PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in rhabdomyosarcoma and significantly improves current risk stratification.

PURPOSE: To improve the risk stratification of patients with rhabdomyosarcoma (RMS) through the use of clinical and molecular biologic data. PATIENTS AND METHODS: Two independent data sets of gene-expression profiling for 124 and 101 patients with RMS were used to derive prognostic gene signatures by using a meta-analysis. These and a previously published metagene signature were evaluated by using cross validation analyses. A combined clinical and molecular risk-stratification scheme that incorporated the PAX3/FOXO1 fusion gene status was derived from 287 patients with RMS and evaluated. RESULTS: We showed that our prognostic gene-expression signature and the one previously published performed well with reproducible and significant effects. However, their effect was reduced when cross validated or tested in independent data and did not add new prognostic information over the fusion gene status, which is simpler to assay. Among nonmetastatic patients, patients who were PAX3/FOXO1 positive had a significantly poorer outcome compared with both alveolar-negative and PAX7/FOXO1-positive patients. Furthermore, a new clinicomolecular risk score that incorporated fusion gene status (negative and PAX3/FOXO1 and PAX7/FOXO1 positive), Intergroup Rhabdomyosarcoma Study TNM stage, and age showed a significant increase in performance over the current risk-stratification scheme. CONCLUSION: Gene signatures can improve current stratification of patients with RMS but will require complex assays to be developed and extensive validation before clinical application. A significant majority of their prognostic value was encapsulated by the fusion gene status. A continuous risk score derived from the combination of clinical parameters with the presence or absence of PAX3/FOXO1 represents a robust approach to improving current risk-adapted therapy for RMS.

Compliance management is becoming a major issue in IS design

This article aims at improving the information systems management support to Risk and Compliance Management process, i.e. the management of all compliance imperatives that impact an organization, including both legal and stra- tegically self-imposed imperatives. We propose a process to achieve such regula- tory compliance by aligning the Governance activities with the Risk Management ones, and we suggest Compliance should be considered as a requirement for the Risk Management platform. We will propose a framework to align law and IT compliance requirements and we will use it to underline possible directions of investigation resumed in our discussion section. This work is based on an exten- sive review of the existing literature and on the results of a four-month internship done within the IT compliance team of a major financial institution in Switzer- land, which has legal entities situated in different countries.

An interactive web-GIS tool for risk analysis: a case study in the Fella River basin, Italy

This paper presents a prototype of an interactive web-GIS tool for risk analysis of natural hazards, in particular for floods and landslides, based on open-source geospatial software and technologies. The aim of the presented tool is to assist the experts (risk managers) in analysing the impacts and consequences of a certain hazard event in a considered region, providing an essential input to the decision-making process in the selection of risk management strategies by responsible authorities and decision makers. This tool is based on the Boundless (OpenGeo Suite) framework and its client-side environment for prototype development, and it is one of the main modules of a web-based collaborative decision support platform in risk management. Within this platform, the users can import necessary maps and information to analyse areas at risk. Based on provided information and parameters, loss scenarios (amount of damages and number of fatalities) of a hazard event are generated on the fly and visualized interactively within the web-GIS interface of the platform. The annualized risk is calculated based on the combination of resultant loss scenarios with different return periods of the hazard event. The application of this developed prototype is demonstrated using a regional data set from one of the case study sites, Fella River of northeastern Italy, of the Marie Curie ITN CHANGES project.

From Regional Landslide Detection to Site-Specific Slope Deformation Monitoring and Modelling Based on Active Remote Sensors

Landslide processes can have direct and indirect consequences affecting human lives and activities. In order to improve landslide risk management procedures, this PhD thesis aims to investigate capabilities of active LiDAR and RaDAR sensors for landslides detection and characterization at regional scales, spatial risk assessment over large areas and slope instabilities monitoring and modelling at site-specific scales. At regional scales, we first demonstrated recent boat-based mobile LiDAR capabilities to model topography of the Normand coastal cliffs. By comparing annual acquisitions, we validated as well our approach to detect surface changes and thus map rock collapses, landslides and toe erosions affecting the shoreline at a county scale. Then, we applied a spaceborne InSAR approach to detect large slope instabilities in Argentina. Based on both phase and amplitude RaDAR signals, we extracted decisive information to detect, characterize and monitor two unknown extremely slow landslides, and to quantify water level variations of an involved close dam reservoir. Finally, advanced investigations on fragmental rockfall risk assessment were conducted along roads of the Val de Bagnes, by improving approaches of the Slope Angle Distribution and the FlowR software. Therefore, both rock-mass-failure susceptibilities and relative frequencies of block propagations were assessed and rockfall hazard and risk maps could be established at the valley scale. At slope-specific scales, in the Swiss Alps, we first integrated ground-based InSAR and terrestrial LiDAR acquisitions to map, monitor and model the Perraire rock slope deformation. By interpreting both methods individually and originally integrated as well, we therefore delimited the rockslide borders, computed volumes and highlighted non-uniform translational displacements along a wedge failure surface. Finally, we studied specific requirements and practical issues experimented on early warning systems of some of the most studied landslides worldwide. As a result, we highlighted valuable key recommendations to design new reliable systems; in addition, we also underlined conceptual issues that must be solved to improve current procedures. To sum up, the diversity of experimented situations brought an extensive experience that revealed the potential and limitations of both methods and highlighted as well the necessity of their complementary and integrated uses.

