Application of an integrated approach to evaluate health risks for toxic chemicals by linking multimedia environmental and PBPK models

The paradigm of health risk assessment may consist of two main pillars, i.e., the exposure and dose-response assessments. Human exposure to chemicals via multiple pathways can be estimated by environmental multimedia models, which calculate the distribution of chemicals in the component media, i.e., air, water, soil, plants, and animal media. Combined with the information about human behaviors such as dietary habits, time spent outside, and etc, the multimedia models can provide an estimation of the daily chemical intake by inhalation or ingestion by humans. Physiologically based pharmacokinetic (PBPK) models are used to estimate the body burden of toxic chemicals throughout the entire human lifespan, integrating the evolution of the physiology and anatomy from childhood to advanced aged. The use of such PBPK models overcomes the limitations that dose-response modelling holds, e.g., it simply determines the relationship between the dose and the probability of an effect. The European project 2-FUN (Full-chain and UNcertainty Approaches for Assessing Health Risks in FUture ENvironmental Scenarios) aims at improving the approaches currently used in exposure and dose-response assessments. According to the aim of that project, an environmental multimedia model and a generic PBPK model are coupled as an integrated tool (2-FUN tool) and built up on a platform system, Ecolego. This study presents here the first application of the integrated tool to perform the full-chain risk assessment of a chemical for human health, considering multiple exposure pathways of chemical via inhalation of out-door air, and ingestion of water and foods. For this application of the tool, a case study was designed based on the information available in a region situated on the Seine river watershed, downstream of the Paris megacity and Benzo(a)pyrene (B(a)P) was selected as a target chemical substance. This study focuses especially on the propagation of uncertainty and inter-individual variability along the modelling chain. A probabilistic simulation was then performed to identify the input parameters and exposure pathways sensitive to model outputs (e.g., internal effective concentrations in organs)

Around the tangent cone theorem

A cornerstone of the theory of cohomology jump loci is the Tangent Cone theorem, which relates the behavior around the origin of the characteristic and resonance varieties of a space. We revisit this theorem, in both the algebraic setting provided by cdga models, and in the topological setting provided by fundamental groups and cohomology rings. The general theory is illustrated with several classes of examples from geometry and topology: smooth quasi-projective varieties, complex hyperplane arrangements and their Milnor fibers, configuration spaces, and elliptic arrangements.Comment: 39 pages; to appear in the proceedings of the Configurations Spaces Conference (Cortona 2014), Springer INdAM serie

