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Constantinos Kallis,1– 3 Amit Kaura,1,3 Nathan A Samuel,4 Abdulrahim Mulla,3 Ben Glampson,3 Kevin O’Gallagher,5 Jim Davies,4 Dimitri Papadimitriou,3 Kerrie J Woods,4 Anoop D Shah,6,7 Bryan Williams,6,7 Folkert W Asselbergs,6,7 Erik K Mayer,3,8 Richard W Lee,1,9 Christopher Herbert,10 Stuart W Grant,11 Nick Curzen,12 Iain B Squire,13 Thomas Johnson,14 Ajay M Shah,15 Divaka Perera,5 Rajesh K Kharbanda,4 Riyaz S Patel,6 Keith M Channon,4 Jamil Mayet,1,3 Jennifer K Quint1– 3 1National Heart and Lung Institute, Imperial College London, London, UK; 2School of Public Health, Imperial College London, London, UK; 3NIHR Imperial Biomedical Research Centre, Imperial College London and Imperial College Healthcare NHS Trust, London, UK; 4NIHR Oxford Biomedical Research Centre, University of Oxford and Oxford University Hospitals NHS Foundation Trust, Oxford, UK; 5NIHR King’s Biomedical Research Centre, King’s College London and King’s College Hospital NHS Foundation Trust, London, UK; 6NIHR University College London Biomedical Research Centre, University College London and University College London Hospitals NHS Foundation Trust, London, UK; 7Institute of Health Informatics, University College London, London, UK; 8Imperial Clinical Analytics, Research & Evaluation (iCARE) and Department of Surgery & Cancer, Imperial College London, London, UK; 9Early Diagnosis and Detection Centre, NIHR BRC at The Royal Marsden and Institute of Cancer Research, London, UK; 10NIHR Leeds Clinical Research Facility, Leeds Teaching Hospitals Trust and University of Leeds, Leeds, UK; 11NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust and the University of Manchester, Manchester, UK; 12NIHR Southampton Clinical Research Facility and Biomedical Research Centre, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK; 13NIHR Leicester Biomedical Research Centre, Glenfield Hospital, and Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; 14NIHR Bristol Biomedical Research Centre, University of Bristol and University Hospitals Bristol NHS Foundation Trust, Bristol, UK; 15NIHR Guys & St Thomas’ Hospital Clinical Research Facility, King’s College Hospital, and King’s College London British Heart Foundation Centre of Excellence, London, UKCorrespondence: Jennifer K Quint, School of Public Health, Imperial College London, Floor 9, Sir Michael Uren Building, 86 Wood Ln, London, W12 0BZ, United Kingdom, Email j.quint@imperial.ac.ukBackground: No single biomarker currently risk stratifies chronic obstructive pulmonary disease (COPD) patients at the time of an exacerbation, though previous studies have suggested that patients with elevated troponin at exacerbation have worse outcomes. This study evaluated the relationship between peak cardiac troponin and subsequent major adverse cardiac events (MACE) including all-cause mortality and COPD hospital readmission, among patients admitted with COPD exacerbation.Methods: Data from five cross-regional hospitals in England were analysed using the National Institute of Health Research Health Informatics Collaborative (NIHR-HIC) acute coronary syndrome database (2008– 2017). People hospitalised with a COPD exacerbation were included, and peak troponin levels were standardised relative to the 99th percentile (upper limit of normal). We used Cox Proportional Hazard models adjusting for age, sex, laboratory results and clinical risk factors, and implemented logarithmic transformation (base-10 logarithm). The primary outcome was risk of MACE within 90 days from peak troponin measurement. Secondary outcome was risk of COPD readmission within 90 days from peak troponin measurement.Results: There were 2487 patients included. Of these, 377 (15.2%) patients had a MACE event and 203 (8.2%) were readmitted within 90 days from peak troponin measurement. A total of 1107 (44.5%) patients had an elevated troponin level. Of 1107 patients with elevated troponin at exacerbation, 256 (22.8%) had a MACE event and 101 (9.0%) a COPD readmission within 90 days from peak troponin measurement. Patients with troponin above the upper limit of normal had a higher risk of MACE (adjusted HR 2.20, 95% CI 1.75– 2.77) and COPD hospital readmission (adjusted HR 1.37, 95% CI 1.02– 1.83) when compared with patients without elevated troponin.Conclusion: An elevated troponin level at the time of COPD exacerbation may be a useful tool for predicting MACE in COPD patients. The relationship between degree of troponin elevation and risk of future events is complex and requires further investigation.Keywords: COPD, CVD, exacerbation

