Analyse du modèle CHIMIOTOX du point de vue de ses implications toxicologiques [Article bilingue]

Le modèle CHIMIOTOX a été mis au point comme outil de gestion dans le but de réduire de façon importante la quantité de substances toxiques déversées dans le fleuve Saint-Laurent. Ce modèle effectue un calcul dont le résultat est une valeur numérique qui se veut représentative de la charge toxique présente dans un effluent industriel. Pour ce faire, le modèle attribue à chaque substance toxique une constante de toxicité, le facteur de pondération toxique (Ftox), dont la valeur est déterminée à partir des critères de qualité de l'eau du ministère de l'Environnement du Québec. Le Ftox sert à calculer l'unité CHIMIOTOX (UC) qui est le produit de Ftox par la charge journalière du polluant (kg/jour). La sommation des UC de toutes les substances ciblées donne l'indice CHIMIOTOX (IC) qui doit représenter le potentiel toxique de l'effluent. Dans la présente étude, le modèle CHIMIOTOX a été analysé du point de vue de ses implications au plan toxicologique. Les résultats de cette analyse montrent les faits saillants suivants. En premier lieu, le calcul du potentiel toxique théorique se fait selon l'équation d'une droite de pente Ftox. Ceci implique que le potentiel toxique calculé est directement proportionnel à la quantité de la substance, et cela, quel que soit le niveau supposé d'exposition. Cette démarche n'est pas compatible avec le concept fondamental de la dose-réponse, basé sur l'observation expérimentale. À cette étape du modèle, l'estimation du théorique risque de s'écarter considérablement de la réalité. En second lieu, l'UC est calculé en utilsant la charge journalière moyenne de l'effluent à partir de mesures effectuées sur trois jours. Le modèle fait abstraction des variations ponctuelles dans le temps, variations qui peuvent influencer de manière significative le profil d'exposition des organismes, et par conséquent, la toxicité. En troisième lieu, l'IC, qui est la sommation des UC, ne tient pas compte des interactions toxiques pouvant survenir dans le cas d'un mélange de substances, ni de la bioaccumulation dans la chaîne trophique. Une comparaison du CHIMIOTOX avec le modèle des TEF (Toxic Equivalency Factor) développé pour les dibenzo-p-dioxines et les dibenzofurannes polychlorés, a été effectuée afin de souligner la difficulté d'obtenir des valeurs théoriques prédictives de la toxicité de mélanges complexes, même lorsque ses composants possèdent un mécanisme d'action commun, ce qui n'est pas le cas pour la plupart des substances considérées par le CHIMIOTOX. Au total, le modèle CHIMIOTOX génère une incertitude qui s'accroît à chaque étape du calcul. Ceci l'empêche d'avoir une véritable valeur quantitative et limite considérablement son utilité dans l'évaluation du rique environnemental associé aux substances toxiques.CHIMIOTOX is a model designed to provide a numerical indicator of toxic discharges for the purpose of comparing and integrating sampling results. CHIMIOTOX was also intended to be used as a tool in managing toxic substances. In this paper, the CHIMIOTOX model has been analysed from the standpoint of its toxicological implications. The analysis shows that the model's numerical indicator does not integrate principles such as the dose-response relationship, the level of exposure of the target organisms in the receiving waters, the transformation of toxic substances in the environment and their bioaccumulation, or the possible interactions between the different components of a complex mixture of toxic substances. The CHIMIOTOX model has been compared to the toxic equivalency factor (TEF) approach developed for polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans to illustrate the difficulties in obtaining reliable predictive values for the toxicity of mixtures even when their components share a similar mechanism of action, which is not the case for most substances subjected to CHIMIOTOX. Because CHIMIOTOX generates a high degree of uncertainty that increases at each step of the calculation, and because this uncertainty is not taken into account, the usefulness of the model from the point of view of ecotoxicological risk assessment and management appears significantly limited