Treatment outcome in infant acute lymphoblastic leukemia

peer reviewe

ASSESSING THE EFFICIENCY OF MODIFIED CLAYS FOR DECONTAMINATE AGRICULTURAL WASTE WATER BY PESTICIDE RESIDUES

Many anthropic activities, including the agricultural and food industries, give rise to environmental problems for which it is necessary to find solutions. The presence of undesirable substances in water, the soil and foodstuffs can pose a risk to the health and hygiene to humans and animals. It is therefore essential to study methods for removing pollutants from these matrices, as to make them compatible with the maintenance of healthy environmental conditions. This paper aims at verifying the possibility of using modified clays (or organic-clays) to remove contaminants from waste water coming from different areas. This work derives from the necessity to overcome the numerous, negative aspects of current techniques and offers new, effective, easy to use and economic methods. The adsorption of the different pesticides onto micelle-clay complexes and unmodified montmorillonite clay were measured to allow the determination of the maximum pesticide quantity adsorbed in order to obtain a dose-effect relationship for practical applications. The modified clay Cloisite 20A was showed to be more efficient for use in treatment plants for the adsorption of chlorpyrifos and penconazole from aqueous solutions whereas metalaxyl is more efficiently removed by Cloisite 30B. Adsorption tests in laboratory using Cloisite 20 A were also developed for cyazofamid and cyprodinil and the results showed a high affinity of the both fungicides for the organoclay. Therefore Cloisite 20 A was show to be the most efficient organoclay from those tested in this study. This, in part, is explained by the structure of the modifier quaternary salt which contains two aliphatic chains on the structure and determinate a higher space between the layers of the montmorillonite. Subsequently a depuration scheme was developed to test the practical applicability of the Cloisite 20A organoclay and the results showed it to be efficient for decontaminating pesticide-containing water derived from vineyards. The adsorption tests in the pilot system show a removal of three of the pesticide considered, cyazofamid, penconazole and cyprodinil, to be similar to that predicted from the adsorption tests developed in the laboratory. The recovery of the modified clay after the adsorption was shown to be dependent on the presence of surfactants in the pesticide formulation. For the adsorption test of penconazole, which contains a higher quantity of surfactants in the formulation, if compared with the formulation of cyazofamid, the recovery of Cloisite 20 A was 20% higher. For the fungicide cyprodinil, formulated with antifoaming agents, an alternative treatment of the clay-water suspension was necessary. After adsorption the suspension was passed through a compost layer which determinates the sedimentation of the clay at the compost surface. Concerning the waste disposal, for instance the organoclay composted after the adsorption, additional treatments appear to be necessary for pesticides with moderate and high persistence in soil as penconazole and cyprodinil. The fungicide cyazofamid shows a significant decrease after 90 days, in favourable conditions of compost humidity and environment temperature. The results of the modelling exercise shows that the FOCUS PEARL model, generally used for calculating leaching and drainage of PPP from open field cultivations to ground/surface water could be parameterised to simulate PPP emissions from greenhouses to surface water. For the case study, weather conditions were found to have a major role on the PPP emissions from glasshouses and the open field. The more controlled climate in the greenhouse prevented a substantial precipitation excess as was observed for the open field, which had a large effect on the leaching concentrations. Furthermore, in greenhouse cultivation it was noticed that the temperature has a slightly higher influence on CC-M emissions from the greenhouse than the irrigation excess volume. However, the main conclusion of this exercise was that there are potential PPP emissions to surface water associated with crop cultivation in greenhouses, contrary to what is stated in the European Council Regulation 1107/2009, article 3. Therefore a possible use of the outputs of this exercise is in future work to develop decontamination systems for greenhouses or for open field cultivation

Correlation effects during liquid infiltration into hydrophobic nanoporous mediums

Correlation effects arising during liquid infiltration into hydrophobic porous medium are considered. On the basis of these effects a mechanism of energy absorption at filling porous medium by nonwetting liquid is suggested. In accordance with this mechanism, the absorption of mechanical energy is a result expenditure of energy for the formation of menisci in the pores on the shell of the infinite cluster and expenditure of energy for the formation of liquid-porous medium interface in the pores belonging to the infinite cluster of filled pores. It was found that in dependences on the porosity and, consequently, in dependences on the number of filled pores neighbors, the thermal effect of filling can be either positive or negative and the cycle of infiltration-defiltration can be closed with full outflow of liquid. It can occur under certain relation between percolation properties of porous medium and the energy characteristics of the liquid-porous medium interface and the liquid-gas interface. It is shown that a consecutive account of these correlation effects and percolation properties of the pores space during infiltration allow to describe all experimental data under discussion

Differential impact of drugs on the outcome of ETV6-RUNX1 positive childhood B-cell precursor acute lymphoblastic leukaemia : results of the EORTC CLG 58881 and 58951 trials

info:eu-repo/semantics/publishe

EURL ECVAM Workshop on New Generation of Physiologically-Based Kinetic Models in Risk Assessment

