1,720,966 research outputs found
Developing a new anti-sporozoite malaria vaccine
No full textMalaria is one of the leading infectious causes of morbidity and mortality. There was an estimated 241 million malaria cases and 627,000 deaths in 2020 across 85 malaria endemic countries. When compared with data from recent years, this suggests that global progress has stalled, and that malaria mortality is increasing. There is an urgent need to develop new tools to combat this.
Significant progress has been made in malaria vaccine development, with the first malaria vaccine, RTS,S/AS01, achieving prequalification this year (2022). However, the current production capacity of RTS,S/AS01 may not, at least initially, meet the needs of the target population. At the same time, the WHO goal of developing a malaria vaccine with protective efficacy of ≥75% against clinical malaria, for at-risk groups in malaria-endemic areas, over at least 2 years, has not yet been met.
R21 is produced by using recombinant HBsAg particles expressing the central repeat and the C-terminus of the Plasmodium falciparum circumsporozoite protein. R21 was initially developed at the University of Oxford and is now manufactured by the Serum Institute of India Pvt. Ltd (SIIPL). R21 is combined with an adjuvant, Matrix-M, manufactured by Novavax AB, to produce the vaccine candidate R21/Matrix-M which targets P. falciparum malaria.
In this thesis, I describe the clinical development assessing safety, immunogenicity and efficacy of the R21/Matrix-M malaria vaccine candidate across a phase I/IIa clinical trial in UK adults (chapter 3); a phase Ib clinical trial in Kenya in adults, young children and infants (chapter 4); and a phase IIb clinical trial in infants in Burkina Faso (chapter 5). I evaluate the composition of the gut microbiome of infants living in malaria endemic areas (the target population for R21/Matrix-M) to assess if this is affected by any specific participant factors. I also assess if the baseline gut microbiome suggests any correlation with antibody responses generated by R21/Matrix-M, and if any association exists between the gut microbiome composition and the total number of malaria episodes experienced at 12 months following vaccinations (chapter 6).
The clinical development phases of R21/Matrix-M have demonstrated that the vaccine is safe, immunogenic and protective against malaria. Importantly, efficacy of ≥75% against clinical malaria was noted over 2 years in the target population of African infants, in the phase IIb trial, where vaccinations were administered prior to or at the start of the malaria season. The composition of the gut microbiome varied significantly according to age of the infant but had no impact on the antibody responses to the R21/Matrix-M malaria vaccine or the number of malaria episodes experienced by an infant.
In my conclusions in this thesis, I have reflected on some of the key issues beyond the science that affect deployment and implementation of a successful malaria vaccine. In order to make strides in eliminating malaria in sub-Saharan Africa, it is necessary for there to be cooperation amongst multiple stakeholders; developments in manufacturing and delivery of vaccines; and grassroots participation in vaccine programmes.
The results from these trials have led to a phase III trial across five African sites, in East and West Africa, evaluating the safety and efficacy of R21/Matrix-M in areas of differing malaria transmission in a larger number of infants and children. The aim is licensure of a safe, inexpensive vaccine, with high efficacy, that will significantly reduce the malaria disease burden
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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
No full textWe 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.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn 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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