1,492 research outputs found

    Labile disulfide bonds in human placental insulin receptor.

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    Enhanced motivational interviewing for reducing weight and increasing physical activity in adults with high cardiovascular risk: the MOVE IT three-arm RCT.

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    BACKGROUND: Motivational interviewing (MI) enhanced with behaviour change techniques (BCTs) and deployed by health trainers targeting multiple risk factors for cardiovascular disease (CVD) may be more effective than interventions targeting a single risk factor. OBJECTIVES: The clinical effectiveness and cost-effectiveness of an enhanced lifestyle motivational interviewing intervention for patients at high risk of CVD in group settings versus individual settings and usual care (UC) in reducing weight and increasing physical activity (PA) were tested. DESIGN: This was a three-arm, single-blind, parallel randomised controlled trial. SETTING: A total of 135 general practices across all 12 South London Clinical Commissioning Groups were recruited. PARTICIPANTS: A total of 1742 participants aged 40-74 years with a ≥ 20.0% risk of a CVD event in the following 10 years were randomised. INTERVENTIONS: The intervention was designed to integrate MI and cognitive-behavioural therapy (CBT), delivered by trained healthy lifestyle facilitators in 10 sessions over 1 year, in group or individual format. The control group received UC. RANDOMISATION: Simple randomisation was used with computer-generated randomisation blocks. In each block, 10 participants were randomised to the group, individual or UC arm in a 4 : 3 : 3 ratio. Researchers were blind to the allocation. MAIN OUTCOME MEASURES: The primary outcomes are change in weight (kg) from baseline and change in PA (average number of steps per day over 1 week) from baseline at the 24-month follow-up, with an interim follow-up at 12 months. An economic evaluation estimates the relative cost-effectiveness of each intervention. Secondary outcomes include changes in low-density lipoprotein cholesterol and CVD risk score. RESULTS: The mean age of participants was 69.75 years (standard deviation 4.11 years), 85.5% were male and 89.4% were white. At the 24-month follow-up, the group and individual intervention arms were not more effective than UC in increasing PA [mean 70.05 steps, 95% confidence interval (CI) -288 to 147.9 steps, and mean 7.24 steps, 95% CI -224.01 to 238.5 steps, respectively] or in reducing weight (mean -0.03 kg, 95% CI -0.49 to 0.44 kg, and mean -0.42 kg, 95% CI -0.93 to 0.09 kg, respectively). At the 12-month follow-up, the group and individual intervention arms were not more effective than UC in increasing PA (mean 131.1 steps, 95% CI -85.28 to 347.48 steps, and mean 210.22 steps, 95% CI -19.46 to 439.91 steps, respectively), but there were reductions in weight for the group and individual intervention arms compared with UC (mean -0.52 kg, 95% CI -0.90 to -0.13 kg, and mean -0.55 kg, 95% CI -0.95 to -0.14 kg, respectively). The group intervention arm was not more effective than the individual intervention arm in improving outcomes at either follow-up point. The group and individual interventions were not cost-effective. CONCLUSIONS: Enhanced MI, in group or individual formats, targeted at members of the general population with high CVD risk is not effective in reducing weight or increasing PA compared with UC. Future work should focus on ensuring objective evidence of high competency in BCTs, identifying those with modifiable factors for CVD risk and improving engagement of patients and primary care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN84864870. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 69. See the NIHR Journals Library website for further project information. This research was part-funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London

    HIV-related stigma in the UK then and now: to what extent are we on track to eliminate stigma? A qualitative investigation

