The Evolution of Oxygen and Magnesium in the Bulge and Disk of the Milky Way

We show that the Galactic bulge and disk share a similar, strong, decline in [O/Mg] ratio with [Mg/H]. The similarity of the [O/Mg] trend in these two, markedly different, populations suggests a metallicity-dependent modulation of the stellar yields from massive stars, by mass loss from winds, and related to the Wolf-Rayet phenomenon, as proposed by McWilliam & Rich (2004). We have modified existing models for the chemical evolution of the Galactic bulge and the solar neighborhood with the inclusion of metallicity-dependent oxygen yields from theoretical predictions for massive stars that include mass loss by stellar winds. Our results significantly improve the agreement between predicted and observed [O/Mg] ratios in the bulge and disk above solar metallicity; however, a small zero-point normalization problem remains to be resolved. The zero-point shift indicates that either the semi-empirical yields of Francois et al. (2004) need adjustment, or that the bulge IMF is not quite as flat as found by Ballero et al. (2007); the former explanation is preferred. Our result removes a previous inconsistency between the interpretation of [O/Fe] and [Mg/Fe] ratios in the bulge, and confirms the conclusion that the bulge formed more rapidly than the disk, based on the over-abundances of elements produced by massive stars. We also provide an explanation for the long-standing difference between [Mg/Fe] and [O/Fe] trends among disk stars more metal-rich than the sun.Comment: 22 pages including 5 figures. Submitted to the Astronomical Journa

Aminoglycoside-induced nephrotoxicity in children

Aminoglycoside antibiotics, in particular gentamicin and tobramycin, are still commonly used in paediatric clinical practice. These drugs cause nephrotoxicity, which particularly affects the proximal tubule epithelial cells due to selective endocytosis and accumulation of aminoglycosides via the multi-ligand receptor megalin. Recent epidemiological studies, using more widely accepted definitions of acute kidney injury (AKI), have suggested that AKI may occur in between 20 and 33 % of children exposed to aminoglycosides. A consensus set of phenotypic criteria for aminoglycoside-induced nephrotoxicity have recently been published. These are specifically designed to provide robust phenotyping for pharmacogenomic studies, but they can pave the way for standardisation for all clinical studies. Novel renal biomarkers, in particular kidney injury molecule-1, identify aminoglycoside-induced proximal tubular injury earlier than traditional markers and have shown promise in observational studies. Further studies need to demonstrate a clear association with clinically relevant outcomes to inform translation into clinical practice. Extended interval dosing of aminoglycosides results in a reduction in nephrotoxicity, but its use needs to become more widespread. Inhibition of megalin-mediated endocytosis by statins represents a novel approach to the prevention of aminoglycoside-induced nephrotoxicity which is currently being evaluated in a clinical trial. Recommendations for future directions are provided

Insights into the chemical composition of the metal-poor Milky Way halo globular cluster NGC 6426

We present our detailed spectroscopic analysis of the chemical composition of four red giant stars in the halo globular cluster NGC 6426. We obtained high-resolution spectra using the Magellan2/MIKE spectrograph, from which we derived equivalent widths and subsequently computed abundances of 24 species of 22 chemical elements. For the purpose of measuring equivalent widths, we developed a new semi-automated tool, called EWCODE. We report a mean Fe content of [Fe/H] =−2.34 ± 0.05 dex (stat.) in accordance with previous studies. At a mean α-abundance of [(Mg, Si, Ca)/3 Fe] = 0.39 ± 0.03 dex, NGC 6426 falls on the trend drawn by the Milky Way halo and other globular clusters at comparably low metallicities. The distribution of the lighter α-elements as well as the enhanced ratio [Zn/Fe] = 0.39 dex could originate from hypernova enrichment of the pre-cluster medium. We find tentative evidence for a spread in the elements Mg, Si, and Zn, indicating an enrichment scenario, where ejecta of evolved massive stars of a slightly older population have polluted a newly born younger one. The heavy element abundances in this cluster fit well into the picture of metal-poor globular clusters, which in that respect appear to be remarkably homogeneous. The pattern of the neutron-capture elements heavier than Zn points toward an enrichment history governed by the r-process with little, if any, sign of s-process contributions. This finding is supported by the striking similarity of our program stars to the metal-poor field star HD 108317

Urinary Biomarkers of Aminoglycoside-Induced Nephrotoxicity in Cystic Fibrosis: Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin

Aminoglycosides are commonly used for the treatment of pulmonary exacerbations in patients with cystic fibrosis (CF). However, they are potentially nephrotoxic. This prospective observational cohort study aimed to investigate the potential validity of two urinary renal biomarkers, Kidney Injury Molecule-1 (KIM-1) and Neutrophil Gelatinase-associated Lipocalin (NGAL), in identifying aminoglycoside-induced nephrotoxicity in children with CF. Children and young adults up to 20 years of age with a confirmed diagnosis of CF were recruited from ten United Kingdom hospitals. Participants provided urine samples for measurement of KIM-1 and NGAL concentrations, at baseline, at regular outpatient appointments, and before, during and after exposure to clinically-indicated treatment with the aminoglycoside tobramycin. 37/158 patients recruited (23.4%) received at least one course of IV tobramycin during the study. The median peak fold-change during tobramycin exposure for KIM-1 was 2.28 (IQR 2.69) and 4.02 (IQR 7.29) for NGAL, in the absence of serum creatinine changes. Baseline KIM-1 was positively associated with cumulative courses of IV aminoglycosides (R2 = 0.11; β = 0.03; p < 0.0001). KIM-1, in particular, may be a useful, non-invasive, biomarker of acute and chronic proximal tubular injury associated with exposure to aminoglycosides in patients with CF, but its clinical utility needs to be further evaluated in prospective studies