Measures to eradicate multidrug-resistant organism outbreaks: How much does it cost?

This study aimed to assess the economic burden of infection control measures that succeeded in eradicating multidrug-resistant organisms (MDROs) in emerging epidemic contexts in hospital settings. The MEDLINE, EMBASE and Ovid databases were systematically interrogated for original English-language articles detailing costs associated with strict measures to eradicate MDROs published between 1 January 1974 and 2 November 2014. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Overall, 13 original articles were retrieved reporting data on several MDROs, including glycopeptide-resistant enterococci (n = 5), carbapenemase-producing Enterobacteriacae (n = 1), methicillin-resistant Staphylococcus aureus (n = 5), and carbapenem-resistant Acinetobacter baumannii (n = 2). Overall, the cost of strict measures to eradicate MDROs ranged from €285 to €57 532 per positive patient. The major component of these overall costs was related to interruption of new admissions, representing €2466 to €47 093 per positive patient (69% of the overall mean cost; range, 13-100%), followed by mean laboratory costs of €628 to €5849 (24%; range, 3.3-56.7%), staff reinforcement costs of €6204 to €148 381 (22%; range, 3.3-52%), and contact precautions costs of €166 to €10 438 per positive patient (18%; range, 0.7-43.3%). Published data on the economic burden of strict measures to eradicate MDROs are limited, heterogeneous, and weakened by several methodological flaws. Novel economic studies should be performed to assess the financial impact of current policies, and to identify the most cost-effective strategies to eradicate emerging MDROs in healthcare facilities

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

Biochemical properties of Paracoccus denitrificans FnrP:Reactions with molecular oxygen and nitric oxide

In Paracoccus denitrificans, three CRP/FNR family regulatory proteins, NarR, NnrR and FnrP, control the switch between aerobic and anaerobic (denitrification) respiration. FnrP is a [4Fe-4S] cluster containing homologue of the archetypal O2 sensor FNR from E. coli and accordingly regulates genes encoding aerobic and anaerobic respiratory enzymes in response to O2, and also NO, availability. Here we show that FnrP undergoes O2-driven [4Fe-4S] to [2Fe-2S] cluster conversion that involves up to 2 O2 per cluster, with significant oxidation of released cluster sulfide to sulfane observed at higher O2 concentrations. The rate of the cluster reaction was found to be ~6-fold lower than that of E. coli FNR, suggesting that FnrP can remain transcriptionally active under microaerobic conditions. This is consistent with a role for FnrP in activating expression of the high O2 affinity cytochrome c oxidase under microaerobic conditions. Cluster conversion resulted in dissociation of the transcriptionally active FnrP dimer into monomers. Therefore, along with E. coli FNR, FnrP belongs to the subset of FNR proteins in which cluster type is correlated with association state. Interestingly, two key charged residues, Arg140 and Asp154, that have been shown to play key roles in the monomer-dimer equilibrium in E. coli FNR are not conserved in FnrP, indicating that different protomer interactions are important for this equilibrium. Finally, the FnrP [4Fe-4S] cluster is shown to undergo reaction with multiple NO molecules, resulting in iron nitrosyl species and dissociation into monomers

Climatic implications of background acidity and other chemistry derived from electrical studies of the Greenland Ice Core Project ice core

© 1997 by the American Geophysical Union. High-resolution continuous profiles were obtained on the Greenland Ice Core Project (GRIP) ice core using two different electrical methods. After correction for temperature and density, the electrical conductivity method (ECM) technique responds only to acidity, while dielectric profiling (DEP) responds to acid, ammonium, and chloride. Detailed chemistry on a section of glacial-age ice allows us to confirm the calibration factor for chloride in DEP. Acidity dominates the DEP variability in the Holocene, Allerod/Bolling, and larger interstadials; ammonium dominates in the Younger Dryas, while chloride is the major contributor in cold periods including smaller interstadials. From the electrical signals plotted on a linear timescale we can deduce the background (nonvolcanic) acidity of the ice, varying from always acidic in the Holocene to always alkaline in the cold periods. In the interstadials, the ice is close to neutral, with most of it acidic in larger interstadials, most of it alkaline in smaller ones, and rapid alternations within interstadials. It is not clear whether neutralization of individual acidic particles occurred in the atmosphere or whether acid and alkaline particles coexisted until deposition in the snowpack. The changes in acidity observed at GRIP apply at least to all of Greenland and probably to much of North America. There would have been ecological effects and important changes in the uptake of some chemicals onto ice. If acidic sulfate particles were neutralized and removed from the atmosphere, which remains uncertain, then there are atmospheric chemistry and radiative effects that require further investigation

