Parametric g-formula for Testing Time-Varying Causal Effects: What It Is, Why It Matters, and How to Implement It in Lavaan.

Psychologists leverage longitudinal designs to examine the causal effects of a focal predictor (i.e., treatment or exposure) over time. But causal inference of naturally observed time-varying treatments is complicated by treatment-dependent confounding in which earlier treatments affect confounders of later treatments. In this tutorial article, we introduce psychologists to an established solution to this problem from the causal inference literature: the parametric g-computation formula. We explain why the g-formula is effective at handling treatment-dependent confounding. We demonstrate that the parametric g-formula is conceptually intuitive, easy to implement, and well-suited for psychological research. We first clarify that the parametric g-formula essentially utilizes a series of statistical models to estimate the joint distribution of all post-treatment variables. These statistical models can be readily specified as standard multiple linear regression functions. We leverage this insight to implement the parametric g-formula using lavaan, a widely adopted R package for structural equation modeling. Moreover, we describe how the parametric g-formula may be used to estimate a marginal structural model whose causal parameters parsimoniously encode time-varying treatment effects. We hope this accessible introduction to the parametric g-formula will equip psychologists with an analytic tool to address their causal inquiries using longitudinal data.

Are we tackle ready? Cross-sectional video analysis of match tackle characteristics in elite women's Rugby Union.

The tackle contest is the most common and most injurious match contact event in rugby and is an indicator of performance. Tackle Ready is World Rugby's tackle technique education program. Limited research has characterized the tackle contest in women's rugby. The purpose of this study is to: (1) identify the match situational characteristics, ball-carrier and tackler technical actions demonstrated in elite women's Rugby Union and (2) to determine the extent to which Tackle Ready recommended tackle techniques were exhibited. Technical characteristics for 1500 tackle events in the 2022-2023 Women's Six Nations Championship were visually assessed according to a predefined coding framework and the Tackle Ready program. Tackles lacked full completion (0.2%) of the 22 coded Tackle Ready techniques with 47% of the recommended techniques demonstrated in each tackle on average (range 15%-98%). A high proportion of tackles involved two defenders (48%), approaching ball-carriers from the side (38%) or oblique angles (39%), in an upright position (30%), and with initial contact made with the arm (51%). Incorrect pre-contact head positioning and head placement upon contact accounted for 50% and 15% of tackles, respectively, and there was a mean of 14 (95% CI 11-18) head and neck contacts to a tackler and 18 (95% CI 14-22) head and neck contacts to a ball-carrier per game. Targeted interventions to encourage adoption of recommended techniques are needed to reduce tackle-related injury risk in women's rugby. This study provides valuable context for future discussion across law enforcement, coach education and gender-specific tackle coaching in the women's game.

Head Contact and Suspected Concussion Rates in Youth Basketball: Time to Target Head Contact Penalties for Prevention.

OBJECTIVE: To compare game events, head contact (HC) rates, and suspected concussion incidence rates (IRs) in boys' and girls' youth basketball. DESIGN: Cross-sectional. SETTING: Canadian club basketball teams (U16-U18). PARTICIPANTS: Players from 24 boys' and 24 girls' Canadian club basketball teams during the 2022 season. ASSESSMENT OF RISK FACTORS: Recorded games were analyzed using Dartfish video analysis software to compare sexes. MAIN OUTCOME MEASURES: Poisson regression analyses were used to estimate HCs [direct (HC1) and indirect (HC2)], suspected concussion IRs, and IR ratios (IRRs). Game event, court location, and HC1 fouls were reported. RESULTS: Division 1 HC rates did not differ between boys (n = 238; IR = 0.50/10 player-minutes; 95% confidence interval [CI], 0.43-0.56) and girls (n = 220; IR = 0.46/10 player-minutes; 95% CI, 0.40-0.52). Division 2 boys experienced 252 HCs (IR = 0.53/10 player-minutes; 95% CI, 0.46-0.59); girls experienced 192 HCs (IR = 0.40/10 player-minutes; 95% CI, 0.35-0.46). Division 2 boys sustained higher HC1 IRs compared with Division 2 girls (IRR = 1.42; 95% CI, 1.15-1.74). Head contacts, rates did not differ between boys and girls in either Division. Suspected concussion IRs were not significantly different for boys and girls in each Division. Head contacts occurred mostly in the key for boys and girls in each Division. Despite illegality, HC1 penalization ranged from 3.9% to 19.7%. Head contact mechanisms varied across Divisions and sexes. CONCLUSIONS: Despite current safety measures, both HCs and suspected concussions occur in boys' and girls' basketball. Despite the illegality and potential danger associated with HC, only a small proportion of direct HCs were penalized and therefore targeting greater enforcement of these contacts may be a promising prevention target.