Non equilibrium inertial dynamics of colloidal systems

We consider the properties of a one dimensional fluid of brownian inertial hard-core particles, whose microscopic dynamics is partially damped by a heat-bath. Direct interactions among the particles are represented as binary, instantaneous elastic collisions. Collisions with the heath bath are accounted for by a Fokker-Planck collision operator, whereas direct collisions among the particles are treated by a well known method of kinetic theory, the Revised Enskog Theory. By means of a time multiple time-scale method we derive the evolution equation for the average density. Remarkably, for large values of the friction parameter and/or of the mass of the particles we obtain the same equation as the one derived within the dynamic density functional theory (DDF). In addition, at moderate values of the friction constant, the present method allows to study the inertial effects not accounted for by DDF method. Finally, a numerical test of these corrections is provided.Comment: 13 pages+ 3 Postscript figure

Comparison of Models for Olfactometer Data

Olfactometer experiments are used to study the responses of arthropods to potential attractants, for purposes such as understanding natural defenses of plants against their herbivores. Such experiments typically lead to multivariate data consisting of small correlated counts, which are overdispersed relative to standard models. In this paper models that account for the overdispersion under different hypotheses on insect behaviour are described and illustrated with an example, and a graphical approach to discriminating among them is briefly discussed

Invisible students: institutional invisibility and access to education for undocumented children

PURPOSE: In Canada, undocumented children are “institutionally invisible” – their access to education to be found in unwritten and discretionary practices. Drawing on the experience of a three-year university-community partnership among researchers, institutional and community stakeholders, the purpose of this paper is to examine how undocumented children are constructed as excluded from school. DESIGN/METHODOLOGY/APPROACH: The establishment of this collaborative research space, helped to critically understand how this exclusion was maintained, and highlighted contradictory interpretations of policies and practices. FINDINGS: Proposing the analytical framework of “institutional invisibility”, the authors argue that issues of access and entitlement for undocumented children have to be often understood within unwritten and ambiguous policies and practices that make the lives of young people invisible to the institutional entities with which they interact. ORIGINALITY/VALUE: The notion of institutional invisibility allows the authors to integrate the missing link between questions of access and deservingness. The paper also reflects on the role of action research in both documenting dynamics and pathways of institutional invisibility, as well as in initiating social change – as both horizontal, and vertical mobilisation

Infection with Toxoplasma gondii does not Alter TNFα and IL-6 Secretion by A human Astrocytoma Cell Line

The secretion of tumour necrosis factor-α (TNFα), interleukin-1α (IL-α) and interleukin-6 (IL-6) by a human astrocytoma cell fine was studied 1 h, 3 h, 6 h and 24 h after infection with tachyzoites from three Toxoplasma gondii strains (virulent, RH; cystogentc, 76K and Prugniaud strains). The astrocytoma cell fine constitutively secreted TNFα and IL-6, but no IL-1α. A positive control was obtained by stimulation with phorbol esters inducing a significant increase (p < 0.05) in TNFα and IL- 6 secretion but not in IL-1α, while lipopolysaccharide (alone and after priming), interferon gamma, ionophore A 23187 and sera positive to T. gondii did not induce any increase in cytokine levels. None of the tachyzoites, whatever their virulence, induced a significant increase in cytokine production at any time in the study. Tachyzoites did not inhibit the secretion induced by phorbol esters

Diversity, competition, extinction: the ecophysics of language change

As early indicated by Charles Darwin, languages behave and change very much like living species. They display high diversity, differentiate in space and time, emerge and disappear. A large body of literature has explored the role of information exchanges and communicative constraints in groups of agents under selective scenarios. These models have been very helpful in providing a rationale on how complex forms of communication emerge under evolutionary pressures. However, other patterns of large-scale organization can be described using mathematical methods ignoring communicative traits. These approaches consider shorter time scales and have been developed by exploiting both theoretical ecology and statistical physics methods. The models are reviewed here and include extinction, invasion, origination, spatial organization, coexistence and diversity as key concepts and are very simple in their defining rules. Such simplicity is used in order to catch the most fundamental laws of organization and those universal ingredients responsible for qualitative traits. The similarities between observed and predicted patterns indicate that an ecological theory of language is emerging, supporting (on a quantitative basis) its ecological nature, although key differences are also present. Here we critically review some recent advances lying and outline their implications and limitations as well as open problems for future research.Comment: 17 Pages. A review on current models from statistical Physics and Theoretical Ecology applied to study language dynamic

Limb salvage with isolated perfusion for soft tissue sarcoma: could less TNF-α be better?

