Two alternative methods for the retrieval of somatic cell populations from the mouse ovary

Many modern techniques employed to uncover the molecular fundamentals underlying biological processes require dissociated cells as their starting point/substrate. Investigations into ovarian endocrinology or folliculogenesis therefore necessitate robust protocols for dissociating the ovary into its constituent cell populations. While in the mouse, methods to obtain individual, mature follicles are well-established, the separation and isolation of single cells of all types from early mouse follicles, including somatic cells, has been more challenging. Herein we present two methods for the isolation of somatic cells in the ovary. These methods are suitable for a range of applications relating to the study of folliculogenesis and mouse ovarian development. First, an enzymatic dissociation utilising collagenase and a temporary, primary cell culture step using neonatal mouse ovaries which yields large quantities of granulosa cells from primordial, activating, and primary follicles. Second, a rapid papain dissociation resulting in a high viability single cell suspension of ovarian somatic cells in less than an hour, which can be applied from embryonic to adult ovarian samples. Collectively these protocols can be applied to a broad array of investigations with unique advantages and benefits pertaining to both

Determinants of adults' intention to vaccinate against pandemic swine flu

This article has been made available through the Brunel Open Access Publishing Fund.This article has been made available through the Brunel Open Access Publishing Fund.Background: Vaccination is one of the cornerstones of controlling an influenza pandemic. To optimise vaccination rates in the general population, ways of identifying determinants that influence decisions to have or not to have a vaccination need to be understood. Therefore, this study aimed to predict intention to have a swine influenza vaccination in an adult population in the UK. An extension of the Theory of Planned Behaviour provided the theoretical framework for the study. Methods: Three hundred and sixty two adults from the UK, who were not in vaccination priority groups, completed either an online (n = 306) or pen and paper (n = 56) questionnaire. Data were collected from 30th October 2009, just after swine flu vaccination became available in the UK, and concluded on 31st December 2009. The main outcome of interest was future swine flu vaccination intentions. Results: The extended Theory of Planned Behaviour predicted 60% of adults’ intention to have a swine flu vaccination with attitude, subjective norm, perceived control, anticipating feelings of regret (the impact of missing a vaccination opportunity), intention to have a seasonal vaccine this year, one perceived barrier: “I cannot be bothered to get a swine flu vaccination” and two perceived benefits: “vaccination decreases my chance of getting swine flu or its complications” and “if I get vaccinated for swine flu, I will decrease the frequency of having to consult my doctor,” being significant predictors of intention. Black British were less likely to intend to have a vaccination compared to Asian or White respondents. Conclusions: Theoretical frameworks which identify determinants that influence decisions to have a pandemic influenza vaccination are useful. The implications of this research are discussed with a view to maximising any future pandemic influenza vaccination uptake using theoretically-driven applications.This article is available through the Brunel Open Access Publishing Fund

A facilitated home-based cardiac rehabilitation intervention for people with heart failure and their caregivers:a research programme including the REACH-HF RCT