Paving the path for injury prevention in rugby-7s: A systematic review and meta-analysis.

This review and meta-analysis aimed to describe the current rugby-7s injury epidemiological literature by examining injury data from both sexes, all levels of play, and their associated risk factors. Studies published up until March 2024 were included. These studies were retrieved from six databases using search terms related to rugby-7s or sevens, tackle, collision, collision sport, injury, athlete, incidence rate, mechanism, and risk factor. Only peer-reviewed original studies using prospective or retrospective cohort designs with a clearly defined rugby-7s sample were considered. Included studies needed to report one injury outcome variable. Non-English and qualitative studies; reviews, conference papers, and abstracts were excluded. Twenty studies were included. The meta-analysis used the DerSimonian-Laird continuous random-effects method to calculate the pooled estimated means and 95% confidence interval. The estimated mean injury incidence rate for men was 108.5/1000 player-hours (95% CI: 85.9-131.0) and 76.1/1000 player-hours (95% CI: 48.7-103.5) for women. The estimated mean severity for men was 33.9 days (95% CI: 20.7-47.0) and 44.2 days (95% CI: 32.1-56.3) for women. Significantly more match injuries occurred in the second half of matches, were acute, located at the lower limb, diagnosed as joint/ligament, and resulted from being tackled. Fatigue, player fitness, and previous injuries were associated with an increased risk of injury. There were no statistically significant differences between women's and men's injury profiles. However, the inherent cultural and gendered factors which divide the two sports should not be ignored. The findings from this review will help pave the way forward beyond the foundational stages of injury prevention research in rugby-7s.

Injury in Starting and Replacement Players from Five Professional Men's Rugby Unions.

OBJECTIVES: The aim of this study was to compare the incidence, severity, and burden of injury in starting and replacement players from professional men's teams of five rugby unions. METHODS: Match injuries of greater than 24 h time-loss (including data on the severity, match quarter, event, body region) and player minutes of match exposure data were collated for all starting and replacement players in the men's English Premiership, Welsh Pro14 (both 2016/17-2018/19 seasons), and Australian, New Zealand, and South African Super Rugby (all 2016-2018 seasons) teams. Injury incidences and mean injury burden (incidence × days missed) were calculated, and rate ratios (RRs) (95% confidence intervals [CIs]) were used to compare injury incidence and burden between starting (reference group) and replacement players. RESULTS: Overall injury incidence was not different between starters and replacements for all injuries (RR = 0.98, 95% CI 0.88-1.10), nor for concussions (RR = 0.85; 95% CI 0.66-1.11). Mean injury burden was higher for replacement players (RR = 1.31, 95% CI 1.17-1.46). Replacement injury incidence was lower than the starters in the third (RR = 0.68, 95% CI 0.51-0.92) and fourth (RR = 0.78, 95% CI 0.67-0.92) match quarters. Injury incidence was not different between starters and replacements for any match event or body region, but compared with starters, replacements' injury burden was higher in lower limbs (RR = 1.24, 95% CI 1.05-1.46) and in the tackled player (RR = 1.30, 95% CI 1.01-1.66). CONCLUSION: This study demonstrated a lower injury incidence in replacement players compared with starters in the second half of matches, with a higher injury burden for replacement players due to higher mean injury severity.

Mechanism of single-stranded DNA annealing by RAD52-RPA complex.

