LAUSR

Expanding the database THE TEAM of collaborators self-named as the Medical Countermeasures Against Radiological Threats (MCART)Consortium and other respected colleagues have provided a series of three issues in Health Physics, published in 2012 (volume 103, issue 4), 2014 (volume 106, issue 1), and 2015 (volume 109, issue 5). The issues focused on the continued development of a clinically relevant animal model research platform designed to adhere to the criteria of the US Food and Drug Administration (FDA) guidance document for product development under the FDA Animal Rule and the qualification process for drug development tools (US FDA 2014, 2015). The research effort is focused on the acute radiation syndrome (ARS), delayed effects of acute radiation exposure (DEARE), and multiple-organ injury (MOI) by developing a strategic and tactical approach to link radiation effects, animal models, medical countermeasures (MCMs), and biomarker development to predict clinical outcome. Two successive issues of Health Physics have been devoted to a number of studies conducted in both small and large mouse, rat, and nonhuman primate (NHP) animal models. The first issue, herein, is devoted to studies that used the NHP while the second issue will focus on studies that utilized the mouse, rat, and NHP. There is a special section devoted to biomarkers: “Biomarkers: a multidisciplinary approach to predict clinical outcome in mouse and NHP models of MOI.” The animal model research platform utilized (1) smallto-large animal species to include the mouse, rat, and NHP; (2) radiation facilities using 320-kVp x radiation (10–13 mA, 1.2–2.3-mm copper half-value layer [HVL]), Cs gamma radiation, and 6MV linac-derived photons; (3) dose rates ranging from 0.6 to 1.4 Gy min−1 d−1 from homogeneous, uniform exposure to totalor partial-body irradiation; (4) an established radiation physics core that ensured consistent and accurate dose delivery across all research sites; and (5) potentially lethal doses that were species, organ sequelae, and study dependent. Each site developed well-designed dose-response relationships (DRR) for mortality due to respective organ-based subsyndromes characteristic of ARS or DEARE. The respective studies in these, the fourth and fifth MCART-dedicated issues of Health Physics, were conducted at five radiation research and commercial histopathology sites: the University of Maryland Schools of Medicine and Pharmacy, Indiana University School of Medicine, Shin Nippon Biomedical Laboratories (SNBL), the Medical College of Wisconsin, and Charles River Laboratories. Doseand time-dependent radiation-induced ARS, composed of the overt, acute hematopoietic ARS (H-ARS) and gastrointestinal ARS (GI-ARS) and associated MOI, provided the foundation for the concomitant, latent, and overt development of DEARE and MOI. The MCART team and colleagues have focused on (1) developing a more strategic and integrated organ-based approach to determine radiation effects to single and multiple organs characteristic of ARS and DEARE, (2) defining the efficacy of MCM administration in the context of MOI, and (3) developing biomarker paradigms that will predict clinical outcome within the context of use.