Epidemiology of congenital diaphragmatic hernia in Europe: a register-based study.

INTRODUCTION: Published prevalence rates of congenital diaphragmatic hernia (CDH) vary. This study aims to describe the epidemiology of CDH using data from high-quality, population-based registers belonging to the European Surveillance of Congenital Anomalies (EUROCAT). METHODS: Cases of CDH delivered between 1980 and 2009 notified to 31 EUROCAT registers formed the population-based case series. Prevalence over time was estimated using multilevel Poisson regression, and heterogeneity between registers was evaluated from the random component of the intercept. RESULTS: There were 3373 CDH cases reported among 12 155 491 registered births. Of 3131 singleton cases, 353 (10.4%) were associated with a chromosomal anomaly, genetic syndrome or microdeletion, 784 (28.2%) were associated with other major structural anomalies. The male to female ratio of CDH cases overall was 1:0.69. Total prevalence was 2.3 (95% CI 2.2 to 2.4) per 10 000 births and 1.6 (95% CI 1.6 to 1.7) for isolated CDH cases. There was a small but significant increase (relative risk (per year)=1.01, 95% credible interval 1.00-1.01; p=0.030) in the prevalence of total CDH over time but there was no significant increase for isolated cases (ie, CDH cases that did not occur with any other congenital anomaly). There was significant variation in total and isolated CDH prevalence between registers. The proportion of cases that survived to 1 week was 69.3% (1392 cases) for total CDH cases and 72.7% (1107) for isolated cases. CONCLUSIONS: This large population-based study found an increase in total CDH prevalence over time. CDH prevalence also varied significantly according to geographical location. No significant association was found with maternal age.

Assessment of the capacity to consent to treatment in patients admitted to acute medical wards.

BACKGROUND: Assessment of capacity to consent to treatment is an important legal and ethical issue in daily medical practice. In this study we carefully evaluated the capacity to consent to treatment in patients admitted to an acute medical ward using an assessment by members of the medical team, the specific Silberfeld's score, the MMSE and an assessment by a senior psychiatrist. METHODS: Over a 3 month period, 195 consecutive patients of an internal medicine ward in a university hospital were included and their capacity to consent was evaluated within 72 hours of admission. RESULTS: Among the 195 patients, 38 were incapable of consenting to treatment (unconscious patients or severe cognitive impairment) and 14 were considered as incapable of consenting by the psychiatrist (prevalence of incapacity to consent of 26.7%). Agreement between the psychiatrist's evaluation and the Silberfeld questionnaire was poor (sensitivity 35.7%, specificity 91.6%). Experienced clinicians showed a higher agreement (sensitivity 57.1%, specificity 96.5%). A decision shared by residents, chief residents and nurses was the best predictor for agreement with the psychiatric assessment (sensitivity 78.6%, specificity 94.3%). CONCLUSION: Prevalence of incapacity to consent to treatment in patients admitted to an acute internal medicine ward is high. While the standardized Silberfeld questionnaire and the MMSE are not appropriate for the evaluation of the capacity to consent in this setting, an assessment by the multidisciplinary medical team concurs with the evaluation by a senior psychiatrist.

Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells.

Deregulation of the ubiquitin/proteasome system has been implicated in the pathogenesis of many human diseases, including cancer. Ubiquitin-specific proteases (USP) are cysteine proteases involved in the deubiquitination of protein substrates. Functional connections between USP7 and essential viral proteins and oncogenic pathways, such as the p53/Mdm2 and phosphatidylinositol 3-kinase/protein kinase B networks, strongly suggest that the targeting of USP7 with small-molecule inhibitors may be useful for the treatment of cancers and viral diseases. Using high-throughput screening, we have discovered HBX 41,108, a small-molecule compound that inhibits USP7 deubiquitinating activity with an IC(50) in the submicromolar range. Kinetics data indicate an uncompetitive reversible inhibition mechanism. HBX 41,108 was shown to affect USP7-mediated p53 deubiquitination in vitro and in cells. As RNA interference-mediated USP7 silencing in cancer cells, HBX 41,108 treatment stabilized p53, activated the transcription of a p53 target gene without inducing genotoxic stress, and inhibited cancer cell growth. Finally, HBX 41,108 induced p53-dependent apoptosis as shown in p53 wild-type and null isogenic cancer cell lines. We thus report the identification of the first lead-like inhibitor against USP7, providing a structural basis for the development of new anticancer drugs.

Hirschsprung's disease prevalence in Europe: A register based study.

