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The ENVISION project (2019-2021) supported the development of a participatory approach to the management of PAs, inclusive conservation, with the aim of improving biodiversity and human well-being. Inclusive conservation is an approach for accommodating and balancing different stakeholder visions and values for PA management to achieve socially relevant and environmentally sustainable outcomes in protected areas. This brief provides a current description of the international policy landscape for conservation and protected areas and outlines a set of tools to enhance inclusive management of protected areas. These tools have been developed and applied across four case study areas by a team of international researchers.

The Sierra de Guadarrama National Park is located in the Central MountainSystem of the Iberian Peninsula. It was established in 2013, becomingSpain's newest national park. This National Park covers 34,000 hectaresacross the regions of Madrid (64% of the territory) and Castilla y León.The National Park’s authority in the areais intertwined with the different scales of decision-making of multiplestate administrations. To compound this complexity, the Sierra deGuadarrama is the second most visited national park in Spain, and thereare a great variety of local stakeholders engaged in diverse activitiessuch as outdoor sports, extensive livestock farming, and environmentalconservation, education and research. The multiple and sometimescompeting uses and values create social tensions around how the parkshould be governed.Researchersareconducting research to provide practical guidance to understand, navigateand consider different visions, preferences, tensions, responsibilities andpower relations between stakeholders, in order to move towards bettersocial engagement in conservation decision-making.&nbsp

This report corresponds to ENVISION milestone 5.3., aiming to develop a workshop for participatory scenario planning to reflect on five possible future scenarios for the Sierra de Guadarrama National Park (Spain). The participatory scenario planning exercise involved a two-day online workshop with 45 participants, including decision-makers, researchers, local users, non-governmental organizations, and other social actors. On the basis of a common assessment of the current socio-ecological conditions and the factors driving change in recent years, they consideredwhat could happen in the next twenty years. The stakeholders discussed whether and how the area might continue to contribute to the quality of life of those who currently enjoy the ecosystem services it provides. Further, by identifying the advantages and disadvantages of the envisioned futurescenarios,who would lose or gain in the respective future scenarios was assessed. The stakeholdersprioritized several strategies to realize their desired futures for the National Park.

Context Most protected areas are managed based on objectives related to scientific ecological knowledge of species and ecosystems. However, a core principle of sustainability science is that understanding and including local ecological knowledge, perceptions of ecosystem service provision and landscape vulnerability will improve sustainability and resilience of social-ecological systems. Here, we take up these assumptions in the context of protected areas to provide insight on the effectiveness of nature protection goals, particularly in highly human-influenced landscapes. Objectives We examined how residents' ecological knowledge systems, comprised of both local and scientific, mediated the relationship between their characteristics and a set of variables that represented perceptions of ecosystem services, landscape change, human-nature relationships, and impacts. Methods We administered a face-to-face survey to local residents in the Sierra de Guadarrama protected areas, Spain. We used bi- and multi-variate analysis, including partial least squares path modeling to test our hypotheses. Results Ecological knowledge systems were highly correlated and were instrumental in predicting perceptions of water-related ecosystem services, landscape change, increasing outdoors activities, and human-nature relationships. Engagement with nature, socio-demographics, trip characteristics, and a rural-urban gradient explained a high degree of variation in ecological knowledge. Bundles of perceived ecosystem services and impacts, in relation to ecological knowledge, emerged as social representation on how residents relate to, understand, and perceive landscapes. Conclusions Our findings provide insight into the interactions between ecological knowledge systems and their role in shaping perceptions of local communities about protected areas. These results are expected to inform protected area management and landscape sustainability.

This deliverable corresponds to ENVISION task 5.1, aiming to identify the governance arrangements behind protected areas (PAs) management, as well as the strengths and gaps in coordination across involved institutions, through a case study in a European PA: The Sierra de Guadarrama National Park (Spain). Aquest lliurament correspon a la tasca 5.1 de ENVISION, l'objectiu de la qual és identificar els acords de governança que subjeuen a la gestió de les àrees protegides (AP), així com els punts forts i les llacunes en la coordinació entre les institucions implicades, a través d'un estudi de cas en un AP europeu: El Parc Nacional de la Serra de Guadarrama (Espanya). Esta entrega corresponde a la tarea 5.1 de ENVISION, cuyo objetivo es identificar los acuerdos de gobernanza que subyacen a la gestión de las áreas protegidas (AP), así como los puntos fuertes y las lagunas en la coordinación entre las instituciones implicadas, a través de un estudio de caso en un AP europeo: El Parque Nacional de la Sierra de Guadarrama (España).

In this paper, we develop a novel interpretation of the internal relationship between value, rent and finance, thereby enabling a new reading of the process of financialisation. As we argue, responding to the important question of how best to conceptualise the relationship between value and finance necessitates an understanding of the internal relations with a third moment, that of rent. We therefore develop a triadic understanding of these three interrelated moments. Crucially, we demonstrate that fictitious capital now actively pursues forms of rent, deepening the interrelationship between value, rent and finance. We conclude with a critical review of the literature on the financialisation of water, showing how the conceptual framework we develop sheds light upon the relations out of which water infrastructure has been financialised, as well as suggesting strategic entry points for its contestation.

Graphical abstract, We have previously reported a series of anilinoquinazoline derivatives as potent and selective biochemical inhibitors of the RET kinase domain. However, these derivatives displayed diminished cellular potency. Herein we describe further optimisation of the series through modification of their physicochemical properties, delivering improvements in cell potency. However, whilst cellular selectivity against key targets could be maintained, combining cell potency and acceptable pharmacokinetics proved challenging.

Deregulation of the receptor tyrosine kinase RET has been implicated in medullary thyroid cancer, a small percentage of lung adenocarcinomas, endocrine-resistant breast cancer and pancreatic cancer. There are several clinically approved multi-kinase inhibitors that target RET as a secondary pharmacology but additional activities, most notably inhibition of KDR, lead to dose-limiting toxicities. There is, therefore, a clinical need for more specific RET kinase inhibitors. Herein we report our efforts towards identifying a potent and selective RET inhibitor using vandetanib 1 as the starting point for structure-based drug design. Phenolic anilinoquinazolines exemplified by 6 showed improved affinities towards RET but, unsurprisingly, suffered from high metabolic clearance. Efforts to mitigate the metabolic liability of the phenol led to the discovery that a flanking substituent not only improved the hepatocyte stability, but could also impart a significant gain in selectivity. This culminated in the identification of 36; a potent RET inhibitor with much improved selectivity against KDR., Graphical abstract, Highlights • Novel anilinoquinazoline RET inhibitors have been prepared. • Phenolic moieties display enhanced potency but decreased metabolic stability. • Substitution patterns adjacent to the phenol improve metabolic stability. • These substituents deliver unanticipated improvements in selectivity. • Improvements in selectivity are explained through X-ray crystallographic studies.

Purpose. To estimate radiation doses from routine pediatric CT scans (body) and to propose dose reduction protocols. Materiel and methods. Study performed with a phantom equivalent to the body of 5 year old child with evaluation of doses delivered to breast, gonads, bone marrow (sternum, T12) and thyroid for GT examinations of the chest, abdomen, pelvis and spine. Extrapolation is made to estimate the doses for 1 year old and 10 year old children. Finally, dose reduction protocols are evaluated. Results. CT of the chest delivers significant doses to breast tissue and bone marrow, CT of the abdomen and pelvis delivers significant doses to the ovaries and CT pf the spine delivers significant doses to thyroid and bone marrow. Optimization can be achieved without degradation of the image quality, by reducing Kv and mAs within reasonable limits. This study may be used in order to evaluate the doses delivered by multi-detector CT units. © Éditions Françaises de Radiologie, 2005.; Objectifs Déterminer la dose organe délivrée pour les scanners pédiatriques courants du tronc et proposer une réduction des doses. Matériel et méthode Une étude sur fantôme correspondant au corps d’un enfant de 5 ans a été menée afin de mesurer la dose délivrée aux gonades, à la moelle osseuse (sternum T12) et à la thyroïde pour les scanners thoraciques, abdominaux, du bassin et du rachis. On a tenté d’optimiser les doses en réduisant les paramètres. Résultats Les doses organes délivrées sont assez significatives pour un scanner thoracique, aux seins et aux sites hématopoïétiques, la dose aux ovaires est importante pour les scanners abdomino-pelviens et le scanner du rachis est très irradiant pour la thyroïde ainsi que pour la moelle rouge. L’optimisation peut se faire sans dégradation de la qualité de l’image en diminuant KV et mAs dans des limites raisonnables. Cette étude doit servir de base à l’évaluation des doses délivrées par les scanners nouvelle génération.

