105 research outputs found

    Towards comprehensive understanding of bacterial genetic diversity:large-scale amplifications in Bordetella pertussis and Mycobacterium tuberculosis

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    Bacterial genetic diversity is often described solely using base-pair changes despite a wide variety of other mutation types likely being major contributors. Tandem duplication/amplifications are thought to be widespread among bacteria but due to their often-intractable size and instability, comprehensive studies of these mutations are rare. We define a methodology to investigate amplifications in bacterial genomes based on read depth of genome sequence data as a proxy for copy number. We demonstrate the approach with Bordetella pertussis , whose insertion sequence element-rich genome provides extensive scope for amplifications to occur. Analysis of data for 2430 B. pertussis isolates identified 272 putative amplifications, of which 94 % were located at 11 hotspot loci. We demonstrate limited phylogenetic connection for the occurrence of amplifications, suggesting unstable and sporadic characteristics. Genome instability was further described in vitro using long-read sequencing via the Nanopore platform, which revealed that clonally derived laboratory cultures produced heterogenous populations rapidly. We extended this research to analyse a population of 1000 isolates of another important pathogen, Mycobacterium tuberculosis . We found 590 amplifications in M. tuberculosis , and like B. pertussis , these occurred primarily at hotspots. Genes amplified in B. pertussis include those involved in motility and respiration, whilst in M. tuberuclosis, functions included intracellular growth and regulation of virulence. Using publicly available short-read data we predicted previously unrecognized, large amplifications in B. pertussis and M. tuberculosis . This reveals the unrecognized and dynamic genetic diversity of B. pertussis and M. tuberculosis , highlighting the need for a more holistic understanding of bacterial genetics

    Planck intermediate results: XVI. Profile likelihoods for cosmological parameters

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    We explore the 2013 Planck likelihood function with a high-precision multi-dimensional minimizer (Minuit). This allows a refinement of the ΛCDM best-fit solution with respect to previously-released results, and the construction of frequentist confidence intervals using profile likelihoods. The agreement with the cosmological results from the Bayesian framework is excellent, demonstrating the robustness of the Planck results to the statistical methodology. We investigate the inclusion of neutrino masses, where more significant differences may appear due to the non-Gaussian nature of the posterior mass distribution. By applying the Feldman-Cousins prescription, we again obtain results very similar to those of the Bayesian methodology. However, the profile-likelihood analysis of the cosmic microwave background (CMB) combination (Planck+WP+highL) reveals a minimum well within the unphysical negative-mass region. We show that inclusion of the Planck CMB-lensing information regularizes this issue, and provide a robust frequentist upper limit ∑ mν ≤ 0.26 eV (95% confidence) from the CMB+lensing+BAO data combination. Reproduced with permission from Astronomy & Astrophysics, © ESO 201

    Planck intermediate results. XIX. An overview of the polarized thermal emission from Galactic dust

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    This paper presents an overview of the polarized sky as seen by Planck HFI at 353 GHz, which is the most sensitive Planck channel for dust polarization. We construct and analyse maps of dust polarization fraction and polarization angle at 1° resolution, taking into account noise bias and possible systematic effects. The sensitivity of the Planck HFI polarization measurements allows for the first time a mapping of Galactic dust polarized emission on large scales, including low column density regions. We find that the maximum observed dust polarization fraction is high (pmax = 19.8%), in particular in some regions of moderate hydrogen column density (NH < 2 × 1021 cm-2). The polarization fraction displays a large scatter at NH below a few 1021 cm-2. There is a general decrease in the dust polarization fraction with increasing column density above NH ≃ 1 × 1021 cm-2 and in particular a sharp drop above NH ≃ 1.5 × 1022 cm-2. We characterize the spatial structure of the polarization angle using the angle dispersion function. We find that the polarization angle is ordered over extended areas of several square degrees, separated by filamentary structures of high angle dispersion function. These appear as interfaces where the sky projection of the magnetic field changes abruptly without variations in the column density. The polarization fraction is found to be anti-correlated with the dispersion of polarization angles. These results suggest that, at the resolution of 1°, depolarization is due mainly to fluctuations in the magnetic field orientation along the line of sight, rather than to the loss of grain alignment in shielded regions. We also compare the polarization of thermal dust emission with that of synchrotron measured with Planck, low-frequency radio data, and Faraday rotation measurements toward extragalactic sources. These components bear resemblance along the Galactic plane and in some regions such as the Fan and North Polar Spur regions. The poor match observed in other regions shows, however, that dust, cosmic-ray electrons, and thermal electrons generally sample different parts of the line of sight. Reproduced with permission, © ESO, 201

    Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed, transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomised, phase 3 trial

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    The prevention of psychopathology in African Americans: An epidemiologic perspective