RAD52 is important for the repair of DNA double-stranded breaks1,2, mitotic DNA synthesis3-5 and alternative telomere length maintenance6,7. Central to these functions, RAD52 promotes the annealing of complementary single-stranded DNA (ssDNA)8,9 and provides an alternative to BRCA2/RAD51-dependent homologous recombination repair10. Inactivation of RAD52 in homologous-recombination-deficient BRCA1- or BRCA2-defective cells is synthetically lethal11,12, and aberrant expression of RAD52 is associated with poor cancer prognosis13,14. As a consequence, RAD52 is an attractive therapeutic target against homologous-recombination-deficient breast, ovarian and prostate cancers15-17. Here we describe the structure of RAD52 and define the mechanism of annealing. As reported previously18-20, RAD52 forms undecameric (11-subunit) ring structures, but these rings do not represent the active form of the enzyme. Instead, cryo-electron microscopy and biochemical analyses revealed that ssDNA annealing is driven by RAD52 open rings in association with replication protein-A (RPA). Atomic models of the RAD52-ssDNA complex show that ssDNA sits in a positively charged channel around the ring. Annealing is driven by the RAD52 N-terminal domains, whereas the C-terminal regions modulate the open-ring conformation and RPA interaction. RPA associates with RAD52 at the site of ring opening with critical interactions occurring between the RPA-interacting domain of RAD52 and the winged helix domain of RPA2. Our studies provide structural snapshots throughout the annealing process and define the molecular mechanism of ssDNA annealing by the RAD52-RPA complex.

Symptom presentation and evolution in the first 48 hours after injury are associated with return to play after concussion in elite Rugby Union.

BACKGROUND: Return to play (RTP) in elite rugby is managed using a 6-stage graduated RTP protocol, which can result in clearance to play within 1 week of injury. We aimed to explore how symptom, cognitive, and balance presentation and evolution during concussion screens 2 h (head injury assessment (HIA) 2) and 48 h (HIA3) after injury were associated with time to RTP) to identify whether a more conservative graduated RTP may be appropriate. METHODS: A retrospective cohort study was conducted in 380 concussed rugby players from elite men's rugby over 3 consecutive seasons. Players were classified as shorter or longer returns, depending on whether RTP occurred within 7 days (allowing them to be considered to play the match 1 week after injury) or longer than 8 days, respectively. Symptom, cognitive, and balance performance during screens was assessed relative to baseline (normal or abnormal) and to the preceding screen (improving or worsening). Associations between sub-test abnormalities and RTP time were explored using odds ratios (OR, longer vs. shorter). Median day absence was compared between players with abnormal or worsening results and those whose results were normal or improving. RESULTS: Abnormal symptom results during screens 2 h and 48 h after concussion were associated with longer return time (HIA2: OR = 2.21, 95% confidence interval (95%CI): 1.39-3.50; HIA3: OR = 3.30, 95%CI: 1.89-5.75). Worsening symptom number or severity from the time of injury to 2 h and 48 h post-injury was associated with longer return (HIA2: OR = 2.49, 95%CI: 1.36-4.58; HIA3: OR = 3.34, 95%CI: 1.10-10.15. Median days absence was greater in players with abnormal symptom results at both HIA2 and HIA3. Cognitive and balance performance were not associated with longer return and did not affect median days absence. CONCLUSION: Symptom presentation and evolution within 48 h of concussion were associated with longer RTP times. This may guide a more conservative approach to RTP, while still adhering to individualized concussion management principles.

Shoulder Check: Investigating Shoulder Injury Rates, Types, Severity, Mechanisms, and Risk Factors in Canadian Youth Ice Hockey.

OBJECTIVE: To describe shoulder-related injury rates (IRs), types, severity, mechanisms, and risk factors in youth ice hockey players during games and practices. DESIGN: Secondary analysis of data from a 5-year prospective cohort study, Safe-to-Play (2013-2018). SETTING: Canadian youth ice hockey. PARTICIPANTS: Overall, 6584 player-seasons (representing 4417 individual players) participated. During this period, 118 shoulder-related games and 12 practice injuries were reported. ASSESSMENT OF RISK FACTORS: An exploratory multivariable mixed-effects Poisson regression model examined the risk factors of body checking policy, weight, biological sex, history of injury in the past 12 months, and level of play. MAIN OUTCOME MEASURES: Injury surveillance data were collected from 2013 to 2018. Injury rates with 95% confidence interval (CI) were estimated using Poisson regression. RESULTS: The shoulder IR was 0.35 injuries/1000 game-hours (95% CI, 0.24-0.49). Two-thirds of game injuries (n = 80, 70%) resulted in >8 days of time-loss, and more than one-third (n = 44, 39%) resulted in >28 days of time-loss. An 83% lower rate of shoulder injury was associated with policy prohibiting body checking compared with leagues allowing body checking (incidence rate ratio [IRR], 0.17; 95% CI, 0.09-0.33). A higher shoulder IR was observed for those who reported any injury in the last 12-months compared with those with no history (IRR, 2.00; 95% CI, 1.33-3.01). CONCLUSIONS: Most shoulder injuries resulted in more than 1 week of time-loss. Risk factors for shoulder injury included participation in a body-checking league and recent history of injury. Further study of prevention strategies specific to the shoulder may merit further consideration in ice hockey.

