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).

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.

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.

Simulation-based density estimation for time series using covariate data

This paper proposes a simulation-based density estimation technique for time series that exploits information found in covariate data. The method can be paired with a large range of parametric models used in time series estimation. We derive asymptotic properties of the estimator and illustrate attractive finite sample properties for a range of well-known econometric and financial applications.

Writing embodied practice from the inside : outside the exegesis

The textual turn is a good friend of expert spectating, where it assumes the role of writing-productive apparatus, but no friend at all of expert practices or practitioners (Melrose, 2003). Introduction The challenge of time-based embodied performance when the artefact is unstable As a former full-time professional practitioner with an embodied dance practice as performer, choreographer and artistic director for three decades, I somewhat unexpectedly entered the world of academia in 2000 after completing a practice-based PhD, which was described by its examiners as ‘pioneering’. Like many artists my intention was to deepen and extend my practice through formal research into my work and its context (which was intercultural) and to privilege the artist’s voice in a research world where it was too often silent. Practice as research, practice-based research, and practice-led research were not yet fully named. It was in its infancy and my biggest challenge was to find a serviceable methodology which did not betray my intentions to keep practice at the centre of the research. Over the last 15 years, practice led doctoral research, where examinable creative work is placed alongside an accompanying (exegetical) written component, has come a long way. It has been extensively debated with a range of theories and models proposed (Barrett & Bolt, 2007, Pakes, 2003 & 2004, Piccini, 2005, Philips, Stock & Vincs 2009, Stock, 2009 & 2010, Riley & Hunter 2009, Haseman, 2006, Hecq, 2012). Much of this writing is based around epistemological concerns where the research methodologies proposed normally incorporate a contextualisation of the creative work in its field of practice, and more importantly validation and interrogation of the processes of the practice as the central ‘data gathering’ method. It is now widely accepted, at least in the Australian creative arts context, that knowledge claims in creative practice research arise from the material activities of the practice itself (Carter, 2004). The creative work explicated as the tangible outcome of that practice is sometimes referred to as the ‘artefact’. Although the making of the artefact, according to Colbert (2009, p. 7) is influenced by “personal, experiential and iterative processes”, mapping them through a research pathway is “difficult to predict [for] “the adjustments made to the artefact in the light of emerging knowledge and insights cannot be foreshadowed”. Linking the process and the practice outcome most often occurs through the textual intervention of an exegesis which builds, and/or builds on, theoretical concerns arising in and from the work. This linking produces what Barrett (2007) refers to as “situated knowledge… that operates in relation to established knowledge” (p. 145). But what if those material forms or ‘artefacts’ are not objects or code or digitised forms, but live within the bodies of artist/researchers where the nature of the practice itself is live, ephemeral and constantly transforming, as in dance and physical performance? Even more unsettling is when the ‘artefact’ is literally embedded and embodied in the work and in the maker/researcher; when subject and object are merged. To complicate matters, the performing arts are necessarily collaborative, relying not only on technical mastery and creative/interpretive processes, but on social and artistic relationships which collectively make up the ‘artefact’. This chapter explores issues surrounding live dance and physical performance when placed in a research setting, specifically the complexities of being required to translate embodied dance findings into textual form. Exploring how embodied knowledge can be shared in a research context for those with no experiential knowledge of communicating through and in dance, I draw on theories of “dance enaction” (Warburton, 2011) together with notions of “affective intensities” and “performance mastery” (Melrose, 2003), “intentional activity” (Pakes, 2004) and the place of memory. In seeking ways to capture in another form the knowledge residing in live dance practice, thus making implicit knowledge explicit, I further propose there is a process of triple translation as the performance (the living ‘artefact’) is documented in multi-facetted ways to produce something durable which can be re-visited. This translation becomes more complex if the embodied knowledge resides in culturally specific practices, formed by world views and processes quite different from accepted norms and conventions (even radical ones) of international doctoral research inquiry. But whatever the combination of cultural, virtual and genre-related dance practices being researched, embodiment is central to the process, outcome and findings, and the question remains of how we will use text and what forms that text might take.

Healthcare-associated infections in Australia : time for national surveillance

Abstract Objective. Healthcare-associated infection (HAI) surveillance programs are critical for infection prevention. Australia does not have a comprehensive national HAI surveillance program. The purpose of this paper is to provide an overview of established international and Australian statewide HAI surveillance programs and recommend a pathway for the development of a national HAI surveillance program in Australia. Methods. This study examined existing HAI surveillance programs through a literature review, a review of HAI surveillance program documentation, such as websites, surveillance manuals and data reports and direct contact with program representatives. Results. Evidence from international programs demonstrates national HAI surveillance reduces the incidence of HAIs. However, the current status of HAI surveillance activity in Australian states is disparate, variation between programs is not well understood, and the quality of data currently used to compose national HAI rates is uncertain. Conclusions. There is a need to develop a well-structured, evidence-based national HAI program in Australia to meet the increasing demand for validated reliable national HAI data. Such a program could be leveraged off the work of existing Australian and international programs.

A Memetic Algorithm for the location-based continuously operating reference stations placement problem in Network Real-Time Kinematic

Network Real-Time Kinematic (NRTK) is a technology that can provide centimeter-level accuracy positioning services in real time, and it is enabled by a network of Continuously Operating Reference Stations (CORS). The location-oriented CORS placement problem is an important problem in the design of a NRTK as it will directly affect not only the installation and operational cost of the NRTK, but also the quality of positioning services provided by the NRTK. This paper presents a Memetic Algorithm (MA) for the location-oriented CORS placement problem, which hybridizes the powerful explorative search capacity of a genetic algorithm and the efficient and effective exploitative search capacity of a local optimization. Experimental results have shown that the MA has better performance than existing approaches. In this paper we also conduct an empirical study about the scalability of the MA, effectiveness of the hybridization technique and selection of crossover operator in the MA.