637 research outputs found

    Piperacillin-Tazobactam versus Other Antibacterial Agents for Treatment of Bloodstream Infections Due to AmpC β-Lactamase-Producing Enterobacteriaceae

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    In vivo induction of AmpC beta-lactamases produces high-level resistance to many beta-lactam antibiotics in Enterobacteriaceae, often resulting in the need to use carbapenems or cefepime (FEP). The clinical effectiveness of piperacillin-tazobactam (TZP), a weak inducer of AmpC beta-lactamases, is poorly understood. Here, we conducted a case-control study of adult inpatients with bloodstream infections (BSIs) due to Enterobacter, Serratia, or Citrobacter species from 2009 to 2015 to assess outcomes following treatment with TZP compared to FEP or meropenem (MEM). We collected clinical data and screened all isolates for the presence of ampC alleles by PCR. Primary study outcomes were 30-day mortality and persistent bacteremia at \u3e/=72 h from the time of treatment initiation. Of 493 patients with bacteremia, 165 patients met the inclusion criteria, of which 88 were treated with TZP and 77 with FEP or MEM. To minimize differences between covariates, we carried out propensity score matching, which yielded 41 matched pairs. Groups only differed by age, with patients in the TZP group significantly older (P = 0.012). There were no significant differences in 30-day mortality, persistent bacteremia, 7-day mortality, or treatment escalation between the two treatment groups, including in the propensity score-matched cohort. PCR amplification and sequencing of ampC genes revealed the presence of ampC in isolates with cefoxitin MICs below 16 mug/ml, in particular in Serratia spp., and demonstrated that these alleles were highly genetically diverse. Taken together, TZP may be a valuable treatment option for BSIs due to AmpC beta-lactamase-producing Enterobacteriaceae, diminishing the need for broader-spectrum agents. Future studies are needed to validate these findings

    Computation of optimized arrays for 3-D electrical imaging surveys

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    3-D electrical resistivity surveys and inversion models are required to accurately resolve structures in areas with very complex geology where 2-D models might suffer from artefacts. Many 3-D surveys use a grid where the number of electrodes along one direction (x) is much greater than in the perpendicular direction (y). Frequently, due to limitations in the number of independent electrodes in the multi-electrode system, the surveys use a roll-along system with a small number of parallel survey lines aligned along the x-direction. The ‘Compare R' array optimization method previously used for 2-D surveys is adapted for such 3-D surveys. Offset versions of the inline arrays used in 2-D surveys are included in the number of possible arrays (the comprehensive data set) to improve the sensitivity to structures in between the lines. The array geometric factor and its relative error are used to filter out potentially unstable arrays in the construction of the comprehensive data set. Comparisons of the conventional (consisting of dipole-dipole and Wenner-Schlumberger arrays) and optimized arrays are made using a synthetic model and experimental measurements in a tank. The tests show that structures located between the lines are better resolved with the optimized arrays. The optimized arrays also have significantly better depth resolution compared to the conventional array

    Reprocessed height time series for GPS stations

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    Precise weekly positions of 403 Global Positioning System (GPS) stations located worldwide are obtained by reprocessing GPS data of these stations for the time span from 4 January 1998 until 29 December 2007. The processing algorithms and models used as well as the solution and results obtained are presented. Vertical velocities of 266 GPS stations having a tracking history longer than 2.5 yr are computed; 107 of them are GPS stations located at tide gauges (TIGA observing stations). The vertical velocities calculated in this study are compared with the estimates from the co-located tide gauges and other GPS solutions. The formal errors of the estimated vertical velocities are 0.01–0.80 mm yr−1. The vertical velocities of our solution agree within 1 mm yr−1 with those of the recent solutions (ULR5 and ULR3) of the Université de La Rochelle for about 67–75 per cent of the common stations. Examples of typical behaviour of station height changes are given and interpreted. The derived height time series and vertical motions of continuous GPS at tide gauges stations can be used for correcting the vertical land motion in tide gauge records of sea level changes

    The RNA-binding protein ATX-2 regulates cytokinesis through PAR-5 and ZEN-4

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    The spindle midzone harbors both microtubules and proteins necessary for furrow formation and the completion of cytokinesis. However, the mechanisms that mediate the temporal and spatial recruitment of cell division factors to the spindle midzone and midbody remain unclear. Here we describe a mechanism governed by the conserved RNA-binding protein ATX-2/Ataxin-2, which targets and maintains ZEN-4 at the spindle midzone. ATX-2 does this by regulating the amount of PAR-5 at mitotic structures, particularly the spindle, centrosomes, and midbody. Preventing ATX-2 function leads to elevated levels of PAR-5, enhanced chromatin and centrosome localization of PAR-5-GFP, and ultimately a reduction of ZEN-4-GFP at the spindle midzone. Codepletion of ATX-2 and PAR-5 rescued the localization of ZEN-4 at the spindle midzone, indicating that ATX-2 mediates the localization of ZEN-4 upstream of PAR-5. We provide the first direct evidence that ATX-2 is necessary for cytokinesis and suggest a model in which ATX-2 facilitates the targeting of ZEN-4 to the spindle midzone by mediating the posttranscriptional regulation of PAR-5

    537Microparticles and exosomes differentially impact on endothelial cell function in coronary artery disease

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    Background and Purpose: Microparticles (MPs) and exosomes are released by cells using different mechanisms. Thus, quantitative as well as qualitative changes of both particle populations, MPs and exosomes, in patients with coronary artery disease (CAD) might reflect an altered activation status of the endothelium, platelets and leukocytes. Moreover, they might exert differential effects on the target organs, such as the endothelium. Yet, alterations in both populations have not been studied side-by-side so far. The aim of the study was to compare the impact of MPs and exosomes from healthy subjects and CAD patients on endothelial cell (EC) functional characteristics. Methods: MPs and exosomes were isolated by stepwise filtration and ultracentrifugation from citrate-plasma and verified by electron microscopy and dynamic light scattering. MP and exosome fractions, as well as the vehicle (PBS), were added to human arterial ECs and EC apoptosis, number, size, capacity for in vitro-reendothelialisation after scratching, expression of adhesion molecules ICAM-1 and VCAM-1 were assessed. In parallel, platelet-, endothelial- and leukocyte-derived MPs were quantified. In a separate sub-study, the same parameters were assessed in plasma of CAD patients undergoing standard medical rehabilitation or an exercise-based cardiac rehabilitation programme. Results: MPs of healthy, but not of CAD patients supported in vitro re-endothelialisation, while exosomes had no influence. Exercise, but not standard rehabilitation improved CAD MP capacity to support in vitro rehabilitation. This was negatively correlated to the number of leukocyte- and endothelial-derived MPs, but not total or platelet MPs. EC number was negatively affected by exposure to CAD MPs. ANCOVA analysis identified disease, but not the particle type as influencing factor. Instead, apoptotic cell death was influenced by particle type, but not by the disease, and was not altered in rehabilitation. Similarly, ICAM-1 and VCAM-1 expression were enhanced on ECs after incubation with exosomes, but not with MPs, with no effect of disease or rehabilitation. Conclusion: MPs and exosomes differentially affect endothelial cell function and underlie differential modulation in disease and rehabilitation. Those findings might in the future help to optimize and monitor cardiovascular therap
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