Large slope deformations detection and monitoring along shores of the Potrerillos dam reservoir, Argentina, based on a small-baseline InSAR approach

The Argentina National Road 7 that crosses the Andes Cordillera within the Mendoza province to connect Santiago de Chile and Buenos Aires is particularly affected by natural hazards requiring risk management. Integrated in a research plan that intends to produce landslide susceptibility maps, we aimed in this study to detect large slope movements by applying a satellite radar interferometric analysis using Envisat data, acquired between 2005 and 2010. We were finally able to identify two large slope deformations in sandstone and clay deposits along gentle shores of the Potrerillos dam reservoir, with cumulated displacements higher than 25mm in 5years and towards the reservoir. There is also a body of evidences that these large slope deformations are actually influenced by the seasonal reservoir level variations. This study shows that very detailed information, such as surface displacements and above all water level variation, can be extracted from spaceborne remote sensing techniques; nevertheless, the limitations of InSAR for the present dataset are discussed here. Such analysis can then lead to further field investigations to understand more precisely the destabilising processes acting on these slope deformations.

Promise for plant pest control: root-associated pseudomonads with insecticidal activities.

Insects are an important and probably the most challenging pest to control in agriculture, in particular when they feed on belowground parts of plants. The application of synthetic pesticides is problematic owing to side effects on the environment, concerns for public health and the rapid development of resistance. Entomopathogenic bacteria, notably Bacillus thuringiensis and Photorhabdus/Xenorhabdus species, are promising alternatives to chemical insecticides, for they are able to efficiently kill insects and are considered to be environmentally sound and harmless to mammals. However, they have the handicap of showing limited environmental persistence or of depending on a nematode vector for insect infection. Intriguingly, certain strains of plant root-colonizing Pseudomonas bacteria display insect pathogenicity and thus could be formulated to extend the present range of bioinsecticides for protection of plants against root-feeding insects. These entomopathogenic pseudomonads belong to a group of plant-beneficial rhizobacteria that have the remarkable ability to suppress soil-borne plant pathogens, promote plant growth, and induce systemic plant defenses. Here we review for the first time the current knowledge about the occurrence and the molecular basis of insecticidal activity in pseudomonads with an emphasis on plant-beneficial and prominent pathogenic species. We discuss how this fascinating Pseudomonas trait may be exploited for novel root-based approaches to insect control in an integrated pest management framework.

Psychiatrie et violence : quel est le risque acceptable ?

L'évolution des connaissances et des compétences en matière d'évaluation et de gestion du risque de violence a permis une indiscutable avancée. Néanmoins les instruments utilisés restent encore source de controverses et prêtent le flanc à de nombreuses critiques. Dans ce contexte le climat sécuritaire actuel fait peser une lourde pression sur les équipes soignantes qui ont aussi à faire face à la violence des patients. Une réflexion sur les possibilités et les limites autant du soin que de la privation de liberté permet, peut-être d'envisager ce qu'est un risque acceptable. Evolution of knowledge and skills in violence risk management and assessment allowed an indisputable progress. Nevertheless instruments used such as HCR-20 still remain source of controversy and gives occurrence to numerous criticisms. In this context, the current high security climate puts added pressure on the medical teams which also have to deal with the violence of patients. A reflection on the possibilities and the limits of care as well as freedom deprivation may allow us to envision what is an acceptable risk.

Rapid bacterial genome sequencing: methods and applications in clinical microbiology.

The recent advances in sequencing technologies have given all microbiology laboratories access to whole genome sequencing. Providing that tools for the automated analysis of sequence data and databases for associated meta-data are developed, whole genome sequencing will become a routine tool for large clinical microbiology laboratories. Indeed, the continuing reduction in sequencing costs and the shortening of the 'time to result' makes it an attractive strategy in both research and diagnostics. Here, we review how high-throughput sequencing is revolutionizing clinical microbiology and the promise that it still holds. We discuss major applications, which include: (i) identification of target DNA sequences and antigens to rapidly develop diagnostic tools; (ii) precise strain identification for epidemiological typing and pathogen monitoring during outbreaks; and (iii) investigation of strain properties, such as the presence of antibiotic resistance or virulence factors. In addition, recent developments in comparative metagenomics and single-cell sequencing offer the prospect of a better understanding of complex microbial communities at the global and individual levels, providing a new perspective for understanding host-pathogen interactions. Being a high-resolution tool, high-throughput sequencing will increasingly influence diagnostics, epidemiology, risk management, and patient care.

