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An experimental challenge model in lactating dairy cows using Streptococcus uberis for antibiotic efficacy testing : a thesis presented in partial fulfilment of the requirements for the degree of Master of Philosophy in Veterinary Science at Massey University, Palmerston North, New Zealand
The aim of this project was to develop a challenge model to test the efficacy of novel intramammary antimicrobial treatments for clinical mastitis. The use of the model, can reduces the costs of testing efficacy and accelerate the process of registration of new products. It provides controlled conditions which safeguard animal welfare.
The experimental challenge model using Streptococcus uberis developed in this thesis can provide the pharmaceutical industry and animal health research groups with a cost-effective method to test the efficacy of new antimicrobial products for treatment of mastitis in a safe and controlled environment. Two Cloxacillin-based antimicrobials with different formulations and treatment frequency were tested for their efficacy to cure S. uberis infections after infections were induced using the challenge model developed as described in the third chapter of this thesis.
The objective of the first study presented in this thesis was to choose one suitable strain from four strains of S. uberis, to be used in future challenge studies. Four strains were tested for their virulence and susceptibility to antibiotic therapy. A further study objective was to determine the dose (number of pathogens infused, expressed as colony forming units (CFU)) required for the tested strains to produce an acceptable proportion of clinical mastitis cases to enable future studies. The strain which accomplished the desired characteristics was then chosen and was utilised for experimental challenge in further studies (Chapters 4 and 5). The overall incidence of clinical mastitis obtained in this study at a quarter level was 54% (26/48). This study showed significant differences in the ability of different strains of S. uberis to cause clinical mastitis when inoculated via the intramammary route. However, only one of the four strains tested demonstrated favourable characteristics as a strain to be used in experimentally induced clinical mastitis studies.
Chapters 4 and 5 describe two challenge studies conducted using the experimental challenge model (Chapter 3) to test the efficacy of different antimicrobial drug formulations. In Chapter 4, the cure rate of one cloxacillin based product applied every 24 hr. was compared with the cure rate of a penicillin-based product applied every 12 hr. During the observation period of this investigation all challenged cows developed clinicalThe aim of this project was to develop a challenge model to test the efficacy of novel intramammary antimicrobial treatments for clinical mastitis. The use of the model, can reduces the costs of testing efficacy and accelerate the process of registration of new products. It provides controlled conditions which safeguard animal welfare.
The experimental challenge model using Streptococcus uberis developed in this thesis can provide the pharmaceutical industry and animal health research groups with a cost-effective method to test the efficacy of new antimicrobial products for treatment of mastitis in a safe and controlled environment. Two Cloxacillin-based antimicrobials with different formulations and treatment frequency were tested for their efficacy to cure S. uberis infections after infections were induced using the challenge model developed as described in the third chapter of this thesis.
The objective of the first study presented in this thesis was to choose one suitable strain from four strains of S. uberis, to be used in future challenge studies. Four strains were tested for their virulence and susceptibility to antibiotic therapy. A further study objective was to determine the dose (number of pathogens infused, expressed as colony forming units (CFU)) required for the tested strains to produce an acceptable proportion of clinical mastitis cases to enable future studies. The strain which accomplished the desired characteristics was then chosen and was utilised for experimental challenge in further studies (Chapters 4 and 5). The overall incidence of clinical mastitis obtained in this study at a quarter level was 54% (26/48). This study showed significant differences in the ability of different strains of S. uberis to cause clinical mastitis when inoculated via the intramammary route. However, only one of the four strains tested demonstrated favourable characteristics as a strain to be used in experimentally induced clinical mastitis studies.
Chapters 4 and 5 describe two challenge studies conducted using the experimental challenge model (Chapter 3) to test the efficacy of different antimicrobial drug formulations. In Chapter 4, the cure rate of one cloxacillin based product applied every 24 hr. was compared with the cure rate of a penicillin-based product applied every 12 hr. During the observation period of this investigation all challenged cows developed clinical mastitis in at least one quarter. The incidence of clinical mastitis at the quarter level was high, with 91.25% (73/80) of challenged quarters being affected. After diagnosis of infections, the cows were randomly allocated to two treatment groups and treated accordingly. Clinical cases in which the quarter did not respond to three applications of the allocated antimicrobial product received an extended treatment of the same product. As the allocation to the extended treatment was not random, clinical and bacteriological cures were statistically evaluated for the short treatment only. Clinical cure rates for the short treatment (3 syringes) were 52.63% and 43.75% for the cloxacillin- and penicillin-based products, respectively. There was no significant difference between the treatments (P = 0.8) in their efficacy for the treatment of experimentally induced S. uberis clinical mastitis.
