important for companies and future investors because opportunities to study the complex relationships that ultimately drive consumer behaviour and their intention to purchase intelligent robotic goods and services are provided.

Migratory species use different habitats and pathways across their migratory route. Pathway contribution metrics are transient metrics of population growth, derived from population models, and quantify the predicted contribution of an individual, travelling along a specified migratory route, to the total population over a specified length of time. Environmental disturbances or management actions may occur temporally or spatially throughout the process of migration. The impact that a given perturbation may have on pathway contribution metrics is not always obvious owing to the propagation of the perturbation through the migratory cycle. Here, we develop a general modelling framework that incorporates perturbations into a class of matrix migratory population models, and which quantifies the effect that perturbations to the model, in terms of the transition rates of habitats and pathways, have on pathway contribution metrics. We also detail how to calculate the sensitivity of pathway contribution metrics to the perturbations considered. Our framework may be used to provide insights into the impact that environmental disturbances or management actions have on migratory populations. These insights may be used to inform management actions which either buffer against possible deleterious disturbances or increase the population size through targeted interventions. Our theoretical results are illustrated via hypothetical examples and a model inspired by the monarch butterfly; we uncover results that are not clear from the calculation of the pathway contribution metrics alone.

Several current measurements of b→sl+l− processes are in tension with Standard Model predictions, whereas others (e.g. RK and RK⁎) are in reasonable agreement with them. We examine some recent Z′ models that fit the data as a whole appreciably better than does the Standard Model, confronting the models with ATLAS resonance searches in the e+e− and μ+μ− channels. The models are constrained by both channels; we find that the searches rule out less than one fifth of the allowed range of MZ′. We estimate that the HL-LHC can roughly double the current sensitivity in MZ′, but to cover the whole of the parameter space would take a more powerful machine, such as a 100 TeV pp collider.

Local and national policymakers are seeking innovative solutions to create healthier food environments around the world. Between 2009 and 2017, 35 local authorities across England (UK) adopted planning guidance designed to limit the proliferation of hot food takeaways near schools. Whilst these policies are intended to improve population health, they are also likely to have economic impacts. Often a decision to introduce such policies comes down to consideration of whether the short-term economic imperatives of allowing new takeaway outlets to open outweighs the potential long-term public health implications and associated economic consequences. These potential negative and positive economic impacts have not previously been clearly described and are summarised here. The aim of this paper is to provide an overview of the potential economic impacts of takeaway management zones. In particular, we present a Causal Loop Diagram (CLD) that outlines the possible economic impacts of takeaway management zones based on researcher knowledge of the interventions and the industry. Potential negative impacts fall across sectors and may include a loss of employment opportunities and reductions in local and national tax receipts, and may impact the economic vitality of local communities. In the longer term, there is the potential for positive impacts such as reductions in healthcare resource utilisation, social care expenditure and sickness-related absence from work. Part of a robust case would a better economic understanding, that would enable local authorities to improve understanding of the trade-offs associated with the policy, such as short-versus long-term, and business-related versus society-related health benefits and costs.

Australia's History educators frequently face challenges regarding the value of post-school qualifications in history. Comments from Australian Government ministers have intensified claims that history degrees lack broad skills valued by employers. This study addresses the dearth of research examining the alignment between learning outcomes from history degrees and occupational skills. A comprehensive analysis was conducted on learning outcomes from 27 history degrees offered by Australian universities. These outcomes were mapped against the Australian Government's Skills Classification Core Competencies and Occupation Listings, employing a rigorous curriculum mapping methodology. The results identified 126 occupations that align with the skills and competencies developed through history degrees. This research not only challenges misconceptions about the employability of history graduates but also provides empirical evidence of the broad applicability of historical skills across various sectors. The findings reveal a significant concentration of history graduates in managerial and professional roles, indicating the high value placed on critical thinking, analytical, and communication skills developed by studying history. However, the study also highlights areas for improvement, particularly in digital engagement and numeracy skills. The research demonstrates that history degrees cultivate a range of transferable skills highly sought after in the modern job market, including advanced communication, critical analysis, research proficiency, and adaptability. These skills position history graduates to excel in diverse fields such as public policy, journalism, law, business, and education. Furthermore, the study underscores the importance of interdisciplinary approaches in curriculum design to enhance graduate employability. This research contributes valuable insights for curriculum development and career guidance in history education, demonstrating that history degrees lead to diverse and meaningful employment outcomes. It also provides a robust evidence base for advocating the value of historical studies in an increasingly skills-focused higher education landscape.

