The cis-Regulatory Atlas of the Mouse Immune System.

A complete chart of cis-regulatory elements and their dynamic activity is necessary to understand the transcriptional basis of differentiation and function of an organ system. We generated matched epigenome and transcriptome measurements in 86 primary cell types that span the mouse immune system and its differentiation cascades. This breadth of data enable variance components analysis that suggests that genes fall into two distinct classes, controlled by either enhancer- or promoter-driven logic, and multiple regression that connects genes to the enhancers that regulate them. Relating transcription factor (TF) expression to the genome-wide accessibility of their binding motifs classifies them as predominantly openers or closers of local chromatin accessibility, pinpointing specific cis-regulatory elements where binding of given TFs is likely functionally relevant, validated by chromatin immunoprecipitation sequencing (ChIP-seq). Overall, this cis-regulatory atlas provides a trove of information on transcriptional regulation through immune differentiation and a foundational scaffold to define key regulatory events throughout the immunological genome.

Factors that affect handball execution in Australian Football.

A handball is one of two technical skills used to dispose of the ball in Australian Football. Previous research has only considered handball effectiveness in the analysis of team performance and there is a need to understand whether there are other more important characteristics of handball execution that explain effectiveness (i.e., performance). 1342 handballs from Australian Football League matches were analysed. Ten characteristic variables were created that represent the context and execution of each handball included in the analysis. A mixed effects generalised linear model was used to evaluate the effect of the (ten) characteristics on handball outcome. Three out of ten characteristics were associated with handball outcome, and these related to the posture of the handballer and the type of defensive pressure applied to the handballer and the receiver of the handball. These findings explain both how to increase handball effectiveness and how to reduce the handball effectiveness of an opposition team. Given the important role of handballing in passing sequences and maintaining ball possession, the practical application of these findings could enhance overall team performance.

Type 2 inflammation drives an airway basal stem cell program through insulin receptor substrate signaling.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2 (T2) inflammatory disease associated with an increased number of airway basal cells (BCs). Recent studies have identified transcriptionally distinct BCs, but the molecular pathways that support or inhibit human BC proliferation and differentiation are largely unknown. OBJECTIVE: We sought to determine the role of T2 cytokines in regulating airway BCs. METHODS: Single-cell and bulk RNA sequencing of sinus and lung airway epithelial cells was analyzed. Human sinus BCs were stimulated with IL-4 and IL-13 in the presence and absence of inhibitors of IL-4R signaling. Confocal analysis of human sinus tissue and murine airway was performed. Murine BC subsets were sorted for RNA sequencing and functional assays. Fate labeling was performed in a murine model of tracheal injury and regeneration. RESULTS: Two subsets of BCs were found in human and murine respiratory mucosa distinguished by the expression of basal cell adhesion molecule (BCAM). BCAM expression identifies airway stem cells among P63+KRT5+NGFR+ BCs. In the sinonasal mucosa, BCAMhi BCs expressing TSLP, IL33, CCL26, and the canonical BC transcription factor TP63 are increased in patients with CRSwNP. In cultured BCs, IL-4/IL-13 increases the expression of BCAM and TP63 through an insulin receptor substrate-dependent signaling pathway that is increased in CRSwNP. CONCLUSIONS: These findings establish BCAM as a marker of airway stem cells among the BC pool and demonstrate that airway epithelial remodeling in T2 inflammation extends beyond goblet cell metaplasia to the support of a BC stem state poised to perpetuate inflammation.

Understanding passing network characteristics and their link to match outcome in elite Netball.

Player interactions in Netball are critical during attacking phases of play to ensure possession is maintained and scoring opportunities are created. This study aims to analyse the characteristics of the passing networks of elite Netball teams and their association with performance outcomes (i.e., win/loss and final margin). Five network metrics used to represent the characteristics of teamwork were calculated for all team performances (n = 112) from one season of professional Netball in Australia. A two-way ANOVA and multiple linear modelling were used to compare characteristics between teams and match outcomes and to predict score margin, respectively. Pass density (F = 65.09, df = 102, p < .001) and pass centrality (F = 7.61, df = 102, p < .01) differed (were higher) in wins/losses. They were also statistically significant contributors (p ≤ .005) to the linear model that predicted a score margin (R2 = .731). Key player centrality and mutual connectedness were different between teams but did not differ by match outcome. The results suggest that, ideally, Netball teams should maximise the number of connections between player pairings, while also relying on a subset of players to be heavily involved in passing sequences. Team cohesion (via passing) therefore appears to be an important measure of team success in elite Netball.

