Due to the spread of resistance, antibiotic exposure receives increasing attention. Ecological consequences for the different niches of individual microbiomes are, however, largely ignored. Here, we ...report the effects of widely used antibiotics (clindamycin, ciprofloxacin, amoxicillin, and minocycline) with different modes of action on the ecology of both the gut and the oral microbiomes in 66 healthy adults from the United Kingdom and Sweden in a two-center randomized placebo-controlled clinical trial. Feces and saliva were collected at baseline, immediately after exposure, and 1, 2, 4, and 12 months after administration of antibiotics or placebo. Sequences of 16S rRNA gene amplicons from all samples and metagenomic shotgun sequences from selected baseline and post-antibiotic-treatment sample pairs were analyzed. Additionally, metagenomic predictions based on 16S rRNA gene amplicon data were performed using PICRUSt. The salivary microbiome was found to be significantly more robust, whereas the antibiotics negatively affected the fecal microbiome: in particular, health-associated butyrate-producing species became strongly underrepresented. Additionally, exposure to different antibiotics enriched genes associated with antibiotic resistance. In conclusion, healthy individuals, exposed to a single antibiotic treatment, undergo considerable microbial shifts and enrichment in antibiotic resistance in their feces, while their salivary microbiome composition remains unexpectedly stable. The health-related consequences for the gut microbiome should increase the awareness of the individual risks involved with antibiotic use, especially in a (diseased) population with an already dysregulated microbiome. On the other hand, understanding the mechanisms behind the resilience of the oral microbiome toward ecological collapse might prove useful in combating microbial dysbiosis elsewhere in the body.
Many health care professionals use antibiotic prophylaxis strategies to prevent infection after surgery. This practice is under debate since it enhances the spread of antibiotic resistance. Another important reason to avoid nonessential use of antibiotics, the impact on our microbiome, has hardly received attention. In this study, we assessed the impact of antibiotics on the human microbial ecology at two niches. We followed the oral and gut microbiomes in 66 individuals from before, immediately after, and up to 12 months after exposure to different antibiotic classes. The salivary microbiome recovered quickly and was surprisingly robust toward antibiotic-induced disturbance. The fecal microbiome was severely affected by most antibiotics: for months, health-associated butyrate-producing species became strongly underrepresented. Additionally, there was an enrichment of genes associated with antibiotic resistance. Clearly, even a single antibiotic treatment in healthy individuals contributes to the risk of resistance development and leads to long-lasting detrimental shifts in the gut microbiome.
Geographic variation in phenotypes plays a key role in fundamental evolutionary processes such as local adaptation, population differentiation and speciation, but the selective forces behind it are ...rarely known. We found support for the hypothesis that geographic variation in plumage traits of the pied flycatcher Ficedula hypoleuca is explained by character displacement with the collared flycatcher Ficedula albicollis in the contact zone. The plumage traits of the pied flycatcher differed strongly from the more conspicuous collared flycatcher in a sympatric area but increased in conspicuousness with increasing distance to there. Phenotypic differentiation (PST) was higher than that in neutral genetic markers (FST), and the effect of geographic distance remained when statistically controlling for neutral genetic differentiation. This suggests that a cline created by character displacement and gene flow explains phenotypic variation across the distribution of this species. The different plumage traits of the pied flycatcher are strongly to moderately correlated, indicating that they evolve non‐independently from each other. The flycatchers provide an example of plumage patterns diverging in two species that differ in several aspects of appearance. The divergence in sympatry and convergence in allopatry in these birds provide a possibility to study the evolutionary mechanisms behind the highly divergent avian plumage patterns.
The role of natural selection in shaping adaptive trait differentiation in natural populations has long been recognized. Determining its molecular basis, however, remains a challenge. Here, we search ...for signals of selection in candidate genes for colour and its perception in a passerine bird. Pied flycatcher plumage varies geographically in both its structural and pigment-based properties. Both characteristics appear to be shaped by selection. A single-locus outlier test revealed 2 of 14 loci to show significantly elevated signals of divergence. The first of these, the follistatin gene, is expressed in the developing feather bud and is found in pathways with genes that determine the structure of feathers and may thus be important in generating variation in structural colouration. The second is a gene potentially underlying the ability to detect this variation: SWS1 opsin. These two loci were most differentiated in two Spanish pied flycatcher populations, which are also among the populations that have the highest UV reflectance. The follistatin and SWS1 opsin genes thus provide strong candidates for future investigations on the molecular basis of adaptively significant traits and their co-evolution.
Since echinocandins are recommended as first line therapy for invasive candidiasis, detection of resistance, mainly due to alteration in FKS protein, is of main interest. EUCAST AFST recommends ...testing both MIC of anidulafungin and micafungin, and breakpoints (BPs) have been proposed to detect echinocandin-resistant isolates. We analyzed MIC distribution for all three available echinocandins of 2,787 clinical yeast isolates corresponding to 5 common and 16 rare yeast species, using the standardized EUCAST method for anidulafungin and modified for caspofungin and micafungin (AM3-MIC). In our database, 64 isolates of common pathogenic species were resistant to anidulafungin, according to the EUCAST BP, and/or to caspofungin, using our previously published threshold (AM3-MIC ≥ 0.5 mg/L). Among these 64 isolates, 50 exhibited 21 different FKS mutations. We analyzed the capacity of caspofungin AM3-MIC and anidulafungin MIC determination in detecting isolates with FKS mutation. They were always identified using caspofungin AM3-MIC and the local threshold while some isolates were misclassified using anidulafungin MIC and EUCAST threshold. However, both methods misclassified four wild-type C. glabrata as resistant. Based on a large data set from a single center, the use of AM3-MIC testing for caspofungin looks promising in identifying non-wild-type C. albicans, C. tropicalis and P. kudiravzevii isolates, but additional multicenter comparison is mandatory to conclude on the possible superiority of AM3-MIC testing compared to the EUCAST method.
Generalized Fisher matrices Heavens, A F; Seikel, M; Nord, B D ...
Monthly notices of the Royal Astronomical Society,
12/2014, Letnik:
445, Številka:
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Journal Article
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The Fisher Information Matrix formalism (Fisher 1935) is extended to cases where the data are divided into two parts (X, Y), where the expectation value of Y depends on X according to some ...theoretical model, and X and Y both have errors with arbitrary covariance. In the simplest case, (X, Y) represent data pairs of abscissa and ordinate, in which case the analysis deals with the case of data pairs with errors in both coordinates, but X can be any measured quantities on which Y depends. The analysis applies for arbitrary covariance, provided all errors are Gaussian, and provided the errors in X are small, both in comparison with the scale over which the expected signal Y changes, and with the width of the prior distribution. This generalizes the Fisher Matrix approach, which normally only considers errors in the 'ordinate' Y. In this work, we include errors in X by marginalizing over latent variables, effectively employing a Bayesian hierarchical model, and deriving the Fisher Matrix for this more general case. The methods here also extend to likelihood surfaces which are not Gaussian in the parameter space, and so techniques such as DALI (Derivative Approximation for Likelihoods) can be generalized straightforwardly to include arbitrary Gaussian data error covariances. For simple mock data and theoretical models, we compare to Markov Chain Monte Carlo experiments, illustrating the method with cosmological supernova data. We also include the new method in the FISHER4CAST software.
