Role of beta-(1→3)(1→6)-D-glucan derived from yeast on natural killer (NK) cells and breast cancer cell lines in 2D and 3D cultures.

BACKGROUND: Beta-(1,3)(1,6)-D-glucan is a complex polysaccharide, which is found in the cell wall of various fungi, yeasts, bacteria, algae, barley, and oats and has immunomodulatory, anticancer and antiviral effects. In the present study, we investigated the effect of beta-(1,3)(1,6)-D-glucan derived from yeast on the proliferation of primary NK cells and breast cancer cell lines in 2D and 3D models, and on the cytotoxicity of primary NK cells against breast cancer cell lines in 2D and 3D models. METHODS: In this study, we investigated the effects of different concentrations of yeast-derived beta-(1→3)(1→6)-D-glucan on the proliferation and cytotoxicity of human NK cells and breast cancer cell lines in 2D and 3D models using the XTT cell proliferation assay and the CellTiter-Glo® 2.0 assay to determine the cytotoxicity of human NK cells on breast cancer cell lines in 2D and 3D models. RESULTS: We found that the co-incubation of NK cells with beta-glucan in the absence of IL2 at 48 h significantly increased the proliferation of NK cells, whereas the co-incubation of NK cells with beta-glucan in the presence of IL2 (70 U/ml) increased the proliferation of NK cells but not significantly. Moreover, beta-glucan significantly inhibited the proliferation of breast cancer cell lines in 2D model and induced a weak, non-significant growth inhibitory effect on breast cancer multicellular tumor spheroids (3D). In addition, the cytotoxicity of NK cells against breast cancer cell lines was examined in 2D and 3D models, and beta-glucan significantly increased the cytotoxicity of NK cells against MCF-7 (in 2D). CONCLUSIONS: Yeast derived beta-(1,3)(1,6)-D-glucan could contribute to the treatment of cancer by enhancing NK cell immune response as well as contributing to inhibition of breast cancer cell growth.

Next Generation CD44v6-Specific CAR-NK Cells Effective against Triple Negative Breast Cancer.

There is a medical need to develop new and effective therapies against triple-negative breast cancer (TNBC). Chimeric antigen receptor (CAR) natural killer (NK) cells are a promising alternative to CAR-T cell therapy for cancer. A search for a suitable target in TNBC identified CD44v6, an adhesion molecule expressed in lymphomas, leukemias and solid tumors that is implicated in tumorigenesis and metastases. We have developed a next-generation CAR targeting CD44v6 that incorporates IL-15 superagonist and checkpoint inhibitor molecules. We could show that CD44v6 CAR-NK cells demonstrated effective cytotoxicity against TNBC in 3D spheroid models. The IL-15 superagonist was specifically released upon recognition of CD44v6 on TNBC and contributed to the cytotoxic attack. PD1 ligands are upregulated in TNBC and contribute to the immunosuppressive tumor microenvironment (TME). Competitive inhibition of PD1 neutralized inhibition by PD1 ligands expressed on TNBC. In total, CD44v6 CAR-NK cells are resistant to TME immunosuppression and offer a new therapeutic option for the treatment of BC, including TNBC.

RNAi-based small molecule repositioning reveals clinically approved urea-based kinase inhibitors as broadly active antivirals.

