Lipid regulation of the glucagon receptor family.

The glucagon receptor family are typical class B1 G protein-coupled receptors (GPCRs) with important roles in metabolism, including the control of pancreas, brain, and liver function. As proteins with 7 transmembrane domains, GPCRs are intimately in contact with lipid bilayers and therefore can be putatively regulated by interactions with their lipidic components, including cholesterol, sphingolipids, and other lipid species. Additionally, these receptors, as well as the agonists they bind to, can undergo lipid modifications, which can influence their binding capacity and/or elicit modified or biased signalling profiles. While the effect of lipids, and in particular cholesterol, has been widely studied for other GPCR classes, information about their role in regulating the glucagon receptor family is only beginning to emerge. Here we summarise our current knowledge on the effects of cholesterol modulation of glucagon receptor family signalling and trafficking profiles, as well as existing evidence for specific lipid-receptor binding and indirect effects of lipids via lipid modification of cognate agonists. Finally, we discuss the different methodologies that can be employed to study lipid-receptor interactions and summarise the importance of this area of investigation to increase our understanding of the biology of this family of metabolically relevant receptors.

The bioequivalence study design recommendations for immediate-release solid oral dosage forms in the international pharmaceutical regulators programme participating regulators and organisations: differences and commonalities.

Bioequivalence (BE) studies are considered the standard for demonstrating that the performance of a generic drug product in the human body is sufficiently similar to that of its comparator product. The objective of this article is to describe the recommendations from participating Bioequivalence Working Group for Generics (BEWGG) members of the International Pharmaceutical Regulators Programme (IPRP) regarding the conduct and acceptance criteria for BE studies of immediate release solid oral dosage forms. A survey was conducted among BEWGG members regarding their BE recommendations and requirements related to study subjects, study design, sample size, single or multiple dose administration, study conditions (fasting or fed), analyte to be measured, selection of product strength, drug content, handling of endogenous substances, BE acceptance criteria, and additional design aspects. All members prefer conducting single dose cross-over designed studies in healthy subjects with a minimum of 12 subjects and utilizing the parent drug data to assess BE. However, differences emerged among the members when the drug's pharmacokinetics and pharmacodynamics become more complex, such that the study design (e.g., fasting versus fed conditions) and BE acceptance criteria (e.g., highly variable drugs, narrow therapeutic index drugs) may be affected. The survey results and discussions were shared with the ICH M13 Expert Working Group (EWG) and played an important role in identifying and analyzing gaps during the harmonization process. The draft ICH M13A guideline developed by the M13 EWG was endorsed by ICH on 20 December 2022, under Step 2.

Computational modelling of dynamic cAMP responses to GPCR agonists for exploration of GLP-1R ligand effects in pancreatic ß-cells and neurons.

The glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) which plays important physiological roles in insulin release and promoting fullness. GLP-1R agonists initiate cellular responses by cyclic AMP (cAMP) pathway signal transduction. Understanding of the potential of GLP-1R agonists in the treatment of type 2 diabetes may be advanced by considering the cAMP dynamics for agonists at GLP-1R in both pancreatic ß-cells (important in insulin release) and neurons (important in appetite regulation). Receptor desensitisation in the cAMP pathway is known to be an important regulatory mechanism, with different ligands differentially promoting G protein activation and desensitisation. Here, we use mathematical modelling to quantify and understand experimentally obtained cAMP timecourses for two GLP-1R agonists, exendin-F1 (ExF1) and exendin-D3 (ExD3), which give markedly different signals in ß-cells and neurons. We formulate an ordinary differential equation (ODE) model for the dynamics of cAMP signalling in response to G protein-coupled receptor (GPCR) ligands, encompassing ligand binding, receptor activation, G protein activation, desensitisation and second messenger generation. We validate our model initially by fitting to timecourse data for HEK293 cells, then proceed to parameterise the model for ß-cells and neurons. Through numerical simulation and sensitivity studies, our analysis adds support to the hypothesis that ExF1 offers more potential glucose regulation benefit than ExD3 over long timescales via signalling in pancreatic ß-cells, but that there is little difference between the two ligands in the potential appetite suppression effects offered via long-time signalling in neurons on the same timescales.

When to Pull the Trigger: Conceptual Considerations for Approximating Head Acceleration Events Using Instrumented Mouthguards.

