Organic anion-transporting polypeptides (OATPs) mediate the hepatic uptake of many drugs. Hepatic uptake is crucial for the therapeutic effect of pravastatin, a cholesterol-lowering drug and OATP1A/1B substrate. We aimed to gain empirical insight into the relationship between OATPs and pravastatin pharmacokinetics and toxicity. We therefore compared the distribution and toxicity of pravastatin in wild-type and Oatp1a/1b-null mice. Intestinal absorption of pravastatin was not affected by Oatp1a/1b absence, but systemic plasma exposure (AUC) increased up to 30-fold after oral bolus administration. This increased plasma exposure resulted from reduced hepatic uptake, as evident from 10 to 100-fold lower liver-to-plasma concentration ratios. However, the reductions in liver exposure were far smaller (<2-fold) than the increases in plasma exposure. Reduced pravastatin liver uptake in Oatp1a/1b-null mice was more obvious shortly after intravenous administration, with 8-fold lower biliary pravastatin excretion. Although mice chronically exposed to pravastatin for 60 days evinced little muscular toxicity, Oatp1a/1b-null mice displayed 10-fold higher plasma concentrations and 8-fold lower liver concentrations than wild-type mice. Thus, Oatp1a/1b transporters importantly control the hepatic uptake of pravastatin. Activity-reducing human OATP1B polymorphisms may therefore both reduce pravastatin therapeutic efficacy in the liver and increase systemic toxicity risks, thus compromising its therapeutic index in a two-edged way.

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This paper reports on the introduction of a set of 'Augmented Reality' (AR) tasks, offering an innovative, real world and problem based set of activities for a group of first year University Gaming and Computer Science students. Our initial research identifies a gap in the perceptions of STEM students between the usefulness of discipline based modules and a compulsory 'Professional Development' module where more 'employability' based skills were delivered. It had a history of poor student engagement and attendance, and failed to provide a compelling narrative/links to the outside world. The AR tasks were designed to facilitate group-working and multi-channel communication, and to engage students through the use of a more creative technology. Framed as a rich case study, insights are captured through student blogs, video interviews and a questionnaire. Initial findings indicate higher levels of satisfaction and an appreciation of groupwork tasks, enhanced student engagement and a greater awareness of the value of transferable skills.

This article seeks to show that a virtual world can provide a useful addition in the use of computer-mediated learning tools. We discuss the underlying educational context and link this to the properties of virtual worlds and, in particular, that of Second Life. We report on the progress of a project for developing group work that seeks to link affordances in the environment to learning outcomes and employs a socially situated, constructivist, pedagogical framework. We found that a virtual world environment can enable autonomous, differentiated learning through the use of suitably structured tasks, and postulate that an individual’s depth of engagement with the environment may be linked to the learning style.