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Self-expanding (SE) and balloon-expandable (BE) transcatheter heart valves (THVs) have not been extensively studied in valve-in-valve transcatheter aortic valve replacement (ViV-TAVR). We compared outcomes of supra-annular SE and BE THVs used for ViV-TAVR via a retrospective analysis of institutional data (2013-2023) including all patients undergoing ViV-TAVR (TAVR in previous surgical AVR). Unmatched and propensity-matched (1:1) comparisons of clinical and echocardiographic outcomes were undertaken between SE and BE THV along with Kaplan-Meier survival analysis. A total of 315 patients undergoing ViV-TAVR were included of which 73% received a SE THV. Median age was 77 years and women comprised 42.5% of the population. Propensity-score matching (1:1) yielded 81 matched pairs. Implanted aortic valve size was comparable between the groups (23 mm [23-26] vs. 23mm [23-26], p=0.457). At 30 days following ViV-TAVR, the SE group had a lower mean aortic valve gradient (14 mmHg [11-18] vs. 17.5 mmHg [13-25], p=0.007). A higher number of BE patients had severe prosthesis-patient mismatch (PPM) (16% vs. 6.2%, p=0.04). At one-year follow-up, the SE group had a lower aortic valve gradient (14.0 mmHg [9.6-19] vs. 17 mmHg [13-25], p=0.04) compared to the BE group. 30-day mortality was 2.7% while one-year mortality was 7.5% and comparable between the groups. Survival and stroke incidence were similar in both groups up to 5 years. In conclusion, both SE and BE THVs had comparable survival following ViV-TAVR. The higher residual aortic valve gradients in BE THVs are likely due to valve design and warrant long-term evaluation for potential structural valve degeneration.

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AIMS/HYPOTHESIS: Dietary patterns characterised by high intakes of vegetables may lower the risk of pre-eclampsia and premature birth in the general population. The effect of dietary patterns in women with type 1 diabetes, who have an increased risk of complications in pregnancy, is not known. The aim of this study was to investigate the relationship between dietary patterns and physical activity during pregnancy and maternal complications and birth outcomes in women with type 1 diabetes. We also compared dietary patterns in women with and without type 1 diabetes. METHODS: Diet was assessed in the third trimester using a validated food frequency questionnaire in participants followed prospectively in the multi-centre Environmental Determinants of Islet Autoimmunity (ENDIA) study. Dietary patterns were characterised by principal component analysis. The Pregnancy Physical Activity Questionnaire was completed in each trimester. Data for maternal and birth outcomes were collected prospectively. RESULTS: Questionnaires were completed by 973 participants during 1124 pregnancies. Women with type 1 diabetes (n=615 pregnancies with dietary data) were more likely to have a 'fresh food' dietary pattern than women without type 1 diabetes (OR 1.19, 95% CI 1.07, 1.31; p=0.001). In women with type 1 diabetes, an increase equivalent to a change from quartile 1 to 3 in 'fresh food' dietary pattern score was associated with a lower risk of pre-eclampsia (OR 0.37, 95% CI 0.17, 0.78; p=0.01) and premature birth (OR 0.35, 95% CI 0.20, 0.62, p<0.001). These associations were mediated in part by BMI and HbA1c. The 'processed food' dietary pattern was associated with an increased birthweight (ß coefficient 56.8 g, 95% CI 2.8, 110.8; p=0.04). Physical activity did not relate to outcomes. CONCLUSIONS/INTERPRETATION: A dietary pattern higher in fresh foods during pregnancy was associated with sizeable reductions in risk of pre-eclampsia and premature birth in women with type 1 diabetes.

