Royal Devon and Exeter Hospital

About: Royal Devon and Exeter Hospital is a healthcare organization based out in Exeter, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 2282 authors who have published 2526 publications receiving 78866 citations. The organization is also known as: RD&E.

The French Paradox

Abstract: In this chapter, clinical and experimental evidence is reviewed with respect to implant survival in relation to cement mantle thickness. The so-called French paradox of excellent survival with thin cement mantles is discussed. Cement mantles perceived as ≫thin≪ may in fact by thicker than expected.

Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer.

Abstract: Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.

Action research: politics, ethics and participation

Abstract: Aim. This paper contributes to an understanding of the political and ethical aspects of action research (AR). Background. Action research is growing in popularity in nursing and health care as a means of changing practice and generating new knowledge. As a methodology, AR relies on a close collaborative working relationship between researcher and participants, but this close relationship is also the source of political and ethical problems faced by researchers and participants. Content. We argue that action researchers and participants working in their own organizations should be clear about the extent to which they are engaged in a political activity, and that AR does not offer the same ethical guarantees concerning confidentiality and anonymity, informed consent, and protection from harm as other research methodologies (both quantitative and qualitative). This argument is illustrated by our experiences of participation in an AR study. Conclusion. We outline three areas where AR is implicitly political, and three areas where it is ethically problematic. We recommend that researchers and participants recognize, discuss and negotiate these problematic areas before starting their work.