The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) Strategy Document on Toxicokinetics (TK) outlines strategies to enable prediction of systemic toxicity by applying new approach methodologies (NAM). The central feature of the strategy focuses on using physiologically-based kinetic (PBK) modelling to integrate data generated by in vitro and in silico methods for absorption, distribution, metabolism, and excretion (ADME) in humans for predicting whole-body TK behaviour, for environmental chemicals, drugs, nano-materials, and mixtures. In order to facilitate acceptance and use of this new generation of PBK models, which do not rely on animal/human in vivo data in the regulatory domain, experts were invited by EURL ECVAM to (i) identify current challenges in the application of PBK modelling to support regulatory decision making; (ii) discuss challenges in constructing models with no in vivo kinetic data and opportunities for estimating parameter values using in vitro and in silico methods; (iii) present the challenges in assessing model credibility relying on non-animal data and address strengths, uncertainties and limitations in such an approach; (iv) establish a good kinetic modelling practice workflow to serve as the foundation for guidance on the generation and use of in vitro and in silico data to construct PBK models designed to support regulatory decision making. To gauge the current state of PBK applications, experts were asked upfront of the workshop to fill a short survey. In the workshop, using presentations and discussions, the experts elaborated on the importance of being transparent about the model construct, assumptions, and applications to support assessment of model credibility. The experts offered several recommendations to address commonly perceived limitations of parameterization and evaluation of PBK models developed using non-animal data and its use in risk assessment, these include: (i) develop a decision tree for model construction; (ii) set up a task force for independent model peer review; (iii) establish a scoring system for model evaluation; (iv) attract additional funding to develop accessible modelling software.; (v) improve and facilitate communication between scientists (model developers, data provider) and risk assessors/regulators; and (vi) organise specific training for end users. The experts also acknowledged the critical need for developing a guidance document on building, characterising, reporting and documenting PBK models using non-animal data. This document would also need to include guidance on interpreting the model analysis for various risk assessment purposes, such as incorporating PBK models in integrated strategy approaches and integrating them with in vitro toxicity testing and adverse outcome pathways. This proposed guidance document will promote the development of PBK models using in vitro and silico data and facilitate the regulatory acceptance of PBK models for assessing safety of chemicals

A mixed finite element discretization scheme for a concrete carbonation model with concentration-dependent porosity

We discuss a prototypical reaction-diffusion-flow problem in saturated/unsaturated porous media. The special features of our problem are: the reaction produces water and therefore the flow and transport are coupled in both directions and moreover, the reaction may alter the microstructure. This means we have a variable porosity in our model. For the spatial discretization we propose a mass conservative scheme based on the mixed finite element method (MFEM). The scheme is semi-implicit in time. Error estimates are obtained for some particular cases. We apply our finite element methodology for the case of concrete carbonation – one of the most important physico-chemical processes affecting the durability of concrete

Whale-watching contributions for the study of cetacean-cephalopod interactions

Cephalopods are the primary source of food for several species of odontocetes. The unstable nature of this trophic resource is likely to affect the ecology of their cetacean predators. This can be reflected in whale conservation status but also in the tourist activities which focus on cetacean observation. However, the study of cetacean-cephalopod interactions is limited by the complicated and heavy logistics of dedicated scientific campaigns. Fortunately, this limitation can be overcome by coupling modern molecular tools with indirect sampling methods. In this note we present the first results of a project to involve whale watching companies, which represent an intense observation effort worldwide, in the collection of biological material and information for studies of cetacean-cephalopod interactions and cephalopod distribution. In early 2020 we contacted all whale watching companies on São Miguel Island, Azores. All of them welcomed the invitation and received training and a sampling kit. Nine cephalopod tissue samples were collected, most of them in close association with sperm whales. All samples were determined by DNA barcoding (confirmed in a few cases by morphological observation) to belong to the gelatinous giant octopod Haliphron atlanticus (Octopoda, Alloposidae). We believe that, although the Azores may have particularly favourable conditions for participatory science, similar programs can be replicated elsewhere.info:eu-repo/semantics/publishedVersio

Lifted graphical models: a survey

Lifted graphical models provide a language for expressing dependencies between different types of entities, their attributes, and their diverse relations, as well as techniques for probabilistic reasoning in such multi-relational domains. In this survey, we review a general form for a lifted graphical model, a par-factor graph, and show how a number of existing statistical relational representations map to this formalism. We discuss inference algorithms, including lifted inference algorithms, that efficiently compute the answers to probabilistic queries over such models. We also review work in learning lifted graphical models from data. There is a growing need for statistical relational models (whether they go by that name or another), as we are inundated with data which is a mix of structured and unstructured, with entities and relations extracted in a noisy manner from text, and with the need to reason effectively with this data. We hope that this synthesis of ideas from many different research groups will provide an accessible starting point for new researchers in this expanding field