Propositional, Probabilistic and Evidential Reasoning: Integrating numerical and symbolic approaches

Current software projects have generally to deal with producing and managing large and complex software products. It is generally believed that applying software development methods are useful in coping with this complexity and for supporting quality. As such numerous object-oriented software development methods have been defined. Nevertheless, methods often provide a complexity by their own due to their large number of artifacts, method rules and their complicated processes. We think that automation of software development methods is a valuable support for the software engineer in coping with this complexity and for improving quality. This paper presents a summary and a discussion of the ideas that were raised during the workshop on automating object-oriented software development methods

Cardiovascular mortality following liver transplantation: predictors and temporal trends over 30 years

Aims There has been significant evolution in operative and post-transplant therapies following liver transplantation (LT). We sought to study their impact on cardiovascular (CV) mortality, particularly in the longer term. Methods and results A retrospective cohort study was conducted of all adult LTs in Australia and New Zealand across three 11-year eras from 1985 to assess prevalence, modes, and predictors of early (≤30 days) and late (>30 days) CV mortality. A total of 4265 patients were followed-up for 37 409 person-years. Overall, 1328 patients died, and CV mortality accounted for 228 (17.2%) deaths. Both early and late CV mortality fell significantly across the eras (P < 0.001). However, CV aetiologies were consistently the leading cause of early mortality and accounted for ∼40% of early deaths in the contemporary era. Cardiovascular deaths occurred significantly later than non-cardiac aetiologies (8.8 vs. 5.2 years, P < 0.001). On multivariable Cox regression, coronary artery disease [hazard ratio (HR) 4.6, 95% confidence interval (CI) 1.2-21.6; P = 0.04] and era of transplantation (HR 0.44; 95% CI 0.28-0.70; P = 0.01) were predictors of early CV mortality, while advancing age (HR 1.05, 95% CI 1.02-1.10; P = 0.005) was an independent predictors of late CV mortality. Most common modes of CV death were cardiac arrest, cerebrovascular events, and myocardial infarction. Conclusion Despite reductions in CV mortality post-LT over 30 years, they still account for a substantial proportion of early and late deaths. The late occurrence of CV deaths highlights the importance of longitudinal follow-up to study the efficacy of targeted risk-reduction strategies in this unique patient population.Anoop N Koshy, Paul J Gow, Hui-Chen Han, Andrew W Teh, Robert Jones, Adam Testro ... et al

New direct-acting antivirals in the development for hepatitis C virus infection

A large number of new therapies are in development for chronic hepatitis C including direct-acting antiviral drugs (DAA), which target specific hepatitis C virus enzymes. Two of these compounds have already advanced into phase 3 development in the USA and EU, and many more are in phase 2 trials and likely to advance. In this review, the results of recent studies on ribavirin analogues, nonstructural (NS) 3/4 serine protease inhibitors, NS5B polymerase inhibitors, cyclophilin inhibitors, silimarin components, and thiazolides have been updated. Each compound includes a brief summary of its proposed mechanism of action, results of early clinical trials, and more advanced trial data where available. These compounds are likely to be the first approved in the USA and EU and will initially be used in combination with the current standard of care. It is possible that future treatment paradigms with these agents will offer the potential of interferon-free regimens. It is most likely that patients for these new therapies will be selected carefully by identifying and treating first those who have excellent sustained virologic response rates with 24 weeks of pegylated interferon and ribavirin, the current standard of care. It is also likely that there will be a need to identify those patients who are not likely to have a sustained virologic response with the addition of a protease inhibitor to the current standard of care and delaying their therapy until combination viral suppression therapy becomes an option. The cost and side effects of the DAA will be important considerations for treating physicians. This review is current through 2009; however, data are rapidly changing

Treating chronic hepatitis delta : the need for surrogate markers of treatment efficacy

Chronic hepatitis delta represents the most severe form of chronic viral hepatitis. The current treatment of hepatitis delta virus (HDV) infection consists of the use of interferons and is largely unsatisfactory. Several new compounds are currently in development for the treatment of HDV infection. However, surrogate markers that can be used to develop clinical endpoints in HDV infection are not well defined. In the current manuscript, we aimed to evaluate the existing data on treatment of HDV infection and to suggest treatment goals (possible \u201ctrial endpoints\u201d) that could be used across different clinical trials