The role of HER1-HER4 and EGFRvIII in hormone-refractory prostate cancer

<b>Purpose</b>: The role of the type I receptor tyrosine kinase (HER) family in progression of prostate cancer is controversial. Breast cancer studies show that these receptors should be investigated as a family. The current study investigates expression of HER1-HER4 and EGFRvIII in matched hormone-sensitive and hormone-refractory prostate tumors. <b>Experimental Design</b>: Immunohistochemical analysis was used to investigate protein expression of HER1-HER4, EGFRvIII, and phosphorylated Akt (pAkt) in matched hormone-sensitive and hormone-refractory prostate tumors. <b>Results</b>: Surprisingly, high HER2 membrane expression in hormone-sensitive tumors was associated with an increased time to biochemical relapse (<i>P</i> = 0.0003), and this translated into longer overall survival (<i>P</i> = 0.0021). Consistent with other studies, HER4 membrane expression in hormone-sensitive tumors was associated with longer time to biochemical relapse (<i>P</i> = 0.042), and EGFRvIII membrane expression was associated with shorter time to biochemical relapse (<i>P</i> = 0.015). An increase in pAkt expression was associated with reduced survival (<i>P</i> = 0.0098). Multivariate analysis showed that HER2 was an independent positive predictive marker of time to relapse in hormone-sensitive prostate tumors (<i>P</i> = 0.014). In contrast, high HER2 expression in hormone-refractory tumors was associated with decreased time to death from biochemical relapse (<i>P</i> = 0.039), and EGFRvIII nuclear expression was associated with decreased time to death from biochemical relapse and decreased overall survival (<i>P</i> = 0.02 and <i>P</i> = 0.005). <b>Conclusion</b>: These results suggest that the HER family may have multiple roles in prostate cancer, and that expression of the proteins alone is insufficient to predict the biological response that they may elicit

Impact case studies submitted to REF2014: the hidden impact of nursing research

The UK’s Research Excellence Framework (REF) 2014 rated the research from 154 universities and the impact of research was evaluated in 6975 impact case studies. Nursing was returned within unit of Assessment (UoA) 3 which also included Dentistry, Pharmacy, Allied Health Professions, although nursing research was also submitted within other UoAs. The study aim was to collate and categorise available REF impact case studies involving nursing researchers or on topics of relevance to nursing. Using nurs* as a search term 469 case study entries were retrieved from the REF database and placed into three categories determined by the level of involvement of nurses. Some 80 impact case studies were submitted by nurses across 11 UoAs: the majority being in UoA3 (n=55). A further 50 revealed some relevant impact, though nurses did not have an obvious research role. A total of 248 case studies described actual or potential impact on health or social care but were not associated specifically with nursing. Nursing research has demonstrable impact, however there is a significant body of research with relevance for nursing that has not been associated with the profession in the REF. More attention should be paid to the ‘hidden impact’ of nursing research to ensure the full impact of nursing is recognised

Service Learning Models Connecting Computer Science to the Community

Service learning is an educational experience that enables students to apply material learned in the classroom by volunteering in a real-world situation. This paper provides a brief review of service learning and describes two models that the computer science department at Saint Anselm College implemented successfully

Correlated sampling in quantum Monte Carlo: a route to forces

In order to find the equilibrium geometries of molecules and solids and to perform ab initio molecular dynamics, it is necessary to calculate the forces on the nuclei. We present a correlated sampling method to efficiently calculate numerical forces and potential energy surfaces in diffusion Monte Carlo. It employs a novel coordinate transformation, earlier used in variational Monte Carlo, to greatly reduce the statistical error. Results are presented for first-row diatomic molecules.Comment: 5 pages, 2 postscript figure