Real time prediction of match outcomes in Australian football.

This study aimed to determine whether machine learning models based on technical performance and not score margin could be used to predict end-of-match outcome of Australian football matches in real-time. If efficacious, these models could be used to generate insights about team performance and support the decision-making of coaches during matches. A database of 168 team technical performance indicators from 829 Australian Football League matches played between 2017 and 2021 was used. Two feature sets (data-driven and data-informed) were used to train and evaluate six models (generalised linear model, random forest and adaboost) on match outcome prediction (Win/Loss) over 120 epochs (a representation of normalised time during each match). All models performed well (mean classification accuracy = 73.5-75.8%) in comparison with a benchmark score-based model (mean classification accuracy = 77.4%). Data-informed feature sets performed better than data-driven in most cases. Classification accuracy was low at the start of a match (45.7-48.8%) but increased to a peak near the end of a match (87.2-92.7%). These findings suggest that any of the employed models can be used to formulate in-match decision support. The model which is best in practice will depend on factors such as time-cost trade-off, feasibility and the perceived value of its suggestions.

Is injury associated with team performance in elite Australian football? 20 years of player injury and team performance data that include measures of individual player value.

OBJECTIVES: To determine whether specific injury measures were associated with team performance in the Australian Football League (AFL). METHODS: 15 289 injuries caused players from 18 teams to miss 51 331 matches between 1997 and 2016. Data were aggregated to the team level. We analysed the associations among injury measures and team performance (reaching finals/playoffs and specific ladder/table position). Injury measures per team included: injury incidence, injury severity, injury burden, player match availability and percentage of the full player roster injured. We also weighted injury measures by five measures of player value. RESULTS: AFL teams' injury burden and player match availability were associated with final table position (r2=0.03, p<0.05). Player value weighted injury burden was different between finalists and non-finalists (mean difference=-8, p<0.001) and explained 12% of the variation in the table position of teams (p<0.001). For a team, nine missed matches due to injury (burden weighted by a best and fairest player rating system) was associated with one lower table position. Player match availability weighted by player value was higher for finalists than non-finalists (mean difference=1.7, p<0.01) and explained 7% of the variation in the table position of teams (p<0.001). DISCUSSION AND POTENTIAL IMPLICATIONS: The impact of injury (burden weighted by best and fairest) explained up to 12% of the variation in final table position-this is particularly relevant to making/not making playoffs as well as home ground/travel advantages for those teams that make the one-game format of AFL playoffs (not home-away or best of seven format).

Performance analysis and prediction in triathlon.

Performance in triathlon is dependent upon factors that include somatotype, physiological capacity, technical proficiency and race strategy. Given the multidisciplinary nature of triathlon and the interaction between each of the three race components, the identification of target split times that can be used to inform the design of training plans and race pacing strategies is a complex task. The present study uses machine learning techniques to analyse a large database of performances in Olympic distance triathlons (2008-2012). The analysis reveals patterns of performance in five components of triathlon (three race "legs" and two transitions) and the complex relationships between performance in each component and overall performance in a race. The results provide three perspectives on the relationship between performance in each component of triathlon and the final placing in a race. These perspectives allow the identification of target split times that are required to achieve a certain final place in a race and the opportunity to make evidence-based decisions about race tactics in order to optimise performance.

Induced Alkalosis and Gastrointestinal Symptoms After Sodium Citrate Ingestion: a Dose-Response Investigation.

