Deliverable 9.1 - Report on mixtures and implementation strategy in Europe – Assessment of chemical mixtures under consideration of current and future regulatory requirements and scientific approaches

This report gives an overview on the regulatory processes and requirements for risk assessment of chemical mixtures, identifies gaps in the European legislation and summarises potential approaches for the health risk assessment of chemical mixtures

Développement d'outils microbiologiques et chimiques permettant d'identifier l'origine des pollutions fécales dans les eaux de baignades

La pollution organique issue des effluents d'élevage et des stations d'épuration urbaines conduit à un problème essentiel de santé publique lié à la contamination des eaux de surface où s'exercent des activités sensibles telles que la baignade. S'il est possible de déterminer les pollutions localisées liées à un dysfonctionnement des systèmes de traitement, il est beaucoup plus difficile d'identifier les pollutions organiques diffuses qui participent pourtant majoritairement à la dégradation de la qualité des eaux de surface. La problématique des pollutions diffuses est d'autant plus importante que la nouvelle réglementation européenne concernant les eaux de baignade (Directive 2006/7/CE) demande de constituer des profils de baignade qui nécessitent une identification et une hiérarchisation des sources de pollutions fécales. Le dénombrement de Escherichia coli et des entérocoques intestinaux stipulé par les textes réglementaires européens, représente actuellement le seul outil analytique permettant la mise en évidence d'une contamination fécale du milieu aquatique, sans toutefois différencier l'origine humaine ou animale de cette contamination. Il est donc nécessaire de développer de nouvelles méthodes de détection de la pollution fécale qui puissent non seulement mettre en évidence une contamination mais aussi en indiquer l'origine. C'est d'ailleurs dans cet objectif que s'est développé depuis quelques années, le concept de "Microbial Source Tracking" ("Traceurs de Sources Microbiennes") qui consiste à identifier à l'aide de marqueurs microbiologiques ou chimiques les sources de pollutions fécales. Dans ce contexte, six laboratoires de recherche se sont associés pour développer des techniques de traçage des contaminations fécales afin de proposer un outil opérationnel utilisable pour différencier les sources de pollution, de leur point d'émission jusqu'au milieu récepteur final que constituent les eaux de surface. Les marqueurs qui ont fait l'objet de cette étude sont des molécules chimiques naturelles (stéroïdes, caféine), des molécules de synthèse retrouvées dans les effluents de stations d'épuration ou des rapports de fluorescence de la matière organique ainsi que des micro-organismes (bactériophages, bactéries). A la suite des développements méthodologiques, plusieurs marqueurs ont été sélectionnés : - bactéries appartenant aux groupes bactériens dominants du tractus intestinal humain (Bifidobacterium adolescentis) et porcin (Lactobacillus amylovorus) ; - Bacteroidales spécifiques des humains, porcins et bovins (HF183, Pig-2-Bac, Rum-2-Bac); - génogroupes humains des bactériophages F ARN spécifiques; - rapports de stéroïdes : coprostanol/(24ethylcoprostanol+coprostanol) (R1) et sitostanol/coprostanol (R2); - caféine, benzophénone et tri(2-chloroethyl)phosphate (TCEP)

Oxygen Tension and the VHL-Hif1α Pathway Determine Onset of Neuronal Polarization and Cerebellar Germinal Zone Exit.

Postnatal brain circuit assembly is driven by temporally regulated intrinsic and cell-extrinsic cues that organize neurogenesis, migration, and axo-dendritic specification in post-mitotic neurons. While cell polarity is an intrinsic organizer of morphogenic events, environmental cues in the germinal zone (GZ) instructing neuron polarization and their coupling during postnatal development are unclear. We report that oxygen tension, which rises at birth, and the von Hippel-Lindau (VHL)-hypoxia-inducible factor 1α (Hif1α) pathway regulate polarization and maturation of post-mitotic cerebellar granule neurons (CGNs). At early postnatal stages with low GZ vascularization, Hif1α restrains CGN-progenitor cell-cycle exit. Unexpectedly, cell-intrinsic VHL-Hif1α pathway activation also delays the timing of CGN differentiation, germinal zone exit, and migration initiation through transcriptional repression of the partitioning-defective (Pard) complex. As vascularization proceeds, these inhibitory mechanisms are downregulated, implicating increasing oxygen tension as a critical switch for neuronal polarization and cerebellar GZ exit

Mechanical design of rotors for permanent magnet high speed electric motors for turbocharger applications

Realization of electrically boosted turbochargers requires electric motors capable of operating at very high speeds. These motors often use a permanent magnet rotor with the magnets retained within an interference fit external sleeve. Whilst it is possible to model such systems numerically, these models are an inefficient tool for design optimization. Current analytical models of rotors typically consider the stresses induced by the shrink fit of the sleeve separately from the stresses generated by centripetal forces due to rotation. However, such an approach ignores the frictional interaction between the components in the axial direction. This paper presents an analytical model that simultaneously accounts for interaction between the magnet and outer sleeve in both the radial and axial directions at designed interference and with the assembly subjected to centripetal and thermal loads. Numerical models presented show that with only moderate coefficients of friction and rotor lengths; axial load transfer between magnet and sleeve takes place over a short distance at the ends of the assembly. The paper then demonstrates how the analytical model aids definition of a feasible set of rotor designs and selection of an optimum design

Evaluating Knowledge to Support Climate Action: A Framework for Sustained Assessment. Report of an Independent Advisory Committee on Applied Climate Assessment

