A Two-Phase Chemical Enrichment Model for the Milky Way Globular Cluster System

Many globular cluster systems have a distinct bimodal metallicity distribution function (MDF) which has strikingly similar features in many large galaxies of all types. By using the Milky Way cluster system as a typical example, we show that bimodal MDFs can be very well matched with a double ``accreting-box'' chemical enrichment model in which both the halo (metal-poor) and bulge (metal-rich) clusters form during an early phase of gas inflow simultaneously with star formation. However, differences in effective yield between the two phases are not enough by themselves to reproduce the observed MDF shape: gas infall is required for both phases, and either the initial gas or the infalling gas must have very different metallicities in the two separate phases.Comment: 12 pages, 2 figures, accepted for publication in A

X-ray Point Sources in the Sombrero Galaxy: Supersoft sources, the globular cluster/LMXB connection, and an overview

We report on the population of point sources discovered during an 18.5 ksec Chandra ACIS-S observation of the Sombrero Galaxy. We present the luminosity function, the spectra of the 6 brightest sources, consider correlations with globular clusters (GCs) and with planetary nebulae (PNe), and study the galaxy's population of SSSs. We detected 122 sources, 22 of them are identified as luminous supersoft X-ray sources (SSSs). There is an over density of SSSs within 1.5 kpc of the nucleus, which is itself the brightest X-ray source. SSSs are also found in the disk and halo, with 1 SSS in a globular cluster (GC). Several sources in Sombrero's halo are good candidates for SSS models in which the accretor is a nuclear-burning white dwarf. In total, 32 X-ray sources are associated with GCs. The majority of sources with luminosity > 1e38 erg/s are in GCs. These results for M104, an Sa galaxy, are similar to what has been found for elliptical galaxies and for the late-type spiral M31. We find that those optically bright GCs with X-ray sources house only the brightest X-ray sources. We find that, in common with other galaxies, there appears to be a positive connection between young (metal-rich) GCs and X-ray sources, but that the brightest X-ray sources are equally likely to be in metal-poor GCs. We propose a model which can explain the trends seen in the data sets from the Sombrero and other galaxies. Thermal-time scale mass transfer can occur in some of the the younger clusters in which the turn-off mass is slightly greater than $0.8 M_\odot$; multiplicity may play a role in some of the most massive clusters; accretion from giant stars may be the dominant mechanism in some older, less massive and less centrally concentrated clusters.Comment: 13 pages, 7 figures. ApJ submitte

Microbiological efficacy of early MRSA treatment in cystic fibrosis in a randomised controlled trial

OBJECTIVE: To evaluate microbiological effectiveness, that is, culture negativity of a non-blinded eradication protocol (Rx) compared with observation (Obs) in clinically stable cystic fibrosis participants with newly positive methicillin resistant Staphylococcusaureus (MRSA) cultures. DESIGN: This non-blinded trial randomised participants ages 4-45 years with first or early (≤2 positive cultures within 3 years) MRSA-positive culture without MRSA-active antibiotics within 4 weeks 1:1 to Rx or Obs. The Rx protocol was: oral trimethoprim-sulfamethoxazole or if sulfa-allergic, minocycline plus oral rifampin; chlorhexidine mouthwash for 2 weeks; nasal mupirocin and chlorhexidine body wipes for 5 days and environmental decontamination for 21 days. The primary end point was MRSA culture status at day 28. RESULTS: Between 1 April 2011 to September 2014, 45 participants (44% female, mean age 11.5 years) were randomised (24 Rx, 21 Obs). At day 28, 82% (n=18/22) of participants in the Rx arm compared with 26% (n=5/19) in the Obs arm were MRSA-negative. Adjusted for interim monitoring, this difference was 52% (95% CI 23% to 80%, p<0.001). Limiting analyses to participants who were MRSA-positive at the screening visit, 67% (8/12) in the Rx arm and 13% (2/15) in the Obs arm were MRSA-negative at day 28, adjusted difference: 49% (95% CI 22% to 71%, p<0.001). Fifty-four per cent in the Rx arm compared with 10% participants in the Obs arm remained MRSA-negative through day 84. Mild gastrointestinal side effects were higher in the Rx arm. CONCLUSIONS: This MRSA eradication protocol for newly acquired MRSA demonstrated microbiological efficacy with a large treatment effect. TRIAL REGISTRATION NUMBER: NCT01349192

