1,721,033 research outputs found
LIVER-RELATED MORTALITY DURING THE HAART ERA IN MACS AND WIHS
Full text linkIt is not clear how the risk of liver-related mortality (LRM) among people infected with HIV has changed during the 20 years since the introduction of HAART; Thus, this study was designed to 1) characterize changes in all-cause mortality and LRM rates since the introduction of HAART in 1996, and 2) examine the effect of HIV/viral hepatitis co- infection on LRM among those infected with HBV or HCV.
Methods: This observational cohort study included all participants with known HBV and HCV status being followed in the Multicenter Center AIDS Cohort Study (MACS) and Women’s Interagency HIV Study (WIHS) between 1996 and 2013. Poisson and Cox regression methods were used to examine the rate of and risk factors for the study outcomes of all-cause mortality and LRM.
Results: The overall all-cause mortality and LRM rates during the study period were 15.2 and 2.3 per 1000 person-years, respectively. Following adjustment, all-cause mortality decreased significantly by 3.6% (95% CI: 2.2% - 5.1%) while LRM did not (decreased by 2.2% (95% CI: -1.7% - 5.8%) annually). Importantly, both all-cause mortality and LRM decreased over time among those with CH-B and increased among those with CH-C. Adjusted for age, race, education, income, and blood pressure, CH-B, CH-C and HIV infection were independently associated with a higher LRM (HRs of 9.09 (95% CI, 5.35 – 15.43), 11.63 (95% CI, 7.52 – 17.98), and 1.84 (95% CI, 0.99 – 3.42), respectively), and HAART use was significantly associated with a lower LRM risk (HR, 0.61; 95% CI, 0.42 – 0.88).
Conclusions: During the 20 years since HAART was introduced, liver disease has become an increasingly important cause of death among people infected with HIV. Although CH-B was associated with higher LRM during the early HAART era, LRM has been higher among those with CH-C in recent years; a shift that might be related to our findings that HARRT was associated with lower LRM. Collectively, the findings from our study suggest that there is an urgent need to increase the awareness of hepatitis among people infected with HIV, and that effective strategies to prevent, detect, and treat hepatitis infections are important in this population
EFFECTS OF COMMON GENETIC VARIANTS IN TP53 AND TLR8 ON IMMUNE RESPONSE AND RISK OF CANCER IN PEOPLE WITH HIV/AIDS
Full text linkBackground: Cancer represents a significant source of morbidity and mortality in people living with HIV/AIDS (PLWHA) and risk of most cancer exceeds that observed in the general population. A substantial proportion of cancers in PLWHA may be attributable to infection, with risk largely due to HIV-related immune deficiency and co-infection with oncogenic pathogens. p53 is a tumor suppressor also involved in innate immune signaling via the Toll-like receptor 8 (TLR8). SNPs in both the TP53 (rs1042522) and TLR8 (rs3764880) genes may mediate the innate immune response, with the TP53 G and TLR8 A alleles hypothesized to be jointly protective against cancer.
Methods: Seven hundred and sixty participants enrolled in the Multicenter AIDS Cohort Study (MACS) provided blood samples for ascertainment of SNP genotypes. Outcomes assessed were diagnosis of any cancer, AIDS-defining cancer, non-AIDS-defining cancer, and infection-related cancer up to two years after participants’ last visits. Exact Poisson regression was used to estimate unadjusted and adjusted incidence rate ratios associated with SNP genotypes for each outcome. Joint SNP effects were estimated using an interaction term.
Results: SNPs were found to be jointly protective against any cancer (interaction IRR: 0.46, 95% CI: 0.01-42.71), ADCs (interaction IRR: 0.47, 95% CI: 0.01-48.55), and infection-related cancers (interaction IRR: 0.40, 95% CI: 0.01-39.37) in multivariable models while main effects of SNPs were slightly protective or had no effect for all outcomes.
Discussion: These findings are consistent with a hypothesized synergistic effect of SNPs on the immune response. Weak main SNP effects and strong interaction indicate a protective effect of SNPs only in the presence of each other. Future work will address missing data using imputation and potential effects of sex by adding data collected by the Women’s Interagency HIV Study
A Candidate Gene Study of the Association of TLR4 Polymorphisms rs4986790 and rs4986791 with HIV Disease Progression and Response to HAART Treatment in Men
Full text linkBackground. Host genetic factors have been shown to be associated with the diversity in the HIV/AIDS disease progression. In addition, lipopolysaccharides (LPSs) are recognized by Toll-Like Receptor 4 (TLR4), and are associated with the HIV viral load in macrophages. Furthermore, TLR4 polymorphisms rs4986790 and rs4986791 have been shown to be associated with the HIV viral setpoint. Together, these findings suggest that these TLR4 polymorphisms are associated with HIV disease progression.