Head acceleration events (HAEs) are acceleration responses of the head following external short-duration collisions. The potential risk of brain injury from a single high-magnitude HAE or repeated occurrences makes them a significant concern in sport. Instrumented mouthguards (iMGs) can approximate HAEs. The distinction between sensor acceleration events, the iMG datum for approximating HAEs and HAEs themselves, which have been defined as the in vivo event, is made to highlight limitations of approximating HAEs using iMGs. This article explores the technical limitations of iMGs that constrain the approximation of HAEs and discusses important conceptual considerations for stakeholders interpreting iMG data. The approximation of HAEs by sensor acceleration events is constrained by false positives and false negatives. False positives occur when a sensor acceleration event is recorded despite no (in vivo) HAE occurring, while false negatives occur when a sensor acceleration event is not recorded after an (in vivo) HAE has occurred. Various mechanisms contribute to false positives and false negatives. Video verification and post-processing algorithms offer effective means for eradicating most false positives, but mitigation for false negatives is less comprehensive. Consequently, current iMG research is likely to underestimate HAE exposures, especially at lower magnitudes. Future research should aim to mitigate false negatives, while current iMG datasets should be interpreted with consideration for false negatives when inferring athlete HAE exposure.

Innovation in sport medicine and science: a global social network analysis of stakeholder collaboration in rugby union.

Objectives: To investigate the network of stakeholders involved in rugby union research across the globe. Methods: Using author affiliations listed on scientific publications, we identified the organisations that contributed to rugby union research from 1977 to 2022 and examine collaboration through coauthorship indicators. We determined the locations and sectors of identified organisations and constructed a collaboration network. Network metrics, including degree centrality and betweenness centrality, are computed to identify influential organisations and measure intersector collaboration. Results: There is an increase in scientific knowledge creation and collaboration between organisations for rugby union research over time. Among the sectors, the university, professional sports team and sports governing body sectors exhibit the highest intersectoral and intrasectoral density. Predominantly, influential actors are located in England, Australia, France, New Zealand, Ireland and South Africa. Australian Catholic University, Leeds Beckett University, Stellenbosch University, Swansea University, University College London and the University of Cape Town emerge as influential actors between 2016 and 2022. Conclusions: Our study underscores the ongoing growth of scientific knowledge generation in rugby union, primarily led by organisations in tier 1 rugby-playing nations within the university sector. Intersectoral collaboration with sports governing bodies plays a crucial role, acting as a broker between sectors. However, the overall collaboration landscape between and within sectors is low. These results highlight an opportunity for improved collaboration opportunities, as the organisations driving knowledge creation have been identified.

The Frequency and Severity of Gastrointestinal Symptoms in Rugby Players.

This study aimed to assess the self-reported frequency and severity of gastrointestinal symptoms (GIS) at rest and around rugby training and match play in male and female rugby union players. An online questionnaire was sent to registered rugby union players (sevens or fifteens). Thirteen GIS were assessed alongside perceptions of appetite around rugby and rest using Likert and visual analog scales. Questions investigating a range of medical and dietary factors were included. Three hundred and twenty-five players (male n=271, female n=54) participated in the study. More frequent GIS (at least one GIS experienced weekly/more often) was reported by players at rest (n=203; 62%) compared to around rugby (n=154; 47%). The overall severity of GIS was low (mild discomfort), but a portion of players (33%) did report symptoms of moderate severity around rugby. Female players reported more frequent and severe symptoms compared to male counterparts (p<0.001). Self-reported appetite was significantly lower after matches compared to training. There were no dietary or medical factors associated with GIS severity scores. This study describes GIS characteristics in male and female rugby union players. Half of the players assessed experienced some form of GIS that may affect nutrition, training, or performance, and should thus be a consideration for practitioners supporting this cohort.

Review article: Emergency medical services transfer of severe traumatic brain injured patients to a neuroscience centre: A systematic review.