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    Background The introduction of effective antiretroviral treatment in the late 1990s led to the perception that HIV was a chronic but manageable condition. Nevertheless, stigma remains one of the major hurdles for people living with HIV (PLWH) to accessing healthcare and biomedical preventions. Thus, Fast Track Cities has set a target of zero HIV discrimination by 2030 as part of its strategy to end HIV transmission. Methods Fifty-three participants from the United Kingdom, including PLWH (n = 21, 40%), health and social care workers (n = 24, 45%), and charity workers and activists (n = 13, 25%), were recruited. Semi-structured interviews investigated stigma and discrimination, focusing on both before and after the widespread use of effective antiretroviral treatment in the late 1990s. Data were analysed using a thematic approach. Results Before effective antiretroviral treatment narratives were shaped by two main themes: 1) the media’s role in influencing public opinion and contributing to misunderstandings of HIV transmission; and 2) personal experiences of HIV-related stigma, which for PLWH included incidents of physical violence and aggression, as well as fears of their HIV status being publicised. Contemporary narratives on stigma experiences were organised around four themes: 1) discrimination in healthcare settings; 2) stigma amongst men who have sex with men (MSM); 3) stigma towards African and Afro-Caribbean PLWH; and 4) the limits of change in public HIV-related knowledge and attitudes. Contemporary narratives indicated a reduction in enacted stigma, but continued anticipation of discrimination and self-reported shame, particularly in MSM and African and Afro-Caribbean PLWH. Conclusion The nature of stigma against those with HIV has evolved. The intersection of PLWH and minority groups (e.g. MSM and African and Afro-Caribbean persons) may enhance anticipatory and internalised stigma, with some suggestion that this may contribute to reduced engagement in HIV care and prevention services. Our findings indicate the need for further research in this area, as well as proactive interventions with community groups to enhance knowledge of HIV

    The COMPLETE Nature of the Warm Dust Ring in Perseus

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    The Perseus molecular cloud complex is a ~30pc long chain of molecular clouds most well-known for the two star-forming clusters NGC1333 and IC348 and the well-studied outflow source in B5. However, when studied at mid- to far-infrared wavelengths the region is dominated by a ~10pc diameter shell of warm dust, likely generated by an HII region caused by the early B-star HD278942. Using a revised calibration technique the COMPLETE team has produced high-sensitivity temperature and column-density maps of the Perseus region from IRAS Sky Survey Atlas (ISSA) 60 and 100um data. In this paper, we combine the ISSA based dust-emission maps with other observations collected as part of the COMPLETE Survey, along with archival H-alpha and MSX observations. Molecular line observations from FCRAO and extinction maps constructed by applying the NICER method to the 2MASS catalog provide independent estimates of the ``true'' column-density of the shell. H-alpha emission in the region of the shell confirms that it is most likely an HII region located behind the cloud complex, and 8um data from MSX indicates that the shell may be interacting with the cloud. Finally, the two polarisation components previously seen towards background stars in the region can be explained by the association of the stronger component with the shell. If confirmed, this would be the first observation of a parsec-scale swept-up magnetic field.Comment: Accepted by ApJ. Figures have been compressed - full resolution version available at http://cfa-www.harvard.edu/COMPLETE/results.htm

    Light-stable rhodopsin. I. A rhodopsin analog reconstituted with a nonisomerizable 11-cis retinal derivative

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    With the aim of preparing a light-stable rhodopsin-like pigment, an analog, II, of 11-cis retinal was synthesized in which isomerization of the C11-C12 cis-double bond is blocked by a cyclohexene ring built around the C10 to C13-methyl. The analog II formed a rhodopsin-like pigment (rhodopsin-II) with opsin expressed in COS-1 cells and with opsin from rod outer segments. The rate of rhodopsin-II formation from II and opsin was ~10 times slower than that of rhodopsin from 11-cis retinal and opsin. After solubilization in dodecyl maltoside and immunoaffinity purification, rhodopsin-II displayed an absorbance ratio (A280nm/A512nm) of 1.6, virtually identical with that of rhodopsin. Acid denaturation of rhodopsin-II formed a chromophore with λmax, 452 nm, characteristic of protonated retinyl Schiff base. The ground state properties of rhodopsin-II were similar to those of rhodopsin in extinction coefficient (41,200 M-1 cm-1) and opsin-shift (2600 cm-1). Rhodopsin-II was stable to hydroxylamine in the dark, while light-dependent bleaching by hydroxylamine was slowed by ~2 orders of magnitude relative to rhodopsin. Illumination of rhodopsin-II for 10 s caused ~3 nm blue-shift and 3% loss of visible absorbance. Prolonged illumination caused a maximal blue-shift up to ~20 nm and ~40% loss of visible absorbance. An apparent photochemical steady state was reached after 12 min of illumination. Subsequent acid denaturation indicated that the retinyl Schiff base linkage was intact. A red-shift (~12 nm) in λmax and a 45% recovery of visible absorbance was observed after returning the 12-min illuminated pigment to darkness. Rhodopsin-II showed marginal light-dependent transducin activation and phosphorylation by rhodopsin kinase