Influenza viruses (IVs) tend to rapidly develop resistance to virus-directed vaccines and common antivirals targeting pathogen determinants, but novel host-directed approaches might preclude resistance development. To identify the most promising cellular targets for a host-directed approach against influenza, we performed a comparative small interfering RNA (siRNA) loss-of-function screen of IV replication in A549 cells. Analysis of four different IV strains including a highly pathogenic avian H5N1 strain, an influenza B virus (IBV) and two human influenza A viruses (IAVs) revealed 133 genes required by all four IV strains. According to gene enrichment analyses, these strain-independent host genes were particularly enriched for nucleocytoplasmic trafficking. In addition, 360 strain-specific genes were identified with distinct patterns of usage for IAVs versus IBV and human versus avian IVs. The strain-independent host genes served to define 43 experimental and otherwise clinically approved drugs, targeting reportedly fourteen of the encoded host factors. Amongst the approved drugs, the urea-based kinase inhibitors (UBKIs) regorafenib and sorafenib exhibited a superior therapeutic window of high IV antiviral activity and low cytotoxicity. Both UBKIs appeared to block a cell signaling pathway involved in IV replication after internalization, yet prior to vRNP uncoating. Interestingly, both compounds were active also against unrelated viruses including cowpox virus (CPXV), hantavirus (HTV), herpes simplex virus 1 (HSV1) and vesicular stomatitis virus (VSV) and showed antiviral efficacy in human primary respiratory cells. An in vitro resistance development analysis for regorafenib failed to detect IV resistance development against this drug. Taken together, the otherwise clinically approved UBKIs regorafenib and sorafenib possess high and broad-spectrum antiviral activity along with substantial robustness against resistance development and thus constitute attractive host-directed drug candidates against a range of viral infections including influenza.

Baseline SCAT Performance in Men and Women: Comparison of Baseline Concussion Screens Between 6288 Elite Men's and 764 Women's Rugby Players.

OBJECTIVE: This study compared Sports Concussion Assessment Tool (SCAT) performance in elite male (6288 players) and female (764 players) rugby players, to determine whether reference limits used for the management and diagnosis of concussion should differ between sexes. DESIGN: Cross-sectional census sample. SETTING: Data from World Rugby's Head Injury Assessment management system were analyzed. This data set covers global professional rugby. PARTICIPANTS: All professional players who underwent baseline SCAT testing as part of World Rugby's concussion management requirement formed the study cohort. Ten thousand seven hundred fifty-four SCAT assessments from 6288 elite male rugby players and 1071 assessments from 764 elite female players were analyzed. INTERVENTION: Elite men and women rugby players are independent variables. MAIN OUTCOME MEASURES: Sports Concussion Assessment Tool performance, including symptoms endorsed, cognitive submode performance, and balance performance. RESULTS: Women endorsed significantly more symptoms, with greater symptom severity, than men (relative ratio 1.34, 95% confidence interval, 1.25-1.45 women vs men). Women outperformed men in cognitive submodes with the exception of immediate memory and delayed recall and made fewer balance errors than men during the modified Balance Error Scoring System. Clinical reference limits, defined as submode score achieved by the worst-performing 50% of the cohort, did not differ between men and women. CONCLUSIONS: Women and men perform differently during SCAT baseline testing, although differences are small and do not affect either the baseline or clinical reference limits that identify abnormal test results for most submodes. The greater endorsement of symptoms by women suggests increased risk of adverse concussion outcomes and highlights the importance of accurate evaluation of any symptom endorsement at baseline.

Sport Concussion Assessment Tool: Fifth Edition Normative Reference Values for Professional Rugby Union Players.

OBJECTIVE: To describe distributions and establish normative ranges for new or changed subcomponents of the Sports Concussion Assessment Tool (SCAT)-5. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Professional Rugby Union players performing 2017 preseason baseline SCAT-5 testing. INDEPENDENT VARIABLES: Subcomponent tests newly introduced or changed in the SCAT-5. MAIN MEASUREMENTS: The 10-word immediate and delayed recall tests and the rapid neurological screen. RESULTS: Thousand two hundred three players were included in complete case analyses. The 10-word immediate recall test [median score 15, interquartile range (IQR) 15-22, range 3-30] showed an asymmetrical, bimodal distribution. The delayed recall test (median score 7, IQR 5-9, range 0-10) demonstrated a left skewed distribution. The diplopia and reading/following instruction tests of the neurological screen were performed normally by virtually all participants (98.5% and 99.6%, respectively). Normative classification ranges for each SCAT-5 subcomponents of interest were determined. CONCLUSIONS: The increased spread of scores, with improved midrange centering, suggests that the increase to 10-word list lengths should improve the performance of immediate and delayed recall tests. Normative ranges will provide a distribution against which postinjury SCAT-5 scores can be compared and interpreted.