Patients with severe traumatic brain injuries require urgent medical attention at a hospital. We evaluated whether transporting adult patients with a severe traumatic brain injury (TBI) to a Neuroscience Centre is associated with reduced mortality. We reviewed studies published between 2010 and 2023 on severe TBI in adults (>18 years) using Medline, CINAHL, Google Scholar and Cochrane databases. We focused on mortality rates and the impact of transferring patients to a Neuroscience Centre, delays to neurosurgery and EMS triage accuracy. This review analysed seven studies consisting of 53 365 patients. When patients were directly transported to a Neuroscience Centre, no improvement in survivability was demonstrated. Subsequently, transferring patients from a local hospital to a Neuroscience Centre was significantly associated with reduced mortality in one study (adjusted odds ratio: 0.79, 95% confidence interval: 0.64-0.96), and 24-h (relative risk [RR]: 0.31, 0.11-0.83) and 30-day (RR: 0.66, 0.46-0.96) mortality in another. Patients directly transported to a Neuroscience Centre were more unwell than those taken to a local hospital. Subsequent transfers increased time to CT scanning and neurosurgery in several studies, although these were not statistically significant. Additionally, EMS could accurately triage. None of the included studies demonstrated statistically significant findings indicating that direct transportation to a Neuroscience Centre increased survivability for patients with severe traumatic brain injuries. Subsequent transfers from a non-Neuroscience Centre to a Neuroscience Centre reduced mortality rates at 24 h and 30 days. Further research is required to understand the differences between direct transport and subsequent transfers to Neuroscience Centres.

Injury Profile in Youth Female Athletes: A Systematic Review and Meta-Analysis.

BACKGROUND: An increasing number of epidemiological studies assessing the incidence, prevalence and severity of injury in youth female sport are available. However, no study has sought to synthesise the current evidence base across all youth female sport. As such, a systematic review and meta-analysis of injury in this cohort is necessary to understand the diversity of injury and its associated burden between sports in addition to identifying the density of research available. OBJECTIVE: To conduct a systematic review and meta-analysis of epidemiological data of injuries in youth female athletes with particular attention to injury incidence, mean days lost and injury burden. METHODS: Searches were performed in PubMed, EBSCO (SPORTDiscus with Full Text MEDLINE, APA PsycINFO, CINAHL, Academic Search Complete) and Cochrane databases. Studies were considered if they reported time-loss injury incidence or prevalence in youth female (≤ 19 years old) athletes. Study quality and risk of bias were assessed using STROBE-SIIS extension, Newcastle-Ottawa Scale, and funnel plots, respectively. Injury incidence and burden rate data were modelled using a mixed-effect Poisson regression model. Days lost data were modelled using a generalised linear mixed model. RESULTS: Thirty-two studies were included. The overall incidence rate, mean days lost per injury, and burden rate were 4.4 injuries per 1000 h (95% CI 3.3-5.9), 10 days (95% CI 6-15), and 46 days per 1000 h (95% CI 23-92), respectively. Forty percent of athletes sustained at least one time-loss injury. Competitive level was a significant moderator of match and training injury incidence, with elite youth athletes presenting greater pooled injury incidence estimates than non-elite athletes (p = 0.0315 and p = 0.0047, respectively). The influence of moderators on days lost and injury burden could not be determined due to an insufficient number of studies for analysis. CONCLUSION: Despite a broad inclusion criterion, there is limited injury surveillance research available across youth female sport. Outside of soccer, little research density is evidenced with single studies available in popular team sports such as Australian football and rugby union. Insufficient study numbers reporting mean days lost and injury burden data were available for analysis, and pooled days lost data could only be estimated for soccer. This highlights a need for future research to report days lost data alongside injury number and exposure so burden can be calculated and the full risk of injury to youth female athletes can be identified.

Bridging Eulerian and Lagrangian Poisson-Boltzmann solvers by ESES.

The Poisson-Boltzmann (PB) model is a widely used electrostatic model for biomolecular solvation analysis. Formulated as an elliptic interface problem, the PB model can be numerically solved on either Eulerian meshes using finite difference/finite element methods or Lagrangian meshes using boundary element methods. Molecular surface generators, which produce the discretized dielectric interfaces between solutes and solvents, are critical factors in determining the accuracy and efficiency of the PB solvers. In this work, we investigate the utility of the Eulerian Solvent Excluded Surface (ESES) software for rendering conjugated Eulerian and Lagrangian surface representations, which enables us to numerically validate and compare the quality of Eulerian PB solvers, such as the MIBPB solver, and the Lagrangian PB solvers, such as the TABI-PB solver. Furthermore, with the ESES software and its associated PB solvers, we are able to numerically validate an interesting and useful but often neglected source-target symmetric property associated with the linearized PB model.

