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Concussions in contact sports are challenging for athletes, health professionals and sporting bodies to prevent, detect and manage. Design of interventions for primary prevention, early recognition of concussion and continuing to improve postconcussion management are essential for protecting athletes and promoting brain health. Over the last decade, there have been advancements in video technology for analysing head impact events and improvements in the clinical management of concussions. This study protocol describes how researchers, clinicians and staff from the Australasian National Rugby League (NRL) have brought these advancements together and developed a database of videos with head impact events and clinical outcomes. The intended outputs from this work will enhance the understanding of head impact events in NRL, from biomechanical and gameplay factors to concussion and return to play outcomes. Publishing this protocol increases the transparency of this large-scale effort to better identify head impacts and their relationship to concussions and player movement behaviour to contextualise these variables to generate new knowledge and support the reproducibility of these emerging findings. Between 2017 and 2023, over 5250 head contact cases were recorded in the database, from which >1700 head injury assessments were performed, and >600 concussions were diagnosed. Future studies using these data are planned to inform both primary and secondary injury prevention initiatives, such as risk analysis and prediction of game scenarios that result in concussion, as well as investigation of features and factors that help to inform the duration of recovery and return to play.

Objective To examine the likelihood of head acceleration events (HAEs) as a function of previously identified risk factors: match time, player status (starter or substitute) and pitch location in elite-level men’s and women’s rugby union matches.Methods Instrumented mouthguard data were collected from 179 and 107 players in the men’s and women’s games and synchronised to video-coded match footage. Head peak resultant linear acceleration (PLA) and peak resultant angular acceleration were extracted from each HAE. Field location was determined for HAEs linked to a tackle, carry or ruck. HAE incidence was calculated per player hour across PLA recording thresholds with 95% CIs estimated. Propensity was calculated as the percentage of contact events that caused HAEs across PLA recording thresholds, with a 95% CI estimated. Significance was assessed by non-overlapping 95% CIs.Results 29 099 and 6277 HAEs were collected from 1214 and 577 player-matches in the men’s and women’s games. No significant differences in match quarter HAE incidence or propensity were found. Substitutes had higher HAE incidence than starters at lower PLA recording thresholds for men but similar HAE propensity. HAEs were more likely to occur in field locations with high contact event occurrence.Conclusion Strategies to reduce HAE incidence need not consider match time or status as a substitute or starter as HAE rates are similar throughout matches, without differences in propensity between starters and substitutes. HAE incidence is proportional to contact frequency, and strategies that reduce either frequency or propensity for contact to cause head contact may be explored.

Background: This study examines the impact of participating in a seven-week football programme on the personal well-being of male asylum seekers residing in contingency accommodation in the UK. Methods: This repeated measures study included a cohort of participants who engaged in weekly football sessions and completed a well-being questionnaire (ONS4) over a continuous seven-week period. Longitudinal linear regression analysis using generalized estimating equations (GEE) was used to assess the relationship between personal well-being and weekly minutes of football participation (M1). A second model incorporating the total number of non-football activity sessions in the past week as a covariate was also implemented (M2). Results: Of the 73 participants who completed the questionnaire, 23 responded twice or more across the study period and were subsequently included in the analysis. Results revealed that 2 h of football participation within 7 days significantly improved aspects of personal well-being when compared with no football participation, including improved life satisfaction, feeling life is worthwhile, and happiness. Both models demonstrated a shift from ‘low’ to ‘medium’ ONS4 categorical score. Anxiety levels remained unchanged regardless of participation and model. Conclusion: We provide important evidence on the potential benefits of football participation for promoting personal well-being among male asylum seekers residing in contingency accommodation.

Background: Rugby league is a popular collision sport among Australian adolescent and young adult men. Concussion is one of the more common injuries in rugby league. Few studies have examined concussion in youth rugby league. To examine medically diagnosed concussions from a single season within two elite-level pathway rugby league competitions by evaluating game play risk factors and conducting a video review of potential concussion signs. Methods: All players involved in the Queensland Rugby League's (QRL) under 18 years and under 20 years age group competitions during the 2019 season were included in this study. Data included all head injury assessments (HIAs) identified in real-time through the QRL injury surveillance system for these two QRL age group competitions. The purpose of this study was to (i) report the rates of HIAs and medically diagnosed concussions; (ii) examine video signs of potential concussion; (iii) review game play risk factors related to HIAs and concussions; and (iv) determine the number of days until a concussed player returned to match play and the number of subsequent games missed by concussed players. Results: There were 86 HIAs and 30 medically diagnosed concussions from the two competitions. The concussion incidence was 2.93 per 1000 player match hours in the under 18-year age group and 5.75 per 1000 player match hours in the under 20-year age group. Slow to stand was the most commonly observed video sign (78.6%; 22/28 concussions). Most concussed players (91%, 21/23) missed at least one subsequent game (M ​= ​1.4, SD ​= ​1.7, range ​= ​0–7 games), with the average days to return-to-play being 15.7 (SD ​= ​7.0, range ​= ​7–41 days). Conclusions: In elite-level pathway rugby league, the incidences of HIAs and medically diagnosed concussions were higher in the under 20 age group than the under 18 age group. Both age groups had lower incidences of HIAs and concussions than professional adult rugby league players. Return-to-play following concussion was similar across the two age groups and differed considerably compared to the elite level, with a longer time before return to play for the younger elite level development pathway players.