We present cosmological results from a combined analysis of galaxy clustering and weak gravitational lensing, using 1321 deg2 of griz imaging data from the first year of the Dark Energy Survey (DES ...Y1). We combine three two-point functions: (i) the cosmic shear correlation function of 26 million source galaxies in four redshift bins, (ii) the galaxy angular autocorrelation function of 650,000 luminous red galaxies in five redshift bins, and (iii) the galaxy-shear cross-correlation of luminous red galaxy positions and source galaxy shears. To demonstrate the robustness of these results, we use independent pairs of galaxy shape, photometric-redshift estimation and validation, and likelihood analysis pipelines. To prevent confirmation bias, the bulk of the analysis was carried out while “blind” to the true results; we describe an extensive suite of systematics checks performed and passed during this blinded phase. The data are modeled in flat ΛCDM and wCDM cosmologies, marginalizing over 20 nuisance parameters, varying 6 (for ΛCDM) or 7 (for wCDM) cosmological parameters including the neutrino mass density and including the 457×457 element analytic covariance matrix. We find consistent cosmological results from these three two-point functions and from their combination obtain S8≡σ8(Ωm/0.3)0.5=0.773−0.020+0.026 and Ωm=0.267−0.017+0.030 for ΛCDM; for wCDM, we find S8=0.782−0.024+0.036, Ωm=0.284−0.030+0.033, and w=−0.82−0.20+0.21 at 68% C.L. The precision of these DES Y1 constraints rivals that from the Planck cosmic microwave background measurements, allowing a comparison of structure in the very early and late Universe on equal terms. Although the DES Y1 best-fit values for S8 and Ωm are lower than the central values from Planck for both ΛCDM and wCDM, the Bayes factor indicates that the DES Y1 and Planck data sets are consistent with each other in the context of ΛCDM. Combining DES Y1 with Planck, baryonic acoustic oscillation measurements from SDSS, 6dF, and BOSS and type Ia supernovae from the Joint Lightcurve Analysis data set, we derive very tight constraints on cosmological parameters: S8=0.802±0.012 and Ωm=0.298±0.007 in ΛCDM and w=−1.00−0.04+0.05 in wCDM. Upcoming Dark Energy Survey analyses will provide more stringent tests of the ΛCDM model and extensions such as a time-varying equation of state of dark energy or modified gravity.
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Objectives. The prevalence of obesity is increasing. Overweight and obese people have increased mortality compared with normal weight people. We investigated the effect of weight change on ...mortality.
Design. Prospective population study.
Setting. We utilized data from two large population‐based health studies conducted in 1984–86 and 1995–97 respectively. Cox proportional hazards models were used to calculate mortality rate ratios (RRs) with 95% confidence intervals (CIs) between people with a stable weight and people who lost or gained weight.
Subjects. Totally 20 542 men and 23 712 women aged 20 years or more, without cardiovascular disease or diabetes at the first survey and without a history of cancer at the second survey were followed up on all‐cause mortality for 5 years after the second survey.
Results. We found no association between weight gain and mortality. People who lost weight had a higher total mortality rate compared with those who were weight stable RR was 1.6 (95% CI: 1.4–1.8) in men and 1.7 (95% CI: 1.5–2.0) in women. Similar associations were found for cardiovascular and noncardiovascular mortality. Additional analysis showed a linear increase in mortality rates across categories of weight loss for both men and women (P < 0.001). There was a statistically significant interaction between weight change and initial BMI, but only amongst men (P = 0.001).
Conclusions. Weight loss, but not weight gain, was associated with increased mortality amongst men and women. Although underlying undiagnosed disease is the most plausible explanation for this finding, the similar associations found for total mortality, cardiovascular mortality, and noncardiovascular mortality makes the causal pathway somewhat enigmatic.
We report a measurement of the angular distributions of Drell-Yan dimuons produced using an 800 GeV/c proton beam on a deuterium target. The muon angular distributions in the dilepton rest frame have ...been measured over the kinematic range 4.5<m{mu mu}<15 GeV/c{2}, 0<p{T}<4 GeV/c, and 0<x{F}<0.8. No significant cos2phi dependence is found in these proton-induced Drell-Yan data, in contrast with the situation for pion-induced Drell-Yan data. The data are compared with expectations from models which attribute the cos2phi distribution to a QCD vacuum effect or to the presence of the transverse-momentum-dependent Boer-Mulders structure function h{1}{perpendicular}. Constraints on the magnitude of the sea-quark h{1}{perpendicular} structure functions are obtained.
We report a high statistics measurement of Upsilon production with an 800 GeV/c proton beam on hydrogen and deuterium targets. The dominance of the gluon-gluon fusion process for Upsilon production ...at this energy implies that the cross section ratio, sigma(p+d-->Upsilon)/2sigma(p+p-->Upsilon), is sensitive to the gluon content in the neutron relative to that in the proton. Over the kinematic region 0<x(F)<0.6, this ratio is found to be consistent with unity, in striking contrast to the behavior of the Drell-Yan cross section ratio sigma(p+d)(DY)/2sigma(p+p)(DY). This result shows that the gluon distributions in the proton and neutron are very similar. The Upsilon production cross sections are also compared with the p+d and p+Cu cross sections from earlier measurements.
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