Extent of differential allelic expression of candidate breast cancer genes is similar in blood and breast.

INTRODUCTION: Normal gene expression variation is thought to play a central role in inter-individual variation and susceptibility to disease. Regulatory polymorphisms in cis-acting elements result in the unequal expression of alleles. Differential allelic expression (DAE) in heterozygote individuals could be used to develop a new approach to discover regulatory breast cancer susceptibility loci. As access to large numbers of fresh breast tissue to perform such studies is difficult, a suitable surrogate test tissue must be identified for future studies. METHODS: We measured differential allelic expression of 12 candidate genes possibly related to breast cancer susceptibility (BRCA1, BRCA2, C1qA, CCND3, EMSY, GPX1, GPX4, MLH3, MTHFR, NBS1, TP53 and TRXR2) in breast tissue (n = 40) and fresh blood (n = 170) of healthy individuals and EBV-transformed lymphoblastoid cells (n = 19). Differential allelic expression ratios were determined by Taqman assay. Ratio distributions were compared using t-test and Wilcoxon rank sum test, for mean ratios and variances respectively. RESULTS: We show that differential allelic expression is common among these 12 candidate genes and is comparable between breast and blood (fresh and transformed lymphoblasts) in a significant proportion of them. We found that eight out of nine genes with DAE in breast and fresh blood were comparable, as were 10 out of 11 genes between breast and transformed lymphoblasts. CONCLUSIONS: Our findings support the use of differential allelic expression in blood as a surrogate for breast tissue in future studies on predisposition to breast cancer.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A review of health utilities across conditions common in paediatric and adult populations

<p>Abstract</p> <p>Background</p> <p>Cost-utility analyses are commonly used in economic evaluations of interventions or conditions that have an impact on health-related quality of life. However, evaluating utilities in children presents several challenges since young children may not have the cognitive ability to complete measurement tasks and thus utility values must be estimated by proxy assessors. Another solution is to use utilities derived from an adult population. To better inform the future conduct of cost-utility analyses in paediatric populations, we reviewed the published literature reporting utilities among children and adults across selected conditions common to paediatric and adult populations.</p> <p>Methods</p> <p>An electronic search of Ovid MEDLINE, EMBASE, and the Cochrane Library up to November 2008 was conducted to identify studies presenting utility values derived from the Health Utilities Index (HUI) or EuroQoL-5Dimensions (EQ-5D) questionnaires or using time trade off (TTO) or standard gamble (SG) techniques in children and/or adult populations from randomized controlled trials, comparative or non-comparative observational studies, or cross-sectional studies. The search was targeted to four chronic diseases/conditions common to both children and adults and known to have a negative impact on health-related quality of life (HRQoL).</p> <p>Results</p> <p>After screening 951 citations identified from the literature search, 77 unique studies included in our review evaluated utilities in patients with asthma (n = 25), cancer (n = 23), diabetes mellitus (n = 11), skin diseases (n = 19) or chronic diseases (n = 2), with some studies evaluating multiple conditions. Utility values were estimated using HUI (n = 33), EQ-5D (n = 26), TTO (n = 12), and SG (n = 14), with some studies applying more than one technique to estimate utility values. 21% of studies evaluated utilities in children, of those the majority being in the area of oncology. No utility values for children were reported in skin diseases. Although few studies provided comparative information on utility values between children and adults, results seem to indicate that utilities may be similar in adolescents and young adults with asthma and acne. Differences in results were observed depending on methods and proxies.</p> <p>Conclusions</p> <p>This review highlights the need to conduct future research regarding measurement of utilities in children.</p

An evolutionarily-unique heterodimeric voltage-gated cation channel found in aphids

We describe the identification in aphids of a unique heterodimeric voltage-gated sodium channel which has an atypical ion selectivity filter and, unusually for insect channels, is highly insensitive to tetrodotoxin. We demonstrate that this channel has most likely arisen by adaptation (gene fission or duplication) of an invertebrate ancestral mono(hetero)meric channel. This is the only identifiable voltage-gated sodium channel homologue in the aphid genome(s), and the channel's novel selectivity filter motif (DENS instead of the usual DEKA found in other eukaryotes) may result in a loss of sodium selectivity, as indicated experimentally in mutagenised Drosophila channels

