Molecular subtyping of breast cancer: Opportunities for new therapeutic approaches

Evidence is accumulating that breast cancer is not one disease but many separate diseases. DNA microarray-based gene expression profiling has demonstrated subtypes with distinct phenotypic features and clinical responses. Prominent among the new subtypes is 'basal-like' breast cancer, one of the 'intrinsic' subtypes defined by negativity for the estrogen, progesterone, and HER2/neu receptors and positivity for cytokeratins-5/6. Focusing on basal-like breast cancer, we discuss how molecular technologies provide new chemotherapy targets, optimising treatment whilst sparing patients from un-necessary toxicity. Clinical trials are needed that incorporate long-term follow-up of patients with well-characterised tumour markers. Whilst the absence of an obvious dominant oncogene driving basallike breast cancer and the lack of specific therapeutic agents are serious stumbling blocks, this review will highlight several promising therapeutic candidates currently under evaluation. Thus, new molecular technologies should provide a fundamental foundation for better understanding breast and other cancers which may be exploited to save lives.

Approaches to the Implementation of the Water Framework Directive: Targeting Mitigation Measures at Critical Source Areas of Diffuse Phosphorus in Irish Catchments

The Water Framework Directive (WFD) has initiated a shift towards a targeted approach to implementation through its focus on river basin districts as management units and the natural ecological characteristics of waterbodies. Due to its role in eutrophication, phosphorus (P) has received considerable attention, resulting in a significant body of research, which now forms the evidence base for the programme of measures (POMs) adopted in WFD River Basin Management Plans (RBMP). Targeting POMs at critical sources areas (CSAs) of P could significantly improve environmental efficiency and cost effectiveness of proposed mitigation strategies. This paper summarises the progress made towards targeting mitigation measures at CSAs in Irish catchments. A review of current research highlights that knowledge related to P export at field scale is relatively comprehensive however; the availability of site-specific data and tools limits widespread identification of CSA at this scale. Increasing complexity of hydrological processes at larger scales limits accurate identification of CSA at catchment scale. Implementation of a tiered approach, using catchment scale tools in conjunction with field-by-field surveys could decrease uncertainty and provide a more practical and cost effective method of delineating CSA in a range of catchments. Despite scientific and practical uncertainties, development of a tiered CSA-based approach to assist in the development of supplementary measures would provide a means of developing catchment-specific and cost-effective programmes of measures for diffuse P. The paper presents a conceptual framework for such an approach, which would have particular relevance for the development of supplementary measures in High Status Waterbodies (HSW). The cost and resources necessary for implementation are justified based on HSWs’ value as undisturbed reference condition ecosystems.

New Approaches to the Total Synthesis of the Bryostatin Antitumour Macrolides

In this Focus Review, we give an overview of various bryostatin total syntheses. We also discuss the synthesis of various bryostatin analogues and their biological activity. Work reviewed includes that of Masamune, Evans, Nishiyama and Yamamura, Hale and Manaviazar, Trost, Wender, Keck, Burke, Thomas, and Krische. Our coverage is primarily for the period 2001–2009, since detailed reviews already exist on bryostatin total synthesis work and biology up to this time.

Seen but never heard: rethinking approaches to researching racism and young children

This paper is concerned with the methodology underlying attempts to understand the nature and impact of racism among young children. In drawing upon data gathered from a year-long ethnographic study of five- and six-year-old children in an English multi-ethnic, inner-city primary school, the paper provides a critique of traditional approaches to the study of racial attitudes among young children. It is argued that such research has been conceived through the articulation of two, inter-related discourses on children and on 'race'; the former couched in traditional socialisation and developmental models of childhood with their tendency to neglect the agency and social competency of young children and the latter being embedded within essentialist notions of 'race' and ethnicity that tend to deny the contingent and context-specific nature of racialised identities. The paper argues that the result of this has been that while children have often been the objects of research they have rarely been the subjects; in other words they are often seen but never heard. The paper argues for the need to move beyond the methodological confines set by these discourses and rethink alternative approaches that begin with the assumption that young children are socially competent. One such approach, drawing upon ethnographic methods and fore-grounding the importance of largely unstructured small group interviews with young children, is illustrated. Through the use of a number of examples, it is shown how this approach can help to emphasise the ability of children as young as five and six to respond to and negotiate their social worlds and more specifically within this the competency with which they are able to appropriate, rework and reproduce a number of discourses on 'race' to make sense of their own social experiences. In doing this the paper also illustrates the way in which it provides a methodology able to draw out and highlight the contradictions, contingency and complexity of racialised identities among young children. Ultimately, it is an approach concerned with placing the children themselves central within the research processes and foregrounding their voices and experiences.