Importance of site of infection and antibiotic selection in the treatment of carbapenem-resistant Pseudomonas aeruginosa sepsis

ABSTRACT In a retrospective analysis of 215 patients with carbapenem-resistant Pseudomonas aeruginosa sepsis, we observed a significantly higher risk of mortality associated with respiratory tract infection (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.04 to 1.39; P = 0.010) and lower risk with urinary tract infection (RR, 0.80; 95% CI, 0.71 to 0.90; P = 0.004). Aminoglycoside monotherapy was associated with increased mortality, even after adjusting for confounders (adjusted RR, 1.72; 95% CI, 1.03 to 2.85; P = 0.037), consistent across multiple sites of infection. </jats:p

Vancomycin 24-Hour Area under the Curve/Minimum Bactericidal Concentration Ratio as a Novel Predictor of Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia

While previous studies have examined the association between vancomycin (VAN) exposure and MIC with regard to outcomes in methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B), none have explored if a relationship exists with the VAN minimum bactericidal concentration (MBC). The objective of this study was to evaluate the VAN 24-h area under the curve (AUC24)/MBC ratio as a pharmacodynamic predictor of mortality. This retrospective cohort study included patients treated with VAN for MRSA-B with the primary outcome of 30-day all-cause mortality. Data collected included patient demographics, comorbidities, antimicrobial treatment data, therapeutic drug levels, and laboratory and microbiological data. Vancomycin MICs and MBCs were determined by Etest (MIC only) and broth microdilution (BMD). The vancomycin AUC24 was determined by pharmacokinetic maximum a posteriori probability Bayesian (MAP-Bayesian) analysis. The most significant breakpoint for 30-day mortality was determined by classification and regression tree (CART) analysis. The association between pharmacodynamic parameters (VAN AUC24/MICBMD, VAN AUC24/MICEtest, and AUC24/MBCBMD) and mortality were determined by χ2 and multivariable Poisson regression. Overall mortality in this cohort (n = 53) was 20.8% (n = 11/53), and all corresponding MRSA blood isolates were VAN susceptible (MIC range, 0.5 to 2 μg/ml; MIC50, 1 μg/ml; MIC90, 1 μg/ml). The CART-derived breakpoints for mortality were 176 (VAN AUC24/MBC) and 334 (VAN AUC24/MICBMD). In multivariable analysis, the association between a VAN AUC24/MBC of ≥176 and survival persisted, but VAN AUC24/MICBMD values (≥334 or ≥400) were not associated with improved mortality. In conclusion, VAN AUC24/MBC was a more important predictor of 30-day mortality than VAN AUC24/MIC for MRSA-B

Extracellular vesicles: Novel communicators in lung diseases

This work is licensed under a Creative Commons Attribution 4.0 International License.The lung is the organ with the highest vascular density in the human body. It is therefore perceivable that the endothelium of the lung contributes significantly to the circulation of extracellular vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies. In addition to the endothelium, EVs may arise from alveolar macrophages, fibroblasts and epithelial cells. Because EVs harbor cargo molecules, such as miRNA, mRNA, and proteins, these intercellular communicators provide important insight into the health and disease condition of donor cells and may serve as useful biomarkers of lung disease processes. This comprehensive review focuses on what is currently known about the role of EVs as markers and mediators of lung pathologies including COPD, pulmonary hypertension, asthma, lung cancer and ALI/ARDS. We also explore the role EVs can potentially serve as therapeutics for these lung diseases when released from healthy progenitor cells, such as mesenchymal stem cells.NiH R01DA042715NIH R01HL129875NIH P20 GM10363

The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat

The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC(0-24h) were significantly reduced by PCN pre-treatment. Biliary digoxin clearance increased 2-fold following PCN treatment. PCN significantly increased net digoxin secretion (2.05- and 4.5-fold respectively) in ileum and colon but not in duodenum or jejunum. This increased secretion correlated with increased Pgp protein expression in ileum and colon. Both intestinal and biliary excretion therefore contribute to altered digoxin disposition following PCN

The SDSS-III Baryon Oscillation Spectroscopic Survey: Quasar Target Selection for Data Release Nine

The SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), a five-year spectroscopic survey of 10,000 deg^2, achieved first light in late 2009. One of the key goals of BOSS is to measure the signature of baryon acoustic oscillations in the distribution of Ly-alpha absorption from the spectra of a sample of ~150,000 z>2.2 quasars. Along with measuring the angular diameter distance at z\approx2.5, BOSS will provide the first direct measurement of the expansion rate of the Universe at z > 2. One of the biggest challenges in achieving this goal is an efficient target selection algorithm for quasars over 2.2 < z < 3.5, where their colors overlap those of stars. During the first year of the BOSS survey, quasar target selection methods were developed and tested to meet the requirement of delivering at least 15 quasars deg^-2 in this redshift range, out of 40 targets deg^-2. To achieve these surface densities, the magnitude limit of the quasar targets was set at g <= 22.0 or r<=21.85. While detection of the BAO signature in the Ly-alpha absorption in quasar spectra does not require a uniform target selection, many other astrophysical studies do. We therefore defined a uniformly-selected subsample of 20 targets deg^-2, for which the selection efficiency is just over 50%. This "CORE" subsample will be fixed for Years Two through Five of the survey. In this paper we describe the evolution and implementation of the BOSS quasar target selection algorithms during the first two years of BOSS operations. We analyze the spectra obtained during the first year. 11,263 new z>2.2 quasars were spectroscopically confirmed by BOSS. Our current algorithms select an average of 15 z > 2.2 quasars deg^-2 from 40 targets deg^-2 using single-epoch SDSS imaging. Multi-epoch optical data and data at other wavelengths can further improve the efficiency and completeness of BOSS quasar target selection. [Abridged]Comment: 33 pages, 26 figures, 12 tables and a whole bunch of quasars. Submitted to Ap

Scientists' Warning to Humanity on Threats to Indigenous and Local Knowledge Systems

The knowledge systems and practices of Indigenous Peoples and local communities play critical roles in safeguarding the biological and cultural diversity of our planet. Globalization, government policies, capitalism, colonialism, and other rapid social-ecological changes threaten the relationships between Indigenous Peoples and local communities and their environments, thereby challenging the continuity and dynamism of Indigenous and Local Knowledge (ILK). In this article, we contribute to the “World Scientists' Warning to Humanity,” issued by the Alliance of World Scientists, by exploring opportunities for sustaining ILK systems on behalf of the future stewardship of our planet. Our warning raises the alarm about the pervasive and ubiquitous erosion of knowledge and practice and the social and ecological consequences of this erosion. While ILK systems can be adaptable and resilient, the foundations of these knowledge systems are compromised by ongoing suppression, misrepresentation, appropriation, assimilation, disconnection, and destruction of biocultural heritage. Three case studies illustrate these processes and how protecting ILK is central to biocultural conservation. We conclude with 15 recommendations that call for the recognition and support of Indigenous Peoples and local communities and their knowledge systems. Enacting these recommendations will entail a transformative and sustained shift in how ILK systems, their knowledge holders, and their multiple expressions in lands and waters are recognized, affirmed, and valued. We appeal for urgent action to support the efforts of Indigenous Peoples and local communities around the world to maintain their knowledge systems, languages, stewardship rights, ties to lands and waters, and the biocultural integrity of their territories—on which we all depend.Peer reviewe

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version