Differences in injury and concussion rates in a cohort of Canadian female and male youth Rugby Union: a step towards targeted prevention strategies.

OBJECTIVE: To examine differences in match and training musculoskeletal injury and concussion rates and describe mechanisms of concussion while considering previous playing experience in female and male Canadian high school Rugby Union ('rugby') players. METHODS: A 2-year prospective cohort study was completed in a high school league (n=361 females, 421 player-seasons; n=429 males, 481 player-seasons) in Calgary, Canada over the 2018 and 2019 rugby playing seasons. Baseline testing was completed at the start of each season and injury surveillance and individual player participation through session attendance was documented to quantify individual-level player exposure hours. Injury incidence rates (IRs) and incidence rate ratios (IRRs) were calculated using Poisson regression, offset by player exposure hours and clustered by team. RESULTS: Overall match IR for females was 62% higher than males (overall IRR=1.62, 95% CI: 1.20 to 2.18) and the overall training IR was twice as high for females (overall IRR=2.15, 95% CI: 1.40 to 3.32). The female match concussion IR was 70% higher than the males (concussion IRR=1.70, 95% CI: 1.08 to 2.69). Females had a 75% greater tackle-related IR compared with males (IRR=1.75, 95% CI: 1.20 to 2.56). Additionally, female tacklers had a twofold greater rate of injury compared with male tacklers (IRR=2.17, 95% CI: 1.14 to 4.14). Previous playing experience was not associated with tackle-related injury or concussion IRs. CONCLUSION: The rate of injury and concussion was significantly higher in females within this Canadian high school cohort. These results emphasise the need for development, implementation and evaluation of female-specific injury and concussion prevention strategies to reduce injury and concussion in female youth rugby.

Mechanism of substrate hydrolysis by the human nucleotide pool sanitiser DNPH1.

Poly(ADP-ribose) polymerase (PARP) inhibitors are used in the clinic to treat BRCA-deficient breast, ovarian and prostate cancers. As their efficacy is potentiated by loss of the nucleotide salvage factor DNPH1 there is considerable interest in the development of highly specific small molecule DNPH1 inhibitors. Here, we present X-ray crystal structures of dimeric DNPH1 bound to its substrate hydroxymethyl deoxyuridine monophosphate (hmdUMP). Direct interaction with the hydroxymethyl group is important for substrate positioning, while conserved residues surrounding the base facilitate target discrimination. Glycosidic bond cleavage is driven by a conserved catalytic triad and proceeds via a two-step mechanism involving formation and subsequent disruption of a covalent glycosyl-enzyme intermediate. Mutation of a previously uncharacterised yet conserved glutamate traps the intermediate in the active site, demonstrating its role in the hydrolytic step. These observations define the enzyme's catalytic site and mechanism of hydrolysis, and provide important insights for inhibitor discovery.

How to harness and improve on video analysis for youth rugby player safety: a narrative review.

Video analysis is a useful tool for injury surveillance in rugby union. There are few video analysis studies in the professional female game, with most studies published in the male elite/professional settings. Moreover, there is a sparsity of literature in youth rugby settings. The following narrative review outlines the strengths and limitations of the current video analysis literature for injury surveillance in youth rugby union, highlights the importance of video analysis for youth rugby player safety and welfare, and discusses recommendations for using video analysis to inform player safety in youth rugby.

Method to generate Holliday junction recombination intermediates via RecA-mediated four-strand exchange.

DNA molecules that contain single Holliday junctions have served as model substrates to investigate the pathway in which homologous recombination intermediates are processed. However, the preparation of DNA containing Holliday junctions in high yield remains a challenge. In this work, we used a nicking endonuclease to generate gapped DNA, from which α-structured DNA or figure-8 DNA were created via RecA-mediated reactions. The resulting DNA molecules were found to serve as good substrates for Holliday junction resolvases. The simplified method negates the requirement for radioactive labelling of DNA, making the generation of Holliday junction DNA more accessible to non-experts.

