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Multiple myeloma (MM), a hematologic malignancy that preferentially colonizes the bone marrow, remains incurable with a survival rate of 3 to 6 mo for those with advanced disease despite great efforts to develop effective therapies. Thus, there is an urgent clinical need for innovative and more effective MM therapeutics. Insights suggest that endothelial cells within the bone marrow microenvironment play a critical role. Specifically, cyclophilin A (CyPA), a homing factor secreted by bone marrow endothelial cells (BMECs), is critical to MM homing, progression, survival, and chemotherapeutic resistance. Thus, inhibition of CyPA provides a potential strategy to simultaneously inhibit MM progression and sensitize MM to chemotherapeutics, improving therapeutic response. However, inhibiting factors from the bone marrow endothelium remains challenging due to delivery barriers. Here, we utilize both RNA interference (RNAi) and lipid-polymer nanoparticles to engineer a potential MM therapy, which targets CyPA within blood vessels of the bone marrow. We used combinatorial chemistry and high-throughput in vivo screening methods to engineer a nanoparticle platform for small interfering RNA (siRNA) delivery to bone marrow endothelium. We demonstrate that our strategy inhibits CyPA in BMECs, preventing MM cell extravasation in vitro. Finally, we show that siRNA-based silencing of CyPA in a murine xenograft model of MM, either alone or in combination with the Food and Drug Administration (FDA)-approved MM therapeutic bortezomib, reduces tumor burden and extends survival. This nanoparticle platform may provide a broadly enabling technology to deliver nucleic acid therapeutics to other malignancies that home to bone marrow.
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Mieloma Múltiplo , Estados Unidos , Humanos , Animais , Camundongos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Medula Óssea , RNA Interferente Pequeno/genética , Células Endoteliais , Ciclofilina A , Lipídeos , Microambiente TumoralRESUMO
This study aimed to optimise performance prediction in short-course swimming through Principal Component Analyses (PCA) and multiple regression. All women's freestyle races at the European Short-Course Swimming Championships were analysed. Established performance metrics were obtained including start, free-swimming, and turn performance metrics. PCA were conducted to reduce redundant variables, and a multiple linear regression was performed where the criterion was swimming time. A practical tool, the Potential Predictor, was developed from regression equations to facilitate performance prediction. Bland and Altman analyses with 95% limits of agreement (95% LOA) were used to assess agreement between predicted and actual swimming performance. There was a very strong agreement between predicted and actual swimming performance. The mean bias for all race distances was less than 0.1s with wider LOAs for the 800 m (95% LOA -7.6 to + 7.7s) but tighter LOAs for the other races (95% LOAs -0.6 to + 0.6s). Free-Swimming Speed (FSS) and turn performance were identified as Key Performance Indicators (KPIs) in the longer distance races (200 m, 400 m, 800 m). Start performance emerged as a KPI in sprint races (50 m and 100 m). The successful implementation of PCA and multiple regression provides coaches with a valuable tool to uncover individual potential and empowers data-driven decision-making in athlete training.
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Desempenho Atlético , Análise de Componente Principal , Natação , Humanos , Natação/fisiologia , Desempenho Atlético/fisiologia , Feminino , Modelos Lineares , Comportamento Competitivo/fisiologiaRESUMO
Chromosome 13q deletion [del(13q)], harboring the miR-15a/16-1 cluster, is one of the most common genetic alterations in mature B-cell malignancies, which originate from germinal center (GC) and post-GC B cells. Moreover, miR-15a/16 expression is frequently reduced in lymphoma and multiple myeloma (MM) cells without del(13q), suggesting important tumor-suppressor activity. However, the role of miR-15a/16-1 in B-cell activation and initiation of mature B-cell neoplasms remains to be determined. We show that conditional deletion of the miR-15a/16-1 cluster in murine GC B cells induces moderate but widespread molecular and functional changes including an increased number of GC B cells, percentage of dark zone B cells, and maturation into plasma cells. With time, this leads to development of mature B-cell neoplasms resembling human extramedullary plasmacytoma (EP) as well as follicular and diffuse large B-cell lymphomas. The indolent nature and lack of bone marrow involvement of EP in our murine model resembles human primary EP rather than MM that has progressed to extramedullary disease. We corroborate human primary EP having low levels of miR-15a/16 expression, with del(13q) being the most common genetic loss. Additionally, we show that, although the mutational profile of human EP is similar to MM, there are some exceptions such as the low frequency of hyperdiploidy in EP, which could account for different disease presentation. Taken together, our studies highlight the significant role of the miR-15a/16-1 cluster in the regulation of the GC reaction and its fundamental context-dependent tumor-suppression function in plasma cell and B-cell malignancies.
