146 research outputs found

    Maximising retention in a longitudinal study of genital Chlamydia trachomatis among young women in Australia

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    <p>Abstract</p> <p>Background</p> <p>Cohort studies are an important study design however they are difficult to implement, often suffer from poor retention, low participation and bias. The aims of this paper are to describe the methods used to recruit and retain young women in a longitudinal study and to explore factors associated with loss to follow up.</p> <p>Methods</p> <p>The Chlamydia Incidence and Re-infection Rates Study (CIRIS) was a longitudinal study of Australian women aged 16 to 25 years recruited from primary health care clinics. They were followed up via the post at three-monthly intervals and required to return questionnaires and self collected vaginal swabs for chlamydia testing. The protocol was designed to maximise retention in the study and included using recruiting staff independent of the clinic staff, recruiting in private, regular communication with study staff, making the follow up as straightforward as possible and providing incentives and small gifts to engender good will.</p> <p>Results</p> <p>The study recruited 66% of eligible women. Despite the nature of the study (sexual health) and the mobility of the women (35% moved address at least once), 79% of the women completed the final stage of the study after 12 months. Loss to follow up bias was associated with lower education level [adjusted hazard ratio (AHR): 0.7 (95% Confidence Interval (CI): 0.5, 1.0)], recruitment from a sexual health centre as opposed to a general practice clinic [AHR: 1.6 (95% CI: 1.0, 2.7)] and previously testing positive for chlamydia [AHR: 0.8 (95% CI: 0.5, 1.0)]. No other factors such as age, numbers of sexual partners were associated with loss to follow up.</p> <p>Conclusions</p> <p>The methods used were considered effective for recruiting and retaining women in the study. Further research is needed to improve participation from less well-educated women.</p

    Maximising retention in a longitudinal study of genital Chlamydia trachomatis among young women in Australia

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Cohort studies are an important study design however they are difficult to implement, often suffer from poor retention, low participation and bias. The aims of this paper are to describe the methods used to recruit and retain young women in a longitudinal study and to explore factors associated with loss to follow up.</p> <p>Methods</p> <p>The Chlamydia Incidence and Re-infection Rates Study (CIRIS) was a longitudinal study of Australian women aged 16 to 25 years recruited from primary health care clinics. They were followed up via the post at three-monthly intervals and required to return questionnaires and self collected vaginal swabs for chlamydia testing. The protocol was designed to maximise retention in the study and included using recruiting staff independent of the clinic staff, recruiting in private, regular communication with study staff, making the follow up as straightforward as possible and providing incentives and small gifts to engender good will.</p> <p>Results</p> <p>The study recruited 66% of eligible women. Despite the nature of the study (sexual health) and the mobility of the women (35% moved address at least once), 79% of the women completed the final stage of the study after 12 months. Loss to follow up bias was associated with lower education level [adjusted hazard ratio (AHR): 0.7 (95% Confidence Interval (CI): 0.5, 1.0)], recruitment from a sexual health centre as opposed to a general practice clinic [AHR: 1.6 (95% CI: 1.0, 2.7)] and previously testing positive for chlamydia [AHR: 0.8 (95% CI: 0.5, 1.0)]. No other factors such as age, numbers of sexual partners were associated with loss to follow up.</p> <p>Conclusions</p> <p>The methods used were considered effective for recruiting and retaining women in the study. Further research is needed to improve participation from less well-educated women.</p

    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

    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

    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

    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

    Setting research priorities to improve global newborn health and prevent stillbirths by 2025.

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    BACKGROUND: In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. METHODS: We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. RESULTS: Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. CONCLUSION: These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed

    The interpretations and uses of fitness landscapes in the social sciences

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    __Abstract__ This working paper precedes our full article entitled “The evolution of Wright’s (1932) adaptive field to contemporary interpretations and uses of fitness landscapes in the social sciences” as published in the journal Biology & Philosophy (http://link.springer.com/article/10.1007/s10539-014-9450-2). The working paper features an extended literature overview of the ways in which fitness landscapes have been interpreted and used in the social sciences, for which there was not enough space in the full article. The article features an in-depth philosophical discussion about the added value of the various ways in which fitness landscapes are used in the social sciences. This discussion is absent in the current working paper. Th

    Setting research priorities to improve global newborn health and prevent stillbirths by 2025

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    Background In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. Methods We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. Results Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. Conclusion These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed

    Host galaxy identification for supernova surveys

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    Host galaxy identification is a crucial step for modern supernova (SN) surveys such as the Dark Energy Survey (DES) and the Large Synoptic Survey Telescope (LSST), which will discover SNe by the thousands. Spectroscopic resources are limited, so in the absence of real-time SN spectra these surveys must rely on host galaxy spectra to obtain accurate redshifts for the Hubble diagram and to improve photometric classification of SNe. In addition, SN luminosities are known to correlate with host-galaxy properties. Therefore, reliable identification of host galaxies is essential for cosmology and SN science. We simulate SN events and their locations within their host galaxies to develop and test methods for matching SNe to their hosts. We use both real and simulated galaxy catalog data from the Advanced Camera for Surveys General Catalog and MICECATv2.0, respectively. We also incorporate "hostless" SNe residing in undetected faint hosts into our analysis, with an assumed hostless rate of 5%. Our fully automated algorithm is run on catalog data and matches SNe to their hosts with 91% accuracy. We find that including a machine learning component, run after the initial matching algorithm, improves the accuracy (purity) of the matching to 97% with a 2% cost in efficiency (true positive rate). Although the exact results are dependent on the details of the survey and the galaxy catalogs used, the method of identifying host galaxies we outline here can be applied to any transient survey
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