The long-term impact of folic acid in pregnancy on offspring DNA methylation : follow-up of the Aberdeen folic acid supplementation trial (AFAST)

Funding This work was supported by the NIHR Bristol Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. R.C.R., G.C.S., N.K., T.G., G.D.S. and C.L.R. work in a unit that receives funds from the University of Bristol and the UK Medical Research Council (MC_UU_12013/1, MC_UU_12013/2 and MC_UU_12013/8). This work was also supported by CRUK (grant number C18281/A19169) and the ESRC (grant number ES/N000498/1). C.M.T. is supported by a Wellcome Trust Career Re-entry Fellowship (grant number 104077/Z/14/Z).Peer reviewedPublisher PD

Video Summary of How Credible is Online Physical Activity Advice? The Accuracy of Free Adult Educational Materials

The uploaded work is a video summary of original research. The video is less than seven minutes long. The original research summarized in the video examined the credibility of physical activity advice presented in online educational materials for lay adults. The video highlights main points of the research, leads the viewer through steps to judge the credibility of lay material, and provides links to resources for further education and guidance. The video has several supplemental files. They are as follows: (a) the full transcript text to the video narration, which includes the links to the resource material that are listed at the end of the video, (b) a copy of the video summary for free download, and (c) a copy of the closed-captioning file with English subtitles. In conclusion, the uploaded video summary and its supplemental files are for use in a variety of educational settings, serving students and professionals

SARS-CoV-2 transmission dynamics should inform policy

Funding: JM is supported in part by the U.S. National Institute of Allergy and Infectious Diseases [K01AI122853].It is generally agreed that striking a balance between resuming economic and social activities and keeping the effective reproductive number (R0) below 1 using non-pharmaceutical interventions is an important goal until and even after effective vaccines become available. Therefore, the need remains to understand how the virus is transmitted in order to identify high-risk environments and activities that disproportionately contribute to its spread so that effective preventative measures could be put in place. Contact tracing and household studies in particular provide robust evidence about the parameters of transmission. In this viewpoint, we discuss the available evidence from large-scale, well-conducted contact tracing studies from across the world and argue that SARS-CoV-2 transmission dynamics should inform policy decisions about mitigation strategies for targeted interventions according to the needs of the society by directing attention to the settings, activities and socioeconomic factors associated with the highest risks of transmission.PostprintPeer reviewe

Patient-reported outcome (PRO) questionnaires for men who have radical surgery for prostate cancer: a conceptual review of existing instruments.

To critically review conceptual frameworks for available patient-reported outcome (PRO) questionnaires in men having radical prostatectomy (RP), psychometrically evaluate each questionnaire, and identify whether each is appropriate for use at the level of the individual patient. We searched PubMed, the Reports and Publications database of the University of Oxford Patient-Reported Outcomes Measurement Group and the website of the International Consortium for Health Outcomes Measurement (ICHOM) for psychometric reviews of prostate cancer-specific PRO questionnaires. From these we identified relevant questionnaires and critically appraised the conceptual content, guided by the Wilson and Cleary framework and psychometric properties, using well established criteria. The searches found four reviews and one recommendation paper. We identified seven prostate cancer-specific PROs: the Expanded Prostate Cancer Index Composite-26 (EPIC-26), Expanded Prostate Cancer Index Composite-50 (EPIC-50), University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), Functional Assessment of Cancer Therapy - Prostate Cancer Subscale (FACT-P PCS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - prostate specific 25-item (EORTC QLQ-PR25), Prostate Cancer - Quality of Life (PC-QoL), and Symptom Tracking and Reporting (STAR). Six out of seven measures purported to measure health-related quality of life (HRQL), but items focused strongly on urinary and sexual symptoms/functioning. The remaining questionnaire (STAR) claimed to assess functional recovery after RP. The psychometric evidence for these questionnaires was incomplete and variable in quality; none had evidence that they were appropriate for use with individual patients. Several questionnaires provide the basis of measures of urinary and/or sexual symptoms/functioning. Further work should explore other aspects of HRQL that are important for men having RP. Further psychometric work is also needed to determine whether they can be used at the individual level

Challenges and novel approaches for investigating molecular mediation

Understanding mediation is useful for identifying intermediates lying between an exposure and an outcome which, when intervened upon, will block (some or all of) the causal pathway between the exposure and outcome. Mediation approaches used in conventional epidemiology have been adapted to understanding the role of molecular intermediates in situations of high-dimensional omics data with varying degrees of success. In particular, the limitations of observational epidemiological study including confounding, reverse causation and measurement error can afflict conventional mediation approaches and may lead to incorrect conclusions regarding causal effects. Solutions to analysing mediation which overcome these problems include the use of instrumental variable methods such as Mendelian randomization, which may be applied to evaluate causality in increasingly complex networks of omics data

Microbial players and processes involved in phytoplankton bloom utilization in the water column of a fast-flowing, river-dominated estuary