Objectives: Co-agonists at the glucagon-like peptide-1 and glucagon receptors (GLP1R/GCGR) show promise as treatments for metabolic dysfunction-associated steatotic liver disease (MASLD). Although most co-agonists to date have been heavily GLP1R-biased, glucagon directly acts on the liver to reduce fat content. The aims of this study were to investigate a GCGR-biased co-agonist as treatment for hepatic steatosis in mice. Methods: Mice with diet-induced obesity (DIO) were treated with Dicretin, a GLP1/GCGR co-agonist with high potency at the GCGR, Semaglutide (GLP1R monoagonist) or food restriction over 24 days, such that their weight loss was matched. Hepatic steatosis, glucose tolerance, hepatic transcriptomics, metabolomics and lipidomics at the end of the study were compared with Vehicle-treated mice. Results: Dicretin lead to superior reduction of hepatic lipid content when compared to Semaglutide or equivalent weight loss by calorie restriction. Markers of glucose tolerance and insulin resistance improved in all treatment groups. Hepatic transcriptomic and metabolomic profiling demonstrated many changes that were unique to Dicretin-treated mice. These include some known targets of glucagon signaling and others with as yet unclear physiological significance. Conclusions: Our study supports the development of GCGR-biased GLP1/GCGR co-agonists for treatment of MASLD and related conditions.

The eight-toothed spruce bark-beetle Ips typographus is the most damaging insect pest of Norway spruce in Europe, and it poses a serious risk to spruce in other countries where it is not currently present but might be introduced. The beetle is not native to the UK and before 2018 it had not been found established anywhere within the country. In November 2018, however, several adult Ips typographus were found in a billet trap set up as part of annual surveys that the UK carries out to monitor for this and other quarantine bark beetle pests. The finding of adult beetles in the billet trap, a few miles south of Ashford in Kent, led to the discovery of a breeding population in an adjacent woodland. Delimiting surveys to 1 km and further surveys to 50 km showed that the infestation was confined to a single stand of Norway spruce. The stand was felled in January and February 2019, and the material destroyed, and beetles emerging on the site were trapped out using pheromone traps, billet piles and trap trees. These prompt actions eradicated the breeding population, but small numbers of adult Ips typographus continued to be caught on the outbreak site in 2020 and 2021. These captures, and numerous adult Ips typographus caught in pheromone traps set up across the region in response to the outbreak, indicate that incursions of adult Ips typographus are occurring on a regular basis, most likely from source populations in northern France and Belgium. The arrival of adult Ips typographus over a wide area and the potential for further outbreaks represents a continuing threat to spruce woodlands in south-east England, and has important implications for surveillance and monitoring and the management of spruce in this part of the UK.

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.

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.

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 highspeed 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 highintensity < -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.

This study aims to establish the validity and reliability of the prone Yo-YoIRL1 in elite female rugby league players (part one) and determine the anthropometric and physical characteristics contributing to 15m prone Yo-YoIRL1 performance (part two). Part one, 21 subjects completed one Yo-YoIRL1, one 20m and two 15m prone Yo-YoIRL1 tests over four sessions, with 7-14 days in-between. Part two, ten subjects completed a testing battery, including body mass, height, dual-energy x-ray absorptiometry, isometric mid-thigh pull, isometric bench-press, 10m and 20m sprints and an incremental treadmill test ([Formula: see text]). The 15m prone YoYoIRL1 demonstrated poor reliability with a typical error of 68m (21%) and a smallest worthwhile change of 54m (9%). Validity analysis found the prone versions of the YoYoIRL1 were not sensitive measures of intermittent running performance. Both prone YoYoIRL1 test distances demonstrated large mean bias (76% and -37% respectively) and typical error of the estimate (19% and 21%, respectively) in comparison to the YoYoIRL1. Body mass (r = -0.89), lean mass (r = -0.64), body fat % (r = -0.68), [Formula: see text] (l∙min-1) (r = -0.64), IMTP (r = -0.69), IBP (r = -0.15), 10m (r = -0.77) and 20m (r = -0.72) momentum displayed large negative relationships with 15m prone Yo-YoIRL1 performance. Due to the poor validity of the 20m prone YoYoIRL1, the poor validity and reliability of the 15m prone YoYoIRL1, and the anthropometric and physical characteristics which negatively impact performance, practitioners should reconsider the use of the prone YoYoIRL1 test to monitor high intensity intermittent running performance.