Objective. We studied the association of the TLR4 polymorphisms rs4986790 and rs4986791 with HIV viral setpoint, and the virologic and immunological responses to HAART treatment.
Methods. We designed both cross-sectional and prospective components of this cohort study to utilize men enrolled in the Multicenter AIDS Cohort Study (MACS) who had been genotyped for single nucleotide polymorphisms (SNPs) in the TLR4 region. We applied linear regression to model the HIV viral setpoint, and log-binomial regression as well as Poisson regression with robust estimation of variance to model the virologic and immunological responses to HAART.
Results. The results suggest that the two TLR4 SNPs have protective effects in terms of decreased HIV setpoint in a recessive model. The mean log10 HIV viral setpoint among men with rs4986791-TT was 0.11 lower than that among men with at least one C allele, and the mean log10 HIV setpoint among men with rs4986790-GG was 0.30 lower than that among men with at least one A allele. For the virologic response to HAART, we found that the probability of achieving an undetectable HIV RNA level within two years of HAART initiation was 47% higher among men with rs4986791-TT compared to men with at least one C at rs4986791 adjusting for cofactors, while the probability of achieving an undetectable HIV RNA level within two years of HAART initiation was 40% higher among men with rs4986790-GG compared to men with at least one A at rs4986790 adjusting for cofactors. In contrast, the two TLR4 SNPs were not associated with the immunological response of achieving 100 cells/microliters increase in CD4+ T cells within two years following HAART treatment.
Conclusions. The results from this study are in accordance with previous findings that rs4986790 and rs4986791 were associated with HIV viral load, and they extended that observation by suggesting that TLR4 genotype might also be associated with achieving undetectable viral load after HAART treatment. This novel observation needs to be confirmed in other cohorts
The Impact of Highly Active Antiretroviral Therapy on Cancer Survival in the Multicenter AIDS Cohort Study and the Women’s Interagency HIV Study
Full text linkOBJECTIVES: To characterize and compare cancer survival among HIV-infected and –uninfected individuals diagnosed with cancer in the pre-HAART (1984-1994) and the HAART (1995-2013) eras, and to describe cancer survival in the HAART era by HIV status and use of HAART.
DESIGN: A prospective cohort study nested within the Multicenter AIDS Cohort (MACS) and Women’s Interagency HIV Study (WIHS).
STUDY PARTICIPANTS: We studied 911 individuals from the time of cancer diagnosis until the earliest of death or the last study visit attended. Only the initial primary cancers that were diagnosed after enrollment in the MACS or WIHS were included. Second primaries and subsequent metastases were not considered in the analysis. Participants with an unknown cancer diagnosis date were excluded, as were participants with more than a 2-year gap between their last visit prior to cancer diagnosis and the diagnosis date, participants whose SEER Site ICD-0-3 cancer code was an epithelial-cell skin cancer, and those with less than 24 hours of follow-up.
METHODS: Cox regression was used to calculate adjusted hazard ratios of death. The proportional hazard assumption was assessed using complementary log-log regression plots and by fitting unadjusted Cox time-dependent Relative Hazards models.
RESULTS: Among MACS participants, HIV-infected individuals with cancers diagnosed in the HAART era compared to those diagnosed in the pre-HAART era had better survival, and the difference between these two groups increased with time following cancer diagnosis. There was no significant difference in survival in the HAART era comparing HIV-infected and HIV-uninfected individuals (adjusted HR: 0.70; 95% CI: 0.35 – 1.38). Survival did not differ for HIV-infected individuals diagnosed with ADMs as compared
to those diagnosed with NADMs in the HAART era, but individuals taking HAART at the visit prior to cancer diagnosis had a lower hazard of death than did those not taking HAART (p = 0.03). Interestingly, we also found that HAART use was associated with survival (adjusted HR: 0.36, 95% CI: 0.19 – 0.69) for individuals diagnosed with infection-related cancers, but not among those diagnosed with non-infection-related cancers (adjusted HR: 1.07, 95% CI: 0.67 – 1.72).
CONCLUSIONS: The results of this study demonstrate that HAART use prior to diagnosis with infection-related cancers among HIV-infected individuals is associated with improved survival, but this was not the case for non-infection-related cancers. Future research should further assess the survival benefit of HAART for individual infection-related cancers to determine whether our finding is generally relevant for all cancers in this class or for just a select few
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
