Shorter time to diagnosis and improved stage at presentation in Swiss patients with retinoblastoma treated from 1963 to 2004.

OBJECTIVES: Retinoblastoma is the most frequent intraocular malignancy in children. Early diagnosis is essential for globe salvage and patient survival. The aim of our study was to determine how time to diagnosis of retinoblastoma has evolved over a 40-year period in Switzerland. METHOD AND PATIENTS: A retrospective study of 139 Swiss patients with retinoblastoma was performed comparing 3 periods: (1) 1963-1983; (2) 1984-1993; and (3) 1994-2004. Factors taken into account were gender, laterality of retinoblastoma, age at first symptoms, type and first observer of symptoms, time to diagnosis, age at diagnosis, disease stage, and family history. RESULTS: Thirty-seven patients (26.6%) were treated in period 1, 44 (31.7%) in period 2, and 58 (41.7%) in period 3. Overall, the diagnostic interval decreased in a significant way from 6.97 months in period 1 to 3.58 in period 2 and to 2.25 in period 3. When looking separately at unilateral and bilateral disease, the decrease of the diagnostic interval remained statistically significant in unilateral retinoblastoma; there was also a significant reduction in the number of patients with advanced group E disease (Murphree classification) (61.5% in period 1, 46.7% in period 2, 22.2% in period 3). In bilateral disease, the same observations were made to a lesser extent. However, there were no cases with group E disease in 10 patients with positive family history. Leukocoria (48.2%) and strabismus (20.1%) were the 2 most frequent symptoms throughout the 3 periods. The only factors that statistically influenced the chances of having a diagnosis of group E disease were the diagnostic interval and period of diagnosis. CONCLUSIONS: Progress has been made in the diagnosis of retinoblastoma in Switzerland, notably in unilateral disease. Improvement to a lesser extent has also been observed in bilateral cases but without statistical significance. Greater effort is needed to teach physicians-in-training to recognize the importance of ocular symptoms and refer patients earlier.

Tissue biomarker development in a multicentre trial context: a feasibility study on the PETACC3 stage II and III colon cancer adjuvant treatment trial.

PURPOSE: We evaluated the feasibility of biomarker development in the context of multicenter clinical trials. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded (FFPE) tissue samples were collected from a prospective adjuvant colon cancer trial (PETACC3). DNA was isolated from tumor as well as normal tissue and used for analysis of microsatellite instability, KRAS and BRAF genotyping, UGT1A1 genotyping, and loss of heterozygosity of 18 q loci. Immunohistochemistry was used to test expression of TERT, SMAD4, p53, and TYMS. Messenger RNA was retrieved and tested for use in expression profiling experiments. RESULTS: Of the 3,278 patients entered in the study, FFPE blocks were obtained from 1,564 patients coming from 368 different centers in 31 countries. In over 95% of the samples, genomic DNA tests yielded a reliable result. Of the immmunohistochemical tests, p53 and SMAD4 staining did best with reliable results in over 85% of the cases. TERT was the most problematic test with 46% of failures, mostly due to insufficient tissue processing quality. Good quality mRNA was obtained, usable in expression profiling experiments. CONCLUSIONS: Prospective clinical trials can be used as framework for biomarker development using routinely processed FFPE tissues. Our results support the notion that as a rule, translational studies based on FFPE should be included in prospective clinical trials.

La surveillance active dans la prise en charge du cancer de la prostate précoce. [Active surveillance for early-stage prostate cancer]

Diagnostic and treatment management of prostate cancer at its initial stage continues to raise important debates within the involved medical community. To establish a protocol for active surveillance, a validated option in specific conditions of localised prostate cancer management for eight years, is a unique opportunity to gather different specialists in this field. This paper presents this concept.

A non-interventional phase IV Belgian survey to assess the antiviral effectiveness of pegylated interferon-alpha-2b and ribavirin treatment according to the stage of liver fibrosis in previously untreated patients with genotype 1/4/5/6 chronic hepatitis C (PRACTICE).

