Advances in studying phasic dopamine signaling in brain reward mechanisms

The last sixty years of research has provided extraordinary advances of our knowledge of the reward system. Since its discovery as a neurotransmitter by Carlsson and colleagues (1), dopamine (DA) has emerged as an important mediator of reward processing. As a result, a number of electrochemical techniques have been developed to measure DA in the brain. Together, these techniques have begun to elucidate the complex roles of tonic and phasic DA signaling in reward processing and addiction. In this review, we will first provide a guide for the most commonly used electrochemical methods for DA detection and describe their utility in furthering our knowledge about DA's role in reward and addiction. Second, we will review the value of common in vitro and in vivo preparations and describe their ability to address different types of questions. Last, we will review recent data that has provided new mechanistic insight of in vivo phasic DA signaling and its role in reward processing and reward-mediated behavior

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)

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

Human health risk assessment from combined exposure in the framework of plant protection products and biocidal products

Cumulative risk assessment (CRA) is of major importance and one of the biggest challenges for the future as a legal requirement within the EU for active substances used in plant protection products (PPP) and biocidal products (BP). Therefore, it is important to develop a methodology to take into account cumulative and synergistic effects for both active substances and substances of concern (SoC). The implementation of cumulative aspects in regulatory decisions is highly demanded and promoted by EU parliament, EU commission, European Food Safety Authority (EFSA), European Chemicals Agency (ECHA) and national authorities. Based on EFSA’s and ECHA’s work on CRA, the Federal Institute for Risk Assessment (BfR) drafted a concept on how to take cumulative aspects into account in the regulatory context in risk assessments for operators, consumers and other uninvolved third parties. Application of this concept as part of the routine risk assessment for PPP and BP is envisaged as soon as suitable experience has been gained in a testing phase. The BfR draft concept uses dose-addition of individual active substances and SoC as the toxicological standard concept for CRA and proposes a tiered approach. It recommends to start with calculation of a hazard index (HI) for all relevant substances contained in the PPP or BP under consideration. Proceeding to higher tiers is currently foreseen if the HI is larger than 1, i.e., an unacceptable risk cannot be excluded. In higher tiers, the HI should be calculated with respect to common targets and might consider effect-specific NOAEL’s (No Observed Adverse Effect Level) or relative potency factors, if available. Refinements should consider both the toxicity and the exposure part of the CRA and will depend on availability of relevant data. BfR acknowledges the complexity of the refinement work in mixture risk assessment to be done. The exposure assessment for operators, bystanders/residents and workers as well as the acute exposure assessment for consumers rely mainly on the active substances in a PPP or BP under consideration or on combinations of products for which simultaneous use is notified. Chronic consumer exposure assessment needs to take into account all relevant substances contained in the PPP or BP under consideration, but also the residue background of other pesticides in food, which have to be derived from representative food monitoring programmes. A representative food monitoring database is currently being developed. The assessment requires the application of complex probabilistic methods. It is planned that BfR will review the chronic CRA for each active substance and each CAG regularly as soon as all essential monitoring data are available. It is planned to carry out case studies on the impact on regulatory decisions. The paper is intended to promote further discussions of risk assessors, risk managers as well as stakeholders in this area on the applicability of CRA in routine authorisation procedures for PPP and BP and to encourage the flexible use of strategies in CRA

Scientific principles for the identification of endocrine-disrupting chemicals: a consensus statement

Endocrine disruption is a specific form of toxicity, where natural and/or anthropogenic chemicals, known as "endocrine disruptors" (EDs), trigger adverse health effects by disrupting the endogenous hormone system. There is need to harmonize guidance on the regulation of EDs, but this has been hampered by what appeared as a lack of consensus among scientists. This publication provides summary information about a consensus reached by a group of world-leading scientists that can serve as the basis for the development of ED criteria in relevant EU legislation. Twenty-three international scientists from different disciplines discussed principles and open questions on ED identification as outlined in a draft consensus paper at an expert meeting hosted by the German Federal Institute for Risk Assessment (BfR) in Berlin, Germany on 11-12 April 2016. Participants reached a consensus regarding scientific principles for the identification of EDs. The paper discusses the consensus reached on background, definition of an ED and related concepts, sources of uncertainty, scientific principles important for ED identification, and research needs. It highlights the difficulty in retrospectively reconstructing ED exposure, insufficient range of validated test systems for EDs, and some issues impacting on the evaluation of the risk from EDs, such as non-monotonic dose-response and thresholds, modes of action, and exposure assessment. This report provides the consensus statement on EDs agreed among all participating scientists. The meeting facilitated a productive debate and reduced a number of differences in views. It is expected that the consensus reached will serve as an important basis for the development of regulatory ED criteria

Technical summary

Human interference with the climate system is occurring. Climate change poses risks for human and natural systems. The assessment of impacts, adaptation, and vulnerability in the Working Group II contribution to the IPCC's Fifth Assessment Report (WGII AR5) evaluates how patterns of risks and potential benefits are shifting due to climate change and how risks can be reduced through mitigation and adaptation. It recognizes that risks of climate change will vary across regions and populations, through space and time, dependent on myriad factors including the extent of mitigation and adaptation

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