186 research outputs found

    Geriatric oncology health services research: Cancer and Aging Research Group infrastructure core

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    Founded by the late Dr. Arti Hurria, the Cancer and Aging Research Group (CARG) is a collaborative, interdisciplinary team of investigators dedicated to improving the care of older adults with cancer through research, advocacy, and other scholarly initiatives.1 As part of the CARG National Institute on Aging R21/R33 infrastructure grant to harness the available expertise and prioritize the development of high-impact research, the Health Services Research (HSR) Core was developed to foster and advance HSR in geriatric oncology. The mission of the HSR Core is to support clinical investigators to design and conduct highquality HSR focused on older adults with cancer and their caregivers including patterns of care, comparative effectiveness, and care delivery. At the first R21/R33 conference held at City of Hope in October 2018, Dr. Harvey Jay Cohen (Chair, CARG Oversight Board and HSR Core) led the development of this Core. In this perspective paper, we present a review of HSR in geriatric oncology to build a foundation for the Core rationale; proposed Core function, workflow, policies, and procedures; anticipated interactions with other CARG Cores; and proposed plans for sustainabilit

    Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center.

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    The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed that a vector-prime protein boost combined vaccine strategy was better than when used alone. Here we have studied three different priming vectors-plasmid DNA, recombinant MVA, and recombinant VSV, all encoding clade C transmitted/founder Env 1086 C gp140, for priming three groups of six non-human primates each, followed by a protein boost with adjuvanted 1086 C gp120 protein. Our data showed that MVA-priming favors the development of higher antibody binding titers and neutralizing activity compared with other vectors. Analyses of the draining lymph nodes revealed that MVA-prime induced increased germinal center reactivity characterized by higher frequencies of germinal center (PNA <sup>hi</sup> ) B cells, higher frequencies of antigen-specific B-cell responses as well as an increased frequency of the highly differentiated (ICOS <sup>hi</sup> CD150 <sup>lo</sup> ) Tfh-cell subset

    Multi-system neurological disease is common in patients with OPA1 mutations

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    Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal ‘dominant optic atrophy plus’ variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44–6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08–4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment

    Towards evidence-based marketing: The case of childhood obesity

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    Contentious commodities such as tobacco, alcohol and fatty foods are bringing marketing under scrutiny from consumers and policymakers. Yet there is little agreement on whether marketing is harmful to society. Systematic review (SR), a methodology derived from clinical medicine, offers marketers a tool for providing resolution and allowing policymakers to proceed with greater confidence. This article describes how SR methods were applied for the first time to a marketing problem -- the effects of food promotion to children. The review withstood scrutiny and its findings were formally ratified by government bodies and policymakers, demonstrating that SR methods can transfer from clinical research to marketing

    Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

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    Search for the associated production of the Higgs boson with a top-quark pair

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    A search for the standard model Higgs boson produced in association with a top-quark pair t t ÂŻ H (ttÂŻH) is presented, using data samples corresponding to integrated luminosities of up to 5.1 fb −1 and 19.7 fb −1 collected in pp collisions at center-of-mass energies of 7 TeV and 8 TeV respectively. The search is based on the following signatures of the Higgs boson decay: H → hadrons, H → photons, and H → leptons. The results are characterized by an observed t t ÂŻ H ttÂŻH signal strength relative to the standard model cross section, μ = σ/σ SM ,under the assumption that the Higgs boson decays as expected in the standard model. The best fit value is μ = 2.8 ± 1.0 for a Higgs boson mass of 125.6 GeV

    Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at √S^{S}NN = 5.02 TeV

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    The second-order Fourier coefficients (υ2_{2}) characterizing the azimuthal distributions of ΄(1S) and ΄(2S) mesons produced in PbPb collisions at sNN\sqrt{s_{NN}} = 5.02 TeV are studied. The ΄mesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb−1^{-1}. The scalar product method is used to extract the υ2_{2} coefficients of the azimuthal distributions. Results are reported for the rapidity range |y| < 2.4, in the transverse momentum interval 0 < pT_{T} < 50 GeV/c, and in three centrality ranges of 10–30%, 30–50% and 50–90%. In contrast to the J/ψ mesons, the measured υ2_{2} values for the ΄ mesons are found to be consistent with zero

    Measurement of prompt D0^{0} and D‟\overline{D}0^{0} meson azimuthal anisotropy and search for strong electric fields in PbPb collisions at root SNN\sqrt{S_{NN}} = 5.02 TeV

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    The strong Coulomb field created in ultrarelativistic heavy ion collisions is expected to produce a rapiditydependent difference (Av2) in the second Fourier coefficient of the azimuthal distribution (elliptic flow, v2) between D0 (uc) and D0 (uc) mesons. Motivated by the search for evidence of this field, the CMS detector at the LHC is used to perform the first measurement of Av2. The rapidity-averaged value is found to be (Av2) = 0.001 ? 0.001 (stat)? 0.003 (syst) in PbPb collisions at ?sNN = 5.02 TeV. In addition, the influence of the collision geometry is explored by measuring the D0 and D0mesons v2 and triangular flow coefficient (v3) as functions of rapidity, transverse momentum (pT), and event centrality (a measure of the overlap of the two Pb nuclei). A clear centrality dependence of prompt D0 meson v2 values is observed, while the v3 is largely independent of centrality. These trends are consistent with expectations of flow driven by the initial-state geometry. ? 2021 The Author. Published by Elsevier B.V. This is an open access article under the CC BY licens
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