458 research outputs found

    Factors Associated with D-Dimer Levels in HIV-Infected Individuals

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    Background: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. Methods: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4(+) count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol. Results: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels. Conclusions: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels

    Removing noise from pyrosequenced amplicons

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    <b>Background</b><p></p> In many environmental genomics applications a homologous region of DNA from a diverse sample is first amplified by PCR and then sequenced. The next generation sequencing technology, 454 pyrosequencing, has allowed much larger read numbers from PCR amplicons than ever before. This has revolutionised the study of microbial diversity as it is now possible to sequence a substantial fraction of the 16S rRNA genes in a community. However, there is a growing realisation that because of the large read numbers and the lack of consensus sequences it is vital to distinguish noise from true sequence diversity in this data. Otherwise this leads to inflated estimates of the number of types or operational taxonomic units (OTUs) present. Three sources of error are important: sequencing error, PCR single base substitutions and PCR chimeras. We present AmpliconNoise, a development of the PyroNoise algorithm that is capable of separately removing 454 sequencing errors and PCR single base errors. We also introduce a novel chimera removal program, Perseus, that exploits the sequence abundances associated with pyrosequencing data. We use data sets where samples of known diversity have been amplified and sequenced to quantify the effect of each of the sources of error on OTU inflation and to validate these algorithms. <p></p> <b>Results</b><p></p> AmpliconNoise outperforms alternative algorithms substantially reducing per base error rates for both the GS FLX and latest Titanium protocol. All three sources of error lead to inflation of diversity estimates. In particular, chimera formation has a hitherto unrealised importance which varies according to amplification protocol. We show that AmpliconNoise allows accurate estimates of OTU number. Just as importantly AmpliconNoise generates the right OTUs even at low sequence differences. We demonstrate that Perseus has very high sensitivity, able to find 99% of chimeras, which is critical when these are present at high frequencies. <p></p> <b>Conclusions</b><p></p> AmpliconNoise followed by Perseus is a very effective pipeline for the removal of noise. In addition the principles behind the algorithms, the inference of true sequences using Expectation-Maximization (EM), and the treatment of chimera detection as a classification or 'supervised learning' problem, will be equally applicable to new sequencing technologies as they appear.<p></p&gt

    JOAO WANDERLEY GERALDI: THE LINGUIST RESEARCHER, TRAINING TEACHER AND UNIQUE BRAZILIAN READER OF BAKHTIN AND HIS STUDY CIRCLE

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    This article aims to honor and discuss our meeting with Joao Wanderley Geraldi, the linguist researcher, teacher trainer and unique reader of Bakhtin and his Study circle. Our subject matter in this paper is the meetings we held with the author in his research and teaching activities throughout his years of activism, and in specially during the Linguistics V program taken at Unicamp in 2005. From mediations with Geraldi on language studies, we chose to share our understanding of speech genres - involving life and education - that converge around this construction. Finally, we show how this knowledge guides us to maintain the inseparable relationship between language and literature in dialogue through a poem by Manoel de Barros, a poet who was also introduced to us by Geraldi.Univ Fed Santa Catarina UFSC, Programa Posgrad Linguist PPGL UFSC, Florianopolis, BrazilUniv Fed Santa Catarina, GEBAP Grp Estudos Bakhtinianos Pampa, Nucleo Estudos & Pesquisas Alfabetizacao & Ensino, Florianopolis, BrazilUniv Fed Santa Catarina, NEPALP, Nucleo Estudos & Pesquisas Alfabetizacao & Ensino, Florianopolis, BrazilNELA UFSC, Nucleo Estudos Linguist Aplicada, Florianopolis, BrazilGrp UNESP, Grp Estudos Alfabetizacao Brasil, Sao Paulo, BrazilUNIPAMPA Univ Fed Pampa, Curso Letras Linguas Adicionais, Campus Bage, RS, BrazilGEBAP Grp Estudos Bakhtinianos Pampa, Bage, BrazilGrp UNESP, Grp Estudos Alfabetizacao Brasil, Sao Paulo, Brazi

    Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population

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    Due to the success of antiretroviral therapy (ART), it is relevant to ask whether death rates in optimally treated HIV are higher than the general population. The objective was to compare mortality rates in well controlled HIV-infected adults in the SMART and ESPRIT clinical trials with the general population

    Long-term safety and efficacy of subcutaneous immunoglobulin IgPro20 in CIDP PATH extension study

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    Objective To investigate the long-term safety and efficacy of weekly subcutaneous IgPro20 (Hizentra, CSL Behring) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods In a 48-week open-label prospective extension study to the PATH study, patients were initially started on 0.2 g/kg or on 0.4 g/kg weekly and-if clinically stable-switched to 0.2 g/kg weekly after 24 weeks. Upon CIDP relapse on the 0.2 g/kg dose, 0.4 g/kg was (re)initiated. CIDP relapse was defined as a deterioration by at least 1 point in the total adjusted Inflammatory Neuropathy Cause and Treatment score. Results Eighty-two patients were enrolled. Sixty-two patients initially received 0.4 g/kg, 20 patients 0.2 g/kg weekly. Seventy-two received both doses during the study. Sixty-six patients (81%) completed the 48-week study duration. Overall relapse rates were 10% in 0.4 g/kg-treated patients and 48% in 0.2 g/kg-treated patients. After dose reduction from 0.4 to 0.2 g/kg, 51% (27/53) of patients relapsed, of whom 92% (24 of 26) improved after reinitiation of the 0.4 g/kg dose. Two-thirds of patients (19/28) who completed the PATH study without relapse remained relapse-free on the 0.2 g/kg dose after dose reduction in the extension study. Sixty-two patients had adverse events (AEs) (76%), of which most were mild or moderate with no related serious AEs. Conclusions Subcutaneous treatment with IgPro20 provided long-term benefit at both 0.4 and 0.2 g/kg weekly doses with lower relapse rates on the higher dose. Long-term dosing should be individualized to find the most appropriate dose in a given patient. Classification of evidence This study provides Class IV evidence that for patients with CIDP, long-term treatment with SCIG beyond 24 weeks is safe and efficacious.Peer reviewe

    Accuracy of the Adaptive GRP Scheme and the Simulation of 2-D Riemann Problems for Compressible Euler Equations

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    The adaptive generalized Riemann problem (GRP) scheme for 2-D compressible fluid flows has been proposed in [J. Comput. Phys., 229 (2010), 1448-1466] and it displays the capability in overcoming difficulties such as the start-up error for a single shock, and the numerical instability of the almost stationary shock. In this paper, we will provide the accuracy study and particularly show the performance in simulating 2-D complex wave configurations formulated with the 2-D Riemann problems for compressible Euler equations. For this purpose, we will first review the GRP scheme briefly when combined with the adaptive moving mesh technique and consider the accuracy of the adaptive GRP scheme via the comparison with the explicit formulae of analytic solutions of planar rarefaction waves, planar shock waves, the collapse problem of a wedge-shaped dam and the spiral formation problem. Then we simulate the full set of wave configurations in the 2-D four-wave Riemann problems for compressible Euler equations [SIAM J. Math. Anal., 21 (1990), 593-630], including the interactions of strong shocks (shock reflections), vortex-vortex and shock-vortex etc. This study combines the theoretical results with the numerical simulations, and thus demonstrates what Ami Harten observed "for computational scientists there are two kinds of truth: the truth that you prove, and the truth you see when you compute" [J. Sci. Comput., 31 (2007), 185-193].http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000298763800002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Physics, MathematicalSCI(E)16ARTICLE3577-6061
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