BACKGROUND AND STUDY AIMS: This was an observational, non-interventional, multicenter, phase IV study, in patients with genotype 1/4/5/6 chronic hepatitis C (CHC). The primary objectives were to evaluate SVR in patients with no or minimal fibrosis (METAVIR F0-F1) versus well established fibrosis (F2-F4), and to estimate response on Weeks 12, 24 and 48 on treatment in previously untreated patients with genotypes 1/4/5/6 CHC. PATIENTS AND METHODS: 538 patients treated with pegylated interferon alfa 2b 1.5 mcg/kg in combination with ribavirin 800-1200 mg/day were enrolled in 55 sites in Belgium and Luxembourg, 505 being considered for the analysis. 40% of the patients were female and 60% male, the average age was 47.5 years, 10.5% were 65 or older. RESULTS: SVR was observed in 35% of the patients, EVR in 68%, of which pEVR in 33% and cEVR in 35%. SVR was observed in 43% of the low fibrosis group (F0, F1) and 30% of the high fibrosis group (F2, F3, F4) (p = 0.005). SVR rates were 34% for genotype 1, 37% for genotype 4, and 47% for genotype 5 (NS). Multivariate analysis showed that EVR and baseline METAVIR score are independent prognostic factors for SVR. CONCLUSIONS: This trial confirms that fibrosis stage and early viral response are the most important key-factors to predict sustained response, suggesting that the earlier patients are treated, the better the outcome. Non-invasive techniques enable us to closely monitor progression of fibrosis, allowing a better selection of patients for antiviral treatment in the DAA-era.

Stage De Français Langue Étrangére Projet FLE Comme Outil D´ Integration

Université De Bretagne Occidentale

Memoire de Stage L’analyse des Dossiers de Crédit Professionnels

Université Jean Monnet Saint Etienne

Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial.

PURPOSE: A multicenter, phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non-small-cell lung cancer (NSCLC) and examined prognostic factors for patients not benefiting from surgery. PATIENTS AND METHODS: Ninety patients with previously untreated, potentially operable stage IIIA (mediastinoscopically pN2) NSCLC received three cycles of docetaxel 85 mg/m2 day 1 plus cisplatin 40 mg/m2 days 1 and 2, with subsequent surgical resection. RESULTS: Administered dose-intensities were docetaxel 85 mg/m2/3 weeks (range, 53 to 96) and cisplatin 95 mg/m2/3 weeks (range, 0 to 104). The 265 cycles were well tolerated, and the overall response rate was 66% (95% confidence interval [CI], 55% to 75%). Seventy-five patients underwent tumor resection with positive resection margin and involvement of the uppermost mediastinal lymph node in 16% and 35% of patients, respectively (perioperative mortality, 3%; morbidity, 17%). Pathologic complete response occurred in 19% of patients with tumor resection. In patients with tumor resection, downstaging to N0-1 at surgery was prognostic and significantly prolonged event-free survival (EFS) and overall survival (OS; P =.0001). At median follow-up of 32 months, the median EFS and OS were 14.8 months (range, 2.4 to 53.4) and 33 months (range, 2.4 to 53.4), respectively. Local relapse occurred in 27% of patients with tumor resection, with distant metastases in 37%. Multivariate analyses identified mediastinal clearance (hazard ratio, 0.22; P =.0003) and complete resection (hazard ratio, 0.26; P =.0006) as strongly prognostic for increased survival. CONCLUSION: Neoadjuvant docetaxel-cisplatin is effective and tolerable in stage IIIA pN2 NSCLC. Resection is recommended only for patients with mediastinal downstaging after chemotherapy.

Seasonality and Temperature:Turtles in Hot Water?

Variation in temperature affects the biology of sea turtles at a range of scales. To elucidate the drivers of seasonality of nesting and duration of season, databases across four species of sea turtles (Caretta caretta n=37, Chelonia mydas n=64, Dermochelys coriacea n=44 and Eretmochelys imbricata n=36) at a global scale were created. By using remotely sensed sea surface temperature data, thermal profiles across the nesting season were generated. Duration of nesting season was correlated with latitude in all species but was more tightly coupled with temperature; seasons were significantly longer with increased mean SST. In general, nesting seasonality occurred at warmest time of the year. SST for the month before, month after and the month of peak nesting significantly affected the month of peak nesting.

