L'intégration du principe de continuité écologique dans les schémas de cohérence territoriale (SCOT) Analyse de 21 expériences de SCOT

Cette étude s'inscrit dans le cadre des travaux du Comité opérationnel Trame verte et bleue mis en place pour réfléchir aux modalités de mise en place d'une Trame verte et bleue en France, mesure inscrite dans le projet de loi Grenelle 2. À travers un recueil d'expériences de vingt et un schémas de cohérence territoriale (SCOT), l'étude analyse les différentes méthodes d'identification des trames vertes et bleues, les modalités d'intégration de cet outil d'aménagement dans les projets de territoire et les démarches participatives mises en place pour faire adhérer les différents acteurs socio-économiques au projet. L'étude est ponctuée de recommandations pour intégrer la Trame verte et bleue dans un SCOT dans le respect des orientations nationales. / This study is part of the work for the operational committee (COMOP) in charge of formulating the rules and recommendations for implementation of the French ecological network created by the "Grenelle II" law. Based on 21 local development plans (SCOT), the study analyses the different methods used to position local ecological networks, how this planning tool is used in the local development plans and how participative approaches have been developed to ensure that local stakeholders support the project. The study has produced recommendations on how to integrate an ecological network in a SCOT in compliance with national guidelines

L'information géographique au service de la forêt : définitions et enjeux.

Introduction et sommaire détaillé des travaux du groupe "Systèmes d information, informatique et forêt méditerranéenne" de Foresterranée 99

Imaging angiogenesis in atherosclerosis in large arteries with 68Ga-NODAGA-RGD PET/CT: relationship with clinical atherosclerotic cardiovascular disease.

Integrin alpha-V-beta-3 (αvβ3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. The aim of this study was to assess the clinical correlates of arterial wall accumulation of <sup>68</sup> Ga-NODAGA-RGD, a specific α <sub>v</sub> β <sub>3</sub> integrin ligand for PET. The data of 44 patients who underwent <sup>68</sup> Ga-NODAGA-RGD PET/CT scans were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed semi-quantitatively by blood-pool-corrected target-to-background ratios. Tracer uptake was compared with clinically documented atherosclerotic cardiovascular disease, cardiovascular risk factors and calcified plaque burden. Data were compared using the Mann-Whitney U test, Pearson correlation and Spearman correlation. <sup>68</sup> Ga-NODAGA-RGD arterial uptake was significantly higher in patients with previous clinically documented atherosclerotic cardiovascular disease (mean TBR 2.44 [2.03-2.55] vs. 1.81 [1.56-1.96], p = 0.001) and showed a significant correlation with prior cardiovascular or cerebrovascular event (r = 0.33, p = 0.027), BMI (ρ = 0.38, p = 0.01), plaque burden (ρ = 0.31, p = 0.04) and hypercholesterolemia (r = 0.31, p = 0.04). <sup>68</sup> Ga-NODAGA-RGD holds promise as a non-invasive marker of disease activity in atherosclerosis, providing information about intraplaque angiogenesis

First in-human radiation dosimetry of (68)Ga-NODAGA-RGDyK.

Integrin-targeting radiopharmaceuticals have potential broad applications, spanning from cancer theranostics to cardiovascular diseases. We have previously reported preclinical dosimetry results of (68)Ga-NODAGA-RGDyK in mice. This study presents the first human dosimetry of (68)Ga-NODAGA-RGDyK in the five consecutive patients included in a clinical imaging protocol of carotid atherosclerotic plaques. Five male patients underwent whole-body time-of-flight (TOF) PET/CT scans 10, 60 and 120 min after tracer injection (200 MBq). Quantification of (68)Ga activity concentration was first validated by a phantom study. To be used as input in OLINDA/EXM, time-activity curves were derived from manually drawn regions of interest over the following organs: brain, thyroid, lungs, heart, liver, spleen, stomach, kidneys, red marrow, pancreas, small intestine, colon, urinary bladder and whole body. A separate dosimetric analysis was performed for the choroid plexuses. Female dosimetry was extrapolated from male data. Effective doses (EDs) were estimated according to both ICRP60 and ICRP103 assuming 30-min and 1-h voiding cycles. The body regions receiving the highest dose were urinary bladder, kidneys and choroid plexuses. For a 30-min voiding cycle, the EDs were 15.7 and 16.5 μSv/MBq according to ICRP60 and ICRP103, respectively. The extrapolation to female dosimetry resulted in organ absorbed doses 17% higher than those of male patients, on average. The 1-h voiding cycle extrapolation resulted in EDs of 19.3 and 19.8 μSv/MBq according to ICRP60 and ICRP103, respectively. A comparison is made with previous mouse dosimetry and with other human studies employing different RGD-based radiopharmaceuticals. According to ICRP60/ICRP103 recommendations, an injection of 200 MBq (68)Ga-NODAGA-RGDyK leads to an ED in man of 3.86/3.92 mSv. For future therapeutic applications, specific attention should be directed to delivered dose to kidneys and potentially also to the choroid plexuses. Clinical trial.gov, NCT01608516