Research in metal matrix composites (MMCs) indicates that superior mechanical properties may be achieved by embedding reinforcement materials. However, the development of new composite powder for additive manufacturing requires an in-depth understanding of its key characteristics prior to its use in the fabrication process. This paper focuses on the low-energy ball milling (LEBM) of aluminium 2024 alloy (AA2024) reinforced with graphene nanoplatelets (GNPs). The main aim is to investigate the effect of the milling time (from 0.5 to 16 h) on the morphology and flowability of the powder. The study shows that, while short milling times (under 2 h) could not break the Van der WaRals forces between nanoparticles, GNPs were well separated and sufficiently covered the powder surface after 4 h of milling, thanks to the continuously applied impact energy. Longer milling time provides increasingly similar flowability results, confirmed by both the experimental work and discrete element model (DEM) simulations. Moreover, the ball milling process decreases the crystallite size of the milled powder by 24%, leading to a 3% higher microhardness. Lastly, the surface energy of the powder was determined as 1.4 mJ/m2 by DEM, using the angle of repose of the as-received powder from experimental work.

Early nutritional management approach greatly impacts broilers’ performance and resistance against coccidiosis. The current study explored the impact of post-hatch feeding with a combination of glutamine (Glut) and different levels of omega-3 on broiler chickens’ growth performance, muscle building, intestinal barrier, antioxidant ability and protection against avian coccidiosis. A total of six hundred Cobb 500 was divided into six groups: first group (fed basal diet and unchallenged (control) and challenged (negative control, NC) groups were fed a basal diet without additives, and the other groups were infected with Eimeria spp and supplemented with 1.5% Glut alone or with three different levels of omega-3 (0.25, 0.5 and 1%) during the starter period. Notable improvement in body weight gain was observed in the group which fed basal diet supplemented with glut and 1% omega 3 even after coccidia infection (increased by 25% compared challenged group) while feed conversion ratio was restored to control. Myogeneis was enhanced in the group supplemented with Glut and omega-3 (upregulation of myogenin, MyoD, mechanistic target of rapamycin kinase and insulin like growth factor-1 and downregulating of myostatin genes). Groups supplemented with Glut and higher levels of omega-3 highly expressed occluding, mucin-2, junctional Adhesion Molecule 2, b-defensin-1 and cathelicidins-2 genes. Group fed 1% Glut + omega-3 showed an increased total antioxidant capacity and glutathione peroxidase and super oxide dismutase enzymes activities with reduced levels of malondialdehyde, reactive oxygen species and H2O2. Post-infection, dietary Glut and 1% omega-3 increased intestinal interleukin-10 (IL) and secretory immunoglobulin-A and serum lysozyme, while decreased the elevated inflammatory mediators comprising interleukin IL-6, tumor necrosis factor-alpha, nitric oxide (NO) and inducible NO synthase. Fecal oocyst excretion and lesions score severity were lowered in the group fed 1% Glut and omega 3. Based on these findings, dietary Glut and omega-3 supplementation augmented restored overall broilers’ performance after coccidial challenge.

