Less healthy, but more active: Opposing selection biases when recruiting older people to a physical activity study through primary care.

BACKGROUND: Physical activity studies in older people experience poor recruitment. We wished to assess the influence of activity levels and health status on recruitment to a physical activity study in older people. METHODS: Comparison of participants and non-participants to a physical activity study using accelerometers in patients aged > or = 65 years registered with a UK primary care centre. Logistic regression was used to calculate odds ratios (OR) of participants in the accelerometer study with various adjustments. Analyses were initially adjusted for age, sex and household clustering; the health variables were then adjusted for physical activity levels and vice versa to look for independent effects. RESULTS: 43%(240/560) participated in the physical activity study. Age had no effect but males were more likely to participate than females OR 1.4(1.1-1.8). 46% (76/164) of non-participants sent the questionnaire returned it. The 240 participants reported greater physical activity than the 76 non-participants on all measures, eg faster walking OR 3.2(1.4-7.7), or 10.4(3.2-33.3) after adjustment for health variables. Participants reported more health problems; this effect became statistically significant after controlling for physical activity, eg disability OR 2.4(1.1-5.1). CONCLUSION: Physical activity studies on older primary care patients may experience both a strong bias towards participants being more active and a weaker bias towards participants having more health problems and therefore primary care contact. The latter bias could be advantageous for physical activity intervention studies, where those with health problems need targeting

ZMYM2 inhibits NANOG-mediated reprogramming.

Background: NANOG is a homeodomain-containing transcription factor which forms one of the hubs in the pluripotency network and plays a key role in the reprogramming of somatic cells and epiblast stem cells to naïve pluripotency.  Studies have found that NANOG has many interacting partners and some of these were shown to play a role in its ability to mediate reprogramming. In this study, we set out to analyse the effect of NANOG interactors on the reprogramming process. Methods: Epiblast stem cells and somatic cells were reprogrammed to naïve pluripotency using MEK/ERK inhibitor PD0325901, GSK3β inhibitor CHIR99021 and Leukaemia Inhibitory Factor (together termed 2i Plus LIF). Zmym2 was knocked out using the CRISPR/Cas9 system or overexpressed using the PiggyBac system. Reprogramming was quantified after ZMYM2 deletion or overexpression, in diverse reprogramming systems. In addition, embryonic stem cell self renewal was quantified in differentiation assays after ZMYM2 removal or overexpression. Results: In this work, we identified ZMYM2/ZFP198, which physically associates with NANOG as a key negative regulator of NANOG-mediated reprogramming of both epiblast stem cells and somatic cells. In addition, ZMYM2 impairs the self renewal of embryonic stem cells and its overexpression promotes differentiation. Conclusions: We propose that ZMYM2 curtails NANOG's actions during the reprogramming of both somatic cells and epiblast stem cells and impedes embryonic stem cell self renewal, promoting differentiation.This study was supported by the Wellcome Trust through a Wellcome Trust Fellowship to J.C.R.S. [101861], Wellcome Trust Studentship to M.L. [079249], and a core funding grant jointly with the Medical Research Council (MRC) to the Wellcome-MRC Cambridge Stem Cell Institute [079249]

A Primary Care Nurse-Delivered Walking Intervention in Older Adults: PACE (Pedometer Accelerometer Consultation Evaluation)-Lift Cluster Randomised Controlled Trial.

Background: Brisk walking in older people can increase step-counts and moderate to vigorous intensity physical activity (MVPA) in ≥10-minute bouts, as advised in World Health Organization guidelines. Previous interventions have reported step-count increases, but not change in objectively measured MVPA in older people. We assessed whether a primary care nurse-delivered complex intervention increased objectively measured step-counts and MVPA. Methods and Findings: A total of 988 60–75 year olds, able to increase walking and randomly selected from three UK family practices, were invited to participate in a parallel two-arm cluster randomised trial; randomisation was by household. Two-hundred-ninety-eight people from 250 households were randomised between 2011 and 2012; 150 individuals to the intervention group, 148 to the usual care control group. Intervention participants received four primary care nurse physical activity (PA) consultations over 3 months, incorporating behaviour change techniques, pedometer step-count and accelerometer PA intensity feedback, and an individual PA diary and plan. Assessors were not blinded to group status, but statistical analyses were conducted blind. The primary outcome was change in accelerometry assessed average daily step-counts between baseline and 3 months, with change at 12 months a secondary outcome. Other secondary outcomes were change from baseline in time in MVPA weekly in ≥10-minute bouts, accelerometer counts, and counts/minute at 3 months and 12 months. Other outcomes were adverse events, anthropometric measures, mood, and pain. Qualitative evaluations of intervention participants and practice nurses assessed the intervention’s acceptability. At 3 months, eight participants had withdrawn or were lost to follow-up, 280 (94%) individuals provided primary outcome data. At 3 months changes in both average daily step-counts and weekly MVPA in ≥10-minute bouts were significantly higher in the intervention than control group: by 1,037 (95% CI 513–1,560) steps/day and 63 (95% CI 40–87) minutes/week, respectively. At 12 months corresponding differences were 609 (95% CI 104–1,115) steps/day and 40 (95% CI 17–63) minutes/week. Counts and counts/minute showed similar effects to steps and MVPA. Adverse events, anthropometry, mood, and pain were similar in the two groups. Participants and practice nurses found the intervention acceptable and enjoyable. Conclusions : The PACE-Lift trial increased both step-counts and objectively measured MVPA in ≥10-minute bouts in 60–75 year olds at 3 and 12 months, with no effect on adverse events. To our knowledge, this is the first trial in this age group to demonstrate objective MVPA increases and highlights the value of individualised support incorporating objective PA assessment in a primary care setting. Trial Registration: Controlled-Trials.com ISRCTN4212256

