Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine.

AIMS
To examine the allelic variation of three enzymes involved in 6-mercaptopurine/azathioprine (6-MP/AZA) metabolism and evaluate the in?uence of these polymorphisms on toxicity, haematological parameters and metabolite levels in patients with acute lymphoblastic leukaemia (ALL) or in?ammatory bowel disease (IBD).
METHODS
Clinical data and blood samples were collected from 19 ALL paediatric patients and 35 IBD patients who were receiving 6-MP/AZA therapy. All patients were screened for seven genetic polymorphisms in three enzymes involved in mercaptopurine metabolism [xanthine oxidase, inosine triphosphatase (C94?A and IVS2+21A?C) and thiopurine methyltransferase]. Erythrocyte and plasma metabolite concentrations were also determined. The associations between the various genotypes and myelotoxicity, haematological parameters and metabolite concentrations were determined.
RESULTS
Thiopurine methyltransferase variant alleles were associated with a preferential metabolism away from 6-methylmercaptopurine nucleotides (P = 0.008 in ALL patients,P = 0.038 in IBD patients) favouring 6-thioguanine nucleotides (6-TGNs) (P = 0.021 in ALL patients). Interestingly, carriers of inosine triphosphatase IVS2+21A?C variants among ALL and IBD patients had signi?cantly higher concentrations of the active cytotoxic metabolites, 6-TGNs (P = 0.008 in ALL patients,P = 0.047 in IBD patients). The study con?rmed the association of thiopurine methyltransferase heterozygosity with leucopenia and neutropenia in ALL patients and reported a signi?cant association between inosine triphosphatase IVS2+21A?C variants with thrombocytopenia (P = 0.012).
CONCLUSIONS
Pharmacogenetic polymorphisms in the 6-MP pathway may help identify patients at risk for associated toxicities and may serve as a guide for dose
individualization.

Fruit and vegetable consumption in older individuals in Northern Ireland: levels and patterns

Low intakes of fruit and vegetables have previously been reported in the older population of Great Britain, particularly among certain socio-demographic groups. Levels and patterns of consumption in the older population of Northern Ireland, however, remain unknown. A representative sample of 1000 members of the older population of Northern Ireland were contacted by telephone to assess average intake of all fruits and vegetables and various demographic details. Data from 426 individuals (representative of the whole population) reported a mean consumption of 4.0 (SD 1-3) and 4.1 (SD 1-3) portions of fruit and vegetables per weekday and per weekend day respectively. Regression analyses revealed greater consumption on weekdays by females (B 0.53; P

Communication, recognition and social work: Aligning the ethical theories of Habermas and Honneth

The modern world is replete with ethical challenges of Orwellian proportions. The violation of human rights and misrecognition of identities are two of the most pressing examples. In this paper, the ethical theories of Habermas and Honneth are aligned as a way of addressing these specific challenges within social work. It is suggested that these theories are complementary, mutually rectifying and concordant at the meta-ethical level of analysis. The alignment is also justified, pargmatically, through the construction of three hypothetical vignettes demonstrating different kinds of practice dilemmas. The need for egalitarian communication and the imperative to recognise human identity in all its dimensions subsequently emerge as the two foundation stones for ethical deliberation in social work.

Democratic Participation, Engagement, and Freedom

It is commonly supposed that democracies should encourage greater political participation and civic engagement. This article identifies two distinct perspectives on political participation and civic engagement: a ‘freedom-centred’ model and an ‘ethical’ model. The ‘freedom-centred’ model defended here draws on the republican concept of freedom as non-domination, together with the political liberal notion of fair deliberative proceduralism, while the ethical model draws on Aristotelian, perfectionist, sources. It is argued that the ‘ethical’ model is overly concerned with the ‘moral renewal’ of modern social life, and is insensitive to problems of domination posed by its account of civic reciprocity and trust. By contrast, the ‘freedom-centred’ model developed offers a systematic account of personal and political freedom, which provides qualified support for deliberative modes of participation and engagement.

Children’s perceptions of primary science assessment in England and Wales

This study builds on and contributes to work on assessment of children in primary school, particularly in science. Previous research has examined primary science assessment from different standpoints, but no studies have speci?cally addressed children’s perspectives. This article provides additional insight into issues surrounding children’s assessment in primary school and how the assessment of science might develop in England after the science SATs (Standard Assessment Tests) were abolished in 2009. Some research suggests that primary science assessment via SATs is a major reason for the observed decline in children’s engagement with science in upper primary and lower secondary school. The analytic focus on engaging children as coresearchers to assist in the process of gathering informed views and interpreting ?ndings from a large sample of children’s views enables another contribution. The study, based on a survey of 1000 children in primary and secondary schools in England and Wales, reveals that despite being assessed under two different regimes (high-stakes national tests in England and moderated teacher assessment in Wales), children’s views of science assessment are remarkably consistent. Most appreciate the usefulness of science assessment and value frequent, non-SATs testing for monitoring/improving science progress. There was a largely negative impact, however, of science
assessment on children’s well-being, particularly due to stress. The paper demonstrates that children provide an important perspective on assessment and that including their views can improve policy-making in relation to primary science assessment.

‘Playing it by the rules': the politics of research in ‘race' and education

This article offers an examination of the interplay between politics, ethics, theory and methodology as they impact upon social research, through a critical analysis of the ethnographic study conducted by Peter Foster. It will be argued that his highly contentious claim to have found no manifestations of racism (either direct or indirect) throughout his study of an inner-city, multi-ethnic comprehensive school was, in the last analysis, both misleading and inaccurate. It will be contended that such claims were based upon a research design and methodology which were ultimately determined by his own political orientation and the ethical and theoretical positions which he developed as a consequence.