Background: The optimal dose of TNF-α delivered by isolated limb perfusion (ILP) in patients with locally advanced soft tissue sarcoma is still unknown. Patients and methods: Randomised phase II trial comparing hyperthermic ILP (38-40°) with melphalan and one of the four assigned doses of TNF-α: 0.5 mg, 1 mg, 2 mg, and 3/4 mg upper/lower limb. The main end point was objective tumour response on MRI. Secondary end points were histological response, rate of amputation and toxicity. Resection of the remnant tumour was performed 2-3 months after ILP. The sample size was calculated assuming a linear increase of 10% in the objective response rates between each dose level group. Results: One hundred patients (25 per arm) were included. Thirteen per cent of patients had a systemic leakage with a cardiac toxicity in six patients correlated with high doses of TNF-α. Objective tumour responses were: 68%, 56%, 72% and 64% in the 0.5 mg, 1 mg, 2 mg and 3 or 4 mg arms, respectively (NS). Sixteen per cent of patients were not operated, 71% had a conservative surgery and 13% were amputated with no difference between the groups. With a median follow-up of 24 months, the 2 year overall and disease-free survival rates (95% CI) were 82% (73% to 89%) and 49% (39% to 59%), respectively. Conclusion: At the range of TNF-α doses tested, there was no dose effect detected for the objective tumour response, but systemic toxicity was significantly correlated with higher TNF-α doses. Efficacy and safety of low-dose TNF-α could greatly facilitate ILP procedures in the near futur

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p &lt; 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM &gt; 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM &gt; 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Topological reversibility and causality in feed-forward networks

Systems whose organization displays causal asymmetry constraints, from evolutionary trees to river basins or transport networks, can be often described in terms of directed paths (causal flows) on a discrete state space. Such a set of paths defines a feed-forward, acyclic network. A key problem associated with these systems involves characterizing their intrinsic degree of path reversibility: given an end node in the graph, what is the uncertainty of recovering the process backwards until the origin? Here we propose a novel concept, \textit{topological reversibility}, which rigorously weigths such uncertainty in path dependency quantified as the minimum amount of information required to successfully revert a causal path. Within the proposed framework we also analytically characterize limit cases for both topologically reversible and maximally entropic structures. The relevance of these measures within the context of evolutionary dynamics is highlighted.Comment: 9 pages, 3 figure

Heterogeneity in the longitudinal courses of global functioning in children at familial risk of major psychiatric disorders: Association with trauma and familial characteristics

Abstract Objectives The extent to which heterogeneity in childhood risk trajectories may underlie later heterogeneity in schizophrenia (SZ), bipolar disorder (BP), and major depressive disorder (MDD) remains a chief question. Answers may optimally be found by studying the longitudinal trajectories of children born to an affected parent. We aimed to differentiate trajectories of global functioning and their sensitive periods from the age of 6 to 17 years in children at familial risk (FHRs). Methods First, a latent class mixed model analysis (LCMM) was applied to yearly ratings of the Children's Global Assessment Scale (CGAS) from the age of 6 to 17 years in 170 FHRs born to a parent affected by DSM-IV SZ (N = 37), BP (N = 82) or MDD (N = 51). Then, we compared the obtained Classes or trajectories of FHRs in terms of sex, parental diagnosis, IQ, child clinical status, childhood trauma, polygenic risk score (PRS), and outcome in transition to illness. Results The LCMM on yearly CGAS trajectories identified a 4-class solution showing markedly different childhood and adolescence dynamic courses and temporal vulnerability windows marked by a functioning decline and a degree of specificity in parental diagnosis. Moreover, IQ, trauma exposure, PRS level, and timing of later transition to illness differentiated the trajectories. Almost half (46%) of the FHRs exhibited a good and stable global functioning trajectory. Conclusions FHRs of major psychiatric disorders show heterogeneous functional decline during development associated with parental diagnosis, polygenic risk loading, and childhood trauma