How young people find out about their family history of Huntington's disease

Family communication about adult-onset hereditary illness can be problematic, leaving some relatives inadequately informed or ignorant of their risk. Although studies have explored the barriers and facilitators in family communication about genetic risk, questions remain about when, what, how and indeed whether to tell relatives. The process of disclosure is also dependent upon the way in which genetic information is realized and understood by recipients, but research here is limited. Our paper explores young people’s experiences of finding out about a family history of the hereditary disorder Huntington’s disease (HD). In-depth interviews explored how and when young people found out, their reactions to different communication styles and any impact on family relations. We recruited young people through the North of Scotland regional genetics clinic and the Scottish Huntington’s Association (SHA). Thirtythree young people (aged 9–28) were interviewed. A qualitative analysis was undertaken which revealed four types of disclosure experiences: (1) having always been told, (2) gradually told, (3) HD was kept a secret, or (4) HD as a new diagnosis. In particular, the timing and style of disclosure from relatives, and one’s stage of awareness, were fundamental in structuring participants’ accounts. This article focuses on questions of when, how and indeed whether to tell children, and sits within a broader set of research and practice issues about what professionals and families (should) tell children about parental illness and genetic risk.Wellcome Trust’s Programme in Biomedical Ethic

Optimal distribution and utilization of donated human breast milk: a novel approach

Background: The nutritional content of donated expressed breast milk (DEBM) is variable. Using DEBM to provide for the energy requirements of neonates is challenging. Objective: The authors hypothesized that a system of DEBM energy content categorization and distribution would improve energy intake from DEBM. Methods: We compared infants’ actual cumulative energy intake with projected energy intake, had they been fed using our proposed system. Eighty-five milk samples were ranked by energy content. The bottom, middle, and top tertiles were classified as red, amber, and green energy content categories, respectively. Data on 378 feeding days from 20 babies who received this milk were analyzed. Total daily intake of DEBM was calculated in mL/kg/day and similarly ranked. Infants received red energy content milk, with DEBM intake in the bottom daily volume intake tertile; amber energy content milk, with intake in the middle daily volume intake tertile; and green energy content milk when intake reached the top daily volume intake tertile. Results: Actual median cumulative energy intake from DEBM was 1612 (range, 15-11 182) kcal. Using DEBM with the minimum energy content from the 3 DEBM energy content categories, median projected cumulative intake was 1670 (range 13-11 077) kcal, which was not statistically significant (P = .418). Statistical significance was achieved using DEBM with the median and maximum energy content from each energy content category, giving median projected cumulative intakes of 1859 kcal (P = .0006) and 2280 kcal (P = .0001), respectively. Conclusion: Cumulative energy intake from DEBM can be improved by categorizing and distributing milk according to energy content

The Pedagogical Practice of Locative Experience

We work collectively with varied locative-type projects and look to integrate our students into contemporary experience design culture. Students experience the ‘how and what’ of locative by becoming participant users, being exposed to contemporary works, and placing themselves in the role of the designer producing their own located works

Feasibility and acceptability of the use of patient-reported outcome measures (PROMs) in the delivery of nurse-led supportive care to people with colorectal cancer

Purpose Logistical issues pertinent to the use of patient-reported outcome measures (PROMs) by colorectal cancer nurse specialists (CNS) to identify the needs of people with colorectal cancer (CRC) in acute care remain unknown. We explored the feasibility and acceptability of PROMs-driven, CNS-led consultations to enhance delivery of supportive care to people with CRC completing adjuvant chemotherapy. Methods A systematic literature review and focus groups with patients and CNS (Phase 1) were followed by a repeated-measures, exploratory study (Phase 2), whereby pre-consultation PROM data were collected during three consecutive, monthly consultations, and used by the CNS to enable delivery of personalised supportive care. Results Based on Phase 1 data, the Supportive Care Needs Survey was selected for use in Phase 2. Fourteen patients were recruited (recruitment rate: 56%); thirteen (93%) completed all study assessments. Forty in-clinic patient-clinician consultations took place. At baseline, 219 unmet needs were reported in total, with a notable 21% (T2) and 32% (T3) over-time reduction. Physical/daily living and psychological domain scores declined from T1 to T3, yet not statistically significantly. In exit interviews, patients described how using the PROM helped them shortlist and prioritise their needs. CNS stressed how the PROM helped them tease out more issues with patients than they would normally. Conclusions Nurse-led, PROMs-driven needs assessments with patients with CRC appear to be feasible and acceptable in clinical practice, possibly associated with a sizeable reduction in the frequency of unmet needs, and smaller decreases in physical/daily living and psychosocial needs in the immediate post-chemotherapy period

Identifying barriers to help seeking for non-motor symptoms in people with Parkinson’s disease

Non-motor Symptoms (NMS) of Parkinson’s disease (PD) have a significant impact on quality of life. Despite this many NMS remain unreported by patients and consequently untreated. The present study explored barriers to help-seeking using two theoretical frameworks, the Common Sense Model of illness and Theoretical Domains Framework. 20 Participants completed semi-structured interviews to explore symptom beliefs and help-seeking behaviour. Uncertainty about the relationship of NMS to PD and lack of clarity around treatments were common. Embarrassment and communication difficulties were common for potentially sensitive symptoms such as sexual dysfunction. Symptom perceptions and beliefs about help-seeking acted as barriers to reporting NMS

The DDX6-4E-T interaction mediates translational repression and P-body assembly.

4E-Transporter binds eIF4E via its consensus sequence YXXXXLΦ, shared with eIF4G, and is a nucleocytoplasmic shuttling protein found enriched in P-(rocessing) bodies. 4E-T inhibits general protein synthesis by reducing available eIF4E levels. Recently, we showed that 4E-T bound to mRNA however represses its translation in an eIF4E-independent manner, and contributes to silencing of mRNAs targeted by miRNAs. Here, we address further the mechanism of translational repression by 4E-T by first identifying and delineating the interacting sites of its major partners by mass spectrometry and western blotting, including DDX6, UNR, unrip, PAT1B, LSM14A and CNOT4. Furthermore, we document novel binding between 4E-T partners including UNR-CNOT4 and unrip-LSM14A, altogether suggesting 4E-T nucleates a complex network of RNA-binding protein interactions. In functional assays, we demonstrate that joint deletion of two short conserved motifs that bind UNR and DDX6 relieves repression of 4E-T-bound mRNA, in part reliant on the 4E-T-DDX6-CNOT1 axis. We also show that the DDX6-4E-T interaction mediates miRNA-dependent translational repression and de novo P-body assembly, implying that translational repression and formation of new P-bodies are coupled processes. Altogether these findings considerably extend our understanding of the role of 4E-T in gene regulation, important in development and neurogenesis.BBSRC [BB/J00779X/1 to N.S.]; CNRS PICS (to D.W.); Agence Nationale pour la Recherche [ANR-14-CE09-0013-01ANR to D.W.]; Gates Cambridge Foundation (to A.K.); Fondation Wiener – Anspach of the Université Libre de Bruxelles and the Cambridge Newton Trust (C.V.). Funding for open access charge: BBSRC

Identifying factors associated with sedentary time after stroke. Secondary analysis of pooled data from nine primary studies.

<p><b>Background</b>: High levels of sedentary time increases the risk of cardiovascular disease, including recurrent stroke.</p> <p><b>Objective</b>: This study aimed to identify factors associated with high sedentary time in community-dwelling people with stroke.</p> <p><b>Methods</b>: For this data pooling study, authors of published and ongoing trials that collected sedentary time data, using the activPAL monitor, in community-dwelling people with stroke were invited to contribute their raw data. The data was reprocessed, algorithms were created to identify sleep-wake time and determine the percentage of waking hours spent sedentary. We explored demographic and stroke-related factors associated with total sedentary time and time in uninterrupted sedentary bouts using unique, both univariable and multivariable, regression analyses.</p> <p><b>Results</b>: The 274 included participants were from Australia, Canada, and the United Kingdom, and spent, on average, 69% (SD 12.4) of their waking hours sedentary. Of the demographic and stroke-related factors, slower walking speeds were significantly and independently associated with a higher percentage of waking hours spent sedentary (p = 0.001) and uninterrupted sedentary bouts of <i>>30</i> and <i>>60 min</i> (p = 0.001 and p = 0.004, respectively). Regression models explained 11–19% of the variance in total sedentary time and time in prolonged sedentary bouts.</p> <p><b>Conclusion</b>: We found that variability in sedentary time of people with stroke was largely unaccounted for by demographic and stroke-related variables. Behavioral and environmental factors are likely to play an important role in sedentary behavior after stroke. Further work is required to develop and test effective interventions to address sedentary behavior after stroke.</p

Parents’ views of genetic testing and treatment of familial hypercholesterolemia in children : a qualitative study

Open Access via Springer Compact Agreement. We would like to thank all the participants who took part and the genetics/lipid services who helped with recruitment, particularly Hazel Hailey and Margaretha van Mourik. We also thank our project advisory team, patient representatives and Zoe Skea. KFK was supported by a Postdoctoral Fellowship from the Chief Scientist Office of the Scottish Government (PDF/10/06). The views of this paper are the authors own.Peer reviewedPublisher PD

Stable isotope dynamic labeling of secretomes (SIDLS) identifies authentic secretory proteins released by cancer and stromal cells

Supported by a grant from North West Cancer Research.Analysis of secretomes critically underpins the capacity to understand the mechanisms determining interactions between cells and between cells and their environment. In the context of cancer cell micro-environments, the relevant interactions are recognised to be an important determinant of tumor progression. Global proteomic analyses of secretomes are often performed at a single time point and frequently identify both classical secreted proteins (possessing an N-terminal signal sequence), as well as many intracellular proteins, the release of which is of uncertain biological significance. Here, we describe a mass spectrometry-based method for stable isotope dynamic labeling of secretomes (SIDLS) that, by dynamic SILAC, discriminates the secretion kinetics of classical secretory proteins and intracellular proteins released from cancer and stromal cells in culture. SIDLS is a robust classifier of the different cellular origins of proteins within the secretome and should be broadly applicable to non-proliferating cells and cells grown in short term culture.PostprintPeer reviewe