Sink or Swim? A survival analysis of sport dropout in Australian youth swimmers.

OBJECTIVES: To examine long-term participation and dropout rates in Australian youth swimming using survival analyses and to determine whether multiple individual, socio-demographic, and competition-related factors influenced dropout. DESIGN: Retrospective cohort study of registration and competitive performance data. METHODS: Part 1-Registration data from N = 17 161 female (n = 9400) and male (n = 7761) New South Wales (NSW) swimmers aged 10-15 years (inclusive). Part 2-Competition level involvement in a subsample of female (n = 1011) and male (n = 811) swimmers, aged 12-15 years, was also examined. To determine dropout rates and influential factors, Kaplan-Meier survival analyses supplemented by Cox regression were used. RESULTS: (1) Kaplan-Meier analyses identified median sustained participation rates of four years (95% CI = 3.93-4.06), with 15.9% maintaining participation over 10 years. Cox regressions identified age-group was associated with dropout (P < .001), with a 184.9% higher Hazard Rate (HR) for 10- vs 15-year-olds. Residential proximity to major cities was associated with dropout (P < .001), with urban swimmers reporting a 24.8% higher HR rate than rural swimmers. Sex and relative age were not associated with dropout. (2) The subsample median sustained participation was five years (95% CI = 4.79-5.20), with 25.3% maintaining participation for ten years. Level of competition was associated (P < .001), with an 86% higher HR when considering lower competition levels (ie, club/district v national). CONCLUSION: In a large representative sample of swimmers, survival analyses identified age-group, competition level, and city proximity were associated with increased swimming dropout rates.

Testing the application of corrective adjustment procedures for removal of relative age effects in female youth swimming.

The purpose of this study was (1) accurately estimate longitudinal relationships between decimal age (i.e., chronological and relative) and performance in Australian female 100 m (N = 765) and 200 m (N = 428) Breaststroke swimmers (10-18 years); and (2) determine whether corrective adjustment procedures could remove Relative Age Effects (RAEs) in an independent sample of age-matched 100 m (N = 2,491) and 200 m (N = 1,698) state/national level Breaststroke swimmers. In Part 1, growth curve modelling quantified longitudinal relationships between decimal age and swimming performance. In Part 2, relative age distributions (Quartile 1-4) for "All", "Top 25%" and "10%" of swimming times were examined based on raw and correctively adjusted swim times for age-groups. Based on raw swim times, finding identified RAE effect sizes increased in magnitude (small-medium) with selection level ("All"-"Top 25%") in 12-14 years age-groups for both events. However, when correctively adjusted swim performances were examined, RAEs were primarily absent across all age-groups and selection levels. Using longitudinal reference data, corrective adjustment procedures removed relative age advantages in female youth Breaststroke performance. Removing the influence of relative age-related differences is predicted to improve the accuracy of identifying genuinely skilled youth swimmers.

A Newly Discovered Antifibrotic Pathway Regulated by Two Fatty Acid Receptors: GPR40 and GPR84.

Numerous clinical conditions can lead to organ fibrosis and functional failure. There is a great need for therapies that could effectively target pathophysiological pathways involved in fibrosis. GPR40 and GPR84 are G protein-coupled receptors with free fatty acid ligands and are associated with metabolic and inflammatory disorders. Although GPR40 and GPR84 are involved in diverse physiological processes, no evidence has demonstrated the relevance of GPR40 and GPR84 in fibrosis pathways. Using PBI-4050 (3-pentylbenzeneacetic acid sodium salt), a synthetic analog of a medium-chain fatty acid that displays agonist and antagonist ligand affinity toward GPR40 and GPR84, respectively, we uncovered an antifibrotic pathway involving these receptors. In experiments using Gpr40- and Gpr84-knockout mice in models of kidney fibrosis (unilateral ureteral obstruction, long-term post-acute ischemic injury, and adenine-induced chronic kidney disease), we found that GPR40 is protective and GPR84 is deleterious in these diseases. Moreover, through binding to GPR40 and GPR84, PBI-4050 significantly attenuated fibrosis in many injury contexts, as evidenced by the antifibrotic activity observed in kidney, liver, heart, lung, pancreas, and skin fibrosis models. Therefore, GPR40 and GPR84 may represent promising molecular targets in fibrosis pathways. We conclude that PBI-4050 is a first-in-class compound that may be effective for managing inflammatory and fibrosis-related diseases.