Abolishing ß-arrestin recruitment is necessary for the full metabolic benefits of G protein-biased glucagon-like peptide-1 receptor agonists.

AIM: Earlier studies have shown that peptide glucagon-like peptide-1 receptor (GLP-1R) agonists with reduced ß-arrestin recruitment show enhanced anti-hyperglycaemic efficacy through avoidance of GLP-1R desensitization. However, the ligand modifications needed to decrease ß-arrestin recruitment usually also reduces GLP-1R affinity, therefore higher doses are needed. Here we aimed to develop new, long-acting, G protein-biased GLP-1R agonists with acute signalling potency comparable with semaglutide, to provide insights into specific experimental and therapeutic scenarios. MATERIALS AND METHODS: New GLP-1R agonist peptides were assessed using a variety of in vitro and in vivo assays. RESULTS: First, we show that very substantial reductions in ß-arrestin recruitment efficacy are required to realize fully the benefits of GLP-1R agonism on blood glucose lowering in mice, with more moderate reductions being less effective. Secondly, our lead compound (SRB107) performs substantially better than semaglutide for effects on blood glucose and weight loss, which may be jointly attributable to its biased agonist action and protracted pharmacokinetics. Thirdly, we show that biased agonist-specific GLP-1R internalization profiles occur at clinically relevant pharmacological concentrations. Finally, we show that SRB107 cAMP signalling is differentially modulated by single and double GLP1R coding variants seen in human populations, with implications for GLP-1R agonist pharmacogenomics. CONCLUSIONS: Completely abolishing ß-arrestin recruitment improves the anti-hyperglycaemic effects of GLP-1R agonists in mice.

Specialist healthcare services for concussion/mild traumatic brain injury in England: a consensus statement using modified Delphi methodology.

OBJECTIVE: To establish a consensus on the structure and process of healthcare services for patients with concussion in England to facilitate better healthcare quality and patient outcome. DESIGN: This consensus study followed the modified Delphi methodology with five phases: participant identification, item development, two rounds of voting and a meeting to finalise the consensus statements. The predefined threshold for agreement was set at ≥70%. SETTING: Specialist outpatient services. PARTICIPANTS: Members of the UK Head Injury Network were invited to participate. The network consists of clinical specialists in head injury practising in emergency medicine, neurology, neuropsychology, neurosurgery, paediatric medicine, rehabilitation medicine and sports and exercise medicine in England. PRIMARY OUTCOME MEASURE: A consensus statement on the structure and process of specialist outpatient care for patients with concussion in England. RESULTS: 55 items were voted on in the first round. 29 items were removed following the first voting round and 3 items were removed following the second voting round. Items were modified where appropriate. A final 18 statements reached consensus covering 3 main topics in specialist healthcare services for concussion; care pathway to structured follow-up, prognosis and measures of recovery, and provision of outpatient clinics. CONCLUSIONS: This work presents statements on how the healthcare services for patients with concussion in England could be redesigned to meet their health needs. Future work will seek to implement these into the clinical pathway.

Evaluation of a COVID-19 fundamental nursing care guideline versus usual care: The COVID-NURSE cluster randomized controlled trial.

AIM: To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVID-19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient health-related quality of life and cost-effectiveness. DESIGN: Parallel two-arm, cluster-level randomized controlled trial. METHODS: Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVID-19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patient-reported co-primary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intention-to-treat analyses. RESULTS: We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570-572 (98.1%-98.5%) patient participants in 14 clusters. We found no evidence of between-group differences on any patient, nurse or economic outcomes. We found between-group differences over time, in favour of the intervention, for three of our five co-primary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the 'other' ethnicity subgroup. CONCLUSION: We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on non-white British patients' experience of care. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required. IMPACT: Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on non-white British patients' experience of care. REPORTING METHOD: CONSORT and CONSERVE. PATIENT OR PUBLIC CONTRIBUTION: Patients with experience of hospitalization with COVID-19 were involved in guideline development and writing, trial management and interpretation of findings.

The speed and acceleration of the ball carrier and tackler into contact during front-on tackles in rugby league.

