1,720,979 research outputs found
Modelling HIV Drug Resistance in Southern Africa.
Full text linkSouthern Africa is the region most affected by HIV globally. In South Africa, for example, the
prevalence of HIV reaches 17% among adults. In the early 2000s, the roll-out of antiretroviral
therapy (ART), a non-nucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside
reverse transcriptase inhibitors (NRTIs), had a dramatic impact on decreasing mortality
related to acquired immunodeficiency syndrome (AIDS). However, the recent emergence of
resistance to NNRTI threatens the long-term efficacy of such regimen. As a response, a new
ART first-line regimen is introduced in several countries of Southern Africa, where the NNRTI
drug is replaced by an integrase strand transfer inhibitor (InSTI) drug, called dolutegravir
(DTG). DTG has a high genetic barrier to resistance, is highly effective, well tolerated and
affordable in resource-limited settings. In this thesis, I develop mathematical models aimed
at characterizing different aspects of the dynamics of HIV drug resistance in Southern Africa.
In Chapter 1, I give a brief timeline of the HIV-epidemic in Southern Africa. I then introduce
basic concepts on HIV, ART, and HIV drug resistance. I present the different strategies that
have been implemented in Southern Africa to fight HIV. Finally, I discuss the increasing role
that mathematical models play to gain insight on the HIV-epidemic.
In Chapter 2, I run a systematic review and meta-analysis estimating the prevalence
of NRTI/NNRTI drug resistance mutations among adults failing a first-line NNRTI-based
regimenin Southern Africa. I develop a Bayesianhierarchicalmodelthat synthesizes evidence
from the collected studies. The model estimates high levels of K65 and M184 mutations
after 2 years of regimen including emtricitabine or lamivudine (FTC/3TC) and tenofovir
(TDF), the two NRTI backbones that are now commonly associated in first-line regimen. The
K65 and M184 mutations confer high levels of resistance to FTC/3TC and TDF, respectively.
Therefore, it suggests that between 43% and 55% of people failing a NNRTI-based regimen,
will switch to DTG-based regimen with substantially compromised NRTI backbones, if they
are not optimized. These results show the importance of monitoring DTG-response in this
population, as they have higher risk of DTG-failure, where resistance could develop.
In Chapter 3, I develop a compartmental model, the MARISA model, which captures both
the general HIV-epidemic and the dynamic of NNRTI drug resistance in South Africa.
Data from several sources, including cohort data on thousands of people living with HIV
(PLWH), are used to calibrate the model. The MARISA model also assesses the impact
of counterfactual scenarios reflecting alternative countrywide policies during 2005-2016,
considering either increasing ART coverage, improving management of treatment failure,
broadening ART eligibility, or implementing drug resistance testing before ART initiation. I
identify key driversof theNNRTI resistance epidemic: large-scaleARTroll-out andinsufficient
monitoring of first-line treatment failure. The results also suggest that no simple measure
CHAPTER . ABSTRACT
could have prevented the rise ofNNRTI resistance in the South African context, whereNNRTIs
have been rapidly rolled out.
In Chapter 4, I adapt the MARISA model to assess the impact of different strategies of DTG
introduction on the level of NNRTI resistance in South Africa. I investigate the impact of two
scenarios of the DTG-introduction: 1) DTG as a first-line ART, or 2) DTG replacing NNRTIs for
all patients, including patients on NNRTI-based regimen. Due to safety concerns related to
DTG during pregnancy, the model also considers scenarios whereDTG is prescribed to all men
and in addition to i) women beyond reproductive age, ii) women beyond reproductive age or
using contraception, and iii) allwomen. The simulations showthat, while somestrategies can
stabilize the level of NNRTI resistance, none of the different strategies introducing DTG leads
to its elimination. To halt the increase of NNRTI resistance, DTG should become accessible to
both women and people currently on NNRTI-based therapy. As some women (e.g. women
at risk of pregnancy) will continue to rely on NNRTI-based ART in the future, controlling the
resistance to NNRTI is key to provide them with an effective alternative to DTG.
The Chapter 5 discusses some important public-health questions regarding HIV drug
resistance in sub-Saharan Africa. It stresses the central role of mathematical modelling to
quantify the risk of HIV drug resistance when data is scarcely available. It also discusses the
modelling idea used in Chapters 3 and 4 and shows howmathematical models can bridge the
gap between the wide availability of HIV epidemiological data and the limited knowledge on
HIV drug resistance in the African regions.
In Chapter 6, I summarize the main findings presented in Chapters 2-4 and discuss their
implications. I also present the strengths and weaknesses of the project. Finally, I discuss
the perspective of the potential emergence of resistance to DTG. The Chapter 7 presents an
additional study, in which I was involved but which does not represent the core ofmy thesis.
In this study, a mathematical model reproduces the dynamics of the SARS-CoV-2 epidemics
in several regions of the world and provides estimates of the age-specific mortality related to
SARS-CoV-2.
In this thesis, I use mathematical modelling to capture the emergence of NNRTI resistance in
South Africa. I identify some factors that have driven the development of NNRTI resistance,
such as the long time spent on a failing regimen. Due to its flexibility, the MARISA model is
adapted to investigate future strategies, such as the impact of the DTG-introduction on the
levels of NNRTI resistance. This shows that processes such as the acquisition and the spread
of HIV drug resistance can be reproduced at the population-level using mathematical models
calibrated with clinical resistance data. As South Africa is currently introducing DTG-based
regimen, such modelling approach can be implemented to investigate the future risk of
emergence of DTG resistance. However, even if mathematical models could help to bridge
the gaps between clinical and real-world resource-limited settings, more real-world data
is needed to understand the actual risk of DTG resistance development in the context of a
countrywide implementation of DTG. The meta-analysis in Chapter 2 adds to the body of
evidence, as it highlights the potential threat on the long-term efficacy of DTG posed by the
switch of patients with elevated viral load. Close follow-up and resistancemonitoring of these
patients are therefore key to ensure an early detection of DTG resistance and prevent it from
spreading through the population
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
- …
