Relationship Between Jump Landing Kinematics and Peak ACL Force During a Jump in Downhill Skiing: A Simulation Study

Recent data highlight that competitive skiers face a high risk of injuries especially during off-balance jump landing maneuvers in downhill skiing. The purpose of the present study was to develop a musculo-skeletal modeling and simulation approach to investigate the cause-and-effect relationship between a perturbed landing position, i.e., joint angles and trunk orientation, and the peak force in the anterior cruciate ligament (ACL) during jump landing. A two-dimensional musculo-skeletal model was developed and a baseline simulation was obtained reproducing measurement data of a reference landing movement. Based on the baseline simulation, a series of perturbed landing simulations (n=1000) was generated. Multiple linear regression was performed to determine a relationship between peak ACL force and the perturbed landing posture. Increased backward lean, hip flexion, knee extension, and ankle dorsiflexion as well as an asymmetric position were related to higher peak ACL forces during jump landing. The orientation of the trunk of the skier was identified as the most important predictor accounting for 60% of the variance of the peak ACL force in the simulations. Teaching of tactical decisions and the inclusion of exercise regimens in ACL injury prevention programs to improve trunk control during landing motions in downhill skiing was concluded

Relationship Between Jump Landing Kinematics and Peak ACL Force During a Jump in Downhill Skiing: A Simulation Study

Recent data highlight that competitive skiers face a high risk of injuries especially during off-balance jump landing maneuvers in downhill skiing. The purpose of the present study was to develop a musculo-skeletal modeling and simulation approach to investigate the cause-and-effect relationship between a perturbed landing position, i.e., joint angles and trunk orientation, and the peak force in the anterior cruciate ligament (ACL) during jump landing. A two-dimensional musculo-skeletal model was developed and a baseline simulation was obtained reproducing measurement data of a reference landing movement. Based on the baseline simulation, a series of perturbed landing simulations (n=1000) was generated. Multiple linear regression was performed to determine a relationship between peak ACL force and the perturbed landing posture. Increased backward lean, hip flexion, knee extension, and ankle dorsiflexion as well as an asymmetric position were related to higher peak ACL forces during jump landing. The orientation of the trunk of the skier was identified as the most important predictor accounting for 60% of the variance of the peak ACL force in the simulations. Teaching of tactical decisions and the inclusion of exercise regimens in ACL injury prevention programs to improve trunk control during landing motions in downhill skiing was concluded

Active recovery of the finger flexors enhances intermittent handgrip performance in rock climbers

This study aimed to (1) evaluate the effect of hand shaking during recovery phases of intermittent testing on the time–force characteristics of performance and muscle oxygenation, and (2) assess inter-individual variability in the time to achieve the target force during intermittent testing in rock climbers. Twenty-two participants undertook three finger flexor endurance tests at 60% of their maximal voluntary contraction until failure. Performances of a sustained contraction and two intermittent contractions, each with different recovery strategies, were analysed by time–force parameters and near-infrared spectroscopy. Recovery with shaking of the forearm beside the body led to a significantly greater intermittent test time (↑ 22%, P < .05), force–time integral (↑ 28%, P < .05) and faster muscle re-oxygenation (↑ 32%, P < .05), when compared to the hand over hold condition. Further, the ratio of intermittent to continuous test time distinguished specific aerobic muscular adaptations among sport climbers (2.02), boulderers (1.74) and lower grade climbers (1.25). Lower grade climbers and boulderers produced shorter duration contractions due to the slower development of target force during the intermittent test, indicating worse kinaesthetic differentiation. Both the type of recovery and climbing discipline determined muscle re-oxygenation and intermittent performance in rock climbers

What static and dynamic properties should slalom skis possess? Judgments by advanced and expert skiers