Tackling concussion in professional rugby union: a case-control study of tackle-based risk factors and recommendations for primary prevention.

BACKGROUND/AIM: Concussion, the most common injury in professional rugby union, occurs most commonly during the tackle. Thus, we investigated the association between tackle characteristics and concussion. METHODS: 182 video clips of tackles leading to clinically diagnosed concussion and 4619 tackles that did not were coded across three professional rugby union competitions. A variable selection process was undertaken to identify the most important variables for interpretation. A multivariate generalised linear model was used to model the association between retained variables and concussion risk. Magnitude-based inferences provided an interpretation of the real-world relevance of the outcomes. RESULTS: The four retained variables were: accelerating player, tackler speed, head contact type and tackle type. Overall, 70% of concussions occurred to the tackler and 30% to the ball carrier. There was a higher risk of concussion if the tackler accelerated into the tackle (OR: 2.49, 95% CI 1.70 to 3.64) or the tackler was moving at high speed (OR: 2.64, 95% CI 1.92 to 3.63). Head contact with the opposing player's head (OR: 39.9, 95% CI 22.2 to 71.1) resulted in a substantially greater risk of concussion compared with all other head contact locations. CONCLUSIONS: Interventions that reduce the speed and acceleration of the tackler and reduce exposure to head-to-head contact would likely reduce concussion risk in professional rugby union.

International consensus definitions of video signs of concussion in professional sports.

BACKGROUND: The use of video to assist professional sporting bodies with the diagnosis of sport-related concussion (SRC) has been well established; however, there has been little consistency across sporting codes with regards to which video signs should be used, and the definitions of each of these signs. AIM: The aims of this study were to develop a consensus for the video signs considered to be most useful in the identification of a possible SRC and to develop a consensus definition for each of these video signs across the sporting codes. METHODS: A brief questionnaire was used to assess which video signs were considered to be most useful in the identification of a possible concussion. Consensus was defined as >90% agreement by respondents. Existing definitions of these video signs from individual sports were collated, and individual components of the definitions were assessed and ranked. A modified Delphi approach was then used to create a consensus definition for each of the video signs. RESULTS: Respondents representing seven sporting bodies (Australian Football League, Cricket Australia, Major League Baseball, NFL, NHL, National Rugby League, World Rugby) reached consensus on eight video signs of concussion. Thirteen representatives from the seven professional sports ranked the definition components. Consolidation and refinement of the video signs and their definitions resulted in consensus definitions for six video signs of possible concussion: lying motionless, motor incoordination, impact seizure, tonic posturing, no protective action-floppy and blank/vacant look. CONCLUSIONS: These video signs and definitions have reached international consensus, are indicated for use by professional sporting bodies and will form the basis for further collaborative research.

International study of video review of concussion in professional sports.

BACKGROUND: Video review has become an important tool in professional sporting codes to help sideline identification and management of players with a potential concussion. AIM: To assess current practices related to video review of concussion in professional sports internationally, and compare protocols and diagnostic criteria used to identify and manage potential concussions. METHODS: Current concussion management guidelines from professional national and international sporting codes were reviewed. Specific criteria and definitions of video signs associated with concussion were compared between codes. Rules and regulations adopted across the codes for processes around video review were also assessed. RESULTS: Six sports with specific diagnostic criteria and definitions for signs of concussion identified on video review participated in this study (Australian football, American football, world rugby, cricket, rugby league and ice hockey). Video signs common to all sports include lying motionless/loss of responsiveness and motor incoordination. The video signs considered by the majority of sports as most predictive of a diagnosis of concussion include motor incoordination, impact seizure, tonic posturing and lying motionless. Regulatory requirements, sideline availability of video, medical expertise of video reviewers and use of spotters differ across sports and geographical boundaries. By and large, these differences reflect a pragmatic approach from each sport, with limited underlying research and development of the video review process in some instances. CONCLUSIONS: The use of video analysis in assisting medical staff with the diagnosis or identification of potential concussion is well established across different sports internationally. The diagnostic criteria used and the expertise of the video review personnel are not clearly established, and research efforts would benefit from a collaborative harmonisation across sporting codes.

Implementation of the 2017 Berlin Concussion in Sport Group Consensus Statement in contact and collision sports: a joint position statement from 11 national and international sports organisations.

The 2017 Berlin Concussion in Sport Group Consensus Statement provides a global summary of best practice in concussion prevention, diagnosis and management, underpinned by systematic reviews and expert consensus. Due to their different settings and rules, individual sports need to adapt concussion guidelines according to their specific regulatory environment. At the same time, consistent application of the Berlin Consensus Statement's themes across sporting codes is likely to facilitate superior and uniform diagnosis and management, improve concussion education and highlight collaborative research opportunities. This document summarises the approaches discussed by medical representatives from the governing bodies of 10 different contact and collision sports in Dublin, Ireland in July 2017. Those sports are: American football, Australian football, basketball, cricket, equestrian sports, football/soccer, ice hockey, rugby league, rugby union and skiing. This document had been endorsed by 11 sport governing bodies/national federations at the time of being published.

Eight-season epidemiological study of injuries in men's international Under-20 rugby tournaments.

The aim of this study was to define the incidence and nature of match injuries sustained in men's international under-20 rugby. The study comprised an 8-season prospective study of 16 international under-20 rugby tournaments. Procedures complied with the consensus statement for epidemiological studies in rugby. Outputs included players' mean age, stature and body mass and incidence, severity, location, type and cause of match injuries. The overall incidence of injury was 49.7 injuries/1000 player-match-hours (backs: 48.3; forwards: 50.9) with a mean severity of 32.2 days-absence (backs: 29.4; forwards: 34.4). There were no significant changes in incidence or severity of injury over the study period. Shoulder/clavicle (18.3%), head/face (16.4%), knee (13.7%) and ankle (13.7%) were the most common injury locations and ligament sprain (35.4%), haematoma/bruise (15.9%), concussion (12.5%) and muscle strain (11.2%) the most common types of injury. Being-tackled (29.2%), tackling (24.0%) and collisions (14.3%) were the most common events leading to injury. The results confirm that international under-20 rugby has a high incidence and severity of injury but the incidence is half that reported for senior international players. There was no significant change in the overall incidence of injury at the Under-20 level in the period 2008 to 2016.

Herpesviral capture of immunomodulatory host genes.

Herpesviruses have acquired numerous genes from their hosts. Although these homologs are not essential for viral replication, they often have important immunomodulatory functions that ensure viral persistence in the host. Some of these viral molecules are called virokines as they mimic cellular cytokines of their host such as interleukin-10 (cIL-10). In recent years, many viral homologs of IL-10 (vIL-10s) have been discovered in the genome of members of the order Herpesvirales. For some, gene and protein structure as well as biological activity and potential use in the clinical context have been explored. Besides virokines, herpesviruses have also captured genes encoding membrane-bound host immunomodulatory proteins such as major histocompatibility complex (MHC) molecules. These viral MHC mimics also retain many of the functions of the cellular genes, in particular directly or indirectly modulating the activity of natural killer cells. The mechanisms underlying capture of cellular genes by large DNA viruses are still enigmatic. In this review, we provide an update of the advances in the field of herpesviral gene piracy and discuss possible scenarios that could explain how the gene transfer from host to viral genome was achieved.

Elevated hepatic 11ß-hydroxysteroid dehydrogenase type 1 induces insulin resistance in uremia.

Insulin resistance and associated metabolic sequelae are common in chronic kidney disease (CKD) and are positively and independently associated with increased cardiovascular mortality. However, the pathogenesis has yet to be fully elucidated. 11ß-Hydroxysteroid dehydrogenase type 1 (11ßHSD1) catalyzes intracellular regeneration of active glucocorticoids, promoting insulin resistance in liver and other metabolic tissues. Using two experimental rat models of CKD (subtotal nephrectomy and adenine diet) which show early insulin resistance, we found that 11ßHSD1 mRNA and protein increase in hepatic and adipose tissue, together with increased hepatic 11ßHSD1 activity. This was associated with intrahepatic but not circulating glucocorticoid excess, and increased hepatic gluconeogenesis and lipogenesis. Oral administration of the 11ßHSD inhibitor carbenoxolone to uremic rats for 2 wk improved glucose tolerance and insulin sensitivity, improved insulin signaling, and reduced hepatic expression of gluconeogenic and lipogenic genes. Furthermore, 11ßHSD1(-/-) mice and rats treated with a specific 11ßHSD1 inhibitor (UE2316) were protected from metabolic disturbances despite similar renal dysfunction following adenine experimental uremia. Therefore, we demonstrate that elevated hepatic 11ßHSD1 is an important contributor to early insulin resistance and dyslipidemia in uremia. Specific 11ßHSD1 inhibitors potentially represent a novel therapeutic approach for management of insulin resistance in patients with CKD.

Human memory T cells from the bone marrow are resting and maintain long-lasting systemic memory.

In the bone marrow, a population of memory T cells has been described that promotes efficient secondary immune responses and has been considered to be preactivated, owing to its expression of CD69 and CD25. Here we show that human bone marrow professional memory T cells are not activated but are resting in terms of proliferation, transcription, and mobility. They are in the G0 phase of the cell cycle, and their transcriptome is that of resting T cells. The repertoire of CD4(+) bone marrow memory T cells compared with CD4(+) memory T cells from the blood is significantly enriched for T cells specific for cytomegalovirus-pp65 (immunodominant protein), tetanus toxoid, measles, mumps, and rubella. It is not enriched for vaccinia virus and Candida albicans-MP65 (immunodominant protein), typical pathogens of skin and/or mucosa. CD4(+) memory T cells specific for measles are maintained nearly exclusively in the bone marrow. Thus, CD4(+) memory T cells from the bone marrow provide long-term memory for systemic pathogens.

2016 Rio Olympics: an epidemiological study of the men's and women's Rugby-7s tournaments.

OBJECTIVE: To determine the incidence, severity and nature of injuries sustained during the men's and women's 2014/2015 and 2015/2016 Sevens World Series (SWS) and 2016 Olympic Games Rugby Sevens tournaments. DESIGN: A prospective cohort study. PARTICIPANTS: All players from the core teams competing in the men's and women's 2014/2015 and 2015/2016 SWS (men: 15 teams; women: 11 teams) and all players from the men's (12 teams) and women's (12 teams) 2016 Rio Olympics tournaments. RESULTS: The gold, silver and bronze medal-winning women's teams contained bigger players (body mass and stature) than other teams but the men's medal winning teams came from across the size spectrum of men's teams competing at Rio 2016. The incidences of injury in the men's tournaments (2014/2015 SWS: 107.7 injuries/1000 player-match-hours (95% CI 90.9 to 127.4); 2015/2016 SWS: 109.7 (95% CI 93.7 to 128.6); Rio 2016: 124.5 (95% CI 73.7 to 210.2)) were higher but not statistically significant than those in the equivalent women's tournaments (2014/2015 SWS: 88.5 (95% CI 68.4 to 114.5), p=0.250; 2015/2016 SWS: 109.4 (95% CI 84.2 to 142.2), p=0.984; Rio 2016: 71.1 (95% CI 35.6 to 142.2), p=0.208). There were no statistically significant differences between the incidences of injury at the men's and women's 2016 Rio Olympics and the equivalent 2014/2015 (men: p=0.603; women: p=0.562) and 2015/2016 (men: p=0.652; women: p=0.254) SWS. CONCLUSIONS: The incidence, severity and nature of the injuries sustained during the men's and women's Rio 2016 Rugby-7s tournaments fell within the normal range of values for international Rugby-7s tournaments.

