The challenge of consent in clinical genome-wide testing

Genome-wide testing methods include array comparative genomic hybridisation (aCGH), multiple gene panels, whole exome sequencing (WE) and whole genome sequencing (WGS). Here we introduce some of the key ethical and social considerations relating to informed consent for the testing of children, particularly the management of incidental findings and variants of unknown significance.</jats:p

Estrogen receptor-? signaling and localization regulates autophagy and unfolded protein response activation in ER+ breast cancer

Antiestrogen therapy is commonly used to treat estrogen receptor (ER)+ breast cancers but acquired and de novo resistance limits their overall curative potential. An endoplasmic reticulum stress pathway, the unfolded protein response, and autophagy are both implicated in the development of antiestrogen therapy resistance in estrogen receptor-? (ER) positive breast cancer. Thus, we recently investigated how ER? can regulate autophagy and the unfolded protein response (Cook et al., FASEBJ, 2014). We showed that inhibiting ER? signaling stimulates autophagosome formation and flux. Moreover, we showed that ER? knockdown inhibited the unfolded protein response (UPR) signaling components. Here we support and extend this recent report showing additional data on ER? localization and provide a schematic of the overall signaling implicated by our results. Differential activation of UPR and autophagy highlight the pivotal role of ER? in regulating pro-survival signaling in breast cancer through UPR and autophagy. Furthermore, these data suggest new approaches to successful targeting ER? and preventing the regulation of key pro-survival signaling that confers resistance to endocrine therapies.&nbsp

The response of Greek key proteins to changes in connectivity depends on the nature of their secondary structure.

What governs the balance between connectivity and topology in regulating the mechanism of protein folding? We use circular permutation to vary the order of the helices in the all-α Greek key protein FADD (Fas-associated death domain) to investigate this question. Unlike all-β Greek key proteins, where changes in the order of secondary structure cause a shift in the folding nucleus, the position of the nucleus in FADD is unchanged, even when permutation reduces the complexity significantly. We suggest that this is because local helical contacts are so dominant that permutation has little effect on the entropic cost of forming the folding nucleus whereas, in all-β Greek key proteins, all interactions in the nucleus are long range. Thus, the type of secondary structure modulates the sensitivity of proteins to changes in connectivity.This work was supported by the Wellcome Trust (WT095195) (J.C), Engineering and Physical Sciences Research Council (UK) Grant EP/J016764/1 (D.D.S.) and an Engineering and Physical Sciences Research Council (UK) studentship (K.R.K.). J.C. is a Wellcome Trust Senior Research fellow.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0022283615002168#

PR:EPARe: A game-based approach to relationship guidance for adolescents

AbstractEnsuring adolescents are equipped with the necessary skills to handle coercion and pressure from peers is a central component of effective relationship education. However, for teachers attempting to convey these principles, didactic methods have been shown to meet with limited success, as the highest-risk students may fail to engage with the subject matter in a meaningful fashion. In this paper, the potential a digital game may hold as a component of a blended learning solution to this problem is explored though the development of PR:EPARe (Positive Relationships: Eliminating Coercion and Pressure in Adolescent Relationships). Adopting a participatory design approach, designers considered relevant input from stakeholders, subject experts, teachers and students in the development of PR:EPARe. Participatory involvement has allowed the game to be developed in such a way that draws focus on the role of the end user to extend from the traditional concern of the student's learning needs to consider that of the practitioner's needs as another primary condition of successful game based learning. An examination of the first section of the PR:EPARe game is undertaken through a cluster randomized control trial of 507 students across three UK schools. Using ANOVA to demonstrating significant differences between control and game groups (p<0.05) for responses to a range of questions on preparedness and self-efficacy. An overall significant positive effect of the game over time when compared to the control (p<0.001) is observed. Based on these preliminary findings, the participatory approach to development is shown to lead to a developed game which is well- received by students, offering the potential to provide a valuable resource for teachers attempting to address this difficult subject within a classroom-based context

Speech and language therapy versus placebo or no intervention for speech problems in Parkinson's disease

Parkinson's disease patients commonly suffer from speech and vocal problems including dysarthric speech, reduced loudness and loss of articulation. These symptoms increase in frequency and intensity with progression of the disease). Speech and language therapy (SLT) aims to improve the intelligibility of speech with behavioural treatment techniques or instrumental aids

Cranberries and Cancer: An Update of Preclinical Studies Evaluating the Cancer Inhibitory Potential of Cranberry and Cranberry Derived Constituents

Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques, whereas in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy in high risk cohorts should be considered