Flexural and torsional rigidity are important properties of skis. However, the flexural and torsional rigidity that lead to optimal performance remain to be established. In the present study, four pairs of slalom skis that differed in flexural and torsional rigidity were tested by advanced and expert skiers. Using a 10-item questionnaire, different aspects of the skis’ performance were rated on a 9-point scale. For each pair of skis, physical measurements were compared with the ratings of the two groups of skiers. Correlations (Spearman) were then determined between (i) different mechanical properties of the skis (static and dynamic), (ii) subjective assessments of the participants, and (iii) properties of the skis and the participants’ assessments. The latter showed that expert skiers rate the aspects of the skis more accurately than advanced skiers. Importantly, expert skiers are particularly sensitive to torsion of the skis. These results suggest that such highly rated elements should be addressed in future ski designs

Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)

OBJECTIVE: Friedreich's ataxia (FRDA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FRDA. We investigated the safety and efficacy of omaveloxolone in patients with FRDA. METHODS: We conducted an international, double-blind, randomized, placebo-controlled parallel-group, registrational phase 2 trial at 11 institutions in the United States, Europe, and Australia (NCT02255435, EudraCT2015-002762-23). Eligible patients, 16 to 40 years of age with genetically confirmed FRDA and baseline modified Friedreich's Ataxia Rating Scale (mFARS) scores between 20 and 80, were randomized 1:1 to placebo or 150 mg per day of omaveloxolone. The primary outcome was change from baseline in the mFARS score in those treated with omaveloxolone compared with those on placebo at 48 weeks. RESULTS: 155 patients were screened and 103 were randomly assigned to receive omaveloxolone (n=51) or placebo (n=52), with 40 omaveloxolone patients and 42 placebo patients analyzed in the full analysis set. Changes from baseline in mFARS scores in omaveloxolone (-1.55 ± 0.69) and placebo (0.85 ± 0.64) patients showed a difference between treatment groups of -2.40 ± 0.96; p=0.014). Transient reversible increases in aminotransferase levels were observed with omaveloxolone without increases in total bilirubin or other signs of liver injury. Headache, nausea, and fatigue were also more common among patients receiving omaveloxolone. INTERPRETATION: In the MOXIe trial, omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. It represents a potential therapeutic agent in FRDA. This article is protected by copyright. All rights reserved

Progression characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS): a 4-year cohort study

BACKGROUND: The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia. METHODS: EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry. Patients with genetically confirmed Friedreich's ataxia were seen annually at 11 clinical centres in seven European countries (Austria, Belgium, France, Germany, Italy, Spain, and the UK). Data from baseline to 4-year follow-up were included in the current analysis. Our primary endpoints were the Scale for the Assessment and Rating of Ataxia (SARA) and the activities of daily living (ADL). Linear mixed-effect models were used to analyse annual disease progression for the entire cohort and subgroups defined by age of onset and ambulatory abilities. Power calculations were done for potential trial designs. This study is registered with ClinicalTrials.gov, NCT02069509. FINDINGS: Between Sept 15, 2010, and Nov 20, 2018, of 914 individuals assessed for eligibility, 602 patients were included. Of these, 552 (92%) patients contributed data with at least one follow-up visit. Annual progression rate for SARA was 0·82 points (SE 0·05) in the overall cohort, and higher in patients who were ambulatory (1·12 [0·07]) than non-ambulatory (0·50 [0·07]). ADL worsened by 0·93 (SE 0·05) points per year in the entire cohort, with similar progression rates in patients who were ambulatory (0·94 [0·07]) and non-ambulatory (0·91 [0·08]). Although both SARA and ADL showed slightly greater worsening in patients with typical onset (symptom onset at ≤24 years) than those with late onset (symptom onset ≥25 years), differences in progression slopes were not significant. For a 2-year parallel-group trial, 230 (115 per group) patients would be required to detect a 50% reduction in SARA progression at 80% power: 118 (59 per group) if only individuals who are ambulatory are included. With ADL as the primary outcome, 190 (95 per group) patients with Friedreich's ataxia would be needed, and fewer patients would be required if only individuals with early-onset are included. INTERPRETATION: Our findings for stage-dependent progression rates have important implications for clinicians and researchers, as they provide reliable outcome measures to monitor disease progression, and enable tailored sample size calculation to guide upcoming clinical trial designs in Friedreich's ataxia. FUNDING: European Commission, Voyager Therapeutics, and EuroAtaxia