Apport de la systématique dans l'amélioration de la compréhension des systèmes de prise en compte des risques en entreprise

La gestion des risques est souvent appréhendée par l'utilisation de méthodes linéaires mettant l'accent sur des raisonnements de positionnement et de type causal : à tel événement correspond tel risque et telle conséquence. Une prise en compte des interrelations entre risques est souvent occultée et les risques sont rarement analysés dans leurs dynamiques et composantes non linéaires. Ce travail présente ce que les méthodes systémiques et notamment l'étude des systèmes complexes sont susceptibles d'apporter en matière de compréhension, de management et d'anticipation et de gestion des risques d'entreprise, tant sur le plan conceptuel que de matière appliquée. En partant des définitions relatives aux notions de systèmes et de risques dans différents domaines, ainsi que des méthodes qui sont utilisées pour maîtriser les risques, ce travail confronte cet ensemble à ce qu'apportent les approches d'analyse systémique et de modélisation des systèmes complexes. En mettant en évidence les effets parfois réducteurs des méthodes de prise en compte des risques en entreprise ainsi que les limitations des univers de risques dues, notamment, à des définitions mal adaptées, ce travail propose également, pour la Direction d'entreprise, une palette des outils et approches différentes, qui tiennent mieux compte de la complexité, pour gérer les risques, pour aligner stratégie et management des risques, ainsi que des méthodes d'analyse du niveau de maturité de l'entreprise en matière de gestion des risques. - Risk management is often assessed through linear methods which stress positioning and causal logical frameworks: to such events correspond such consequences and such risks accordingly. Consideration of the interrelationships between risks is often overlooked and risks are rarely analyzed in their dynamic and nonlinear components. This work shows what systemic methods, including the study of complex systems, are likely to bring to knowledge, management, anticipation of business risks, both on the conceptual and the practical sides. Based on the definitions of systems and risks in various areas, as well as methods used to manage risk, this work confronts these concepts with approaches of complex systems analysis and modeling. This work highlights the reducing effects of some business risk analysis methods as well as limitations of risk universes caused in particular by unsuitable definitions. As a result this work also provides chief officers with a range of different tools and approaches which allows them a better understanding of complexity and as such a gain in efficiency in their risk management practices. It results in a better fit between strategy and risk management. Ultimately the firm gains in its maturity of risk management.

NanoImpactNet - Stakeholders' knowledge needs for research on the health and environmental impact of nanomaterials

NanoImpactNet (NIN) is a multidisciplinary European Commission funded network on the environmental, health and safety (EHS) impact of nanomaterials. The 24 founding scientific institutes are leading European research groups active in the fields of nanosafety, nanorisk assessment and nanotoxicology. This 4−year project is the new focal point for information exchange within the research community. Contact with other stakeholders is vital and their needs are being surveyed. NIN is communicating with 100s of stakeholders: businesses; internet platforms; industry associations; regulators; policy makers; national ministries; international agencies; standard−setting bodies and NGOs concerned by labour rights, EHS or animal welfare. To improve this communication, internet research, a questionnaire distributed via partners and targeted phone calls were used to identify stakeholders' interests and needs. Knowledge gaps and the necessity for further data mentioned by representatives of all stakeholder groups in the targeted phone calls concerned: potential toxic and safety hazards of nanomaterials throughout their lifecycles; fate and persistence of nanoparticles in humans, animals and the environment; risks associated to nanoparticle exposure; participation in the preparation of nomenclature, standards, methodologies, protocols and benchmarks; development of best practice guidelines; voluntary schemes on responsibility; databases of materials, research topics and themes. Findings show that stakeholders and NIN researchers share very similar knowledge needs, and that open communication and free movement of knowledge will benefit both researchers and industry. Consequently NIN will encourage stakeholders to be active members. These survey findings will be used to improve NIN's communication tools to further build on interdisciplinary relationships towards a healthy future with nanotechnology.

Mycophenolic acid formulations in adult renal transplantation - update on efficacy and tolerability.

The description more than 30 years ago of the role of de novo purine synthesis in T and B lymphocytes clonal proliferation opened the possibility for selective immunosuppression by targeting specific enzymatic pathways. Mycophenolic acid (MPA) blocks the key enzyme inosine monophosphate dehydrogenase and the production of guanosine nucleotides required for DNA synthesis. Two MPA formulations are currently used in clinical transplantation as part of the maintenance immunosuppressive regimen. Mycophenolate mofetil (MMF) was the first MPA agent to be approved for the prevention of acute rejection following renal transplantation, in combination with cyclosporine and steroids. Enteric-coated mycophenolate sodium (EC-MPS) is an alternative MPA formulation available in clinical transplantation. In this review, we will discuss the clinical trials that have evaluated the efficacy and safety of MPA in adult kidney transplantation for the prevention of acute rejection and their use in new combination regimens aiming at minimizing calcineurin inhibitor toxicity and chronic allograft nephropathy. We will also discuss MPA pharmacokinetics and the rationale for therapeutic drug monitoring in optimizing the balance between efficacy and safety in individual patients.