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Linfoma Difuso de Grandes Células B/genética , MicroRNAs/genética , Neoplasias de Plasmócitos/genética , Animais , Linfócitos B/metabolismo , Linfócitos B/patologia , Deleção Cromossômica , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/patologia , Cromossomos Humanos Par 13/genética , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/patologia , Camundongos Endogâmicos C57BL , Família Multigênica , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Neoplasias de Plasmócitos/patologia , Plasmócitos/metabolismo , Plasmócitos/patologia , Plasmocitoma/genética , Plasmocitoma/patologiaRESUMO
The aims of the study were to provide benchmarks and normative data for 100 m, 200 m, and 400 m short-course individual medley (IM) races, investigate differences between the various swimming strokes and turns involved in IM, and quantify the effect and contribution of various race sections on swimming performance. All IM races (n = 320) at the 2019 European Short-Course Swimming Championships were video monitored and digitized with interrater reliability described by a mean intra-class correlation coefficient of 0.968. Normative data were provided for the eight finalists of each event (FINA points = 886 ± 37) and the eight slowest swimmers from each event (FINA points = 688 ± 53). Contribution and effects of race sections on swimming performance were investigated using stepwise regression analysis based on all races of each event. Regression analysis explained 97-100% of total variance in race time and revealed turn time (ß ≥ 0.53) as distinguishing factor in short-course IM races in addition to swim velocity (ß ≥ -0.28). Start time only affected 100 m (ß ≥ 0.14) and 200 m (ß ≥ 0.04) events. Fastest turn times were found for the butterfly/backstroke turn. Breaststroke showed slowest swim velocities and no difference between fastest and slowest 100 m IM swimmers. Therefore, breaststroke may provide largest potential for future development in IM race times. Correlation analyses revealed that distance per stroke (r ≥ -0.39, P < 0.05) rather than stroke rate (r ≤ -0.18, P > 0.05) is a performance indicator and may be used by coaches and performance analysts to evaluate stroke mechanics in male IM swimmers despite its more complex assessment. Performance analysts, coaches, and swimmers may use the present normative data to establish minimal and maximal requirements for European Championship participation and to create specific drills in practice.
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Desempenho Atlético , Natação , Comportamento Competitivo , Humanos , Masculino , Análise de Regressão , Reprodutibilidade dos TestesRESUMO
The aims of the study were to assess the robustness and non-reactiveness of wearable near-infrared spectroscopy (NIRS) technology to monitor exercise intensity during a real race scenario, and to compare oxygenation between muscle groups important for cross-country skiing (XCS). In a single-case study, one former elite XCS (age: 39 years, peak oxygen uptake: 65.6 mL/kg/min) was equipped with four NIRS devices, a high-precision global navigation satellite system (GNSS), and a heart rate (HR) monitor during the Vasaloppet long-distance XCS race. All data were normalized to peak values measured during incremental laboratory roller skiing tests two weeks before the race. HR reflected changes in terrain and intensity, but showed a constant decrease of 0.098 beats per minute from start to finish. Triceps brachii (TRI) muscle oxygen saturation (SmO2) showed an interchangeable pattern with HR and seems to be less affected by drift across the competition (0.027% drop per minute). Additionally, TRI and vastus lateralis (VL) SmO2 revealed specific loading and unloading pattern of XCS in uphill and downhill sections, while rectus abdominus (RA) SmO2 (0.111% drop per minute) reflected fatigue patterns occurring during the race. In conclusion, the present preliminary study shows that NIRS provides a robust and non-reactive method to monitor exercise intensity and fatigue mechanisms when applied in an outdoor real race scenario. As local exercise intensity differed between muscle groups and central exercise intensity (i.e., HR) during whole-body endurance exercise such as XCS, NIRS data measured at various major muscle groups may be used for a more detailed analysis of kinetics of muscle activation and compare involvement of upper body and leg muscles. As TRI SmO2 seemed to be unaffected by central fatigue mechanisms, it may provide an alternative method to HR and GNSS data to monitor exercise intensity.
