1,720,986 research outputs found
Monocyte dysfunction in alcoholic hepatitis
Severe alcoholic hepatitis (SAH) is the most florid form of alcohol-related liver disease (ALD). It is caused by hepatic inflammation after a prolonged period of heavy alcohol drinking. Causes of death include liver failure and infection. Inflammatory hepatic injury and systemic immunoparesis are therefore key features in disease pathogenesis.
This thesis seeks to evaluate this immune dysfunction in detail, focussing on a key component of the innate immune system, the circulating monocyte. A variety of techniques such as flow cytometry, Western blotting and polymerase-chain reaction (PCR) were used to characterise the phenotype and function of monocytes from peripheral blood. Dysfunction was then related to patient outcome and treatments administered by the randomised placebo controlled Steroids and Pentoxyfilline for Alcoholic Hepatitis (STOPAH) clinical trial.
Novel findings from this work include the identification of preserved uptake of bacteria by phagocytosis but defective monocyte oxidative burst and bacterial killing of Escherichia coli. Further, I show that the presence of this defect predicts the subsequent development of infection. In addition, this defect is associated with reduced expression of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme and may be treatable with N-acetylcysteine (NAC). Secondly, I identify an expanded population of an inflammatory intermediate monocyte subset in SAH that bears high expression of chemokine CC chemokine receptor type 5 (CCR-5), and may be amenable to targeted antibody therapy to reduce hepatic inflammation in SAH patients.Open Acces
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
The role of gut proteases in determining intestinal permeability for patients with alcohol-related liver disease
The precise mechanism of increased intestinal permeability and bacterial translocation in the pathogenesis of alcohol-related liver disease (ArLD) remains unclear. Recent data has implicated gut-derived virulence factors in the development of alcoholic hepatitis but it is not yet fully established how these gain access to the systemic circulation. This thesis aims to examine the effect that gut proteases may have on intestinal permeability and the link with alterations in the gut microbiome seen in ArLD.
Stool samples were collected from patients with ArLD. Faecal water protease activity was measured and correlated with indirect markers of intestinal permeability and biochemical markers of liver disease. A monolayer model of the gut barrier using Madin Darby canine kidney (MDCK) cells enabled the effect of faecal water protease to be measured. Gelatin zymography differentiated stool proteases by weight followed by mass spectrometry. Protease-indicator agar allowed bacterial isolates showing a protease-producing phenotype to be characterised following DNA extraction. Stool protease activity on tight junction proteins was assessed using tight junction antibodies against MDCK monolayers and duodenal tissue samples taken from patients with ArLD.
No correlation was seen between faecal protease activity and markers of intestinal permeability or biochemical markers of liver disease. A significant correlation was seen between faecal protease activity and the change in gut permeability as measured in the MDCK monolayer model. This correlation was abolished with the addition of a broad protease-inhibitor. Taxonomic characterisation of stool samples revealed reduced alpha diversity in samples from patients with ArLD but a higher proportion of Enterococcus. Tight junction protein staining was reduced in duodenal samples from patients with decompensated ArLD and in MDCK cells treated with ArLD faecal water compared to controls.
These data suggest that faecal proteases may play a role in increasing intestinal permeability in ArLD through their effects on tight junction proteins.Open Acces
Dispelling the Myths Behind First-author Citation Counts
We 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
We 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.
Author-wise bibliometric analysis based on entropy.</p
- …