BACKGROUND: Hirschsprung's disease is a congenital gut motility disorder, characterised by the absence of the enteric ganglion cells along the distal gut. The aim of this study was to describe the epidemiology of Hirschsprung's disease, including additional congenital anomalies, total prevalence, trends, and association with maternal age. METHODS: Cases of Hirschsprung's disease delivered during 1980 to 2009 notified to 31 European Surveillance of Congenital Anomaly registers formed the population-based case-series. Prevalence rates and 95% confidence intervals were calculated as the number of cases per 10,000 births. Multilevel Poisson regression was performed to investigate trends in prevalence, geographical variation and the association with maternal age. RESULTS: There were 1,322 cases of Hirschsprung's disease among 12,146,210 births. The total prevalence was 1.09 (95% confidence interval, 1.03-1.15) per 10,000 births and there was a small but significant increase in prevalence over time (relative risk = 1.01; 95% credible interval, 1.00-1.02; p = 0.004). There was evidence of geographical heterogeneity in prevalence (p < 0.001). Excluding 146 (11.0%) cases with chromosomal anomalies or genetic syndromes, there were 1,176 cases (prevalence = 0.97; 95% confidence interval, 0.91-1.03 per 10,000 births), of which 137 (11.6%) had major structural anomalies. There was no evidence of a significant increased risk of Hirschsprung's disease in cases born to women aged ≥35 years compared with those aged 25 to 29 (relative risk = 1.09; 95% credible interval, 0.91-1.31; p = 0.355). CONCLUSION: This large population-based study found evidence of a small increasing trend in Hirschsprung's disease and differences in prevalence by geographic location. There was also no evidence of an association with maternal age. Birth Defects Research (Part A), 100:695-702, 2014. © 2014 Wiley Periodicals, Inc.

Les Passions filmées: des codes en appropriation, un cinéma en canonisation

Constituant l'un des premiers « genres » de l'histoire du cinéma (dont Burch et Gaudreault ont montré le rôle fondateur dans la standardisation des procédures de montage institutionnalisées), les films mettant en scène la Vie et la Passion du Christ fixent leurs normes en s'appropriant des codes iconographiques préétablis. Dans cet article, Valentine Robert s'attache à déployer le « palimpseste » de ces Passions des premiers temps, à démêler les « séries culturelles » impliquées, à dégager les phénomènes de reprises d'une bande à l'autre, et à replacer certains de ces jeux référentiels dans leur visée de légitimation - ou doit-on dire « canonisation » ? - du médium cinématographique.

Distribuição hídrica no período crítico do milho e produção de grãos

A cultura do milho pode sofrer reduções na produção de grãos quando há déficit hídrico no período crítico do ciclo da cultura, que ocorre desde o pendoamento até o início de enchimento de grãos. O objetivo deste trabalho foi estabelecer relações entre o suprimento de água durante o período crítico do milho e a produção de grãos. Experimentos foram conduzidos em Eldorado do Sul, RS (30º5'S; 51º40'W; 40 m altitude), nas safras 1998/1999 e 2002/2003, anos em que ocorreram os fenômenos La Niña e El Niño, respectivamente. Os dados de rendimento de grãos e seus componentes foram obtidos em experimentos de campo, sob diferentes volumes de aplicação de água via irrigação. A produtividade de grãos foi inversa à média geral do Estado, nos dois anos analisados. Em 1998/1999, durante uma estiagem longa, 46,8 mm de chuva no período crítico garantiram rendimento próximo de 8.000 kg ha-1 sem irrigação. Em 2002/2003 uma curta estiagem no período crítico reduziu a produtividade para menos de 2.000 kg ha-1 no mesmo tratamento, afetando o número de espigas por planta e o número de grãos por espiga. Portanto, em anos de El Niño, mesmo que as previsões climáticas apontem para uma distribuição favorável de chuvas, há risco na produção esperada de milho, se o suprimento de água no período crítico da cultura não for adequado.

Comparação de modelos matemáticos na estimativa das perdas de produtividade de grãos em arroz irrigado

Os objetivos deste trabalho foram comparar modelos matemáticos e identificar, entre variáveis morfológicas, a de melhor ajuste na previsão de perdas de produtividade em arroz irrigado por interferência da cultivar EEA 406, simuladora de arroz-vermelho. Foram realizados quatro experimentos, sendo um no campo e os demais em casa de vegetação. Três cultivares de arroz, BRS-38 Ligeirinho, IRGA 417 e BR-IRGA 409, foram estudadas no campo, com espaçamento entrelinhas de 15 e 25 cm, além de populações da cultivar competidora (dez níveis). Em casa de vegetação, realizaram-se experimentos em monocultivos e em série de substituição. A análise dos dados foi realizada com aplicação de modelos lineares e não lineares de regressão. O melhor ajuste dos dados de perdas de produtividade em arroz foi encontrado com o modelo de dois parâmetros. Área foliar e cobertura do solo estimaram melhor as perdas de produtividade de grãos do que a massa seca da cultivar simuladora. Os modelos testados indicam que a redução do espaçamento entrelinhas aumenta a habilidade competitiva das cultivares de arroz em relação à cultivar concorrente.