Visualization of direct and diffusion-assisted RAD51 nucleation by full-length human BRCA2 protein.

Homologous recombination (HR) is essential for error-free repair of DNA double-strand breaks, perturbed replication forks (RFs), and post-replicative single-stranded DNA (ssDNA) gaps. To initiate HR, the recombination mediator and tumor suppressor protein BRCA2 facilitates nucleation of RAD51 on ssDNA prior to stimulation of RAD51 filament growth by RAD51 paralogs. Although ssDNA binding by BRCA2 has been implicated in RAD51 nucleation, the function of double-stranded DNA (dsDNA) binding by BRCA2 remains unclear. Here, we exploit single-molecule (SM) imaging to visualize BRCA2-mediated RAD51 nucleation in real time using purified proteins. We report that BRCA2 nucleates and stabilizes RAD51 on ssDNA either directly or through an unappreciated diffusion-assisted delivery mechanism involving binding to and sliding along dsDNA, which requires the cooperative action of multiple dsDNA-binding modules in BRCA2. Collectively, our work reveals two distinct mechanisms of BRCA2-dependent RAD51 loading onto ssDNA, which we propose are critical for its diverse functions in maintaining genome stability and cancer suppression.

A case-control study of tackle based head impact event (HIE) risk factors from the first three seasons of the National Rugby League Women's competition.

Objective: The 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. Methods: We 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. Results: The 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. Conclusions: In 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.

Prevention strategies and modifiable risk factors for sport-related concussions and head impacts: a systematic review and meta-analysis.

OBJECTIVES: To evaluate prevention strategies, their unintended consequences and modifiable risk factors for sport-related concussion (SRC) and/or head impact risk. DESIGN: This systematic review and meta-analysis was registered on PROSPERO (CRD42019152982) and conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: Eight databases (MEDLINE, CINAHL, APA PsycINFO, Cochrane (Systematic Review and Controlled Trails Registry), SPORTDiscus, EMBASE, ERIC0 were searched in October 2019 and updated in March 2022, and references searched from any identified systematic review. ELIGIBILITY CRITERIA: Study inclusion criteria were as follows: (1) original data human research studies, (2) investigated SRC or head impacts, (3) evaluated an SRC prevention intervention, unintended consequence or modifiable risk factor, (4) participants competing in any sport, (5) analytic study design, (6) systematic reviews and meta-analyses were included to identify original data manuscripts in reference search and (7) peer-reviewed. Exclusion criteria were as follows: (1) review articles, pre-experimental, ecological, case series or case studies and (2) not written in English. RESULTS: In total, 220 studies were eligible for inclusion and 192 studies were included in the results based on methodological criteria as assessed through the Scottish Intercollegiate Guidelines Network high ('++') or acceptable ('+') quality. Evidence was available examining protective gear (eg, helmets, headgear, mouthguards) (n=39), policy and rule changes (n=38), training strategies (n=34), SRC management strategies (n=12), unintended consequences (n=5) and modifiable risk factors (n=64). Meta-analyses demonstrated a protective effect of mouthguards in collision sports (incidence rate ratio, IRR 0.74; 95% CI 0.64 to 0.89). Policy disallowing bodychecking in child and adolescent ice hockey was associated with a 58% lower concussion rate compared with bodychecking leagues (IRR 0.42; 95% CI 0.33 to 0.53), and evidence supports no unintended injury consequences of policy disallowing bodychecking. In American football, strategies limiting contact in practices were associated with a 64% lower practice-related concussion rate (IRR 0.36; 95% CI 0.16 to 0.80). Some evidence also supports up to 60% lower concussion rates with implementation of a neuromuscular training warm-up programme in rugby. More research examining potentially modifiable risk factors (eg, neck strength, optimal tackle technique) are needed to inform concussion prevention strategies. CONCLUSIONS: Policy and rule modifications, personal protective equipment, and neuromuscular training strategies may help to prevent SRC. PROSPERO REGISTRATION NUMBER: CRD42019152982.

