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Ingre Keita,1 Isabelle Aubin-Auger,2–4 Christophe Lalanne,4 Jean-Pierre Aubert,2–4 Olivier Chassany,2,4 Martin Duracinsky,4 Isabelle Mahé1,2,4 1Internal Medicine Department, Louis Mourier Hospital, APHP, Colombes, 2Paris 7 University, 3General Medicine Department, Université Paris 7, Paris, 4Recherche Clinique Ville-Hôpital, Méthodologies et Société (REMES) EA 7334, Université Paris Diderot, Sorbonne Paris Cité, Paris, France Introduction: Direct oral anticoagulants (DOACs) have shown non-inferiority and ease of use compared to vitamin K antagonists (VKA) in the treatment of venous thromboembolism (VTE). No study so far has been directed toward real-life experience of outpatients receiving anticoagulants for VTE in France.Methods: This is an observational descriptive real-life epidemiological study, using three validated questionnaires (Morisky Medication Adherence Scale-8, EQ-5D, and part 2 of the Perception of Anticoagulant Treatment Questionnaire), to assess adherence, quality of life, and satisfaction in 100 VTE outpatients receiving anticoagulation therapy by VKA (primary or switched from DOAC to VKA) or by DOAC (primary or switched from VKA to DOAC).Results: Patients were very much satisfied with their treatment in both DOAC and VKA groups. Despite advantages of DOACs, therapeutic adherence was only moderate. The best adherence scores were observed in the primary VKA switched to DOAC for at least 3 months (S-DOAC) subgroup. Quality of life was better in the DOAC group mainly because of the absence of the requirement for blood testing. Most of the complaints concerned the pain/discomfort dimension in the VKA group and anxiety/depression dimension in the DOAC group.Conclusion: Patients were satisfied with their anticoagulant treatment, especially when they were involved in choosing the anticoagulant, and the treatment suited them. Quality of life of patients in the DOAC group was better than in the VKA group, but adherence remains to be improved. This study highlights the importance of the physician–patient relationship, pretreatment initiation, and follow-up of any anticoagulation therapy throughout. Keywords: medication adherence, oral anticoagulant, deep venous thrombosis, pulmonary embolism, quality of life, treatment satisfaction

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Cet ouvrage collectif, qui est le résultat d’une collaboration entre l’International Institute for Asian Studies (IIAS), des Pays-Bas, et la National Science Council (NSC), de Taïwan, est le fruit d’une conférence qui s’est tenue en septembre2006 sur le thème des « mariages transfrontaliers en Asie et en Europe ». Les coordinateurs de l’ouvrage sont Wen-Shan Yang, chercheur à l’Institut of Sociology, Academia Sinica de Taïwan, et Melody Chia-Wen Lu, chercheur à l’International Institute for A...

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Article soumis à HYLO'06; We presente spatial logics and spatio-temporal logics in the paradigm of hybrid modal logics. These hybrid logics have some particularities: they have a topological semantic, the topological spaces associated with them are T0 -spaces and have a cellular structure and the nominals of the hybrid logics are sorted. From this particular case, we look at general semantic structures and the completeness of a sorted hybrid logic with pure axioms in a ”sorted sense”!