Is M. ulcerans able to colonize neuronal cells?

Buruli ulcer, or Mycobacterium ulcerans infection, is an emerging disease, principally diagnosed in humid tropical countries and inducing large skin ulcers. These lesions are painless, a distinct feature that suggests that the mycolactone toxin and/or M. ulcerans impedes the signal transmission by the nervous system. In this context, the aim of this work was to study the interaction between M. ulcerans and neuronal cells by using in vitro and in vivo models. We showed that a virulent strain of M. ulcerans is able to enter into neurons cultivated from neonatal rat hippocampus. On the contrary, this phenomenon was less observed with a mycolactone-deficient strain. To support these data, we analysed nerve fibres from mouse-infected tissues and few bacilli were found in close contact with nerve fibres. The invasion process established by M. ulcerans to colonize the nervous system remains uncharacterised, but we hypothesise that this ability could be involved in the painless of the M. ulcerans infection

Assessing the role of EO in biodiversity monitoring: options for integrating in-situ observations with EO within the context of the EBONE concept

The European Biodiversity Observation Network (EBONE) is a European contribution on terrestrial monitoring to GEO BON, the Group on Earth Observations Biodiversity Observation Network. EBONE’s aims are to develop a system of biodiversity observation at regional, national and European levels by assessing existing approaches in terms of their validity and applicability starting in Europe, then expanding to regions in Africa. The objective of EBONE is to deliver: 1. A sound scientific basis for the production of statistical estimates of stock and change of key indicators; 2. The development of a system for estimating past changes and forecasting and testing policy options and management strategies for threatened ecosystems and species; 3. A proposal for a cost-effective biodiversity monitoring system. There is a consensus that Earth Observation (EO) has a role to play in monitoring biodiversity. With its capacity to observe detailed spatial patterns and variability across large areas at regular intervals, our instinct suggests that EO could deliver the type of spatial and temporal coverage that is beyond reach with in-situ efforts. Furthermore, when considering the emerging networks of in-situ observations, the prospect of enhancing the quality of the information whilst reducing cost through integration is compelling. This report gives a realistic assessment of the role of EO in biodiversity monitoring and the options for integrating in-situ observations with EO within the context of the EBONE concept (cfr. EBONE-ID1.4). The assessment is mainly based on a set of targeted pilot studies. Building on this assessment, the report then presents a series of recommendations on the best options for using EO in an effective, consistent and sustainable biodiversity monitoring scheme. The issues that we faced were many: 1. Integration can be interpreted in different ways. One possible interpretation is: the combined use of independent data sets to deliver a different but improved data set; another is: the use of one data set to complement another dataset. 2. The targeted improvement will vary with stakeholder group: some will seek for more efficiency, others for more reliable estimates (accuracy and/or precision); others for more detail in space and/or time or more of everything. 3. Integration requires a link between the datasets (EO and in-situ). The strength of the link between reflected electromagnetic radiation and the habitats and their biodiversity observed in-situ is function of many variables, for example: the spatial scale of the observations; timing of the observations; the adopted nomenclature for classification; the complexity of the landscape in terms of composition, spatial structure and the physical environment; the habitat and land cover types under consideration. 4. The type of the EO data available varies (function of e.g. budget, size and location of region, cloudiness, national and/or international investment in airborne campaigns or space technology) which determines its capability to deliver the required output. EO and in-situ could be combined in different ways, depending on the type of integration we wanted to achieve and the targeted improvement. We aimed for an improvement in accuracy (i.e. the reduction in error of our indicator estimate calculated for an environmental zone). Furthermore, EO would also provide the spatial patterns for correlated in-situ data. EBONE in its initial development, focused on three main indicators covering: (i) the extent and change of habitats of European interest in the context of a general habitat assessment; (ii) abundance and distribution of selected species (birds, butterflies and plants); and (iii) fragmentation of natural and semi-natural areas. For habitat extent, we decided that it did not matter how in-situ was integrated with EO as long as we could demonstrate that acceptable accuracies could be achieved and the precision could consistently be improved. The nomenclature used to map habitats in-situ was the General Habitat Classification. We considered the following options where the EO and in-situ play different roles: using in-situ samples to re-calibrate a habitat map independently derived from EO; improving the accuracy of in-situ sampled habitat statistics, by post-stratification with correlated EO data; and using in-situ samples to train the classification of EO data into habitat types where the EO data delivers full coverage or a larger number of samples. For some of the above cases we also considered the impact that the sampling strategy employed to deliver the samples would have on the accuracy and precision achieved. Restricted access to European wide species data prevented work on the indicator ‘abundance and distribution of species’. With respect to the indicator ‘fragmentation’, we investigated ways of delivering EO derived measures of habitat patterns that are meaningful to sampled in-situ observations

