Human Adipose Tissue As A Reservoir For Memory Cd4(+) T Cells And Hiv

Objective: The objective of this study is to determine whether adipose tissue functions as a reservoir for HIV-1. Design: We examined memory CD4(+) T cells and HIV DNA in adipose tissue-stromal vascular fraction (AT-SVF) of five patients [four antiretroviral therapy (ART)-treated and one untreated]. To determine whether adipocytes stimulate CD4(+) T cells and regulate HIV production, primary human adipose cells were cocultured with HIV-infected CD4(+) T cells. Methods: AT-SVF T cells were studied by flow cytometry, and AT-SVF HIV DNA (Gag and Env) was examined by nested PCR and sequence analyses. CD4(+) T-cell activation and HIV production were measured by flow cytometry and ELISA. Results: AT-SVF CD3(+) T cells were activated (\u3e60% CD69(+)) memory CD4(+) and CD8(+) T cells in uninfected and HIV-infected persons, but the AT-SVF CD4(+)/CD8(+) ratio was lower in HIV patients. HIV DNA(Gag and Env) was detected in AT-SVF of all five patients examined by nested PCR, comparably to other tissues [peripheral blood mononuclear cell (PBMC), lymph node or thymus]. In coculture experiments, adipocytes increased CD4(+) T-cell activation and HIV production approximately two to three-fold in synergy with gamma-chain cytokines interleukin (IL)-2, IL7 or IL15. These effects were mitigated by neutralizing antibodies against IL6 and integrin-alpha 1 beta 1. Adipocytes also enhanced T-cell viability. Conclusion: Adipose tissues of ART-treated patients harbour activated memory CD4(+) T cells and HIV DNA. Adipocytes promote CD4(+) T-cell activation and HIV production in concert with intrinsic adipose factors. Adipose tissue may be an important reservoir for HIV. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved

Impact of lower strength alcohol labelling on consumption: A randomised controlled trial

Objective: Labels indicating low/light versions of tobacco and foods are perceived as less harmful which may encourage people to consume more. There is an absence of evidence concerning the impact on consumption of labelling alcohol products as lower in strength. The current study tests the hypothesis that labelling wine and beer as lower in alcohol increases their consumption. Methods: Weekly wine and beer drinkers (n=264) sampled from a representative panel of the general population of England were randomised to one of three groups to taste test drinks in a bar-laboratory varying only in the label displayed; Group 1: verbal descriptor Super Low combined with 4%ABV for wine/1%ABV for beer; Group 2: verbal descriptor Low combined with 8%ABV for wine/3%ABV for beer; Group 3: No verbal descriptors of strength (Regular). Primary outcome was total volume (ml) of drink consumed. Results: The results supported the study hypothesis: the total amount of drink consumed increased as the label on the drink denoted successively lower alcohol strength, BLin=.71, p=.015, [95%CI=0.13/1.30]. Group contrasts showed significant differences between those offered drinks labelled as Super Low (M=213.77) compared to Regular (M=176.85), B=1.43, p=.019, [95%CI=0.24/2.61]. There was no significant difference in amount consumed between those offered drinks labelled as Low compared to Regular. Conclusions: These results suggest that labelling drinks as lower in strength increases the amount consumed. Further studies are warranted to test for replication in non-laboratory settings and to estimate whether any effects are at a level with the potential to harm health. Trial registration: ISRCTN1553080

Wine glass size and wine sales: A replication study in two bars

Objective. Wine glass size may influence perceived volume and subsequently purchasing and consumption. Using a larger glass to serve the same portions of wine was found to increase wine sales by 9.4% (95% CI: 1.9, 17.5) in a recent study conducted in one bar. The current study aimed to replicate this previous work in two other bars using a wider range of glass sizes. To match the previous study, a repeated multiple treatment reversal design, during which wine was served in glasses of the same design but different sizes, was used. The study was conducted in two bars in Cambridge, England, using glass sizes of 300ml, 370ml, 510ml (Bar 1) and 300ml and 510ml (Bar 2). Customers purchased their choice of a 750ml bottle, or standard UK measures of 125ml, 175ml or 250ml of wine, each of which was served with the same glass. Results. Bar 1: Daily wine volume purchased was 10.5% (95% CI: 1.0, 20.9) higher when sold in 510ml compared to 370ml glasses; but sales were not significantly higher with 370ml vs. 300ml glasses (6.5%, 95% CI: -5.2, 19.6). Bar 2: findings were inconclusive as to whether daily wine purchased differed when using 510ml vs. 300ml glasses (-1.1%, 95% CI: -12.6, 11.9). These results provide a partial replication of previous work showing that introducing larger glasses (without manipulating portion size) increases purchasing. Understanding the mechanisms by which wine glass size influences consumption may elucidate when the effect can be expected and when not.The research reported in this publication was funded by the Department of Health Policy Research Programme (http://prp.dh.gov.uk/) (Policy Research Unit in Behaviour and Health [PR-UN-0409-10109])

Medicines and Healthcare products Regulatory Agency’s “Consultation on proposals for legislative changes for clinical trials”: a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing

AbstractIn the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals “to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines”. The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing — making anonymised individual-level clinical trial data available to other investigators for further use — is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council’s Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.</jats:p

Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma)

The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma and Bs0 -> phi gamma has been measured using 0.37 fb-1 of pp collisions at a centre of mass energy of sqrt(s) = 7 TeV, collected by the LHCb experiment. The value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) = 1.12 +/- 0.08 ^{+0.06}_{-0.04} ^{+0.09}_{-0.08}, where the first uncertainty is statistical, the second systematic and the third is associated to the ratio of fragmentation fractions fs/fd. Using the world average for BR(B0 -> K*0 gamma) = (4.33 +/- 0.15) x 10^{-5}, the branching fraction BR(Bs0 -> phi gamma) is measured to be (3.9 +/- 0.5) x 10^{-5}, which is the most precise measurement to date.Comment: 15 pages, 1 figure, 2 table

Measurement of the mass and lifetime of the Ωb−\Omega_b^- baryon

A proton-proton collision data sample, corresponding to an integrated luminosity of 3 fb$^{-1}$ collected by LHCb at $\sqrt{s}=7$ and 8 TeV, is used to reconstruct $63\pm9$ $\Omega_b^-\to\Omega_c^0\pi^-$, $\Omega_c^0\to pK^-K^-\pi^+$ decays. Using the $\Xi_b^-\to\Xi_c^0\pi^-$, $\Xi_c^0\to pK^-K^-\pi^+$ decay mode for calibration, the lifetime ratio and absolute lifetime of the $\Omega_b^-$ baryon are measured to be \begin{align*} \frac{\tau_{\Omega_b^-}}{\tau_{\Xi_b^-}} &= 1.11\pm0.16\pm0.03, \\ \tau_{\Omega_b^-} &= 1.78\pm0.26\pm0.05\pm0.06~{\rm ps}, \end{align*} where the uncertainties are statistical, systematic and from the calibration mode (for $\tau_{\Omega_b^-}$ only). A measurement is also made of the mass difference, $m_{\Omega_b^-}-m_{\Xi_b^-}$, and the corresponding $\Omega_b^-$ mass, which yields \begin{align*} m_{\Omega_b^-}-m_{\Xi_b^-} &= 247.4\pm3.2\pm0.5~{\rm MeV}/c^2, \\ m_{\Omega_b^-} &= 6045.1\pm3.2\pm 0.5\pm0.6~{\rm MeV}/c^2. \end{align*} These results are consistent with previous measurements.Comment: 11 pages, 5 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-008.htm

Observation of two new Ξb−\Xi_b^- baryon resonances

Two structures are observed close to the kinematic threshold in the $\Xi_b^0 \pi^-$ mass spectrum in a sample of proton-proton collision data, corresponding to an integrated luminosity of 3.0 fb$^{-1}$ recorded by the LHCb experiment. In the quark model, two baryonic resonances with quark content $bds$ are expected in this mass region: the spin-parity $J^P = \frac{1}{2}^+$ and $J^P=\frac{3}{2}^+$ states, denoted $\Xi_b^{\prime -}$ and $\Xi_b^{*-}$. Interpreting the structures as these resonances, we measure the mass differences and the width of the heavier state to be $m(\Xi_b^{\prime -}) - m(\Xi_b^0) - m(\pi^{-}) = 3.653 \pm 0.018 \pm 0.006$ MeV$/c^2$, $m(\Xi_b^{*-}) - m(\Xi_b^0) - m(\pi^{-}) = 23.96 \pm 0.12 \pm 0.06$ MeV$/c^2$, $\Gamma(\Xi_b^{*-}) = 1.65 \pm 0.31 \pm 0.10$ MeV, where the first and second uncertainties are statistical and systematic, respectively. The width of the lighter state is consistent with zero, and we place an upper limit of $\Gamma(\Xi_b^{\prime -}) < 0.08$ MeV at 95% confidence level. Relative production rates of these states are also reported.Comment: 17 pages, 2 figure