This is the first study to assess longitudinal changes in anthropometric, physiological, and physical qualities of international women's rugby league players. Thirteen forwards and 11 backs were tested three times over a 10-month period. Assessments included: standing height and body mass, body composition measured by dual x-ray absorptiometry (DXA), a blood panel, resting metabolic rate (RMR) assessed by indirect calorimetry, aerobic capacity (i.e.,[Formula: see text]) evaluated by an incremental treadmill test, and isometric force production measured by a force plate. During the pre-season phase, lean mass increased significantly by ~2% for backs (testing point 1: 47 kg; testing point 2: 48 kg) and forwards (testing point 1: 50 kg; testing point 2: 51 kg) (p = ≤ 0.05). Backs significantly increased their [Formula: see text] by 22% from testing point 1 (40 ml kg-1 min-1) to testing point 3 (49 ml kg-1 min-1) (p = ≤ 0.04). The [Formula: see text] of forwards increased by 10% from testing point 1 (41 ml kg-1 min-1) to testing point 3 (45 ml kg-1 min-1), however this change was not significant (p = ≥ 0.05). Body mass (values represent the range of means across the three testing points) (backs: 68 kg; forwards: 77-78 kg), fat mass percentage (backs: 25-26%; forwards: 30-31%), resting metabolic rate (backs: 7 MJ day-1; forwards: 7 MJ day-1), isometric mid-thigh pull (backs: 2106-2180 N; forwards: 2155-2241 N), isometric bench press (backs: 799-822 N; forwards: 999-1024 N), isometric prone row (backs: 625-628 N; forwards: 667-678 N) and bloods (backs: ferritin 21-29 ug/L, haemoglobin 137-140 g/L, iron 17-21 umol/L, transferrin 3 g/L, transferring saturation 23-28%; forwards: ferritin 31-33 ug/L, haemoglobin 141-145 g/L, iron 20-23 umol/L, transferrin 3 g/L, transferrin saturation 26-31%) did not change (p = ≥ 0.05). This study provides novel longitudinal data which can be used to better prepare women rugby league players for the unique demands of their sport, underpinning female athlete health.

The application of pattern mining algorithms to extract movement patterns from sports big data can improve training specificity by facilitating a more granular evaluation of movement. Since movement patterns can only occur as consecutive, non-consecutive, or non-sequential, this study aimed to identify the best set of movement patterns for player movement profiling in professional rugby league and quantify the similarity among distinct movement patterns. Three pattern mining algorithms (l-length Closed Contiguous [LCCspm], Longest Common Subsequence [LCS] and AprioriClose) were used to extract patterns to profile elite rugby football league hookers (n = 22 players) and wingers (n = 28 players) match-games movements across 319 matches. Jaccard similarity score was used to quantify the similarity between algorithms' movement patterns and machine learning classification modelling identified the best algorithm's movement patterns to separate playing positions. LCCspm and LCS movement patterns shared a 0.19 Jaccard similarity score. AprioriClose movement patterns shared no significant Jaccard similarity with LCCspm (0.008) and LCS (0.009) patterns. The closed contiguous movement patterns profiled by LCCspm best-separated players into playing positions. Multi-layered Perceptron classification algorithm achieved the highest accuracy of 91.02% and precision, recall and F1 scores of 0.91 respectively. Therefore, we recommend the extraction of closed contiguous (consecutive) over non-consecutive and non-sequential movement patterns for separating groups of players.

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.

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.

Control of tropical theileriosis, caused by the apicomplexan Theileria annulata, depends on the use of a single drug, buparvaquone, the efficacy of which is compromised by the emergence of resistance. The present study was undertaken to improve understanding of the role of mutations conferring buparvaquone resistance in T. annulata, and the effects of selection pressures on their emergence and spread. First, we investigated genetic characteristics of the cytochrome b locus associated with buparvaquone resistance in 10 susceptible and 7 resistant T. annulata isolates. The 129G (GGC) mutation was found in the Q01 binding pocket and 253S (TCT) and 262S (TCA) mutations were identified within the Q02 binding pocket. Next, we examined field isolates and identified cytochrome b mutations 129G (GGC), 253S (TCT) and 262S (TCA) in 21/75 buffalo-derived and 19/119 cattle-derived T. annulata isolates, providing evidence of positive selection pressure. Both hard and soft selective sweeps were identified, with striking differences between isolates. For example, 19 buffalo-derived and 7 cattle-derived isolates contained 129G (GGC) and 253S (TCT) resistance haplotypes at a high frequency, implying the emergence of resistance by a single mutation. Two buffalo-derived and 12 cattle-derived isolates contained equally high frequencies of 129G (GGC), 253S (TCT), 129G (GGC)/253S (TCT) and 262S (TCA) resistance haplotypes, implying the emergence of resistance by pre-existing or recurrent mutations. Phylogenetic analysis further revealed that 9 and 21 unique haplotypes in buffalo and cattle-derived isolates were present in a single lineage, suggesting a single origin. We propose that animal migration between farms is an important factor in the spread of buparvaquone resistance in endemic regions of Pakistan. The overall outcomes will be useful in understanding how drug resistance emerges and spreads, and this information will help design strategies to optimise the use and lifespan of the single most drug use to control tropical theileriosis.

