Biomechanical analyses of the performance of Paralympians: From foundation to elite level

Biomechanical analysis of sport performance provides an objective method of determining performance of a particular sporting technique. In particular, it aims to add to the understanding of the mechanisms influencing performance, characterization of athletes, and provide insights into injury predisposition. Whilst the performance in sport of able-bodied athletes is well recognised in the literature, less information and understanding is known on the complexity, constraints and demands placed on the body of an individual with a disability. This paper provides a dialogue that outlines scientific issues of performance analysis of multi-level athletes with a disability, including Paralympians. Four integrated themes are explored the first of which focuses on how biomechanics can contribute to the understanding of sport performance in athletes with a disability and how it may be used as an evidence-based tool. This latter point questions the potential for a possible cultural shift led by emergence of user-friendly instruments. The second theme briefly discusses the role of reliability of sport performance and addresses the debate of two-dimensional and three-dimensional analysis. The third theme address key biomechanical parameters and provides guidance to clinicians, and coaches on the approaches adopted using biomechanical/sport performance analysis for an athlete with a disability starting out, to the emerging and elite Paralympian. For completeness of this discourse, the final theme is based on the controversial issues on the role of assisted devices and the inclusion of Paralympians into able-bodied sport is also presented. All combined, this dialogue highlights the intricate relationship between biomechanics and training of individuals with a disability. Furthermore, it illustrates the complexity of modern training of athletes which can only lead to a better appreciation of the performances to be delivered in the London 2012 Paralympic Games

Tribal Nations and Abortion Access: A Path Forward

In the wake of Dobbs and its upending the constitutional right to abortion care, commentators have explored the possibility of an abortion “safe harbor” in Indian country. These narratives largely contemplate co-opting tribal sovereignty to provide safety from state criminal and civil liability for non-Native people seeking abortion care. It does not consider the complicated legal and practical considerations that would face Tribes pursuing this strategy, nor the risk to providers and patients. Moreover, Indigenous people are already less likely to receive abortion care. Native reproductive care has long been the target of assimilationist and even genocidal policies, while also being greatly underfunded and neglected, resulting in a population with devastating rates of violence and maternal mortality, and with extremely limited access to abortion care.However, despite numerous legal hurdles, and a historical context steeped in restricted reproductive health, Tribes, as sovereign nations, may be a position to fill a part of the enormous health care gap to serve their citizens and communities. Tribes have numerous reasons to be unsatisfied with the prospect of delegating their regulatory authority regarding reproductive care to the states. Native authority generally is under increasing threat from state encroachment and federal disestablishment, including in the most recent U.S. Supreme Court holding in Indian law, Oklahoma v. Castro-Huerta. But more fundamentally, Tribes have sovereign obligations to their Indigenous citizenry that include robustly asserting Native reproductive well-being as a human right, and zealously defending that right. This article outlines the legal realities of providing abortion care in Indian country, particularly in the context of avoiding state prohibitions. Abortion care is a fundamental human right of Indigenous people. The ability to safely end a pregnancy is consistent with Tribal conceptions of autonomy, privacy, and individual self-determination

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T cell immune awakening in response to immunotherapy is age dependent

BACKGROUND: Precision immuno-oncology approaches are needed to improve cancer care. We recently demonstrated that in patients with metastatic melanoma, an increase of clonality or diversity of the T cell receptor (TCR) repertoire of peripheral T cells following one cycle of immunotherapy is coincident with response to immune-checkpoint blockade (ICB). We also identified a subset of peripheral CD8(+) immune-effector memory T cells (T(IE) cells) whose expansion was associated with response to ICB and increased overall survival. To improve our understanding of peripheral T cell dynamics, we examined the clinical correlates associated with these immune signatures. METHODS: Fifty patients with metastatic melanoma treated with first-line anti-PD-1 ICB were included. We analysed TCR repertoire and peripheral T(IE) cell dynamics by age before treatment (T0) and after the first cycle of treatment at week 3 (W3). RESULTS: We observed a correlation between T(IE) abundance and age at T0 (r = 0.40), which reduced following treatment at W3 (r = 0.07). However, at W3, we observed two significantly opposing patterns (p = 0.03) of TCR repertoire rearrangement in patients who responded to treatment, with patients ≥70 years of age showing an increase in TCR clonality and patients <70 years of age showing an increase in TCR diversity. CONCLUSIONS: We demonstrate that immunotherapy-induced immune-awakening patterns in patients with melanoma are age-related and may impact patient response to ICB, and thus have implications for biomarker development and planning of personalised therapeutic strategies

