1,721,434 research outputs found
Brominated flame retardants : bioactive metabolites and biomarker of human Exposure
No full textLes retardateurs de flamme bromés sont des agents ignifuges utilisés dans de nombreux produits manufacturés. Les plus courants sont les polybromodiphényl éther (PBDE), le tétrabromo-bisphénol A (TBBPA) et l'hexabromocyclododécane (HBCD). Ces composés considérés comme des polluants organiques persistants (POPs) sont désormais retrouvés dans l'environnement et chez l'Homme, et sont suspectés, ainsi que leurs métabolites, d'être des perturbateurs endocriniens. Des développements analytiques basés sur la spectrométrie de masse ont été engagés afin d'étudier le métabolisme in vitro du TBBPA et des PBDE et rechercher les composés parents et leurs métabolites dans différents prélèvements d'origine humaine. Les métabolites formés chez l'Homme ont ainsi été identifiés comme étant des conjugués pour le TBBPA, et des dérivés hydroxylés, dihydrodiol et conjugués pour les PBDE. La plupart de ces métabolites ont été identifiés et quantifiés dans les fluides biologiques humains, démontrant ainsi l'exposition du fœtus et du nouveau-né à ces composés, à des niveaux similaires à ceux retrouvé dans d'autres pays. D'un point de vue qualitatif, la présence de métabolites potentiellement actifs sur des cibles cellulaires a été mise en évidence, ainsi que le passage des résidus vers le lait (TBBPA, HBCD) et/ou au travers de la barrière placentaire (TBBPA et PBDE). Un métabolite spécifique, présent en importantes (octa-BDE hydroxylé) pourrait être un bon biomarqueur d'exposition, et son potentiel toxique devrait par ailleurs être étudié.Brominated Flame Retardants are widely used for the manufacture of fire-proofed industrial products and consumer goods. Major BFRs are polybromodiphenyl ether (PBDE), tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCD). Considered as persistent organic pollutants (POPs), they are detected in various environmental compartments and human samples. Parent compounds as well as several metabolites could act as endocrine disruptors. Methodological developments based on mass spectrometry, in vitro approaches (TBBPA, PBDE) and an extensive review of the available literature have been used to sharpen our current knowledge of the fate of BFR, and to identify both parent compounds and metabolite in human samples. Results obtained in vitro using human primary hepatocyte cultures as well as human cell lines show that human cells biotransform TBBPA into conjugated metabolites and PBDE into hydroxylated, dihydrodiol and conjugated metabolites. Those metabolites were detected in human samples, demonstrating foetal and newborn exposition. BFR and some of their metabolites, including bioactive compounds, are transferred through the placental barrier (TBBPA, PBDE) and/or into milk (TBBPA, HBCD). Even though the monitored concentration levels were found to be low, one of these metabolites, namely (OH-octaBDE) was found to be abundant in almost all serum samples, and appears to be a relevant candidate biomarker of exposur
Développement d'approches de profilage non ciblé pour la mise en évidence de dangers chimiques émergents : Application à l'identification de nouveaux marqueurs d'exposition interne chez l'Homme au service de la biosurveillance et de l'étude du lien entre exposition chimique et santé humaine
No full textL’exposition de l’Homme aux contaminants chimiques présente un risque pour sa santé. Des programmes de biosurveillance sont menés dans de nombreux pays pour évaluer à la fois cette exposition, son impact en terme de santé, ainsi que l’efficacité des mesures de gestion et des dispositions réglementaires mises en place. L’Union Européenne a lancé en 2017 le projet Human Biomonitoring for Europe (HBM4EU) afin de consolider un réseau pan-Européen dans ce domaine, et de mieux documenter la réalité de l’exposition chimique des citoyens européens et son impact sur la santé humaine. Les approches historiquement mises en œuvre pour caractériser l’exposition, de type ciblées, sont très performantes pour rechercher et quantifier les contaminants déjà connus. En revanche, elles ne permettent pas de rendre compte de la complexité des expositions, en particulier vis-à-vis des contaminants émergents. Pour pallier ce manque d’exhaustivité, de nouvelles approches dites non-ciblées sont aujourd’hui développées. Le présent travail de thèse, inscrit dans le projet HBM4EU, a eu pour objectif le développement de stratégies analytiques non-ciblées depuis la préparation d’échantillons, leur profilage par couplage LC- et GC-HRMS, jusqu’au retraitement des données. Plusieurs matrices humaines ont été considérées avec un focus autour de l’exposition périnatale. Ce travail a abouti à une première preuve de concept démontrant la capacité de ces approches pour l’identification de composés émergent sans a priori. Ces recherches ont également permis de mettre en évidence les principaux défis associées à ces approches pour tous laboratoiresHuman exposure to chemical contaminants may impact his health. Biomonitoring programs are conducted in many countries to assess both this exposure, its consequence on human health, and the efficiency