Advancing athlete development: How Percentile Comparison Methods (PCMs) can identify youth developmental profiles.

OBJECTIVES: Inter-individual developmental differences confound the capability to accurately evaluate youth athletic performance, highlighting the need for considerate methodology and analytical approaches. The present study demonstrated how Percentile Comparison Methods (PCMs) were developed, tested, and applied to identify athlete developmental profiles in Australian youth swimming. DESIGN: Cross-sectional. METHODS: Participants were N = 866 female 100-metre (m) Front-Crawl swimmers, aged 9-15 years, competing at 36 Australian regional-national level long course events. At respective events, swim performance time was collated alongside, age, date of birth, and anthropometric measures to identify age group, relative age, and maturity status. Quadratic relative age and maturity status with 100-m performance regression trendlines were generated. Then, individual swim performances at a given relative age or maturity status were converted into percentile rank distributions and compared with raw (unadjusted) annual age-group performance percentile ranks. RESULTS: At a cohort level, initial testing confirmed relative age and maturity-adjusted percentile rankings were associated with general rank improvements for relatively younger and later maturing swimmers compared to raw ranks (and vice versa). When assessing individual swimmer plots, where three percentile rank scores were compared and rank change threshold criteria applied, five Percentile Comparison Method profile types were identified, namely: 'Early Developing' (19 %); 'Later Developing' (18 %); 'Consistent' (15 %); 'Mixed' (38 %) and 'Counteracting' (10 %). Percentile Comparison Method plots helped identify developmentally (dis-)advantaged swimmers; specific factors leading to (dis-)advantage, and likely onward development trajectories. CONCLUSIONS: Overall and with practical considerations, Percentile Comparison Methods can improve the validity of youth athletic performance evaluation as well as inform athlete development programming.

Mitigating against relative age effects in youth Track & Field: Validating corrective adjustment procedures across multiple events.

OBJECTIVES: With the aim to better identify talented Track & Field performance development, this study estimated the relationships between chronological (decimal) age with 60-m sprint, high jump, triple jump, and pole vault performance. Then, to mitigate against expected Relative Age Effects (RAEs), Corrective Adjustment Procedures (CAPs) were applied to an independent sample. DESIGN: Mixed-longitudinal design examining public data between 2005 and 2019. METHODS: The performances of 5339 Italian sprinters and jumpers (53.1 %) spanning 11.01-17.99 years of age were examined, with trendlines between chronological age and performance established. Related to an independent sample (N = 40,306; female 45.5 %), trendlines were then utilised to apply CAPs and adjust individual performance. Considering raw and adjusted performance data, RAE distributions were examined for the top 25 % and 10 % performers. RESULTS: For all male and female events, quadratic models best summarised the relationships between chronological age and performance (R2 = 0.74-0.89). When examining independent athletes in similar event, RAEs were more pronounced in males (Cramer's V = 0.35-0.14) than females (Cramer's V = 0.29-0.07). For both sexes, RAE magnitude decreased with age and increased according to performance level (i.e., Top25%-Top10%). However, following CAP applications, RAEs were reduced or removed within annual age groups and performance levels. CONCLUSIONS: With RAEs prevalent across Italian youth Track & Field events, findings validate CAPs as a strategy to account for the influence of relative age differences on athletic performance. CAPs help establish a more equitable strategy for performance evaluation and could help improve the efficacy of long-term athlete development programming.

The Longitudinal Mediating Influence of Maturation on the Relationship Between Strength and Performance in Male Youth Swimmers.