The patient, a 30-year-old woman, presented with a sudden, painless, and severe decrease in vision in both eyes. The ophthalmological examination revealed a normal anterior segment and intraocular pressure, but a fundus examination showed bilateral macular hemorrhage. In the absence of a known history, a metabolic and hematological biological assessment was conducted. The assessment revealed megaloblastic anemia with a significantly reduced serum vitamin B12 level. Further examination confirmed Biermer’s disease as the cause of her anemia. The patient was started on a regimen of monthly vitamin B12 supplementation, which she will continue for life. This case report highlights the importance of recognizing megaloblastic anemia as a potential cause of spontaneous bilateral retinal hemorrhages. Moreover, it underscores the urgency for healthcare practitioners to promptly investigate and determine the root cause of megaloblastic anemia.

This study presents the model setup and results from the first calibrated, physically-based, spatially-distributed hydrological modelling of combined land cover and climate change impacts on a large sample of UK river catchments. The SHETRAN hydrological model was automatically calibrated for 698 UK catchments then driven by the 12 regional climate model projections from UKCP18, combined with urban development and natural flood management scenarios. The automatic calibration of SHETRAN produces a median Nash-Sutcliffe efficiency value of 0.82 with 581 catchments having a value greater than 0.7. 24 summary metrics were calculated to capture changes to important aspects of the flow regime. The UKCP18 realisations in SHETRAN indicate that a warming climate will cause river flows, on average, to decrease. These decreases are simulated to be greatest in the south and east of the UK, with droughts becoming longer and more severe. While high flows also decrease on average, an increased number of extremes are exhibited, implying a greater number of extreme flood events in the future, particularly in the north and west of the UK. In the urban development scenarios, for flood events there is an increase in flow with the increased urbanization, with the 1 in 3-year peak flow event showing the greatest increase. The natural flood management scenarios consider the effect of increasing woodland and adding surface water storage ponds. The inclusion of these features produces a complex response but overall, the modelling shows a reduction in low, median, and high flows, although the more extreme the flow event the smaller the percentage change in flow. Simulated timeseries and summary metric datasets are freely available on the CEDA archive.

Data centralization is increasingly non-viable in the changing landscape of data privacy and data governance. New models of data sharing are needed, in particular when privacy-preserving record linkages (PPRL) are being used to connect data within restricted data enclaves and public open enclaves. We share a privacy-preserving data-sharing infrastructure that employs a linkage honest broker implementation of PPRL connecting structured electronic health record data between the National Center for Advancing Translational Science (NCATS) National Clinical Cohort Collaborative (N3C), a restricted data enclave, with the National Cancer Institute (NCI) Cancer Imaging Archive (TCIA), a public open enclave. In particular we will address: • Data governance models needed when linking data from restricted vs. public enclaves • Specific privacy-preserving consideration when linking to imaging data which contain specific structured data and imaging considerations • Privacy-preserving data aggregation when combining multi-modal data from restricted data enclaves with publicly discoverable imaging data

It has been suggested that the effects of renormalization significantly reduce the amplitude of the inflationary spectra at scales measurable in the cosmic microwave background. Via a gauge-invariant analysis, we compute the renormalized scalar and tensor power spectra and follow their evolution in an inflating universe that undergoes a transition to an FRW phase with a growing horizon. For perturbations originating from Minkowski vacuum fluctuations, we show that the standard prediction for the spectra on superhorizon scales is a late-time attractor, while they are UV finite at all times. Our result is independent of the equation of state after inflation, showing that the standard prediction is fully robust.

Abstract Flying foxes of the genus Pteropus, especially those inhabiting islands, face increasing pressure from anthropogenic threats. A first step to implementing effective conservation actions is to establish monitoring projects to understand a species’ population status and trend. Pteropus species are highly affected by seasonality which further requires regular, repeated, and long-term data to understand population trends, and reactions to severe weather events. In the present case study, a regular, bi-annual population census was implemented on Comoros between 2016 and 2023 for the highly threatened Livingstone’s fruit bat, Pteropus livingstonii, and compared the results of standardized monitoring to historical population data. Seasonality had a large impact on the number of bats found at roost sites, with more bats present in the wet season, but the data over the past eight years revealed no significant in- or decrease in the number of bats counted on the island Anjouan. We estimated around 1,200–1,500 bats on Anjouan and 300–400 bats on Mohéli, and found that landcover type has no measurable effect on population distribution at roost sites. Our study highlights the need for long-term surveys to understand past population trends and that single counts are not sufficient to draw final conclusions of a species’ status.

