1,720,965 research outputs found

    Role of Physiologically Based Kinetic modelling in addressing environmental chemical mixtures – A review

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    The role of Physiologically Based Kinetic (PBK) modelling in assessing mixture toxicology has been growing for the last three decades. It has been widely used to investigate and address interactions in mixtures. This review describes the current state-of-the-art of PBK models for chemical mixtures and to evaluate the applications of PBK modelling for mixtures with emphasis on their role in chemical risk assessment. A total of 35 mixture PBK models were included after searching web resources (Scopus, PubMed, Web of Science, and Google Scholar), screening for duplicates, and excluding articles based on eligibility criteria. Binary mixtures and volatile organic compounds accounted for two-thirds of the chemical mixtures identified. The most common exposure route and modelled system were found to be inhalation and rats respectively. Twenty two (22) models were for binary mixtures, 5 for ternary mixtures, 3 for quaternary mixtures, and 5 for complex mixtures. Both bottom-up and top-down PBK modelling approaches are described. Whereas bottom-up approaches are based on a series of binary interactions, top-down approaches are based on the lumping of mixture components. Competitive inhibition is the most common type of interaction among the various types of mixtures, and usually becomes a concern at concentrations higher than environmental exposure levels. It leads to reduced biotransformation that either means a decrease in the amount of toxic metabolite formation or an increase in toxic parent chemical accumulation. The consequence is either lower or higher toxicity compared to that estimated for the mixture based on the additivity principle. Therefore, PBK modelling can play a central role in predicting interactions in chemical mixture risk assessment

    Grouping of multi-walled carbon nanotubes to read-across genotoxicity: A case study to evaluate the applicability of regulatory guidance

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    Multi-walled carbon nanotubes (MWCNTs) consist of multiple layers of graphene sheets in a tubular shape. Depending on the synthesis and purification method, MWCNTs may differ in size, shape, rigidity and other properties. Previous research has shown that physicochemical properties can influence the translocation and toxicity of MWCNTs. Extensive in vitro and in vivo testing may be required to characterise the hazard of various physical forms of MWCNTs. Grouping of MWCNTs to read-across data for toxicological endpoints could efficiently contribute to reduce and focus MWCNT testing. This paper describes a case study to explore and illustrate read-across of genotoxicity data by following the “Recommendations for nanomaterials applicable to the Guidance on QSARs and Grouping”, developed by the European Chemicals Agency (ECHA). The grouping hypothesis was supported by the use of chemoinformatics techniques such as hierarchical clustering and principal components analysis. The uncertainties of the present case study were evaluated using the Read-Across Assessment Framework (RAAF) developed by ECHA. While the aim of this study was not to conduct a hazard assessment, the study data chosen for illustrative purposes suggest that the MWCNTs analogues selected are not genotoxic. No (major) differences between the analogues were observed which could be attributed to differences in physicochemical properties such as length, diameter or rigidity/straightness. Such properties, however, may have an impact on other hazard endpoints such as carcinogenicity. This study shows the practical application of the ECHA framework for grouping of nanomaterials (NMs) as well as use of the ECHA RAAF for NMs, and how this can be supported by chemoinformatics techniques. Some adaptations to the workflow are suggested for a more practical and straightforward narrative in the reporting

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

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    “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

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    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

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    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

    Author Index

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    The virtual cell based assay: Current status and future perspectives

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    extcopyright 2017 The Authors In order to replace the use of animals in toxicity testing, there is a need to predict in vivo toxic doses from concentrations that cause toxicological effects in relevant in vitro systems. The Virtual Cell Based Assay (VCBA) estimates time-dependent concentration of a test chemical in the cell and cell culture for a given in vitro system. The concentrations in the different compartments of the cell and test system are derived from ordinary differential equations, physicochemical parameters of the test chemical and properties of the cell line. The VCBA has been developed for a range of cell lines including BALB/c 3T3 cells, HepG2, HepaRG, lung A459 cells, and cardiomyocytes. The model can be used to design and refine in vitro experiments and extrapolate in vitro effective concentrations to in vivo doses that can be applied in risk assessment. In this paper, we first discuss potential applications of the VCBA: i) design of in vitro High Throughput Screening (HTS) experiments; ii) hazard identification (based on acute systemic toxicity); and iii) risk assessment. Further extension of the VCBA is discussed in the second part, exploring potential application to i) manufactured nanomaterials, ii) additional cell lines and endpoints, and considering iii) other opportunities.In order to replace the use of animals in toxicity testing, there is a need to predict in vivo toxic doses from concentrations that cause toxicological effects in relevant in vitro systems. The Virtual Cell Based Assay (VCBA) estimates time-dependent concentration of a test chemical in the cell and cell culture for a given in vitro system. The concentrations in the different compartments of the cell and test system are derived from ordinary differential equations, physicochemical parameters of the test chemical and properties of the cell line. The VCBA has been developed for a range of cell lines including BALB/c 3T3 cells, HepG2, HepaRG, lung A459 cells, and cardiomyocytes. The model can be used to design and refine in vitro experiments and extrapolate in vitro effective concentrations to in vivo doses that can be applied in risk assessment. In this paper, we first discuss potential applications of the VCBA: i) design of in vitro High Throughput Screening (HTS) experiments; ii) hazard identification (based on acute systemic toxicity); and iii) risk assessment. Further extension of the VCBA is discussed in the second part, exploring potential application to i) manufactured nanomaterials, ii) additional cell lines and endpoints, and considering iii) other opportunities

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    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
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