694 research outputs found

    Kaptive Web: User-Friendly Capsule and Lipopolysaccharide Serotype Prediction for Klebsiella Genomes.

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    As whole-genome sequencing becomes an established component of the microbiologist's toolbox, it is imperative that researchers, clinical microbiologists, and public health professionals have access to genomic analysis tools for the rapid extraction of epidemiologically and clinically relevant information. For the Gram-negative hospital pathogens such as Klebsiella pneumoniae, initial efforts have focused on the detection and surveillance of antimicrobial resistance genes and clones. However, with the resurgence of interest in alternative infection control strategies targeting Klebsiella surface polysaccharides, the ability to extract information about these antigens is increasingly important. Here we present Kaptive Web, an online tool for the rapid typing of Klebsiella K and O loci, which encode the polysaccharide capsule and lipopolysaccharide O antigen, respectively. Kaptive Web enables users to upload and analyze genome assemblies in a web browser. The results can be downloaded in tabular format or explored in detail via the graphical interface, making it accessible for users at all levels of computational expertise. We demonstrate Kaptive Web's utility by analyzing >500 K. pneumoniae genomes. We identify extensive K and O locus diversity among 201 genomes belonging to the carbapenemase-associated clonal group 258 (25 K and 6 O loci). The characterization of a further 309 genomes indicated that such diversity is common among the multidrug-resistant clones and that these loci represent useful epidemiological markers for strain subtyping. These findings reinforce the need for rapid, reliable, and accessible typing methods such as Kaptive Web. Kaptive Web is available for use at http://kaptive.holtlab.net/, and the source code is available at https://github.com/kelwyres/Kaptive-Web

    A Deep Chandra ACIS Study of NGC 4151. III. the Line Emission and Spectral Analysis of the Ionization Cone

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    This paper is the third in a series in which we present deep Chandra ACIS-S imaging spectroscopy of the Seyfert 1 galaxy NGC 4151, devoted to study its complex circum-nuclear X-ray emission. Emission features in the soft X-ray spectrum of the bright extended emission (L[0.3-2keV]~10^40 erg/s) at r>130 pc (2") are consistent with the brighter OVII, OVIII, and NeIX lines seen in the Chandra HETGS and XMM-Newton RGS spectra below 2 keV. We construct emission line images of these features and find good morphological correlations with the narrow line region clouds mapped in [OIII]5007A. Self-consistent photoionization models provide good descriptions of the spectra of the large scale emission, as well as resolved structures, supporting the dominant role of nuclear photoionization, although displacement of optical and X-ray features implies a more complex medium. Collisionally ionized emission is estimated to be <12% of the extended emission. Presence of both low and high ionization spectral components and extended emission in the X-ray image perpendicular to the bicone indicates leakage of nuclear ionization, likely filtered through warm absorbers, instead of being blocked by a continuous obscuring torus. The ratios of [OIII]/soft X-ray flux are approximately constant (~15) for the 1.5 kpc radius spanned by these measurements, indicating a relatively constant ionization parameter, consistent with the photoionized outflow of a wind-like density profile. Using spatially resolved features, we estimate that the mass outflow rate in NGC 4151 is ~2Msun/yr at 130 pc and the kinematic power of the ionized outflow is 1.7x10^41 erg/s, approximately 0.3% of the bolometric luminosity of NGC 4151.Comment: 45 pages. 18 figures. Accepted to Ap

    Outside options: another reason to choose the first-price auction

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    Pre-print draft dated October 2005. Final version published by Elsevier; available online at http://www.sciencedirect.com/In this paper we study equilibrium and experimental bidding behaviour in first-price and second-price auctions with outside options. We find that bidders do respond to outside options and to variations of common knowledge about competitors’ outside options. However, overbidding in first-price auctions is significantly higher with outside options than without. First-price auctions yield more revenue than second-price auctions. This revenue-premium is significantly higher with outside options. In second-price auctions the introduction of outside options has only a small effect

    Whole genome sequencing data used for surveillance of Campylobacter infections:detection of a large continuous outbreak, Denmark, 2019

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    BACKGROUND: Campylobacter is one of the most frequent causes of bacterial gastroenteritis. Campylobacter outbreaks are rarely reported, which could be a reflection of a surveillance without routine molecular typing. We have previously shown that numerous small outbreak-like clusters can be detected when whole genome sequencing (WGS) data of clinical Campylobacter isolates was applied. AIM: Typing-based surveillance of Campylobacter infections was initiated in 2019 to enable detection of large clusters of clinical isolates and to match them to concurrent retail chicken isolates in order to react on ongoing outbreaks. METHODS: We performed WGS continuously on isolates from cases (n = 701) and chicken meat (n = 164) throughout 2019. Core genome multilocus sequence typing was used to detect clusters of clinical isolates and match them to isolates from chicken meat. RESULTS: Seventy-two clusters were detected, 58 small clusters (2–4 cases) and 14 large clusters (5–91 cases). One third of the clinical isolates matched isolates from chicken meat. One large cluster persisted throughout the whole year and represented 12% of all studied Campylobacter cases. This cluster type was detected in several chicken samples and was traced back to one slaughterhouse, where interventions were implemented to control the outbreak. CONCLUSION: Our WGS-based surveillance has contributed to an improved understanding of the dynamics of the occurrence of Campylobacter strains in chicken meat and the correlation to clusters of human cases

    Whole-Genome Sequencing to Detect Numerous Campylobacter jejuni Outbreaks and Match Patient Isolates to Sources, Denmark, 2015-2017

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    Whole-Genome Sequencing to Detect Numerous Campylobacter jejuni Outbreaks and Match Patient Isolates to Sources, Denmark, 2015–2017 Scientific publication financially supported by ORION/One Health European Joint Programme (grant agreement nos. 773830)

    Autism and the right to education in the EU: policy mapping and scoping review of Nordic countries Denmark, Finland, and Sweden.

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    Introduction:The universal right to education for people with disabilities has been highlighted by the Universal Declaration on Human Rights and the Convention on the Rights of Persons with Disabilities. In this paper, we mapped policies addressing the right to education and special education needs of autistic children in Denmark, Sweden, and Finland. Methods:A policy path analysis was carried out using a scoping review as an underlying framework for data gathering. Policy mapping was performed independently by both lead authors to increase reliability. Results and discussion:The values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities have been closely translated into the respective education systems of the countries under study, offering special education needs services and support in mainstream education with the aim of including as many children into mainstream education as possible. Even though the education systems are comparable, the approaches between the countries under study are slightly different. Denmark and Sweden have passed several policies specifically geared towards special education needs, while Finland incorporates this more in general education policy. Conclusion:All countries under study have incorporated the values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities in their respective education systems while emphasising the need to include as many children in the mainstream system as possible

    The diversity of Klebsiella pneumoniae surface polysaccharides.

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    Klebsiella pneumoniae is considered an urgent health concern due to the emergence of multi-drug-resistant strains for which vaccination offers a potential remedy. Vaccines based on surface polysaccharides are highly promising but need to address the high diversity of surface-exposed polysaccharides, synthesized as O-antigens (lipopolysaccharide, LPS) and K-antigens (capsule polysaccharide, CPS), present in K. pneumoniae. We present a comprehensive and clinically relevant study of the diversity of O- and K-antigen biosynthesis gene clusters across a global collection of over 500 K. pneumoniae whole-genome sequences and the seroepidemiology of human isolates from different infection types. Our study defines the genetic diversity of O- and K-antigen biosynthesis cluster sequences across this collection, identifying sequences for known serotypes as well as identifying novel LPS and CPS gene clusters found in circulating contemporary isolates. Serotypes O1, O2 and O3 were most prevalent in our sample set, accounting for approximately 80 % of all infections. In contrast, K serotypes showed an order of magnitude higher diversity and differ among infection types. In addition we investigated a potential association of O or K serotypes with phylogenetic lineage, infection type and the presence of known virulence genes. K1 and K2 serotypes, which are associated with hypervirulent K. pneumoniae, were associated with a higher abundance of virulence genes and more diverse O serotypes compared to other common K serotypes