Knowledge representation for product and processes development planning in collaborative environments

Efficiency in the management of integrated product and processes development is a basic requisite to guarantee competitiveness and success for manufacturing companies. This means that operational management of activities and human and material resources is extremely important, especially in virtual OKP (one-of-a-kind production) systems, and must cover related aspects of their capabilities and social character as well as assignment criteria. In this context, and to facilitate collaborative resources management, an ontology focused on resources and capabilities is proposed in this work. This ontology supports the necessary knowledge for generic and collaborative process planning, providing a shared common semantic for all the members of the virtual company. This work differs from other proposed ontologies in the area of process planning where the resources considered are all those elements that participate in the execution of the different activity types involved in this wide and complex process. The ontology directly covers the shared, social nature of the resources, the agentive behaviour of many of them and a characterisation of their capabilities, thus providing specific solutions to the needs of the collaborative integrated development of products, processes and resources (CIDP2R) process.This work has been possible thanks to funding received from the Ministry of Science and Education through the COAPP Research Project - reference DPI2007-66871-C02-01/02.Solano García, L.; Rosado Castellano, P.; Romero Subirón, F. (2014). Knowledge representation for product and processes development planning in collaborative environments. International Journal of Computer Integrated Manufacturing. 27(8):787-801. doi:10.1080/0951192X.2013.834480S78780127

The Development of Peptide-Based Tools for the Analysis of Angiogenesis

SummaryLimitations to the application of molecularly targeted cancer therapies are the inability to accurately match patient with effective treatment and the absence of a prompt readout of posttreatment response. Noninvasive agents that rapidly report vascular endothelial growth factor (VEGF) levels using positron emission tomography (PET) have the potential to enhance anti-angiogenesis therapies. Using phage display, two distinct classes of peptides were identified that bind to VEGF with nanomolar affinity and high selectivity. Co-crystal structures of these different peptide classes demonstrate that both bind to the receptor-binding region of VEGF. 18F-radiolabelling of these peptides facilitated the acquisition of PET images of tumor VEGF levels in a HM7 xenograph model. The images obtained from one 59-residue probe, 18F-Z-3B, 2 hr postinjection are comparable to those obtained with anti-VEGF antibody B20 72 hr postinjection. Furthermore, VEGF levels in growing SKOV3 tumors were followed using 18F-Z-3B as a PET probe with VEGF levels increasing with tumor size

Efficacy of Continuous Interleukin 1 Blockade in Mevalonate Kinase Deficiency: A Multicenter Retrospective Study in 13 Adult Patients and Literature Review

OBJECTIVE: To report efficacy and tolerance of interleukin 1 blockade in adult patients with mevalonate kinase deficiency (MKD). METHODS: We retrospectively collected data on 13 patients with MKD who had received anakinra (n = 10) and canakinumab (n = 7). RESULTS: Anakinra resulted in complete or partial remission in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to canakinumab led to partial remission. Canakinumab resulted in complete or partial remission in 3/7 and 4/7 patients, respectively. CONCLUSION: These data support frequent partial responses, showing a better response with canakinumab. The genotype and therapeutic outcomes correlation should help in the personalization of treatment