Towards improved management of coastal submersion crises - CRISMA-WAVE solution as an example of CRISMA Framework application

Coping with various types of natural or man-made hazards the FP7 SECURITY CRISMA project (http://www.crisrnaprojecteu) has designed and developed an experimental software framework allowing building crisis management simulation application. One of the five pilot applications of CRISMA dealing with preparedness to the coastal submersions was developed and implemented using return of experience of the reference Xynthia storm surge event in the Charente Maritime County in France. The paper addresses the generic CRISMA Framework applicability to simulate mitigation effects of a coastal submersion through CRISMA-Wave implementation of a full modelling cycle. The CRISMA-Wave paradigm reflects user needs for simulation of "what-if" scenarios for short and long-term actions and the paper describes in particular its different components : *Simulation of submersion effects at a range of temporal and spatial scales, *Preparedness Planning, *Assessment of impacts depending on scenarios based on options for managing the inundation risks, *Cascading effects and *Evaluation of damages with comparison of submersion defence scenarios based on cost-benefit and multi criteria analysis

Nasal cavity lobular capillary hemangioma due to insect sting

SummaryIntroductionLobular capillary hemangioma is a frequent benign vascular inflammatory lesion of the skin tissue. It rarely reaches the mucous membrane, and the nasal fossa involvement is exceptional.Case reportA 68-year-old woman presented with an ulcerous hemorrhagic mass blocking the left nasal fossa, which had appeared a few weeks after a wasp sting in the nose. The insect was evacuated only three weeks after the sting. The clinical and radiological data suggested malignancy. Biopsy under local anesthesia proved non-contributory and was complicated by 1 week's hospitalization for severe nosebleed. Surgical excision under video-endoscopy confirmed diagnosis. At 31 months’ follow-up, the patient was free of recurrence.Discussion/conclusionThe pathogeny of lobular capillary hemangioma is uncertain. No previous cases affecting the mucous membrane after insect sting have been reported. Except in the typical contexts of long-term packing or pregnancy, diagnosis can be difficult and misleading. It can mimic a malignant pathology. Its rich vascularization requires caution during biopsy, and the risk of recurrence requires excision to be complete

Ge2Sb2Te5 layer used as solid electrolyte in conductive-bridge memory devices fabricated on flexible substrate

7 pagesInternational audienceThis paper shows that the well-know chalcogenide Ge2Sb2Te5 (GST) in its amorphous state may be advantageously used as solid electrolyte material to fabricate Conductive-Bridge Random Access Memory (CBRAM) devices. GST layer was sputtered on preliminary inkjet-printed silver lines acting as active electrode on either silicon or plastic substrates. Whatever the substrate, the resistance switching is unambiguously attested at a nanoscale by means of conductive-atomic force microscopy (C-AFM) using a Pt-Ir coated tip on the GST surface acting as a passive electrode. The resistance change is correlated to the appearance or disappearance of concomitant hillocks and current spots at the surface of the GST layer. This feature is attributed to the formation/dissolution of a silver-rich protrusion beneath the AFM tip during set/reset operation. Beside, this paper constitutes a step toward the elaboration of crossbar memory arrays on flexible substrates since CBRAM operations were demonstrated on W/GST/Ag crossbar memory cells obtained from an heterogeneous fabrication process combining physical deposition and inkjet-printing

Ontology-guided data preparation for discovering genotype-phenotype relationships

International audienceComplexity of post-genomic data and multiplicity of mining strategies are two limits to Knowledge Discovery in Databases (KDD) in life sciences. Because they provide a semantic frame to data and because they benefit from the progress of semantic web technologies, bio-ontologies should be considered for playing a key role in the KDD process. In the frame of a case study relative to the search of genotype-phenotype relationships, we demonstrate the capability of bio-ontologies to guide data selection during the preparation step of the KDD process. We propose three scenarios to illustrate how domain knowledge can be taken into account in order to select or aggregate data to mine, and consequently how it can facilitate result interpretation at the end of the process

Nitric oxide synthases in infants and children with pulmonary hypertension and congenital heart disease

Nitric oxide is an important regulator of vascular tone in the pulmonary circulation. Surgical correction of congenital heart disease limits pulmonary hypertension to a brief period. The study has measured expression of endothelial (eNOS), inducible (iNOS), and neuronal nitric oxide synthase (nNOS) in the lungs from biopsies of infants with pulmonary hypertension secondary to cardiac abnormalities (n = 26), compared to a control group who did not have pulmonary or cardiac disease (n = 8). eNOS, iNOS and nNOS were identified by immunohistochemistry and quantified in specific cell types. Significant increases of eNOS and iNOS staining were found in pulmonary vascular endothelial cells of patients with congenital heart disease compared to control infants. These changes were confined to endothelial cells and not present in other cell types. Patients who strongly expressed eNOS also had strong expression of iNOS. Upregulation of eNOS and iNOS occurs at an early stage of pulmonary hypertension, and may be a compensatory mechanism limiting the rise in pulmonary artery pressure

Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma

Frequent allelic imbalances (AIs) including loss of heterozygosity and microsatellite instability on a specific chromosomal region have been identified in a variety of human malignancies. The objective of our study was to assess the possibility of prognostication and monitoring of oral squamous cell carcinoma (SCC) by microsatellite blood assay. DNA from normal and tumorous tissues and serum DNA obtained at three time points (preoperatively, postoperatively, and 4 weeks postoperatively) from 64 patients with oral SCC was examined at nine microsatellite loci. In all, 38 (59%) DNA samples from tumorous tissues and 52% from serum showed AIs in at least one locus. Patterns of AIs in the serum DNA were matched to those detected in tumour DNA. Of them, AIs were frequently detected preoperatively (44%, 28 of 64), and postoperatively (20%, 13 of 64). Moreover, among 12 cases with AIs during the postoperative period, six had no evidence of an AI 4 weeks postoperatively, and they had no recurrence and were disease free. In contrast, six patients with AI-positive DNA 4 weeks postoperatively have died with distant metastasis within 44 weeks. Thus, our results suggest that the assessment of microsatellite status in the serum DNA could be a useful predictive tool to monitor disease prognosis

Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas

Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity

The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers

Background: The TP53 pathway, in which TP53 and its negative regulator MDM2 are the central elements, has an important role in carcinogenesis, particularly in BRCA1- and BRCA2-mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of MDM2 (309T>G, rs2279744) and a coding SNP of TP53 (Arg72Pro, rs1042522) have been shown to be of functional significance. Methods: To investigate whether these SNPs modify breast cancer risk for BRCA1 and BRCA2 mutation carriers, we pooled genotype data on the TP53 Arg72Pro SNP in 7011 mutation carriers and on the MDM2 309T>G SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework. Results: No association was found between these SNPs and breast cancer risk for BRCA1 (TP53: per-allele hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.93–1.10, Ptrend=0.77; MDM2: HR=0.96, 95%CI: 0.84–1.09, Ptrend=0.54) or for BRCA2 mutation carriers (TP53: HR=0.99, 95%CI: 0.87–1.12, Ptrend=0.83; MDM2: HR=0.98, 95%CI: 0.80–1.21, Ptrend=0.88). We also evaluated the potential combined effects of both SNPs on breast cancer risk, however, none of their combined genotypes showed any evidence of association. Conclusion: There was no evidence that TP53 Arg72Pro or MDM2 309T>G, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers. O M Sinilnikova1,2, A C Antoniou3, J Simard4, S Healey5, M Léoné1, D Sinnett6,7, A B Spurdle5, J Beesley5, X Chen5, kConFab8, M H Greene9, J T Loud9, F Lejbkowicz10, G Rennert10, S Dishon10, I L Andrulis11,12, OCGN11, S M Domchek13, K L Nathanson13, S Manoukian14, P Radice15,16, I Konstantopoulou17, I Blanco18, A L Laborde19, M Durán20, A Osorio21, J Benitez21, U Hamann22, F B L Hogervorst23, T A M van Os24, H J P Gille25, HEBON23, S Peock3, M Cook3, C Luccarini26, D G Evans27, F Lalloo27, R Eeles28, G Pichert29, R Davidson30, T Cole31, J Cook32, J Paterson33, C Brewer34, EMBRACE3, D J Hughes35, I Coupier36,37, S Giraud1, F Coulet38, C Colas38, F Soubrier38, E Rouleau39, I Bièche39, R Lidereau39, L Demange40, C Nogues40, H T Lynch41, GEMO1,2,42, R K Schmutzler43, B Versmold43, C Engel44, A Meindl45, N Arnold46, C Sutter47, H Deissler48, D Schaefer49, U G Froster50, GC-HBOC43,44,45,46,47,48,49,50, K Aittomäki51, H Nevanlinna52, L McGuffog3, D F Easton3, G Chenevix-Trench5 and D Stoppa-Lyonnet42 on behalf of the Consortium of Investigators of Modifiers of BRCA1/

An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia

The transcription factor Hypoxia-inducible factor 1 (HIF-1) plays a central role in the transcriptional response to oxygen flux. To gain insight into the molecular pathways regulated by HIF-1, it is essential to identify the downstream-target genes. We report here a strategy to identify HIF-1-target genes based on an integrative genomic approach combining computational strategies and experimental validation. To identify HIF-1-target genes microarrays data sets were used to rank genes based on their differential response to hypoxia. The proximal promoters of these genes were then analyzed for the presence of conserved HIF-1-binding sites. Genes were scored and ranked based on their response to hypoxia and their HIF-binding site score. Using this strategy we recovered 41% of the previously confirmed HIF-1-target genes that responded to hypoxia in the microarrays and provide a catalogue of predicted HIF-1 targets. We present experimental validation for ANKRD37 as a novel HIF-1-target gene. Together these analyses demonstrate the potential to recover novel HIF-1-target genes and the discovery of mammalian-regulatory elements operative in the context of microarray data sets