Introduction Patients with episodes of supraventricular tachycardia (SVT), a common heart arrhythmia, are often attended by ambulance services. International guidelines advocate treatment with the Valsalva manoeuvre (VM), but this simple physical treatment has a low success rate, with most patients requiring conveyance to hospital. The Valsalva Assist Device (VAD) is a simple device that might help practitioners and patients perform a more effective VM and reduce the need for patients to be taken to hospital.Methods and analysis This stepped wedge cluster randomised controlled trial, conducted within a UK ambulance service, compares the current standard VM with a VAD-delivered VM in stable adult patients presenting to the ambulance service with SVT. The primary outcome is conveyance to hospital; secondary outcomes measures include cardioversion rates, duration of ambulance care and number of subsequent episodes of SVT requiring ambulance service care. We plan to recruit approximately 800 patients, to have 90% power to detect an absolute reduction in conveyance rate of 10% (from 90% to 80%) between the standard VM (control) and VAD-delivered VM (intervention). Such a reduction in conveyance would benefit patients, the ambulance service and receiving emergency departments. It is estimated potential savings would pay for devices for the entire ambulance trust within 7 months.Ethics and dissemination The study has been approved by the Oxford Research Ethics Committee (reference 22/SC/0032). Dissemination will be through peer-reviewed journal publication, presentation at national and international conferences and by the Arrhythmia Alliance, a patient support charity.Trial registration number ISRCTN16145266.

A ventilation timing light (VTL) is a small commercially available single-use device that is programmed to light up at six-second intervals prompting rescuers to provide a single controlled breath during manual ventilation. The device also indicates the duration of the breath by remaining illuminated for the duration of the inspiratory time. The aim of this study was to evaluate the impact of the VTL on a selection of CPR quality metrics. Methods: A total of 71 paramedic students who were already proficient in performing high-performance CPR (HPCPR) were required to perform HPCPR with and without a VTL. The quality of the HPCPR delivered, reflected by the selected quality metrics; chest compression fraction (CCF), chest compression rate (CCR), and ventilation rate (VR), was then evaluated. Results: While HPCPR with and without a VTL were both able to achieve guideline-based performance targets of CCF, CCR, and VR, the group who had used the VTL to deliver HPCPR were able to consistently provide 10 ventilations for every minute of asynchronous compressions (10 breath/min vs 8.7 breath/min p 80%), and chest compression rates when used during the delivery of HPCPR in a simulated OHCA event.

ObjectiveThe tackle is the most injurious event in rugby league and carries the greatest risk of concussion. This study aims to replicate previous research conducted in professional men's rugby league by examining the association between selected tackle characteristics and head impact events (HIEs) in women's professional rugby league.MethodsWe reviewed and coded 83 tackles resulting in an HIE and every tackle (6,318 tackles) that did not result in an HIE for three seasons (2018–2020) of the National Rugby League Women's (NRLW) competition. Tackle height, body position of the tackler and ball carrier, as well as the location of head contact with the other player's body were evaluated. Propensity of each situation that caused an HIE was calculated as HIEs per 1,000 tackles.ResultsThe propensity for tacklers to sustain an HIE was 6.60 per 1,000 tackles (95% CI: 4.87–8.92), similar to that of the ball carrier (6.13 per 1,000 tackles, 95% CI: 4.48–8.38). The greatest risk of an HIE to either the tackler or ball carrier occurred when head proximity was above the sternum (21.66 per 1,000 tackles, 95% CI: 16.55–28.35). HIEs were most common following impacts between two heads (287.23 HIEs per 1,000 tackles, 95% CI: 196.98–418.84). The lowest propensity for both tackler (2.65 per 1,000 tackles, 95% CI: 0.85–8.20) and ball carrier HIEs (1.77 per 1,000 tackles, 95% CI: 0.44–7.06) occurred when the head was in proximity to the opponent's shoulder and arm. No body position (upright, bent or unbalanced/off feet) was associated with an increased propensity of HIE to either tackler or ball carrier.ConclusionsIn the NRLW competition, tacklers and ball carriers have a similar risk of sustaining an HIE during a tackle, differing from men's NRL players, where tacklers have a higher risk of HIEs. Further studies involving larger samples need to validate these findings. However, our results indicate that injury prevention initiatives in women's rugby league should focus on how the ball carrier engages in contact during the tackle as well as how the tackler executes the tackle.

Central glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) signaling is critical in GIP-based therapeutics’ ability to lower body weight, but pathways leveraged by GIPR pharmacology in the brain remain incompletely understood. We explored the role of Gipr neurons in the hypothalamus and dorsal vagal complex (DVC) — brain regions critical to the control of energy balance. Hypothalamic Gipr expression was not necessary for the synergistic effect of GIPR/GLP-1R coagonism on body weight. While chemogenetic stimulation of both hypothalamic and DVC Gipr neurons suppressed food intake, activation of DVC Gipr neurons reduced ambulatory activity and induced conditioned taste avoidance, while there was no effect of a short-acting GIPR agonist (GIPRA). Within the DVC, Gipr neurons of the nucleus tractus solitarius (NTS), but not the area postrema (AP), projected to distal brain regions and were transcriptomically distinct. Peripherally dosed fluorescent GIPRAs revealed that access was restricted to circumventricular organs in the CNS. These data demonstrate that Gipr neurons in the hypothalamus, AP, and NTS differ in their connectivity, transcriptomic profile, peripheral accessibility, and appetite-controlling mechanisms. These results highlight the heterogeneity of the central GIPR signaling axis and suggest that studies into the effects of GIP pharmacology on feeding behavior should consider the interplay of multiple regulatory pathways.