    Added Value Report: University of Westminster Transformation in Students Project

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    One of the core aims that all Higher Education institutions share is to enhance graduate employability, and develop a workforce that is ready for the constantly changing labour market. While the concept of employability is shifting and variable (e.g. students as ‘customers’ and/or ‘partners’ (Skea, 2017), it is necessary to develop inclusive measures of employability that can extend beyond generic skills, and include values and identity-driven attributes. The literature recognises that graduate attributes are a set of desirable skills, qualities and understandings that both the University and students deem as important for employment and for shaping identities within the labour market (O’Leary, 2016; Bridgstock, 2009; Tomlinson, 2007). Thus, focus groups and interviews were carried out with undergraduates, postgraduates and alumni to explore their experiences at the University of Westminster, and to elicit the values and qualities that they consider important and personally valuable to their success in the future. This report presents qualitative findings on students’ experiences of gaining “added value” from their time at Westminster. Subsequently, we will use the results to create a robust survey that gives a scientific measurement of students’ attribute development throughout their studies at University

    Response bias to a randomised controlled trial of a lifestyle intervention in people at high risk of cardiovascular disease: a cross-sectional analysis

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    Background Research evaluating lifestyle interventions for prevention of cardiovascular disease (CVD) may not reach those most at risk. We compared the response rate to a randomised controlled trial (RCT) of a lifestyle intervention by CVD risk, ethnicity and level of deprivation. Methods Primary care patients with a QRisk2 score ≥ 20% were invited to participate in a RCT of an intensive lifestyle intervention versus usual care. This cross-sectional analysis compares anonymised data of responders and non-responders with multiple logistic regression, using adjusted odds ratios (AORs) for QRisk2 score, ethnicity, Index of Multiple Deprivation (IMD 2010) quintile, age and sex. Results From 60 general practices, 8902 patients were invited and 1489 responded. The mean age was 67.3 years and 21.0% were female. Of all patients invited, 69.9% were of white ethnic background, 13.9% ethnic minority backgrounds and 16.2% had no ethnicity data recorded in their medical records. Likelihood of response decreased as QRisk2 score increased (AOR 0.82 per 5 percentage points, 95% CI 0.77–0.88). Black African or Caribbean patients (AOR 0.67; 95% CI 0.45–0.98) and those with missing ethnicity data (AOR 0.55; 95% CI 0.46–0.66) were less likely to respond compared to participants of white ethnicity, but there was no difference in the response rates between south Asian and white ethnicity (AOR 1.08; 95% CI 0.84–1.38). Patients residing in the fourth (AOR 0.70; 95% CI 0.56–0.87) and fifth (AOR 0.52; 95% CI 0.40–0.68) most deprived IMD quintile were less likely to respond compared to the least deprived quintile. Conclusions Evaluations of interventions intended for those at high risk of CVD may fail to reach those at highest risk. Hard to reach patient groups may require different recruitment strategies to maximise participation in future trials. Improvements in primary care ethnicity data recording is required to aid understanding of how successfully study samples represent the target population

    Palmitoylation of bovine opsin and its cysteine mutants in COS cells.

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    Niche differentiation is spatially and temporally regulated in the rhizosphere.

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    The rhizosphere is a hotspot for microbial carbon transformations, and is the entry point for root polysaccharides and polymeric carbohydrates that are important precursors to soil organic matter (SOM). However, the ecological mechanisms that underpin rhizosphere carbohydrate depolymerization are poorly understood. Using Avena fatua, a common annual grass, we analyzed time-resolved metatranscriptomes to compare microbial functions in rhizosphere, detritusphere, and combined rhizosphere-detritusphere habitats. Transcripts were binned using a unique reference database generated from soil isolate genomes, single-cell amplified genomes, metagenomes, and stable isotope probing metagenomes. While soil habitat significantly affected both community composition and overall gene expression, the succession of microbial functions occurred at a faster time scale than compositional changes. Using hierarchical clustering of upregulated decomposition genes, we identified four distinct microbial guilds populated by taxa whose functional succession patterns suggest specialization for substrates provided by fresh growing roots, decaying root detritus, the combination of live and decaying root biomass, or aging root material. Carbohydrate depolymerization genes were consistently upregulated in the rhizosphere, and both taxonomic and functional diversity were highest in the combined rhizosphere-detritusphere, suggesting coexistence of rhizosphere guilds is facilitated by niche differentiation. Metatranscriptome-defined guilds provide a framework to model rhizosphere succession and its consequences for soil carbon cycling
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