1,720,953 research outputs found
Advancing assessments of endocrine disruptors using adverse outcome pathways and novel methodologies
No full textProtecting human and environmental health from adverse effects of endocrine disruptors (EDs) is a high priority in the EU. These substances cause a range of adverse effects, such as reproductive toxicity, neurotoxicity, metabolic disruption, and cancer. If an organism is exposed during a developmental life stage, the effects may also be permanent. Assessing if a substance has endocrine disrupting properties is a lengthy and complex process that requires considerable amounts of animal data. There is a demand to phase-out animal testing in the EU and, simultaneously, there is growing use of alternative methods, like in silico, in chemico, and in vitro methods. Hence, there is a need, and an opportunity, to move toward ED assessments based on mechanistic data from alternative methods. However, there is a lack of methodology to connect these types of novel and complex data to adverse outcomes for use in ED assessments.The aim of my doctoral project was to develop and explore methodologies for the assessment of endocrine disruptors based on mechanistic data. The Adverse Outcome Pathway (AOP) framework was crucial to achieve this and was used across all subprojects of the thesis. I explored many complex aspects of the AOP framework, including development and application of AOP network and quantitative AOPs (qAOPs). Literature-based, computational, and experimental approaches were utilized, as well as combinations of these.In Study I, I developed a data-driven approach to generate AOP networks. This approach combines a systematic approach to identifying relevant AOPs in the AOP-Wiki with a computational approach to process and filter AOP-Wiki data. The output could then be imported into a software for visualization and analysis of networks.In Study II, I conducted and compared a standard ED assessment according to current guidance, to a mechanism-based assessment without in vivo data. A thyroid-related AOP network was utilized for identifying relevant search terms and for mapping collected data to identify a potential Mode of Action. This case study was performed using perfluorooctane sulfonic acid (PFOS) as a model substance, investigating its potential for thyroid disruption and developmental neurotoxicity.In Study III, RNA-sequencing of zebrafish embryos exposed to either cadmium (Cd) or 3,3',4,4',5-pentachlorobiphenyl (PCB126) was performed to investigate how transcriptomics data can be coupled to an AOP network. Multiple different data analysis approaches were explored, and their potential connection to an estrogen, androgen, thyroid, and steroidogenesis (EATS) related AOP network was evaluated. Ultimately, I developed and compared a data-driven and an expert-driven approach to connect Gene Ontology (GO) terms from enrichment analysis to key events (KEs) in the network.In Study IV, I developed an approach to quantify a Key Event Relationship (KER) based on data from published literature, and applied this approach on a KER linking decreased circulating testosterone levels to decreased sperm count. The approach consists of two parts, (1) A structured search strategy, study reliability assessment, and standardized data extraction to collect and assess data for quantification, and (2) a statistical modelling approach to make the best use of the collected data.Through the development and application of AOP networks (Study I and III) I identified several opportunities for improving AOP development and functionality of the AOP-Wiki. The issues identified hinder topological analysis and application of data-driven approaches to connect mechanistic data to the network. In Study II, based on the standard ED assessment, I concluded that PFOS fulfils the scientific criteria as an ED based on thyroid disruption and developmental neurotoxicity. On the other hand, in the mechanism-based assessment, I could only identify endocrine activity and not endocrine-mediated adversity. There was a lack of quantitative understanding of the AOPs in the network, which was essential to inferring adversity based on mechanistic data. Study III revealed that both cadmium and PCB126 potentially have endocrine disrupting properties. Endocrine activity, and adversity likely mediated by EATS or non- EATS modalities, were observed. The data-driven approach to connect transcriptomics data to the AOP network yielded very few results, while the expert-driven approach provided many more connections. Gene expression measurements followed by enrichment analysis may be fit for connecting data to intermediate and late KEs, but not for early KEs and molecular initiating events (MIEs). In Study IV, the quantified KER can be used to predict decreased sperm count based on a decrease in circulating testosterone levels, including some uncertainty in the circulating testosterone levels. The model can potentially be used to reduce or replace animal experiments if coupled to e.g., in vitro testosterone synthesis experiments or physiologically based kinetic (PBK) models.To conclude, I have developed and applied novel risk assessment methodologies to maximize the use of mechanistic data for ED assessment. Both opportunities and challenges with these approaches have been explored, and future research needs have been identified. Moreover, endocrine disrupting properties of chemicals not yet classified as EDs (perfluorooctane sulfonic acid , cadmium, and 3,3',4,4',5- pentachlorobiphenyl) were investigated. Altogether, these results pave the way toward non-animal mechanism-based assessment of EDs and improved protection of human health.List of scientific papersI. Wiklund L, Caccia S, Pipal M, Nymark P, Beronius A. Development of a data-driven approach to Adverse Outcome Pathway network generation: a case study on the EATS-modalities. Front Toxicol. 2023 May 9; 5:1183824. https://doi.org/10.3389/ftox.2023.1183824II. Wiklund L, Pipal M, Weiss J, Beronius A. Exploring a mechanism-based approach for the identification of endocrine disruptors using Adverse Outcome Pathways (AOPs) and New Approach Methodologies (NAMs): A perfluorooctane sulfonic acid case study. Toxicology. 2024 May; 504:153794. https://doi.org/10.1016/j.tox.2024.153794III. Wiklund L, Wincent E, Beronius A. Using transcriptomics data and Adverse Outcome Pathway networks to explore endocrine disrupting properties of Cadmium and PCB-126. Environ Int. 2025 Mar; 197:109352. https://doi.org/10.1016/j.envint.2025.109352IV. Wiklund L, Ristovska M, Moe J, Beronius, A. Quantification of the Key Event Relationship "Decreased circulating testosterone leading to impaired spermatogenesis" based on data from peer-reviewed studies. [Manuscript]</p
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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