1,720,956 research outputs found
Estimating antimalarial drug activity in vivo: an interdisciplinary approach combing novel experimental data with mathematical modelling
Get PDFMalaria infections led to an estimated 627 000 deaths in 2020. Artemisinin-based combination therapies are the current first-line malaria treatments. However, it is urgent to develop better antimalarial because artemisinin-resistant parasites are spreading, and the international efforts to eradicate malaria have stalled. There are currently 46 drugs in development by the Medicines for Malaria Venture at different phases of the drug development pipeline. During development, antimalarial drugs are tested in pre-clinical animal models and early-stage clinical trials to determine in vivo drug activity and safety. In these early phases, the criteria used to assess a candidate antimalarial drug's activity in vivo is the rapid clearance of parasites from the peripheral circulation called 'parasite clearance'. Short parasite clearance half-lives are interpreted to mean rapid drug action.
These parasite clearance data are used to parameterise PK/PD models that relate the drug's concentration with its killing activity in vivo. These models are used to predict and optimise dosing strategies for later clinical trials. However, it has recently been demonstrated that parasite clearance does not reflect how fast a drug kills parasites. The use of parasite clearance as a metric for assessing candidate antimalarial drugs must be revisited. Here, I consider novel parasite viability data from humanised mice and humans treated with two antimalarial drugs to develop a model of antimalarial drug activity and build a more nuanced understanding of parasite killing and host removal of dead parasites.
The new assay we use for estimating parasite viability is highly sensitive and can quantify down to one viable parasite per blood sample. Considering these parasites' viability estimates - rather than simply measuring parasite clearance - results in a more consistent PK/PD model that can better explain the parasite recrudescence after treatment. Moreover, the parasite-killing half-life is more sensitive to drug exposure time, dose and treatment regimen than the parasite clearance half-life.
In vivo drug activity estimates determine which antimalarial drug candidates will proceed down the development pipeline. My work shows that considering parasite viability increases PK/PD models' accuracy in explaining drug activity. Such models will provide a more precise measure of drug efficacy and can be used to assist in identifying the best treatment amongst the possible antimalarial candidates
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
Tutti frutti: Metabolomics Meets Machine Learning for Juicy Discoveries
No full textUnderstanding and predicting fruit phenotypes during development is crucial for quality improvement and food industry applications. Metabolomics, which analyzes the complete set of metabolites within biological samples, is particularly interesting in the case of multi-species studies. It offers a global view of the biochemical processes underlying phenotypes and provides data for many metabolites shared between species, which are therefore interoperable variables. In this study, we combined metabolomics data with machine learning techniques to predict diverse phenotypic traits across the development of ten fruits.By integrating metabolomics profiles with phenotype annotations, we constructed predictive models capable of associating metabolic variable abundance with traits such as growth rate, developmental stage, acidity or sugar content all along fruit development. Supervised machine learning algorithms, including Ridge, Elastic-Net and LASSO regression, Random Forests and Support Vector Machines were used to capture the complex relationships between metabolic profiles and phenotypic variations. Feature selection methods were used to identify key metabolic variables driving the prediction of each phenotype, providing insights into the metabolic functions potentially governing fruit development. Cross-validation procedures and independent validation datasets were employed to assess the robustness and generalization performance of the predictive models.In conclusion, the application of metabolomics on this multispecies datasets represents a significant advancement in our understanding of fruit development and offers unprecedented opportunities for innovation. By combining the power of metabolomics and advanced machine learning techniques, we will be able to unravel intricate molecular mechanisms governing phenotypic traits across multispecies experiments.Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovationCentre français de phénomique végétaleGlobal Omic Data Integration on Animal, Vegetal and Environment Sector
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
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