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    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

    Modulating the counter-regulatory renin angiotensin system axis in experimental ischaemic stroke

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    Stroke is a leading cause of death and disability worldwide, yet treatment options are limited. Stroke can be caused by a ruptured cerebral blood vessel, known as haemorrhagic stroke, or more commonly by the blockage of a blood vessel within the brain, known as ischaemic stroke. Starvation of the brain tissue of oxygen and glucose during ischaemia results in a pathophysiological cascade of damage consisting of ionic dysregulation, excitotoxicity, oxidative stress and inflammation. Recanalization of the vessel, either pharmacologically using a clot busting drug or by mechanical clot removal known as thrombectomy, paradoxically results in further injury by similar mechanisms, known as reperfusion injury. Different aspects of stroke pathophysiology have been previously targeted as neuroprotective strategies, but none have proven effective in improving patient outcomes following stroke. Efforts by the preclinical stroke community to improve methodological rigor in experimental stroke research have been well implemented and will hopefully aid in the translation of novel neuroprotectants for stroke care. Targeting the renin angiotensin system (RAS) has been successful clinically for modulating hypertension, the major modifiable risk factor for stroke. In this system, the biologically active peptide, angiotensin II (Ang II) is produced through the actions of the enzymes renin and angiotensin converting enzyme (ACE), and acts upon the Ang II type 1 receptor (AT1R) to produce an increase in blood pressure, but also local tissue specific effects such as cardiac hypertrophy, fibrosis and neuronal cell death. A counter-regulatory axis of this system exists, consisting of an alternative enzyme, ACE2, which produces the peptides, Ang-(1-9) and Ang-(1-7), and alternative receptors, the Ang II type 2 receptor (AT2R) and Mas receptor (MasR). These peptides act upon these receptors, respectively, producing antagonistic effects to AT1R signalling. More recently, studies have demonstrated the neuroprotective potential of the counter-regulatory RAS, in particular agonism of AT2R. Ang-(1-9) is a novel peptide of the counter-regulatory RAS which acts upon the AT2R but, to date, this peptide has not been investigated in the setting of ischaemic stroke. The primary aim of this thesis was to investigate the therapeutic potential of Ang-(1-9) in a comorbid experimental stroke model, with secondary aims of investigating modulation of the RAS within the brain of this animal following stroke, and establishment of an in vitro model to study Ang-(1-9) effects on oxygen-glucose deprivation (OGD). In Chapter 3, the expression of RAS mRNA was confirmed in the brain of stroke prone spontaneously hypertensive rats (SHRSP). This animal was used throughout these studies as a comorbid animal model displaying chronic hypertension and resulting end-organ damage because hypertension is the key modifiable risk factor for ischaemic stroke. It was hypothesised that SHRSP would have different RAS gene expression to the normotensive Wistar Kyoto strain (WKY) and that brain RAS gene expression would be altered by salt-loading. Results, using reverse transcription quantitative PCR (RT-qPCR), demonstrated similar baseline RAS gene expression in the cortical tissue between the two strains but salt-loading in the SHRSP induced an downregulation of AT1R and upregulation of MasR compared to WKY, suggesting a differential response of RAS and counter-regulatory RAS receptor expression to this stressor between the two strains. It was also hypothesised that RAS gene expression would be altered in the SHRSP brain following experimental stroke. A transient middle cerebral artery occlusion (tMCAO) filament model of stroke was utilised without reperfusion or with 2-24 hr reperfusion in order to assess gene expression changes longitudinally post-stroke. Results demonstrated that genes for the components of the classical RAS, ACE and AT1R, were downregulated 24 hr following tMCAO in the SHRSP brain in line with previous reports in other animal models. Components of the counter-regulatory RAS axis, ACE2, AT2R and MasR, were also downregulated 24 hr following tMCAO in the SHRSP brain which contradicts previous studies in healthy mice or rats. Interestingly, however, during the MCA occlusion period, AT2R was significantly upregulated in line with previous reports of AT2R expression following permanent MCAO. Together, these results suggest that SHRSP may display altered RAS expression in response to insult compared to healthy animals but give reassurance for the ability to target AT2R in SHRSP due to its acute upregulation. A further interesting finding of this chapter was that AT2R