International audience; Within the frame work of implementation of Directive 97/43, a French dosimetry campaign in diagnostic radiology was carried out, from April 2001 to February 2003, under supervision of a steering Committee, involving representatives of scientific and professional societies, of the Directorate-General for Nuclear Safety and Radiation Protection (DGSNR) and experts of the Institute of Radiation Protection and Nuclear Safety (IRSN). The aim was to assess patient dose associated to the standardized radiology procedures recommended by the "Société française de radiologie" and to determine national dose reference levels (DRL) in diagnostic radiology. On the basis of protocols and data sheets established by the "Société française de physique médicale" and the IRSN, measurements were performed by multidisciplinary team (radiologist, physicists and radiographer) in 24 volunteer centers. The treatment of measured and collected data was in charge of the IRSN. For each of the 8 examinations selected, (4 in Conventional Radiology (CR) and 4 in Computed Tomography (CT)), data and dose measurements were assessed for 20 adult patients in each center. In CR, the entrance surface dose for each exposure was measured on 1231 patients using thermoluminescent dosimeters. In CT, the weighted Computed Tomography Dose Index and the Dose-Length Product were calculated for 667 patients, on base of the procedure parameters and the scanner normalized dose index values. For each type of examination, mean dose values and third quartile values were determined: depending on the type of examination, the results are either similar or lower than 1996 European DRL. These results are analyzed according the dose influencing parameters. Despite the 24 involved hospitals were not randomly selected, this preliminary study emphasizes the feasibility and great interest of a larger campaign of measurements based on a precise statistical survey of radiological practices in order to determine French DRL and to facilitate their periodic review in a continuous process of unnecessary doses reduction. © 2004 EDP Sciences.; Dans le cadre des travaux de transposition en droit français de la directive 97/43 Euratom relative à la radioprotection des patients, une campagne nationale de dosimétrie en radiodiagnostic s’est déroulée entre avril 2001 et février 2003, à l’initiative conjointe des sociétés savantes et professionnelles, de la Direction générale de la Sûreté nucléaire et de la radioprotection (DGSNR) et de l’Institut de radioprotection et de sûreté nucléaire (IRSN). Son objectif était d’associer des niveaux de doses aux procédures radiologiques standardisées, élaborées dans une étape précédente par la Société française de radiologie, et d’engager une première étude pour la détermination de niveaux de référence diagnostiques (NRD) français. Sur la base de protocoles de mesures et de fiches d’informations établis par l’IRSN et la Société française de physique médicale, la campagne a reposé sur des équipes pluridisciplinaires (radiologue, physicien, technicien), dans 24 services de radiologie volontaires. Son organisation pratique, la centralisation des données et le traitement des résultats ont été assurés par l’IRSN. Pour les 8 examens sélectionnés (4 en radiologie classique et 4 en scanographie), dans chaque service, 20 sujets d’âge adulte et de morphologie moyenne devaient faire l’objet d’une dosimétrie. En radiologie classique, la dose à l’entrée a été mesurée par dosimètres thermoluminescents placés à la peau, pour 1231 patients. En scanographie l’indice de dose de scanographie pondéré et le produit dose × longueur ont été déterminés pour 667 patients à partir des paramètres de l’examen et des données de base du scanner. Pour chaque type d’examen les valeurs moyennes de chacune de ces grandeurs ainsi que celles du 75e percentile ont été calculées. Pour la grande majorité des examens et des centres ayant participé à l’étude, il apparaît que ces valeurs se situent en dessous des NRD proposés par la Commission européenne en 1996. Ces résultats, analysés en fonction des facteurs d’influence sur la dose et des limites méthodologiques de l’étude (volontariat des services participant), prouvent la faisabilité et le grand intérêt d’une campagne nationale de mesures de doses en radiologie, à plus grande échelle, qui permettrait d’établir des NRD spécifiques à la pratique française, de prévoir leur révision périodique et de définir les démarches d’optimisation appropriées.