Abstract Drug discovery is an intricate and costly process. Repurposing existing drugs and active compounds offers a viable pathway to develop new therapies for various diseases. By leveraging publicly available biomedical information, it is possible to predict compounds’ activity and identify their potential targets across diverse organisms. In this study, we aimed to assess the antiplasmodial activity of compounds from the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library using in vitro and bioinformatics approaches. We assessed the in vitro antiplasmodial activity of the compounds using blood-stage and liver-stage drug susceptibility assays. We used protein sequences of known targets of the ReFRAME compounds with high antiplasmodial activity (EC50

In this paper, we study the problem of prescribing Q-Curvature on higher dimensional standard spheres. The problem consists in finding the right assumptions on a function K so that it is the Q-Curvature of a metric conformal to the standard one on the sphere. Using some pinching condition, we track the change in topology that occurs when crossing a critical level (or a virtually critical level if it is a critical point at infinity) and then compute a certain Euler-Poincaré index which allows us to prove the existence of many solutions. The locations of the levels sets of these solutions are determined in a very precise manner. These type of multiplicity results are new and are proved without any assumption of symmetry or periodicity on the function K.

We confirm the previously revised stereochemistry of spiroviolene by X-ray crystallographically characterizing a hydrazone derivative of 9-oxospiroviolane, which is synthesized by hydroboration/oxidation of spiroviolene followed by oxidation of the resultant hydroxy group. An unexpected thermal boron migration occurred during the hydroboration process of spiroviolene that resulted in the production of a mixture of 1α-hydroxyspiroviolane, 9α- and 9β-hydroxyspiroviolane after oxidation. The assertion of the cis-orientation of the 19- and 20-methyl groups provided further support for the revised cyclization mechanism of spiroviolene.

Abstract Two-dimensional (2D) materials combine many fascinating properties that make them more interesting than their three-dimensional counterparts for a variety of applications. For example, 2D materials exhibit stronger electron-phonon and electron-hole interactions, and their energy gaps and effective carrier masses can be easily tuned. Surprisingly, published band gaps of several 2D materials obtained with the G W approach, the state-of-the-art in electronic-structure calculations, are quite scattered. The details of these calculations, such as the underlying geometry, the starting point, the inclusion of spin-orbit coupling, and the treatment of the Coulomb potential can critically determine how accurate the results are. Taking monolayer MoS2 as a representative material, we employ the linearized augmented planewave + local orbital method to systematically investigate how all these aspects affect the quality of G 0 W 0 calculations, and also provide a summary of literature data. We conclude that the best overall agreement with experiments and coupled-cluster calculations is found for G 0 W 0 results with HSE06 as a starting point including spin-orbit coupling, a truncated Coulomb potential, and an analytical treatment of the singularity at q = 0.

Abstract Background Penile cancer is a rare male genital malignancy. Surgical excision of the primary tumour is followed by radical inguinal lymphadenectomy if there is metastatic disease detected by biopsy, fine needle aspiration cytology (FNAC) or following sentinel lymph node biopsy in patients with impalpable disease. However, radical inguinal lymphadenectomy is associated with a high morbidity rate, and there is increasing usage of a videoendoscopic approach as an alternative. Methods A pragmatic, UK-wide multicentre feasibility randomised controlled trial (RCT), comparing videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy. Patients will be identified and recruited from supraregional multi-disciplinary team meetings (sMDT) and must be aged 18 or over requiring inguinal lymphadenectomy, with no contraindications to surgical intervention for their cancer. Participants will be followed up for 6 months following randomisation. The primary outcome is the ability to recruit patients for randomisation across all selected sites and the rate of loss to follow-up. Other outcomes include acceptability of the trial and intervention to patients and healthcare professionals assessed by qualitative research and obtaining resource utilisation information for health economic analysis. Discussion There are currently no other published RCTs comparing videoendoscopic versus open radical inguinal lymphadenectomy. Ongoing study is required to determine whether randomising patients to either procedure is feasible and acceptable to patients. The results of this study may determine the design of a subsequent trial. Trial registration Clinicaltrials.gov PRS registry, registration number NCT05592639. Date of registration: 13th October 2022, retrospectively registered