Sodium citrate induces alkalosis and can provide a performance benefit in high-intensity exercise. Previous investigations have been inconsistent in the ingestion protocols used, in particular the dose and timing of ingestion before the onset of exercise. The primary aim of the current study was to quantify blood pH, blood bicarbonate concentration and gastrointestinal symptoms after ingestion of three doses of sodium citrate (500 mg⋅kg-1, 700 mg⋅kg-1 and 900 mg⋅kg-1). Thirteen participants completed four experimental sessions, each consisting of a different dose of sodium citrate or a taste-matched placebo solution. Blood pH and blood bicarbonate concentration were measured at 30-min intervals via analysis of capillary blood samples. Gastrointestinal symptoms were also monitored at 30-min intervals. Statistical significance was accepted at a level of p < .05. Both measures of alkalosis were significantly greater after ingestion of sodium citrate compared with placebo (p < .001). No significant differences in alkalosis were found between the three sodium citrate doses (p > .05). Peak alkalosis following sodium citrate ingestion ranged from 180 to 212 min after ingestion. Gastrointestinal symptoms were significantly higher after sodium citrate ingestion compared with placebo (p < .001), while the 900 mg.kg-1 dose elicited significantly greater gastrointestinal distress than 500 mg⋅kg-1 (p = .004). It is recommended that a dose of 500 mg⋅kg-1 of sodium citrate should be ingested at least 3 hr before exercise, to achieve peak alkalosis and to minimize gastrointestinal symptoms before and during exercise.

Mast cells recruited to mesenteric lymph nodes during helminth infection remain hypogranular and produce IL-4 and IL-6.

Mast cells (MC) and basophils share expression of the high-affinity receptor for IgE (FcεRI) but can be distinguished by their divergent expression of KIT and CD49b. In BALB/c mice, MC lineage cells expressing high levels of FcεRI by flow cytometry were seen only in bone marrow whereas those expressing intermediate levels of FcεRI were present in bone marrow and spleen of naive mice and in mesenteric lymph nodes (mLN) of Trichinella spiralis-infected mice. These FcεRI(+)KIT(+)CD49b(-) cells had a membrane phenotype similar to i.p. connective tissue-type MC, but were smaller and hypogranular by flow cytometry forward and side scatter profiles, respectively. Consistent with this, they lacked the prominent secretory granules identified by histochemistry and immunodetection for the MC-specific granule proteases that are readily seen in mature jejunal mucosal MC that also are induced by the infection and present at the same time. The concentration of these MC lineage cells in mLN determined by flow cytometry was comparable to that of MC progenitors (MCp) measured by limiting dilution and clonal expansion with maturation. We observed upregulation of IL-4 transcription by MCp in mLN and spleens of helminth-infected 4get mice, and we demonstrated by intracellular cytokine staining production of IL-4 and IL-6 by the mLN MCp in helminth-infected mice. Furthermore, treatment of helminth-infected mice with anti-FcεRI mAb, a protocol known to deplete basophils, also depleted mLN MCp. Thus, this study identifies a hypogranular subset of MCp recruited to mLN by helminth infection that may be an important unrecognized source of cytokines.

Shots at goal in Australian Football: Historical trends, determinants of accuracy and common strategies.

OBJECTIVES: To understand the historical context of and relationships between, the characteristics of shots at goal and match outcome in the Australian Football League. DESIGN: Observational. METHODS: Descriptive statistics of shots at goal were calculated and compared across 20 seasons. The location, type, and outcome of all shots at goal (n = 43,254), by all teams (2017-19 & 21), were compared with match outcome. RESULTS: The total number of shots per match and the accuracy of shots haven't changed in two decades. Most teams win by having more shots at goal (Wilcoxon-r effect size 0.63) than their opponent (i.e. "majority strategy") and of these, the number of open shots (0.48) is slightly more important than set shots (0.43), followed by shot accuracy (0.29). However, some teams (14 %) win by taking fewer shots at goal from field locations with a higher likelihood of scoring a goal (i.e. "minority strategy"). Arc angle and shot type can be used to predict the outcome of a shot at goal with 60.3 % classification accuracy. The novel shot-outcome prediction model reported here provides a better opportunity to evaluate goal kicking performance of teams and players, because it accounts for the type and difficulty of the shot. CONCLUSIONS: Teams can evaluate the shot accuracy of their players more fairly, by accounting for shot location using the method reported here. Coaches can compare the two shot strategies identified and implement the one that suits the skill profile of their players and increase their likelihood of winning.

Modelling and analysing track cycling Omnium performances using statistical and machine learning techniques.