Background: The adulteration of milk is an important issue that needs to be addressed because of its deleterious effects on health. Detection of adulterants in milk can be done in laboratories or by purchasing adulteration detection kits. There are few home-based rapid tests to detect common milk adulterants, which are less known by our community. Objectives of this study were to estimate the proportion of milk adulteration and to identify common adulterants, to determine the association of milk adulteration with gastrointestinal and renal diseases; and also to validate rapid home-based tests by comparing its result with standard milk adulteration detection kit. Materials and Methods: A community-based study was conducted on 330 medical and paramedical staff. Collected milk samples during family visits were tested by standard milk adulteration detection tests and rapid home-based tests. Results: Among 330 tested milk samples, 233 samples were adulterated with one or more than one adulterant. The most common adulteration observed was the addition of water to milk, followed by detergent, urea, and neutralizer. The specificity of the rapid tests was found to be almost 100% in the detection of water and detergent in milk and accuracy was above 80%; with “substantial agreement” (kappa = 0.7) between rapid tests and standard tests on kappa statistics. Conclusion: The present study has identified a large extent of milk adulteration and common adulterants, which may have harmful effects on health. The utility of home-based rapid tests is clearly proven to detect common adulterants.

Current research aims to assess the therapeutic impact of Mucuna pruriens seed extract on PROTAMIN (PRM) I and II gene expression and hormones in chlorpromazine-induced endocrine disruptions and reproductive toxicity in male rats. Thirty male Wistar rats were categorized into five groups: the negative control group, rats that received distilled water for 52 days; the induction group, rats that received (20 mg/kg) of chlorpromazine for 52 days; and three treatment groups that were pretreated with chlorpromazine (similar to the induction group) that received a low, medium, and high dose of Mucuna pruriens (500, 1000, and 2000 mg/kg, respectively). Serum samples were collected to measure testosterone, FSH (follicular stimulating hormone), LH (luteinizing hormone), and prolactin serum levels using the ELISA technique. Tissue samples were collected to measure PRM I and II gene expression and for histopathological study. The PRM I and II genes were significantly downregulated in the chlorpromazine-treated group. These genes were also significantly upregulated in Mucuna pruriens-treated groups. The Mucuna pruriens-treated groups revealed a significant rise in serum LH, testosterone, and FSH concentrations, decreased serum prolactin, and improved histology of testicular damage compared to the induction group. In conclusion, the endocrine disruption and hormonal changes induced by chlorpromazine improved when Mucuna pruriens was administered, improving the impairment in gene expression and hormones.

Abstract Background Heart failure (HF) with preserved or mildly reduced ejection fraction includes a heterogenous group of patients. Reclassification into distinct phenogroups to enable targeted interventions is a priority. This study aimed to identify distinct phenogroups, and compare phenogroup characteristics and outcomes, from electronic health record data. Methods 2,187 patients admitted to five UK hospitals with a diagnosis of HF and a left ventricular ejection fraction ≥ 40% were identified from the NIHR Health Informatics Collaborative database. Partition-based, model-based, and density-based machine learning clustering techniques were applied. Cox Proportional Hazards and Fine-Gray competing risks models were used to compare outcomes (all-cause mortality and hospitalisation for HF) across phenogroups. Results Three phenogroups were identified: (1) Younger, predominantly female patients with high prevalence of cardiometabolic and coronary disease; (2) More frail patients, with higher rates of lung disease and atrial fibrillation; (3) Patients characterised by systemic inflammation and high rates of diabetes and renal dysfunction. Survival profiles were distinct, with an increasing risk of all-cause mortality from phenogroups 1 to 3 (p

Abstract Background Cardiac troponin is commonly raised in patients presenting with malignancy. The prognostic significance of raised troponin in these patients is unclear. Objectives We sought to investigate the relation between troponin and mortality in a large, well characterised cohort of patients with a routinely measured troponin and a primary diagnosis of malignancy. Methods We used the National Institute for Health Research (NIHR) Health Informatics Collaborative data of 5571 patients, who had troponin levels measured at 5 UK cardiac centres between 2010 and 2017 and had a primary diagnosis of malignancy. Patients were classified into solid tumour or haematological malignancy subgroups. Peak troponin levels were standardised as a multiple of each laboratory’s 99th -percentile upper limit of normal (xULN). Results 4649 patients were diagnosed with solid tumours and 922 patients with haematological malignancies. Raised troponin was an independent predictor of mortality in all patients (Troponin > 10 vs.

