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The role of microbial translocation and gut microbiota in HIV-1 infection
No full textHIV-1 infection is characterized by persistent systemic inflammation and immune activation, even in patients receiving effective antiretroviral therapy (ART). Translocation of microbial compounds from a leaky gut to systemic circulation, so called microbial translocation (MT), is a major driver of the immune activation. Additionally, gut microbiota dysbiosis in HIV-1 infected patients further facilitate and fuel MT. The objectives of this thesis were to study: * how different ART regimens and usage of antibiotics affect markers of MT (I, II), * the alternations of gut microbiota during HIV-1 infection and the effect of ART (III,IV).In a clinical randomized trial, HIV-1 infected subjects started ART based on efavirenz (n=37) or ritonavir-boosted lopinavir (n=34). Levels of MT markers and of enterocyte death were elevated at baseline (BL), and MT markers declined until follow up after 72 weeks, but the reduction of anti-flagellin IgG antibodies was significant only in lopinavir treated patients. Levels of Intestinal Fatty Acid Binding Protein (I-FABP) remained unchanged at 72 weeks, but were temporarily increased after one month in efavirenz treated patients. 29 subjects with concomitant use of antibiotics had superior reduction of soluble CD14 (sCD14) levels. These data show that choice of ART and antibiotics usage could affect the kinetics of some MT markers.To further explore the impact of antibiotics usage on MT, we performed a longitudinal study on HIV-1 patients initiating ART without (n=13) or with (n=13) co-trimoxazole (TMP-SMX) as prophylaxis against Pneumocystis jirovecii. Following ART, levels of LPS-binding protein (LBP) were reduced only in the TMP-SMX group, whilst levels of sCD14 declined in both groups after one year. The LBP decrease remained significant in a multivariate analysis model adjusting for co-variates including BL CD4+ T-cell count. This study confirmed that concomitant use of antibiotics and ART in severely immune deteriorated individuals may beneficially influence the kinetics of MT markers.In the third study, the composition of gut microbiota was determined by 16S rRNA sequencing in 28 HIV-1 progressors, 3 Elite controllers (EC) and 9 uninfected controls at BL, and additionally after ten months of ART in 16 subjects. Gut microbiome α-diversity was reduced in HIV-1 infected individuals as compared to controls, and further declined after introduction of ART. At BL, α-diversity was positively correlated with CD4+ T-cell counts, but in contrary several markers of MT/immune activation were inversely correlated. Microbiome of EC had the lowest interindividual variation (ß-diversity), clustering together in PCoA analysis. The bacterial composition at genus level was altered in HIV-1 progressors with higher abundance of Lactobacillus, and depletion of Lachnobacterium, Faecalibacterium and Hemophilus. Thus, this study showed that the alternations of gut microbiota during HIV-1 infection are associated with the level of immune dysfunction, and that almost one year of ART does not restore the shifts in the gut microbiome.In the last work, we studied the gut microbiome of 16 EC in relation to 32 matched ART naive HIV-1 positive individuals and 16 uninfected controls. The number of observed genera and richness indices Chao-1 and ACE were significantly higher in EC as compared to naive patients. The gut microbiota in EC was enriched in genera Succinivibrio, Sutterella, Rhizobium, Delftia, Anaerofilum and Oscillospira, whilst Blautia and Anaerostipes were reduced. Determination of inferred bacterial functionality by PICRUSt analysis revealed that carbohydrate metabolism related genes were depleted in EC. In contrary, pathways related to fatty acid metabolism, PPAR-signaling and lipid biosynthesis proteins were more abundant in EC vs naive. The kynurenine pathway of tryptophan metabolism was altered only during progressive HIV-1 infection, and kynurenine tryptophan (K/T) ratio was inversely associated with gut microbiota richness. This study shows that EC have richer gut microbiota than untreated HIV-1 patients with progressive infection, with a unique bacterial composition and a distinct metabolic profile which may be involved in the control of HIV-1.In summary, data from the studies in my thesis reveal that MT in HIV-1 infection is reduced by ART but also that the choice of ART influences this decline. Additionally, the antibiotics usage may affect the levels of MT. The complexity, composition and functionality of gut microbiota are disturbed in HIV-1 infected individuals with progressive disease, whilst EC have a unique gut microbiota profile that eventually contributes to their control of HIV-1.List of scientific papersI. Vesterbacka Jan, Nowak Piotr, Barqasho Babilonia, Abdurahman Samir, Nyström Jessica, Nilsson Staffan, Funaoka Hiroyuki, Kanda Tatsuo, Andersson Lars-Magnus, Gisslèn Magnus, Sönnerborg Anders. Kinetics of microbial translocation markers in patients on efavirenz or lopinavir/r based antiretroviral therapy. PLoS One. 2013;8(1):e55038. https://doi.org/10.1371/journal.pone.0055038 II. Vesterbacka Jan, Barqasho Babilonia, Häggblom Amanda, Nowak Piotr. Effects of Co-Trimoxazole on Microbial Translocation in HIV-1-Infected Patients Initiating Antiretroviral Therapy. AIDS Res Hum Retroviruses. 2015 Aug;31(8):830-6. https://doi.org/10.1089/AID.2014.0366 III. Nowak Piotr, Troseid Marius, Avershina Ekatarina, Barqasho Babilonia, Neogi Ujjwal, Holm Kristian, Hov Johannes R, Noyan Kajsa, Vesterbacka Jan, Svärd Jenny, Rudi Knut, Sönnerborg Anders. Gut microbiota diversity predicts immune status in HIV-1 infection. AIDS. 2015 Nov;29(18):2409-18. https://doi.org/10.1097/QAD.0000000000000869 IV. Vesterbacka Jan, Rivera Javier, Noyan Kajsa, Parera Mariona, Neogi Ujjwal, Calle Malu, Paredes Roger, Sönnerborg Anders, Noguera-Julian Marc, Nowak Piotr. Richer gut microbiota with distinct metabolic profile in HIV infected Elite Controllers. Sci Rep. 2017 Jul 24;7(1):6269. https://doi.org/10.1038/s41598-017-06675-1 </p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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