MRSA eradication of newly acquired lower respiratory tract infection in cystic fibrosis

UK cystic fibrosis (CF) guidelines recommend eradication of methicillin-resistant Staphylococcus aureus (MRSA) when cultured from respiratory samples. As there is no clear consensus as to which eradication regimen is most effective, we determined the efficacy of eradication regimens used in our CF centre and long-term clinical outcome. All new MRSA positive sputum cultures (n=37) that occurred between 2000 and 2014 were reviewed. Eradication regimen characteristics and clinical, microbiological and long-term outcome data were collected. Rifampicin plus fusidic acid was the most frequently used regimen (24 (65%) out of 37 patients), with an overall success rate of 79% (19 out of 24 patients). Eradication failure was more likely in patients with an additional MRSA-positive peripheral screening swab (p=0.03) and was associated with worse survival (p=0.04). Our results demonstrate the feasibility and clinical benefits of MRSA eradication. As peripheral colonisation was associated with lower eradication success, strategies combining systemic and topical treatments should be considered to optimise outcomes in CF patients

Ethical challenges in researching and telling the stories of recently deceased people

This paper explores ethical challenges encountered when conducting research about, and telling, the stories of individuals who had died before the research began. Cases were explored where individuals who lived alone had died alone at home and where their bodies had been undiscovered for an extended period. The ethical review process had not had anything significant to say about the deceased ‘participants’. As social researchers we considered whether it was ethical to involve deceased people in research when they had no opportunity to decline, and we were concerned about how to report such research. The idea that the dead can be harmed did not help our decision-making processes, but the notion of the dead having limited human rights conferred upon them was useful and aided us in clarifying how to conduct our research and disseminate our findings.Peer reviewe

The correlation of dust and gas emission in star-forming environments

This is the final version of the article. Available from the publisher via the DOI in this record.We present ammonia maps of portions of the W3 and Perseus molecular clouds in order to compare gas emission with submillimetre continuum thermal emission which are commonly used to trace the same mass component in star-forming regions, often under the assumption of local thermodynamic equilibrium (LTE). The Perseus and W3 star-forming regions are found to have significantly different physical characteristics consistent with the difference in size scales traced by our observations. Accounting for the distance of theW3 region does not fully reconcile these differences, suggesting that there may be an underlying difference in the structure of the two regions. Peak positions of submillimetre and ammonia emission do not correlate strongly. Also, the extent of diffuse emission is only moderately matched between ammonia and thermal emission. Source sizes measured from our observations are consistent between regions, although there is a noticeable difference between the submillimetre source sizes with sources in Perseus being significantly smaller than those in W3. Fractional abundances of ammonia are determined for our sources which indicate a dip in the measured ammonia abundance at the positions of peak submillimetre column density. Virial ratios are determined which show that our sources are generally bound in both regions, although there is considerable scatter in both samples. We conclude that sources in Perseus are bound on smaller scales than in W3 in a way that may reflect their previous identification as low-and high-mass, respectively. Our results indicate that assumptions of local thermal equilibrium and/or the coupling of the dust and gas phases in star-forming regions may not be as robust as commonly assumed. © 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.The authors would like to thank Neal Evans and Erik Rosolowsky for insightful and thorough comments on this work which have considerably improved its quality. The authors acknowledge the data analysis facilities provided by the Starlink Project under continual development by the JAC. In addition, the following Starlink packages have been used: Kappa, Cupid, GAIA, Convert and Coco. We would like to thank the helpful staff of the GBT in the collection of data used in this paper related to the project GBT10C_024. LKM is supported by a STFC postdoctoral grant (ST/G001847/1) and DJE is supported by a STFC PhD studentship. This research would not have been possible without the SIMBAD astronomical data base service operated at CDS, Strasbourg, France and the NASA Astrophysics Data System Bibliographic Services

Natural ventilation for the prevention of airborne contagion.