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Premise plumbing water quality degradation has led to negative health impacts from pathogen outbreaks (e.g., Legionella pneumophila and non-tuberculous mycobacteria), as well as chronic effects from exposure to heavy metals or disinfection by-products (DBP). Common water quality management interventions include flushing, heat shock (thermal disinfection), supplemental disinfection (shock or super chlorination), and water heater temperature setpoint change. In this study, a Legionella pneumophila- colonized Leadership in Energy and Environmental Design (LEED) certified building was monitored to study health-relevant water quality changes before and after three controlled management interventions: (1) flushing at several points throughout the building; (2) changing the water heater set point; and (3) a combination of interventions (1) and (2) by flushing during a period of elevated water heater set point (incompletely performed due to operational issues). Microbial (culturable L. pneumophila, the L. pneumophila mip gene, and cATP) and physico-chemical (pH, temperature, conductivity, disinfectant residual, disinfection by-products (DBPs; total trihalomethanes, TTHM), and heavy metals) water quality were monitored alongside building occupancy as approximated using Wi-Fi logins. Flushing alone resulted in a significant decrease in cATP and L. pneumophila concentrations (p = 0.018 and 0.019, respectively) and a significant increase in chlorine concentrations (p = 0.002) as well as iron and DBP levels (p = 0.002). Copper concentrations increased during the water heater temperature setpoint increase alone to 140°F during December 2022 (p = 0.01). During the flushing and elevated temperature in parts of the building in February 2023, there was a significant increase in chlorine concentrations (p = 0.002) and iron (p = 0.002) but no significant decrease in L. pneumophila concentrations in the drinking water samples (p = 0.27). This study demonstrated the potential impacts of short term or incompletely implemented interventions which in this case were not sufficient to holistically improve water quality. As implementing interventions is logistically- and time-intensive, more effective and holistic approaches are needed for informing preventative and corrective actions that are beneficial for multiple water quality and sustainability goals.

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This commentary outlines the development of an Inclusion Collaborative in a large health district in Sydney, New South Wales Australia. The Collaborative grew out of ongoing efforts to reduce stigma associated with blood borne viruses while recognising that there are many health conditions and situations where people feel judged when attending services for health care. The formation of the Collaborative drew in health workers in other sectors to create a critical mass of voices calling for stigma reduction, move beyond siloed responses to stigma and to reframe conversations about stigma to a more positive description of "inclusion". The involvement of consumer representatives (paid for their time) was a key principle of the Collaborative. The members of the Collaborative identified the common experience of their clients being 'othered' by the mainstream services and that services can be unwelcoming or not supportive of difference, and therefore create a significant barrier to accessing healthcare. The group considered ways to highlight these issues among colleagues from mainstream services and community members who were not 'othered'. The Collaborative designed and carried out a range of activities including a Festival of Inclusion, a series of seeding grants for staff and consumer-focused initiatives, promotion of diversity days and an audit of compliance with strategic priorities. The Inclusion Collaborative is an example of a structured approach for efforts to reducing stigma that draws on the ambitions of many parts of a large, complex public health service to deliver better outcomes for its staff and consumers.

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Tarsal coalition is an uncommon cause of insidious-onset foot pain typically affecting adolescents. Cuboid-navicular coalitions are among the rarest variety, comprising less than 1% of all tarsal coalitions. This case report describes a female competitive gymnast in middle childhood with a 6-month history of worsening insidious onset right foot pain that forced withdrawal from all sporting activities. The patient reported a background of intermittent foot pain and bilateral ankle instability over the past 2 years. A comprehensive history and physical examination, alongside MRI, enabled the diagnosis of a fibro-osseous cuboid-navicular coalition. Through early diagnosis, a targeted and prompt trial of non-operative management was implemented, consisting of physiotherapy, a deloading protocol, orthotics and analgesia. At 6-month follow-up, this led to improvements in pain symptoms and functional outcomes as well as a return to competitive sport. Early recognition of cuboid-navicular coalition is essential to prevent early degenerative joint disease.

