Impact of extra-curricular activities on adolescents\u27 connectedness and cigarette smoking: annual report

Cigarette smoking is the primary cause of preventable death in Australia, killing approximately 19,000 people every year.8 Up to 90% of smokers begin smoking by 18 years of age.9,10 In spite of the obvious public health burden, current approaches have led to very modest decreases in adolescent smoking in the past 10 years. 11 The Smoking Cessation for Youth Project (SCYP)4 was a cluster randomised control trial that resulted in lower cigarette smoking among Year 10 students who received a harm minimisation intervention over two years. This project also led to the identification of connectedness as a key mediator of cigarette smoking. In a subsequent formative evaluation, we have explored the role of extra-curricular activities in mediating school connectedness (details later). This longitudinal cohort study seeks to quantify the potential benefits of participation in extra-curricular activities, via increases in school, family and community connectedness, in reducing cigarette smoking and a range of other health compromising behaviours

An engineered protein antagonist of K-Ras/B-Raf interaction

Ras is at the hub of signal transduction pathways controlling cell proliferation and survival. Its mutants, present in about 30% of human cancers, are major drivers of oncogenesis and render tumors unresponsive to standard therapies. Here we report the engineering of a protein scaffold for preferential binding to K-Ras G12D. This is the first reported inhibitor to achieve nanomolar affinity while exhibiting specificity for mutant over wild type (WT) K-Ras. Crystal structures of the protein R11.1.6 in complex with K-Ras WT and K-Ras G12D offer insight into the structural basis for specificity, highlighting differences in the switch I conformation as the major defining element in the higher affinity interaction. R11.1.6 directly blocks interaction with Raf and reduces signaling through the Raf/MEK/ERK pathway. Our results support greater consideration of the state of switch I and provide a novel tool to study Ras biology. Most importantly, this work makes an unprecedented contribution to Ras research in inhibitor development strategy by revealing details of a targetable binding surface. Unlike the polar interfaces found for Ras/effector interactions, the K-Ras/R11.1.6 complex reveals an extensive hydrophobic interface that can serve as a template to advance the development of high affinity, non-covalent inhibitors of K-Ras oncogenic mutants.National Institutes of Health (U.S.) (Grant 5-R01-CA096504-15

Establishing a core outcome set for peritoneal dialysis : report of the SONG-PD (standardized outcomes in nephrology-peritoneal dialysis) consensus workshop

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD

Epidemiology of athletic head and neck injuries

Données statistiques sur les traumatismes crâniens et cervicaux, les lésions médullaires; facteurs de risque et prévalence des blessures selon le sport pratiqué : football américain, hockey sur glace... Statistiques sur les coûts financiers relatifs à la prise en charge de ces sportifs blessés, aux Etats-Unis