Background: Downhill running (DR) has been used extensively to investigate recovery from muscle-damaging exercise. There is no consensus on the optimal conditions (duration, severity, intensity) for a DR protocol. The purpose of this research was to determine the most effective DR conditions to induce muscle damage. Methods: The research was comprised a 3x3 within-between participant design. Recreationally active males’ (n = 12) muscle damage was assessed using gold standard indirect markers (force loss and muscle soreness) at baseline, 24 and 48h post one of three DR conditions (a. 45min at -10% gradient b. 45min at -12% c. 30min at -15%). DR was completed on a motorised treadmill at 70% velocity of V̇O2peak achieved during an incremental exercise test to exhaustion. Results: Isometric force (p = .005, ηp2 = 0.45) and muscle soreness (p = .002, ηp2 = 0.49) were impaired 24h post-exercise; no difference (p > .05) was evident between conditions. At 48h the impairments in force loss and muscle soreness were no longer evident (p > .05) across all conditions. There was no difference (p = .82) in HR between the DR conditions. Findings: Independent of duration and gradient all conditions resulted in a similar response in force loss and muscle soreness, indicating muscle damage had occurred. Interestingly, the 30-min protocol produced the same response in less time, without requiring individuals to work at a greater intensity. Therefore, the 30-min condition is suggested as the most appropriate protocol for use in the scientific investigation of muscle damage from DR.

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.

The aim of this study was to identify between-position (forwards vs. backs) differences in movement variability in cumulative tackle events training during both attacking and defensive roles. Eleven elite adolescent male rugby league players volunteered to participate in this study (mean ± SD, age; 18.5 ± 0.5 years, height; 179.5 ± 5.0 cm, body mass; 88.3 ± 13.0 kg). Participants performed a drill encompassing four blocks of six tackling (i.e. tackling an opponent) and six tackled (i.e. being tackled by an opponent while carrying a ball) events (i.e. 48 total tackles) while wearing a micro-technological inertial measurement unit (WIMU, Realtrack Systems, Spain). The acceleration data were used to calculate sample entropy (SampEn) to analyse the movement variability during tackles performance. In tackling actions SampEn showed significant between-position differences in block 1 (p = 0.0001) and block 2 (p = 0.0003). Significant between-block differences were observed in backs (block 1 vs 3, p = 0,0021; and block 1 vs 4, p = 0,0001) but not in forwards. When being tackled, SampEn showed significant between-position differences in block 1 (p = 0.0007) and block 3 (p = 0.0118). Significant between-block differences were only observed for backs in block 1 vs 4 (p = 0,0025). Movement variability shows a progressive reduction with cumulative tackle events, especially in backs and when in the defensive role (tackling). Forwards present lower movement variability values in all blocks, particularly in the first block, both in the attacking and defensive role. Entropy measures can be used by practitioners as an alternative tool to analyse the temporal structure of variability of tackle actions and quantify the load of these actions according to playing position.

This study examined performance and physiological responses (power output, tissue saturation index) to repeat sprint cycling with oxygen supplementation (O2Supp [fraction of inspired oxygen 1.00]). Fourteen amateur male cyclists took part. Two visits to the laboratory entailed; 15min relative intensity warm-up, 10min of passive recovery, followed by 10x15s repeated sprints, during which air inspired had FiO2 1.00 oxygen or normal air. Outcome measures include, mean power (W) and change in Tissue Saturation Index (ΔTSI%). Repeated measures ANOVA were used to examine difference between conditions in mean power output. Paired samples t-tests were used to examine differences between conditions in ΔTSI (%) and rate of muscle reoxygenation and deoxygenation (%·s-1). Mean power output was 4% higher in the oxygen condition compared to normoxia (p < .01). There was a significant positive correlation between power output and reoxygenation rate during O2Supp (r = 0.65, p = .04). No correlation was seen between power output and reoxygenation rate during normoxia (r = -0.30, p = .40). A significantly increased deoxy rate was seen in the O2Supp condition compared to normoxia (p = .05). Oxygen supplementation appears to elicit the greatest performance improvements in mean power, potentially facilitated by an increasing muscle reoxygenation rate. This evidences the utility of oxygen as an ergogenic aid to in cycling performance.