A conservação de tartarugas marinhas baseada na comunidade: contribuição para a gestão dos recursos costeiros das ilhas de Santo Antão, São Vicente e São Nicolau, Cabo Verde

Embora cada vez mais assumida como um imperativo institucional pelo mundo todo, em Cabo Verde, as experiencias de participação das comunidades locais na gestão da biodiversidade e recursos naturais são até hoje, muito fracas. No entanto, embora legalmente protegidas, ano após ano as populações de tartarugas marinhas vem-se cada vez mais reduzidas, com os respectivos habitats degradados. Num contexto em que importantes recursos da pesca artesanal se encontram em franca diminuição, ou já não são comercialmente viáveis,as comunidades piscatórias enfrentam cada dia condições adversas face a globalização do desenvolvimento económico. Consequentemente, a introdução de sistemas de gestão de recursos costeiros, mais inclusivos, eficazes e eficientes e que reforcem a participação das comunidades, constituem um imperativo. Dessa forma, a conservação das tartarugas marinhas na região de Barlavento, mais propriamente nas ilhas à Noroeste, foi concebida para promover o envolvimento de comunidades costeiras na preservação dessas espécies e de outros recursos marinhos ameaçados, tudo isto em prol do desenvolvimento rural sustentável e redução da pobreza. Os resultados indicam que a abordagem é eficaz, traduzindo-se em 1) Redução efectiva das capturas e consumo local de tartarugas marinhas; 2) Identificação local das espécies, sua distribuição e, identificação das ameaças que enfrentam. Assim, a população de fêmeas da Caretta caretta em São Nicolau, foi identificada como uma das mais abundantes do arquipélago. 3) Trabalhos relevantes no reforço da consciência ambiental da população no geral. As comunidades piscatórias têm livremente apoiado não só na redução da captura de tartarugas mas também tem estado envolvidas em acções de vigilância e fiscalização de praias, prevenindo mesmo a extracção de areia em zonas de postura. Internamente, têm promovido luta contra práticas irresponsáveis de pesca, tais como o uso de dinamite na pesca de pequenos pelágicos. 4) Adopção de instrumentos integradores promovendo a participação interinstitucional e multidisciplinar e, particularmente, a mobilização de recursos, criando espaços para o envolvimento directo das comunidades na concepção e planificação de acções e planos locais de conservação. 5) Investigação participativa, apropriadamente articulada com a comunicação social e fiscalização como responsabilidade compartilhada, enquanto escola eficaz de aprendizagem interactiva de formas alternativas de gestão e utilização sustentável de recursos naturais costeiros. Os desafios resumem na 1) necessidade de um contexto político e legal que oriente e regulamente a implementação de iniciativas de conservação de tartarugas marinhas baseadas na comunidade, em regimes de gestão concertada (co-gestão); 2) no engajamento e apropriação efectiva, assim como a devida articulação institucional e, 3) sustentabilidade económica das acções.

Developmental stage-specific expression of cyclic adenosine 3',5'-monophosphate response element-binding protein CREB during spermatogenesis involves alternative exon splicing.

Spermatogenesis is a temporally regulated developmental process by which the gonadotropin-responsive somatic Sertoli and Leydig cells act interdependently to direct the maturation of the germinal cells. The metabolism of Sertoli and Leydig cells is regulated by the pituitary gonadotropins FSH and LH, which, in turn, activate adenylate cyclase. Because the cAMP-second messenger pathway is activated by FSH and LH, we postulated that the cAMP-responsive element-binding protein (CREB) plays a physiological role in Sertoli and Leydig cells, respectively. Immunocytochemical analyses of rat testicular sections show a remarkably high expression of CREB in the haploid round spermatids and, to some extent, in pachytene spermatocytes and Sertoli cells. Although most of the CREB antigen is detected in the nuclei, some CREB antigen is also present in the cytoplasm. Remarkably, the cytoplasmic CREB results from the translation of a unique alternatively spliced transcript of the CREB gene that incorporates an exon containing multiple stop codons inserted immediately up-stream of the exons encoding the DNA-binding domain of CREB. Thus, the RNA containing the alternatively spliced exon encodes a truncated transcriptional transactivator protein lacking both the DNA-binding domain and nuclear translocation signal of CREB. Most of the CREB transcripts detected in the germinal cells contain the alternatively spliced exon, suggesting a function of the exon to modulate the synthesis of CREB. In the Sertoli cells we observed a striking cyclical (12-day periodicity) increase in the levels of CREB mRNA that coincides with the splicing out of the restrictive exon containing the stop codons. Because earlier studies established that FSH-stimulated cAMP levels in Sertoli cells are also cyclical, and the CREB gene promoter contains cAMP-responsive enhancers, we suggest that the alternative RNA splicing controls a positive autoregulation of CREB gene expression mediated by cAMP.