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Esqui , Adulto , Fadiga , Humanos , Perna (Membro) , Músculo Esquelético , Consumo de Oxigênio , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
PURPOSE: We compared the accuracy of orbital volume correction between the transorbital and transantral reconstructive techniques. MATERIALS AND METHODS: A retrospective cohort study was performed of patients who had undergone repair of isolated, unilateral orbital floor blowout fractures at Legacy Emanuel Hospital from 2013 to 2018. A total of 21 patients were identified and included in the predictor variable cohorts of the transorbital versus transantral repair technique. The outcome variable of orbital volume correction was evaluated by comparing the volume of the postoperative repaired orbits with that of the contralateral noninjured orbits. Additional ordinal variables analyzed included the preoperative orbital defect size and analysis of the transantral cohort stratified by the plating technique used. Data were assessed using analysis of variance and paired t tests. RESULTS: A transantral approach was used for orbital repair in 9 patients. In these patients, the postoperative orbital volume in the injured orbit was 2.69% greater than that in the uninjured orbit. The 12 patients who had undergone transantral repair had a postoperative orbital volume in the injured orbit that was 0.56% smaller than that of the uninjured orbit (P = .033). Division of the transantral cohort into 2 different plating techniques identified a less than 1% difference in mean orbital volume correction between the 2 techniques (P = .104). The average defect volume before transorbital repair was 4.87 cm3 compared with 5.22 cm3 for transantral repair (P = .907). CONCLUSIONS: The results from the present study have shown that the accuracy of orbital volume correction using the transantral approach will be comparable to that of the transorbital approach, as shown by a small, but statistically significant, increased accuracy in the volume correction with the transantral approach. Additional investigation to establish clinical correlations with these findings should be conducted.
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Fraturas Orbitárias/cirurgia , Procedimentos de Cirurgia Plástica , Fixação Interna de Fraturas , Humanos , Órbita/cirurgia , Estudos RetrospectivosRESUMO
Keller, S, Koob, A, Corak, D, von Schöning, V, and Born, DP. How to improve change-of-direction speed in junior team sport athletes-Horizontal, vertical, maximal, or explosive strength training? J Strength Cond Res 34(2): 473-482, 2020-The purpose of the study was to compare the effects of 4 different training methods on change-of-direction (COD) speed in junior team sport athletes. Specifically, we investigated whether horizontal load training incorporating lateral acceleration and deceleration would induce superior performance adaptations with respect to COD speed, compared with common vertically oriented maximal strength (squats and deadlifts), explosive strength (power clean and high pull), and vertical jumping exercises. Male U15 team sport athletes (n = 45) were assigned to 1 of 4 groups and performed 2 intervention training sessions per week for 4 weeks, in addition to their usual sport-specific training. Before and after the training period, COD speed, countermovement and drop jump heights, 1-legged lateral jump, and standing long jump performance were assessed. All 4 training groups improved COD speed (p ≤ 0.01, effect size [ES] ≥1.35). Countermovement and 1-legged lateral jump performance improved with the horizontal load (p < 0.01, ES = 0.81 and p < 0.01, ES = 1.36), maximal (p = 0.01, ES = 0.56 and p < 0.01, ES = 1.14), and explosive strength training (p < 0.01, ES = 0.95 and p < 0.01, ES = 1.60, respectively). The standing long jump improved with the maximal (p < 0.01, ES = 1.14) and explosive strength training (p < 0.01, ES = 0.60). In conclusion, all 4 training methods improved the COD speed in junior U15 team sport athletes. These findings emphasize the importance of well-developed lower-body strength and power, which contribute to fast COD speed. From a practical perspective, conditioning programs for junior athletes can incorporate horizontally and vertically oriented exercises with similar effectiveness on COD speed.
