1,721,032 research outputs found
Dysregulated Coagulation in Haemodialysis - Vascular access and Cerebrovascular disease
Get PDFUraemia confers a prothrombotic tendency in tandem with a bleeding diathesis through platelet dysfunction that is most evident in patients with renal failure who are dependent on haemodialysis. This form of renal replacement therapy accentuates this clinical paradox by its procoagulant nature and the use of regular anticoagulation to prevent dialysis circuit and vascular access thrombotic dysfunction. This thesis evaluates such dysregulated coagulation in the extracorporeal circuit, the central venous catheter and dialyser, and in the twin substrates of cerebrovascular disease, thromboembolism and haemorrhage.
Firstly the comparative effect of catheter site on thrombosis is evaluated by the jugular and translumbar routes before examining catheter type as a determinant in a randomised, controlled clinical trial. Subsequently novel use of catheter flow monitoring as a predictive tool for thrombotic dysfunction is presented and the efficacy of thrombolytic therapies assessed. Lastly a prospective pharmacokinetic evaluation of tinzaparin in dialysis circuit anticoagulation which revealed a novel influence of gender on anti-factor Xa activity.
Stroke incidence and risk is examined in one of the largest studies to date before two specific risk factors for thromboembolic stroke are examined, intracranial arterial calcification and transient ischaemic attack. A potential association between intracranial arterial calcification and this stroke subtype is described for the first time in haemodialysis and results from the first prospective screening study for transient ischaemic attack in haemodialysis are presented. Finally renal dysfunction is shown to be a determinant of thrombolytic efficacy in acute ischaemic stroke.
All these studies advance our understanding of thrombotic catheter dysfunction, its thrombolytic management and the behaviour of tinzaparin in haemodialysis. In addition they afford unique insights into cerebrovascular disease in haemodialysis that challenge traditional paradigms of a pathology with high incidence in these patients
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
The Role of O-Linked Glycosylation in VWF Function
Get PDFDuring synthesis Von Willebrand Factor (VWF) undergoes O-linked glycosylation (OLG) but the functional significance of this has not been fully explored. In this study the 10 OLG sites in VWF were mutated to alanine, individually and as clusters on either or both sides of the A1 domain: Clus-1 (N-terminal side), Clus-2 (C-terminal side) and double cluster (DC). All mutants demonstrated normal expression, multimeric structure and collagen and heparin binding functions. Furthermore, mass spectroscopy analysis showed that the OLG structures presented on recombinant VWF were similar in structure to those on plasma derived VWF including the presence of a rare disialosyl motif. The variants T1486 (C-terminal side of the A1 domain), Clus-2 and DC were less susceptible to ADAMTS13 proteolysis under static and pseudo-shear stress conditions and showed increased binding to ADAMTS13 when in solution. Using an optimised plate-based ELISA assay, it was demonstrated that mutation of the OLG sites on the N-terminal side of the VWF-A1 domain enhanced sensitivity to ristocetin-mediated binding to recombinant GPIbα. Increased GPIbα binding was also observed with desialylated VWF and this effect was attributed to sialic acid residues on the OLGs. Similar results were obtained using the conventional ristocetin cofactor assay. To further investigate these findings, an in vitro flow assay was optimised to analyse the interaction of VWF and platelets under shear stress. Mutation of the OLG sites on the N-terminal side of the A1 domain, increased platelet rolling velocity but did not significantly alter the dissociation rate of the VWF-A1:GPIbα bond. However, they did decrease the number of transient tethering events as a function of time when VWF was immobilised directly on to the flow surface. Interestingly, when compared with wtVWF the T1255A and Clus-1 variants mediated increased platelet capture to collagen under high shear stress.
The data presented in this thesis demonstrates that the OLG clustered at the C-terminal side of the A1 domain alter susceptibility of VWF to ADAMTS13 cleavage. Whilst OLGs clustered at the N-terminal side of A1 modulate its interaction with GPIbα both under static and shear conditions. A unifying hypothesis would be that VWF OLG alter conformational stability around the A1 domain and modulate its interactions with adjacent domains and with other molecules. However different effects may predominate under static and flow conditions. Importantly, VWF-platelet interaction in flow assays depends on the way VWF has been immobilised
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
Understanding the genetic basis of rare inherited bleeding and platelet disorders: the utility of next-generation sequencing
Get PDFInherited bleeding and platelet disorders (BPD) are rare, heterogeneous and rarely receive a specific genetic diagnosis. The BRIDGE-Bleeding and platelet disorders consortium was set up to address this using high-throughput sequencing (HTS). More than one thousand probands with inherited BPD of unknown aetiology were recruited to an international consortium study with two over-arching aims: to identify novel genetic loci involved in BPD and provide a better diagnosis for patients. Through applying comprehensive, standardised phenotyping to this large dataset combined with novel analytical methods, several novel candidate genes for BPD have been identified. HTS has also identified variants in known BPD genes, many of them pathogenic, thus providing a diagnosis to many patients with BPD.
In this thesis I present the study design and methodology for recruitment and data collection for the BRIDGE-BPD study. I describe the optimisation and application of the Human Phenotype Ontology to phenotype rare BPD and show how this has facilitated gene discovery and improvements in patient diagnosis. In chapters 4 and 5 I show how HTS has identified many variants in known BPD genes and illustrate the challenges faced and methods required for the interpretation of these variants. Many novel candidate BPD genes have also been identified and in chapters 6 and 7 some examples are highlighted with methods for their characterisation.
Overall, this thesis demonstrates the utility of HTS in the diagnosis of rare BPD and many of the challenges faced in the interpretation of data from large whole genome sequencing projects and application of this technology to rare diseases.Open Acces
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
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