Construire dans les espaces agricoles et naturels

L’étalement urbain fait l’objet d’une « fabrique réglementaire » dans les territoires ruraux et périurbains. En effet, si le mitage est encore largement à l’œuvre dans de nombreuses communes en France, c’est en grande partie parce qu’il est organisé comme tel par la réglementation que les élus choisissent d’adopter. La recherche présentée ici est le fruit de l’analyse d’un ensemble de 88 documents d’urbanisme élaborés dans un panel de communes de la région Provence-Alpes-Côte d’Azur entre 2000 et 2010. Grâce à l’étude des outils de planification, nous faisons l’hypothèse qu’il est possible d’identifier les pratiques juridiques par lesquelles s’exerce la pression sur les espaces agricoles et naturels.Urban sprawl is a “regulatory construction” in many rural and peri-urban areas. If urban scattering remains prevalent in many French municipalities, it is in large part because it is orchestrated through the regulatory measures that elected officials choose to adopt. The research presented here is based on the analysis of a collection of eighty-eight urban planning documents drafted by a panel of municipalities in the Provence-Alpes-Côte d’Azur region between 2000 and 2010. Based on an examination of the planning tools in place, we argue that it is possible to identify the legal practices through which pressure is exerted on agricultural and natural areas

Counter-Rotating Open Rotor (CROR) : flow physics and simulation

La propulsion par hélices contrarotatives est à l'étude dans le contexte des recherches menées sur la réduction de la consommation et du bruit aéronautiques. Dans un Open Rotor, on cherche notamment à maîtriser la nappe tourbillonnaire issue de l'hélice amont car elle vient impacter l'hélice aval, contribuant majoritairement au bruit rayonné. Des simulations avancées de ce problème seront présentées et discutées sur le plan de la mécanique des fluides et de l'acoustique

GERMLINE GAIN-OF-FUNCTION MUTATIONS of ALK DISRUPT CENTRAL NERVOUS SYSTEM DEVELOPMENT

International audienceNeuroblastoma (NB) is a frequent embryonal tumour of sympathetic ganglia and adrenals with extremely variable outcome. Recently, somatic amplification and gain-of-function mutations of the anaplastic lymphoma receptor tyrosine kinase (ALK, MIM 105590) gene, either somatic or germline, were identified in a significant proportion of NB cases. Here we report a novel syndromic presentation associating congenital NB with severe encephalopathy and abnormal shape of the brainstem on brain MRI in two unrelated sporadic cases harbouring de novo, germline, heterozygous ALK gene mutations. Both mutations are gain-of-function mutations that have been reported in NB and NB cell lines. These observations further illustrate the role of oncogenes in both tumour predisposition and normal development, and shed light on the pleiotropic and activity-dependent role of ALK in humans. More generally, missing germline mutations relative to the spectrum of somatic mutations reported for a given oncogene may be a reflection of severe effects during embryonic development, and may prompt mutation screening in patients with extreme phenotypes

Incidence and prognostic value of tumour cells detected by RT–PCR in peripheral blood stem cell collections from patients with Ewing tumour

To retrospectively evaluate the incidence of tumour cell contamination of peripheral blood stem cell (PBSC) collections and to correlate these data with the clinical outcome after high-dose chemotherapy (HDCT) with stem cell rescue in patients with a high-risk Ewing tumour. Peripheral blood stem cell collections obtained from 171 patients were analysed. Tumour contamination was assessed by reverse transcriptase–polymerase chain reaction (RT–PCR). The files of 88 patients who underwent HDCT followed by PBSC reinfusion were reviewed in detail, and their outcome compared to the PBSC RT–PCR results. Seven of 88 PBSC collections (8%) contained tumour cells as detected by RT–PCR. Peripheral blood stem cells were collected after a median of five cycles of chemotherapy. No clinical factor predictive of tumour cell contamination of PBSC harvest could be identified. Event-free survival (EFS) and overall survival (OS) of the whole study population were 45.3 % and 51.8 % at 3 years from the date of the graft, respectively. Forty-five patients relapsed with a median time of 15 months after graft, only four of whom had tumour cell contamination of the PBSC harvest. Tumour cell contamination of PBSC collection is rare and does not seem to be associated with a significantly poorer EFS or OS in this high-risk population

ALK germline mutations in patients with neuroblastoma: a rare and weakly penetrant syndrome

Neuroblastic tumours may occur in a predisposition context. Two main genes are involved: PHOX2B, observed in familial cases and frequently associated with other neurocristopathies (Ondine's and Hirschsprung's disease); and ALK, mostly in familial tumours. We have assessed the frequency of mutations of these two genes in patients with a presumable higher risk of predisposition. We sequenced both genes in 26 perinatal cases (prebirth and o1 month of age, among which 10 were multifocal), 16 multifocal postnatal (41 month) cases, 3 pairs of affected relatives and 8 patients with multiple malignancies. The whole coding sequences of the two genes were analysed in tumour and/or constitutional DNAs. We found three ALK germline mutations, all in a context of multifocal tumours. Two mutations (T1151R and R1192P) were inherited and shared by several unaffected patients, thus illustrating an incomplete penetrance. Younger age at tumour onset did not seem to offer a relevant selection criterion for ALK analyses. Conversely, multifocal tumours might be the most to benefit from the genetic screening. Finally, no PHOX2B germline mutation was found in this series. In conclusion, ALK deleterious mutations are rare events in patients with a high probability of predisposition. Other predisposing genes remain to be discovered