Sleep duration and eating behaviours are associated with body composition in 5-year-old children: findings from the ROLO longitudinal birth cohort study

Inadequate sleep and poor eating behaviours are associated with higher risk of childhood overweight and obesity. Less is known about the influence sleep has on eating behaviours and consequently body composition. Furthermore, whether associations differ in boys and girls has not been investigated extensively. We investigate associations between sleep, eating behaviours and body composition in cross-sectional analysis of 5-year-old children. Weight, height, BMI, mid upper arm circumference (MUAC), abdominal circumference (AC) and skinfold measurements were obtained. Maternal reported information on child’s eating behaviour and sleep habits were collected using validated questionnaires. Multiple linear regression examined associations between sleep, eating behaviours and body composition. Sleep duration was negatively associated with BMI, with 1-h greater sleep duration associated with 0·24 kg/m2 (B = 0·24, CI −0·42, −0·03, P = 0·026) lower BMI and 0·21 cm lower (B = –0·21, CI −0·41, −0·02, P = 0·035) MUAC. When stratified by sex, girls showed stronger inverse associations between sleep duration (h) and BMI (kg/m2) (B = –0·32; CI −0·60, −0·04, P = 0·024), MUAC (cm) (B = –0·29; CI −0·58, 0·000, P = 0·05) and AC (cm) (B = –1·10; CI −1·85, −0·21, P = 0·014) than boys. Positive associations for ‘Enjoys Food’ and ‘Food Responsiveness’ with BMI, MUAC and AC were observed in girls only. Inverse associations between sleep duration and ‘Emotional Undereating’ and ‘Food Fussiness’ were observed in both sexes, although stronger in boys. Sleep duration did not mediate the relationship between eating behaviours and BMI. Further exploration is required to understand how sleep impacts eating behaviours and consequently body composition and how sex influences this relationship

The People's Trial : supporting the public's understanding of randomised trials

Acknowledgements The People’s Trial team members acknowledge with gratitude the study participants. We would also like to acknowledge and thank Simone Lepage, Aoife O’Shaughnessy, and Louise Foley for their support with the research project. We would also like to thank Rob & Paul Digital Design™, Galway, Ireland. In addition, we would like to thank Marina Zaki for her support of The People’s Trial, in particular her expertise in promoting The People’s Trial through social media channels. Funding This research was funded by the Health Research Board in Ireland, through the Health Research Board – Trials Methodology Research Network as part of a Knowledge Exchange and Dissemination Scheme Award (grant reference KEDS-2018-012) 2018. The funder of the study had no role in the study design, data collection, data analysis, data interpretation or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit.Peer reviewedPublisher PD

Does reading a book in bed make a difference to sleep in comparison to not reading a book in bed? : The People's Trial- an online, pragmatic, randomised trial

Acknowledgements The People’s Trial team members acknowledge with gratitude the study participants. We would also like to acknowledge and thank Claire O’Connell, Simone Lepage, Aoife O’Shaughnessy and Louise Foley for their support with the research project. Trial funder This research was funded by the Health Research Board in Ireland, through the Health Research Board – Trials Methodology Research Network as part of a Knowledge Exchange and Dissemination Scheme Award 2018 (grant reference KEDS-2018-012). The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit.Peer reviewedPublisher PD

Evaluation of effectiveness and safety of pharmacist independent prescribers in care homes : cluster randomised controlled trial

Acknowledgments We thank all participating care home residents, care homes, and general practices; the pharmacist independent prescribers; our patient and public involvement group; our pharmacist trainers and assessors; Norwich Clinical Trials Unit; Comprehensive Research Network Eastern; our sponsor (Norfolk and Waveney CCG); members of our Programme Steering Committee and Data Monitoring and Ethics Committee; our funders; and all the many other people who supported the delivery of the programme of research that culminated in this trial. Funding: This work was funded by National Institutes of Health Research (NIHR) through their Programme Grant for Applied Research (PGfAR) stream (RP-PG-0613-20007). The funder had no role in design, data collection, data analysis, data interpretation, or writing of this paper.Peer reviewedPublisher PD