Background: Rates of participation in centre (hospital)-cardiac rehabilitation by patients with heart failure are suboptimal. Heart failure has two main phenotypes differing in underlying pathophysiology: Heart failure with reduced ejection fraction is characterised by depressed left ventricular systolic function (‘reduced ejection fraction’), whereas heart failure with preserved ejection fraction is diagnosed after excluding other causes of dyspnoea with normal ejection fraction. This programme aimed to develop and evaluate a facilitated home-based cardiac rehabilitation intervention that could increase the uptake of cardiac rehabilitation while delivering the clinical benefits of centre-based cardiac rehabilitation. Objectives: To develop an evidence-informed, home-based, self-care cardiac rehabilitation programme for patients with heart failure and their caregivers [the REACH-HF (Rehabilitation Enablement in Chronic Heart Failure) intervention]. To conduct a pilot randomised controlled trial to assess the feasibility of a full trial of the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with preserved ejection fraction. To assess the short- and long-term clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with reduced ejection fraction and their caregivers. Design: Intervention mapping to develop the REACH-HF intervention; uncontrolled feasibility study; pilot randomised controlled trial in those with heart failure with preserved ejection fraction; randomised controlled trial with a trial-based cost-effectiveness analysis in those with heart failure with reduced ejection fraction; qualitative studies including process evaluation; systematic review of cardiac rehabilitation in heart failure; and modelling to assess long-term cost-effectiveness (in those with heart failure with reduced ejection fraction). Setting: Four centres in England and Wales (Birmingham, Cornwall, Gwent and York); one centre in Scotland (Dundee) for a pilot randomised controlled trial. Participants: Adults aged ≥ 18 years with heart failure with reduced ejection fraction (left ventricular ejection fraction &lt; 45%) for the main randomised controlled trial (n = 216), and those with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥ 45%) for the pilot randomised controlled trial (n = 50). Intervention: A self-care, facilitated cardiac rehabilitation manual was offered to patients (and participating caregivers) at home over 12 weeks by trained health-care professionals in addition to usual care or usual care alone. Main outcome measures: The primary outcome was disease-specific health-related quality of life measured using the Minnesota Living with Heart Failure Questionnaire at 12 months. Secondary outcomes included deaths and hospitalisations. Results: The main randomised controlled trial recruited 216 participants with heart failure with reduced ejection fraction and 97 caregivers. A significant and clinically meaningful between-group difference in the Minnesota Living with Heart Failure Questionnaire score (primary outcome) at 12 months (–5.7 points, 95% confidence interval –10.6 to –0.7 points) favoured the REACH-HF intervention (p = 0.025). Eight (4%) patients (four in each group) had died at 12 months. There was no significant difference in hospital admissions, at 12 months, with 19 participants in the REACH-HF intervention group having at least one hospital admission, compared with 24 participants in the control group (odds ratio 0.72, 95% confidence interval 0.35 to 1.51; p = 0.386). The mean cost of the intervention was £418 per participant with heart failure with reduced ejection fraction. The costs at 12 months were, on average, £401 higher in the intervention group than in the usual care alone group. Model-based economic evaluation, extrapolating from the main randomised controlled trial in those with heart failure with reduced ejection fraction over 4 years, found that adding the REACH-HF intervention to usual care had an estimated mean cost per participant of £15,452 (95% confidence interval £14,240 to £16,780) and a mean quality-adjusted lifeyear gain of 4.47 (95% confidence interval 3.83 to 4.91) years, compared with £15,051 (95% confidence interval £13,844 to £16,289) and 4.24 (95% confidence interval 4.05 to 4.43) years, respectively, for usual care alone. This gave an incremental cost per quality-adjusted life-year of £1721. The probabilistic sensitivity analysis indicated 78% probability that the intervention plus usual care versus usual care alone has a cost-effectiveness below the willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained. The intervention was well received by participants with heart failure with reduced ejection fraction and those with heart failure with preserved ejection fraction, as well as their caregivers. Both randomised controlled trials recruited to target, with &gt; 85% retention at follow-up. Limitations: Key limitations included (1) lack of blinding – given the nature of the intervention and the control we could not mask participants to treatments, so our results may reflect participant expectation bias; (2) that we were not able to capture consistent participant-level data on level of intervention adherence; (3) that there may be an impact on the generalisability of findings due to the demographics of the trial patients, as most were male (78%) and we recruited only seven people from ethnic minorities. Conclusions: Evaluation of the comprehensive, facilitated, home-based REACH-HF intervention for participants with heart failure with reduced ejection fraction and caregivers indicated clinical effectiveness in terms of health-related quality of life and patient self-care but no other secondary outcomes. Although the economic analysis conducted alongside the full randomised controlled trial did not produce significant differences on the EuroQol-5 Dimensions or in quality-adjusted life-years, economic modelling suggested greater cost-effectiveness of the intervention than usual care. Our REACH-HF intervention offers a new evidence-based cardiac rehabilitation option that could increase uptake of cardiac rehabilitation in patients with heart failure not attracted to or able to access hospital-based programmes. Future work: Systematic collection of real-world data would track future changes in uptake of and adherence to alternative cardiac rehabilitation interventions in heart failure with reduced ejection fraction and increase understanding of how changes in service delivery might affect clinical and health economic outcomes. The findings of our pilot randomised controlled trial in patients with heart failure with preserved ejection fraction support progression to a full multicentre randomised controlled trial. </p