of regulatory and risk management provisions. The European Union launched the Human Biomonitoring for Europe (HBM4EU) project in 2017 to consolidate a pan-European network in this field, and better document the reality of chemical exposure of European citizens and establish the possible link with human health. The historical approaches used to characterise the exposure, known as targeted methods, are efficient to monitor and quantify already known substances. However, they do not allow to reflect the complexity of human exposure and in particular do notcapture new contaminants of emerging concern. To overcome this lack of completeness, new approaches such as suspect and non-targeted screening are today developed. The present thesis work, part of the HBM4EU project, aimed to develop such non-targeted analytical strategies from sample preparation, LC- and GC-HRMS profiling, to data processing. Several human matrices were considered with special emphasis on perinatal exposure. This work led to a first proof-of-concept demonstrating the interest of these approaches for identifying emerging chemicals without a priori. These researches have also highlighted main challenges to be faced in the development of these approaches for all laboratories wishing to join this dynamic
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
Release and toxicity of adipose tissue-stored TCDD: Direct evidence from a xenografted fat model
No full text1873-6750 Joffin, Nolwenn Noirez, Philippe Antignac, Jean-Philippe Kim, Min-Ji Marchand, Philippe Falabregue, Marion Le Bizec, Bruno Forest, Claude Emond, Claude Barouki, Robert Coumoul, Xavier Journal Article Netherlands Environ Int. 2018 Oct 31. pii: S0160-4120(18)31382-5. doi: 10.1016/j.envint.2018.10.027.International audienceBackgroundPersistent organic pollutants (POPs) are known to accumulate in adipose tissues (AT). This storage may be beneficial by diverting POPs from other sensitive tissues or detrimental because of chronic release of pollutants as indirectly suggested during weight loss. The aim is to study the biological and/or toxic effects that chronic POP release from previously contaminated grafted AT could exert in a naïve mouse.MethodsC57BL/6J male mice were exposed intraperitoneally to 2,3,7,8-tetrachlorodibenzo-p-doxin (TCDD); their epididymal fat pads were collected and grafted on the back skin of uncontaminated recipient mice whose brain, liver, and epididymal ATs were analyzed (TCDD concentration, relevant gene expression). Kinetics of release and redistribution were modeled using Physiologically Based PharmacoKinetics (PBPK).ResultsThe grafts released TCDD over a period of 10 weeks with different kinetics of distribution in the three organs studied. A PBPK model was used to simulate the AT releasing process and the incorporation of TCDD into the major organs. At three weeks post-graft, we observed significant changes in gene expression in the liver and the host AT with signatures reminiscent of inflammation, gluconeogenesis and fibrosis as compared to the control.ConclusionsThis study confirms that AT-stored TCDD can be released and distributed to the organs of the recipient hence leading to distinct changes in gene expression. This original model provides direct evidence of the potential toxic-relevant effects when endogenous sources of contamination are present
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
Relationship between exposure to persistent organic pollutants and endometriosis
No full textL’endométriose est une maladie gynécologique pour laquelle l’exposition à certains contaminants chimiques environnementaux est évoquée parmi les facteurs de risque associés. Les conclusions des études épidémiologiques existantes restent toutefois non convergentes. Leur hétérogénéité en termes de lésions décrites, de méthodologie et d’effectifs contribuent à ce constat, de même que l’étendue limitée des marqueurs d’exposition considérés dans ces études. Nous avons réalisé une étude cas-témoins appariés à partir d’une bio-collection de 113 patientes réunissant68 cas de patientes opérées d’endométriose profonde et 45 patientes témoins. Un ensemble unique de 78 polluants organiques persistants a été recherché, incluant dioxines, polychlorobiphényles, retardateurs de flamme polybromés, et pesticides organochlorés. Les niveaux d’exposition interne des sujets ont été mesurés à la fois dans les tissus adipeux pariétal et épiploïque ainsi que dans le sérum. La distribution de ces différents polluants au sein de ces trois compartiments a tout d’abord été caractérisée. Celle-ci a permis la prise en compte encore très rare de l’équilibre entre compartiments de stockage et compartiment circulant, ce rapport de concentration apparaissant comme un potentiel indicateur additionnel permettant d’affiner d’éventuels liens de causalité entre exposition chronique à des dangers chimiques et pathologie chez l’homme. Certains des contaminants ciblés sont ensuite apparus significativement associés à l’endométriose profonde, la stratification plus fine de notre population de cas indiquant un lien d’autant plus significatif en présence d’endométriome. Les mécanismes sous-jacents de cette association restent toutefois à élucider.Endometriosis is a gynecological disease for whichexposure to some environmental chemicals is evocatedamong the associated risk factors. Epidemiological studies are however globally non convergent and finally fairly conclusive. Their heterogeneity in terms of lesion localization and sub-phenotype, methodology, size and nature of the populations studied, as well as the limited number of monitored markers of exposure contribute to this situation. We realized a matched case-control study based on a biocollection of 113 patients including 68 patients suffering of deep endometriosis and 45 controls. We characterized the internal exposure levels of an extended range of around 78 persistent organic pollutants (including dioxins, polychlorobiphenyls, brominated flame retardants and organochlorine pesticides). Internal level exposures were measured in three biological compartments (omental fat, subcutaneous fat and serum). First, the distribution of these chemicals was characterized within these compartments. These extended exposure data from deep infiltrating endometriosis patients are the first ones available for France and give a new insight about the equilibrium of chemicals between storage and circulating compartments that should be further considered as a potential indicator permitting to establish a possible association between a chronic exposure to chemical hazards and human pathology. Afterwards, some of the targeted chemicals appeared significantly associated with deep endometriosis. A sub-stratification of our case population indicated a more significant relationship with the presence of endometrioma. Underlying mechanisms remain to be determined
The challenge of multi-residue analysis of estrogenic endocrine disruptors in biological fluids and human tissues : choice of strategies for sample preparation and measurement by mass spectrometry
No full textDepuis plus d’une vingtaine d’années, la problématique des perturbateurs endocriniens (PE) mobilise la communauté scientifique et les pouvoirs publics en raison des effets néfastes, avérés ou suspectés, de ces composés sur la santé de l’Homme. En particulier, la génération de données d’exposition interne (imprégnation) chez certaines sous-populations reconnues ou supposées plus sensibles (femmes enceintes, foetus, nourrissons) est à la fois une priorité et un domaine exigeant associé à une certaine rareté. De par leur diversité au plan structural et en termes de propriétés physico-chimiques, l’analyse simultanée d’un large panel de PE reste de nos jours un véritable challenge analytique. Dans ce contexte, l’objectif de ce travail consistait à développer une méthode multi-résidus permettant l’isolement et la mesure simultanée de PE à effet estrogénique (13 PE au total). En premier lieu, une méthode de mesure par couplage chromatographie en phase liquide-spectrométrie de masse en tandem (UPLC-MS/MS) après dérivation chimique par le chlorure de dansyle a été développée. En second lieu, un support de type polymère à empreinte moléculaire (MIP phénolique) a été mis en oeuvre pour l’extraction simultanée du panel de PE ciblés à partir du milieu aqueux et de matrices biologiques de complexité croissante (urine, sérum, lait maternel). La stratégie développée sur MIP phénolique a été appliquée, après prévalidation, à un ensemble d’échantillons de sérum maternel, sérum du cordon et urine de nouveaux-nés. Enfin, un support de type colonne greffée par du récepteur aux estrogènes α (colonne ERα) a été appliqué pour l’isolement simultané des composés ciblés à partir d’un milieu aqueux.For over twenty years, the issue of endocrine disruptors (EDs) mobilizes the scientific community and public authorities because of the negative effects, actual or suspected, of these compounds on human health. In particular, the generation of internal exposure data (impregnation) in some subpopulations, which are recognized or assumed as being sensitive (pregnant women, fetuses, infants), is both a priority and a demanding field associated with a certain rarity. Considering their structural diversity and with regards to their physicochemical properties, the simultaneous analysis of a large panel of EDs remains a real analytical challenge. In this context, the objective of this work was to develop a multi-residue method for the simultaneous isolation and measurement of estrogenic endocrine disruptors (13 EDs in total). Firstly, an analysis method using liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) after chemical derivatisation by dansyl chloride was developed. Secondly, a molecularly imprinted polymer (MIP with phenolic imprint) was implemented for the simultaneous extraction of the targeted EDs from aqueous medium and biological matrices of increasing complexity (urine, serum, breast milk). The strategy developed on MIP was applied, after validation, to a set of samples (maternal serum, cord serum and urine of newborns). Finally, a column support grafted with estrogen receptor α (ERα column) was applied for the simultaneous isolation of the targeted compounds from an aqueous medium
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
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