Le vendredi 7 juin 2024 s’est tenu le 13e colloque annuel Méthodes quantitatives en sciences humaines (MQSH) à l’Université TÉLUQ à Montréal. Cinq conférenciers et conférencières ont présenté leurs travaux dans le domaine. Eric Frenette a discuté de l’évolution du modèle Bifacteur, depuis sa proposition par Holzinger, suite aux travaux de Spearman en 1927, jusqu’à sa version contemporaine, version digne du monstre de Frankenstein, qu’elle est devenue en y transfigurant ses hypothèses sous-jacentes et en y rapiéçant des paramètres augmentant son potentiel explicatif. Sophie Vanbelle, conférencière invitée pour l’évènement, a exposé les principales mesures statistiques et leur interprétation pour déterminer la fiabilité et l’accord dans le cas d’une échelle binaire. Elle a discuté de l’importance de rapporter les différents indices d’accord, de calculer l’effectif d’échantillon nécessaire pour avoir des mesures fiables de l’accord interjuges (et intrajuges) et du besoin de lignes directrices pour les chercheurs et chercheuses. André Achim a proposé une approche novatrice de l’analyse factorielle exploratoire reposant non pas sur la décomposition de matrices, mais plutôt sur l’annulation du signal, ce qui permet d’extraire toutes les informations pertinentes, le nombre de facteurs et la structure factorielle, tout en réduisant le nombre d’options décisionnelles. Ibtissem Ben Alaya a présenté le processus de validation en sept étapes d’un questionnaire portant sur les compétences socioémotionnelles des enseignants et enseignantes tout en discutant des défis rencontrés ainsi que des choix psychométriques pris. Louis Laurencelle, dans sa présentation, a critiqué le raisonnement et les critères d’altération du taux d’erreur de type I (seuil alpha), telles la correction de Bonferroni et celle de Tukey, lesquels torpillent la puissance statistique des travaux de recherche en sciences humaines. Il a examiné et argumenté la nocivité d’une telle approche et son absurdité. En conclusion, cette 13e édition du colloque MQSH fut digne de sa bannière : compétence, critique et créativité.

Abstract We present a comprehensive analysis of electroweak, flavor, and collider bounds on the complete set of dimension-six SMEFT operators in the U(2)5-symmetric limit. This operator basis provides a consistent framework to describe a wide class of new physics models and, in particular, the motivated class of models where the new degrees of freedom couple mostly to the third generation. By analyzing observables from all three sectors, and consistently including renormalization group evolution, we provide bounds on the effective scale of all 124 U(2)5-invariant operators. The relation between flavor-conserving and flavor-violating observables is analyzed taking into account the leading U(2)5 breaking in the Yukawa sector, which is responsible for heavy-light quark mixing. We show that under simple, motivated, and non-tuned hypotheses for the parametric size of the Wilson coefficients at the high scale, all present bounds are consistent with an effective scale as low as 1.5 TeV. We also show that a future circular e + e − collider program such as FCC-ee would push most of these bounds by an order of magnitude. This would rule out or provide clear evidence for a wide class of compelling new physics models that are fully compatible with present data.

Abstract Mobile Health (mHealth) has the potential to be transformative in the management of chronic conditions. Machine learning can leverage self-reported data collected with apps to predict periods of increased health risk, alert users, and signpost interventions. Despite this, mHealth must balance the treatment burden of frequent self-reporting and predictive performance and safety. Here we report how user engagement with a widely used and clinically validated mHealth app, myCOPD (designed for the self-management of Chronic Obstructive Pulmonary Disease), directly impacts the performance of a machine learning model predicting an acute worsening of condition (i.e., exacerbations). We classify how users typically engage with myCOPD, finding that 60.3% of users engage frequently, however, less frequent users can show transitional engagement (18.4%), becoming more engaged immediately (

Introduction: Patient medicines helpline services (PMHS) can reduce harm and improve medicines adherence and patient satisfaction after hospital discharge. There is little evidence of which PMHS attributes are most important to patients. This would enable PMHS providers to prioritise their limited resources to maximise patient benefit.Methods: Patient preferences for PMHS attributes were measured using a discrete choice experiment. Seven attributes were identified from past research, documentary analysis and stakeholder consultation. These were used to produce a D-efficient design with two blocks of ten choice sets incorporated into an online survey. Adults in the UK who took more than one medicine were eligible to complete the survey and were recruited via the Research for the Future database. Preferences were estimated using conditional logistic regression. Associations between participant characteristics and preferences were investigated with latent class models.Results: 460 participants completed the survey. The most valued attributes were weekend opening (willingness-to-pay, WTP: £11.20), evening opening (WTP: £8.89), and receiving an answer on the same day (WTP: £9.27). Alternative contact methods, immediate contact with a pharmacist and helpline location were valued less. Female gender and full-time work were associated with variation in preferences. For one latent class containing 27% of participants, PMHS location at the patient’s hospital was the most valued attribute.Discussion: PMHS providers should prioritise extended opening hours and answering questions on the same day. Limitations include a non-representative sample in terms of ethnicity, education and geography, and the exclusion of people without internet access.

