The Clinical Translation Gap in Child Health Exercise Research: A Call for Disruptive Innovation

In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the child health spectrum

Optimized material composition to improve the physical and mechanical properties of extruded wood-plastic composites (WPCs)

Wood-plastic composite (WPC) is an environmentally progress way of combining recycled plastics and wood flour. The composite typically consists of four major elements: wood flour, thermoplastic plastics, coupling agent, and lubricant. The physical and mechanical properties of WPCs highly depend on the material formulation, and the optimal material composition is an essential topic of current research. This study investigated the effects of changing material compositions on the physical and mechanical properties of WPCs. The studied WPCs were extruded molding WPCs manufactured using recycled polypropylene (RPP) plastics and wood flour. The study evaluated four parameters: (1) wood flour particle size; (2) coupling agent dosage; (3) lubricant content; and (4) the mass ratio of wood and RPPs. The results showed that using finer wood flour (smaller than 125 pm) can improve the tensile and flexural strength of WPCs, and reduce the swelling due to water adsorption. The optimal concentration of the coupling agent (Maleic Anhydride Polypropylene) and lubricant (Zinc stearate) in WPCs were both 3%. Adding the proper amount of coupling agent can improve the mechanical properties and significantly reduce the swelling, but over-dosing the lubricant significantly increased swelling and reduced all the mechanical properties of the WPCs. Maintaining wood content at 50% or less produced the best mechanical properties, and wood content above approximately 50% resulted in reduction of all physical and mechanical properties of WPCs. The study demonstrated the relationship between moisture adsorption to thickness swelling. Reducing thickness swelling from water adsorption, or reducing the exposure of wood fibers to atmosphere, may also improve all the mechanical performances of WPCs. (C) 2011 Elsevier Ltd. All rights reserved

Double-Blind, Randomized, Placebo-controlled Studies Evaluating Apaziquone (E09, Qapzola) Intravesical Instillation Post Transurethral Resection of Bladder Tumors for the Treatment of Low-risk Non-Muscle Invasive Bladder Cancer

Contains fulltext : 195581.pdf (Publisher’s version ) (Open Access)Background: Guidelines recommend a single postoperative instillation of intravesical chemotherapy within 24 hours of transurethral resection of bladder tumors (TURBT) in patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC) to reduce recurrence risk. Objective: To evaluate the 2-year recurrence rate (2-YRR) of bladder cancer in randomized patients with Ta, G1-G2 histology who receive TURBT plus apaziquone versus TURBT plus placebo. Methods: Two nearly identical Phase 3, multinational, randomized, double-blind, placebo-controlled trials were conducted in patients with histologically confirmed Ta, G1-G2 NMIBC (Target Population) to evaluate the efficacy/safety of a single instillation of apaziquone post-TURBT. A single intravesical instillation of apaziquone (4 mg/40 mL) or placebo was administered within 6 hours post-TURBT. The primary and secondary efficacy endpoints were 2-YRR and time to recurrence (TTR) respectively. Results: Overall, 1614 patients were enrolled, including 1146 patients in the Target Population. Individually, the two studies did not meet statistical significance for 2-YRR (38.0% vs 44.6% ; 39.7% vs. 46.3%). Because apaziquone is rapidly metabolized in blood, a post hoc subgroup analysis was performed by time window of drug instillation post-TURBT. Patients who had drug instilled in the time window 60+/-30 minutes post-TURBT demonstrated 20.3% and 20.8% reduction in 2-YRR and 56% (HR = 0.44) and 45% (HR = 0.55) reduction in hazards for TTR in two studies respectively. Apaziquone was well tolerated with minimal toxicity. Conclusions: Two identical Phase 3 studies supported the safety of apaziquone (4 mg/40 mL) administered as a single intravesical instillation post-TURBT and identified efficacy when instilled within 60+/-30-minutes time interval which requires further study

Design of optimal step–stress accelerated life tests under progressive type I censoring with random removals

Progressive type I censoring with random removal (PCRR), Step–stress, Accelerated life testing, Asymptotic variance, Variance (V)-optimality, Determinant (D)-optimality,