In Chapter 5, two long-acting cloxacillin containing products were compared in their efficacy to cure experimentally induced S. uberis infections. One commercially available product was compared with a novel long acting product (applied every 48 hr.). Out of 80 challenged quarters, 41 quarters developed clinical mastitis after inoculation (51.25%). Treatment with the novel product resulted in a total treatment success rate of 93.1% based on clinical examination, and 96.0% based on the bacteriological cure rate. Treatment with the control product resulted in total treatment success rate of 100% based on clinical and bacteriological cure rate. There was no significant difference between the products (P=0.19) in their efficacy for the treatment of experimentally induced S. uberis clinical mastitis.
Results in this thesis showed that experimental challenge models can be a useful tool in animal research to test the efficacy of new products in a safe and cost effective manner
The physiology of the keratin plug formation in the teat canal of dairy cattle and its interaction with current and novel methods for prevention of intramammary infections : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science, Massey University, Turitea, Palmerston North, New Zealand
Chapter 6 was published as an open access article in the Journal of Dairy Science under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 (CC BY-NC-ND) license.
Chapter 7 was published as an open access article in Veterinary Sciences under a Creative Commons Attribution (CC BY) license. Both articles are attached.The incidence of intramammary infections (IMI) in dairy cows in the early dry period is the highest of the lactation cycle when methods to prevent IMI are not applied. This high incidence is comparable only with that observed near calving. At the
end of lactation, the teat is sealed by a plug formed mainly by keratinised cells, detritus and proteinaceous material. Research suggests that the keratin plug acts as a physicochemical barrier throughout the dry period that impedes the entrance of
bacteria. However, the physiological mechanism of keratin plug formation is still uncertain. The main objectives of this thesis were to characterise the physiological functions of the teat canal (TC) during the early dry period and assess how they
associate with the presence of IMI. A further objective was to evaluate the modes of action of a current mastitis preventative containing bismuth subnitrate and a novel formulation of micronized keratin that is under investigation as a teat seal for
preventing IMI during the early dry period.
To address these objectives a novel biopsy method was developed to allow investigation of the physiological characteristics of the epithelial tissues of the TC. A transcriptomic analysis of the TC epithelium after drying off showed that epithelial
cells decreased expression of mitotic and immune-response related genes.
A Streptococcus uberis strain was used in a challenge study aiming to examine mechanisms of colonization in the TC and the response of the epithelial tissue to progressing infection. This Streptococcus uberis challenge did not result in colonization
of the TC nor in IMI with S. uberis. Nevertheless, a reduction in the thickness of the stratum granulosum and the keratin layer of the TC epithelium was observed. This coincided with an increase in TC colonization by non-pathogenic bacteria and a decline
in the concentration of certain cytokines after drying off. These changes observed in the TC epithelium support previous reports showing increased incidence of IMI by non-pathogenic bacteria during the early dry period.
Antimicrobial effects and neutrophil cell responses were evaluated in vitro in two studies to test previously hypothesised action mechanisms for bismuth subnitrate and a novel keratin-based internal teat sealant (ITS) formulation. Bismuth subnitrate
showed an inhibitory effect on bacterial growth, contrary to the current description of ITS as non-pharmacological, inert physical barriers. No activation of a cellular response was observed for keratin or bismuth formulations in vitro. Bismuth
subnitrate and keratin were also tested in vivo for their effect on the formation of the keratin plug. The hypothesis of this study was that these treatments induce expression of mitogenic genes that induce a faster sealing of the teat canal. There was no
modification of gene expression after treating cows with bismuth subnitrate or the novel keratin-based ITS formulation during the formation of the natural keratin plug, and no modification of the closure status of the teat canal lumen, suggesting that
neither of the two treatments induced an improved sealing of the teat canal after drying off through increased keratin production.
These findings contribute to the knowledge of keratin plug formation and physiological characteristics of the TC during involution. They align with and partially explain some of the literature-reported events observed during the early dry period.
The knowledge gained provides support for future product development aimed to increase protection of the mammary gland during the dry period
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
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
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