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61.
62.
Kathryn Whetten Kristen Shirey Brian Wells Pence Jia Yao Nathan Thielman Rachel Whetten Julie Adams Bernard Agala Jan Ostermann Karen O'Donnell Amy Hobbie Venance Maro Dafrosa Itemba Elizabeth Reddy for the CHAT Research Team 《PloS one》2013,8(10)
Background
As antiretroviral therapy (ART) for HIV becomes increasingly available in low and middle income countries (LMICs), understanding reasons for lack of adherence is critical to stemming the tide of infections and improving health. Understanding the effect of psychosocial experiences and mental health symptomatology on ART adherence can help maximize the benefit of expanded ART programs by indicating types of services, which could be offered in combination with HIV care.Methodology
The Coping with HIV/AIDS in Tanzania (CHAT) study is a longitudinal cohort study in the Kilimanjaro Region that included randomly selected HIV-infected (HIV+) participants from two local hospital-based HIV clinics and four free-standing voluntary HIV counselling and testing sites. Baseline data were collected in 2008 and 2009; this paper used data from 36 month follow-up interviews (N = 468). Regression analyses were used to predict factors associated with incomplete self-reported adherence to ART.Results
Incomplete ART adherence was significantly more likely to be reported amongst participants who experienced a greater number of childhood traumatic events: sexual abuse prior to puberty and the death in childhood of an immediate family member not from suicide or homicide were significantly more likely in the non-adherent group and other negative childhood events trended toward being more likely. Those with incomplete adherence had higher depressive symptom severity and post-traumatic stress disorder (PTSD). In multivariable analyses, childhood trauma, depression, and financial sacrifice remained associated with incomplete adherence.Discussion
This is the first study to examine the effect of childhood trauma, depression and PTSD on HIV medication adherence in a low income country facing a significant burden of HIV. Allocating spending on HIV/AIDS toward integrating mental health services with HIV care is essential to the creation of systems that enhance medication adherence and maximize the potential of expanded antiretroviral access to improve health and reduce new infections. 相似文献63.
Rachel Heyard Jean-François Timsit Leonhard Held COMBACTE-MAGNET consortium 《Biometrical journal. Biometrische Zeitschrift》2020,62(3):643-657
Clinical prediction models play a key role in risk stratification, therapy assignment and many other fields of medical decision making. Before they can enter clinical practice, their usefulness has to be demonstrated using systematic validation. Methods to assess their predictive performance have been proposed for continuous, binary, and time-to-event outcomes, but the literature on validation methods for discrete time-to-event models with competing risks is sparse. The present paper tries to fill this gap and proposes new methodology to quantify discrimination, calibration, and prediction error (PE) for discrete time-to-event outcomes in the presence of competing risks. In our case study, the goal was to predict the risk of ventilator-associated pneumonia (VAP) attributed to Pseudomonas aeruginosa in intensive care units (ICUs). Competing events are extubation, death, and VAP due to other bacteria. The aim of this application is to validate complex prediction models developed in previous work on more recently available validation data. 相似文献
64.
65.
Resolving the polymorphism-in-probe problem is critical for correct interpretation of expression QTL studies 总被引:1,自引:0,他引:1
Adaikalavan Ramasamy Daniah Trabzuni J. Raphael Gibbs Allissa Dillman Dena G. Hernandez Sampath Arepalli Robert Walker Colin Smith Gigaloluwa Peter Ilori Andrey A. Shabalin Yun Li Andrew B. Singleton Mark R. Cookson for NABEC John Hardy for UKBEC Mina Ryten Michael E. Weale 《Nucleic acids research》2013,41(7):e88
66.
Michael?R. Knowles Margaret?W. Leigh Lawrence?E. Ostrowski Lu Huang Johnny?L. Carson Milan?J. Hazucha Weining Yin Jonathan?S. Berg Stephanie?D. Davis Sharon?D. Dell Thomas?W. Ferkol Margaret Rosenfeld Scott?D. Sagel Carlos?E. Milla Kenneth?N. Olivier Emily?H. Turner Alexandra?P. Lewis Michael?J. Bamshad Deborah?A. Nickerson Jay Shendure Maimoona?A. Zariwala the Genetic Disorders of Mucociliary Clearance?Consortium 《American journal of human genetics》2013,92(1):99-106
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 14 genes, but they collectively account for only ∼60% of all PCD. To identify mutations that cause PCD, we performed exome sequencing on six unrelated probands with ciliary outer dynein arm (ODA) defects. Mutations in CCDC114, an ortholog of the Chlamydomonas reinhardtii motility gene DCC2, were identified in a family with two affected siblings. Sanger sequencing of 67 additional individuals with PCD with ODA defects from 58 families revealed CCDC114 mutations in 4 individuals in 3 families. All 6 individuals with CCDC114 mutations had characteristic oto-sino-pulmonary disease, but none had situs abnormalities. In the remaining 5 individuals with PCD who underwent exome sequencing, we identified mutations in two genes (DNAI2, DNAH5) known to cause PCD, including an Ashkenazi Jewish founder mutation in DNAI2. These results revealed that mutations in CCDC114 are a cause of ciliary dysmotility and PCD and further demonstrate the utility of exome sequencing to identify genetic causes in heterogeneous recessive disorders. 相似文献
67.
Elin Grundberg Eshwar Meduri Johanna?K. Sandling ?sa?K. Hedman Sarah Keildson Alfonso Buil Stephan Busche Wei Yuan James Nisbet Magdalena Sekowska Alicja Wilk Amy Barrett Kerrin?S. Small Bing Ge Maxime Caron So-Youn Shin the Multiple Tissue Human Expression Resource Consortium Mark Lathrop Emmanouil T. Dermitzakis Mark I. McCarthy Timothy D. Spector Jordana T. Bell Panos Deloukas 《American journal of human genetics》2013,93(5):876-890
Epigenetic modifications such as DNA methylation play a key role in gene regulation and disease susceptibility. However, little is known about the genome-wide frequency, localization, and function of methylation variation and how it is regulated by genetic and environmental factors. We utilized the Multiple Tissue Human Expression Resource (MuTHER) and generated Illumina 450K adipose methylome data from 648 twins. We found that individual CpGs had low variance and that variability was suppressed in promoters. We noted that DNA methylation variation was highly heritable (h2median = 0.34) and that shared environmental effects correlated with metabolic phenotype-associated CpGs. Analysis of methylation quantitative-trait loci (metQTL) revealed that 28% of CpGs were associated with nearby SNPs, and when overlapping them with adipose expression quantitative-trait loci (eQTL) from the same individuals, we found that 6% of the loci played a role in regulating both gene expression and DNA methylation. These associations were bidirectional, but there were pronounced negative associations for promoter CpGs. Integration of metQTL with adipose reference epigenomes and disease associations revealed significant enrichment of metQTL overlapping metabolic-trait or disease loci in enhancers (the strongest effects were for high-density lipoprotein cholesterol and body mass index [BMI]). We followed up with the BMI SNP rs713586, a cg01884057 metQTL that overlaps an enhancer upstream of ADCY3, and used bisulphite sequencing to refine this region. Our results showed widespread population invariability yet sequence dependence on adipose DNA methylation but that incorporating maps of regulatory elements aid in linking CpG variation to gene regulation and disease risk in a tissue-dependent manner. 相似文献
68.
Ole?A. Andreassen Srdjan Djurovic Wesley?K. Thompson Andrew?J. Schork Kenneth?S. Kendler Michael?C. O’Donovan Dan Rujescu Thomas Werge Martijn van?de?Bunt Andrew?P. Morris Mark?I. McCarthy International Consortium for Blood Pressure GWAS Diabetes Genetics Replication Meta-analysis Consortium Psychiatric Genomics Consortium Schizophrenia Working Group J.?Cooper Roddey Linda?K. McEvoy Rahul?S. Desikan Anders?M. Dale 《American journal of human genetics》2013,92(2):197-209
Several lines of evidence suggest that genome-wide association studies (GWASs) have the potential to explain more of the “missing heritability” of common complex phenotypes. However, reliable methods for identifying a larger proportion of SNPs are currently lacking. Here, we present a genetic-pleiotropy-informed method for improving gene discovery with the use of GWAS summary-statistics data. We applied this methodology to identify additional loci associated with schizophrenia (SCZ), a highly heritable disorder with significant missing heritability. Epidemiological and clinical studies suggest comorbidity between SCZ and cardiovascular-disease (CVD) risk factors, including systolic blood pressure, triglycerides, low- and high-density lipoprotein, body mass index, waist-to-hip ratio, and type 2 diabetes. Using stratified quantile-quantile plots, we show enrichment of SNPs associated with SCZ as a function of the association with several CVD risk factors and a corresponding reduction in false discovery rate (FDR). We validate this “pleiotropic enrichment” by demonstrating increased replication rate across independent SCZ substudies. Applying the stratified FDR method, we identified 25 loci associated with SCZ at a conditional FDR level of 0.01. Of these, ten loci are associated with both SCZ and CVD risk factors, mainly triglycerides and low- and high-density lipoproteins but also waist-to-hip ratio, systolic blood pressure, and body mass index. Together, these findings suggest the feasibility of using genetic-pleiotropy-informed methods for improving gene discovery in SCZ and identifying potential mechanistic relationships with various CVD risk factors. 相似文献
69.
Male and female gametophytes of Desmarestia aculeata have been grown as clonal cultures. Red light permits vegetative growth only. Differentiation of oogonia and antheridia takes place under illumination with blue light as has been previously reported for several species of Laminaria. Morphological details for differentiation of oogonia and antheridia are presented, stressing the strong resemblance with the respective processes in Laminaria. Experimental evidence indicates the presence of a hormonal factor secreted by the eggs, which is responsible for discharge and subsequent attraction of spermatozoids to the egg. 相似文献
70.
Umberto Raucci Rossella Rossi Roberto Da Cas Concita Rafaniello Nadia Mores Giulia Bersani Antonino Reale Nicola Pirozzi Francesca Menniti-Ippolito Giuseppe Traversa Italian Multicenter Study Group for Vaccine Safety in Drug Children 《PloS one》2013,8(7)