Microbiological efficacy of early MRSA treatment in cystic fibrosis in a randomised controlled trial

http://deepblue.lib.umich.edu/bitstream/2027.42/192032/2/Microbiologic Efficacy of early MRSA treatment in cystic fibrosis in a randomized controlled trial.pdfPublished versionDescription of Microbiologic Efficacy of early MRSA treatment in cystic fibrosis in a randomized controlled trial.pdf : Published versio

Building global development strategies for cf therapeutics during a transitional cftr modulator era

As CFTR modulator therapy transforms the landscape of cystic fibrosis (CF) care, its lack of uniform access across the globe combined with the shift towards a new standard of care creates unique challenges for the development of future CF therapies. The advancement of a full and promising CF therapeutics pipeline remains a necessary priority to ensure maximal clinical benefits for all people with CF. It is through collaboration across the global CF community that we can optimize the evaluation and approval process of new therapies. To this end, we must identify areas for which harmonization is lacking and for which efficiencies can be gained to promote ethical, feasible, and credible study designs amidst the changing CF care landscape. This article summarizes the counsel from core advisors across multiple international regions and clinical trial networks, developed during a one-day workshop in October 2019. The goal of the workshop was to identify, in consideration of the highly transitional era of CFTR modulator availability, the drug development areas for which global alignment is currently uncertain, and paths forward that will enable advancement of CF therapeutic development. (C) 2020 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved

The photometric evolution of star clusters and the preferential loss of low-mass bodies – with an application to globular clusters

Context. To obtain an accurate description of broad-band photometric star cluster evolution, certain effects should be accounted for. Energy equipartition leads to mass segregation and the preferential loss of low-mass stars, while stellar remnants severely influence cluster mass-to-light ratios. Moreover, the stellar initial mass function and cluster metallicity affect photometry as well. Due to the continuous production of stellar remnants, their impact on cluster photometry is strongest for old systems like globular clusters. This, in combination with their low metallicities, evidence for mass segregation, and a possibly deviating stellar initial mass function, makes globular clusters interesting test cases for cluster models. Aims. In this paper we describe cluster models that include the effects of the preferential loss of low-mass stars, stellar remnants, choice of initial mass function and metallicity. The photometric evolution of clusters is predicted, and the results are applied to Galactic globular clusters. Methods. The cluster models presented in this paper represent an analytical description of the evolution of the underlying stellar mass function due to stellar evolution and dynamical cluster dissolution. Stellar remnants are included by using initial-remnant mass relations, while cluster photometry is computed from the Padova 1999 isochrones. Results. Our study shows that the preferential loss of low-mass stars strongly affects cluster magnitude, colour and mass-to-light ratio evolution, as it increases cluster magnitudes and strongly decreases mass-to-light ratios. The effects of stellar remnants are prominent in the evolution of cluster mass, magnitude and mass-to-light ratio, while variations of the initial mass function induce similar, but smaller changes. Metallicity plays an important role for cluster magnitude, colour and mass-to-light ratio evolution. The different effects can be clearly separated with our models. We apply the models to the Galactic globular cluster population. Its properties like the magnitude, colour and mass-to-light ratio ranges are well reproduced with our models, provided that the preferential loss of lowmass stars and stellar remnants are included. We also show that the mass-to-light ratios of clusters with similar ages and metallicities cannot be assumed to be constant for all cluster luminosities due to the mass-dependence of the half-mass relaxation time. Instead, mass-to-light ratio increases with cluster luminosity and mass. Conclusions. These models underline the importance of more detailed cluster models when considering cluster photometry. By including the preferential loss of low-mass stars and the presence of stellar remnants, the magnitude, colour and mass-to-light ratio ranges of modelled globular clusters are significantly altered. With the analytic framework provided in this paper, observed cluster properties can be interpreted in a more complete perspective