Low-frequency variation near common germline susceptibility loci are associated with risk of Ewing sarcoma

Background: Ewing sarcoma (EwS) is a rare, aggressive solid tumor of childhood, adolescence and young adulthood associated with pathognomonic EWSR1-ETS fusion oncoproteins altering transcriptional regulation. Genome-wide association studies (GWAS) have identified 6 common germline susceptibility loci but have not investigated low-frequency inherited variants with minor allele frequencies below 5% due to limited genotyped cases of this rare tumor. Methods We investigated the contribution of rare and low-frequency variation to EwS susceptibility in the largest EwS genome-wide association study to date (733 EwS cases and 1,346 unaffected controls of European ancestry). Results We identified two low-frequency variants, rs112837127 and rs2296730, on chromosome 20 that were associated with EwS risk (OR = 0.186 and 2.038, respectively;P-value < 5x10(-8)) and located near previously reported common susceptibility loci. After adjusting for the most associated common variant at the locus, only rs112837127 remained a statistically significant independent signal (OR = 0.200, P-value = 5.84x10(-8)). Conclusions: These findings suggest rare variation residing on common haplotypes are important contributors to EwS risk. Impact Motivate future targeted sequencing studies for a comprehensive evaluation of low-frequency and rare variation around common EwS susceptibility loci

Methylation-associated PHOX2B gene silencing is a rare event in human neuroblastoma.

International audienceNeuroblastoma (NB), an embryonic tumour originating from neural crest cells, is one of the most common solid tumours in childhood. Although NB is characterised by numerous recurrent, large-scale chromosome rearrangements, the genes targeted by these imbalances have remained elusive. We recently identified the paired-like homeobox 2B (PHOX2B, MIM 603851) gene as disease-causing in dysautonomic disorders including Congenital Central Hypoventilation Syndrome (CCHS), Hirschsprung disease (HSCR) and NB in various combinations. Most patients with NB due to a germline heterozygous PHOX2B gene mutation are familial and/or syndromic. PHOX2B, at chromosome 4p12, does not lie in a commonly rearranged locus in NB. To evaluate the role of PHOX2B in sporadic, isolated NB, we analysed 13 NB cell lines and 45 tumours for expression, mutations of coding and promoter sequences, loss of heterozygosity (LOH), or aberrant hypermethylation of PHOX2B (13 cell lines and 18 tumours). We didn't identify any mutation but LOH in about 10% of the cases and aberrant CpG dinucleotide methylation of the 500 bp PHOX2B promoter region in 4/31 tumours and cell lines (12.9%). Altogether, both germinal and somatic anomalies at the PHOX2B locus are found in NB

Analyse des déterminants des choix de préservation des espaces agricoles et naturels dans les politiques locales d'urbanisme. Apports d'une approche multi-méthodes

Dans un contexte de forte croissance spatiale des villes et d’enjeu social émergeant sur la protection des espaces agricoles périurbains, nous nous intéressons aux éléments qui déterminent les choix publics locaux de gestion du développement urbain, en termes de consommation d’espace et de choix de densité. Nous partons de cadres d’analyse économiques issus de l’économie urbaine et de l’économie du choix social (Welfare Economics) qui renseignent les processus de décision inhérents à la planification urbaine. Puis, nous analysons comment une approche multi-méthodes (analyse de discours et statistiques textuelles couplées à de l’économétrie utilisant une importante base de données communales) peut aider à l’élaboration d’un cadre théorique adapté à un contexte régulé et décentralisé, tel que le contexte français. Nous appliquons cette approche aux documents d’urbanisme communaux de la région PACA. Il en résulte un cadre théorique enrichi qui montre l’importance de déterminants peu évoqués dans la littérature et une évaluation de leurs effets sur la décision publique. Sont notamment mis en évidence les rôles particuliers des caractéristiques de l’activité agricole, de la légitimité des élus, des réglementations supracommunales et de certaines caractéristiques politiques communales ainsi que des relations entre communes. Nous mettons également en lumière la complémentarité entre les méthodes qualitatives et quantitatives employées – les analyses de discours et textuelles et les formalisations économétriques – notamment dans une perspective de généralisation à des contextes institutionnels et géographiques hétérogènes. Des pistes de recherches futures et quelques recommandations à destination des décideurs publics sont finalement proposées pour approfondissement

Land supply effects and drivers of town planning choices. Some empirical observations in a metropolitan modeling perspective

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