A facilitated home-based cardiac rehabilitation intervention for people with heart failure and their caregivers:a research programme including the REACH-HF RCT

Background: Rates of participation in centre (hospital)-cardiac rehabilitation by patients with heart failure are suboptimal. Heart failure has two main phenotypes differing in underlying pathophysiology: Heart failure with reduced ejection fraction is characterised by depressed left ventricular systolic function (‘reduced ejection fraction’), whereas heart failure with preserved ejection fraction is diagnosed after excluding other causes of dyspnoea with normal ejection fraction. This programme aimed to develop and evaluate a facilitated home-based cardiac rehabilitation intervention that could increase the uptake of cardiac rehabilitation while delivering the clinical benefits of centre-based cardiac rehabilitation. Objectives: To develop an evidence-informed, home-based, self-care cardiac rehabilitation programme for patients with heart failure and their caregivers [the REACH-HF (Rehabilitation Enablement in Chronic Heart Failure) intervention]. To conduct a pilot randomised controlled trial to assess the feasibility of a full trial of the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with preserved ejection fraction. To assess the short- and long-term clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with reduced ejection fraction and their caregivers. Design: Intervention mapping to develop the REACH-HF intervention; uncontrolled feasibility study; pilot randomised controlled trial in those with heart failure with preserved ejection fraction; randomised controlled trial with a trial-based cost-effectiveness analysis in those with heart failure with reduced ejection fraction; qualitative studies including process evaluation; systematic review of cardiac rehabilitation in heart failure; and modelling to assess long-term cost-effectiveness (in those with heart failure with reduced ejection fraction). Setting: Four centres in England and Wales (Birmingham, Cornwall, Gwent and York); one centre in Scotland (Dundee) for a pilot randomised controlled trial. Participants: Adults aged ≥ 18 years with heart failure with reduced ejection fraction (left ventricular ejection fraction &lt; 45%) for the main randomised controlled trial (n = 216), and those with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥ 45%) for the pilot randomised controlled trial (n = 50). Intervention: A self-care, facilitated cardiac rehabilitation manual was offered to patients (and participating caregivers) at home over 12 weeks by trained health-care professionals in addition to usual care or usual care alone. Main outcome measures: The primary outcome was disease-specific health-related quality of life measured using the Minnesota Living with Heart Failure Questionnaire at 12 months. Secondary outcomes included deaths and hospitalisations. Results: The main randomised controlled trial recruited 216 participants with heart failure with reduced ejection fraction and 97 caregivers. A significant and clinically meaningful between-group difference in the Minnesota Living with Heart Failure Questionnaire score (primary outcome) at 12 months (–5.7 points, 95% confidence interval –10.6 to –0.7 points) favoured the REACH-HF intervention (p = 0.025). Eight (4%) patients (four in each group) had died at 12 months. There was no significant difference in hospital admissions, at 12 months, with 19 participants in the REACH-HF intervention group having at least one hospital admission, compared with 24 participants in the control group (odds ratio 0.72, 95% confidence interval 0.35 to 1.51; p = 0.386). The mean cost of the intervention was £418 per participant with heart failure with reduced ejection fraction. The costs at 12 months were, on average, £401 higher in the intervention group than in the usual care alone group. Model-based economic evaluation, extrapolating from the main randomised controlled trial in those with heart failure with reduced ejection fraction over 4 years, found that adding the REACH-HF intervention to usual care had an estimated mean cost per participant of £15,452 (95% confidence interval £14,240 to £16,780) and a mean quality-adjusted lifeyear gain of 4.47 (95% confidence interval 3.83 to 4.91) years, compared with £15,051 (95% confidence interval £13,844 to £16,289) and 4.24 (95% confidence interval 4.05 to 4.43) years, respectively, for usual care alone. This gave an incremental cost per quality-adjusted life-year of £1721. The probabilistic sensitivity analysis indicated 78% probability that the intervention plus usual care versus usual care alone has a cost-effectiveness below the willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained. The intervention was well received by participants with heart failure with reduced ejection fraction and those with heart failure with preserved ejection fraction, as well as their caregivers. Both randomised controlled trials recruited to target, with &gt; 85% retention at follow-up. Limitations: Key limitations included (1) lack of blinding – given the nature of the intervention and the control we could not mask participants to treatments, so our results may reflect participant expectation bias; (2) that we were not able to capture consistent participant-level data on level of intervention adherence; (3) that there may be an impact on the generalisability of findings due to the demographics of the trial patients, as most were male (78%) and we recruited only seven people from ethnic minorities. Conclusions: Evaluation of the comprehensive, facilitated, home-based REACH-HF intervention for participants with heart failure with reduced ejection fraction and caregivers indicated clinical effectiveness in terms of health-related quality of life and patient self-care but no other secondary outcomes. Although the economic analysis conducted alongside the full randomised controlled trial did not produce significant differences on the EuroQol-5 Dimensions or in quality-adjusted life-years, economic modelling suggested greater cost-effectiveness of the intervention than usual care. Our REACH-HF intervention offers a new evidence-based cardiac rehabilitation option that could increase uptake of cardiac rehabilitation in patients with heart failure not attracted to or able to access hospital-based programmes. Future work: Systematic collection of real-world data would track future changes in uptake of and adherence to alternative cardiac rehabilitation interventions in heart failure with reduced ejection fraction and increase understanding of how changes in service delivery might affect clinical and health economic outcomes. The findings of our pilot randomised controlled trial in patients with heart failure with preserved ejection fraction support progression to a full multicentre randomised controlled trial. </p