    Dissecting the heterogeneous cortical anatomy of autism spectrum disorder using normative models

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    International audienceBACKGROUNDThe neuroanatomical basis of autism spectrum disorder (ASD) has remained elusive, mostly owing to high biological and clinical heterogeneity among diagnosed individuals. Despite considerable effort toward understanding ASD using neuroimaging biomarkers, heterogeneity remains a barrier, partly because studies mostly employ case-control approaches, which assume that the clinical group is homogeneous.METHODS:Here, we used an innovative normative modeling approach to parse biological heterogeneity in ASD. We aimed to dissect the neuroanatomy of ASD by mapping the deviations from a typical pattern of neuroanatomical development at the level of the individual and to show the necessity to look beyond the case-control paradigm to understand the neurobiology of ASD. We first estimated a vertexwise normative model of cortical thickness development using Gaussian process regression, then mapped the deviation of each participant from the typical pattern. For this, we employed a heterogeneous cross-sectional sample of 206 typically developing individuals (127 males) and 321 individuals with ASD (232 males) (6-31 years of age).RESULTS:We found few case-control differences, but the ASD cohort showed highly individualized patterns of deviations in cortical thickness that were widespread across the brain. These deviations correlated with severity of repetitive behaviors and social communicative symptoms, although only repetitive behaviors survived corrections for multiple testing.CONCLUSIONS:Our results 1) reinforce the notion that individuals with ASD show distinct, highly individualized trajectories of brain development and 2) show that by focusing on common effects (i.e., the "average ASD participant"), the case-control approach disguises considerable interindividual variation crucial for precision medicine

    Gray matter covariations and core symptoms of autism: the EU-AIMS Longitudinal European Autism Project.

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    BACKGROUND: Voxel-based morphometry (VBM) studies in autism spectrum disorder (autism) have yielded diverging results. This might partly be attributed to structural alterations being associating with the combined influence of several regions rather than with a single region. Further, these structural covariation differences may relate to continuous measures of autism rather than with categorical case-control contrasts. The current study aimed to identify structural covariation alterations in autism, and assessed canonical correlations between brain covariation patterns and core autism symptoms. METHODS: We studied 347 individuals with autism and 252 typically developing individuals, aged between 6 and 30 years, who have been deeply phenotyped in the Longitudinal European Autism Project. All participants' VBM maps were decomposed into spatially independent components using independent component analysis. A generalized linear model (GLM) was used to examine case-control differences. Next, canonical correlation analysis (CCA) was performed to separately explore the integrated effects between all the brain sources of gray matter variation and two sets of core autism symptoms. RESULTS: GLM analyses showed significant case-control differences for two independent components. The first component was primarily associated with decreased density of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and increased density of caudate nucleus in the autism group relative to typically developing individuals. The second component was related to decreased densities of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to typically developing individuals. The CCA results showed significant correlations between components that involved variation of thalamus, putamen, precentral gyrus, frontal, parietal, and occipital lobes, and the cerebellum, and repetitive, rigid and stereotyped behaviors and abnormal sensory behaviors in autism individuals. LIMITATIONS: Only 55.9% of the participants with autism had complete questionnaire data on continuous parent-reported symptom measures. CONCLUSIONS: Covaried areas associated with autism diagnosis and/or symptoms are scattered across the whole brain and include the limbic system, basal ganglia, thalamus, cerebellum, precentral gyrus, and parts of the frontal, parietal, and occipital lobes. Some of these areas potentially subserve social-communicative behavior, whereas others may underpin sensory processing and integration, and motor behavior
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