The aim was to use a combination of video analysis and microtechnology (10 Hz global positioning system [GPS]) to quantify and compare the speed and acceleration of ball-carriers and tacklers during the pre-contact phase (contact - 0.5s) of the tackle event during rugby league match-play. Data were collected from 44 professional male rugby league players from two Super League clubs across two competitive matches. Tackle events were coded and subject to three stages of inclusion criteria to identify front-on tackles. 10 Hz GPS data was synchronised with video to extract the speed and acceleration of the ball-carrier and tackler into each front-on tackle (n = 214). Linear mixed effects models (effect size [ES], confidence intervals, p-values) compared differences. Overall, ball-carriers (4.73 ± 1.12 m∙s-1) had greater speed into front-on tackles than tacklers (2.82 ± 1.07 m∙s-1; ES = 1.69). Ball-carriers accelerated (0.67 ± 1.01 m∙s-2) into contact whilst tacklers decelerated (-1.26 ± 1.36 m∙s-2; ES = 1.74). Positional comparisons showed speed was greater during back vs. back (ES = 0.66) and back vs. forward (ES = 0.40) than forward vs. forward tackle events. Findings can be used to inform strategies to improve performance and player welfare.

A comparison of activity demands between trial matches and in-season matches across multiple teams and seasons in semi-professional, male rugby league players.

Trial matches are frequently used for team preparation in rugby league competitions, making it essential to understand the demands experienced to assess their specificity to actual competition. Consequently, this study aimed to compare the activity demands between pre-season trial matches and early in-season rugby league matches. Following a repeated-measures observational design, 39 semi-professional, male rugby league players from two clubs were monitored using microsensors during two trial matches and the first two in-season matches across two consecutive seasons. Total distance, average speed, peak speed, absolute and relative high-speed running (HSR; > 18 km · h-1) and low-speed running (LSR; < 18 km · h-1) distance, as well as absolute and relative impacts, accelerations (total and high-intensity > 3 m · s-2), and decelerations (total and high-intensity < -3 m · s-2) were measured. Linear mixed models and Cohen's d effect sizes were used to compare variables between match types. Playing duration was greater for in-season matches (p < 0.001, d = 0.64). Likewise, higher (p < 0.001, d = 0.45-0.70) activity volumes were evident during in-season matches indicated via total distance, HSR distance, LSR distance, total accelerations, high-intensity accelerations, total decelerations, and high-intensity decelerations. Regarding activity intensities, a higher average speed (p = 0.008, d = 0.31) and relative LSR distance (p = 0.005, d = 0.31) only were encountered during in-season matches. Despite players completing less volume, the average activity intensities and impact demands were mostly similar between trial and early in-season matches. These findings indicate trial matches might impose suitable activity stimuli to assist players in preparing for early in-season activity intensities.

X as a proxy for tackle safety culture? Sentiment analysis of social media posts on red-carded and yellow-carded tackles during the 2019 Rugby World Cup.

Objectives: This study analysed the overall sentiment of attitudes, opinions, views and emotions expressed in posts on X related to red-carded and yellow-carded tackles during the 2019 Rugby World Cup (RWC). Methods: Sentiment analysis was conducted on posts on X about red or yellow cards issued at the 2019 RWC. Posts were classified as 'agree', 'disagree' and 'neutral'. The frequency of posts, red cards, yellow cards, all injuries, tackle injuries and total number of tackles per match were also synced to the 45-match playing schedule. Results: Five tackle-related red cards were issued during the 2019 RWC, and 15 tackle-related yellow cards, with 337 and 302 posts identified for each card decision, respectively. For red cards, 42% of posts (n=158/377) agreed with the referee's decision, 19% (n=71/377) disagreed and 40% were neutral. For yellow cards, 24% (n=73/302) agreed with the referee's decision, 33% (n=99/302) disagreed and 43% were neutral. Conclusions: For red cards, posts were 2.2 times more likely to agree with the referee's decision than disagree. Posts that agreed with a red card decision were also more likely to be shared (reposted) than posts that disagreed with a red card decision. In contrast, sentiments expressed for yellow card decisions were mixed. This may be related to interpreting the degree of danger and whether mitigation is applied. Within the ecosystem of rugby, sharing sentiments on social media plays a powerful role in creating a positive player welfare narrative.

Instrumented Mouthguards in Elite-Level Men's and Women's Rugby Union: The Incidence and Propensity of Head Acceleration Events in Matches.

