6 research outputs found

    The Problem of Late ART Initiation in Sub-Saharan Africa: A Transient Aspect of Scale-up or a Long-term Phenomenon?

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    Efforts to scale-up HIV care and treatment have been successful at initiating large numbers of patients onto antiretroviral therapy (ART), although persistent challenges remain to optimizing scale-up effectiveness in both resource-rich and resource-limited settings. Among the most important are very high rates of ART initiation in the advanced stages of HIV disease, which in turn drive morbidity, mortality, and onward transmission of HIV. With a focus on sub-Saharan Africa, this review article presents a conceptual framework for a broader discussion of the persistent problem of late ART initiation, including a need for more focus on the upstream precursors (late HIV diagnosis and late enrollment into HIV care) and their determinants. Without additional research and identification of multilevel interventions that successfully promote earlier initiation of ART, the problem of late ART initiation will persist, significantly undermining the long-term impact of HIV care scale-up on reducing mortality and controlling the HIV epidemic

    Effect of various normalization methods on Applied Biosystems expression array system data

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    BACKGROUND: DNA microarray technology provides a powerful tool for characterizing gene expression on a genome scale. While the technology has been widely used in discovery-based medical and basic biological research, its direct application in clinical practice and regulatory decision-making has been questioned. A few key issues, including the reproducibility, reliability, compatibility and standardization of microarray analysis and results, must be critically addressed before any routine usage of microarrays in clinical laboratory and regulated areas can occur. In this study we investigate some of these issues for the Applied Biosystems Human Genome Survey Microarrays. RESULTS: We analyzed the gene expression profiles of two samples: brain and universal human reference (UHR), a mixture of RNAs from 10 cancer cell lines, using the Applied Biosystems Human Genome Survey Microarrays. Five technical replicates in three different sites were performed on the same total RNA samples according to manufacturer's standard protocols. Five different methods, quantile, median, scale, VSN and cyclic loess were used to normalize AB microarray data within each site. 1,000 genes spanning a wide dynamic range in gene expression levels were selected for real-time PCR validation. Using the TaqMan(Âź )assays data set as the reference set, the performance of the five normalization methods was evaluated focusing on the following criteria: (1) Sensitivity and reproducibility in detection of expression; (2) Fold change correlation with real-time PCR data; (3) Sensitivity and specificity in detection of differential expression; (4) Reproducibility of differentially expressed gene lists. CONCLUSION: Our results showed a high level of concordance between these normalization methods. This is true, regardless of whether signal, detection, variation, fold change measurements and reproducibility were interrogated. Furthermore, we used TaqMan(Âź )assays as a reference, to generate TPR and FDR plots for the various normalization methods across the assay range. Little impact is observed on the TP and FP rates in detection of differentially expressed genes. Additionally, little effect was observed by the various normalization methods on the statistical approaches analyzed which indicates a certain robustness of the analysis methods currently in use in the field, particularly when used in conjunction with the Applied Biosystems Gene Expression System

    Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

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    Signaling Properties of CD38 in the Mouse Immune System: Enzyme-dependent and -independent Roles in Immunity

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    The 5th international CD38 meeting, held in Torino, Italy, spanned a range of topics from the role of CD38 as a signaling receptor in lymphocytic tumors to the importance of CD38-derived metabolites in NAD(+) metabolism, calcium signaling, and immune function. This meeting was particularly exciting as data were presented demonstrating that collaborative experiments between enzymologists, biochemists, cell biologists, immunologists, and clinicians have started to unravel the secrets of CD38 biology. It is now clear that all of the products of the CD38 enzyme reaction regulate calcium signal transduction in cell types as diverse as sea urchin oocytes and mammalian lymphocytes. It is also apparent that CD38 plays important immunomodulatory role(s), however there is still much debate on how CD38 mediates its immunoregulatory functions and whether the enzymatic products generated by CD38 are important for immunity. The data presented at this meeting have begun to resolve some of these controversies. First, CD38 regulates the function of leukocytes by enzyme-dependent and enzyme-independent mechanisms. Second, CD38 regulates inflammatory responses by modulating the activity of the responding leukocytes and by altering the activity of non-hematopoietic cells in the inflamed tissue. Finally, crosstalk between CD38 and other NAD(+) utilizing enzymes such as ART2, SIRT1, and PARP-1 impacts NAD(+) homeostasis, inflammation, and immunity. Thus, immunity is regulated by CD38 in multiple and unexpected ways and the new research challenge will be to determine whether we can exploit the complex biology of CD38 to therapeutically regulate the immune system
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