PURPOSE: To examine the longitudinal relationships between shoulder internal and external rotation (IR and ER) strength, maturity status, and swim performance (aim 1). To determine whether maturity status mediated (partially/fully) the relationship between shoulder IR/ER strength and performance in age-group swimmers (aim 2). METHODS: Using a repeated-measures design, anthropometrics, maturity status, shoulder IR/ER strength, and 200-m front-crawl velocity were assessed over 3 competition seasons in N = 82 Australian male competitive swimmers (10-15 y). For aim 1, linear mixed models examined longitudinal relationships between assessed variables. For aim 2, causal mediation analyses examined proportional (in)direct contributions of maturity status between shoulder IR strength and swim performance. RESULTS: For aim 1, linear mixed models identified a significant relationship between shoulder IR strength and swim performance over time (F1,341.25 = 16.66, P < .001, marginal R2 = .13, conditional R2 = .91). However, maturity status was influential (ΔAkaike information criterion = -75.8, χ2 = 19.98, P < .001), suggesting removal of the shoulder IR strength-swim velocity relationship (F1,214.1 = 0.02, P = .88). For aim 2, mediation analyses identified maturity status as fully mediating the shoulder IR strength-swim velocity relationship (92.30%, P < .001). CONCLUSIONS: Shoulder IR and ER strength did not account for variance in longitudinal age-group swim performance independent of maturity status. Interindividual differences in maturity status fully explained the relationship between shoulder IR/ER strength and swim performance. For practitioners, findings promote the need to account for maturation status and question the rationale for upper-limb strength assessment during maturational years.

Longitudinal changing relationships between growth tempo and vertical stiffness in movement across maturation.

PURPOSE: To determine whether average growth tempo influenced longitudinal relationships between maturity status and coordination capability using a 15-s hopping task (Aim 1). To investigate how differences in absolute growth tempo were associated with change in coordination capability within and across peak growth (Aim 2). METHODS: Participants were N1 = 110 (Aim 1) and N2 = 71 (Aim 2) Australian male competitive swimmers, aged 10-15 years, exposed to repeated-measures tracking (2-years, and 12-months respectively) of maturity status, growth tempo and movement coordination capability. Coordination capability was estimated via vertical stiffness (KV) in a hopping task, reflected by participant mean KV and between-jump coefficient of variation (CV). RESULTS: For Aim 1, log-linear mixed model trends identified maturity status and growth tempo were significantly associated with KV mean and KV CV. For a given maturity status, mean KV was 9% lower in the 'High' average growth tempo group than the 'Low' average tempo group. For Aim 2, mixed repeated-measures analyses of variance identified how time points of increased growth tempo were significantly associated with 7-11% reductions in mean KV, with similar mean KV decrements irrespective of growth tempo group. Meanwhile, KVCV only illustrated progressive longitudinal reductions. CONCLUSIONS: Within maturational progression, short-term accelerations in growth tempo corresponded with short-term decreases in KV mean, suggesting temporary disruptions to movement coordination capability. Measuring growth tempo and applying hopping tasks in specific movement contexts could help consistently identify disturbances in motor coordination.

Corrective Adjustment Procedures as a strategy to remove Relative Age Effects: Validation across male and female age-group long jumping.

OBJECTIVES: To validate the application of Corrective Adjustment Procedures for removing Relative Age Effects in youth athletic contexts, this study estimated the longitudinal relationships between decimal age (chronological and relative) and performance in male and female long jumpers. Using trendlines, Corrective Adjustment Procedures were applied, and Relative Age Effect distributions associated with performance attainment were re-examined. DESIGN: Retrospective longitudinal design examining competitive long-jump data between 2005 and 2019. METHODS: In Part I, participants were 689 junior Italian long jumpers (age range = 11.01-17.99 years; 56.6% females) who participated in ≥three events. Longitudinal modelling and regression equations quantified the sex-specific relationships between decimal age and long jump performance. In Part II, equations were utilised to adjust individual performance within an independent sample (N = 13,639; 50.1% females) of age-matched jumpers. Relative Age Effect distributions within attainment levels (i.e., Top 25-10%) were examined based on raw and correctively adjusted performance. RESULTS: Irrespective of sex, Relative Age Effects were prevalent across all age-groups with medium-large effect sizes at 12-17 (males and females) and 12-17 years (females) of age (Cramer's V range = 0.07-0.28). Relative Age Effect bias magnitude also increased with attainment level (i.e., Top 25-10%). Following Corrective Adjustment Procedure application, typical Relative Age Effects were removed with non-significant deviations in relative age distributions regardless of sex or age-group or attainment level (Top 25 or 10%). CONCLUSIONS: Findings provide efficacy for Corrective Adjustment Procedure application to remove Relative Age Effects across youth long jumping events. Corrective Adjustment Procedures suggest potential in improving performance evaluation, identification of technically skilled performers, and sporting experiences.