This article describes the utilisation of an unsupervised machine learning technique and statistical approaches (e.g., the Kolmogorov-Smirnov test) that assist cycling experts in the crucial decision-making processes for athlete selection, training, and strategic planning in the track cycling Omnium. The Omnium is a multi-event competition that will be included in the summer Olympic Games for the first time in 2012. Presently, selectors and cycling coaches make decisions based on experience and intuition. They rarely have access to objective data. We analysed both the old five-event (first raced internationally in 2007) and new six-event (first raced internationally in 2011) Omniums and found that the addition of the elimination race component to the Omnium has, contrary to expectations, not favoured track endurance riders. We analysed the Omnium data and also determined the inter-relationships between different individual events as well as between those events and the final standings of riders. In further analysis, we found that there is no maximum ranking (poorest performance) in each individual event that riders can afford whilst still winning a medal. We also found the required times for riders to finish the timed components that are necessary for medal winning. The results of this study consider the scoring system of the Omnium and inform decision-making toward successful participation in future major Omnium competitions.

Force-velocity profiles of track cyclists differ between seated and non-seated positions.

The aim of the study was to compare the Force-Velocity profiles of track sprint cyclists obtained in seated and non-seated positions. Athletes were tested on a stationary cycle ergometer for the seated position and on a racing bike at the velodrome for the non-seated position. We modelled torque and power vs. cadence relationships and extracted maximal force (F0), optimal cadence (Copt), maximal power (Pmax), maximal cadence (C0) and Copt/C0 ratio. Torque/power production was larger in the non-seated position for cadences ranging from 20 to 120 rpm, while more torque and power were produced in the seated position at cadences above 160 rpm. The effective pedal force increased by 0.2 times bodyweight at 50 rpm, and the power production increased by 2.5 W. kg-1 at 90 rpm in the non-seated position. Copt (-14 ± 8 rpm, P < 0.05) and C0 (-55 ± 32 rpm, P < 0.05) were lowered, while Pmax (+1.7 ± 1.1 W. kg-1, P < 0.05) and Copt/C0 ratios (+0.07 ± 0.04, P < 0.05) were increased in the non-seated position when compared with the seated position. Our results show that adopting a non-seated position allows sprint cyclists to maximise torque/power production at lower cadences, while torque/power production was maximised at higher cadences when athletes adopted a seated position.

A framework to explain the in-match decision-making of elite Australian football coaches.

The ability to make effective decisions is an important function of any football coach, whether during training, team selection, match-day performance or post-match player evaluation. It is not yet known how elite Australian football coaches make decisions during matches, in time-constrained but well-resourced environments. This study is the first to explore the decision-making of elite Australian football coaches during matches, in pursuit of identifying opportunities to improve the translation and implementation of research findings into the competitive match environment. Using semi-structured interviews and thematic analysis, a six-stage framework of the decision-making of elite Australian football coaches during matches was developed. The stages include (1) Opportunity trigger, (2) Understand the opportunity, (3) Determine the need for action, (4) Explore options, (5) Take action and (6) Evaluate the decision. Coaches relied on subjective and objective sources of information and consulted with assistant coaches, performance analysts, and sport scientists. The findings enable researchers to ensure future interventions to improve decision-making during matches are well integrated. They also provide an opportunity for coaches to reflect on their own decision-making process, identifying targeted areas for improvement in their own practice.

Global positioning system data analysis: velocity ranges and a new definition of sprinting for field sport athletes.

Global positioning system (GPS) technology has improved the speed, accuracy, and ease of time-motion analyses of field sport athletes. The large volume of numerical data generated by GPS technology is usually summarized by reporting the distance traveled and time spent in various locomotor categories (e.g., walking, jogging, and running). There are a variety of definitions used in the literature to represent these categories, which makes it nearly impossible to compare findings among studies. The purpose of this work was to propose standard definitions (velocity ranges) that were determined by an objective analysis of time-motion data. In addition, we discuss the limitations of the existing definition of a sprint and present a new definition of sprinting for field sport athletes. Twenty-five GPS data files collected from 5 different sports (men's and women's field hockey, men's and women's soccer, and Australian Rules Football) were analyzed to identify the average velocity distribution. A curve fitting process was then used to determine the optimal placement of 4 Gaussian curves representing the typical locomotor categories. Based on the findings of these analyses, we make recommendations about sport-specific velocity ranges to be used in future time-motion studies of field sport athletes. We also suggest that a sprint be defined as any movement that reaches or exceeds the sprint threshold velocity for at least 1 second and any movement with an acceleration that occurs within the highest 5% of accelerations found in the corresponding velocity range. From a practical perspective, these analyses provide conditioning coaches with information on the high-intensity sprinting demands of field sport athletes, while also providing a novel method of capturing maximal effort, short-duration sprints.

Reliability of live and video-based coding in netball using the NetballStats application.

Understanding reliability of performance analysis tools is important to ensure match to match comparisons can be undertaken with the knowledge of consistency between coding situations. There are few published studies examining the reliability of commonly used performance analysis tools. The aim of this project was to assess the inter- and intra-rater reliability of the NetballStats application and to make comparisons between live and video-based coding situations. Two 'coders' coded eight netball matches using the NetballStats application, coding each match live, then twice from video. Level of agreement was assessed for frequency counts across the variables coded. Results showed that intra-rater agreement was higher than inter-rater agreement and that reliability from video coding is better than from live coding. High frequency events automatically coded by the application and events that are well defined had greater levels of agreement than lower frequency events and subjectively judged events. Live coding situations underrepresent occurrence of events, particularly for high frequency events such as 'possession'. To ensure reliability between coders, clubs should provide an extensive training program to coders with clear instructions on coding subjective events. Coaches should be aware that live coding underestimates some event types and factor this into their decision making processes.

Understanding load in netball - An analysis of multiple seasons, phases, and teams.

Studies of training and competition load in sport are usually based on data that represents a sample of a league and or annual training program. These studies sometimes explore important factors that are affected by load, such as training adaptations and injury risk. The generalisability of the conclusions of these studies, can depend on how much load varies between seasons, training phases and teams. The interpretation of previous load studies and the design of future load studies should be influenced by an understanding of how load can vary across seasons, training phases and between teams. The current study compared training loads (session rating of perceived exertion x session duration) between all (8) teams in an elite Netball competition for multiple (2) season phases and (2) seasons. A total of 29,545 records of athlete session training loads were included in the analysis. Linear mixed models identified differences between seasons and training phases (p < .05). There were also differences between teams and a complex set of interactions between these three factors (season, phase, and team) (p < .05). While the absolute value of the training loads reported here are only relevant to elite netball, these results illustrate that when data is sampled from a broader context, the range and variation in load may increase. This highlights the importance of cautiously interpreting and generalisation of findings from load studies that use limited data sets.

The effect of team formation on defensive performance in Australian football.

OBJECTIVES: Understanding the successful characteristics of team formation during different scenarios in Australian Football matches can assist coaches in making important tactical match-day and training decisions. The aims of this study were to explore the outcomes of entries inside 50 m of the goal, in Australian Football and to determine whether there was an association between team formation and team defensive performance after a turnover. DESIGN: Observational. METHODS: Global Positioning System (GPS) data, technical event data and video files from 22 matches in one season were obtained from an elite Australian Football club. Of 1092 forward 50 entries, 392 possession chains that resulted in a turnover were analysed. Variables representing team formation of players at the occurrence of turnover were compared between positive and negative outcomes of the subsequent possession chain. Logistic regression and decision tree modelling were also used to explore associations and variable importance. RESULTS: None of 18 team formation characteristics differed between positive and negative outcomes of turnovers. Multivariate modelling identified that having a team formation with greater width than length made it more likely to result in a positive outcome (Decision tree classification accuracy = 69.5%, AUROC = 0.72). CONCLUSIONS: No single characteristic of team formation affects the outcome of a turnover possession chain, however team formation that was wider than it was long may be associated with a more desirable outcome. The lack of association between most team formation characteristics and defensive outcomes, highlight the risk of over emphasising team formation in tactical planning for some phases of play.

The Physical Differences Between Faster and Slower Elite Male and Female Pace Bowlers.