Epidemiology of cleft palate in Europe: implications for genetic research.

OBJECTIVE: To describe the epidemiology of cleft palate (CP) in Europe. DESIGN AND SETTING: A descriptive epidemiological study on 3852 cases of CP, identified (1980 through 1996) from more than 6 million births from the EUROCAT network of 30 registers in 16 European countries. RESULTS: Significant differences in prevalence in Europe between registries and within countries were observed. A total of 2112 (54.8%) CP cases occurred as isolated, 694 (18.0%) were associated with other defects such as multiple congenital anomalies, and 1046 (27.2%) were in recognized conditions. The study confirmed the tendency toward female prevalence (sex ratio [SR] = 0.83), particularly among isolated cases (SR = 0.78) even if SR inversion is reported in some registries. A specific association with neural tube defects (NTDs) in some registers is reported. CONCLUSION: The differences identified in Europe (prevalence, sex, associated anomalies) can be only partially explained by methodological reasons because a common methodology was shared among all registries for case ascertainment and collection, and CP is an easy detectable condition with few induced abortions. The complex model of inheritance and the frequently conflicting results in different populations on the role of genes that constitute risk factors suggest the presence of real biological differences. The association of CP/NTD in an area with a high prevalence of NTDs can identify a group of conditions that can be considered etiologically homogeneous. The epidemiological evaluation can guide genetic research to specify the role of etiological factors in each different population

Ajuste osmótico em milho cultivado em diferentes sistemas de manejo de solo e disponibilidade hídrica

A cultura do milho é sensível ao déficit hídrico, e esta é uma causa freqüente de redução na produção de grãos. O objetivo deste trabalho foi verificar a ocorrência de ajuste osmótico em milho, cultivado em dois sistemas de manejo do solo, com diferentes disponibilidades hídricas. Os tratamentos consistiram do cultivo do milho em semeadura direta (SD) e convencional (SC), com irrigação de forma a manter a umidade do solo próxima à capacidade de campo, e sem irrigação. O ajuste osmótico foi obtido pela diferença do potencial osmótico hidratado entre as plantas irrigadas e sem irrigação. Os maiores valores de potencial mínimo de água na folha ocorreram em plantas cultivadas sob SD, em razão do maior potencial matricial da água no solo nesse sistema. O potencial de pressão e o osmótico hidratado diminuíram em conseqüência do déficit hídrico, o que determinou a ocorrência de ajuste osmótico em ambos os sistemas, que foi mais intenso em manejo convencional. Portanto, o potencial mínimo de água na folha demonstra ser um indicador adequado da condição hídrica das plantas de milho. A cultura apresenta tolerância ao déficit hídrico por meio do mecanismo de ajuste osmótico.

Place branding : a conceptual and theoretical framework

Within the context of rising competition between territories, identity has become the most important element of recognition, differentiation and commodification in the communicative process within which cities, regions and countries position themselves. Geographical spaces thus compete in terms of this identity, which is then subjected to fierce comparison and competition (Nogué, 1999; Anholt, 2007a). The territorial brand thus entails the reinvention of places through a process of brand construction (branding) based on the promotion of the individual and collective identities of geographical spaces; these identities, in turn, are imbued with the intangible factors associated with their respective territorial identities.

Teoría de la comunicación y paisaje. Las geografías del sujeto y la perspectiva interpretativa de la comunicación

El estudio de las implicaciones comunicativas presentes en el paisaje tangible e intangible circundante abre un amplio abanico de posibilidades para el tratamiento de la denominada comunicación en el paisaje. El análisis de los efectos que el entorno genera en los procesos de comunicación humana, el seguimiento de los procesos comunicativos mediante los cuales se mercadea con el paisaje, la construcción de imaginarios individuales y colectivos a partir de la interacción ciudadanía-territorio, el tránsito de espacio a lugar y, más recientemente, la habilitación de identidades territoriales a partir de la construcción de una imagen de marca de ciudad o de país –léase promoción turística, citymarketing y/o branding, entre otros– presentan, en todos los casos, amplias connotaciones de alcance comunicativo. La búsqueda del mensaje presente en el paisaje plantea, en este mismo sentido, el tratamiento del espacio a modo de sistema de comunicación. En cualquier caso, parece claro que, en los últimos tiempos, asistimos a una cierta eclosión de procesos de comunicación concebidos desde la realidad existente en el espacio y más aún, en el paisaje, por lo que se hace necesario avanzar hacia un tratado comunicativo del paisaje.