The Minimal Length of a Lagrangian Cobordism between Legendrians

To investigate the rigidity and flexibility of Lagrangian cobordisms between Legendrian submanifolds, we investigate the minimal length of such a cobordism, which is a $1$-dimensional measurement of the non-cylindrical portion of the cobordism. Our primary tool is a set of real-valued capacities for a Legendrian submanifold, which are derived from a filtered version of Legendrian Contact Homology. Relationships between capacities of Legendrians at the ends of a Lagrangian cobordism yield lower bounds on the length of the cobordism. We apply the capacities to Lagrangian cobordisms realizing vertical dilations (which may be arbitrarily short) and contractions (whose lengths are bounded below). We also study the interaction between length and the linking of multiple cobordisms as well as the lengths of cobordisms derived from non-trivial loops of Legendrian isotopies.Comment: 33 pages, 9 figures. v2: Minor corrections in response to referee comments. More general statement in Proposition 3.3 and some reorganization at the end of Section

End stage renal disease and survival in people with diabetes:a national database linkage study

© The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. Funding This work was supported by the Wellcome Trust through the Scottish Health Informatics Programme (SHIP). The SHIP is collaboration between the Universities of Aberdeen, Dundee, Edinburgh, Glasgow and St Andrews and the Information Services Division of National Health Service National Service Scotland. Funding for diabetes register linkage and data extraction was provided by the Chief Scientist’s Office of the Scottish Government. The Scottish Diabetes Research Network receives financial support from National Health Services Research Scotland. The Scottish Renal Registry is funded by the Information Services Division of National Health Service National Services Scotland but relies heavily on the goodwill of the contributing renal units who spent a large amount time working with Scottish Renal Registry staff to ensure that the data held within the register are accurate and complete.Peer reviewedPublisher PD

Xpf suppresses the mutagenic consequences of phagocytosis in Dictyostelium

As time passes, mutations accumulate in the genomes of all living organisms. These changes promote genetic diversity, but also precipitate ageing and the initiation of cancer. Food is a common source of mutagens, but little is known about how nutritional factors cause lasting genetic changes in the consuming organism. Here, we describe an unusual genetic interaction between DNA repair in the unicellular amoeba Dictyostelium discoideum and its natural bacterial food source. We found that Dictyostelium deficient in the DNA repair nuclease Xpf (xpf−) display a severe and specific growth defect when feeding on bacteria. Despite being proficient in the phagocytosis and digestion of bacteria, over time, xpf− Dictyostelium feeding on bacteria cease to grow and in many instances die. The Xpf nuclease activity is required for sustained growth using a bacterial food source. Furthermore, the ingestion of this food source leads to a striking accumulation of mutations in the genome of xpf− Dictyostelium. This work therefore establishes Dictyostelium as a model genetic system to dissect nutritional genotoxicity, providing insight into how phagocytosis can induce mutagenesis and compromise survival fitness.Medical Research Council (MRC) de Reino Unido. MC_U105178811 y MC_U105115237Wellcome Trust de Reino Unido. WT10620

‘Dead people don’t claim’: A psychopolitical autopsy of UK austerity suicides

One of the symptoms of post financial crisis austerity in the UK has been an increase in the numbers of suicides, especially by people who have experienced welfare reform. This article develops and utilises an analytic framework of psychopolitical autopsy to explore media coverage of ‘austerity suicide’ and to take seriously the psychic life of austerity (internalisation, shame, anxiety), embedding it in a context of social dis-ease. Drawing on three distinct yet interrelated areas of literature (the politics of affect and psychosocial dynamics of welfare, post and anti-colonial psychopolitics, and critical suicidology), the article aims to better understand how austerity ‘kills’. Key findings include understanding austerity suicides as embedded within an affective economy of the anxiety caused by punitive welfare retrenchment, the stigmatisation of being a recipient of benefits, and the internalisation of market logic that assigns value through ‘productivity’ and conceptualises welfare entitlement as economic ‘burden’. The significance of this approach lies in its ability to widen analytic framing of suicide from an individual and psychocentric focus, to illuminate culpability of government reforms while still retaining the complexity of suicide, and thus to provide relevant policy insights about welfare reform