Bioanalytical characterisation of multiple endocrine- and dioxin-like activities in sediments from reference and impacted small rivers.

International audienceA comprehensive evaluation of organic contamination was performed in sediments sampled in two reference and three impacted small streams where endocrine disruptive (ED) effects in fish have been evidenced. The approach combined quantitative chemical analyses of more than 50 ED chemicals (EDCs) and a battery of in vitro bioassays allowing the quantification of receptor-mediated activities, namely estrogen (ER), androgen (AR), dioxin (AhR) and pregnane X (PXR) receptors. At the most impacted sites, chemical analyses showed the presence of natural estrogens, organochlorine pesticides, parabens, polycyclic aromatic hydrocarbons (16 PAHs), bisphenol A and alkylphenols, while synthetic steroids, myco-estrogens and phyto-estrogens were not detected. Determination of toxic-equivalent amounts showed that 28-96% of estrogenic activities in bioassays (0.2-6.3 ng/g 17beta-estradiol equivalents) were explained by 17beta-estradiol and estrone. PAHs were major contributors (20-60%) to the total dioxin-like activities. Interestingly, high PXR and (anti)AR activities were detected; however, the targeted analysed compounds could not explain the measured biological activities. This study highlighted the presence of multiple organic EDCs in French river sediments subjected to mixed diffuse pollution, and argues for the need to further identify AR and PXR active compounds in the aquatic environment

Software Diversity: Challenges to handle the imposed, Opportunities to harness the chosen

National audienceDiversity emerges as a critical concern that spans all activities in software engineering (from design to verification, from deployment to runtime resilience) and appears in all sorts of domains, which rely on software intensive systems, from systems of systems to pervasive combinations of Internet of Things and Internet of Services. If these domains are apparently radically different, we envision a strong convergence of the scientific principles underpinning their construction and validation towards flexible and open yet dependable systems. In this paper, we discuss the software engineering challenges raised by these requirements for flexibility and openness, focusing on four dimensions of diversity: the diversity of functionalities required by the different customers; the diversity of languages used by the stakeholders involved in the construction of these systems; the diversity of runtime environments in which software has to run and adapt; the diversity of failures against which the system must be able to react. In particular, we want to emphasize the challenges for handling imposed diversity, as well as the opportunities to leverage chosen diversity. The main challenge is that software diversity imposes to integrate the fact that software must adapt to changes in the requirements and environment -- in all development phases and in unpredictable ways. Yet, exploiting and increasing software diversity is a great opportunity to allow the spontaneous exploration of alternative software solutions and proactively prepare for unforeseen changes. Concretely, we want to provide software engineers with the ability: to characterize an 'envelope' of possible variations; to compose 'envelopes' (to discover new macro envelopes in an opportunistic manner); to dynamically synthesize software inside a given envelop

Cytokine Profiles in Toxoplasmic and Viral Uveitis

BackgroundUveitis is a major cause of visual impairment throughout the world. Analysis of cytokine profiles in aqueous humor specimens may provide insight into the physiopathological processes that underly retinal damage in this context MethodsUsing a multiplex assay, we determined the concentrations of 17 cytokines and chemokines in aqueous humor specimens obtained from patients with ocular toxoplasmosis or viral uveitis and compared these concentrations with those in specimens obtained from patients with noninfectious intermediate uveitis or cataract ResultsFive mediators (interleukin [IL]-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, IL-4, and IL-10) were detected in >50% of patients in all groups. In contrast, IL-5 and IL-12 were specific for ocular toxoplasmosis, and granulocyte monocyte colony-stimulating factor and IL-1 were specific for viral uveitis; these mediators could present specific markers for diagnostic purposes. Interferon-γ, IL-6, and macrophage inflammatory protein-1β were common markers of ocular toxoplasmosis and viral uveitis. IL-17 was a common marker of ocular toxoplasmosis and intermediate uveitis ConclusionsWe found specific cytokine profiles for each type of uveitis, with large interindividual variations and no etiological or clinical correlations. Ocular cytokine mapping contributes to a better understanding of the physiopathology of specific forms of uveitis and provides guidance for new targeted treatmen

French Roadmap for complex Systems 2008-2009

This second issue of the French Complex Systems Roadmap is the outcome of the Entretiens de Cargese 2008, an interdisciplinary brainstorming session organized over one week in 2008, jointly by RNSC, ISC-PIF and IXXI. It capitalizes on the first roadmap and gathers contributions of more than 70 scientists from major French institutions. The aim of this roadmap is to foster the coordination of the complex systems community on focused topics and questions, as well as to present contributions and challenges in the complex systems sciences and complexity science to the public, political and industrial spheres

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

Classifying signs and symptoms of dry eye disease according to underlying mechanism via the Delphi method: the DIDACTIC study