International audience; In gastric cancer, altered expression of MUC1, MUC2, MUC5AC, and MUC6 mucin genes has already been described. We show in this report by the means of in situ hybridization, reverse transcriptase-polymerase chain reaction, and transfection assays that MUC5B is also abnormally expressed in gastric carcinomatous tissues and cell lines. We thus undertook to elucidate the molecular mechanisms that regulate the transcription of MUC5B in gastric cancer cells. To this end, high expressing (KATO-III) and low expressing (AGS) gastric cancer cell lines were chosen to study human mucin gene MUC5B expression and promoter activity. Sequencing of the promoter region revealed a distal TATA box located 1 kilobase upstream of the proximal TATA box. Functional activity of the promoter was addressed by using deletion mutants covering 2044 nucleotides upstream of the MUC5B transcription start site. We identified a distal promoter 10 times more active than the proximal promoter in KATO-III cells. In AGS cells, both promoters, much less active, showed the same range of activity. Binding assays allowed us to show that the transcription factor ATF-1 binds to a cis-element present in the distal promoter. Sp1, which binds to both promoters specifically transactivates the proximal promoter. Treatment of transfected cells with PMA, cholera toxin A subunit, and calcium ionophore A23187 showed that only PMA led to a substantial activation of the distal promoter. MUC5B 5-flanking region having a high GC content, influence of methylation on the MUC5B expression was assessed. Our results indicate that repression of MUC5B expression visualized in AGS cells is due in part to the presence of numerous methy-lated cytosine residues throughout the 5-flanking region. Altogether these results demonstrate that MUC5B expression in gastric cancer cells is governed by a highly active distal promoter that is up-regulated by protein kinase C and that repression is under the influence of methylation. Mucins are high molecular weight O-glycoproteins synthesized by epithelial cells as large secreted or membrane-bound glycoproteins (1). So far, eight mucin genes have been well characterized (MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7) (1), and cDNAs have been proposed for MUC8, MUC9, MUC11, and MUC12 (1, 2). Numerous studies have now demonstrated that the expression of mucin genes is tissue-and cell-specific and that their expression is altered during the pathogenesis of several diseases, which suggests that human mucin gene expression is tightly regulated and that they may play important roles during cell differentiation and carcinogenesis (3-8). In normal stomach, MUC5AC is expressed at the surface/ foveolar epithelium and MUC6 in the mucous neck cells and in the antral glands (9-11). Other mucin genes expressed in normal gastric mucosae are MUC1 and to a lesser extent MUC2, MUC3, and MUC4. In gastric carcinomas, a decrease of MUC1, MUC5AC and MUC6 expression and an increase of MUC2, MUC3, and MUC4 expression has already been demonstrated (11-15). Human mucin gene MUC5B has been extensively studied in our laboratory. Studies of MUC5B genomic sequence (39.1 kb) 1 showed that it encodes a high molecular weight polypeptide (627,000) (16-20). MUC5B mucin gene is localized on chromosome 11 (band p15) and is clustered with three other mucin genes: MUC2, MUC6, and MUC5AC (21). In normal adult, MUC5B is essentially expressed in trachea, bronchi, submax-illary glands, pancreas, gallbladder, and endocervix (4, 22-24). In cancer, MUC5B has been shown to be highly expressed in colon carcinoma (5), in HT-29 treated with methotrexate (19, 20, 25), and LS174T (20, 24, 26) mucus-secreting colon cancer cell lines. We recently characterized the first 956 nucleotides located upstream of MUC5B transcription start site and studied the promoter functional activity in colon cancer cells (20). The region is characterized by the presence of a TATA box and numerous putative binding sites for ubiquitous (Sp1) and specific transcription factors (NF-B, c-Myc). The high expression of MUC5B was correlated with the mucus-secreting phenotype of the LS174T colon cancer cell line. Introns 1 and 37 of MUC5B have also been studied in our laboratory because they contain tandemly repeated GA-and GC-rich sequences that

International audience; The human mucin gene MUC4 encodes a large trans-membrane mucin that is thought to play important roles in tumor cell biology and that is overexpressed in human pancreatic carcinomas. In this report, we describe the structure and functional activity of the 5-flanking region, including 1.0 kilobase of the promoter. The long 5-untranslated region (2.7 kilobases) is characterized by a high content of GC in its 3-end. The first TATA box was located at ؊2672/؊2668. Multiple transcription start sites and a high density of putative binding sites for Sp1 (GC and CACCC boxes), AP-1/-2/-4, cAMP-responsive element-binding protein, GATA, GR, and STAT transcription factors were found within the 5-flanking region. Transcriptional activity of the promoter was assessed using pGL3-luciferase deletion mutants in two MUC4-expressing (CAPAN-1 and CAPAN-2) and one nonexpressing (PANC-1) pancreatic cancer cell line. Two highly active fragments (؊219/؊1 and ؊2781/؊2572) that drive MUC4 transcription in CAPAN-1 and CAPA-N-2 cells were identified. Gel retardation assays indicated that Sp1 and Sp3 bind to cognate cis-elements found in the 5-flanking region and that Sp1 transactivates, whereas Sp3 inhibits the GC-rich region (؊464/؊1) in CAPAN-2 cells. Activation of protein kinase C with phor-bol ester and treatment of cells with epidermal growth factor and transforming growth factor-␣ resulted in up-regulation of the promoter. Tumor necrosis factor-␣ and interferon (IFN)-␥ inflammatory cytokines had no or mild effect on MUC4 transcriptional activity when used alone. However, a very strong synergistic effect (10-12-fold activation) between IFN-␥ and tumor necrosis factor -␣ or IFN-␥ and transforming growth factor-␣ was obtained in CAPAN-2 cells. Altogether these results demonstrate that the 5-flanking region of MUC4 contains epithelial cell-specific, positive, and negative regulatory cis-elements, that Sp1/Sp3 are important regulators of MUC4 basal expression, and that its regulation in pancreatic cancer cells involves complex interplay between several signaling pathways.

International audience; Our previous works in image analysis dealing with image representations by means of adjacency or boundary graphs, led us to the need for a coherent representation model. In fact, classical approaches to this problem seem to be unsuffcient or even uncoherent; for example they are unclear with the well-known connectivity paradox or with the border description of regions. Diierent works like those of Kovalevsky, Herman and Malandain pointed out the advantages of cellular complex based topologies [Kovalevsky89, Herman90, Malandain93]. But no one of them suggested a formalism that can be applied to any type of image. In this work we propose a topological representation for any type of image, colour or grey-level of whatever dimension. It is based on convex complexes, and looks closely at the elements realizing the connectivity within complexes and later within regions. Futhermore it remains coherent with pixel and voxel only based representations. An important feature is still maintaining a direct correspondance with the classical IR n topology. Finally, we suggest a characterization of regions, their borders and boundaries which is useful as a basic tool for segmentation.