International audience; ICRP publication 73 (Radiological Protection and Safety in Medicine) introduced the concept of "diagnostic reference levels" (DRL), for medical exposures specifically. Because dose limits should not be applied for diagnostic or therapeutic irradiation, the approach to radiological protection is slightly different from that in occupational or public exposures. Reference levels, that are neither optimum levels, nor dose limits, are a tool for optimisation. DRL are set for standard procedures, for groups of patients or standard phantom and not for special exposures and individual patients. They act as a test for identifying situations where patient doses are becoming unusually high and local review of procedures and equipment is required. Within the framework of implementation of Directive 97/43, the Health Directorate entrusted its radiation protection agency (past OPRI, at present time DGSNR and IRSN) to determine the national reference dose levels in diagnostic radiology in close cooperation with relevant scientific and professional societies. The pragmatic way, recommended by European Commission, to assess DRL values is to use the third quartile values observed in wide scale surveys of typical doses for common procedures. In the absence of recent and wide-ranging data for France, in a first step, European DRL have been adopted as starting points. To go further, a campaign of patient dose measurements has been launched by a steering committee (OPRI, SFR and SFPM) to allow the actual establishment of national reference values and to prepare their periodic review in a continuous process of optimization. © 2003 EDP Sciences.

Synthèse des travaux du groupe de travail «Que faire après l'incendie ?» de Foresterranée'99.

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Genetic screens in simple model organisms have identified many of the key components of the conserved signal transduction pathways that are oncogenic when misregulated. Here, we identify H37N21.1 as a gene that regulates vulval induction in let-60(n1046gf), a strain with a gain-of-function mutation in the Caenorhabditis elegans Ras orthologue, and show that somatic deletion of Nrbp1, the mouse orthologue of this gene, results in an intestinal progenitor cell phenotype that leads to profound changes in the proliferation and differentiation of all intestinal cell lineages. We show that Nrbp1 interacts with key components of the ubiquitination machinery and that loss of Nrbp1 in the intestine results in the accumulation of Sall4, a key mediator of stem cell fate, and of Tsc22d2. We also reveal that somatic loss of Nrbp1 results in tumourigenesis, with haematological and intestinal tumours predominating, and that nuclear receptor binding protein 1 (NRBP1) is downregulated in a range of human tumours, where low expression correlates with a poor prognosis. Thus NRBP1 is a conserved regulator of cell fate, that plays an important role in tumour suppression.

This deliverable corresponds to ENVISION task 5.3., aiming to develop a toolbox to provide protected areas managers and practitioners with tools for fostering stakeholder inclusion and active participation in conservation decision-making through a case study in a European PA: The Sierra de Guadarrama National Park (Spain).

This report corresponds to ENVISION milestone 5.3., aiming to develop an online workshop for co-producing tools to support decision-making for inclusive governance in protected areas. The workshop involved 12 decision-makers of the Sierra de Guadarrama National Park and experts on protected areas management. Based on a collective reflection, they analyzed the main challenges and opportunities of the current participatory setting within protected areas’ governance, particularly in the Sierra de Guadarrama National Park. They defined and prioritized management strategies supporting more socially inclusive conservation approaches and assessed 6 ENVISION research tools according to their applicability within the management cycle.

ThisdeliverablecorrespondstoENVISIONtask5.3.,aimingtodevelopatoolboxtoprovideprotectedareasmanagersandpractitionerswith tools for fostering stakeholder inclusion and active participation inconservation decision-makingthrough a case study in a European PA: The Sierra de Guadarrama National Park (Spain).

This report corresponds to ENVISION milestone 5.3., aiming to develop an online workshop for co-producing tools to support decision-making for inclusive governance in protected areas. The workshop involved12 decision-makers of the Sierra de Guadarrama National Park and experts on protected areas management. Based on a collective reflection, they analyzed the main challenges and opportunities of the current participatory setting within protected areas’ governance, particularly in the Sierra de Guadarrama National Park. They defined and prioritizedmanagement strategies supporting more socially inclusive conservation approaches and assessed 6 ENVISION research tools according to their applicability within the management cycle.

Kindergarteners and first graders were tested for discrimination of left-right orientation, letter production, and performance on reading readiness and reading tests. Left-right visual skills were found to be related to reading skills in both grades but to letter production only in kindergarten. These data are viewed in the context of a deficit in left-right coding. The data cautiously suggest that different subgroups of reading-disabled children may benefit from training programs that remediate different deficiencies; affirmation of this strategy awaits further study of treatment.

The ENVISION project develops, tests and validates a novel trans-disciplinary scenario approach for engaging multiple stakeholders and local communities in the protected area management and biodiversity decision-making at multiple scales (refer to our website for a more detailed overview of the approach). This deliverable presents findings from the first step within the inclusive conservation approach – identification of main visions for the fourstudy areas. Three study areasare located in Europe (Netherlands, Spain and Sweden) and one in North America(Alaska, USA).&nbsp