Objective The reduction in circulating low-density lipoprotein cholesterol (LDL-c) is the primary aim of lipid-lowering therapies as a method of atherosclerotic cardiovascular disease risk reduction. Inclisiran is a new and potent lipid-lowering drug that is shown to be effective in reducing LDL-c in randomised controlled trials, however, real-world data of its use are not yet known. We sought to analyse the early effects of this drug in a tertiary centre lipid and cardiovascular risk clinic.Methods We performed a retrospective analysis of the first 80 patients who received a single dose of inclisiran at our lipid clinic between 1 December 2021 and 1 September 2022. Data were collected using electronic healthcare records. Baseline blood tests were taken prior to start of treatment and were repeated at 2 months follow-up. Data on adverse events were also recorded.Results At 2 months after treatment initiation, mean baseline LDL-c fell from 3.5±1.1 mmol/L by 48.6% to 1.8±1.0 mmol/L and total cholesterol from 5.7±1.3 mmol/L by 33.3% to 3.8±1.1 mmol/L (both p

The importance of contributors that can result in negative player outcomes in sport and the feasibility and barriers to modifying these to optimise player health and well-being have yet to be established. Within rugby codes (rugby league, rugby union and rugby sevens), within male and female cohorts across playing levels (full-time senior, part-time senior, age grade), this project aims to develop a consensus on contributors to negative biopsychosocial outcomes in rugby players (known as the CoNBO study) and establish stakeholder perceived importance of the identified contributors and barriers to their management. This project will consist of three parts; part 1: a systematic review, part 2: a three-round expert Delphi study and part 3: stakeholder rating of feasibility and barriers to management. Within part 1, systematic searches of electronic databases (PubMed, Scopus, MEDLINE, SPORTDiscus, CINAHL) will be performed. The systematic review protocol is registered with PROSPERO. Studies will be searched to identify physical, psychological and/or social factors resulting in negative player outcomes in rugby. Part 2 will consist of a three-round expert Delphi consensus study to establish additional physical, psychological and/or social factors that result in negative player outcomes in rugby and their importance. In part 3, stakeholders (eg, coaches, chief executive officers and players) will provide perceptions of the feasibility and barriers to modifying the identified factors within their setting. On completion, several manuscripts will be submitted for publication in peer-reviewed journals. The findings of this project have worldwide relevance for stakeholders in the rugby codes.PROSPERO registration numberCRD42022346751.

Abstract Glucagon receptor agonists show promise as components of next generation metabolic syndrome pharmacotherapies. However, the biology of glucagon action is complex, controversial, and likely context dependent. As such, a better understanding of chronic glucagon receptor (GCGR) agonism is essential to identify and mitigate potential clinical side-effects. Herein we present a novel, long-acting glucagon analogue (GCG104) with high receptor-specificity and potent in vivo action. It has allowed us to make two important observations about the biology of sustained GCGR agonism. First, it causes weight loss in mice by direct receptor signalling at the level of the liver. Second, subtle changes in GCG104-sensitivity, possibly due to interindividual variation, may be sufficient to alter its effects on metabolic parameters. Together, these findings confirm the liver as a principal target for glucagon-mediated weight loss and provide new insights into the biology of glucagon analogues.

The safety and efficacy of a generic product are partly based on demonstrating bioequivalence to the innovator product; however, when the innovator product is no longer available as a comparator product, a survey conducted within the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP) indicated that the criteria for selecting an alternative comparator product varies. For most members of the BEWGG, an existing marketed generic that was approved based on a comparison with the locally registered innovator product can be used, contingent on criteria that ranges from allowing any generic to be used, to allowing only specific criteria-defined generics to be used. Notwithstanding the acceptability of a generic as an alternative comparator, it is not always the preferred comparator for several jurisdictions. Some jurisdictions require the use of a locally sourced alternative innovator comparator (e.g., the same medicinal ingredient manufactured by a different company) or a foreign innovator comparator. Unlike the other members of the BEWGG, the European Union (EU) has no such options available, rather mechanisms are in place to allow manufacturers to develop a new comparator. The criteria described herein regarding the use of an alternative comparator product can also be applied to scenarios where a specific strength of a series of strengths or an innovative fixed dose combination are discontinued. The results of the survey demonstrate that while criteria for selecting alternative comparator products are not harmonized among the BEWGG participants, the common concern for all jurisdictions is to select a comparator product that meets the safety and efficacy standards of the original innovator product.

Structured abstract: Objective: To determine whether glucagon receptor (GCGR) actions are modulated by cellular cholesterol levels. Methods: We determined the effects of experimental cholesterol depletion and loading on glucagon-mediated cAMP production, ligand internalisation and glucose production in human hepatoma cells, mouse and human hepatocytes. GCGR interactions with lipid bilayers were explored using coarse-grained molecular dynamic simulations. Glucagon responsiveness was measured in mice fed a high cholesterol diet with or without simvastatin to modulate hepatocyte cholesterol content. Results: GCGR cAMP signalling was reduced by higher cholesterol levels across different cellular models. Ex vivo glucagon-induced glucose output from mouse hepatocytes was enhanced by simvastatin treatment. Mice fed a high cholesterol diet had increased hepatic cholesterol and a blunted hyperglycaemic response to glucagon, both of which were partially reversed by simvastatin. Simulations identified likely membrane-exposed cholesterol binding sites on the GCGR, including a site where cholesterol is a putative negative allosteric modulator. Conclusions: Our results indicate that cellular cholesterol content influences glucagon sensitivity and indicate a potential molecular basis for this phenomenon. This could be relevant to the pathogenesis of non-alcoholic fatty liver disease, which is associated with both hepatic cholesterol accumulation and glucagon resistance.