BACKGROUND: Institutional transmission of airborne infections such as tuberculosis (TB) is an important public health problem, especially in resource-limited settings where protective measures such as negative-pressure isolation rooms are difficult to implement. Natural ventilation may offer a low-cost alternative. Our objective was to investigate the rates, determinants, and effects of natural ventilation in health care settings. METHODS AND FINDINGS: The study was carried out in eight hospitals in Lima, Peru; five were hospitals of "old-fashioned" design built pre-1950, and three of "modern" design, built 1970-1990. In these hospitals 70 naturally ventilated clinical rooms where infectious patients are likely to be encountered were studied. These included respiratory isolation rooms, TB wards, respiratory wards, general medical wards, outpatient consulting rooms, waiting rooms, and emergency departments. These rooms were compared with 12 mechanically ventilated negative-pressure respiratory isolation rooms built post-2000. Ventilation was measured using a carbon dioxide tracer gas technique in 368 experiments. Architectural and environmental variables were measured. For each experiment, infection risk was estimated for TB exposure using the Wells-Riley model of airborne infection. We found that opening windows and doors provided median ventilation of 28 air changes/hour (ACH), more than double that of mechanically ventilated negative-pressure rooms ventilated at the 12 ACH recommended for high-risk areas, and 18 times that with windows and doors closed (p < 0.001). Facilities built more than 50 years ago, characterised by large windows and high ceilings, had greater ventilation than modern naturally ventilated rooms (40 versus 17 ACH; p < 0.001). Even within the lowest quartile of wind speeds, natural ventilation exceeded mechanical (p < 0.001). The Wells-Riley airborne infection model predicted that in mechanically ventilated rooms 39% of susceptible individuals would become infected following 24 h of exposure to untreated TB patients of infectiousness characterised in a well-documented outbreak. This infection rate compared with 33% in modern and 11% in pre-1950 naturally ventilated facilities with windows and doors open. CONCLUSIONS: Opening windows and doors maximises natural ventilation so that the risk of airborne contagion is much lower than with costly, maintenance-requiring mechanical ventilation systems. Old-fashioned clinical areas with high ceilings and large windows provide greatest protection. Natural ventilation costs little and is maintenance free, and is particularly suited to limited-resource settings and tropical climates, where the burden of TB and institutional TB transmission is highest. In settings where respiratory isolation is difficult and climate permits, windows and doors should be opened to reduce the risk of airborne contagion

A distance-limited sample of massive molecular outflows

We have observed 99 mid-infrared-bright, massive young stellar objects and compact H ii regions drawn from the Red MSX source survey in the J = 3−2 transition of 12CO and 13CO, using the James Clerk Maxwell Telescope. 89 targets are within 6 kpc of the Sun, covering a representative range of luminosities and core masses. These constitute a relatively unbiased sample of bipolar molecular outflows associated with massive star formation. Of these, 59, 17 and 13 sources (66, 19 and 15 per cent) are found to have outflows, show some evidence of outflow, and have no evidence of outflow, respectively. The time-dependent parameters of the high-velocity molecular flows are calculated using a spatially variable dynamic time-scale. The canonical correlations between the outflow parameters and source luminosity are recovered and shown to scale with those of low-mass sources. For coeval star formation, we find the scaling is consistent with all the protostars in an embedded cluster providing the outflow force, with massive stars up to ∼30 M⊙ generating outflows. Taken at face value, the results support the model of a scaled-up version of the accretion-related outflow-generation mechanism associated with discs and jets in low-mass objects with time-averaged accretion rates of ∼10−3 M⊙ yr−1 on to the cores. However, we also suggest an alternative model, in which the molecular outflow dynamics are dominated by the entrained mass and are unrelated to the details of the acceleration mechanism. We find no evidence that outflows contribute significantly to the turbulent kinetic energy of the surrounding dense cores

The Sphaleron Rate in SU(N) Gauge Theory

The sphaleron rate is defined as the diffusion constant for topological number NCS = int g^2 F Fdual/32 pi^2. It establishes the rate of equilibration of axial light quark number in QCD and is of interest both in electroweak baryogenesis and possibly in heavy ion collisions. We calculate the weak-coupling behavior of the SU(3) sphaleron rate, as well as making the most sensible extrapolation towards intermediate coupling which we can. We also study the behavior of the sphaleron rate at weak coupling at large Nc.Comment: 18 pages with 3 figure

Microscopic Observation Drug Susceptibility Assay for Rapid Diagnosis of Lymph Node Tuberculosis and Detection of Drug Resistance.

