1,721,011 research outputs found
Immunogenicity and protective efficacy of an anti-Streptococcus pyogenes vaccine candidate in multiple animal species
Streptococcus pyogenes, also known as Group A Streptococcus (GAS) has been associated with a range of diseases from the mild pharyngitis and pyoderma to more severe invasive infections such as streptococcal toxic shock. GAS also causes a number of non-suppurative post-infectious diseases such as rheumatic fever, rheumatic heart disease and glomerulonephritis. The large extent of GAS disease burden necessitates the need for a prophylactic vaccine that could target the diverse GAS emm types circulating globally. Anti-GAS vaccine strategies have focused primarily on the GAS M-protein, an extracellular virulence factor anchored to GAS cell wall. As opposed to the hypervariable N-terminal region, the C-terminal portion of the protein is highly conserved among different GAS emm types and is the focus of a leading GAS vaccine candidate, J8-DT/alum. The vaccine candidate J8-DT/alum was shown to be immunogenic in mice, rabbits and the non-human primates, hamadryas baboons. Similar responses to J8-DT/alum were observed after subcutaneous and intramuscular immunization with J8-DT/alum, in mice and in rabbits. Further assessment of parameters that may influence the immunogenicity of J8-DT demonstrated that the immune responses were identical in male and female mice and the use of alum as an adjuvant in the vaccine formulation significantly increased its immunogenicity, resulting in a long-lived serum IgG response. Contrary to the previous findings, the data in this thesis indicates that a primary immunization with J8-DT/alum (50ƒÊg) followed by a single boost is sufficient to generate a robust immune response in mice. As expected, the IgG response to J8- DT/alum was a Th2 type response consisting predominantly of the isotype IgG1 accompanied by lower levels of IgG2a. Intramuscular vaccination of rabbits with J8-DT/alum demonstrated that an increase in the dose of J8-DT/alum up to 500ƒÊg does not have an impact on the serum IgG titers achieved. Similar to the immune response in mice, immunization with J8-DT/alum in baboons also established that a 60ƒÊg dose compared to either 30ƒÊg or 120ƒÊg was sufficient to generate a robust immune response. Interestingly, mucosal infection of naive baboons with a M1 GAS strain did not induce a J8-specific serum IgG response. As J8-DT/alum mediated protection has been previously reported to be due to the J8- specific antibody formed, the efficacy of J8-DT antibodies was determined in vitro and in vivo. In vitro opsonization and in vivo passive transfer confirmed the protective potential of J8-DT antibodies. A reduction in the bacterial burden after challenge with a bioluminescent M49 GAS strain in mice that were passively administered J8-DT IgG established that protection due to J8-DT was mediated by antibodies. The GAS burden in infected mice was monitored using bioluminescent imaging in addition to traditional CFU assays. Bioluminescent GAS strains including the ‘rheumatogenic’ M1 GAS could not be generated due to limitations with transformation of GAS, however, a M49 GAS strain was utilized during BLI. The M49 serotype is traditionally a ‘nephritogenic’ serotype associated with post-streptococcal glomerulonephritis. Anti- J8-DT antibodies now have been shown to be protective against multiple GAS strains such as M49 and M1. This study evaluated the immunogenicity of J8-DT/alum in different species of experimental animals in preparation for phase I human clinical trials and provided the ground work for the development of a rapid non-invasive assay for evaluation of vaccine candidates
Island Dreaming: Applied Epidemiology in the Pacific Region
This bound volume describes four significant public health
problems in Australia and the Pacific Island Countries of Fiji
and American Samoa. The four main epidemiological components
are:
1) Australian vaccine preventable disease epidemiological review
series: varicella-zoster virus infections, 1998–2015. The
review was conducted to assess the impact of the national
varicella immunisation program and provide a baseline for
monitoring the impact of the national herpes zoster immunisation
program. The national varicella immunisation program led to
significant reductions in varicella. In Australia, the burden of
herpes zoster is substantial, and high quality and timely
surveillance will be crucial to assess the impact of the national
herpes zoster immunisation program.
2) Investigation into increased lymphogranuloma venereum (LGV) in
New South Wales, Australia. LGV is a sexually transmitted
infection (STI) caused by L1-L3 serovars of chlamydia, and can
lead to irreversible complications. LGV is notifiable condition
in New South Wales (NSW). Following a noticeable increase in
number of LGV notifications, I conducted a retrospective case
series of all cases diagnosed between 1 January 2016 and 31 March
2017. During this period, all reported cases were among men who
have sex with men. This chapter examines factors contributing to
increase in LGV cases in NSW in 2016. It also describes the
challenges associated with investigating STI outbreaks in NSW.
3) An evaluation of an early warning alert and response system
(EWARS in a Box) implemented after Cyclone Winston, Fiji 2016.
The World Health Organization recommends implementation of early
warning systems for timely disease surveillance and early
detection of outbreaks during humanitarian emergencies. This
chapter describes the EWARS system, and its usefulness at timely
monitoring of communicable diseases trends during a national
health emergency. Findings include strengths and limitations of
the system at conducting surveillance, along with practical
recommendations for improving surveillance using EWARS.
4) Identifying residual transmission of lymphatic filariasis in
post-mass drug administration surveillance phase: Comparing
school-based versus community-based surveys – American Samoa,
2016. This study compares the effectiveness of two
cross-sectional survey designs, a school-based and a
community-based survey, for assessing transmission of lymphatic
filariasis. Under the Global Programme for Elimination of
Lymphatic Filariasis, American Samoa conducted seven rounds of
mass drug administration (MDA) from 2000-2006. The World Health
Organization recommends systematic post-MDA surveillance for
epidemiological assessment of recent lymphatic filariasis
transmission. Finger prick blood samples were collected from
study participants to measure the prevalence of circulating
filarial antigen (CFA). I recruited 1143 grade 1 and 2 school
students from 29 elementary schools. For the community survey, 30
out of 70 villages were randomly selected, from which 2507
community members were recruited. The school survey was cheaper
and logistically easier to implement. The estimated CFA
prevalence by school survey was 0.7%, and was significantly lower
than the community survey (6.2%). The community survey was more
effective for collecting information required for identifying
residual transmission of lymphatic filariasis. Both surveys
provided evidence of ongoing lymphatic filariasis transmission in
American Samoa
Health security in the Pacific: expert perspectives to guide health system strengthening
This report seeks to identify and prioritise health system strengthening initiatives that prevent impacts of health security threats and strengthen the ability to respond to these threats in the Pacific region. For this report, we focus on Timor Leste, Papua New Guinea and Pacific Island Countries and Areas, hereafter collectively referred to as ‘the Region’. Pacific Island Countries and Areas include the Cook Islands, Fiji, Kiribati, the Republic of the Marshall Islands, the Federated States of Micronesia, Nauru, Niue, Palau, Samoa, Solomon Islands, the Kingdom of Tonga, Tuvalu and Vanuatu
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
- …