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Desempenho Atlético/fisiologia , Treinamento Resistido/métodos , Aceleração , Adolescente , Atletas , Desaceleração , Teste de Esforço , Humanos , Masculino , Força Muscular/fisiologia , Orientação Espacial/fisiologiaRESUMO
Born, DP, Stöggl, T, Petrov, A, Burkhardt, D, Lüthy, F, and Romann, M. Analysis of freestyle swimming sprint start performance after maximal strength or vertical jump training in competitive female and male junior swimmers. J Strength Cond Res 34(2): 323-331, 2020-To investigate the freestyle swimming sprint start performance before and after 6 weeks of maximal strength compared with vertical jump training. With a between-group repeated-measure design, 21 junior swimmers (12 female and 9 male) competing in national and international championships performed 2 weekly sessions of either maximal strength (heavy-loaded back squat and deadlift exercise) or vertical jump training (unloaded box jumps) for 6 weeks during the precompetition phase of the seasonal main event. Session ratings of perceived exertion were used to compare the load of both training programs. Before and after the training period, sprint start performance was investigated on a starting block equipped with force plates synchronized to a 2-dimensional motion capture system. Total training load did not differ between the 2 groups. Sprint start performance and most kinematic and kinetic parameters remained unaffected. In pooled data of the U17 swimmers, however, 5-m, 15-m, and 25-m split times were improved with maximal strength (p = 0.02, 0.03, and 0.01), but not with vertical jump training (p = 0.12, 0.16, and 0.28). Although there was no global effect, focus on the subgroup of U17 swimmers showed an improved sprint start performance with 2 sessions of maximal strength training integrated into a 16-hour training week. Although outcomes of the conditioning program seemed to be affected by the training history and performance level of the athletes involved, strength and conditioning coaches are encouraged to introduce maximal strength training at a young age.
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Desempenho Atlético/fisiologia , Treinamento Resistido/métodos , Natação/fisiologia , Adolescente , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Força Muscular , Esforço FísicoRESUMO
Farmland is a major land cover type in Europe and Africa and provides habitat for numerous species. The severe decline in farmland biodiversity of the last decades has been attributed to changes in farming practices, and organic and low-input farming are assumed to mitigate detrimental effects of agricultural intensification on biodiversity. Since the farm enterprise is the primary unit of agricultural decision making, management-related effects at the field scale need to be assessed at the farm level. Therefore, in this study, data were collected on habitat characteristics, vascular plant, earthworm, spider, and bee communities and on the corresponding agricultural management in 237 farms in 13 European and two African regions. In 15 environmental and agricultural homogeneous regions, 6-20 farms with the same farm type (e.g., arable crops, grassland, or specific permanent crops) were selected. If available, an equal number of organic and non-organic farms were randomly selected. Alternatively, farms were sampled along a gradient of management intensity. For all selected farms, the entire farmed area was mapped, which resulted in total in the mapping of 11 338 units attributed to 194 standardized habitat types, provided together with additional descriptors. On each farm, one site per available habitat type was randomly selected for species diversity investigations. Species were sampled on 2115 sites and identified to the species level by expert taxonomists. Species lists and abundance estimates are provided for each site and sampling date (one date for plants and earthworms, three dates for spiders and bees). In addition, farmers provided information about their management practices in face-to-face interviews following a standardized questionnaire. Farm management indicators for each farm are available (e.g., nitrogen input, pesticide applications, or energy input). Analyses revealed a positive effect of unproductive areas and a negative effect of intensive management on biodiversity. Communities of the four taxonomic groups strongly differed in their response to habitat characteristics, agricultural management, and regional circumstances. The data has potential for further insights into interactions of farmland biodiversity and agricultural management at site, farm, and regional scale.