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in MicrobiologyOpen 6 (2017): e467, doi:10.1002/mbo3.467.Fueled by seasonal phytoplankton blooms, the Columbia River estuary is a natural bioreactor for organic matter transformations. Prior metagenome analyses indicated high abundances of diverse Bacteroidetes taxa in estuarine samples containing phytoplankton. To examine the hypothesis that Bacteroidetes taxa have important roles in phytoplankton turnover, we further analyzed metagenomes from water collected along a salinity gradient at 0, 5, 15, 25, and 33 PSU during bloom events. Size fractions were obtained by using a 3-μm prefilter and 0.2-μm collection filter. Although this approach targeted bacteria by removing comparatively large eukaryotic cells, the metagenome from the ES-5 sample (5 PSU) nevertheless contained an abundance of diatom DNA. Biogeochemical measurements and prior studies indicated that this finding resulted from the leakage of cellular material due to freshwater diatom lysis at low salinity. Relative to the other metagenomes, the bacterial fraction of ES-5 was dramatically depleted of genes annotated as Bacteroidetes and lysogenic bacteriophages, but was overrepresented in DNA of protists and Myxococcales bacterivores. We suggest the following equally plausible scenarios for the microbial response to phytoplankton lysis: (1) Bacteroidetes depletion in the free-living fraction may at least in part be caused by their attachment to fluvial diatoms as the latter are lysed upon contact with low-salinity estuarine waters; (2) diatom particle colonization is likely followed by rapid bacterial growth and lytic phage infection, resulting in depletion of lysogenic bacteriophages and host bacteria; and (3) the subsequent availability of labile organic matter attracted both grazers and predators to feed in this estuarine biogeochemical “hotspot,” which may have additionally depleted Bacteroidetes populations. These results represent the first detailed molecular analysis of the microbial response to phytoplankton lysis at the freshwater–brackish water interface in the fast-flowing Columbia River estuary.National Science Foundation Grant Numbers: OCE 0424602, MCB 064446

Off-World Mental Health:Considerations for the Design of Well-being-Supportive Technologies for Deep Space Exploration

During future long-duration space exploration missions, humans will be exposed to combinations of extreme physical, psychological, and interpersonal demands. These demands create risks for the safety, performance, health, and well-being of both individuals and crew. The communication latency in deep space means that explorers will increasingly have to operate independently and take responsibility for their own self-care and self-management. At present, several research programs are focused on developing and testing digital technologies and countermeasures that support the effective functioning of deep space crews. Although promising, these initiatives have been stimulated mostly by technological opportunity rather than cogent theory. In this perspective, we argue that digital technologies developed for spaceflight should be informed by well-being–supportive design principles and be cognizant of broader conversations around the development and use of digital health applications, especially pertaining to issues of autonomy, privacy, and trust. These issues are important for designing potentially mission-critical health technologies and may be determining factors in the safe and successful completion of future off-world endeavors.publishedVersio

Lee Silverman voice treatment versus standard NHS speech and language therapy versus control in Parkinson's disease (PD COMM pilot):study protocol for a randomized controlled trial

Background: Parkinson’s disease is a common movement disorder affecting approximately 127,000 people in the UK, with an estimated two thirds having speech-related problems. Currently there is no preferred approach to speech and language therapy within the NHS and there is little evidence for the effectiveness of standard NHS therapy or Lee Silverman voice treatment. This trial aims to investigate the feasibility and acceptability of randomizing people with Parkinson’s disease-related speech or voice problems to Lee Silverman voice treatment or standard speech and language therapy compared to a no-intervention control. Methods/Design: The PD COMM pilot is a three arm, assessor-blinded, randomized controlled trial. Randomization will be computer-generated with participants randomized at a ratio of 1:1:1. Participants randomized to intervention arms will be immediately referred to the appropriate speech and language therapist. The target population are patients with a confirmed diagnosis of idiopathic Parkinson’s disease who have problems with their speech or voice. The Lee Silverman voice treatment intervention group will receive the standard regime of 16 sessions between 50 and 60 minutes in length over four weeks, with extra home practice. The standard speech and language therapy intervention group will receive a dose determined by patients’ individual needs, but not exceeding eight weeks of treatment. The control group will receive standard care with no speech and language therapy input for at least six months post-randomization. Outcomes will be assessed at baseline (pre-randomization) and post- randomization at three, six, and 12 months. The outcome measures include patient-reported voice measures, quality of life, resource use, and assessor-rated speech recordings. The recruitment aim is at least 60 participants over 21 months from 11 sites, equating to at least 20 participants in each arm of the trial. This trial is ongoing and recruitment commenced in May 2012. Discussion: This study will provide information on the feasibility and acceptability of randomizing participants to different speech and language therapies or control/deferred treatment. The findings relating to recruitment, treatment compliance, outcome measures, and effect size will inform a future phase III randomized controlled trial