Rugby World Cup 2015: World Rugby injury surveillance study.

OBJECTIVE: To determine the incidence, severity and nature of injuries sustained during the Rugby World Cup (RWC) 2015 together with the inciting events leading to the injuries. DESIGN: A prospective, whole population study. POPULATION: 639 international rugby players representing 20 countries. METHOD: The study protocol followed the definitions and procedures recommended in the consensus statement for epidemiological studies in rugby union; output measures included players' age (years), stature (cm), body mass (kg) and playing position, and the group-level incidence (injuries/1000 player-hours), mean and median severity (days-absence), location (%), type (%) and inciting event (%) for match and training injuries. RESULTS: Incidence of injury was 90.1 match injuries/1000 player-match-hours (backs: 100.4; forwards: 81.1) and 1.0 training injuries/1000 player-training-hours (backs: 0.9; forwards: 1.2). The mean severity of injuries was 29.8 days-absence (backs: 30.4; forwards: 29.1) during matches and 14.4 days-absence (backs: 6.3; forwards: 19.8) during training. During matches, head/face (22.0%), knee (16.2%), muscle-strain (23.1%) and ligament-sprain (23.1%) and, during training, lower limb (80.0%) and muscle-strain (60.0%) injuries were the most common locations and types of injury. Being-tackled (24.7%) was the most common inciting event for injury during matches and rugby-skills-contact activities (70.0%) the most common during training. CONCLUSIONS: While the incidence, nature and inciting events associated with match injuries at RWC 2015 were similar to those reported previously for RWCs 2007 and 2011, there were increasing trends in the mean severity and total days-absence through injury.

A video analysis of head injuries satisfying the criteria for a head injury assessment in professional Rugby Union: a prospective cohort study.

OBJECTIVES: Concussion is the most common match injury in professional Rugby Union, accounting for 25% of match injuries. The primary prevention of head injuries requires that the injury mechanism be known so that interventions can be targeted to specifically overall incidence by focusing on characteristics with the greatest propensity to cause a head injury. METHODS: 611 head injury assessment (HIA) events in professional Rugby Union over a 3-year period were analysed, with specific reference to match events, position, time and nature of head contact. RESULTS: 464 (76%) of HIA events occur during tackles, with the tackler experiencing a significantly greater propensity for an HIA than the ball carrier (1.40 HIAs/1000 tackles for the tackler vs 0.54 HIAs/1000 tackles for the ball carrier, incidence rate ratio (IRR) 2.59). Propensity was significantly greater for backline players than forwards (IRR 1.54, 95% CI 1.28 to 1.84), but did not increase over the course of the match. Head to head contact accounted for the most tackler HIAs, with the greatest propensity. CONCLUSIONS: By virtue of its high propensity and frequency, the tackle should be the focus for interventions that may include law change and technique education. A specific investigation of the characteristics of the tackle is warranted to refine the approach to preventative strategies.

Evaluation of World Rugby's concussion management process: results from Rugby World Cup 2015.

OBJECTIVE: To evaluate World Rugby's concussion management process during Rugby World Cup (RWC) 2015. DESIGN: A prospective, whole population study. POPULATION: 639 international rugby players representing 20 countries. METHOD: The concussion management process consisted of 3 time-based, multifaceted stages: an initial on-pitch and/or pitch-side assessment of the injury, a follow-up assessment within 3 hours and an assessment at 36-48 hours. The initial on-pitch assessment targeted obvious signs of concussion, which, if identified, lead to a 'permanent removal from play' decision and a diagnosis of concussion. If the on-pitch diagnosis was unclear, a 10-min off-pitch assessment was undertaken for signs and symptoms of concussion leading to a 'suspected concussion with permanent removal from play' or a 'no indication of concussion with return to play' decision. Evaluations at 3 and 36-48 hours postmatch lead to diagnoses of 'confirmed concussion' or 'no concussion'. Medical staff's decision-making was supported during each stage by real-time video review of events. Players diagnosed with confirmed concussion followed a 5-stage graduated-return-to-play protocol before being allowed to return to training and/or competition. RESULTS: Players were evaluated for concussion on 49 occasions, of which 24 resulted in diagnoses of concussion. Fourteen players showing on-pitch signs of concussion were permanently removed from play: 4 of the 5 players removed from play following off-pitch medical room evaluation were later diagnosed with a confirmed concussion. Five players not exhibiting in-match signs or symptoms of concussion were later diagnosed with concussion. The overall incidence of concussion during RWC 2015 was 12.5 concussions/1000 player-match-hours. CONCLUSIONS: This study supports the implementation of a multimodal, multitime-based concussion evaluation process to ensure that immediate and late developing concussions are captured.

