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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.

Software inspection is recognized as an effective verification technique. Despite this fact, the use of inspection is surprisingly low. This paper describes a new inspection technique, called task-directed inspection (TDI), and a light-weight process, that were used to introduce inspection in a particular industrial environment. This environment had no history of inspections, was resistant to the idea of inspection, but had a situation where confidence in a safety-related legacy suite of software had to be increased. The characteristics of TDI are explored. They give rise to a variety of approaches that may encourage more widespread use of inspections. This paper examines the industrial exercise as a case study, with the intent that it be useful in other situations that share characteristics with the situation described.

Software inspections are an intensely people-centric activity. Even though this is routinely recognized in industry, much of the research focuses on inspection mechanics. During three years of inspection experiments, even though the main purpose of the experiments was to investigate the effectiveness of a particular technique, the inspectors involved provided broad comments on many other aspects of inspections. Their comments were collected and organized into themes. These themes are presented here as a set of maxims that cover all the topics that the inspectors felt were important as they endeavoured to do good inspections. Copyright © 2004 John Wiley & Sons, Ltd.

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 discusses rendezvous on multiprocessors. Three different approaches are compared, represented by three specific systems: Ada, Harmony and BNR Pascal. All three permit tasks to run on multiple processors and use blocking communications primitives, but there are significant differences. For example, control over replying to messages out of sequence and over the allocation of tasks to processors is omitted in Ada, but is available in Harmony. The approach represented by BNR Pascal follows a middle road between Harmony and Ada: a low level protocol, invisible to the programmer, is used to ensure communications reliability, but the programmer is aware of when a rendezvous is remote. If performance considerations and verbosity and robustness are ignored, all three approaches are equivalent. To illustrate this equivalence, and to demonstrate clearly the complexity of the Ada rendezvous, an Ada rendezvous administrator written using Harmony is described. A second method of adapting Harmony to Ada is also presented, in which the Harmony primitives are modified to be closer to Ada. In practice, using Harmony primitives directly will usually result in better programs. It is argued that something very much like the rendezvous adminstrator is needed for any actual implementation of the Ada rendezvous.

One of the potential strengths of Model Driven Development (MDD) is the ability to inspect the software sooner and with greater precision than is possible with conventional forms of expression of design. A study was conducted to explore model inspection when the design is expressed in IBM's Rational Rose Real-Time (RoseRT) tool. Four inspectors with varying levels of experience inspected three models. From this study, we present advice for future research and proposed functionality for RoseRT to support inspection.

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.

Real-time object-oriented modeling tools (e.g. Rational Rose-RT, i-Logix Rhapsody) allow developers to focus on software architecture by abstracting away low-level implementation details. We believe that design patterns can be very beneficial in this context, and present the rationale and concepts behind a proposal for the extension of such a toolset to support them explicitly.

A graduate course on software verification and validation (VV approaches to testing; formal methods of verification; and techniques for ensuring that software is trustworthy (more reliable than can be measured). This makes it challenging to decide what to include in a single course. Justifications are given for some of the choices made. Choices of material for undergraduate curricula are even more difficult to make. Some suggestions are offered in this area. Experience with courses on V&V is relatively thin, and the basis for teaching much of the material is rapidly evolving, so stable widely used curricula are still some time away.

In 1986, a rational design process for software was proposed [1]. This paper reports on experience teaching a course based on this process in an undergraduate computer engineering curriculum, with a companion course at the graduate level helping to feed the undergraduate course. Because the courses are for computer engineers, the emphasis is on real-time systems. The main issue is how to simplify the details of the steps so that all the steps can be learned and applied within the bounds of a one semester course. The culmination of the two courses is a project in which all the steps are used to create a working piece of software. In this paper, the steps as taught are described, with the aid of examples, and then some of the issues influencing the particular choice of material taught are discussed.