Abstract Background Policy research aims to provide evidence to inform government policy decisions about health and social care. Engaging and involving the public and patients in this work is widely recognised as essential. Research funders prioritise equality, diversity and inclusion (EDI) in patient and public involvement and engagement (PPIE), but people who are most likely to experience poor outcomes are also those least likely to be involved in research. This paper describes our experience of setting out to understand how to overcome barriers to EDI in PPIE in the research carried out by the National Institute for Health and Care Research (NIHR) Policy Research Unit in Maternal and Neonatal Health and Care (PRU-MNHC), in a PPIE consultation project we called The Listening Series. Methods We convened five video-recorded online discussion groups involving 20 individuals advocating for groups who are under-represented in our research. Those taking part included people working with Black and Asian women and families, young parents, those from socially deprived backgrounds, and women and families with physical and learning disabilities. Discussions focussed on practical solutions to addressing challenges to people being excluded, and how to improve EDI in our research. Learning and reflection Five key themes were identified: ‘build trust’; ‘involve us from the beginning’; ‘show us impact’; ‘use clear, appropriate and inclusive communication’; and ‘imagine life in our shoes’. We used the learning to create a guidance document for researchers and an accompanying 15-minute film. We also took practical steps to embed the learning strategically by expanding our Task Group for PPIE in the PRU-MNHC to include four Listening Series invitees with a remit to champion EDI in our research and ensure that it is embedded in our PPIE activities. We continue to reflect on and work to address the associated challenges. Conclusions The Listening Series helped us rethink our processes for inclusion to go beyond traditional methods of involvement and engagement. The themes identified pose challenges that require time, resource and empathic engagement from researchers to be meaningfully resolved. This has implications for policy makers and research funders who need to consider this in their processes.

Creep is a complex behavior of concrete since it induces different stages of response under loading and unloading with time. It represents the time-dependent strain as a result of a constant sustained load applied with time. In cementitious materials such as engineered cementitious composite concrete, ECC, the loaded cement paste is the principal source of creep strain. Therefore, investigating the overall creep behavior, under the loading and unloading stages, will be beneficial in providing data for the performance of ECC concrete. The test for compressional creep strain is done according to the ASTM C- 512 under controlled temperature (21 oC) and relative humidity (40%). In this research, the loading stage lasted for 9 months, and the unloading stage lasted 3 months. The total creep strain, creep coefficient, and specific creep were recorded for six ECC concrete mixes. The mixes have two strength levels, 30 and 60 MPa at 28 days, and contain polypropylene and polyvinyl alcohol fibers. Results revealed significant enhancement, and lower creep behavior, in mixes including fibers compared to plain mixes. The best promising results for the creep coefficient and specific creep were recorded when using mixes of 60 MPa containing polyvinyl alcohol fibers compared to plain mixes.

Abstract Centrin1 gene deleted Leishmania donovani parasite (LdCen1 −/− ) was developed and extensively tested experimentally as an intracellular stage-specific attenuated and immunoprotective live parasite vaccine candidate ex vivo using human PBMCs and in vivo in animals. Here we report manufacturing and pre-clinical evaluation of current Good-Laboratory Practice (cGLP) grade LdCen1 −/− parasites, as a prerequisite before proceeding with clinical trials. We screened three batches of LdCen1 −/− parasites manufactured in bioreactors under cGLP conditions, for their consistency in genetic stability, attenuation, and safety. One such batch was preclinically tested using human PBMCs and animals (hamsters and dogs) for its safety and protective immunogenicity. The immunogenicity of the CGLP grade LdCen1 −/− parasites was similar to one grown under laboratory conditions. The cGLP grade LdCen1 −/− parasites were found to be safe and non-toxic in hamsters and dogs even at 3 times the anticipated vaccine dose. When PBMCs from healed visceral leishmaniasis (VL) cases were infected with cGLP LdCen1 −/− , there was a significant increase in the stimulation of cytokines that contribute to protective responses against VL. This effect, measured by multiplex ELISA, was greater than that observed in PBMCs from healthy individuals. These results suggest that cGLP grade LdCen1 −/− manufactured under cGMP complaint conditions can be suitable for future clinical trials.