PURPOSE: This study investigated the differences between selected physical attributes and ball release speed in slower and faster male and female elite pace bowlers. METHODS: Twelve physical attributes and ball release speed were retrospectively analyzed from 63 male and 31 female elite pace bowlers over the course of 5 seasons. Pace bowlers were categorized as either fast (>122.9 km/h, males and >97.8 km/h, females) or slow (<122.9 km/h, males and <97.8 km/h, females) for each sex. Differences in physical attributes between slower and faster bowling groups were compared using Cohen d effect sizes. RESULTS: Faster pace bowlers displayed differences in isometric midthigh-pull peak force (d = 0.25, males and d = 0.68, females) and relative peak force (d = 0.62, males and d = 0.77, females). Faster male pace bowlers displayed differences in relative (d = 0.61) and absolute (d = 0.39) countermovement jump heights. Faster female pace bowlers displayed differences in 1-repetition-maximum bench-pull strength (d = 0.45) and run-of-3 performance (relative average, d = 1.22; relative best, d = 1.12; average, d = 0.49; and best, d = 0.40). CONCLUSIONS: Anaerobic dominant physical attributes appear to be important in both male and female pace bowlers. The contribution of these physical attributes to ball release speed appears to differ slightly between males and females. Lower-body strength (males and females), lower-body power (males), relative anaerobic capacities (females), and upper-body strength (females) appear to distinguish between slower and faster elite pace bowlers.

The Physical Qualities of Elite Australian Pace Bowlers: Typical Characteristics and Longitudinal Changes in Men and Women.

PURPOSE: To determine whether the most important physical qualities in elite Australian male and female cricket pace bowlers change with age and phase of the cricket season. METHODS: An existing longitudinal database (7 cricket seasons) of selected and routinely collected physical testing data from 103 male and 58 female elite Australian pace bowlers age 18-30 years was retrospectively analyzed. Male and female physical testing data from the isometric midthigh pull, 1-repetition-maximum bench pull, run-of-3, and countermovement jump (male only) were analyzed separately by performing linear mixed models on each of the physical qualities. Type III analysis-of-variance tests were conducted to determine if a significant effect existed within the fixed effects of age, season phase, and the age × season phase interaction. Appropriate pairwise comparisons were conducted. RESULTS: Absolute and relative measures of force in the isometric midthigh pull and strength in the 1-repetition-maximum bench pull tests were significantly greater in older male and female pace bowlers. Older male pace bowlers demonstrated significantly faster absolute and relative best run-of-3 times. CONCLUSIONS: Most physical qualities across both male and female pace bowlers demonstrated an improvement with age. This is likely due to a training effect and would be anticipated to lead to a gradual enhancement of ball release speed, in accordance with previous research. Future research should look to investigate the relationship between the development of physical qualities and ball release speed among elite male and female pace bowlers.

Considerations for the use of salivary IgA for monitoring mucosal immune function.

INTRODUCTION: We aimed to make recommendations concerning the use of total IgA in saliva (s-IgA) as an aid for monitoring athletic and military training. METHODS: Unstimulated whole saliva was collected from 16 subjects (11 women and 5 men ages 18-57) during nonconsecutive days of fasting and non-fasting. Seven samples were collected from each subject at 0700, 0900, 1200, 1400, 1600, 1800, and 2030 on each day and a further three samples were collected 30 min after three meals on the non-fasting day (at 0730, 1230, and 1830). Strenuous activity was avoided and subjects did not drink caffeine or alcohol-containing beverages. Albumin and s-IgA were measured by commercial nephelometric immunoassays with intra-analytical coefficient of variance (CVA) of 1.8% and 2.9%, respectively. Individual and group variations were determined. Diurnal variation was determined by use of repeated-measures analysis of variance. RESULTS: CV-individual (CV(I)) was 48% for s-IgA concentration and 43% for s-IgA secretion and s-IgA:albumin. CV-group (CVG) for these same measures was 68%, 75%, and 68%, respectively. When measurements were adjusted for saliva flow rates there was no evidence that s-IgA is subject to diurnal variation. There was strong evidence for a postprandial decrease in s-IgA for all measures. CONCLUSION: The high degree of individuality in s-IgA precludes the use of population reference ranges for identifying individual abnormal results. For the purpose of monitoring individuals we recommend using the individual's calculated biological variance (determined from previous serial measurements over a period of days to weeks). Individual abnormal results can then be identified.