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Stochastic deconvolution is a parameter estimation method that calculates drug absorption using a nonlinear mixed-effects model in which the random effects associated with absorption represent a Wiener process. The present work compares (1) stochastic deconvolution and (2) numerical deconvolution, using clinical pharmacokinetic (PK) data generated for an in vitro – in vivo correlation (IVIVC) study of extended release (ER) formulations of a Biopharmaceutics Classification System class III drug substance. The preliminary analysis found that numerical and stochastic deconvolution yielded superimposable fraction absorbed ( F abs ) versus time profiles when supplied with exactly the same externally determined unit impulse response parameters. In a separate analysis, a full population-PK/stochastic deconvolution was applied to the clinical PK data. Scenarios were considered in which immediate release (IR) data were either retained or excluded to inform parameter estimation. The resulting F abs profiles were then used to model level A IVIVCs. All the considered stochastic deconvolution scenarios, and numerical deconvolution, yielded on average similar results with respect to the IVIVC validation. These results could be achieved with stochastic deconvolution without recourse to IR data. Unlike numerical deconvolution, this also implies that in crossover studies where certain individuals do not receive an IR treatment, their ER data alone can still be included as part of the IVIVC analysis.

Learning Objectives: After completing this course, the reader will be able to: Summarize the efficacy outcomes of cabazitaxel pivotal trials in the treatment of hormone-refractory metastatic prostate cancer.Describe the safety profile and most common adverse effects of cabazitaxel in patients with hormone-refractory metastatic prostate cancer. CME This article is available for continuing medical education credit at CME.TheOncologist.com On March 17, 2011 the European Commission issued a marketing authorization valid throughout the European Union for Jevtana® (Sanofi-Aventis, Paris, France) for the treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. The active substance of Jevtana® is cabazitaxel acetone solvate, an antineoplastic agent that acts by disrupting the microtubular network in cells. The recommended dose of cabazitaxel is 25 mg/m2 administered as a 1-hour i.v. infusion every 3 weeks in combination with oral prednisone or prednisolone, 10 mg, administered daily throughout treatment. In the main study submitted for this application, a 2.4-month longer median overall survival time and a 30% lower risk for death were observed for cabazitaxel, compared with mitoxantrone. The most common side effects with cabazitaxel were anemia, leukopenia, neutropenia, thrombocytopenia, and diarrhea. This paper summarizes the scientific review of the application leading to approval in the European Union. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the European Medicines Agency Web site (http://www.ema.europa.eu).

This paper describes one way to include software engineering in undergraduate computer engineering. A description of the context is given, to help readers relate it to their own situations. The need for software engineering in all branches of engineering is clear, but it is difficult to find space in undergraduate curricula. This is illustrated with reference to an electrical engineering curriculum. A set of six software engineering courses is described, as are three other courses that are relevant to students deciding on the software option. Some of the factors that led to the choices made are discussed. Three of the software courses are in the core of computer engineering, while three are taken only by students specializing in software.

In this paper, we consider interface contracts as a possible mechanism for improving semantic integrity in component-based systems. A contract is essentially a formal specification interleaved with code and allowing a component or object to unambiguously specify its behaviour. The existing techniques that we survey are predominantly designed for object-oriented systems; we therefore investigate the extent to which they can be scaled up to the level of components, and embedded in interface specifications rather than code. We conclude that interleaved specifications are viable and useful at the level of components, but that future work is required to develop languages that can express the constraints that are important at this level of granularity.