MEASUREMENT AND MODELING OF THE TOXICITY OF BINARY MIXTURES IN THE NEMATODE CAENORHABDITIS ELEGANS-A TEST OF INDEPENDENT ACTION

Ecological risk assessments must increasingly consider the effects of chemical mixtures on the environment as anthropogenic pollution continues to grow in complexity. Yet testing every possible mixture combination is impractical and unfeasible; thus, there is an urgent need for models that can accurately predict mixture toxicity from single-compound data. Currently, two models are frequently used to predict mixture toxicity from single-compound data: Concentration addition and independent action (IA). The accuracy of the predictions generated by these models is currently debated and needs to be resolved before their use in risk assessments can be fully justified. The present study addresses this issue by determining whether the IA model adequately described the toxicity of binary mixtures of five pesticides and other environmental contaminants (cadmium, chlorpyrifos, diuron, nickel, and prochloraz) each with dissimilar modes of action on the reproduction of the nematode Caenorhabditis elegans. In three out of 10 cases, the IA model failed to describe mixture toxicity adequately with significant or antagonism being observed. In a further three cases, there was an indication of synergy, antagonism, and effect-level-dependent deviations, respectively, but these were not statistically significant. The extent of the significant deviations that were found varied, but all were such that the predicted percentage effect seen on reproductive output would have been wrong by 18 to 35% (i.e., the effect concentration expected to cause a 50% effect led to an 85% effect). The presence of such a high number and variety of deviations has important implications for the use of existing mixture toxicity models for risk assessments, especially where all or part of the deviation is synergistic.

The effects of different forms of advice on the control of a simulated complex system

Three experiments examine the effect of different forms of computer-generated advice on concurrent and subsequent performance of individuals controlling a simulated intensive-care task. Experiment 1 investigates the effect of optional and compulsory advice and shows that both result in an improvement in subjects' performance while receiving the advice, and also in an improvement in subsequent unaided performance. However, although the advice compliance displayed by the optional advice group shows a strong correlation with subsequent unaided performance, compulsory advice has no extra benefit over the optional use of advice. Experiment 2 examines the effect of providing users with on-line explanations of the advice, as well as providing less specific advice. The results show that both groups perform at the same level on the task as the advice groups from Experiment 1, although subjects receiving explanations scored significantly higher on a written post-task questionnaire. Experiment 3 investigates in more detail the relationship between advice compliance and performance. The results reveal a complex relationship between natural ability on the task and the following of advice, in that people who use the advice more tend to perform either better or worse than the more moderate users. The theoretical and practical implications of these experiments are discussed.

Interfacial structure of wild-type and mutant forms of puroindoline-b bound to DPPG monolayers

The interaction of wild-type puroindoline-b (Pin-b+) and two mutant forms having single residue substitutions (G46S or W44R) with L-alpha-dipalmitoylphosphatidyl-dl-glycerol (DPPG) as a Langmuir monolayer at the air/water interface was investigated by neutron reflectivity (NR) and Brewster angle microscopy (BAM). NR profiles were fitted using a three-layer model to enable differences in penetration of protein between the lipid headgroup and acyl regions to be determined. The data showed similar surface excesses for each of the three proteins at the interface; however, it was revealed that the depth of penetration of protein into the lipid region differed for each protein with Pin-b+ penetrating further into the acyl region of the lipid compared to the mutant forms of the protein that interacted with the headgroup region only. BAM images revealed that the domain structure of the DPPG monolayers was disrupted when Pin-b+ adsorption had reached equilibrium, suggesting protein penetration had led to compression of the lipid region. In contrast, the domain structure was unaffected by the W44R mutant, suggesting no change in compression of the lipid region and hence little or no penetration of protein into the lipid layer.

A retrospective audit of medicines use review forms

The medicines use review (MUR) service was introduced in England and Wales in 2005 to improve patients’ knowledge and use of medicines through a private, patient–pharmacist consultation. The pharmacist completes a standard form as a record of the MUR consultation and the patient receives a copy. The 2008 White Paper, Pharmacy in England[1] notes some MURs are of poor or questionable quality and there are anecdotal reports that pharmacists elect to conduct ‘easy’ MURs with patients on a single prescribed medicine only.[2] In 2009, the Royal Pharmaceutical Society of Great Britain (RPSGB) launched a multi-disciplinary audit template to review the effectiveness of MURs and improve their quality.[3] Prior to this, we conducted a retrospective MUR audit in a 1-month period in 2008. Our aims were to report on findings from this audit and the validity of using MUR forms as data for audit.