23 research outputs found

    A cross sectional survey of international horse-racing authorities on injury data collection and reporting practices for professional jockeys

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    Jockey injuries are common in professional horse-racing and can result in life-threatening or career-ending outcomes. Robust injury data are essential to understand the circumstances of injury occurrence and ultimately identify prevention opportunities. This study aimed to identify jockey injury surveillance practices of international horse-racing authorities (HRAs) and the specific data items collected and reported by each HRA. A cross-sectional survey of representatives (e.g. Chief Medical Officer) from international HRAs was conducted. An online and paper questionnaire was designed comprised of 32 questions. Questions considered the barriers and facilitators to data collection within each HRA, and where available, what data were collected and reported by HRAs. Representatives from 15 international racing jurisdictions were included, of which 12 reported collection of race day injuries or falls, using varied definitions of medical attention and time loss. Six HRAs did not have a definition for a jockey injury, and eight HRAs had no parameters for describing injury severity. Race day exposure was collected by two HRAs. Results were commonly presented by HRAs as the number of injuries (n = 9/15) or proportion of injured jockeys (n = 6/15). The lack of a designated role for collection, collation and reporting of data was the main barrier for injury surveillance. Twelve HRAs agreed that mandatory collection would be a strong facilitator to improving practice. Enhancement and standardization of international jockey injury surveillance is required to move forward with evidence informed prevention. Concurrent investigation of how reporting practices can be best supported within existing HRA structures is recommended

    Racehorse welfare across a training season

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    Racehorse welfare is gaining increasing public attention, however scientific evidence in this area is lacking. In order to develop a better understanding of racehorse welfare, it must be measured and monitored. This is the first study to assess racehorse welfare using scientific objective methods across a training season. The aim of this study was threefold, firstly to investigate welfare measures which could be used in the first welfare assessment protocol for racehorses. Secondly, to understand the effect that a racing and training season had on individual racehorses and thirdly to identify risk factors for both good and poor welfare. Thirteen racehorse training yards were visited at the beginning and the peak of the racing season in England. Behavioral observations along with individual environmental and animal-based welfare measures were carried out on 353 horses in 13 training yards selected for variability. In our sample the horses were generally in good physical health: 94% of horses recorded as an ideal body condition score, no horses had signs of hoof neglect and 77.7% had no nasal discharge. The overall prevalence of external Mouth Corner Lesions was 12.9% and was significantly higher for Flat racing than Jump racing horses. The majority of horses (67.5%) showed positive horse human interactions. When stabled 54.1% horses had physical social contact and nasal discharge was not associated with increased physical contact. The training season significantly affected Human Reactivity Tests, Horse Grimace Scale scores and time spent resting and feeding. A total of 14.5% of horses displayed stereotypic behavior on at least two occasions. Horses with windows in their stables spent more time surveying their surroundings. Overall, in this population of racehorses, horses spent around a third of their daytime feeding (33.7%) followed by time spent standing resting (22.6%). The welfare assessment protocol used in this study is suitable for use in industry to collect welfare data on racehorses

    Complement membrane attack complex is an immunometabolic regulator of NLRP3 activation and IL-18 secretion in human macrophages

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    The complement system is an ancient and critical part of innate immunity. Recent studies have highlighted novel roles of complement beyond lysis of invading pathogens with implications in regulating the innate immune response, as well as contributing to metabolic reprogramming of T-cells, synoviocytes as well as cells in the CNS. These findings hint that complement can be an immunometabolic regulator, but whether this is also the case for the terminal step of the complement pathway, the membrane attack complex (MAC) is not clear. In this study we focused on determining whether MAC is an immunometabolic regulator of the innate immune response in human monocyte-derived macrophages. Here, we uncover previously uncharacterized metabolic changes and mitochondrial dysfunction occurring downstream of MAC deposition. These alterations in glycolytic flux and mitochondrial morphology and function mediate NLRP3 inflammasome activation, pro-inflammatory cytokine release and gasdermin D formation. Together, these data elucidate a novel signalling cascade, with metabolic alterations at its center, in MAC-stimulated human macrophages that drives an inflammatory consequence in an immunologically relevant cell type

    Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

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    Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

    Advances in high‐throughput mass spectrometry in drug discovery

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    Abstract High‐throughput (HT) screening drug discovery, during which thousands or millions of compounds are screened, remains the key methodology for identifying active chemical matter in early drug discovery pipelines. Recent technological developments in mass spectrometry (MS) and automation have revolutionized the application of MS for use in HT screens. These methods allow the targeting of unlabelled biomolecules in HT assays, thereby expanding the breadth of targets for which HT assays can be developed compared to traditional approaches. Moreover, these label‐free MS assays are often cheaper, faster, and more physiologically relevant than competing assay technologies. In this review, we will describe current MS techniques used in drug discovery and explain their advantages and disadvantages. We will highlight the power of mass spectrometry in label‐free in vitro assays, and its application for setting up multiplexed cellular phenotypic assays, providing an exciting new tool for screening compounds in cell lines, and even primary cells. Finally, we will give an outlook on how technological advances will increase the future use and the capabilities of mass spectrometry in drug discovery

    Further iterations on using the Problem-analysis Framework

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    A core component of applied educational and child psychology practice is the skilfulness with which practitioners are able to rigorously structure and conceptualise complex real world human problems. This is done in such a way that when they (with others) jointly work on them, there is an increased likelihood of positive outcomes being achieved for clients. The Problem-analysis Framework as discussed in this paper offers one way of working with such complexity which is grounded in a sound knowledge based in applied psychology. This paper provides further clarity on using the framework within applied practice. The authors were all trained in and use the Problem-analysis Framework and now work in many different types of applied settings within Australia, Iceland, New Zealand, Singapore and the United Kingdom. This paper illuminates important aspects of the problem-analysis approach itself for those currently learning it, as well as providing an aide-mémoire to those using it and those who want to develop their skills in this area
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