The HELLAS2XMM survey. V. Near-Infrared observations of X-ray sources with extreme X/O ratios

We present the results of deep near-infrared observations of 11 hard X-ray selected sources in the Hellas2XMM survey, with faint optical magnitude (R>24) and high X-ray-to-optical flux ratio. All but one of the sources have been detected in the Ks band, with bright counterparts (Ks<19) and red colors (R-K>5), and therefore belong to the ERO population. A detailed analysis of the surface brightness profiles allows us to classify all of the NIR counterparts. There are 2 point-like objects, 7 elliptical galaxies and one source with a disky profile. None of the extended sources shows any evidence for the presence of a central unresolved object tracing the putative X-ray emitting AGN. Using both the R-K colors and the morphological information, we have estimated for all the sources a ``minimum photometric redshift'', ranging between 0.8 and 2.4; the elliptical hosts have zmin=0.9-1.4. We computed the X-ray properties using these redshifts: most of the sources have NH>10^{22}, with unabsorbed X-ray luminosities up to 10^{45}erg s^{-1}. These objects therefore belong to the population of obscured (Type II) quasars and, from a statistical point of view, they turn out to be a non-negligible fraction (~10%) of the most luminous AGN. Selecting the high X/O sources for a follow-up study in the NIR is therefore a powerful technique aimed at studying at high redshift the hosts of Type II AGN. Overall, our results seem to indicate that the hosts are mostly elliptical galaxies at z~1, and that these near-IR bright objects would be among the most massive spheroids at these epochs.Comment: 15 pages, 8 figures. Accepted for publication in A&A. V2: minor typos correcte

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

The XXL Survey: VI. The 1000 brightest X-ray point sources

X-ray extragalactic surveys are ideal laboratories for the study of the evolution and clustering of active galactic nuclei (AGN). The XXL Survey spans two fields of a combined 50 $deg^2$ observed for more than 6Ms with XMM-Newton, occupying the parameter space between deep surveys and very wide area surveys; at the same time it benefits from a wealth of ancillary data. This paper marks the first release of the XXL point source catalogue selected in the 2-10 keV energy band with limiting flux $F_{2-10keV}=4.8\cdot10^{-14}\rm{erg\,s^{-1}\,cm^{-2}}$. We use both public and proprietary data sets to identify the counterparts of the X-ray point-like sources and improved upon the photometric redshift determination for AGN by applying a Random Forest classification trained to identify for each object the optimal photometric redshift model library. We also assign a probability to each source to be a star or an outlier. We model with Bayesian analysis the X-ray spectra assuming a power-law model with the presence of an absorbing medium. We find an average unabsorbed photon index of $\Gamma=1.85$ and average hydrogen column density $\log{N_{H}}=21.07 cm^{-2}$. We find no trend of $\Gamma$ or $N_H$ with redshift and a fraction of 26% absorbed sources ($\log N_{H}>22$). We show that the XXL-1000-AGN number counts extended the number counts of the COSMOS survey to higher fluxes and are fully consistent with the Euclidean expectation. We constrain the intrinsic luminosity function of AGN in the 2-10 keV energy band where the unabsorbed X-ray flux is estimated from the X-ray spectral fit up to z=3. Finally, we demonstrate the presence of a supercluster size structure at redshift 0.14, identified by means of percolation analysis of the XXL-1000-AGN sample. The XXL survey, reaching a medium flux limit and covering a wide area is a stepping stone between current deep fields and planned wide area surveys

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Mutation of HIV-1 Genomes in a Clinical Population Treated with the Mutagenic Nucleoside KP1461

The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first “mechanism validation” phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered. A large number (N = 105 per sample) of sequences were analyzed, each derived from individual HIV-1 RNA templates, after 0, 56 and 124 days of therapy from 10 treated and 10 untreated control individuals (>7.1 million base pairs of unique viral templates were sequenced). We found that private mutations, those not found in more than one viral sequence and likely to have occurred in the most recent rounds of replication, increased in treated individuals relative to controls after 56 (p = 0.038) and 124 (p = 0.002) days of drug treatment. The spectrum of mutations observed in the treated group showed an excess of A to G and G to A mutations (p = 0.01), and to a lesser extent T to C and C to T mutations (p = 0.09), as predicted by the mechanism of action of the drug. These results validate the proposed mechanism of action in humans and should spur development of this novel antiretroviral approach.Koronis Pharmaceutical

Portraying the nature of corruption: Using an explorative case-study design

What is the nature of corruption in Western democracies? To answer this research question, the authors study 10 Dutch corruption cases in depth, looking at confidential criminal files. The cases allow them to sketch a general profile of a corruption case. The authors offer nine propositions to portray the nature of corruption. They conclude that corruption usually takes place within enduring relationships, that the process of becoming corrupt can be characterized as a slippery slope, and that important motives for corruption, aside from material gain, include friendship or love, status, and the desire to impress others. The explorative multiple case study methodology helps to expand our understanding of the way in which officials become corrupt. © 2008 The American Society for Public Administration

Family physicians\u27 professional identity formation: a study protocol to explore impression management processes in institutional academic contexts.

BACKGROUND: Despite significant differences in terms of medical training and health care context, the phenomenon of medical students\u27 declining interest in family medicine has been well documented in North America and in many other developed countries as well. As part of a research program on family physicians\u27 professional identity formation initiated in 2007, the purpose of the present investigation is to examine in-depth how family physicians construct their professional image in academic contexts; in other words, this study will allow us to identify and understand the processes whereby family physicians with an academic appointment seek to control the ideas others form about them as a professional group, i.e. impression management. METHODS/DESIGN: The methodology consists of a multiple case study embedded in the perspective of institutional theory. Four international cases from Canada, France, Ireland and Spain will be conducted; the \u22case\u22 is the medical school. Four levels of analysis will be considered: individual family physicians, interpersonal relationships, family physician professional group, and organization (medical school). Individual interviews and focus groups with academic family physicians will constitute the main technique for data generation, which will be complemented with a variety of documentary sources. Discourse techniques, more particularly rhetorical analysis, will be used to analyze the data gathered. Within- and cross-case analysis will then be performed. DISCUSSION: This empirical study is strongly grounded in theory and will contribute to the scant body of literature on family physicians\u27 professional identity formation processes in medical schools. Findings will potentially have important implications for the practice of family medicine, medical education and health and educational policies