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Investigations into the pathogenic mechanisms of the leptospiral pulmonary haemorrhage syndrome (LPHS)
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Investigations into the Epidemiology, Diagnostics and Pathogenic mechanisms of Leptospirosis
No full textLeptospirosis is considered one of the most widespread zoonoses worldwide affecting a broad range of warm and cold-blooded animals. It represents a major public health issue in tropical and subtropical countries. While human leptospirosis remains rare in Switzerland, a dramatic increase in the incidence of canine leptospirosis was documented between 2003 and 2012. Moreover, a previously uncommon, severe form of leptospirosis associated with pulmonary haemorrhage emerged during this period and led to high morbidity amongst dogs. This form of leptospirosis also affects many other species and has become the major cause of mortality from leptospirosis in humans. The pathogenic mechanisms of leptospiral pulmonary haemorrhage syndrome (LPHS) are poorly understood hampering the application of efficient treatment strategies.
With the backdrop of these events, an urgent need to better understand the epidemiology of canine leptospirosis, to validate rapid diagnostic tools and to better understand the pathogenic mechanisms leading to pulmonary haemorrhage was identified and collaborations established to tackle these important questions.
The results of these studies are included in this habilitation.
We demonstrated that despite a very high incidence of acute canine leptospirosis in Switzerland, the prevalence of anti-leptospiral antibodies in the overall canine population is in the mid-range (24%) to what has been described in other areas in Europe (6-49%). Dogs in Switzerland rarely showed evidence of urinary shedding of pathogenic Leptospira spp. (0.001%) and thus probably do not significantly contribute to the spread of Leptospria in the environment. In contrast, dogs in Ireland, showed a much higher rate of urinary shedding (7.8%).These studies showed that there are regional differences in the epidemiology leptospirosis even across Europe, and that the role of the dog in the disease transmission may vary depending on the prevailing serovars in any given region.
Early confirmation of acute leptospirosis is important because of its zoonotic potential. Patient side tests to detect anti-leptospiral IgM have recently become commercially available and claim to have a higher sensitivity in early infection than the gold standard microscopic agglutination test (MAT) because of the early occurrence of IgM in patient serum. Demonstrated that the diagnostic accuracy of two commercial patient side tests, is similar to that of the MAT and thus can be helpful tools in the management of patients suspected to have leptospirosis.
An important part of this work was dedicated to establish the dog as a natural disease model for leptospirosis and LPHS and to further elucidate the pathogenic mechanism of LPHS. Initially we investigated the hypothesis that LPHS in in part mediated by the host immune system. Indeed, we were able to demonstrate deposition of IgG and IgM on alveolar walls of canine patients with LPHS in the absence of leptospiral antigens, which suggests that host rather than leptospiral antigens are targeted by the immune response. However, further extensive work to identify potential autoreactive antigens has so far failed to confirm any specific targets. We therefore also applied a top down proteomics approach to generate new hypotheses. Comparative proteomic analysis of LPHS lung tissue of experimentally infected guinea pigs demonstrated a significant decrease in abundance of proteins involved in the cytoskeleton and cellular organisation, many of them being involved in the maintenance of the endothelial barrier function, thus suggesting a role of the endothelium in the pathogenesis of LPHS.
To further investigate the role of endothelial cell activation and dysfunction in LPHS in vivo, we have validated a human ELISA for measurement of canine Angiopoietin-2. Angiopoietin-2 is an important marker of endothelial cell dysfunction and was significantly elevated in a validation population of dogs with sepsis and systemic inflammatory response syndrome. Furthermore, protocols were established to isolate canine aortic endothelial cells, which represents another important research tool to investigate endothelial dysfunction in leptospirosis using the dog as a natural disease model.
With these tools in place we are now able to study endothelial responses during infection with Leptospira spp both in vitro and in vivo and are currently focussing on the role of the endothelial adherence junction in the breakdown of the endothelial barrier function in LPHS
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
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