OBJECTIVES: The aim of this study was to examine head acceleration event (HAE) propensity and incidence during elite-level men's and women's rugby union matches. METHODS: Instrumented mouthguards (iMGs) were fitted in 92 male and 72 female players from nine elite-level clubs and three international teams. Data were collected during 406 player matches (239 male, 167 female) using iMGs and video analysis. Incidence was calculated as the number of HAEs per player hour and propensity as the proportion of contact events resulting in an HAE at a range of linear and angular thresholds. RESULTS: HAE incidence above 10 g was 22.7 and 13.2 per hour in men's forwards and backs and 11.8 and 7.2 per hour in women's forwards and backs, respectively. Propensity varied by contact event, with 35.6% and 35.4% of men's tackles and carries and 23.1% and 19.6% of women's tackles and carries producing HAEs above 1.0 krad/s2. Tackles produced significantly more HAEs than carries, and incidence was greater in forwards compared with backs for both sexes and in men compared with women. Women's forwards were 1.6 times more likely to experience a medium-magnitude HAE from a carry than women's backs. Propensity was similar from tackles and carries, and between positional groups, while significantly higher in men than women. The initial collision stage of the tackle had a higher propensity than other stages. CONCLUSION: This study quantifies HAE exposures in elite rugby union players using iMGs. Most contact events in rugby union resulted in lower-magnitude HAEs, while higher-magnitude HAEs were comparatively rare. An HAE above 40 g occurred once every 60-100 min in men and 200-300 min in women. Future research on mechanisms for HAEs may inform strategies aimed at reducing HAEs.

Cryphonectria parasitica Detections in England, Jersey, and Guernsey during 2020-2023 Reveal Newly Affected Areas and Infections by the CHV1 Mycovirus.

In England, Cryphonectria parasitica was detected for the first time in 2011 in a nursery and in 2016 in the wider environment. Surveys between 2017 and 2020 identified the disease at different sites in Berkshire, Buckinghamshire, Cornwall, Derbyshire, Devon, Dorset, London, West Sussex, and the island of Jersey, while the present study comprises the results of the 2020-2023 survey with findings in Derbyshire, Devon, Kent, Nottinghamshire, Herefordshire, Leicestershire, London, West Sussex, and the islands of Jersey and Guernsey. A total of 226 suspected samples were collected from 72 surveyed sites, as far north as Edinburgh and as far west as Plymouth (both of which were negative), and 112 samples tested positive by real-time PCR and isolation from 35 sites. The 112 isolates were tested for the vegetative compatibility group (VCG), mating type, and Cryphonectria hypovirus 1 (CHV1). Twelve VCGs were identified, with two of them (EU-5 and EU-22) being the first records in the UK. Both mating types were present (37% MAT-1 and 63% MAT-2), but only one mating type was present per site and VCG, and perithecia were never observed. Cryphonectria hypovirus 1 (CHV1), consistently subtype-I haplotype E-5, was detected in three isolates at a low concentration (5.9, 21.1, and 33.0 ng/µL) from locations in London, Nottinghamshire, and Devon.

I won't let you down; why 20% of Men's and Women's Super League players underreported suspected concussions.

OBJECTIVES: Quantify and identify factors associated with concussion underreporting in Super League rugby league players. DESIGN: Cross sectional survey. METHODS: During the 2022 season preseason, 422 Men's and Women's Super League players completed an online survey quantifying player demographics, rugby playing history, concussion history, prevalence of, and reasons for underreporting concussion, concussion knowledge and long-term implications and perceptions of concussion. RESULTS: Overall, 20% of respondents stated they did not report concussion-related symptoms to medical staff during the 2020 and 2021 seasons. The two most common reasons for underreporting concussion were 'didn't want to be ruled out of a match' (35%) and 'didn't want to let down team' (24%). 65% of players reported an appropriate level of knowledge about concussion and potential long-term implications at the start of their senior rugby career, versus 89% now. In relation to concussion knowledge, symptoms were correctly identified on 74% of occasions. 57% of players surveyed were concerned about the potential long-term implications from concussion, and 11% of players would encourage their/family members' children to not play rugby league. CONCLUSIONS: The proportion of Super League players who did not report concussion symptoms was similar to rugby league players in Australia. The main reasons for not reporting concussion appeared to be due to perceptions of what is beneficial for the team, suggesting both performance and medical staff should collectively encourage players to report concussion. A player's attitude towards concussion is potentially an individual modifiable risk factor and should be considered within the concussion management of players.