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Agricultura/métodos , Biodiversidade , Fazendas , África , Animais , Abelhas , Produtos Agrícolas , Ecossistema , Monitoramento Ambiental , Europa (Continente)RESUMO
PURPOSE: To assess the circadian variations in salivary immunoglobin A (sIgA) and alpha-amylase activity (sAA), biomarkers of mucosal immune function, together with mood during 2 weeks of repeated sprint training in hypoxia (RSH) and normoxia (RSN). METHODS: Over a 2-week period, 17 competitive cross-country skiers performed six training sessions, each consisting of four sets of five 10-s bouts of all-out double-poling under either normobaric hypoxia (FiO2: 13.8%, 3000 m) or normoxia. The levels of sIgA and sAA activity and mood were determined five times during each of the first (T1) and sixth (T6) days of training, as well as during days preceding (baseline) and after the training intervention (follow-up). RESULTS: With RSH, sIgA was higher on T6 than T1 (P = 0.049), and sAA was increased on days T1, T6, and during the follow-up (P < 0.01). With RSN, sIgA remained unchanged and sAA was elevated on day T1 only (P = 0.04). Similarly, the RSH group demonstrated reduced mood on days T1, T6, and during the follow-up, while mood was lowered only on T1 with RSN (P < 0.01). CONCLUSIONS: The circadian variation of sIgA and sAA activity, biomarkers of mucosal immune function, as well as mood were similar on the first day of training when repeated double-poling sprints were performed with or without hypoxia. Only with RSH did the levels of sIgA and sAA activity rise with time, becoming maximal after six training sessions, when mood was still lowered. Therefore, six sessions of RSH reduced mood, but did not impair mucosal immune function.
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Afeto/fisiologia , Desempenho Atlético/fisiologia , Ritmo Circadiano/fisiologia , Hipóxia/metabolismo , Imunoglobulina A/imunologia , Educação Física e Treinamento , Saliva/metabolismo , alfa-Amilases/metabolismo , Adolescente , Adulto , Feminino , Humanos , Masculino , Saliva/imunologia , Adulto JovemRESUMO
The aim of this study was to evaluate the effect of a repeated sprint training with multi-directional change-of-direction (COD) movements (RSmulti) compared to repeated shuttle sprints (RSS) on variables related to COD speed and reactive agility. Nineteen highly-trained male U15 soccer players were assigned into two groups performing either RSmulti or RSS. For both groups, each training session involved 20 repeated 15 s sprints interspersed with 30 s recovery. With RSmulti the COD movements were randomized and performed in response to a visual stimulus, while the RSS involved predefined 180° COD movements. Before and following the six training sessions, performance in the Illinois agility test (IAT), COD speed in response to a visual stimulus, 20 m linear sprint time and vertical jumping height were assessed. Both groups improved their performance in the IAT (p < 0.01, ES = 1.13; p = 0.01, ES = 0.55). The COD speed in response to a visual stimulus improved with the RSmulti (p < 0.01, ES = 1.03), but not the RSS (p = 0.46, ES = 0.28). No differences were found for 20 m sprint time (P=0.73, ES = 0.07; p = 0.14, ES = 0.28) or vertical jumping height (p = 0.46, ES = 0.11; p = 0.29, ES = 0.12) for the RSmulti and RSS, respectively. In conclusion, performance in the IAT improved with the RSmulti as well as RSS. With the RSmulti however, the COD movements are performed in response to a visual stimulus, which may result in specific adaptations that improve COD speed and reactive agility in young highly trained soccer players. Key pointsDuring soccer, the players perform repeated sprints involving multi-directional COD movements, while most of these turns and twists are not pre-planned but executed in response to an external stimulus, such as ball movement, several interacting opponents and changing game situations.Both groups improved performance in the IAT. With the RSmulti on the Speedcourt however, the COD movements are performed in response to a visual stimulus, which may result in specific adaptations that improve COD speed and reactive agility.The Speedcourt could serve as a valuable method to design and individualize specific conditioning drills for young highly-trained soccer players.
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OBJECTIVES: To evaluate the new age groups of the World Junior Championships in swimming from a scientific perspective, establish benchmarks and performance corridors that predict success at peak performance age and compare performance corridors between men and women and short-, middle-, and long-distance freestyle races. DESIGN: Longitudinal big data analysis. METHODS: In total, 347,186 annual best times of male (nâ¯=â¯3360, 561⯱â¯177 Swimming Points) and female freestyle swimmers (nâ¯=â¯2570, 553⯱â¯183 Swimming Points) were collected across all race distances at peak performance age and retrospectively analyzed throughout adolescence. Cumulative Poisson distribution was used to calculate probabilities of becoming world-class finalist, international-class, or national-class swimmer for each age group. Performance corridors were expressed relative to the World Record and compared between performance levels, sex, race distances, and age groups with a 2-way analysis of variance. RESULTS: Females are required to swim faster relative to the World Record at a younger age and show earlier performance plateaus than males at national and international levels. Additionally, world-class long-distance finalists show higher Swimming Points earlier in their career compared to short-distance swimmers. This effect is more distinctive in females than males. CONCLUSIONS: Based on the sex-specific performance corridors and developments, the newly aligned age groups for the World Junior Championships are questionable regarding long-term athlete development. Based on race times from 131 nations, the present benchmarks provide valid international normative values to predict success chances at peak performance age and guide young swimmers along their talent pathway.