Maturation-based Corrective Adjustment Procedures (Mat-CAPs) in youth swimming: Evidence for restricted age-group application in females.

Inter-individual differences in maturation-associated development can lead to variations in physical performance, resulting in performance (dis)advantages and maturation selection bias within youth sport systems. To address such bias and account for maturational differences, Maturation-based Corrective Adjustment Procedures (Mat-CAPs) could be beneficial. The present study aimed to: (1) determine maturity timing distributions in youth female swimming; (2) quantify the relationship between maturation status and 100-m front-crawl (FC) performance; (3) implement Mat-CAPs to remove maturational influences upon swimming performance. For Aim 1 and 2, participants were 663 female (10-15 years) swimmers who participated in 100-m FC events at Australian regional, state, and national-level competitions between 2016-2020 and underwent anthropometric assessment (mass, height and sitting height) to estimate maturity timing and offset. For Aim 3, participants aged 10-13 years were categorised into maturity timing categories. Maturity timing distributions for Raw ('All', 'Top 50%' and 'Top 25%') and Correctively Adjusted swim times were examined. Chi-square, Cramer's V and Odds Ratios determined the presence of maturation biases, while Mat-CAPs identified whether such biases were removed in targeted age and selection-groups. Results identified that between 10-13 years, a significantly higher frequency of 'early' maturers was apparent, although tapered toward higher frequencies of 'Late-normative' maturers by 14-15 years. A curvilinear relationship between maturity-offset and swim performance was identified (R2 = 0.51, p<0.001) and utilised for Mat-CAPs. Following Mat-CAPs application, maturity timing biases evident in affected age-groups (10-13 years), and which were magnified at higher selection levels ('Top 50%' & '25%' of swim performances) were predominantly removed. Findings highlight how maturation advantages in females occurred until approximately 13 years old, warranting restricted Mat-CAPs application. Mat-CAPS has the potential to improve female swimmer participation experiences and evaluation.

Longitudinal Relationships Between Maturation, Technical Efficiency, and Performance in Age-Group Swimmers: Improving Swimmer Evaluation.

PURPOSE: The study aimed to (1) accurately examine longitudinal relationships between maturity status and both technical skill indices and performance in Australian male (N = 64) age-group Front-crawl swimmers (10-15 y) and (2) determine whether individual differences in maturation influenced relationships between technical skill level and swimming performance. METHODS: A repeated-measures design was used to assess maturity status and performance on 200-m Front-crawl trial across 2 competition seasons (2018-2020). Assessments were made on 3 to 5 occasions (median = 3) separated by approximately 4 months. Average horizontal velocity and stroke frequency were used to calculate technical skill indices, specifically stroke index, and arm propelling efficiency. Relationships between variables were assessed using linear mixed models, identifying fixed, and random effect estimates. RESULTS: Curvilinear trends best described significant longitudinal relationships between maturity status with horizontal velocity (F = 10.33 [1, 233.77]; P = .002) and stroke index (F = 5.55 [1, 217.9]; P = .02) during 200-m Front-crawl trials. Maturity status was not significantly related to arm propelling efficiency (P = .08). However, arm propelling efficiency was an independent predictor of Front-crawl velocity (F = 55.89 [1, 210.45]; P < .001). CONCLUSIONS: Maturity status predicted assessment of swimmer technical skill (stroke index) and swimming performance. However, technical skill accessed via arm propelling efficiency was independent of maturation and was predictive of performance. Maturity status influences performance evaluation based on technical skill and velocity. Findings highlight the need to account for maturation and technical skill in age-group swimmers to better inform swimmer evaluation.

Maturity-related developmental inequalities in age-group swimming: The testing of 'Mat-CAPs' for their removal.