ABSTRACTMany plants are well-known for their use in traditional medicine to treat diseases associated with inflammations and oxidative stress. This study aimed to investigate a medicinal plant from the Saharan region of Algeria, Pituranthos chloranthus. Phytochemical analysis showed that it is rich in polyphenols (8.93 ± 0.736 mg GAE/g) and flavonoids (0.78 ± 0.023 mg EQ/g). The treatment of hypoglycemic individuals with a P. chloranthus extract showed effectiveness when compared to control diabetic rats not treated with this extract. The latter showed a high average glucose at 3.11 ± 0.769 g/L when compared to the two treated rat groups, 0.8 ± 023 g/L and 0.54 ± 0.08 g/L when fed 500 and 250 mg/Kg body weight of P. chloranthus extract, respectively. The in vitro antioxidant evaluation, using the DPPH (IC50 = 0.156 ± 0.23 mg/mL) and FRAP (IC50 = 0.718 ± 0.09 mg/mL) tests and ratio to ascorbic acid 0.0037 ± 0.505 mg/mL showed an important antioxidant potential.

Long COVID-19, also known as post-acute sequelae of SARS-CoV-2 infection, is a condition where individuals who have recovered from the acute phase of COVID-19 continue to experience a range of symptoms for weeks or even months afterward. While it was initially thought to primarily affect the respiratory system, it has become clear that Long COVID-19 can involve various organs and systems, including the endocrine system, which includes the pituitary gland. In the context of Long COVID-19, there is a growing understanding of the potential implications for the pituitary gland. The virus can directly affect the pituitary gland, leading to abnormalities in hormone production and regulation. This can result in symptoms such as fatigue, changes in appetite, and mood disturbances. Long COVID-19, the persistent and often debilitating condition following acute COVID-19 infection, may be explained by deficiencies in ACTH and Growth hormone production from the pituitary gland. Corticotropin insufficiency can result in the dysregulation of the body’s stress response and can lead to prolonged feelings of stress, fatigue, and mood disturbances in Long COVID-19 patients. Simultaneously, somatotropin insufficiency can affect growth, muscle function, and energy metabolism, potentially causing symptoms such as muscle weakness, exercise intolerance, and changes in body composition. Recently, some authors have suggested the involvement of the pituitary gland in Post COVID-19 Syndrome. The exact mechanisms of viral action on infected cells remain under discussion, but inflammatory and autoimmune mechanisms are primarily implicated. The aim of our study will be to review the main pituitary complications following COVID-19 infection. Moreover, we will explain the possible involvement of the pituitary gland in the persistence of Post COVID-19 Syndrome.

Abstract Background Germ Defence ( www.germdefence.org ) is an evidence-based interactive website that promotes behaviour change for infection control within households. To maximise the potential of Germ Defence to effectively reduce the spread of COVID-19, the intervention needed to be implemented at scale rapidly. Methods With NHS England approval, we conducted an efficient two-arm (1:1 ratio) cluster randomised controlled trial (RCT) to examine the effectiveness of randomising implementation of Germ Defence via general practitioner (GP) practices across England, UK, compared with usual care to disseminate Germ Defence to patients. GP practices randomised to the intervention arm (n = 3292) were emailed and asked to disseminate Germ Defence to all adult patients via mobile phone text, email or social media. Usual care arm GP practices (n = 3287) maintained standard management for the 4-month trial period and then asked to share Germ Defence with their adult patients. The primary outcome was the rate of GP presentations for respiratory tract infections (RTI) per patient. Secondary outcomes comprised rates of acute RTIs, confirmed COVID-19 diagnoses and suspected COVID-19 diagnoses, COVID-19 symptoms, gastrointestinal infection diagnoses, antibiotic usage and hospital admissions. The impact of the intervention on outcome rates was assessed using negative binomial regression modelling within the OpenSAFELY platform. The uptake of the intervention by GP practice and by patients was measured via website analytics. Results Germ Defence was used 310,731 times. The average website satisfaction score was 7.52 (0–10 not at all to very satisfied, N = 9933). There was no evidence of a difference in the rate of RTIs between intervention and control practices (rate ratio (RR) 1.01, 95% CI 0.96, 1.06, p = 0.70). This was similar to all other eight health outcomes. Patient engagement within intervention arm practices ranged from 0 to 48% of a practice list. Conclusions While the RCT did not demonstrate a difference in health outcomes, we demonstrated that rapid large-scale implementation of a digital behavioural intervention is possible and can be evaluated with a novel efficient prospective RCT methodology analysing routinely collected patient data entirely within a trusted research environment. Trial registration This trial was registered in the ISRCTN registry (14602359) on 12 August 2020.