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Desempenho Atlético , Adolescente , Humanos , Masculino , Feminino , Estudos Retrospectivos , Natação , Atletas , Probabilidade , Comportamento CompetitivoRESUMO
PURPOSE: To investigate performance progression from early-junior to peak performance age and compare variety in race distances and swimming strokes between swimmers of various performance levels. METHODS: Using a longitudinal data analysis and between-groups comparisons 306,165 annual best times of male swimmers (N = 3897) were used to establish a ranking based on annual best times at peak performance age. Individual performance trajectories were retrospectively analyzed to compare distance and stroke variety. Performances of world-class finalists and international- and national-class swimmers (swimming points: 886 [30], 793 [28], and 698 [28], respectively) were compared across 5 age groups-13-14, 15-16, 17-18, 19-20, and 21+ years-using a 2-way analysis of variance with repeated measures. RESULTS: World-class finalists are not significantly faster than international-class swimmers up to the 17- to 18-year age group (F2|774 = 65, P < .001, ηp2=.14) but specialize in short- or long-distance races at a younger age. World-class breaststroke finalists show faster breaststroke times compared to their performance in other swimming strokes from an early age (P < .05), while world-class freestyle and individual medley finalists show less significant differences to their performance in other swimming strokes. CONCLUSIONS: While federation officials should aim for late talent selection, that is, not before the 17- to 18-year age group, coaches should aim to identify swimmers' preferred race distances early on. However, the required stroke variety seems to be specific for each swimming stroke. Breaststroke swimmers could aim for early and strong specialization, while freestyle and individual medley swimmers could maintain large and very large stroke variety, respectively.
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Desempenho Atlético , Humanos , Masculino , Estudos Retrospectivos , Comportamento Competitivo , Natação , Projetos de PesquisaRESUMO
OBJECTIVE: It is heavily discussed whether larger variety or specialization benefit elite performance at peak age. Therefore, this study aimed to determine technical (number of different swimming strokes) and physiological (number of different race distances) variety required to become an international-class swimmer (> 750 swimming points) based on 1'522'803 race results. RESULTS: Correlation analyses showed lower technical variety in higher ranked swimmers (P < 0.001), yet with small effects (0.11-0.30). However, Poisson distribution revealed dose-time-effects and specified number of swimming strokes required during each age group. Specifically, freestyle swimmers showed highest chances when starting to compete in three to four swimming strokes but reduced their variety to three swimming strokes at the ages of 12/13yrs with another transition to two swimming strokes at the ages of 19/21yrs (female/male swimmers, respectively). Although both sexes showed similar specialization pattern throughout their career, earlier specialization was generally evident in female compared to male swimmers. At peak performance age, freestyle was most frequently combined with butterfly. Swimmers who either kept competing in all five swimming strokes or focused on only one at the beginning of their careers showed lowest probability of becoming an international-class swimmer. Physiological variety increased during junior age but declined again to three race distances towards elite age.
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Desempenho Atlético , Masculino , Humanos , Feminino , Desempenho Atlético/fisiologia , Natação/fisiologia , Distribuição de PoissonRESUMO
OBJECTIVE: This study aimed to identify Key Performance Indicators (KPIs) for men's swimming strokes using Principal Component Analysis (PCA) and Multiple Regression Analysis to enhance training strategies and performance optimization. The analyses included all men's individual 100 m races of the 2019 European Short-Course Swimming Championships. RESULTS: Duration from 5 m prior to wall contact (In5) emerged as a consistent KPI for all strokes. Free Swimming Speed (FSS) was identified as a KPI for 'continuous' strokes (Breaststroke and Butterfly), while duration from wall contact to 10 m after (Out10) was a crucial KPI for strokes with touch turns (Breaststroke and Butterfly). The regression model accurately predicted swim times, demonstrating strong agreement with actual performance. Bland and Altman analyses revealed negligible mean biases: Backstroke (0% bias, LOAs - 2.3% to + 2.3%), Breaststroke (0% bias, LOAs - 0.9% to + 0.9%), Butterfly (0% bias, LOAs - 1.2% to + 1.2%), and Freestyle (0% bias, LOAs - 3.1% to + 3.1%). This study emphasizes the importance of swift turning and maintaining consistent speed, offering valuable insights for coaches and athletes to optimize training and set performance goals. The regression model and predictor tool provide a data-driven approach to enhance swim training and competition across different strokes.