Structure and function of the RAD51B-RAD51C-RAD51D-XRCC2 tumour suppressor.

Homologous recombination is a fundamental process of life. It is required for the protection and restart of broken replication forks, the repair of chromosome breaks and the exchange of genetic material during meiosis. Individuals with mutations in key recombination genes, such as BRCA2 (also known as FANCD1), or the RAD51 paralogues RAD51B, RAD51C (also known as FANCO), RAD51D, XRCC2 (also known as FANCU) and XRCC3, are predisposed to breast, ovarian and prostate cancers1-10 and the cancer-prone syndrome Fanconi anaemia11-13. The BRCA2 tumour suppressor protein-the product of BRCA2-is well characterized, but the cellular functions of the RAD51 paralogues remain unclear. Genetic knockouts display growth defects, reduced RAD51 focus formation, spontaneous chromosome abnormalities, sensitivity to PARP inhibitors and replication fork defects14,15, but the precise molecular roles of RAD51 paralogues in fork stability, DNA repair and cancer avoidance remain unknown. Here we used cryo-electron microscopy, AlphaFold2 modelling and structural proteomics to determine the structure of the RAD51B-RAD51C-RAD51D-XRCC2 complex (BCDX2), revealing that RAD51C-RAD51D-XRCC2 mimics three RAD51 protomers aligned within a nucleoprotein filament, whereas RAD51B is highly dynamic. Biochemical and single-molecule analyses showed that BCDX2 stimulates the nucleation and extension of RAD51 filaments-which are essential for recombinational DNA repair-in reactions that depend on the coupled ATPase activities of RAD51B and RAD51C. Our studies demonstrate that BCDX2 orchestrates RAD51 assembly on single stranded DNA for replication fork protection and double strand break repair, in reactions that are critical for tumour avoidance.

Injury Rates, Mechanisms, Risk Factors and Prevention Strategies in Youth Rugby Union: What's All the Ruck-Us About? A Systematic Review and Meta-analysis.

BACKGROUND: Rugby Union is a collision team sport played globally. Despite this, significant concerns have been raised regarding the sport's safety, particularly in youth players. Given this, a review of injury rates, risk factors and prevention strategies is required across different youth age groups as well as in males and females. OBJECTIVE: The objective of this systematic review (SR) and meta-analysis was to investigate injury and concussion rates, risk factors and primary prevention strategies in youth rugby. METHODS: To be included, studies were required to report either rates, risk factors or prevention strategies in youth rugby and to have a randomised controlled trial, quasi-experimental, cohort, case control, or ecological study design. Exclusion criteria included non-peer-reviewed grey literature, conference abstracts, case studies, previous systematic reviews and studies not written in English. Nine databases were searched. The full search strategy and list of sources are available and pre-registered on PROSPERO (Ref: CRD42020208343). Each study was assessed for risk of bias using the Downs and Black quality assessment tool. Meta-analyses were conducted using a DerSimonian Laird random effect model for each age group and sex. RESULTS: Sixty-nine studies were included in this SR. The match injury rates (using a 24-h time-loss definition) were 40.2/1000 match hours (95% CI 13.9-66.5) in males and 69.0/1000 match hours (95% CI 46.8-91.2) in females. Concussion rates were 6.2/1000 player-hours (95% CI 5.0-7.4) for males and 33.9/1000 player-hours (95% CI: 24.1-43.7) for females. The most common injury site was lower extremity (males) and the head/neck (females). The most common injury type was ligament sprain (males) and concussion (females). The tackle was the most common event associated with injury in matches (55% male, 71% females). Median time loss was 21 days for males and 17 days for females. Twenty-three risk factors were reported. The risk factors with the strongest evidence were higher levels of play and increasing age. Primary injury prevention strategies were the focus of only eight studies and included law changes (n = 2), equipment (n = 4), education (n = 1) and training (n = 1). The prevention strategy with the most promising evidence was neuromuscular training. The primary limitations included a broad range of injury definitions (n = 9) and rate denominators (n = 11) used, as well as a limited number of studies which could be included in the meta-analysis for females (n = 2). CONCLUSION: A focus on high-quality risk factor and primary prevention evaluation should be considered in future studies. Targeting primary prevention and stakeholder education remain key strategies in the prevention, recognition and management of injuries and concussions in youth rugby.