Reliably optimizing a new treatment in humans is a critical first step in clinical evaluation since choosing a suboptimal dose or schedule may lead to failure in later trials. At the same time, if promising preclinical results do not translate into a real treatment advance, it is important to determine this quickly and terminate the clinical evaluation process to avoid wasting resources. Bayesian Designs for Phase I–II Clinical Trials describes how phase I–II designs can serve as a bridge or protective barrier between preclinical studies and large confirmatory clinical trials. It illustrates many of the severe drawbacks with conventional methods used for early-phase clinical trials and presents numerous Bayesian designs for human clinical trials of new experimental treatment regimes. Written by research leaders from the University of Texas MD Anderson Cancer Center, this book shows how Bayesian designs for early-phase clinical trials can explore, refine, and optimize new experimental treatments. It emphasizes the importance of basing decisions on both efficacy and toxicity.
A vast number of neural cell surface glycoproteins belonging to the immunoglobulin superfamily have been isolated over the past two decades. In functional studies, many of them have been shown to confer adhesive properties to cells and to play an important role in developmental processes such as cell migration and axon outgrowth. Recent observations implicate Ig superfamily adhesion molecules in the regulation of activity-dependent synaptic plasticity, in regeneration after neural trauma, as well as in the pathogenesis of malformations in the developing nervous systems. This book summarizes the molecular features and some of the cellular functions of this important class of cell surface molecules. It includes detailed information on the molecular structure of the immunoglobulin fold, the common domain of these proteins, the molecular interactions between various neural Ig superfamily members and their role in signal transduction, as well as the role of Ig superfamily adhesion molecules in axon guidance during both vertebrate and invertebrate neurogenesis. Recent observations on a role for these molecules in activity-dependent synaptic plasticity and in the regeneration of injured axons in the peripheral and central nervous system are described. A discussion on the connection between Ig superfamily adhesion molecules and medical genetics is also provided.
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