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    Exercise Intolerance Occurs in a Large Animal Model of Heart Failure with Preserved Ejection Fraction

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    Full Text is available to authenticated members of The University of Auckland only.Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome representing more than 50% of the heart failure (HF) population. HFpEF has been defined by the failure of the left ventricle being unable to accept an adequate blood volume from the left atria, resulting in increased diastolic filling pressure and impaired myocardial relaxation. This results in a blunted heart rate, reduced cardiac output and stroke volume, and reduced oxygen intake particularly in response to exercise (exercise intolerance). Chronic Hypertension is a predominant contributing factor to HFpEF and is seen in over half of all patients with HFpEF. To date, the current treatment options do not improve patient outcomes. This makes animal models of HFpEF a valuable resource and currently there are limited animal models that replicate the clinical characteristics of this disease. Exercise intolerance is a defining factor of HFpEF but is rarely investigated in animal models. We have developed a clinically relevant large animal (ovine) model of HFpEF demonstrating diastolic dysfunction and exercise intolerance. We induced HFpEF over 6 weeks by chronic hypertension using the Goldblatt 2-kidney-1-clip renovascular hypertension model, producing a significant increase in mean arterial pressure (control; 82.6 ± 4.6 vs HFpEF; 116.9 ± 6.6 mmHg, P <0.05). In response to exercise sheep with HFpEF exhibited a significantly blunted heart rate compared with control sheep (control; 149.6 ± 13.6 vs HFpEF 122.1 ± 7.3 bpm, P <0.05), DV/Dt(max) (control; 944.7 ± 239.0 vs HFpEF; 919.3 ± 117.3, P <0.05) and DV/Dt(min) (control; -646.8 ± 160.3 vs HFpEF; -761.3 ± 165.0, P <0.05) with a subsequent trend towards reduction in cardiac output (control; 13.5 ± 1.7 vs HFpEF; 11.3 ± 1.3 L/min, P >0.05) and stroke volume (control; 96.8 ± 12.0 vs 94.8 ± 10.7 m2/mL, P>0.05). We found no differences in resting heart rate or cardiac output between control sheep and HFpEF sheep. Our model demonstrated a blunted heart rate and reduced cardiac output that is consistent with exercise intolerance, likely due to diastolic dysfunction. Our findings suggest that this is a good model to investigate exercise intolerance and investigate potential treatment options with the goal of improving patient outcomes

    Autonomic Control of Coronary Blood Flow in Control and Heart Failure Ovine Models

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    Carotid bodies (CBs) are the main peripheral chemoreceptors that are strategically located at the bifurcation of the common carotid artery. They are the primary sensors of systemic hypoxia, and their stimulation elicits powerful reflex responses such as respiratory, autonomic, and cardiovascular adjustments critical for body homeostasis. Recent studies suggest that CB chemosensitivity is higher in patients with heart failure (HF) and animal models of HF. Activation of the CB is presumed to activate both the sympathetic and parasympathetic nerves to the heart but this has not been directly determined. In addition, the role of the CB in modulating coronary blood flow (CoBF) is unclear. I hypothesized that activation of the CB would increase directly recorded cardiac SNA, which would then lead to coronary vasodilation. I tested this in the conscious control animals. I also hypothesized that inactivation of the CB via hyperoxia would cause a reduction in CoBF in both control and HF groups. Experiments were conducted in conscious sheep implanted with electrodes to record cardiac SNA and diaphragmatic electromyography (dEMG), flow probes to record CoBF and cardiac output (CO) and a catheter to record mean arterial pressure (MAP). To eliminate the contribution of metabolic demand on coronary flow, the heart was paced at a constant rate during CB chemoreflex stimulation. Intra-carotid potassium cyanide (KCN) injection resulted in a significant increase in directly recorded cardiac SNA as well as a dose-dependent increase in MAP and CoBF. The increase in CoBF was augmented in the HF group when the influence of metabolic vasodilation was abolished. The increase in CoBF and coronary vascular conductance (CVC) to intracarotid KCN injection was abolished after propranolol infusion in the control group but not the HF group. The pressor response to activation of the CB was abolished by pre-treatment with intravenous atropine in both groups. My data suggests that CB-mediated increases in CoBF are mediated by an increase in cardiac SNA in the control group but not the HF group. Inactivation of the CBs using hyperoxia caused a significant decrease in MAP and CoBF in the HF group. To further examine the influence of pulmonary afferents, I used a novel airflow therapy, high nasal flow (HNF) and investigated the MAP, renal blood flow (RBF), and renal vascular conductance (RVC) responses to HNF in conscious normotensive and hypertensive sheep. HNF caused a significant decrease in blood pressure and increase in RVC in both groups. Taken together my studies suggest that CBs play an essential role in modulating blood flow to the heart and that HNF can be beneficial in conditions where the CB is hyperactive without causing impairment of blood flow to vital organs

    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

    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
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