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Desempenho Atlético , Natação , Masculino , Humanos , Análise de Regressão , Homens , AtletasRESUMO
Objectives: To compare performance progression and variety in race distances of comparable lengths (timewise) between pool swimming and track running. Quality of within-sport variety was determined as the performance differences between individual athletes' main and secondary race distances across (top-) elite and (highly-) trained swimmers and runners. Methods: A total of 3,827,947 race times were used to calculate performance points (race times relative to the world record) for freestyle swimmers (n = 12,588 males and n = 7,561 females) and track runners (n = 9,230 males and n = 5,841 females). Athletes were ranked based on their personal best at peak performance age, then annual best times were retrospectively traced throughout adolescence. Results: Performance of world-class swimmers differentiates at an earlier age from their lower ranked peers (15-16 vs. 17-20 year age categories, P < 0.05), but also plateaus earlier towards senior age compared to runners (19-20 vs. 23 + year age category, P < 0.05), respectively. Performance development of swimmers shows a logarithmic pattern, while runners develop linearly. While swimmers compete in more secondary race distances (larger within-sport variety), runners specialize in either sprint, middle- or long-distance early in their career and compete in only 2, 4 or 3 other race distances, respectively. In both sports, sprinters specialize the most (P < 0.05). Distance-variety of middle-distance swimmers covers more longer rather than sprint race distances. Therefore, at peak performance age, (top-) elite female 200â m swimmers show significantly slower sprint performances, i.e., 50â m (P < 0.001) and 100â m (P < 0.001), but not long-distance performances, i.e., 800â m (P = 0.99) and 1,500â m (P = 0.99). In contrast, (top-) elite female 800â m middle-distance runners show significantly slower performances in all their secondary race distances (P < 0.001). (Top-) elite female athletes specialize more than (highly-) trained athletes in both sports (P < 0.05). Conclusions: The comparison to track running and lower ranked swimmers, the early performance plateau towards senior age, and the maintenance of a large within-sport distance variety indicates that (top-) elite sprint swimmers benefit from greater within-sport specialization.
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Efforts to cure BCR::ABL1 B cell acute lymphoblastic leukemia (Ph+ ALL) solely through inhibition of ABL1 kinase activity have thus far been insufficient despite the availability of tyrosine kinase inhibitors (TKIs) with broad activity against resistance mutants. The mechanisms that drive persistence within minimal residual disease (MRD) remain poorly understood and therefore untargeted. Utilizing 13 patient-derived xenograft (PDX) models and clinical trial specimens of Ph+ ALL, we examined how genetic and transcriptional features co-evolve to drive progression during prolonged TKI response. Our work reveals a landscape of cooperative mutational and transcriptional escape mechanisms that differ from those causing resistance to first generation TKIs. By analyzing MRD during remission, we show that the same resistance mutation can either increase or decrease cellular fitness depending on transcriptional state. We further demonstrate that directly targeting transcriptional state-associated vulnerabilities at MRD can overcome BCR::ABL1 independence, suggesting a new paradigm for rationally eradicating MRD prior to relapse. Finally, we illustrate how cell mass measurements of leukemia cells can be used to rapidly monitor dominant transcriptional features of Ph+ ALL to help rationally guide therapeutic selection from low-input samples.