RAPPORT NATIONAL SUR L'ETAT DE LA BIODIVERSITE

Informations de base sur la République du Cap Vert L'archipel du Cap Vert est constitué par dix îles et huit îlots situés à environ 500 km de la côte occidentale africaine. Sa superficie est de 4033 km2. Les îles sont d'origine volcanique et sont implantées sur la zone sud-ouest de la plate-forme sénégalaise sur la croûte océanique d'âge comprise entre 140 et 120 millions d'années. Le relief est très accidenté dans les îles les plus jeunes (Fogo, Santiago, Santo Antão et S. Nicolau), mais relativement plat dans les îles plus anciennes (Maio, Boavista e Sal). Les sols sont peu évolués, avec des horizons pédologiques peu différenciés. Par sa situation géographique, dans une zone d'aridité météorologique, le climat du Cap Vert est sahélien du type tropical sec, soumis aux vents alizés du nordest, avec des températures modérées (environ 24ºC) et une faible amplitude thermique dû à l'environnement atlantique. Les précipitations sont généralement faibles sur l'ensemble du pays, ne dépassant pas les 300 mm de moyenne annuelle pour les 65% du territoire situé à moins de 400 m d'altitude. Les zones sous l'influence des alizés étant encore plus sèches (150 mm de moyenne annuelle). Sur les versants situés à plus de 500 m d'altitude faisant face aux alizés, on peut atteindre ou dépasser les 700 mm. Les pluies sont irrégulières et généralement mal distribuées dans le temps et dans l'espace. Le peuplement et son influence sur la biodiversité Après leur colonisation par les humains au cours du XVème siècle, les îles du Cap Vert ont été soumises à une forte exploitation des ressources biologiques. Des facteurs anthropiques avec conséquences directe et indirecte sur la végétation, tels que l'agriculture pluviale, dans la plupart des cas pratiquée sur les fortes pentes des versants, l'utilisation du bois de feu, le surpâturage et l'introduction des espèces exotiques ont contribué à la dégradation graduelle de la végétation et des habitats de l'archipel. Le rôle de ces facteurs a été encore accentué par l'action passif des facteurs intrinsèques tels que l'insularité et la fraction importante du territoire occupée par des zones arides et semi-arides. La végétation des zones arides et semi-arides qui occupent, au Cap Vert, plus de 70% du sol arable du territoire, a un faible pouvoir de régénération. Sa flore insulaire est sensible par le fait d'avoir évolué en l'absence de prédateurs et d'être issues de petites populations avec une diversité génétique limitée et par une aire de dissémination très limitée. La diversité des espèces Il existe au Cap Vert, 110 espèces de bryophytes dont 15 sont endémiques. Du total, 36% sont extinctes ou menacées. Parmi les endémiques 40% sont menacées. Les espèces d’angiospermes sont en nombre de 240 dont 45 sont endémiques. A noter que 27% du total sont extinctes ou menacées. Parmi les endémiques, 54% sont en danger de disparition. La biodiversité animale cours des risques majeures de survie. Des 37 espèces de gastéropodes existantes, 15 sont endémiques dont 67% sont menacées. Les arachnides sont au nombre de 111 dont 46 sont endémiques. Parmi les endémiques, 78% sont menacées. Il existe 470 espèces d'insectes (coléoptères) dont 155 sont endémiques. 