Clinical Trial Design for Alpha-1 Antitrypsin Deficiency: A Model for Rare Diseases

Clinical research in rare diseases, including alpha-1 antitrypsin deficiency (AATD), faces challenges not shared by common disease research. These challenges may include the limited number of patient volunteers available for research, lack of natural history studies on which to base many clinical trial interventions, an urgency for the development of drug therapies given the often poor prognosis of rare diseases and uncertainties about appropriate biomarkers and clinical outcomes critical to clinical trial design. To address these challenges and initiate formal discussions among key stakeholders—patients, researchers, industry, federal regulators—the Alpha-1 Foundation hosted the Clinical Trial Design for Alpha-1 Antitrypsin Deficiency: A Model for Rare Diseases conference February 3-4, 2014 in Bethesda, Maryland. Discussions at the conference led to the conclusions that 1) adaptive designs should be considered for rare disease clinical trials yet more dialogue and study is needed to make these designs feasible for smaller trials and to address current limitations; 2) natural history studies, including the identification of appropriate biomarkers are critically needed and precompetitive collaborations may offer a means of creating these costly studies; and 3) patient registries and databases within the rare disease community need to be more publicly available and integrated, particularly for AATD. This report summarizes the discussions leading to these conclusions

Strengthening Historic Covered Bridges To Carry Modern Traffic

DTFH61-00-C-00081In this research project, the Constructed Facilities Center (CFC) and the Institute for the History of Technology and Industrial Archaeology (IHTIA) of West Virginia University (WVU) teamed up to develop means and methods to strengthen wooden superstructure components of historic covered bridges, using glass-fiber reinforced polymer (GFRP) composite materials. The strengthening methodologies developed in this project were designed to conform to the Secretary of the Interior\u2019s Standard for Historic Preservation. Specifically, tension and bending tests were conducted to establish the bond strength of GFRP rebars embedded in wood, and to establish the bending strength and stiffness of large-scale floor beams reinforced with GFRP pultruded plates and with GFRP rebars. In addition, methods were developed to enhance the shear capacity of large-scale floor beams reinforced with GFRP pultruded plates bonded on edge in narrow, prerouted vertical slots. The GFRP rebars were developed to be used specifically as axial reinforcement for truss members, while the GFRP were developed to increase the bending and shear capacity of floor beams. The test results showed bonded-in GFRP rebars performed very well in terms of pullout force and bond strength, and the strength and stiffness of GFRP-reinforced floor beams improved significantly. Although the shear strength was also expected to improve considerably with the addition of the GFRP plates placed on edge (resulting in a flitched beam), the shear capacity decreased slightly. The flitched beams tested were severely checked, which degraded their shear strength as compared to the solid control specimen. Further testing will continue in a succeeding study. Additionally, during this research, several methods of concealing the reinforcement were investigated. One successful method took advantage of routing a member on the bottom face and bonding a GFRP plate with an integrated veil to match the wood grain and color of the original aged wood