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AIMS: Systemic sclerosis complicated by pulmonary arterial hypertension (SSc-PAH) is a rare condition with poor prognosis. The majority of patients are categorized as intermediate risk of mortality. Cardiovascular magnetic resonance (CMR) is well placed to reproducibly assess right heart size and function, but most patients with SSc-PAH have less overtly abnormal right ventricles than other forms of PAH. The aim of this study was to assess if exercise CMR measures of cardiac size and function could better predict outcome in patients with intermediate risk SSc-PAH compared with resting CMR. METHODS AND RESULTS: Fifty patients with SSc-PAH categorized as intermediate risk underwent CMR-augmented cardiopulmonary exercise testing. Most patients had normal CMR-defined resting measures of right ventricular (RV) size and function. Nine (18%) patients died during a median follow-up period of 2.1 years (range 0.1-4.6). Peak exercise RV indexed end-systolic volume (ESVi) was the only CMR metric to predict prognosis on stepwise Cox regression analysis, with an optimal threshold < 39 mL/m2 to predict favourable outcome. Intermediate-low risk patients with peak RVESVi < 39 mL/m2 had significantly better survival than all other combinations of intermediate-low/-high risk status and peak RVESVi< or ≥39 mL/m2. In our cohort, ventilatory efficiency and resting oxygen consumption (VO2) were predictive of mortality, but not peak VO2, peak cardiac output, or peak tissue oxygen extraction. CONCLUSION: Exercise CMR assessment of RV size and function may help identify SSc-PAH patients with poorer prognosis amongst intermediate risk cohorts, even when resting CMR appears reassuring, and could offer added value to clinical PH risk stratification.

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OBJECTIVE: Perioperative Large Vessel Occlusions (LVOs) occurring during and following surgery are of immense clinical importance. As such, we aim to present risk factors and test if the Society of Thoracic Surgery (STS) mortality and stroke risk scores can be used to assess operative risk. METHODS: Using data containing 7 index cardiac operations at a single tertiary referral center from 2010 to 2022, logistic and multivariate regression analysis was performed to identify factors that correlate to higher operative LVO and stroke rate. Odds ratios and confidence intervals were also obtained to test if the STS-Predicted Risk of Mortality (PROM) and -Predicted Risk of Stroke (PROS) scores were positively correlated to operative LVO and stroke rate. RESULTS: Multivariate modeling showed primary risk factors for an operative LVO were diabetes (OR: 1.727 [95 % CI: 1.060-2.815]), intracranial or extracranial carotid stenosis (OR: 3.661 [95 % CI: 2.126-6.305]), and heart failure as defined by NYHA class (Class 4, OR: 3.951 [95 % CI: 2.092-7.461]; compared to Class 1). As the STS-PROM increased, the relative rate of LVO occurrence increased (very high risk, OR: 6.576 [95 % CI: 2.92-14.812], high risk, OR: 2.667 [1.125-6.322], medium risk, OR: 2.858 [1.594-5.125]; all compared to low risk). STS-PROS quartiles showed a similar relation with LVO risk (quartile 4, OR: 7.768 [95 % CI: 2.740-22.027], quartile 3, OR: 5.249 [1.800-15.306], quartile 2, OR:2.980 [0.960-9.248]; all compared to quartile 1). CONCLUSIONS: Patients with diabetes, carotid disease and heart failure are at high risk for operative LVO. Both STS-PROM and -PROS can be useful metrics for preoperative measuring of LVO risks.

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BACKGROUND: Total arch replacement (TAR) and debranching plus thoracic endovascular aortic repair (TEVAR) serve as significant therapeutic options for aortic arch pathologies. It remains unclear whether one of these approaches should be considered preferable. Our study aimed to compare the long-term outcomes of these 2 approaches. METHODS: We carried out a pooled meta-analysis of time-to-event data extracted from studies published by December 2023. Eligibility criteria included populations with any aortic arch pathology who underwent debranching plus TEVAR or TAR, propensity score-matched (PSM) studies (prospective/retrospective; single-center/multicentric), and the outcomes included follow-up for overall survival/mortality and/or reinterventions. RESULTS: Eleven PSM studies met our eligibility criteria, including a total of 1142 patients (571 matched pairs). We did not observe any statistically significant difference in the risk of all-cause death between the groups (hazard ratio [HR]=1.20, 95% confidence interval [CI]=0.91-1.56, p=0.202), but patients who underwent TAR had a significantly lower risk of late aortic reinterventions compared with patients who underwent debranching plus TEVAR (HR=0.38, 95% CI=0.23-0.64, p<0.001). Our meta-regression analyses for all-cause mortality identified statistically significant coefficients for age (coefficient=-0.047; p=0.012) and type A aortic dissections (coefficient=0.012; p=0.010). CONCLUSIONS: Debranching plus TEVAR and TAR demonstrate no statistically significant differences in terms of survival in patients with aortic arch pathologies, but TAR is associated with lower risk of late aortic reinterventions over time. Although older patients may benefit more from debranching plus TEVAR rather than from TAR, patients with dissections may benefit more from TAR. CLINICAL IMPACT: Although the 2 strategies seem to be equally valuable in terms of survival, total aortic arch replacement (when compared with debranching plus TEVAR to treat patients with aortic arch pathologies) is associated with reduction of late aortic reinterventions over time in patients with and without aortic dissections. However, we should consider debranching plus TEVAR in older patients as it is associated with lower risk of death in this population. The novelty of our study lies in the fact that, instead of comparing study-level effect estimates, we analyzed the outcomes with reconstructed time-to-event data. This offered us the opportunity of performing our analyses with a mathematically appropriate model which consider events and time; however, these findings might be under the influence of treatment allocation bias.