Objectives In part 1, the objective was to undertake a systematic scoping review of applied sports science and sports medicine in women’s rugby, and in part 2 to develop a consensus statement on future research priorities.Design In part 1, a systematic search of PubMed (MEDLINE), Scopus and SPORTDiscus (EBSCOhost) was undertaken from the earliest records to January 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020, the PRISMA extension for Scoping Reviews, and the PRISMA extension protocols were followed. In part 2, 31 international experts in women’s rugby (ie, elite players, sports scientists, medical clinicians, sports administrators) participated in a three-round Delphi consensus method. These experts reviewed the findings from part 1 and subsequently provided a list of priority research topics in women’s rugby. Research topics were grouped into expert-based themes and expert-based subthemes via content analysis. Expert-based themes and expert-based subthemes were ranked from very low to very high research priority on a 1–5 Likert scale. Consensus was defined by ≥70% agreement. The median research priority agreement and IQR were calculated for each expert-based theme and subtheme.Data sources PubMed (MEDLINE), Scopus and SPORTDiscus (EBSCOhost).Eligibility criteria for selecting studies Studies were eligible for inclusion if they investigated applied sports science or sports medicine in women’s rugby.Results In part 1, the systematic scoping review identified 123 studies, which were categorised into six sports science and sports medicine evidence-based themes: injury (n=48), physical performance (n=32), match characteristics (n=26), fatigue and recovery (n=6), nutrition (n=6), and psychology (n=5). In part 2, the Delphi method resulted in three expert-based themes achieving consensus on future research priority in women’s rugby: injury (5.0 (1.0)), female health (4.0 (1.0)) and physical performance (4.0 (1.0)).Summary/Conclusion This two-part systematic scoping review and Delphi consensus is the first study to summarise the applied sports science and sports medicine evidence base in women’s rugby and establish future research priorities. The summary tables from part 1 provide valuable reference information for researchers and practitioners. The three expert-based themes that achieved consensus in part 2 (injury, female health and physical performance) provide clear direction and guidance on future research priorities in women’s rugby. The findings of this two-part study facilitate efficient and coordinated use of scientific resources towards high-priority research themes relevant to a wide range of stakeholders in women’s rugby.

Abstract Background Insulin secretion from the pancreatic β-cell is finely modulated by different signals to allow an adequate control of glucose homeostasis. Incretin hormones such as glucagon-like peptide-1 (GLP-1) act as key physiological potentiators of insulin release through binding to the G protein-coupled receptor GLP-1R. Another key regulator of insulin signaling is the Ser/Thr kinase G protein-coupled receptor kinase 2 (GRK2). However, whether GRK2 affects insulin secretion or if GRK2 can control incretin actions in vivo remains to be analyzed. Results Using GRK2 hemizygous mice, isolated pancreatic islets, and model β-cell lines, we have uncovered a relevant physiological role for GRK2 as a regulator of incretin-mediated insulin secretion in vivo. Feeding, oral glucose gavage, or administration of GLP-1R agonists in animals with reduced GRK2 levels (GRK2+/− mice) resulted in enhanced early phase insulin release without affecting late phase secretion. In contrast, intraperitoneal glucose-induced insulin release was not affected. This effect was recapitulated in isolated islets and correlated with the increased size or priming efficacy of the readily releasable pool (RRP) of insulin granules that was observed in GRK2+/− mice. Using nanoBRET in β-cell lines, we found that stimulation of GLP-1R promoted GRK2 association to this receptor and that GRK2 protein and kinase activity were required for subsequent β-arrestin recruitment. Conclusions Overall, our data suggest that GRK2 is an important negative modulator of GLP-1R-mediated insulin secretion and that GRK2-interfering strategies may favor β-cell insulin secretion specifically during the early phase, an effect that may carry interesting therapeutic applications.

Nutrition strategies and supplements may have a role to play in diminishing exercise associated gastrointestinal cell damage and permeability. The aim of this systematic review was to determine the influence of dietary supplements on markers of exercise-induced gut endothelial cell damage and/or permeability. Five databases were searched through to February 2021. Studies were selected that evaluated indirect markers of gut endothelial cell damage and permeability in response to exercise with and without a specified supplement, including with and without water. Acute and chronic supplementation protocols were included. Twenty-seven studies were included. The studies investigated a wide range of supplements including bovine colostrum, glutamine, probiotics, supplemental carbohydrate and protein, nitrate or nitrate precursors and water across a variety of endurance exercise protocols. The majority of studies using bovine colostrum and glutamine demonstrated a reduction in selected markers of gut cell damage and permeability compared to placebo conditions. Carbohydrate intake before and during exercise and maintaining euhydration may partially mitigate gut damage and permeability but coincide with other performance nutrition strategies. Single strain probiotic strains showed some positive findings, but the results are likely strain, dosage and duration specific. Bovine colostrum, glutamine, carbohydrate supplementation and maintaining euhydration may reduce exercise-associated endothelial damage and improve gut permeability. In spite of a large heterogeneity across the selected studies, appropriate inclusion of different nutrition strategies could mitigate the initial phases of gastrointestinal cell disturbances in athletes associated with exercise. However, research is needed to clarify if this will contribute to improved athlete gastrointestinal and performance outcomes.