Greater rate of weight loss predicts paediatric hospital admission in adolescent typical and atypical anorexia nervosa

Hospital admissions for eating disorders (ED) are rapidly increasing. Limited research exists evidencing the factors that lead to hospital admissions or their outcomes. The current study aimed to identify predictors of hospital admission in adolescents with anorexia nervosa (AN) or atypical anorexia nervosa (AAN). Prospective observational study including participants (n = 205) aged 11–18 and diagnosed with AN or AAN at initial ED assessment, across eight London clinics. Physical health parameters at assessment, including heart rate, blood pressure, temperature and rate of weight loss, were compared between adolescents who were admitted to a paediatric ward following assessment and those who were not admitted. The mean rate of weight loss prior to assessment was significantly higher, and mean energy intake significantly lower, in the admitted vs not admitted groups (1.2 vs 0.6kg/week, p < 0.001 and 565 kcal/day vs 857 kcal/day, p < 0.001), independent of degree of underweight. No significant differences were identified between groups in all other parameters of physical risk. Underweight adolescents with AN were equally likely to be admitted as non-underweight adolescents with AAN. Conclusion: This study provides evidence on predictors of hospital admission, from a sample representing the London area. The assessment of weight loss speed, duration and magnitude are recommended as priority parameters that inform the risk of deterioration and the likelihood of hospital admission in adolescent AN and AAN. Further research investigating outcomes of these hospital admission is needed. What is Known: • Hospital admissions for eating disorders (ED) are rapidly increasing. • Limited research exists evidencing the factors that lead to hospital admissions, or their outcomes. What is New: • This study provides evidence on predictors of hospital admission in young people with typical and atypical anorexia nervosa. • Weight loss speed, duration, and magnitude are recommended as priority parameters that inform the risk of deterioration and the likelihood of hospital admission in this patient group

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Pharmacokinetic Interactions of Maraviroc with Darunavir-Ritonavir, Etravirine, and Etravirine-Darunavir-Ritonavir in Healthy Volunteers: Results of Two Drug Interaction Trials▿†

The effects of darunavir-ritonavir at 600 and 100 mg twice daily (b.i.d.) alone, 200 mg of etravirine b.i.d. alone, or 600 and 100 mg of darunavir-ritonavir b.i.d. with 200 mg etravirine b.i.d. at steady state on the steady-state pharmacokinetics of maraviroc, and vice versa, in healthy volunteers were investigated in two phase I, randomized, two-period crossover studies. Safety and tolerability were also assessed. Coadministration of 150 mg maraviroc b.i.d. with darunavir-ritonavir increased the area under the plasma concentration-time curve from 0 to 12 h (AUC12) for maraviroc 4.05-fold relative to 150 mg of maraviroc b.i.d. alone. Coadministration of 300 mg maraviroc b.i.d. with etravirine decreased the maraviroc AUC12 by 53% relative to 300 mg maraviroc b.i.d. alone. Coadministration of 150 mg maraviroc b.i.d. with etravirine-darunavir-ritonavir increased the maraviroc AUC12 3.10-fold relative to 150 mg maraviroc b.i.d. alone. Maraviroc did not significantly affect the pharmacokinetics of etravirine, darunavir, or ritonavir. Short-term coadministration of maraviroc with darunavir-ritonavir, etravirine, or both was generally well tolerated, with no safety issues reported in either trial. Maraviroc can be coadministered with darunavir-ritonavir, etravirine, or etravirine-darunavir-ritonavir. Maraviroc should be dosed at 600 mg b.i.d. with etravirine in the absence of a potent inhibitor of cytochrome P450 3A (CYP3A) (i.e., a boosted protease inhibitor) or at 150 mg b.i.d. when coadministered with darunavir-ritonavir with or without etravirine