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Precision (individualized) medicine relies on the molecular profiling of tumors' dysregulated characteristics (genomic, epigenetic, transcriptomic) to identify the reliance on key pathways (including genome stability and epigenetic gene regulation) for viability or growth, and then utilises targeted therapeutics to disrupt these survival-dependent pathways. Non-mutational epigenetic changes alter cells' transcriptional profile and are a key feature found in many tumors. In contrast to genetic mutations, epigenetic changes are reversable, and restoring a normal epigenetic profile can inhibit tumor growth and progression. Lysine acetyltransferases (KATs or HATs) protect genome stability and integrity, and Tip60 is an essential acetyltransferase due to its roles as an epigenetic and transcriptional regulator, and as master regulator of the DNA double-strand break response. Tip60 is commonly downregulated and mislocalized in many cancers, and the roles that mislocalized Tip60 plays in cancer are not well understood. Here we categorize and discuss Tip60-regulated genes, evaluate Tip60-interacting proteins based on cellular localization, and explore the therapeutic potential of Tip60-targeting compounds as epigenetic inhibitors. Understanding the multiple roles Tip60 plays in tumorigenesis will improve our understanding of tumor progression and will inform therapeutic options, including informing potential combinatorial regimes with current chemotherapeutics, leading to improvements in patient outcomes.

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BACKGROUND: CRISPR Cas9 and Cas12a are the two most frequently used programmable nucleases reported in plant systems. There is now a wide range of component parts for both which likely have varying degrees of effectiveness and potentially applicability to different species. Our aim was to develop and optimise Cas9 and Cas12a based systems for highly efficient genome editing in the monocotyledons barley and wheat and produce a user-friendly toolbox facilitating simplex and multiplex editing in the cereal community. RESULTS: We identified a Zea mays codon optimised Cas9 with 13 introns in conjunction with arrayed guides driven by U6 and U3 promoters as the best performer in barley where 100% of T0 plants were simultaneously edited in all three target genes. When this system was used in wheat > 90% of T0 plants were edited in all three subgenome targets. For Cas12a, an Arabidopsis codon optimised sequence with 8 introns gave the best editing efficiency in barley when combined with a tRNA based multiguide array, resulting in 90% mutant alleles in three simultaneously targeted genes. When we applied this Cas12a system in wheat 86% & 93% of T0 plants were mutated in two genes simultaneously targeted. We show that not all introns contribute equally to enhanced mutagenesis when inserted into a Cas12a coding sequence and that there is rationale for including multiple introns. We also show that the combined effect of two features which boost Cas12a mutagenesis efficiency (D156R mutation and introns) is more than the sum of the features applied separately. CONCLUSION: Based on the results of our testing, we describe and provide a GoldenGate modular cloning system for Cas9 and Cas12a use in barley and wheat. Proven Cas nuclease and guide expression cassette options found in the toolkit will facilitate highly efficient simplex and multiplex mutagenesis in both species. We incorporate GRF-GIF transformation boosting cassettes in wheat options to maximise workflow efficiency.