This study investigated differences in external training load between microcycle lengths and its variation between microcycles, players, and head coaches. Commonly used external training load variables including total-, high-speed- (5–7 m∙s-1), and sprint-distance (> 7 m∙s-1) alongside combined high acceleration and deceleration distance (> 2 m∙s-2). Which were also expressed relative to time were collected using microtechnology within a repeated measures design from 54 male rugby league players from one Super League team over four seasons. 4337 individual observations across ninety-one separate microcycles and six individual microcycle lengths (5 to 10 day) were included. Linear mixed effects models established the differences in training load between microcycle-length and the variation between-microcycles, players and head coaches. The largest magnitude of difference in training load was seen when comparing 5-day with 9-day (ES = 0.31 to 0.53) and 10-day (ES = 0.19 to 0.66) microcycles. The greatest number of differences between microcycles were observed in high- (ES = 0.3 to 0.53) and sprint-speed (ES = 0.2 to 0.42) variables. Between-microcycle variability ranged between 11% to 35% dependent on training load variable. Training load also varied between players (5–65%) and head coaches (6–20%) with most variability existing within high-speed (19–43%) and sprinting (19–65%). Overall, differences in training load between microcycle lengths exist, likely due to manipulation of session duration. Furthermore, training load varies between microcycle, player and head coach.

Participation in women’s rugby league has been growing since the foundation of the English women’s rugby league Super League in 2017. However, the evidence base to inform women’s rugby league remains sparse. This study provides the largest quantification of anthropometric and physical qualities of women’s rugby league players to date, identifying differences between positions (forwards & backs) and playing level (Women’s Super League [WSL] vs. International). The height, weight, body composition, lower body strength, jump height, speed and aerobic capacity of 207 players were quantified during the pre-season period. Linear mixed models and effects sizes were used to determine differences between positions and levels. Forwards were significantly (p < 0.05) heavier (forwards: 82.5 ± 14.8kg; backs: 67.7 ± 9.2kg) and have a greater body fat % (forwards: 37.7 ± 6.9%; backs: 30.4 ± 6.3%) than backs. Backs had significantly greater lower body power measured via jump height (forwards: 23.5 ± 4.4cm; backs: 27.6 ± 4.9cm), speed over 10m (forwards: 2.12 ± 0.14s; backs: 1.98 ± 0.11s), 20m (forwards: 3.71 ± 0.27s; backs: 3.46 ± 0.20s), 30m (forwards: 5.29 ± 0.41s; backs: 4.90 ± 0.33s), 40m (forwards: 6.91 ± 0.61s; backs: 6.33 ± 0.46s) and aerobic capacity (forwards: 453.4 ± 258.8m; backs: 665.0 ± 298.2m) than forwards. Additionally, international players were found to have greater anthropometric and physical qualities in comparison to their WSL counterparts. This study adds to the limited evidence base surrounding the anthropometric and physical qualities of elite women’s rugby league players. Comparative values for anthropometric and physical qualities are provided which practitioners may use to evaluate the strengths and weaknesses of players, informing training programs to prepare players for the demands of women’s rugby league.

BackgroundElite rugby players experience poor sleep quality and quantity. This lack of sleep could compromise post-exercise recovery. Therefore, it appears central to encourage sleep in order to improve recovery kinetics. However, the effectiveness of an acute ergogenic strategy such as sleep extension on recovery has yet to be investigated among athletes.AimTo compare the effects of a single night of sleep extension to an active recovery session (CON) on post-exercise recovery kinetics.MethodsIn a randomised cross-over design, 10 male rugby union players participated in two evening training sessions (19:30) involving collision activity, 7-days apart. After each session, participants either extended their sleep to 10 hours or attended an early morning recovery session (07:30). Prior to (PRE), immediately after (POST 0 hour [h]), 14h (POST 14) and 36h (POST 36) post training, neuromuscular, perceptual and cognitive measures of fatigue were assessed. Objective sleep parameters were monitored two days before the training session and over the two-day recovery period.ResultsThe training session induced substantial decreases in countermovement jump mean power and wellness across all time points, while heart rate recovery decreased at POST 0 in both conditions. Sleep extension resulted in greater total sleep time (effect size [90% confidence interval]: 5.35 [4.56 to 6.14]) but greater sleep fragmentation than CON (2.85 [2.00 to 3.70]). Between group differences highlight a faster recovery of cognitive performance following sleep extension (-1.53 [-2.33 to -0.74]) at POST 14, while autonomic function (-1.00 [-1.85 to -0.16]) and upper-body neuromuscular function (-0.78 [-1.65 to 0.08]) were better in CON. However, no difference in recovery status between groups was observed at POST 36.ConclusionThe main finding of this study suggests that sleep extension could affect cognitive function positively but did not improve neuromuscular function the day after a late exercise bout.