Abstract Estimating runoff at ground-mounted solar photovoltaic (PV) installations is challenging because of the disconnected nature of impervious solar panels and the pervious ground surface underneath and between panel rows. There is a need for improved tools to estimate how low impact development practices at these solar installations affect stormwater runoff. The objective of this study was to develop an innovative spreadsheet-based runoff calculator that rapidly estimates stormwater runoff from ground-mounted solar PV sites. The calculator is built on a 2-D hydrologic model (Hydrus-2D/3D) calibrated and validated using experimental data from five commercial solar farms in Colorado, Georgia, Minnesota, New York, and Oregon. The Hydrus-2D/3D hydrologic model was then used to generate nomographs for stormwater runoff that were incorporated into an easy-to-use Excel-based solar farm runoff calculator. This calculator allows for rapid estimation of NRCS stormwater runoff curve number (CN) values at solar farms by considering several complex factors unique to PV installations including: soil and topographic characteristics, surface cover, disconnected impervious surface factors associated with various solar panel designs, and climatic factors. The solar farm runoff calculator quickly estimates runoff CN for pre- and post-construction scenarios, and can estimate actual depth of runoff based on a user-specified 24-h design storm depth. Factors that have the most significant impact on stormwater runoff include design storm return frequency, soil texture, soil bulk density, and soil depth. Ground surface cover has a moderate impact on stormwater runoff, and factors that have a lesser impact on stormwater runoff include slope and array size, spacing and orientation on the landscape. The runoff calculator allows for accurate estimates of runoff generated by disconnected impervious surfaces and low impact development practices at solar farms as affected by a wide range of site-specific conditions.

Background The primary objective worldwide during the coronavirus disease 2019 (COVID-19) pandemic had been controlling disease transmission. However, lockdown measures used to mitigate transmission affected human behavior and altered lifestyles, with a likely impact on chronic non-communicable diseases. More than a year into the pandemic, substantial peer-reviewed literature emerged on altered lifestyles following the varying lockdown measures imposed globally to control the virus spread. We explored the impact of lockdown measures on six lifestyle factors, namely diet, physical activity, sleep, stress, social connectedness, and the use of tobacco, alcohol, or other harmful substances. Methods We comprehensively searched PubMed and the World Health Organization’s global literature database on COVID-19 and retrieved 649 relevant articles for the narrative review. A critical interpretative synthesis of the articles was performed. Results Most of the articles included in the review identified the negative effect of lockdown measures on each of the lifestyle factors in many parts of the world. Encouraging lifestyle trends were also highlighted in a few articles. Such trends can positively influence the outcome of lifestyle-related chronic diseases, such as obesity and diabetes. Conclusions The lockdown associated with COVID-19 has largely had a negative impact on the lifestyles of individuals and communities across many countries and cultures. However, some individuals and communities also initiated positive lifestyle-related behavioral changes. If the knowledge generated by studying the impact of COVID-19-related lockdowns on the six lifestyle factors is further consolidated, it could improve chronic disease outcomes. This will help better understand lifestyle behaviors amidst crises and assist in redesigning extreme public health measures such as lockdowns.. It is up to governments, communities, and healthcare/academic entities to derive benefit from lessons learned from the pandemic, with the ultimate objective of better educating and promoting healthy lifestyles among communities.