As states, cities, tribes, and private interests cope with climate damages and seek to increase preparedness and resilience, they will need to navigate myriad choices and options available to them. Making these choices in ways that identify pathways for climate action that support their development objectives will require constructive public dialogue, community participation, and flexible and ongoing access to science- and experience-based knowledge. In 2016, a Federal Advisory Committee (FAC) was convened to recommend how to conduct a sustained National Climate Assessment (NCA) to increase the relevance and usability of assessments for informing action. The FAC was disbanded in 2017, but members and additional experts reconvened to complete the report that is presented here. A key recommendation is establishing a new nonfederal "climate assessment consortium" to increase the role of state/local/tribal government and civil society in assessments. The expanded process would 1) focus on applied problems faced by practitioners, 2) organize sustained partnerships for collaborative learning across similar projects and case studies to identify effective tested practices, and 3) assess and improve knowledge-based methods for project implementation. Specific recommendations include evaluating climate models and data using user-defined metrics; improving benefit-cost assessment and supporting decision-making under uncertainty; and accelerating application of tools and methods such as citizen science, artificial intelligence, indicators, and geospatial analysis. The recommendations are the result of broad consultation and present an ambitious agenda for federal agencies, state/local/tribal jurisdictions, universities and the research sector, professional associations, nongovernmental and community-based organizations, and private-sector firms.New York State Energy Research and Development Authority [123416]; Columbia University's Earth Institute; American Meteorological Society; Kresge Foundation6 month embargo; published online: 21 May 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Constitutive Notch2 signaling in neural stem cells promotes tumorigenic features and astroglial lineage entry

Recent studies identified a highly tumorigenic subpopulation of glioma stem cells (GSCs) within malignant gliomas. GSCs are proposed to originate from transformed neural stem cells (NSCs). Several pathways active in NSCs, including the Notch pathway, were shown to promote proliferation and tumorigenesis in GSCs. Notch2 is highly expressed in glioblastoma multiforme (GBM), a highly malignant astrocytoma. It is therefore conceivable that increased Notch2 signaling in NSCs contributes to the formation of GBM. Here, we demonstrate that mice constitutively expressing the activated intracellular domain of Notch2 in NSCs display a hyperplasia of the neurogenic niche and reduced neuronal lineage entry. Neurospheres derived from these mice show increased proliferation, survival and resistance to apoptosis. Moreover, they preferentially differentiate into astrocytes, which are the characteristic cellular population of astrocytoma. Likewise, we show that Notch2 signaling increases proliferation and resistance to apoptosis in human GBM cell lines. Gene expression profiling of GBM patient tumor samples reveals a positive correlation of Notch2 transcripts with gene transcripts controlling anti-apoptotic processes, stemness and astrocyte fate, and a negative correlation with gene transcripts controlling proapoptotic processes and oligodendrocyte fate. Our data show that Notch2 signaling in NSCs produces features of GSCs and induces astrocytic lineage entry, consistent with a possible role in astrocytoma formation

Overview on legislation and scientific approaches for risk assessment of combined exposure to multiple chemicals: the potential EuroMix contribution

This article reviews the current legislative requirements for risk assessment of combined exposure to multiple chemicals via multiple exposure routes, focusing on human health and particularly on food-related chemicals. The aim is to identify regulatory needs and current approaches for this type of risk assessment as well as challenges of the implementation of appropriate and harmonized guidance at international level. It provides an overview of the current legal requirements in the European Union (EU), the United States and Canada. Substantial differences were identified in the legal requirements for risk assessment of combined exposure to multiple chemicals and its implementation between EU and non-EU countries and across several regulatory sectors. Frameworks currently proposed and in use for assessing risks from combined exposure to multiple chemicals via multiple routes and different durations of exposure are summarized. In order to avoid significant discrepancies between regulatory sectors or countries, the approach for assessing risks of combined exposure should be based on similar principles for all types of chemicals. OECD and EFSA identified the development of harmonized methodologies for combined exposure to multiple chemicals as a key priority area. The Horizon 2020 project “EuroMix” aims to contribute to the further development of internationally harmonized approaches for such risk assessments by the development of an integrated test strategy using in vitro and in silico tests verified for chemical mixtures based on more appropriate data on potential combined effects. These approaches and testing strategies should be integrated in a scientifically based weight of evidence approach to account for complexity and uncertainty, to improve risk assessment

Ergonomics observation: harvesting tasks at oil palm plantation

Objectives: Production agriculture is commonly associated with high prevalence of ergonomic injuries, particularly during intensive manual labor and during harvesting. This paper intends to briefly describe an overview of oil palm plantation management highlighting the ergonomics problem each of the breakdown task analysis. Methods: Although cross-sectional field visits were conducted in the current study, insight into past and present occupational safety and health concerns particularly regarding the ergonomics of oil palm plantations was further exploited. Besides discussion, video recordings were extensively used for ergonomics analysis. Results: The unique commodity of oil palm plantations presents significantly different ergonomics risk factors for fresh fruit bunch (FFB) cutters during different stages of harvesting. Although the ergonomics risk factors remain the same for FFB collectors, the intensity of manual lifting increases significantly with the age of the oil palm trees-weight of FFB. Conclusions: There is urgent need to establish surveillance in order to determine the current prevalence of ergonomic injuries. Thereafter, ergonomics interventions that are holistic and comprehensive should be conducted and evaluated for their efficacy using approaches that are integrated, participatory and cost-effective