In this study, 132 patients with lymphadenopathy were investigated. Fifty-two (39.4%) were diagnosed with tuberculosis (TB). The microscopic observation drug susceptibility (MODS) assay provided rapid (13 days), accurate diagnosis (sensitivity, 65.4%) and reliable drug susceptibility testing (DST). Despite its lower sensitivity than that of other methods, its faster results and simultaneous DST are advantageous in resource-poor settings, supporting the incorporation of MODS into diagnostic algorithms for extrapulmonary TB

Comparison of inhaled antibiotics for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis: systematic literature review and network meta-analysis

PURPOSE: In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF). Levofloxacin inhalation solution (LIS) is the most recently approved inhaled antibiotic for adult patients with CF. A systematic literature review and Bayesian network meta-analysis (NMA) was conducted to compare the relative short-term (4 weeks) and long-term (24 weeks) outcomes of these inhaled antibiotics versus LIS. METHODS: A systematic literature search was conducted on February 16, 2016, using EMBASE and Medline via OvidSP. All randomized controlled trials comparing any of the aforementioned inhaled antibiotics with 4 or 24 weeks of follow-up were evaluated. NMA was performed for the following outcomes: relative and absolute percent changes from baseline in forced expiratory volume in 1 second (FEV1%) predicted, change in P aeruginosa sputum density, respiratory symptoms score from the CF questionnaire-revised, hospitalization, additional antibiotics use, and study withdrawal rates. RESULTS: Of the 685 articles identified, 7 unique studies were included in the 4 weeks' NMA and 9 unique studies were included in the 24 weeks' NMA. Aztreonam was predicted to result in the greatest numerically increase in FEV1% predicted at 4 weeks, whereas LIS were predicted to be numerically greater than colistimethate sodium, tobramycin inhaled solution (TIS), and tobramycin inhaled powder (TIP). However, all of the 95% credibility intervals (CrIs) of these comparisons included zero. At 24 weeks, none of the treatments was significantly more effective than LIS. The estimates for the mean change from baseline to 24 weeks in relative FEV1% versus LIS was -0.55 (95% CrI, -3.91 to 2.80) for TIS, -2.36 (95% CrI, -7.32 to 2.63) for aztreonam, -2.95 (95% CrI, -10.44 to 4.51) for TIP, and -9.66 (95% CrI, -15.01 to -4.33) for placebo. Compared with LIS, the odds ratio for hospitalization at 24 weeks was 1.92 (95% CrI, 1.01-3.30) for TIS, 2.25 (95% CrI, 1.01-4.34) for TIP, and 3.16 (95% CrI, 1.53-5.78) for placebo, all statistically worse than LIS. P aeruginosa sputum density scores, additional use of antipseudomonal antibiotics, and study withdrawal rates were comparable among all inhaled antibiotics at all times. IMPLICATIONS: Based on this NMA, the analyses for many of the outcomes did not provide significant evidence to indicate that the other approved inhaled antibiotics were more effective than LIS for the treatment of chronic P aeruginosa lung infection in patients with CF. Study withdrawal rates seemed to be comparable among these inhaled antibiotics

Fast Ensemble Smoothing

Smoothing is essential to many oceanographic, meteorological and hydrological applications. The interval smoothing problem updates all desired states within a time interval using all available observations. The fixed-lag smoothing problem updates only a fixed number of states prior to the observation at current time. The fixed-lag smoothing problem is, in general, thought to be computationally faster than a fixed-interval smoother, and can be an appropriate approximation for long interval-smoothing problems. In this paper, we use an ensemble-based approach to fixed-interval and fixed-lag smoothing, and synthesize two algorithms. The first algorithm produces a linear time solution to the interval smoothing problem with a fixed factor, and the second one produces a fixed-lag solution that is independent of the lag length. Identical-twin experiments conducted with the Lorenz-95 model show that for lag lengths approximately equal to the error doubling time, or for long intervals the proposed methods can provide significant computational savings. These results suggest that ensemble methods yield both fixed-interval and fixed-lag smoothing solutions that cost little additional effort over filtering and model propagation, in the sense that in practical ensemble application the additional increment is a small fraction of either filtering or model propagation costs. We also show that fixed-interval smoothing can perform as fast as fixed-lag smoothing and may be advantageous when memory is not an issue

Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip

The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed