RELIABILITY OF 3D FRONTAL PLANE KNEE AB/ADDUCTION RANGE OF MOTION DURING RUNNING IN YOUNG ATHLETES

This study quantified within-session and between-session reliability of 3D frontal plane knee ab/adduction range of motion during the stance phase of running gait calculated for 18 long term athlete development programme participants (10 males and 8 females, 11.5 ±1.4 years) during two testing sessions (spaced 10 weeks apart). Average mean differences in frontal plane knee ab/adduction between running trials (for the right or left side) within a session (week 1 or week 10) ranged from 0.2 to 7.2% (ES 0.01–0.26) which were acceptable differences. However, average mean differences between sessions for running trials (for the right or left side) ranged from 0.1 to 20% (ES 0.01–0.6). The mixed model resulted in estimates of knee ab/adduction range of motion for effects of limb side (3.6°), session (2.8°), run trial (0.2°) and subjects (4.5°). Within-session ICCs ranged from 0.80 to 0.92 and between-session ICCs ranged from 0.51 to 0.73. Based on these ICCs, within-session reliability of frontal plane knee ab/adduction is good and between-session reliability is average to good

Exploring Resilience Models in a Sample of Combat-Exposed Military Service Members and Veterans: A Comparison and Commentary

Background: The term resilience is applied in numerous ways in the mental health field, leading to different perspectives of what constitutes a resilient response and disparate findings regarding its prevalence following trauma. Objective: illustrate the impact of various definitions on our understanding and prevalence of resilience, we compared various resilience definitions (absence of PTSD, absence of current mental health diagnosis, absence of generalized psychological distress, and an alternative trauma load–resilience discrepancy model of the difference between actual and predicted distress given lifetime trauma exposure) within a combat-exposed military personnel and veteran sample. Method: In this combat-trauma exposed sample (N = 849), of which approximately half were treatment seeking, rates of resilience were determined across all models, the kappa statistic was used to determine the concordance and strength of association across models, and t-tests examined the models in relation to a self-reported resilience measure. Results: Prevalence rates were 43.7%, 30.7%, 87.4%, and 50.1% in each of the four models. Concordance analyses identified 25.7% (n = 218) considered resilient by all four models (kappa = .40, p \u3c .001). Correlations between models and self-reported resilience were strong, but did not fully overlap. Conclusions:The discussion highlights theoretical considerations regarding the impact of various definitions and methodologies on resilience classifications, links current findings to a systems-based perspective, and ends with suggestions for future research approaches on resilience

Applying ecological systems theory to juvenile legal system interventions outcomes research: a measurement framework

Intervention research and development for youth in the juvenile legal system (JLS) has often focused on recidivism as the primary outcome of interest. Although recidivism is an important outcome, it is ultimately a downstream marker of success and is affected by changes in other domains of youths’ lives (e.g., family and peer relations, neighborhood safety, local and state-level policies). Thus, the present manuscript proposes the application of ecological systems theory to selecting outcomes to assess intervention effects in JLS intervention research to better capture proximal and distal influences on youth behavior. To that end, we first provide an overview of the strengths and limitations of using recidivism as an outcome measure. Next, the current application of social ecology theory to existing research on both risk and protective factors of JLS involvement is discussed, as well as existing work on assessing social-ecological domains within intervention studies. Then, a measurement framework is introduced for selecting pertinent domains of youths’ social ecologies to assess as intervention outcomes, moderators, and mediators. To facilitate this, we provide examples of concrete constructs and measures that researchers may select. We conclude with potential new avenues of research to which our proposed framework could lead, as well as potential limitations of implementing our framework

Prioritization of HCV treatment in the direct-acting antiviral era: an economic evaluation

BACKGROUND & AIMS: We determined the optimal HCV treatment prioritization strategy for interferon-free (IFN-free) HCV direct-acting antivirals (DAAs) by disease stage and risk status incorporating treatment of people who inject drugs (PWID). METHODS: A dynamic HCV transmission and progression model compared the cost-effectiveness of treating patients early vs. delaying until cirrhosis for patients with mild or moderate fibrosis, where PWID chronic HCV prevalence was 20, 40 or 60%. Treatment duration was 12weeks at £3300/wk, to achieve a 95% sustained viral response and was varied by genotype/stage in alternative scenarios. We estimated long-term health costs (in £UK=€1.3=$1.5) and outcomes as quality adjusted life-years (QALYs) gained using a £20,000 willingness to pay per QALY threshold. We ranked strategies with net monetary benefit (NMB); negative NMB implies delay treatment. RESULTS: The most cost-effective group to treat were PWID with moderate fibrosis (mean NMB per early treatment £60,640/£23,968 at 20/40% chronic prevalence, respectively), followed by PWID with mild fibrosis (NMB £59,258 and £19,421, respectively) then ex-PWID/non-PWID with moderate fibrosis (NMB £9,404). Treatment of ex-PWID/non-PWID with mild fibrosis could be delayed (NMB -£3,650). In populations with 60% chronic HCV among PWID it was only cost-effective to prioritize DAAs to ex-PWID/non-PWID with moderate fibrosis. For every one PWID in the 20% chronic HCV setting, 2 new HCV infections were averted. One extra HCV-related death was averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied sustained virological response/duration by genotype/fibrosis stage. CONCLUSIONS: Treating PWID with moderate or mild HCV with IFN-free DAAs is cost-effective compared to delay until cirrhosis, except when chronic HCV prevalence and reinfection risk is very high

Parkinson's disease-linked mutations in VPS35 induce dopaminergic neurodegeneration

Mutations in the vacuolar protein sorting 35 homolog (VPS35) gene at the PARK17 locus, encoding a key component of the retromer complex, were recently identified as a new cause of late-onset, autosomal dominant Parkinson's disease (PD). Here we explore the pathogenic consequences of PD-associated mutations in VPS35 using a number of model systems. VPS35 exhibits a broad neuronal distribution throughout the rodent brain, including within the nigrostriatal dopaminergic pathway. In the human brain, VPS35 protein levels and distribution are similar in tissues from control and PD subjects, and VPS35 is not associated with Lewy body pathology. The common D620N missense mutation in VPS35 does not compromise its protein stability or localization to endosomal and lysosomal vesicles, or the vesicular sorting of the retromer cargo, sortilin, SorLA and cation-independent mannose 6-phosphate receptor, in rodent primary neurons or patient-derived human fibroblasts. In yeast we show that PD-linked VPS35 mutations are functional and can normally complement VPS35 null phenotypes suggesting that they do not result in a loss-of-function. In rat primary cortical cultures the overexpression of human VPS35 induces neuronal cell death and increases neuronal vulnerability to PD-relevant cellular stress. In a novel viral-mediated gene transfer rat model, the expression of D620N VPS35 induces the marked degeneration of substantia nigra dopaminergic neurons and axonal pathology, a cardinal pathological hallmark of PD. Collectively, these studies establish that dominant VPS35 mutations lead to neurodegeneration in PD consistent with a gain-of-function mechanism, and support a key role for VPS35 in the development of PD

Study of the genetic variability in a Parkinson's Disease gene: EIF4G1

Chartier-Harlin and colleagues [2] recently reported mutations in the eukaryotic translation initiation factor 4-gamma (EIF4G1) gene in families with parkinsonism. Large-scale screening found two mutations (p.R1205H and p.A502V) only in affected individuals, although their relative frequency was very low. The aim of this study was to investigate EIF4G1 parkinsonism-related variants in two separate cohorts and study coding variability across the gene. We first screened a series of familial Parkinson's Disease (PD) patients in an attempt to confirm previous results by showing segregation. Then, to determine the extent of coding variation in the gene, we first screened a cohort of sub-Saharan African individuals from the Centre d'Etude du Polymorphisme Humain - Human Genome Diversity Cell Line Panel (HGDP) [1] and then analyzed data from 5350 individuals National Heart, Lung, and Blood Institute (NHLBI) exome sequencing project. We failed to identify any PD-related mutations in the familial samples. Conversely we found the p.A502V variant in the NHLBI population. We observed a high number of coding polymorphism in the exons where the two PD variants have been previously reported. We conclude that either EIF4G1 variants are an extremely rare cause of familial PD in Caucasian cohorts, or that A502V is in fact a rare benign variant not involved in PD aetiology. Our data also suggests that the protein can tolerate some extent of variability particularly at this point of the gene