expression varies greatly across the SHRSP brain following sham surgeries, with higher expression in the lower remainder region and in the “peri-infarct” region compared to cortical “infarct” tissue. In Chapter 4, it was hypothesised that Ang-(1-9) would have a beneficial effect on outcome in the SHRSP following tMCAO when it was delivered prior to stroke via an adeno-associated viral (AAV9) vector (AAV9-Ang-(1-9)) injected directly into the brain at striatal and cortical sites. AAV9 mediated transgene expression was first confirmed near the injection sites at the appropriate time-point for stroke induction, and further tMCAO surgeries were performed for competency training and to provide preliminary data for sample size calculations. Due to higher than expected mortality rate, and early terminations due to animals reaching the severity limit of the procedure, the study was terminated early with under-powered group sizes. Despite the early termination, animals receiving stereotactic AAV9-Ang-(1-9) prior to tMCAO showed trends towards functional improvement, measured by neurological scoring, the tapered beam test and sticky label test, compared to animals receiving burrhole surgery only or injections of control virus AAV9-eGFP (enhanced green fluorescent protein) but infarct volumes were similar across all groups. AAV9-Ang-(1-9) also had no effect on systemic blood pressure but tMCAO surgery induced an overall increase in systemic blood pressure across groups. Despite previous reports of AT2R agonism inducing upregulation of brain derived neurotrophic factor (BDNF), AAV9-Ang-(1-9) did not result in greater expression of BDNF following tMCAO in the SHRSP brain, indeed a trend towards reduced expression was observed. Similarly, despite previous reports of anti-fibrotic vascular effects of Ang-(1-9), AAV9-Ang-(1-9) did not affect vascular collagen deposition in the SHRSP brain following stroke. Both BDNF expression and vascular collagen deposition, however, were increased in the ipsilateral stroke hemisphere compared to the contralateral hemisphere. Overall, the results of this chapter demonstrated promising potential of treating ischaemic stroke with Ang-(1-9) and the use of AAV9 mediated transgene delivery, however due to limitations within the study further conclusive investigations are required to assess Ang-(1-9) in stroke. Furthermore, during this in vivo study, unanticipated changes in the animal unit facilities were implemented. These were explored in further detail in Chapter 5 which presents the observation of differences in post-stroke weight loss and functional outcome when animals were grouped depending on the bedding or cage type used, suggesting the importance of tight regulation of environmental variables in preclinical stroke studies. Finally, in Chapter 6, an in vitro model of ischaemia-reperfusion injury was established using OGD in primary neuronal cultures (PNC) cultured from fetal SHRSP brain tissue. PNC were used due to lack of RAS gene expression and adenoviral transduction observed in rat brain cell lines. It was hypothesised that the OGD PNC model could be used to demonstrate neuroprotective effects of Ang-(1-9) and would allow for mechanistic insight. Optimisation of the OGD protocol proved difficult with no rescue effect of OGD induced loss in cell viability or OGD induced cell death observed by previously published neuroprotective compounds or with Ang-(1-9) peptide or adenoviral mediated Ang-(1-9) expression. Interestingly, under normal culturing conditions, Ang-(1-9) and compound 21 (C21) induced a reduction in BDNF or vascular endothelial growth factor (VEGF) expression in PNC, despite previous reports of C21, the AT2R agonist, inducing upregulation of these molecules. This suggests that SHRSP PNC may respond differently to AT2R agonism depending on the model and disease setting. In summary, the findings presented in this thesis demonstrate encouraging potential for the use of Ang-(1-9) as a treatment for ischaemic stroke. However, this also highlights the difficulties encountered in preclinical stroke research and the need for further optimisation of these models for further investigation of Ang-(1-9) or other drug

    Variations on the Author

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    “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

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    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

    Dispelling the Myths Behind First-author Citation Counts

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    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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    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 Under Sail The Imagination of Jack London, 1893-1902

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    In 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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