Rapid analysis of GSTM1, GSTT1 and GSTP1 polymorphisms using real-time polymerase chain reaction

Polymorphisms of glutathione transferases (GST) are important genetic determinants of susceptibility to environmental carcinogens (Rebbeck, 1997). The GSTs are a multigene family of dimeric enzymes involved in detoxification, and, in a few cases, the bioactivation of a variety of xenobiotics (Hayes et al., 1995). The cytosolic GST enzyme family consists of four major classes of enzymes, referred to as alpha, mu, pi and theta. Several members of this family (for example, GSTM1, GSTT1 and GSTP1) are polymorphic in human populations (Wormhoudt et al., 1999). Molecular epidemiology studies have examined the role of GST polymorphisms as susceptibility factors for environmentally and/or occupationally induced cancers (Wormhoudt et al., 1999). In particular, case-control studies showed a relationship between the GSTM1 null genotype and the development of cancer in association with smoking habits, which has been shown for cancers of the respiratory and gastrointestinal tracts as well as other cancer types (Miller et al., 1997). Only a few molecular epidemiological studies addressed the role of GSTT1 and GSTP1 polymorphisms in cancer susceptibility. Since GSTP1 is a key player in biotransformation/bioactivation of benzo(a)pyrene, GSTP1 may be even more important than GSTM1 in the prevention of tobacco-induced cancers (Harries et al., 1997; Harris et al., 1998). To date, this relationship has not been sufficiently addressed in humans. Comprehensive molecular epidemiological studies may add to the current knowledge of the role of GST polymorphisms in cancer susceptibility and extent of the knowledge gained from approaches that used phenotyping, such as GSTM1 activity as it relates to trans-stilbene oxide, or polymerase chain reaction (PCR) based genotyping of polymorphic isoenzymes (Bell et al., 1993; Pemble et al., 1994; Harries et al., 1997).

Degree of value alignment : a grounded theory of rural nurse resignations

INTRODUCTION: The shortage of nurses willing to work in rural Australian healthcare settings continues to worsen. Australian rural areas have a lower retention rate of nurses than metropolitan counterparts, with more remote communities experiencing an even higher turnover of nursing staff. When retention rates are lower, patient outcomes are known to be poorer. This article reports a study that sought to explore the reasons why registered nurses resign from rural hospitals in the state of New South Wales, Australia. METHODS: Using grounded theory methods, this study explored the reasons why registered nurses resigned from New South Wales rural hospitals. Data were collected from 12 participants using semi-structured interviews; each participant was a registered nurse who had resigned from a rural hospital. Nurses who had resigned due to retirement, relocation or maternity leave were excluded. Interviews were transcribed verbatim and imported into NVivo software. The constant comparative method of data collection and analysis was followed until a core category emerged. RESULTS: Nurses resigned from rural hospitals when their personal value of how nursing should occur conflicted with the hospital's organisational values driving the practice of nursing. These conflicting values led to a change in the degree of value alignment between the nurse and hospital. The degree of value alignment occurred in three dynamic stages that nurses moved through prior to resigning. The first stage, sharing values, was a time when a nurse and a hospital shared similar values. The second stage was conceding values where, due to perceived changes in a hospital's values, a nurse felt that patient care became compromised and this led to a divergence of values. The final stage was resigning, a stage where a nurse 'gave up' as they felt that their professional integrity was severely compromised. The findings revealed that when a nurse and organisational values were not aligned, conflict was created for a nurse about how they could perform nursing that aligned with their internalised professional values and integrity. Resignation occurred when nurses were unable to realign their personal values to changed organisational values - the organisational values changed due to rural area health service restructures, centralisation of budgets and resources, cumbersome hierarchies and management structures that inhibited communication and decision making, out-dated and ineffective operating systems, insufficient and inexperienced staff, bullying, and a lack of connectedness and shared vision. CONCLUSIONS: To fully comprehend rural nurse resignations, this study identified three stages that nurses move through prior to resignation. Effective retention strategies for the nursing workforce should address contributors to a decrease in value alignment and work towards encouraging the coalescence of nurses' and hospitals' values. It is imperative that strategies enable nurses to provide high quality patient care and promote a sense of connectedness and a shared vision between nurse and hospital. Senior managers need to have clear ways to articulate and imbue organisational values and be explicit in how these values accommodate nurses' values. Ward-level nurse managers have a significant responsibility to ensure that a hospital's values (both explicit and implicit) are incorporated into ward culture.

Identification of eusynstyelamide B as a potent cell cycle inhibitor following the generation and screening of an ascidian-derived extract library using a real time cell analyzer

Ascidians are marine invertebrates that have been a source of numerous cytotoxic compounds. Of the first six marine-derived drugs that made anticancer clinical trials, three originated from ascidian specimens. In order to identify new anti-neoplastic compounds, an ascidian extract library (143 samples) was generated and screened in MDA-MB-231 breast cancer cells using a real-time cell analyzer (RTCA). This resulted in 143 time-dependent cell response profiles (TCRP), which are read-outs of changes to the growth rate, morphology, and adhesive characteristics of the cell culture. Twenty-one extracts affected the TCRP of MDA-MB-231 cells and were further investigated regarding toxicity and specificity, as well as their effects on cell morphology and cell cycle. The results of these studies were used to prioritize extracts for bioassay-guided fractionation, which led to the isolation of the previously identified marine natural product, eusynstyelamide B (1). This bis-indole alkaloid was shown to display an IC50 of 5 μM in MDA-MB-231 cells. Moreover, 1 caused a strong cell cycle arrest in G2/M and induced apoptosis after 72 h treatment, making this molecule an attractive candidate for further mechanism of action studies.

Conservation communication camp : come with ideas, leave with a plan

IUCN´s core work involves generating knowledge and tools to influence policy and practice for nature conservation. Whilst it appears that we are collectively making progress in some areas, we acknowledge the need to improve our communication processes and practices to ´move to action´ in this regard. We need to extend the influence of the science and the knowledge beyond the documents to achieve effective impact and action. The training course will focus on the process of getting the conservation messages out to a wider audience. This interactive and participatory training course will develop the skills and knowledge needed to communicate effective conservation messages for a range of IUCN internal and external audiences. The course will cover: • what is communication for conservation? • the communication planning process (developing your communication objectives) • identifying and understanding your target audiences • developing your conservation message • choosing your communication media and • evaluating the effectiveness of your communication strategies. A unique feature of the training course will be the use of Web 2.0 tools in innovative conservation communications e.g. use of social media in concept branding and social marketing. In the spirit of the Forum´s objective of ´Sharing know how´, each participant will bring a current conservation issue to the training course and will leave with their own communication plan. Potentially, the training course adopts a cross-thematic approach as the issues addressed could be drawn from any of the IUCN´s program themes. Primarily though, the training course´s best fit is with the ´Valuing and Conserving Biodiversity´ theme since it will provide concrete and pragmatic solutions to enhancing the implementation of conservation measures through participatory planning and capacity building.

Get a life? The impact of the European working time directive : the case of UK senior doctors

This paper seeks to identify the effect of the implementation of the European Working Time Directive (EWTD) on the working hours of UK doctors. The Labour Force Survey is used to compare the working hours of doctors with a variety of control groups before and after the implementation of the directive. The controls include those unconstrained by the directive and doctor counterparts working in Europe. We use differences-in-differences and matching methods to estimate the impact of this natural experiment, distinguishing between the anticipation and enactment of the EWTD. We find that the legislation reduced the hours of senior doctors by around 8 hours in total including the component attributable to anticipation effects and allowing for (exogenously set) rising wages.