Summary: Endosomal Toll-like receptors (eTLRs) are essential for the sensing of non-self through RNA and DNA detection. Here, using spatiotemporal analysis of vesicular dynamics, super-resolution microscopy studies, and functional assays, we show that endomembrane defects associated with the deficiency of the small GTPase Rab27a cause delayed eTLR ligand recognition, defective early signaling, and impaired cytokine secretion. Rab27a-deficient neutrophils show retention of eTLRs in amphisomes and impaired ligand internalization. Extracellular signal-regulated kinase (ERK) signaling and β2-integrin upregulation, early responses to TLR7 and TLR9 ligands, are defective in Rab27a deficiency. CpG-stimulated Rab27a-deficient neutrophils present increased tumor necrosis factor alpha (TNF-α) secretion and decreased secretion of a selected group of mediators, including interleukin (IL)-10. In vivo, CpG-challenged Rab27a-null mice show decreased production of type I interferons (IFNs) and IFN-γ, and the IFN-α secretion defect is confirmed in Rab27a-null plasmacytoid dendritic cells. Our findings have significant implications for immunodeficiency, inflammation, and CpG adjuvant vaccination.

Summary: During chronic infection, virus-specific CD8+ cytotoxic T lymphocytes (CTLs) progressively lose their ability to mount effective antiviral responses. This “exhaustion” is coupled to persistent upregulation of inhibitory receptor programmed death-1 (PD-1) (Pdcd1)—key in suppressing antiviral CTL responses. Here, we investigate allelic Pdcd1 subnuclear localization and transcription during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Pdcd1 alleles dissociate from transcriptionally repressive chromatin domains (lamin B) in virus-specific exhausted CTLs but not in naive or effector CTLs. Relative to naive CTLs, nuclear positioning and Pdcd1-lamina dissociation in exhausted CTLs reflect loss of Pdcd1 promoter methylation and greater PD-1 upregulation, although a direct correlation is not observed in effector cells, 8 days post-infection. Genetic deletion of B lymphocyte-induced maturation protein 1 (Blimp-1) enhances Pdcd1-lamina dissociation in effector CTLs, suggesting that Blimp-1 contributes to maintaining Pdcd1 localization to repressive lamina. Our results identify mechanisms governing Pdcd1 subnuclear localization and the broader role of chromatin dynamics in T cell exhaustion.

Abstract Global biodiversity is facing an extinction crisis leading to increasing pressure on industries to monitor their potential environmental impact. Relatedly, there is demand for more efficient biodiversity monitoring methods, resulting in growing interest in the use of environmental DNA (eDNA). Many questions, however, regarding the reliability of this relatively novel method remain, particularly for non‐specialist end‐users of the technology. Here, the use of commercially available (in the UK) eDNA assays for monitoring freshwater fish and invertebrate biodiversity was compared to conventional surveillance techniques. Samples were collected from different habitats, on varying spatial scales and using multiple sampling regimes to assess how eDNA results were affected. For aquatic macroinvertebrates and fish, more taxa were detected by eDNA than conventional surveys conducted in parallel, and for fish, all taxa detected by conventional monitoring were confirmed by eDNA. For aquatic macroinvertebrates, several species were only detected through conventional methods, and the number of families detected by eDNA was lower than for conventional monitoring at all sites. eDNA results varied significantly between sampling locations within lentic sites and, for lotic sites, with the number of subsamples collected. Practical implication. This study demonstrates the need for bespoke sampling protocols when collecting eDNA samples. It also improves understanding of using eDNA for detecting aquatic taxa that could inform species surveillance protocols. These are essential if eDNA is to be used by practitioners as a regulatory monitoring tool.

We introduce coloring groups, which are permutation groups obtained from a proper edge coloring of a graph. These groups generalize the generalized toggle groups of Striker (which themselves generalize the toggle groups introduced by Cameron and Fon-der-Flaass). We present some general results connecting the structure of a coloring group to the structure of its graph coloring, providing graph-theoretic characterizations of the centralizer and primitivity of a coloring group. We apply these results particularly to generalized toggle groups arising from trees as well as coloring groups arising from the independence posets introduced by Thomas and Williams.

Clinker and cement production is an energy-intensive and high resource requirement industry with significant environmental impacts, and yet, there is a dearth of environmental research in Tunisia on its Life Cycle Assessment (LCA). Additionally, there is a tendency either to overlook or underestimate the selection of appropriate life cycle impact assessment methods. This study aims to address these issues by conducting a comprehensive LCA of Tunisian cement production with the goal of analyzing and comparing the results using various methods and benchmarking against existing literature. Three different Life Cycle Impact Assessment (LCIA) methods, including IMPACT 2002+, CML (baseline), and ReCiPe Midpoint (2008–2016) (H), were used. These methods were chosen for their different coverage (regional/global) of their impact categories, leading to a more comprehensive comparison of the performance of clinker and cement to the literature. In addition, the similarity with published values demonstrates reliability for LCA results, except ionizing radiation, ozone layer depletion, and respiratory organics in IMPACT 2002+ for clinker, CEM-I, and CEM-II; fresh water aquatic ecotoxicity and marine aquatic ecotoxicity in CML (baseline) for CEM-I; and photochemical oxidant formation: ecosystem quality and human health in ReCiPe for CEM-I. This low variability with the reported values in the literature suggests the capability of using the benchmarking approach as a proxy in a context of lack of data.

