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

Positive allosteric modulators of the μ‐opioid receptor: a novel approach for future pain medications

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109803/1/bph12599.pd

Bachelor of Nursing Honours Programs in Australia: current trends and key challenges

Background: To prepare nurses for a role in knowledge generation they need to engage in research training. Bachelor of Nursing (Honours) programs are a first step in this training. Developing a better understanding of current programs, their challenges and outcomes will provide an evidence base to inform curriculum development and policy making. Aim: The aim of this study was to explore current Australian Bachelor of Nursing (Honours) programs in terms of their composition, delivery and number of enrolments/graduates. Methods: Bachelor of Nursing Honours Coordinators or Heads of Schools of Nursing and Midwifery at Australian Universities were emailed an invitation to participate in an online survey. Findings: Of the 19 academics who responded to the survey, 15 (78.9%) reported currently offering a Bachelor of Nursing (Honours) program in their institution. A steady decline in mean enrolments was evident over recent years. There were clear differences in course delivery and assessment tasks between courses. Conclusion: This paper highlights the need to further explore Bachelor of Nursing (Honours) programs across Australia to ensure consistency in outcomes and to explore innovations in course delivery and project development. Such changes should incorporate feedback from students, supervisors, curriculum developers and professional stakeholders to ensure that programs address their various needs

Age-related penetrance of the C9orf72 repeat expansion

A pathogenic hexanucleotide repeat expansion within the C9orf72 gene has been identified as the major cause of two neurodegenerative syndromes, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation is known to have incomplete penetrance, with some patients developing disease in their twenties and a small portion of carriers surviving to their ninth decade without developing symptoms. Describing penetrance by age among C9orf72 carriers and identifying parameters that alter onset age are essential to better understanding this locus and to enhance predictive counseling. To do so, data from 1,170 individuals were used to model penetrance. Our analysis showed that the penetrance was incomplete and age-dependent. Additionally, familial and sporadic penetrance did not significantly differ from one another; ALS cases exhibited earlier age of onset than FTD cases; and individuals with spinal-onset exhibited earlier age of onset than those with bulbar-onset. The older age of onset among female cases in general, and among female bulbar-onset cases in particular, was the most striking finding, and there may be an environmental, lifestyle, or hormonal factor that is influencing these penetrance patterns. These results will have important applications for future clinical research, the identification of disease modifiers, and genetic counseling.Peer reviewe

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