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OBJECTIVE: The aim of this study was to investigate thermoregulatory, cardiorespiratory, metabolic, and perceptual responses while running in a hot environment (31.7° ± 1.0°C; 42% ± 3% relative humidity) and wearing T-shirts made from different fiber types. METHODS: Eight well-trained men performed 4 tests wearing either a T-shirt made of 100% polyester with 4, 6, or 8 channels, or one made of 100% cotton. Each test consisted of 30 minutes running at 70% of peak oxygen uptake, followed by a ramp test to exhaustion and 15 minutes of recovery. RESULTS: There were no differences in skin, core, and body temperatures between fiber types during submaximal and high-intensity running (best P = .08). During recovery, body temperature and shivering/sweating sensations were lower when wearing 4- and 6-channel fibers (P ≤ .04) compared with cotton. The relative humidity at the chest and back were lower for all polyester T-shirts compared with cotton during and after submaximal and maximal running (P ≤ .007). Heart rate (best P = .10), oxygen uptake (P = .95), respiratory exchange ratio (best P = .93), ventilation (best P = .99), and blood lactate concentration (best P = .97) did not differ between the fiber types. Nor were any differences in time to exhaustion (best P = .76), ratings of perceived exertion (best P = .09), thermal sensation (best P = .07), or sensation of clothing wetness (best P = .36) discovered. CONCLUSIONS: Although statistical analysis revealed lower shivering/sweating sensations while wearing 4- and 6-channel fiber shirts during recovery, with an improved chest and back microenvironment for all polyester T-shirts, the question remains whether these differences are of any practical relevance because the performance of the well-trained men was unaffected.
Assuntos
Regulação da Temperatura Corporal/fisiologia , Vestuário , Temperatura Alta/efeitos adversos , Adulto , Metabolismo Energético , Humanos , Masculino , Percepção/fisiologia , Fatores de TempoRESUMO
Long-term sports participation and performance development are major issues in popular sports and talent development programs. This study aimed to provide longitudinal trends in youth female long jump performance development, participation, and relative age effects (RAEs), as longitudinal data for female athletes are missing. 51'894 season's best results of female long jump athletes (n = 16'189) were acquired from the Swiss Athletics online database and analyzed within a range of 6-22 years of age. To examine longitudinal performance development and RAEs, data from athletes who participated in at least three seasons were selected (n = 41'253) and analyzed. Performance development was analyzed using age groups (AGs) and exact chronological age (CA) at competition. Differences between performances of birth quarters were analyzed using 83% confidence intervals (CIs) and smallest worthwhile change. Odds ratios (ORs) with 95% CI were used to quantify RAEs. With the traditional classification into age groups (AG), performances of athletes born between January and March (Q1) were significantly better than those born between October and December (Q4) from U8 to U17. Using exact CA resulted in similar performances in Q1 and Q4 until the U20 age category. The peak of participation was reached in the U12 category, and then decreased until the U23 category with a substantial drop at U17. Significant RAEs were observed from U8 to U19 and at U22. RAEs continuously decreased from U8 (large effect) to U14 (small effect). The present results show that differences in performance arise from the comparison of athletes in AGs. Thus, going beyond AGs and using exact CA, Q4 athletes could benefit from a realistic performance comparison, which promotes fair performance evaluation, un-biased talent development, realistic feedback, and long-term participation.
RESUMO
The aim of the study was to (1) assess the test-retest reliability of a novel performance analysis system for swimming (KiSwim) including an instrumented starting block and optical motion capture system, (2) identify key performance indicators (KPI) for the kick-start, (3) determine the most beneficial position of the strong leg and (4) investigate the effect of acute reversal of leg positioning. During three sessions, kick-starts of 15 competitive swimmers were investigated. Eighteen kinematic and kinetic parameters showed high reliability (ICC>0.75) from which principal component analysis identified seven KPI (i.e., time to 15 m, time on-block, depth at 7.5 m, horizontal take-off velocity, horizontal impulse back plate, horizontal peak force back plate and vertical peak force front plate). For the preferred start position, the back plate showed a higher horizontal peak force (0.71 vs. 0.96 x body mass; p < 0.001) and impulse (0.191 vs. 0.28Ns/BW; p < 0.001) compared to front plate. Acute reversal of the leg position reduced performance (i.e., increased time to 15 m and reduced horizontal take-off velocity). However, plate-specific kinetic analysis revealed a larger horizontal peak force (p < 0.001) and impulse (p < 0.001) for the back compared to the front plate in any start position investigated. Therefore, swimmers are encouraged to position the strong leg in the back.