OBJECTIVES: To (1) examine the association between maturity timing and performance-based selection levels in (N=708) Australian male 100-m Freestyle swimmers (12-17 years); (2) identify the relationship between maturation status and 100-m Freestyle performance; and (3) determine whether Maturation-based Corrective Adjustment Procedures (Mat-CAPs) could remove maturation-related differences in swimming performance. METHODS: In Part 1, maturity timing category distributions ('Early', 'Early Normative', 'Late Normative' and 'Late') for 'All', 'Top 50%' and '25%' of raw swimming times were examined within and across age-groups. In Part 2, multiple regression analyses quantified the relationship between maturity offset (YPHV) and swimming performance. In Part 3, sample-based maturity timing category distributions were examined based on raw and correctively adjusted swim times for 12-17 year old age-groups. RESULTS: Based on raw swim times, a high prevalence of 'Early-maturing' swimmers, with large effect sizes was identified (e.g., 14 years 'All' - χ2 (3, 151=111.98, p<0.001; 'Early' v 'Late' OR=82.0 95%CI=4.77, 1409.9); while a complete absence of 'Late-maturers' was apparent in the sample (N=708). When maturity categories were re-defined based on sample mean±standard deviation, and when using the expected curvilinear trendline identified in Part 2, Mat-CAPs mitigated maturity timing biases across all age-groups and selection levels, and removed the Freestyle performance advantage afforded by advanced maturity timing and status. CONCLUSIONS: Removing the influence of maturation-related developmental differences could help improve youth swimmer participation experiences and improve the accuracy of identifying genuinely skilled age-group swimmers.

Synthesis and antimicrobial activity of 2-fluorophenyl-4,6-disubstituted [1,3,5]triazines.

A series of 2-fluorophenyl-4,6-disubstituted [1,3,5]triazines (1) and (2) were synthesized and evaluated for their antimicrobial activity against three representative gram-positive bacteria and two fungi. The structure-activity relationship (SAR) demonstrates that the 3- or 4-fluorophenyl component attached directly to the triazine ring was essential for activity. Of these compounds, 14, 15, and 25 demonstrated significant activity against all selected organisms compared to control. These compounds were generally nontoxic and may prove useful as antimicrobial agents.

Fatty acid mimetic PBI-4547 restores metabolic homeostasis via GPR84 in mice with non-alcoholic fatty liver disease.

Non-alcoholic Fatty Liver Disease (NAFLD) is the most common form of liver disease and is associated with metabolic dysregulation. Although G protein-coupled receptor 84 (GPR84) has been associated with inflammation, its role in metabolic regulation remains elusive. The aim of our study was to evaluate the potential of PBI-4547 for the treatment of NAFLD and to validate the role of its main target receptor, GPR84. We report that PBI-4547 is a fatty acid mimetic, acting concomitantly as a GPR84 antagonist and GPR40/GPR120 agonist. In a mouse model of diet-induced obesity, PBI-4547 treatment improved metabolic dysregulation, reduced hepatic steatosis, ballooning and NAFLD score. PBI-4547 stimulated fatty acid oxidation and induced gene expression of mitochondrial uncoupling proteins in the liver. Liver metabolomics revealed that PBI-4547 improved metabolic dysregulation induced by a high-fat diet regimen. In Gpr84-/- mice, PBI-4547 treatment failed to improve various key NAFLD-associated parameters, as was observed in wildtype littermates. Taken together, these results highlight a detrimental role for the GPR84 receptor in the context of meta-inflammation and suggest that GPR84 antagonism via PBI-4547 may reflect a novel treatment approach for NAFLD and its related complications.

Removing relative age effects from youth swimming: The development and testing of corrective adjustment procedures.

