90 research outputs found

    The Economics of Suicide: An Empirical Study

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    This study uses economic theory to investigate the impact of socioeconomic factors on the suicide rate in the United States. Using a utility maximization framework based on Hamermesh and Soss’ 1974 model, a panel data set from 2000-2010 is constructed for the 50 states and District of Columbia. This research adds to the literature in the field by focusing on the more recent past and providing additional variables consistent with today’s challenges. The results from the multiple regression analysis can be used to advocate policies that may reduce the suicide rate in the future

    The X-Ray Derived Cosmological Star Formation History and the Galaxy X-Ray Luminosity Functions in the Chandra Deep Fields North and South

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    The cosmological star formation rate in the combined Chandra Deep Fields North and South is derived from our X-Ray Luminosity Function for Galaxies in these Deep Fields. Mild evolution is seen up to redshift order unity with SFR ~ (1 + z)^{2.7}. This is the first directly observed normal star-forming galaxy X-ray luminosity function (XLF) at cosmologically interesting redshifts (z>0). This provides the most direct measure yet of the X-ray derived cosmic star-formation history of the Universe. We make use of Bayesian statistical methods to classify the galaxies and the two types of AGN, finding the most useful discriminators to be the X-ray luminosity, X-ray hardness ratio, and X-ray to optical flux ratio. There is some residual AGN contamination in the sample at the bright end of the luminosity function. Incompleteness slightly flattens the XLF at the faint end of the luminosity function. The XLF has a lognormal distribution and agrees well with the radio and infrared luminosity functions. However, the XLF does not agree with the Schechter luminosity function for the H-alpha LF indicating that additional and different physical processes may be involved in the establishment of the lognormal form of the XLF. The agreement of our star formation history points with the other star formation determinations in different wavebands (IR, Radio, H-alpha) gives an interesting constraint on the IMF, and X-rays may be measuring directly the binary star formation history of the Universe. X-ray studies will continue to be useful for probing the star formation history of the universe by avoiding problems of obscuration. Star formation may therefore be measured in more detail by deep surveys with future x-ray missions.Comment: Accepted for publication in ApJ. 19 pages with 10 figures formatted with emulateapj. Version with B/W only figures available at http://www.pha.jhu.edu/~ptak/paper

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

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    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

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

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    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

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

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

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    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

    Communicating uncertainty - how Australian television reported H1N1 risk in 2009: a content analysis

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    <p>Abstract</p> <p>Background</p> <p>Health officials face particular challenges in communicating with the public about emerging infectious diseases of unknown severity such as the 2009 H1N1(swine 'flu) pandemic (pH1N1). Statements intended to create awareness and convey the seriousness of infectious disease threats can draw accusations of scare-mongering, while officials can be accused of complacency if such statements are not made. In these communication contexts, news journalists, often reliant on official sources to understand issues are pivotal in selecting and emphasising aspects of official discourse deemed sufficiently newsworthy to present to the public. This paper presents a case-study of news communication regarding the emergence of pH1N1.</p> <p>Methods</p> <p>We conducted a content analysis of all television news items about pH1N1. We examined news and current affairs items broadcast on 5 free-to-air Sydney television channels between April 25 2009 (the first report) and October 9 (prior to the vaccine release) for statements about <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> the seriousness of the disease <abbrgrp><abbr bid="B2">2</abbr></abbrgrp> how the public could minimise contagion <abbrgrp><abbr bid="B3">3</abbr></abbrgrp> government responses to emerging information.</p> <p>Results</p> <p>pH1N1 was the leading health story for eight of 24 weeks and was in the top 5 for 20 weeks. 353 news items were identified, yielding 3086 statements for analysis, with 63.4% related to the seriousness of the situation, 12.9% providing advice for viewers and 23.6% involving assurances from government. Coverage focused on infection/mortality rates, the spread of the virus, the need for public calm, the vulnerability of particular groups, direct and indirect advice for viewers, and government reassurances about effective management.</p> <p>Conclusions</p> <p>Overall, the reporting of 2009 pH1N1 in Sydney, Australia was generally non-alarmist, while conveying that pH1N1 was potentially serious. Daily infection rate tallies and commentary on changes in the pandemic alert level were seldom contextualised to assist viewers in understanding personal relevance. Suggestions are made about how future reporting of emerging infectious diseases could be enhanced.</p

    A cost-utility analysis of cervical cancer vaccination in preadolescent Canadian females

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    <p>Abstract</p> <p>Background</p> <p>Despite the fact that approximately 70% of Canadian women undergo cervical cancer screening at least once every 3 years, approximately 1,300 women were diagnosed with cervical cancer and approximately 380 died from it in 2008. This study estimates the effectiveness and cost-effectiveness of vaccinating 12-year old Canadian females with an AS04-adjuvanted cervical cancer vaccine. The indirect effect of vaccination, via herd immunity, is also estimated.</p> <p>Methods</p> <p>A 12-health-state 1-year-cycle Markov model was developed to estimate lifetime HPV related events for a cohort of 12-year old females. Annual transition probabilities between health-states were derived from published literature and Canadian population statistics. The model was calibrated using Canadian cancer statistics. From a healthcare perspective, the cost-effectiveness of introducing a vaccine with efficacy against HPV-16/18 and evidence of cross-protection against other oncogenic HPV types was evaluated in a population undergoing current screening practices. The base-case analysis included 70% screening coverage, 75% vaccination coverage, 135/doseforvaccine,and3135/dose for vaccine, and 3% discount rate on future costs and health effects. Conservative herd immunity effects were taken into account by estimated HPV incidence using a mathematical model parameterized by reported age-stratified sexual mixing data. Sensitivity analyses were performed to address parameter uncertainties.</p> <p>Results</p> <p>Vaccinating 12-year old females (n = 100,000) was estimated to prevent between 390-633 undiscounted cervical cancer cases (reduction of 47%-77%) and 168-275 undiscounted deaths (48%-78%) over their lifetime, depending on whether or not herd immunity and cross-protection against other oncogenic HPV types were included. Vaccination was estimated to cost 18,672-$31,687 per QALY-gained, the lower range representing inclusion of cross-protective efficacy and herd immunity. The cost per QALY-gained was most sensitive to duration of vaccine protection, discount rate, and the correlation between probability of screening and probability of vaccination.</p> <p>Conclusion</p> <p>In the context of current screening patterns, vaccination of 12-year old Canadian females with an ASO4-ajuvanted cervical cancer vaccine is estimated to significantly reduce cervical cancer and mortality, and is a cost-effective option. However, the economic attractiveness of vaccination is impacted by the vaccine's duration of protection and the discount rate used in the analysis.</p

    Ebola Virus Disease in Pregnancy: Clinical, Histopathologic, and Immunohistochemical Findings.

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    Here we describe clinicopathologic features of Ebola virus disease in pregnancy. One woman infected with Sudan virus in Gulu, Uganda, in 2000 had a stillbirth and survived, and another woman infected with Bundibugyo virus had a live birth with maternal and infant death in Isiro, the Democratic Republic of the Congo in 2012. Ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemical analysis, and no antigen was seen in fetal placental stromal cells or fetal organs. In the Gulu case, ebolavirus antigen localized to malarial parasite pigment-laden macrophages. These data suggest that trophoblast infection may be a mechanism of transplacental ebolavirus transmission
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