Background: intestinal parasitic infections are the most common infections in the world, with the most prevalent burden occurring in poverty-stricken areas. Intestinal parasitic infections are endemic in certain parts of Nigeria as a result of poor hygiene practices and pollution, which result in contamination of food and water. In semi-urban and rural communities where the dwellers are generally poor and uneducated and lack basic amenities like potable water supply and good sanitary facilities, intestinal parasitic infections cause major health problems. This study was to evaluate the influence of socio-demographic factors in the transmission of intestinal parasitoses among the residents of Ekemkpon and Idim Ita Communities of Cross River State, Nigeria. Materials and Methods: this was a cross-sectional survey between April 2019 and August 2019. Samples were obtained from 359 participants in the study areas and examined for stool analysis using direct microscopy and brine floatation technique. Socio-demographic data of the study subjects were obtained using questionnaires. Results: the prevalence of intestinal parasites was higher in Ekemkpon (41.0%) than in Idim Ita (14.9%). Participants with mixed infections in Ekemkpon were 7.9%, while those in Idim Ita were 2.2%. The study has shown that level of education had an influence on the transmission of intestinal parasites in Ekemkpon (p

PURPOSEProstate cancer disproportionately affects men of African descent, yet their representation in tissue-based studies is limited. This multinational, multicenter pilot study aims to establish the groundwork for collaborative research on prostate cancer in sub-Saharan Africa.METHODSThe Men of African Descent and Carcinoma of the Prostate network formed a pathologist working group representing eight institutions in five African countries. Formalin-fixed paraffin-embedded prostate tissue specimens were collected from Senegal, Nigeria, and Ghana. Histology slides were produced and digitally scanned. A central genitourinary pathologist (P.L.) and eight African general pathologists reviewed anonymized digital whole-slide images for International Society of Urological Pathology grade groups and other pathologic parameters. Discrepancies were re-evaluated, and consensus grading was assigned. A virtual training seminar on prostate cancer grading was followed by a second assessment on a subcohort of the same tissue set.RESULTSOf 134 tissue blocks, 133 had evaluable tissue; 13 lacked cancer evidence, and four were of insufficient quality. Post-training, interobserver agreement for grade groups improved to 56%, with a median Cohen's quadratic weighted kappa of 0.83 (mean, 0.74), compared with an initial 46% agreement and a quadratic weighted kappa of 0.77. Interobserver agreement between African pathologist groups was 40%, with a quadratic weighted kappa of 0.66 (95% CI, 0.51 to 0.76). African pathologists tended to overgrade (36%) more frequently than undergrade (18%) compared with the reference genitourinary pathologist. Interobserver variability tended to worsen with a decrease in tissue quality.CONCLUSIONTissue-based studies on prostate cancer in men of African descent are essential for a better understanding of this common disease. Standardized tissue handling protocols are crucial to ensure good tissue quality and data. The use of digital slide imaging can enhance collaboration among pathologists in multinational, multicenter studies.

Primary lymphoepithelial carcinoma of the salivary glands is an exceptional oncological condition that predominantly emerges within the parotid gland. A significant prevalence of lymphoepithelial carcinoma has been reported in the Inuit population, along with an associated positive serology for Epstein-Barr virus in these endemic regions. In this paper, we present a case of primary lymphoepithelial carcinoma of the parotid gland in a 68-year-old female patient with a history of diabetes and hypertension residing in a non-endemic area. Histology plays a critical role in the definitive diagnosis, and confirming the primary origin of lymphoepithelial carcinoma after ruling out metastasis from undifferentiated nasopharyngeal carcinoma. The mainstay of treatment is a combination of surgical resection and adjuvant radiotherapy. Inoperable forms are typically managed with chemoradiotherapy.

Background: Group preoperative education is becoming standard care for patients preparing for surgery, alongside optimisation of exercise, diet, and wellbeing. Although patient education is essential, the effectiveness of group education programmes or ‘surgery schools’ as a means of delivery is unclear. This review examines whether attending group preoperative education improves patient outcomes. Methods: We systematically reviewed studies of group perioperative education before major elective surgery. Observational or intervention studies with a baseline group or control arm were included. All outcomes reported were collected and, where possible, effect estimates were summarised using random effects meta-analysis. Results: Twenty-seven studies reported on 48 different outcomes after group education. Overall, there was a 0.7 (95% confidence interval 0.27–1.13) day reduction in mean length of stay. The odds ratio for postoperative complications after abdominal surgery was 0.56 (95% confidence interval 0.36–0.85; nine studies). Patient-centred outcomes were grouped into themes. Most studies reported a benefit from group education, but only postoperative physical impairment, pain, knowledge, activation, preoperative anxiety, and some elements of quality of life were statistically significant. Conclusion: This review presents a summary of published evidence available for group preoperative education. While these data lend support for such programmes, there is a need for adequately powered prospective studies to evaluate the effectiveness of preoperative education on clinical outcomes and to evaluate whether behaviour change is sustained. Furthermore, the content, timing and mode of delivery, and evaluation measures of preoperative education require standardisation. Systematic review protocol: PROSPERO (166297).