OBJECTIVES: (1) Generate accurate estimates of the relationship between decimal age (i.e., chronological and relative) with swimming performance based on longitudinal data. (2) Determine whether corrective adjustment procedures can remove Relative Age Effects (RAEs) from junior/youth swimming. DESIGN: Longitudinal and repeated years of cross-sectional performance data were examined. METHODS: (1) Participants were 553 male 100m Freestyle swimmers (10-18 years) who participated in ≥five annual events between 1999-2017. Growth curve modelling quantified the relationship between age and swimming performance, permitting corrective adjustment calculations. (2) Participants were N=2141 male 100m Freestyle swimmers (13-16 years) who swam at state/national events in 2015-2017. Relative age distributions for 'All', 'Top 50%', '25%' and '10%' of swimming times were examined based on raw and correctively adjusted swim times. Chi-square, Cramer's V and Odds Ratios (OR) determined whether relative age (quartile) inequalities existed according to age-groups, selection level and correctively adjusted swim times. RESULTS: Based on raw swim times, for 'All' swimmers RAEs was evident at 13 and 14 years-old and dissipated thereafter. But, RAE effect sizes substantially increased with selection level, with large-medium effects between 13-15 years-old (e.g., 15 years - Top 50% Q1v Q4 OR=2.28; Top 10%=6.02). However, when correctively adjusted swim times were examined, RAEs were predominantly absent across age-group and selection levels. CONCLUSIONS: With accurate longitudinal reference data, corrective adjustment procedures effectively removed RAEs from 100m Freestyle swimming performance, suggesting the potential to improve swimming participation experience and performance evaluation.

Transient Relative Age Effects across annual age groups in National level Australian Swimming.

OBJECTIVES: To determine the prevalence, magnitude and transient patterning of Relative Age Effects (RAEs) according to sex and stroke event across all age-groups at the Australian National age swimming Championships. DESIGN: Repeated years of cross-sectional participation data were examined. METHODS: Participants were 6014 unique male (3185) and female (2829) swimmers (aged 12-18 years) who participated in Freestyle (50, 400m) and/or Breaststroke (100, 200m) at the National age swimming Championships between 2000-2014 (inclusive). RAE prevalence, magnitude and transience were determined using Chi-square tests and Cramer's V estimates for effect size. Odds Ratios (OR) and 95% Confidence Intervals (CI) examined relative age quartile discrepancies. These steps were applied across age-groups and according to sex and each stroke event. RESULTS: Consistent RAEs with large-medium effect sizes were evident for males at 12-15 years of age respectively, and with large-medium effects for females at 12-14 respectively across all four swimming strokes. RAE magnitude then consistently reduced with age across strokes (e.g., Q1 vs. Q4 OR range 16year old males=0.94-1.20; females=0.68-1.41). With few exceptions, by 15-16 years RAEs had typically dissipated; and by 17-18 years, descriptive and significant inverse RAEs emerged, reflecting overrepresentation of relatively younger swimmers. CONCLUSIONS: Performance advantages associated with relative age (and thereby likely growth and maturation) are transient. Greater consideration of transient performance and participation in athlete development systems is necessary. This may include revising the emphasis of sport programmes according to developmental stages and delaying forms of athlete selection to improve validity.

Design and Synthesis of New 1,3,5-Trisubstituted Triazines for the Treatment of Cancer and Inflammation.

Low-molecular-weight synthetic molecules 1 with the general 2-(fluorophenylamino)-4,6-disubstituted 1,3,5-triazine structure and showing anti-inflammatory and anticancer activities were explored. Structure-activity relationship studies demonstrated the importance of the aminopentyl chain, the 3- or 4-fluorophenylaniline component, and the presence of at least one substituent, such as a tyramine moiety, attached directly to the triazine ring as essential for good activity. These compounds, represented by leads 4-{2-[4-(5-Aminopentylamino)-6-(3-fluorophenylamino)-1,3,5-triazin-2-ylamino]ethyl}phenol (6) and 4-{2-[4-(5-Aminopentylamino)-6-(4-fluorophenylamino)-1,3,5-triazin-2-ylamino]ethyl}phenol (10), displayed moderate and significant in vitro and in vivo dual activities, respectively, and address the molecular link between inflammation and cancer. Compound 10 demonstrated significant antitumor efficacy upon administration by the oral and intravenous routes in several animal models. This class of triazine compounds is new, safe, and nontoxic and offers a novel approach to the treatment of inflammation and cancer.

2,4,6-trisubstituted triazines as protein a mimetics for the treatment of autoimmune diseases.

A first-in-class series of low molecular weight trisubstituted triazines were synthesized and evaluated for their ability to mimic protein A binding to human IgG antibody. The structure-activity relationship (SAR) demonstrates that the 1,3-phenylenediamine component was essential for robust activity. Twenty-two compounds, represented by lead molecule 34, displayed significant activity compared to protein A. These compounds may prove useful for the treatment of autoimmune disease.