Risk factors for head injury events in professional rugby union: a video analysis of 464 head injury events to inform proposed injury prevention strategies.

OBJECTIVES: The tackle is responsible for the majority of head injuries during rugby union. In order to address head injury risk, risk factors during the tackle must first be identified. This study analysed tackle characteristics in the professional game in order to inform potential interventions. METHODS: 464 tackles resulting in a head injury assessment (HIA) were analysed in detail, with tackle type, direction, speed, acceleration, nature of head contact and player body position the characteristics of interest. RESULTS: Propensity to cause an HIA was significantly greater for active shoulder tackles, front-on tackles, high speeder tackles and an accelerating tackler. Head contact between a tackler's head and ball carrier's head or shoulder was significantly more likely to cause an HIA than contact below the level of the shoulder (incident rate ratio (IRR) 4.25, 95%-CI 3.38 to 5.35). The tackler experiences the majority (78%) of HIAs when head-to-head contact occurs. An upright tackler was 1.5 times more likely to experience an HIA than a bent at the waist tackler (IRR 1.44, 95% CI 1.18 to 1.76). CONCLUSIONS: This study confirms that energy transfer in the tackle is a risk factor for head injury, since direction, type and speed all influence HIA propensity. The study provides evidence that body position and the height of tackles should be a focus for interventions, since lowering height and adopting a bent at the waist body position is associated with reduced risk for both tacklers and ball carriers. To this end, World Rugby has implemented law change based on the present data.

Managing player load in professional rugby union: a review of current knowledge and practices.

BACKGROUND: The loads to which professional rugby players are subjected has been identified as a concern by coaches, players and administrators. In November 2014, World Rugby commissioned an expert group to identify the physical demands and non-physical load issues associated with participation in professional rugby. OBJECTIVE: To describe the current state of knowledge about the loads encountered by professional rugby players and the implications for their physical and mental health. FINDINGS: The group defined 'load' as it relates to professional rugby players as the total stressors and demands applied to the players. In the 2013-2014 seasons, 40% of professional players appeared in 20 matches or more, and 5% of players appeared in 30 matches or more. Matches account for ∼5-11% of exposure to rugby-related activities (matches, team and individual training sessions) during professional competitions. The match injury rate is about 27 times higher than that in training. The working group surmised that players entering a new level of play, players with unresolved previous injuries, players who are relatively older and players who are subjected to rapid increases in load are probably at increased risk of injury. A mix of 'objective' and 'subjective' measures in conjunction with effective communication among team staff and between staff and players was held to be the best approach to monitoring and managing player loads. While comprehensive monitoring holds promise for individually addressing player loads, it brings with it ethical and legal responsibilities that rugby organisations need to address to ensure that players' personal information is adequately protected. CONCLUSIONS: Administrators, broadcasters, team owners, team staff and the players themselves have important roles in balancing the desire to have the 'best players' on the field with the ongoing health of players. In contrast, the coaching, fitness and medical staff exert significant control over the activities, duration and intensity of training sessions. If load is a major risk factor for injury, then managing training loads should be an important element in enabling players to perform in a fit state as often as possible.