Introduction: Radiotherapy (RT) stands as one of the main cancer treatments. The impact of RT and cancer treatment can have a physical and psychological impact on patients and their carers. To gain patient's trust, and ensure they feel valued, information should be provided before, during, and after RT. Patient and public involvement (PPI) has been lacking, and increased engagement with PPI groups could improve this. This rapid review aims to analyse the literature, and describe and report patient perception, experience, and satisfaction regarding the information received concerning their course of RT. Methods: To allow the synthesis of results, a pragmatic decision was made to use a rapid review approach to analyse the literature, providing more timely information to inform future work. This rapid review utilised systematic review methods and was conducted according to a pre-defined protocol including clear inclusion criteria (PROSPERO registration: CRD42023415916).Electronic databases CINAHL, AMED, Pubmed/MEDLINE, EMBASE, and PsycINFO were searched using a comprehensive search for published studies from January 2012 to November 2023. Two independent reviewers applied the eligibility criteria. Evidence from literature was extracted and transcribed into qualitative data and Braun and Clarke’s six-step thematic analysis (TA) was employed to determine themes by one reviewer and checked by a second [26]. Due to the heterogeneity of the included literature, the analysis of this review is presented primarily through narrative synthesis. Results: Sixty eight articles met the inclusion criteria for this review. Emerging themes included; a desire for information based on patient characteristics, information format, patient preparedness, timing e.g. timing of information and changing priorities over time, health care professional (HCP) involvement, barriers to information, and motivators for better information delivery. Conclusions: Several factors can influence a patient’s desire for information, from whom and when they receive it, to what format they would prefer to receive it. There is benefit to be gained in employing PPI and patient advocacy to inform future studies that aim to further understand the themes that emerged from this review. Such studies can therefore inform HCPs in providing patient-specific information and support by utilising multiple teaching strategies available to them.

Abstract Although FOXP3+ regulatory T cells (Treg) depend on IL-2 produced by other cells for their survival and function, the levels of IL-2 in inflamed tissue are low, making it unclear how Treg access this critical resource. Here, we show that Treg use heparanase (HPSE) to access IL-2 sequestered by heparan sulfate (HS) within the extracellular matrix (ECM) of inflamed central nervous system tissue. HPSE expression distinguishes human and murine Treg from conventional T cells and is regulated by the availability of IL-2. HPSE-/- Treg have impaired stability and function in vivo, including in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Conversely, endowing monoclonal antibody-directed chimeric antigen receptor (mAbCAR) Treg with HPSE enhances their ability to access HS-sequestered IL-2 and their ability to suppress neuroinflammation in vivo. Together, these data identify a role for HPSE and the ECM in immune tolerance, providing new avenues for improving Treg-based therapy of autoimmunity.

This study aimed to assess the characteristics of Saharan plants by analyzing the chemical composition and evaluating the antioxidant and anti-inflammatory properties of raw extracts from Matthiola livida DC., collected from the Oued-Souf region. The primary metabolites analysis revealed carbo-hydrates as the dominant components, with a concentration of 35.70 ± 0.03 mg/g dry weight. Using the maceration technique, three unrefined extracts (methanolic, ethanolic, and aqueous) were produced, with the aqueous extract yielding the highest output at 14.61%. Total polyphenol content varied from 170.82 to 102.42 mg of GA/g dry extract, and the ethanol extract had the highest flavonoid content at 97.03 ± 4.14 mg of QE/g dry extract. The DPPH• test showed the methanolic extract as the most potent antioxidant, with an IC50 of 153.56 μg/ml. The ethanolic extract offered the most protection to human erythrocytes, resulting in only 16.93% hemolysis at a concentration of 1 mg/ml. It also showed the strongest anti-inflammatory effects in vitro, with a protein denaturation inhibition equivalent to 11.29±1.10 mg of diclofenac sodium per milligram of dry extract. Additionally, IR spectroscopy identified several functional groups, including hydroxyl (O-H), carbonyl (C=O), and various carbon-hydrogen bonds (C-H, C=C, C-H). Future research should explore the clinical applicability of these findings to enhance the therapeutic potential of Matthiola livida extracts.