Prediction of the disease course in Friedreich ataxia

We explored whether disease severity of Friedreich ataxia can be predicted using data from clinical examinations. From the database of the European Friedreich Ataxia Consortium for Translational Studies (EFACTS) data from up to five examinations of 602 patients with genetically confirmed FRDA was included. Clinical instruments and important symptoms of FRDA were identified as targets for prediction, while variables such as genetics, age of disease onset and first symptom of the disease were used as predictors. We used modelling techniques including generalised linear models, support-vector-machines and decision trees. The scale for rating and assessment of ataxia (SARA) and the activities of daily living (ADL) could be predicted with predictive errors quantified by root-mean-squared-errors (RMSE) of 6.49 and 5.83, respectively. Also, we were able to achieve reasonable performance for loss of ambulation (ROC-AUC score of 0.83). However, predictions for the SCA functional assessment (SCAFI) and presence of cardiological symptoms were difficult. In conclusion, we demonstrate that some clinical features of FRDA can be predicted with reasonable error; being a first step towards future clinical applications of predictive modelling. In contrast, targets where predictions were difficult raise the question whether there are yet unknown variables driving the clinical phenotype of FRDA

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification

Foot Loading Characteristics of Chinese Bound Feet Women: A Comparative Analysis

The custom of bound feet among Chinese women has existed for almost a century. This practice has influenced the daily life of Chinese women, especially during everyday locomotion. The primary aim of this study is to analyze the loading patterns of bound feet. Specifically, the plantar pressure and center of pressure were analyzed for peak pressure, contact area, force time integral, center of pressure displacement velocity and trajectory in the anterior- posterior direction via a comparison with normal feet. The key outcomes from this work were that the forefoot and rearfoot of bound feet bear the whole loading during stance phase. The center of pressure displacement velocity of bound feet was also greatly reduced with the shortening of trajectories. This suggests that the proprioceptive system adjusts motor function to adapt to new loading patterns while maintaining locomotive stability. A biomechanical understanding of bound feet may assist with prevention, treatment and rehabilitation of bound feet disorders

Selected static foot assessments do not predict medial longitudinal arch motion during running

Background: Static assessments of the foot are commonly advocated within the running community to classify the foot with a view to recommending the appropriate type of running shoe. The aim of this work was to determine whether selected static foot assessment could predict medial longitudinal arch (MLA) motion during running. Methods: Fifteen physically active males (27 ± 5 years, 1.77 ± 0.04m, 80 ± 10kg) participated in the study. Foot Posture Index (FPI-6), MLA angle and rearfoot angle were measured in a relaxed standing position. MLA motion was calculated using the position of retro-reflective markers tracked by a VICON motion analysis system, while participants ran barefoot on a treadmill at a self-selected pace (2.8 ± 0.5m.s-1). Bivariate linear regression was used to determine whether the static measures predicted MLA deformation and MLA angles at initial contact, midsupport and toe off. Results: All three foot classification measures were significant predictors of MLA angle at initial contact, midsupport and toe off (p < .05) explaining 41-90% of the variance. None of the static foot classification measures were significant predictors of MLA deformation during the stance phase of running. Conclusion: Selected static foot measures did not predict dynamic MLA deformation during running. Given that MLA deformation has theoretically been linked to running injuries, the clinical relevance of predicting MLA angle at discrete time points during the stance phase of running is questioned. These findings also question the validity of the selected static foot classification measures when looking to characterise the foot during running. This indicates that alternative means of assessing the foot to inform footwear selection are required