Novel mutations in the voltage-gated sodium channel of pyrethroid-resistant Varroa destructor populations from the Southeastern USA

The parasitic mite Varroa destructor has a significant worldwide impact on bee colony health. In the absence of control measures, parasitized colonies invariably collapse within 3 years. The synthetic pyrethroids tau-fluvalinate and flumethrin have proven very effective at managing this mite within apiaries, but intensive control programs based mainly on one active ingredient have led to many reports of pyrethroid resistance. In Europe, a modification of leucine to valine at position 925 (L925V) of the V. destructor voltage-gated sodium channel was correlated with resistance, the mutation being found at high frequency exclusively in hives with a recent history of pyrethroid treatment. Here, we identify two novel mutations, L925M and L925I, in tau-fluvalinate resistant V. destructor collected at seven sites across Florida and Georgia in the Southeastern region of the USA. Using a multiplexed TaqMan® allelic discrimination assay, these mutations were found to be present in 98% of the mites surviving tau-fluvalinate treatment. The mutations were also found in 45% of the non-treated mites, suggesting a high potential for resistance evolution if selection pressure is applied. The results from a more extensive monitoring programme, using the Taqman® assay described here, would clearly help beekeepers with their decision making as to when to include or exclude pyrethroid control products and thereby facilitate more effective mite management programmes

The Care Home Independent Pharmacist Prescriber Study (CHIPPS) : Development and implementation of an RCT to estimate safety, effectiveness and cost-effectiveness

This research was supported by the National Institute for Health and Care Research (NIHR) Yorkshire and Humber Patient Safety Translational Research Centre (NIHR YH PSTRC). The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. This report is dedicated to Kate Massey, an active and enthusiastic member of the CHIPPS patient and public involvement team who sadly passed away during the delivery of this study.Peer reviewedPublisher PD

Protocol for a cluster randomised controlled trial to determine the effectiveness and cost-effectiveness of independent pharmacist prescribing in care home: the CHIPPS study

Background: Prescribing, monitoring and administration of medicines in care homes could be improved. Research has identified the need for one person to assume overall responsibility for the management of medicines within each care home. and shown that a pharmacist independent prescriber service is feasible in this context. Aims and objectives: To conduct a cluster randomised controlled trial to determine the effectiveness and cost-effectiveness of a pharmacist-independent prescribing service in care homes compared to usual general practitioner (GP)-led care. Objectives: To perform a definitive randomised controlled trial (RCT) with an internal pilot to determine the intervention’s effectiveness and cost-effectiveness and enable modelling beyond the end of the trial. Methods: This protocol is for a cluster RCT with a 3-month internal pilot to confirm that recruitment is achievable, and there are no safety concerns. The unit of randomisation is a triad comprising a pharmacist-independent prescriber (PIP) based in a GP practice with sufficient registered patients resident in one or more care homes to allow recruitment of an average of 20 participants. In the intervention group, the PIP will, in collaboration with the GP: assume responsibility for prescribing and managing residents’ medicines including medication review and pharmaceutical care planning; support systematic ordering and administration in the care home, GP practice and supplying pharmacy; train care home and GP practice staff; communicate with GP practice, care home, supplying community pharmacy and study team. The intervention will last 6 months. The primary outcome will be resident falls at 6 months. Secondary outcomes include resident health-related quality of life, falls at 3 months, medication burden, medication appropriateness, mortality and hospitalisations. A full health economic analysis will be undertaken. The target sample size is 880 residents (440) in each arm) from 44 triads. This number is sufficient to detect a decrease in fall rate from 1.5 per individual to 1.178 (relative reduction of 21%) with 80% power and an ICC of 0.05 or less. Discussion: Recruitment is on-going and the trial should complete in early 2020. The trial results will have implications for the future management of residents in care homes and the ongoing implementation of independent pharmacist prescribing. Trial registration: ISRCTN, ID: 17847169. Registered on 15 December 2017