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

Complement C3 variant and the risk of age-related macular degeneration

Background: Age-related macular degeneration is the most common cause of blindness in Western populations. Susceptibility is influenced by age and by genetic and environmental factors. Complement activation is implicated in the pathogenesis.Methods: We tested for an association between age-related macular degeneration and 13 single-nucleotide polymorphisms (SNPs) spanning the complement genes C3 and C5 in case subjects and control subjects from the southeastern region of England. All subjects were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status. To test for replication of the most significant findings, we genotyped a set of Scottish cases and controls.Results: The common functional polymorphism rs2230199 (Arg80Gly) in the C3 gene, corresponding to the electrophoretic variants C3S (slow) and C3F (fast), was strongly associated with age-related macular degeneration in both the English group (603 cases and 350 controls, P=5.9 x 10(sup -5)) and the Scottish group (244 cases and 351 controls, P=5.0 x 10(sup -5)). The odds ratio for age-related macular degeneration in C3 S/F heterozygotes as compared with S/S homozygotes was 1.7 (95% confidence interval [CI], 1.3 to 2.1); for F/F homozygotes, the odds ratio was 2.6 (95% CI, 1.6 to 4.1). The estimated population attributable risk for C3F was 22%.Conclusions: Complement C3 is important in the pathogenesis of age-related macular degeneration. This finding further underscores the influence of the complement pathway in the pathogenesis of this disease

The growth hormone receptor gene deleted for exon three (GHRd3) polymorphism is associated with birth and placental weight.

Human growth hormone receptor (GHR) transcripts have two isoforms, full-length (GHRfl) or exon 3 deleted (GHRd3). An association of these isoforms has been found with small for gestational age (SGA) infants but does not influence adult height. The role of this polymorphism in the birth size spectrum in the general population is unclear

Introduction : Setting the stage

Religion has become a pressing matter in different fields of multicultural European society, which raises the question as to how best to govern religious diversity. What we argue in this book is that a successful governance of religious diversity necessitates the development of religious literacy. As such, religious literacy can be understood in a variety of ways depending on the particular context. This book draws on different empirical case studies concerning Finland, covering traditional Finnish religious movements and issues pertaining to immigration and the growing ethnic and religious diversity of Finnish society. In doing so, it delves, among other matters, into the field of school education and state policies against radicalization and violence.Peer reviewe

Quantification of the SF₆ lifetime based on mesospheric loss measured in the stratospheric polar vortex

Sulfur hexafluoride (SF₆) is a greenhouse gas with one of the highest radiative efficiencies in the atmosphere as well as an important indicator of transport time scales in the stratosphere. The current widely used estimate of the atmospheric lifetime of SF₆ is 3200 years. In this study we use in situ measurements in the 2000 Arctic polar vortex that sampled air with up to 50% SF₆ loss to calculate an SF₆ lifetime. Comparison of these measurements with output from the Whole Atmosphere Community Climate Model (WACCM) shows that WACCM transport into the vortex is accurate and that an important SF₆ loss mechanism, believed to be electron attachment, is missing in the model. Based on the measurements and estimates of the size of the vortex, we calculate an SF₆ lifetime of 850 years with an uncertainty range of 580–1400 years. The amount of SF₆ loss is shown to be consistent with that of HFC‐227ea, which has a lifetime of 670–780 years, adding independent support to our new SF₆ lifetime estimate. Based on the revised lifetime the global warming potential of SF₆ will decrease only slightly for short time horizons (<100 years) but will decrease substantially for time horizons longer than 2000 years. Also, the use of SF6 measurements as an indicator of transport time scales in the stratosphere clearly must account for potential influence from polar vortex air

Functional Big-step Semantics

When doing an interactive proof about a piece of software, it is important that the underlying programming language’s semantics does not make the proof unnecessarily difficult or unwieldy. Both smallstep and big-step semantics are commonly used, and the latter is typically given by an inductively defined relation. In this paper, we consider an alternative: using a recursive function akin to an interpreter for the language. The advantages include a better induction theorem, less duplication, accessibility to ordinary functional programmers, and the ease of doing symbolic simulation in proofs via rewriting. We believe that this style of semantics is well suited for compiler verification, including proofs of divergence preservation. We do not claim the invention of this style of semantics: our contribution here is to clarify its value, and to explain how it supports several language features that might appear to require a relational or small-step approach. We illustrate the technique on a simple imperative language with C-like for-loops and a break statement, and compare it to a variety of other approaches. We also provide ML and lambda-calculus based examples to illustrate its generality