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Recommendations for prosthesis type in older patients who underwent surgical aortic valve replacement (SAVR) are established, albeit undervalidated. The purpose of this study is to compare outcomes after bioprosthetic versus mechanical SAVR across various age groups. This was a retrospective study using an institutional SAVR database. All patients who underwent isolated SAVR were compared across valve types and age strata (<65 years, 65 to 75 years, >75 years). Patients who underwent concomitant operations, aortic root interventions, or previous aortic valve replacement were excluded. Objective survival and aortic valve reinterventions were compared. Kaplan-Meier survival estimation and multivariate regression were performed. A total of 1,847 patients underwent SAVR from 2010 to 2023. A total of 1,452 patients (78.6%) received bioprosthetic valves, whereas 395 (21.4%) received mechanical valves. Of those who received bioprosthetic valves, 349 (24.0%) were aged <65 years, 627 (43.2%) were 65 to 75 years, and 476 (32.8%%) were older than 75 years. For patients who received mechanical valves, 308 (78.0%) were aged <65 years, 84 (21.3%) were between 65 and 75 years, and 3 (0.7%) were >75 years. The median follow-up in the total cohort was 6.2 (2.6 to 8.9) years. No statistically significant differences were observed in early-term Kaplan-Meier survival estimates between SAVR valve types in all age groups. However, the cumulative incidence estimates of aortic valve reintervention were significantly higher in patients aged under 65 years who received bioprosthetic than those who received mechanical valves, with 5-year reintervention rates of 5.8% and 3.1%, respectively (p = 0.002). On competing risk analysis for valve reintervention, bioprosthetic valves were significantly associated with an increased hazard of aortic valve reintervention (hazard ratio 3.35, 95% confidence interval 1.73 to 6.49, p <0.001). In conclusion, SAVR with bioprosthetic valves (particularly, in patients aged <65 years) was comparable in survival to mechanical valve SAVR but significantly associated with increased valve reintervention rates.

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OBJECTIVES: Report two-years of training injury data in senior and academy professional rugby league. DESIGN: Prospective cohort study. METHODS: Match and training time-loss injuries and exposure data were recorded from two-seasons of the European Super League competition. Eleven/12 (2021) and 12/12 (2022) senior and 8/12 (2021) and 12/12 (2022) academy teams participated. Training injuries are described in detail and overall match injuries referred to for comparison only. RESULTS: 224,000 training exposure hours were recorded with 293 injuries at the senior (mean [95 % confidence interval]; 3 [2-3] per 1000 h) and 268 academy level (2 [2-3] per 1000 h), accounting for 31 % and 40 % of all injuries (i.e., matches and training). The severity of training injuries (senior: 35 [30-39], academy: 36 [30-42] days-lost) was similar to match injuries. Lower-limb injuries had the greatest injury incidence at both levels (senior: 1.85 [1.61-2.12], academy: 1.28 [1.08-1.51] per 1000 h). Head injuries at the academy level had greater severity (35 [25-45] vs. 18 [12-14] days-lost; p < 0.01) and burden (17 [16-18] vs. 4 [4-5] days-lost per 1000 h; p = 0.02) than senior level. At the senior level, the incidence of contact injuries was lower than non-contact injuries (risk ratio: 0.29 [0.09-0.88], p = 0.02). CONCLUSIONS: Training injuries accounted for about a third of injuries, with similar injury severity to match-play. Within training there is a higher rate of non-contact vs. contact injuries. Whilst current injury prevention interventions target matches, these data highlight the importance of collecting high quality training injury data to develop and evaluate injury prevention strategies in training.

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INTRODUCTION: Becoming a general practitioner (or family medicine specialist) is challenging, as trainees learn to manage complex and ambiguous situations. Feedback is a key component of this learning. Although research has tended to focus on feedback's momentary processes and impacts, there is value in seeking to understand the work it does over time and how trainees position themselves across multiple feedback encounters. We ask: how do newly qualified GPs narrate themselves and their experiences with complex performance challenges? Within these narratives, what is the role of feedback? METHODS: The research adopts a holistic and sequential narrative analysis approach, with in-depth narrative interviews of 16 general practice trainees who had just completed their training requirements. The analysis involved restorying the participant narratives chronologically. Each narrative formed a unit of analysis where narrative commonalities across plots, characters, emotions and the role of feedback were interpreted. RESULTS: Four plotlines within GP trainees' stories of complex performance challenges were identified: Journeyperson, Hero's Quest, Solo Journeyer and Endless Struggle. Trainees, supervisors and feedback are positioned differently within these plotlines. Narratives were saturated with emotions. DISCUSSION: The plotlines bring together an alternative way of understanding how feedback, learning and becoming are woven together. They illustrate how multiple interactions with patients, supervisors, peers and systems thread together into an overall trajectory. How a trainee positions themselves as protagonists and who they characterise as their antagonists can help direct the focus of supervisors' feedback conversations.

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OBJECTIVES: To compare match injury incidence, severity and burden in men's and women's elite rugby league. DESIGN: A prospective cohort epidemiological study. METHODS: Time loss match injury data were collected from all men's (11,301 exposure hours) and women's (5,244 exposure hours) Super League clubs. RESULTS: Injury incidence and burden were not different between men and women (mean [95 % CI]; 54 [45 to 65] vs. 60 [49 to 74] per 1000 match-hours; p = 0.39, and 2332 [1844 to 2951] vs. 1951 [1560 to 2440] days lost per 1000 match-hours; p = 0.26). However, injury severity was greater for men than women (42 [35-50] vs. 35 [29 to 42]; p = 0.01). Lower limbs accounted for 54 % and 52 % of injuries for men and women, with the head/face the most frequently injured location due to concussion (12 [10 to 15] and 10 [8 to 14] per 1000 match-hours for men and women). Injuries to the knee had the greatest burden for men and women (708 [268-1868] and 863 [320-2328] days lost per 1000 match-hours). Being tackled was the most common injury mechanism for men and women (28 % and 38 %) with greater burden (p < 0.01) than other injury mechanisms. CONCLUSIONS: Male and female rugby league players have similar injury incidence and burden; however, injury severity was higher in men. Head/face injuries have the highest injury incidence and knee injuries have the highest burden. These injuries should be the focus for prevention initiatives at a league (via laws), player, and coach level, with equal and specific focus for both men's and women's rugby league players.

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This study examined the association between a dental implant and changes in adjacent teeth over time. Electronic health records of 1818 patients who received a dental implant were retrospectively evaluated over 14 years (2005-2019) in a university setting. The status of the adjacent tooth and vertical and horizontal distance from the implant platform to adjacent teeth were determined using digital intraoral radiographs taken at baseline and the last follow-up visit (1-14 years, median four years). In total, 1085 dental implants were evaluated. There were 234 instances of a change in the adjacent tooth. Decay was observed in 83 (7.6%) of adjacent teeth; the mean time to development was four years (range 1 to 14 years). Approximately 9% of adjacent teeth received direct restorations, 4.8% received indirect restorations, 1% received endodontic root canal treatment (RCT), and 5.6% were extracted. The mean horizontal distance between the implant platform and the adjacent teeth was 3.56 mm; the mean vertical distance from the contact point to the alveolar crest on the tooth side was 6.2 mm at the 1st time of the reported decay on x-ray. These distances did not significantly influence the occurrence of caries. The prevalence of interproximal contact loss (ICL) was higher on the mesial of the implant crown at 63% compared to 20% on the distal side. This large retrospective analysis identified that teeth adjacent to a dental implant were at risk of decay and changes in their condition. In addition, the implant-to-tooth distance and inadequate emergence profile may contribute as caries risk factors in addition to hygiene and a high sugar level diet. These findings appear essential for clinicians when making treatment decisions and discussing outcomes with patients.

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Recognising and removing players with suspected sport-related concussions is crucial for community sports. OBJECTIVES: Quantify rates and factors associated with non-reporting of concussion symptoms in community rugby league. METHODS: Overall, 484 community rugby league players aged ≥18 years and 965 parents of rugby league players aged <18 years completed an online survey, regarding concussion history, knowledge, prevalence and reasons for non-reporting of concussion, long-term implications and perceptions of concussion. RESULTS: Thirty-five percent of players aged ≥18 years and 22% of parents of players aged <18 years reported at least one concussion in the last two seasons. Forty-three percent of players aged ≥18 years and 5% of parents of players aged<18 years surveyed stated they did not report concussion-related symptoms sustained during 2020 and 2021 seasons. The two most common reasons for non-reporting of concussion symptoms were 'didn't want to be ruled out of a match' and 'didn't want to let down the team'. Players aged ≥18 years who received external coaching pressures around concussion were more likely to not report concussion symptoms. Over 40% of parents and players were concerned about the potential long-term implications. Ten percent of players aged ≥18 years and 7% of parents of players aged <18 years would encourage their family members/children to not play rugby league. CONCLUSIONS: Non-reporting rates of suspected concussion symptoms in adult community players were twice as high as in professional rugby league, with similar reasons (wanting to play and not letting the team down). Engaging coaches to prioritise brain health and providing broader and appropriate education on concussion should be focused on, given the concerns reported by community players and parents.

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INTRODUCTION: The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is an ongoing Australian prospective cohort study investigating how modifiable prenatal and early-life exposures drive the development of islet autoimmunity and type 1 diabetes (T1D) in children. In this profile, we describe the cohort's parental demographics, maternal and neonatal outcomes and human leukocyte antigen (HLA) genotypes. RESEARCH DESIGN AND METHODS: Inclusion criteria were an unborn child, or infant aged less than 6 months, with a first-degree relative (FDR) with T1D. The primary outcome was persistent islet autoimmunity, with children followed until a T1D diagnosis or 10 years of age. Demographic data were collected at enrollment. Lifestyle, clinical and anthropometric data were collected at each visit during pregnancy and clinical pregnancy and birth data were verified against medical case notes. Data were compared between mothers with and without T1D. HLA genotyping was performed on the ENDIA child and all available FDRs. RESULTS: The final cohort comprised 1473 infants born to 1214 gestational mothers across 1453 pregnancies, with 80% enrolled during pregnancy. The distribution of familial T1D probands was 62% maternal, 28% paternal and 11% sibling. The frequency of high-risk HLA genotypes was highest in T1D probands, followed by ENDIA infants, and lowest among unaffected family members. Mothers with T1D had higher rates of pregnancy complications and perinatal intervention, and larger babies of shorter gestation. Parent demographics were comparable to the Australian population for age, parity and obesity. A greater percentage of ENDIA parents were Australian born, lived in a major city and had higher socioeconomic advantage and education. CONCLUSIONS: This comprehensive profile provides the context for understanding ENDIA's scope, methodology, unique strengths and limitations. Now fully recruited, ENDIA will provide unique insights into the roles of early-life factors in the development of islet autoimmunity and T1D in the Australian environment. TRIAL REGISTRATION NUMBER: ACTRN12613000794707.

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Objectives: Tackles making contact above the sternum increase concussion and head injury assessment (HIA) risk in Rugby Union. The sport has introduced harsher sanctions to change tackler behaviours to reduce this risk. This increased high tackle sanction numbers, though it is unknown whether sanction severity is associated with injury risk. Methods: The sanction decision made by match officials for tackles resulting in 157 HIA1 removals, of which 91 were confirmed concussions, was evaluated. The propensity of sanction types, ranging from no foul play to red card, was compared after calculating concussion and HIA1 numbers per 1000 tackles of each sanction, using total tackle number of each sanction type from one season of two elite professional competitions. Results: HIA1 removal and concussion risk increased as sanction severity increased. Red-carded tackles were 271.5 (95% CI 143.8 to 512.6) times more likely to result in concussions than legal tackles. Tacklers and ball carriers were more likely to experience concussions from sanctioned high tackles, with tackler risk 28.5 (95% CI 13.5 to 59.9) times higher for sanctioned high tackles compared with legal tackles, and ball carrier risk elevated 133.7-fold (95% CI 65.5 to 272.8) after sanctioned high tackles. Conclusion: Sanctioned high tackles significantly increase concussion and HIA1 risk to both tacklers and ball carriers. Current decision-making frameworks that guide sanction decisions do identify tackle behaviours that elevate clinical risk. Both tacklers and ball carriers would be less likely to experience concussions and head injuries if the frequency of illegal high tackles is decreased.