84% des taxa endémiques sont menacées. On suppose que du total des 470 espèces, 64% sont disparues ou en danger. L'état actuel de la faune et de la flore a été donné par la Première Liste Rouge du Cap Vert, publiée en 1996 et qui indique un certain nombre de statistiques effrayantes : sont menacées plus de 26% des angiospermes, plus de 40% des bryophytes, plus de 65% des ptéridophytes et plus de 29% des lichens ; plus de 47% des oiseaux, 25% des reptiles terrestres, 64% des coléoptères, plus de 57% des arachnides, plus de 59% des mollusques terrestres. L'archipel du Cap Vert est situé dans la zone tropicale où, selon Nunan (1992), si on exclue les espèces migratoires on peu compter environ 273 espèces de poissons, dont 70% sont endémiques. La liste des espèces de poissons des îles du Cap Vert est assez diversifiée et compte environ une centaine d'espèces appartenant à différentes familles. En matière de diversité biologique marine l'exploitation des ressources dans la ZEE (Zone Economique Exclusive) sont encore loin d'atteindre le potentiel estimé. Néanmoins, il existe quelques espèces qui sont en danger, notamment les tortues et les langoustes. Dans les eaux capverdiennes il existe 5 espèces de tortues : Dermocelys coriacea, Chelonia mydas, Eretmochelys imbricata, Caretta caretta et Lepidochelys olivacea. Les tortues sont d'une façon générale soumises à une exploitation irrationnelle depuis des décades. La viande et les oeufs, surtout de la tortue mâle sont très appréciés. La carapace est utilisée dans la bijouterie (boucles, bagues, colliers, etc.). Parmi les quatre familles de langoustes connues, l'archipel du Cap Vert recèle deux : la Palinuridae (langouste rose, verte et marron) et la Scyllaride (langouste de pierre). A signaler également une espèce endémique, le Palinuris charlestoni. Toutes les espèces existantes au Cap Vert sont exploitées, souvent à la limite de la durabilité. La République du Cap Vert et la Convention sur la Biodiversité Le Cap Vert a signé la Convention sur la biodiversité en juin 1992 et l'a ratifié en mars 1995. Pour remplir les obligations découlant de l'adoption de la Convention, le pays a complété sa Stratégie Nationale et Plan d'Action sur la Biodiversité en février 1999. Une institution responsable pour la mise en oeuvre de la politique nationale en matière de l'environnement a été créée, le Secrétariat Exécutif pour l'Environnement (SEPA). Le Plan d'Action National a identifié 21 objectifs divisés en huit groupes thèmatiques et contient des activités jusqu'à l'an 2010. Parallèlement à ces actions, la Loi de Base pour l'Environnement, le Code de l'Environnement, le Code de l'Eau et le Code Forestier ont été adoptés. Ce nouveau Code Forestier a été élaboré afin d'actualiser les normes pour une gestion durable des ressources et le transfert des compétences aux régions et communautés. Au niveau stratégique le Cap Vert a élaboré son Programme d'Action National pour l'Environnement (PANA) et a développé le Programme d'Action National de Lutte Contre la Désertification (PAN-LCD) en utilisant l'approche participative faisant appel à tous les acteurs de la société civile y inclus les associations et ONG. Au niveau international le Cap Vert a adhéré aux conventions telles que la biodiversité, les changements climatiques et le contrôle de la désertification. Le pays a également signé les conventions suivantes : Convention des Nations Unies sur le Droit de la Mer, Convention relative à la Protection du Patrimoine Mondial Culturel et Naturel, Convention de Bâle sur les mouvements trans-frontaliers, Convention internationale pour la Prévention de la pollution par des bateaux, Convention de Vienne sur la protection de la couche de l'ozone, Protocole de Montréal sur les substances qui appauvrissent la couche de l'ozone. La mise en oeuvre de la stratégie nationale sur la Diversité Biologique permettra une meilleure gestion de l'eau, des ressources naturelles et des espaces, l'introduction de nouvelles espèces et de nouvelles technologies alternatives pour l'agriculture et l'élevage ainsi que la création de nouveaux emplois alternatifs, à partir des activités génératrices de revenus, et de diminuer ainsi, la pression sur les ressources naturelles.