Nonalcoholic fatty liver disease, liver fibrosis, and structural brain imaging:The Cross-Cohort Collaboration

Background and purpose:Prior studies reported conflicting findings regarding the association of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis with measures of brain health. We examined whether NAFLD and liver fibrosis are associated with structural brain imaging measures in middle- and old-age adults. Methods: In this cross-sectional study among dementia- and stroke-free individuals, data were pooled from the Offspring and Third Generation cohorts of the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Study of Health in Pomerania. NAFLD was assessed through abdominal imaging. Transient hepatic elastography (FibroScan) was used to assess liver fibrosis in FHS and RS. Linear regression models were used to explore the relation of NAFLD and liver fibrosis with brain volumes, including total brain, gray matter, hippocampus, and white matter hyperintensities, adjusting for potential confounders. Results were combined using fixed effects meta-analysis. Results:In total, 5660 and 3022 individuals were included for NAFLD and liver fibrosis analyses, respectively. NAFLD was associated with smaller volumes of total brain (β = −3.5, 95% confidence interval [CI] = −5.4 to −1.7), total gray matter (β = −1.9, 95% CI = −3.4 to −0.3), and total cortical gray matter (β = −1.9, 95% CI = −3.7 to −0.01). In addition, liver fibrosis (defined as liver stiffness measure ≥8.2 kPa) was related to smaller total brain volumes (β = −7.3, 95% CI = −11.1 to −3.5). Heterogeneity between studies was low. Conclusions:NAFLD and liver fibrosis may be directly related to brain aging. Larger and prospective studies are warranted to validate these findings and identify liver-related preventive strategies for neurodegeneration.</p

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente