183 research outputs found

    ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy

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    Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients. Baseline and follow-up levels were assessed in 372 additional metastatic PDAC patients who received nab-paclitaxel with gemcitabine (n = 184) or gemcitabine monotherapy (n = 188) in the phase III MPACT trial. Increased levels of ADAM12 were found in PDAC patients compared to healthy controls (p < 0.0001, n = 157 and n = 38). High levels of ADAM12 significantly associated with poor outcome in resected PDAC (HR 2.07, p = 0.04). In the MPACT trial survival was significantly longer for patients who received nab-paclitaxel and had undetectable ADAM12 levels before treatment (OS 12.3 m vs 7.9 m p = 0.0046). Consistently undetectable or decreased ADAM12 levels during treatment significantly associated with longer survival as well (OS 14.4 m and 11.2 m, respectively vs 8.3, p = 0.0054). We conclude that ADAM12 is a blood-borne proxy for stromal activation, the levels of which have prognostic significance and correlate with treatment benefit

    Observation of the astrophysically important 3+ state in 18Ne via elastic scattering of a radioactive 17F beam from 1H

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    The 17F(p, γ)18 reaction is important in stellar explosions, but its rate has been uncertain because of an expected 3+ state in 18Ne that has never been conclusively observed. This state would provide a strong l = 0 resonance and, depending on its excitation energy, could dominate the stellar reaction rate. We have observed this missing 3+ state by measuring the 1H(17F, p)17F excitation function with a radioactive 17F beam at the ORNL Holifield Radioactive Ion Beam Facility. We find that the state lies at a center-of-mass energy of Er = 599.8 ± 1.5stat ± 2.0sys keV (Ex = 4523.7 ± 2.9keV) and has a width of Γ = 18 ± 2stat ± 1sys keV

    The astrophysically important 3+ state in 18Ne and the 17F(py)18Ne stellar rate

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    Knowledge of the [Formula Presented] reaction rate is important for understanding stellar explosions, but it was uncertain because the properties of an expected but previously unobserved [Formula Presented] state in [Formula Presented] were not known. This state would provide a strong s-wave resonance for the [Formula Presented] system and, depending on its excitation energy, could dominate the stellar reaction rate at temperatures above 0.2 GK. We have observed this missing [Formula Presented] state by measuring the [Formula Presented] excitation function with a radioactive [Formula Presented] beam at the ORNL Holifield Radioactive Ion Beam Facility (HRIBF). We find that the state lies at a center-of-mass energy of [Formula Presented] keV [Formula Presented] and has a width of [Formula Presented] The measured properties of the resonance are only consistent with a [Formula Presented] assignment

    The effect of autonomy, training opportunities, age and salaries on job satisfaction in the South East Asian retail petroleum industry

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    South East Asian petroleum retailers are under considerable pressure to improve service quality by reducing turnover. An empirical methodology from this industry determined the extent to which job characteristics, training opportunities, age and salary influenced the level of job satisfaction, an indicator of turnover. Responses are reported on a random sample of 165 site employees (a 68% response rate) of a Singaporean retail petroleum firm. A restricted multivariate regression model of autonomy and training opportunities explained the majority (35.4%) of the variability of job satisfaction. Age did not moderate these relationships, except for employees >21 years of age, who reported enhanced job satisfaction with additional salary. Human Capital theory, Life Cycle theory and Job Enrichment theory are invoked and explored in the context of these findings in the South East Asian retail petroleum industry. In the South East Asian retail petroleum industry, jobs providing employees with the opportunity to undertake a variety of tasks that enhanced the experienced meaningfulness of work are likely to promote job satisfaction, reduce turnover and increase the quality of service

    Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances

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    We use a genome-wide association of 1 million parental lifespans of genotyped subjects and data on mortality risk factors to validate previously unreplicated findings near CDKN2B-AS1, ATXN2/BRAP, FURIN/FES, ZW10, PSORS1C3, and 13q21.31, and identify and replicate novel findings near ABO, ZC3HC1, and IGF2R. We also validate previous findings near 5q33.3/EBF1 and FOXO3, whilst finding contradictory evidence at other loci. Gene set and cell-specific analyses show that expression in foetal brain cells and adult dorsolateral prefrontal cortex is enriched for lifespan variation, as are gene pathways involving lipid proteins and homeostasis, vesicle-mediated transport, and synaptic function. Individual genetic variants that increase dementia, cardiovascular disease, and lung cancer - but not other cancers - explain the most variance. Resulting polygenic scores show a mean lifespan difference of around five years of life across the deciles.Peer reviewe

    History of clinical transplantation

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    How transplantation came to be a clinical discipline can be pieced together by perusing two volumes of reminiscences collected by Paul I. Terasaki in 1991-1992 from many of the persons who were directly involved. One volume was devoted to the discovery of the major histocompatibility complex (MHC), with particular reference to the human leukocyte antigens (HLAs) that are widely used today for tissue matching.1 The other focused on milestones in the development of clinical transplantation.2 All the contributions described in both volumes can be traced back in one way or other to the demonstration in the mid-1940s by Peter Brian Medawar that the rejection of allografts is an immunological phenomenon.3,4 © 2008 Springer New York

    Diving into the vertical dimension of elasmobranch movement ecology

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    Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements
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