BACKGROUND/AIMS: Dry eye disease (DED) is categorised by pathophysiology as aqueous deficient dry eye (ADDE), evaporative dry eye (EDE) or mixed. Treatment should be tailored to DED pathophysiology, but this is challenging to determine. This Delphi consultation aimed to categorise and weight signs and symptoms to help identify the evaporative or aqueous deficient DED origin. METHODS: A panel of French DED experts created an initial list of 77 DED signs and symptoms. In a Delphi consultation, experts categorised items by DED pathophysiology. Likert scoring was used to indicate whether items were strongly or moderately indicative of ADDE or EDE. Items could also be judged non-applicable to DED, with the opportunity to suggest alternative diagnoses. RESULTS: Experts attributed 19 items (of which 11 were strongly indicative) to a pathophysiology of EDE and 12 items (of which four were strongly indicative) to ADDE. Items scored strongly indicative with agreement >90% for EDE were previous chalazia, rosacea/rhinophyma, telangiectasias of eyelid margin and thick non-expressible meibomian gland secretions, and for ADDE were Sjögren syndrome or associated disease, and Schirmer <5 mm after 5 min (without anaesthesia). Seventeen items indicated neither pathophysiology and 18 items were found to be suggestive of alternative diagnoses. CONCLUSIONS: This Delphi consultation categorised signs and symptoms, using an innovative weighting system to identify DED pathophysiology. An algorithm integrating the weighting of each sign and symptom of an individual patient would be valuable to help general ophthalmologists to classify the DED subtype and tailor treatment to DED underlying mechanism

Study of the chemical derivatization of zearalenone and its metabolites for gas chromatography-mass spectrometry analysis of environmental samples.

International audienceThis study compares different silylation procedures of zearalenone and its metabolites: alpha-zearalenol, beta-zearalenol, zearalanone, alpha-zearalanol and beta-zearalanol for gas chromatography-mass spectrometry (GC-MS) analysis. Four silylating agents among the most frequently used to derivatize polar organic compounds were tested: N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA), N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA), N,N-diethyltrimethylsilylamine (TMSDEA) and a commercial mixture of N,O-bis(trimethylsilyl)acetamide, trimethylchlorosilane and N-trimethylsilyimidazole. Previous studies showed that the addition of polar and/or basic solvents can significantly improve the yield of a reaction of derivatization. In this work, four solvents were tested: pyridine, dimethylformamide, acetonitrile and acetone. The influence of each solvent was studied as a function of the silylating agent/solvent ratio. The influences of the temperature and of the reaction time on the reaction yields were also evaluated. A GC-MS quantitation method associating methanol chemical ionization and selected ion storage with three ions was developed and successfully tested on a reconstituted sediment spiked in zearalenone and its metabolites

A Prediction-Driven Adaptation Approach for Self-Adaptive Sensor Networks

International audienceEngineering self-adaptive software in unpredictable environments such as pervasive systems, where network's ability, remaining battery power and environmental conditions may vary over the lifetime of the system is a very challenging task. Many current software engineering approaches leverage run-time architectural models to ease the design of the autonomic control loop of these self-adaptive systems. While these approaches perform well in reacting to various evolutions of the runtime environment, implementations based on reactive paradigms have a limited ability to anticipate problems, leading to transient unavailability of the system, useless costly adaptations, or resources waste. In this paper, we follow a proactive self-adaptation approach that aims at overcoming the limitation of reactive approaches. Based on predictive analysis of internal and external context information, our approach regulates new architecture recon figurations and deploys them using models at runtime. We have evaluated our approach on a case study where we combined hourly temperature readings provided by National Climatic Data Center (NCDC) with re reports from Moderate Resolution Imaging Spectroradiometer (MODIS) and simulated the behavior of multiple systems. The results confirm that our proactive approach outperforms a typical reactive system in scenarios with seasonal behavior

Challenges in Knowledge Management for Structuring Systems

Part 5: PLM and Knowledge ManagementInternational audienceStructuring Systems can be defined as systems, designed, installed, used and maintained within their operational environment for an extremely long duration, answering to the fundamental needs of the society. Examples of such systems are water systems, transport or electricity network. Due to their nature, these systems are characterized to be highly complex, according to the general system theory. In this context, the classical Knowledge Management (KM) approaches are not suited, due to the nature and origins of some data, information and knowledge, the complexity of partner networks that are interacting around the systems, the evolution history of such systems, etc. In this article, we present the main challenges for KM in Structuring Systems, especially in terms of knowledge traceability and heritage from one hand, and knowledge preservation at another one

Dissemination of reconfiguration policies on mesh networks

International audienceComponent-based platforms are widely used to develop and deploy distributed pervasive system that exhibit a high degree of dynam- icity, concurrency, distribution, heterogeneity, and volatility. This paper deals with the problem of ensuring safe yet efficient dynamic adaptation in a distributed and volatile environment. Most current platforms pro- vide capabilities for dynamic local adaptation to adapt these systems to their evolving execution context, but are still limited in their ability to handle distributed adaptations. Thus, a remaining challenge is to safely propagate reconfiguration policies of component-based systems to ensure consistency of the architecture configuration models over a dynamic and distributed system. In this paper we implement a specific algorithm rely- ing on the models at runtime paradigm to manage platform independent models of the current system architecture and its deployed configuration, and to propagate reconfiguration policies. We evaluate a combination of gossip-based algorithms and vector clock techniques that are able to propagate these policies safely in order to preserve consistency of archi- tecture configuration models among all computation nodes of the system. This evaluation is done with a test-bed system running on a large size grid network