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    Although improving the mental health status of African Americans is an important goal, it is not clear that this can be accomplished by increasing access to professional services. Many have argued that stressful social conditions are the major cause of mental disorder in blacks and thus, psychopathology can be prevented by eliminating racism, oppression and poor economic conditions. This review argues that while the notion of primary prevention with African Americans should be taken seriously, there is still a need for more and better epidemiologic research. Three bodies of knowledge relevant to black mental health are addressed: 1) the need for an epidemiologic knowledge base for prevention; 2) coping capacity and vulnerability to stress; 3) risk factor identification. Findings from a national survey of adult African Americans are presented as an example of risk factor identification for the purpose of specifying targets for preventive interventions. The paper concludes that before the prevention of psychopathology in black populations can be achieved, a number of measurement, theoretical and policy issues must be addressed. Specific directions for future research are outlined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44304/1/10597_2004_Article_BF00752393.pd

    Planck intermediate results. XV. A study of anomalous microwave emission in Galactic clouds

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    Anomalous microwave emission (AME) is believed to be due to electric dipole radiation from small spinning dust grains. The aim of this paper is a statistical study of the basic properties of AME regions and the environment in which they emit. We used WMAP and Planck maps, combined with ancillary radio and IR data, to construct a sample of 98 candidate AME sources, assembling SEDs for each source using aperture photometry on 1°-smoothed maps from 0.408 GHz up to 3000 GHz. Each spectrum is fitted with a simple model of free-free, synchrotron (where necessary), cosmic microwave background (CMB), thermal dust, and spinning dust components. We find that 42 of the 98 sources have significant (>5σ) excess emission at frequencies between 20 and 60 GHz. An analysis of the potential contribution of optically thick free-free emission from ultra-compact H ii regions, using IR colour criteria, reduces the significant AME sample to 27 regions. The spectrum of the AME is consistent with model spectra of spinning dust. Peak frequencies are in the range 20−35 GHz except for the California nebula (NGC 1499), which appears to have a high spinning dust peak frequency of (50 ± 17) GHz. The AME regions tend to be more spatially extended than regions with little or no AME. The AME intensity is strongly correlated with the sub-millimetre/IR flux densities and comparable to previous AME detections in the literature. AME emissivity, defined as the ratio of AME to dust optical depth, varies by an order of magnitude for the AME regions. The AME regions tend to be associated with cooler dust in the range 14−20 K and an average emissivity index, βd, of +1.8, while the non-AME regions are typically warmer, at 20−27 K. In agreement with previous studies, the AME emissivity appears to decrease with increasing column density. This supports the idea of AME originating from small grains that are known to be depleted in dense regions, probably due to coagulation onto larger grains. We also find a correlation between the AME emissivity (and to a lesser degree the spinning dust peak frequency) and the intensity of the interstellar radiation field, G0. Modelling of this trend suggests that both radiative and collisional excitation are important for the spinning dust emission. The most significant AME regions tend to have relatively less ionized gas (free-free emission), although this could be a selection effect. The infrared excess, a measure of the heating of dust associated with H ii regions, is typically >4 for AME sources, indicating that the dust is not primarily heated by hot OB stars. The AME regions are associated with known dark nebulae and have higher 12 μm/25 μm ratios. The emerging picture is that the bulk of the AME is coming from the polycyclic aromatic hydrocarbons and small dust grains from the colder neutral interstellar medium phase. Reproduced with permission from Astronomy & Astrophysics, © ESO 201

    High-Impact Extratropical Cyclones along the Northeast Coast of the United States in a Long Coupled Climate Model Simulation

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    High-impact extratropical cyclones (ETCs) cause considerable damage along the northeast coast of the United States through strong winds and inundation, but these relatively rare events are difficult to analyze owing to limited historical records. Using a 1505-yr simulation from the GFDL FLOR coupled model, statistical analyses of extreme events are performed including exceedance probability computations to compare estimates from shorter segments to estimates that could be obtained from a record of considerable length. The most extreme events possess characteristics including exceptionally low central pressure, hurricane-force winds, and a large surge potential, which would greatly impact nearby regions. Return level estimates of metrics of ETC intensity using shorter, historical-length segments of the FLOR simulation are underestimated compared to levels determined using the full simulation. This indicates that if the underlying distributions of observed ETC metrics are similar to those of the 1505-yr FLOR distributions, the actual frequency of extreme ETC events could also be underestimated. Comparisons between FLOR and reanalysis products suggest that not all features of simulated high-impact ETCs are representative of observations. Spatial track densities are similar, but FLOR exhibits a negative bias in central pressure and a positive bias in wind speed, particularly for more intense events. Although the existence of these model biases precludes the quantitative use of model-derived return statistics as a substitute for those derived from shorter observational records, this work suggests that statistics from future models of higher fidelity could be used to better constrain the probability of extreme ETC events and their impacts
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