Disruption of a Proto-Planetary Disk by the Black Hole at the Milky Way Centre

Recently, an ionized cloud of gas was discovered plunging toward the supermassive black hole, SgrA*, at the centre of the Milky Way. The cloud is being tidally disrupted along its path to closest approach at ~3100 Schwarzschild radii from the black hole. Here, we show that the observed properties of this cloud of gas can naturally be produced by a proto-planetary disk surrounding a low-mass star, which was scattered from the observed ring of young stars orbiting SgrA*. As the young star approaches the black hole, its disk experiences both photo-evaporation and tidal disruption, producing a cloud. Our model implies that planets form in the Galactic centre, and that tidal debris from proto-planetary disks can flag low mass stars which are otherwise too faint to be detected.Comment: Accepted to Nature Communications; new Figure 4b provides predicted Br-gamma emission as a function of tim

Measuring Relations Between Concepts In Conceptual Spaces

The highly influential framework of conceptual spaces provides a geometric way of representing knowledge. Instances are represented by points in a high-dimensional space and concepts are represented by regions in this space. Our recent mathematical formalization of this framework is capable of representing correlations between different domains in a geometric way. In this paper, we extend our formalization by providing quantitative mathematical definitions for the notions of concept size, subsethood, implication, similarity, and betweenness. This considerably increases the representational power of our formalization by introducing measurable ways of describing relations between concepts.Comment: Accepted at SGAI 2017 (http://www.bcs-sgai.org/ai2017/). The final publication is available at Springer via https://doi.org/10.1007/978-3-319-71078-5_7. arXiv admin note: substantial text overlap with arXiv:1707.05165, arXiv:1706.0636

Metabolomics demonstrates divergent responses of two Eucalyptus species to water stress

Past studies of water stress in Eucalyptus spp. generally highlighted the role of fewer than five “important” metabolites, whereas recent metabolomic studies on other genera have shown tens of compounds are affected. There are currently no metabolite profiling data for responses of stress-tolerant species to water stress. We used GC–MS metabolite profiling to examine the response of leaf metabolites to a long (2 month) and severe (Ψpredawn < −2 MPa) water stress in two species of the perennial tree genus Eucalyptus (the mesic Eucalyptus pauciflora and the semi-arid Eucalyptus dumosa). Polar metabolites in leaves were analysed by GC–MS and inorganic ions by capillary electrophoresis. Pressure–volume curves and metabolite measurements showed that water stress led to more negative osmotic potential and increased total osmotically active solutes in leaves of both species. Water stress affected around 30–40% of measured metabolites in E. dumosa and 10–15% in E. pauciflora. There were many metabolites that were affected in E. dumosa but not E. pauciflora, and some that had opposite responses in the two species. For example, in E. dumosa there were increases in five acyclic sugar alcohols and four low-abundance carbohydrates that were unaffected by water stress in E. pauciflora. Re-watering increased osmotic potential and decreased total osmotically active solutes in E. pauciflora, whereas in E. dumosa re-watering led to further decreases in osmotic potential and increases in total osmotically active solutes. This experiment has added several extra dimensions to previous targeted analyses of water stress responses in Eucalyptus, and highlights that even species that are closely related (e.g. congeners) may respond differently to water stress and re-waterin

Author Correction: Dynamic regulation of canonical TGFβ signalling by endothelial transcription factor ERG protects from liver fibrogenesis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper