473 research outputs found
Risk of HIV-associated Hodgkin lymphoma during the first months after initiation of combination antiretroviral therapy
Screening the human exome: a comparison of whole genome and whole transcriptome sequencing
BACKGROUND: There is considerable interest in the development of methods to efficiently identify all coding variants present in large sample sets of humans. There are three approaches possible: whole-genome sequencing, whole-exome sequencing using exon capture methods, and RNA-Seq. While whole-genome sequencing is the most complete, it remains sufficiently expensive that cost effective alternatives are important. RESULTS: Here we provide a systematic exploration of how well RNA-Seq can identify human coding variants by comparing variants identified through high coverage whole-genome sequencing to those identified by high coverage RNA-Seq in the same individual. This comparison allowed us to directly evaluate the sensitivity and specificity of RNA-Seq in identifying coding variants, and to evaluate how key parameters such as the degree of coverage and the expression levels of genes interact to influence performance. We find that although only 40% of exonic variants identified by whole genome sequencing were captured using RNA-Seq; this number rose to 81% when concentrating on genes known to be well-expressed in the source tissue. We also find that a high false positive rate can be problematic when working with RNA-Seq data, especially at higher levels of coverage. CONCLUSIONS: We conclude that as long as a tissue relevant to the trait under study is available and suitable quality control screens are implemented, RNA-Seq is a fast and inexpensive alternative approach for finding coding variants in genes with sufficiently high expression levels
The risk of cancer in HIV-infected people in southeast England: a cohort study
This study used data from the Communicable Disease Surveillance Centre's national HIV database and the Thames Cancer Registry to assess the risk of cancer in HIV-infected people in southeast England. Among 26 080 HIV-infected men with 158 660 person-years follow-up, 1851 cancers, and among 7110 HIV-infected women (31 098 person-years), 171 cancers were identified. The standardised incidence ratio (SIR) for all non-AIDS-defining cancers was significantly increased in HIV-infected men (2.8, 95% confidence interval (CI) 2.6–3.1) but was nonsignificant in HIV-infected women (1.1, 95% CI 0.8–1.6). Most of the cancers observed were in men (n=1559) and women (n=127) with AIDS, and among them, the SIR for all non-AIDS-defining cancers was significantly increased in men (8.2, 95% CI 7.2–9.2) and women (2.8, 95% CI 1.6–4.6). The SIR for all non-AIDS-defining cancers was only just significantly increased in men with HIV-infection but not AIDS (1.2, 95% CI 1.0–1.5) and was nonsignificant in such women (0.8, 95% CI 0.5–1.2)
HIV associated thrombocytopenia, misdiagnosed as thrombotic thrombocytopenic purpura: a case report
Risk factors for high anti-HHV-8 antibody titers (≥1:51,200) in black, HIV-1 negative South African cancer patients: a case control study
Background: Infection with human herpesvirus 8 (HHV-8) is the necessary causal agent in the
development of Kaposi's sarcoma (KS). Infection with HIV-1, male gender and older age all increase
risk for KS. However, the geographic distribution of HHV-8 and KS both prior to the HIV/AIDS
epidemic and with HIV/AIDS suggest the presence of an additional co-factor in the development of
KS.
Methods: Between January 1994 and October 1997, we interviewed 2576 black in-patients with
cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1
and HHV-8 and the study was restricted to 2191 HIV-1 negative patients. Antibodies against the
latent nuclear antigen of HHV-8 encoded by orf73 were detected with an indirect
immunofluorescence assay. We examined the relationship between high anti-HHV-8 antibody
titers (≥1:51,200) and sociodemographic and behavioral factors using unconditional logistic
regression models. Variables that were significant at p = 0.10 were included in multivariate analysis.
Results: Of the 2191 HIV-1 negative patients who did not have Kaposi's sarcoma, 854 (39.0%)
were positive for antibodies against HHV-8 according to the immunofluorescent assay. Among
those seropositive for HHV-8, 530 (62.1%) had low titers (1:200), 227 (26.6%) had medium titers
(1:51,200) and 97 (11.4%) had highest titers (1:204,800). Among the 2191 HIV-1 negative patients,
the prevalence of high anti-HHV-8 antibody titers (≥1:51,200) was independently associated with
increasing age (ptrend = 0.04), having a marital status of separated or divorced (p = 0.003), using
wood, coal or charcoal as fuel for cooking 20 years ago instead of electricity (p = 0.02) and
consuming traditional maize beer more than one time a week (p = 0.02; p-trend for increasing
consumption = 0.05) although this may be due to chance given the large number of predictors
considered in this analysis.
Conclusions: Among HIV-negative subjects, patients with high anti-HHV-8 antibody titers are
characterized by older age. Other associations that may be factors in the development of high anti-
HHV-8 titers include exposure to poverty or a low socioeconomic status environment and
consumption of traditional maize beer. The relationship between these variables and high anti-
HHV-8 titers requires further, prospective study
Risk of classic Kaposi sarcoma with exposures to plants and soils in Sicily
<p>Abstract</p> <p>Background</p> <p>Ecologic and in vitro studies suggest that exposures to plants or soil may influence risk of Kaposi sarcoma (KS).</p> <p>Methods</p> <p>In a population-based study of Sicily, we analyzed data on contact with 20 plants and residential exposure to 17 soils reported by 122 classic KS cases and 840 sex- and age-matched controls. With 88 KS-associated herpesvirus (KSHV) seropositive controls as the referent group, novel correlates of KS risk were sought, along with factors distinguishing seronegatives, in multinomial logistic regression models that included matching variables and known KS cofactors - smoking, cortisone use, and diabetes history. All plants were summed for cumulative exposure. Factor and cluster analyses were used to obtain scores and groups, respectively. Individual plants and soils in three levels of exposure with <it>P</it><sub>trend </sub>≤ 0.15 were retained in a backward elimination regression model.</p> <p>Results</p> <p>Adjusted for known cofactors, KS was not related to cumulative exposures to 20 plants [per quartile adjusted odds ratio (OR<sub>adj</sub>) 0.96, 95% confidence interval (CI) 0.73 - 1.25, <it>P</it><sub>trend </sub>= 0.87], nor was it related to any factor scores or cluster of plants (<it>P </it>= 0.11 to 0.81). In the elimination regression model, KS risk was associated with five plants (<it>P</it><sub>trend </sub>= 0.02 to 0.10) and with residential exposure to six soils (<it>P</it><sub>trend </sub>= 0.01 to 0.13), including three soils (eutric regosol, chromic/pellic vertisol) used to cultivate durum wheat. None of the KS-associated plants and only one soil was also associated with KSHV serostatus. Diabetes was associated with KSHV seronegativity (OR<sub>adj </sub>4.69, 95% CI 1.97 - 11.17), but the plant and soil associations had little effect on previous findings that KS risk was elevated for diabetics (OR<sub>adj </sub>7.47, 95% CI 3.04 - 18.35) and lower for current and former smokers (OR<sub>adj </sub>0.26 and 0.47, respectively, <it>P</it><sub>trend </sub>= 0.05).</p> <p>Conclusions</p> <p>KS risk was associated with exposure to a few plants and soils, but these may merely be due to chance. Study of the effects of durum wheat, which was previously associated with cKS, may be warranted.</p
Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection
Approximately three quarters of acute hepatitis C (HCV) infections evolve to a chronic state, while one
quarter are spontaneously cleared. Genetic predispositions strongly contribute to the development
of chronicity. We have conducted a genome-wide association study to identify genomic variants
underlying HCV spontaneous clearance using ImmunoChip in European and African ancestries.
We confrmed two previously reported signifcant associations, in the IL28B/IFNL4 and the major
histocompatibility complex (MHC) regions, with spontaneous clearance in the European population.
We further fne-mapped the association in the MHC to a region of about 50 kilo base pairs, down from
1 mega base pairs in the previous study. Additional analyses suggested that the association in MHC is
stronger in samples from North America than those from Europe
Epidermodysplasia verruciformis human papillomavirus types and carcinoma of the conjunctiva: a pilot study
Risk of breast, ovary, and uterine corpus cancers among 85 268 women with AIDS
By linking HIV/AIDS and cancer surveillance data in 12 US regions, breast and reproductive cancer risks with AIDS were compared to those in the general population. Trends in standardized incidence ratios (SIRs) were assessed by CD4 count, AIDS-relative time, and calendar time. Standardized incidence ratios were indirectly adjusted for cancer risk factors using data from AIDS cohort participants and the general population. With AIDS, 313 women developed breast cancer (SIR 0.69, 95% confidence interval (CI) 0.62–0.77), 42 developed ovary cancer (SIR 1.05, 95% CI, 0.75–1.42), and 31 developed uterine corpus cancer (SIR 0.57, 95% CI, 0.39–0.81). Uterine cancer risk was reduced significantly after age 50 (SIR 0.33). Breast cancer risk was reduced significantly both before (SIR 0.71) and after (SIR 0.66) age 50, and was lower for local or regional (SIR 0.54) than distant (SIR 0.89) disease. Breast cancer risk varied little by CD4 count (Ptrend=0.47) or AIDS-relative time (Ptrend=0.14) or after adjustment for established cancer risk factors. However, it increased significantly between 1980 and 2002 (Ptrend=0.003), approaching the risk of the general population. We conclude that the cancer deficit reflected direct or indirect effects of HIV/AIDS and that anti-HIV therapy reduced these effects
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