Evidence for classification of c.1852_1853AA > GC in MLH1 as a neutral variant for Lynch syndrome

Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients. Conclusions: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.

Avances analíticos en la datación forense de tintas y documentos

380 p. : il., gráf.

Alienação e transcendência: da insuficiência do Estatuto da Cidade para a constituição de um Direito da Cidade com viés crítico

O instituto da gestão democrática da cidade ocupa lugar central nos debates e nas reflexões acerca do Direito da Cidade e do Estatuto da Cidade. Especificamente no que se refere ao conteúdo dessas reflexões, a gestão democrática alcança impressionante consenso, não sendo coisa fácil encontrar razões no sentido de negar a validade da construção de uma cidadania ativa para gestão dos negócios urbanos. Este trabalho quer entender, concretamente, a razão do citado consenso, ancorado em uma concepção crítica que tenta chamar atenção para aspectos do social que não costumam ser contemplados pela análise realizada entre os juristas que se dedicam ao tema. Neste sentido, questões como a da alienação do trabalho e sua relação com a alienação política e a situação real das cidades a partir da categoria de análise da FES (formação econômica e social) não devem ser ignoradas quando das discussões sobre as possibilidades de efetivação de atuação citadina ativa nas cidades brasileiras. Em tempo, é necessário, a partir das categorias destacadas, analisar criticamente os instrumentos do Estatuto da Cidade para que não se permitam maiores ilusões acerca do estado de coisas aqui discutido.

TRANSFER OF ANALYTICAL METHODS FOR THE CHARACTERISATION OF NATURAL PRODUCTS TO R&D PROCESSES OF IDOKI

IDOKI SCF Technologies S.L. is a technology-based company, set up on September 2006 in Derio (Biscay) with the main scope of developing extraction and purification processes based on the use of supercritical fluid extraction technology (SFE) in food processing, extraction of natural products and the production of personal care products. IDOKI¿s researchers have been working on many different R&D projects so far, most of them using this technology. However, the optimization of a SFE method for the different matrices cannot be performed unless we have an analytical method for the characterisation of the extracts obtained in each experiment. The analytical methods are also essential for the quality control of the raw materials that are going to be used and also for the final product. This PhD thesis was born to tackle this problem and therefore, it is based on the development of different analytical methods for the characterisation of the extracts and products. The projects that we could include in this thesis were the following: the extraction propolis, the recovery of agroindustrial residues (soy and wine) and the dealcoholisation of wine.On the one hand, for the extraction of propolis, several UV-Vis spectroscopic methods were used in order to measure the antioxidant capacity and the total polyphenol and flavonoid content of the extracts. A SFC method was also developed in order to measure more specific phenolic compounds. On the other hand, for the recovery of agroindustrial residues UV-Vis spectroscopy was used to determine the total polyphenol content and two SFC methods were developed to analyse different phenolic compounds. Extraction methods such as MAE, FUSE and rotary agitation were also evaluated for the characterisation of the raw materials.Finally, for the dealcoholisation of wine, the development of a SBSE-TD-GC-MS and DHS-TD-GC-MS methods for the analysis of aromas and a NIR spectroscopic method for the determination of ethanol content with the help of chemometrics was necessary. Most of these methods are typically used in IDOKI¿s lab as routine analyses apart from others not included in this PhD thesis.

Doses efficaces en glyphosate et en 2,4-D pour le contrôle chimique des laitue d'eau (Pistia stratiotes, Linn.) et toxicité du glyphosate vis-à-vis des tilapias (Sarotherodon melanotheron)

The toxic effects of two herbicides Round up (gliphosate) and 2,4-D (herbazol) were tested on Pistia stratiotes (Linn. Araceae) samples cultivated in glass aquariums. The gliphosate appears to be more toxic on Pistia Stratiotes than 2,4-D. It was then tested on tilapia Sarotherodon melanotheron juveniles. The lethal dose for tilapia (CL50 = 13.25 mg.l -1) is about 18, 37 and 74 times higher than the glyphosate toxic dose for plants at 1, 2 and 4 meters water depth respectively.

Determinación de compuestos orgánicos potencialmente alérgenos en equipos textiles de protección individual (EPIs) mediante analisis directo por pirólisis acoplado a cromatografía de gases espectrometría de masas (Py-GC/MS).

Nota de aplicación instrumental desarrollada en el Servicio Central de Análisis de Bizkaia (SCAB)

Metodología analítica para el control de calidad en ambientadores higiénicos basados en la cuantificación de sus componentes mediante cromatografía de gases acoplada a espectrometría de masas (GC/MS).

Nota técnica para el análisis de compuestos volátiles en fórmulas higiénicas

Aquaculture vis-a-vis agriculture

The effect of aquaculture, especially shrimp farming, on agriculture has caused heated debate among aquaculturists, agriculturists, and non-governmental organizations. As data on the negative impact of shrimp farming on adjacent rice fields are not available, a study was undertaken in rice fields skirting three shrimp farms: a semi-intensive farm; an extensive farm; and a semi-intensive farm with a buffer zone. The buffer zone was found to be helpful in preventing salinization of the adjacent agricultural fields and the Electrical Conductivity (EC) values (less than 1) reported were found to be harmless to the rice crop. Thus, aquaculture and agriculture can coexist in coastal areas if there are buffer zones in between.

Utilização de diagramas causais em confundimento e viés de seleção.

Apesar do crescente reconhecimento do potencial dos diagramas causais por epidemiologistas, essa técnica ainda é pouco utilizada na investigação epidemiológica. Uma das possíveis razões é que muitos temas de investigação exigem modelos causais complexos. Neste trabalho, a relação entre estresse ocupacional e obesidade é utilizada como um exemplo de aplicação de diagramas causais em questões relacionadas a confundimento. São apresentadas etapas da utilização dos diagramas causais, incluindo a construção do gráfico acíclico direcionado, seleção de variáveis para ajuste estatístico e a derivação das implicações estatísticas de um diagrama causal. A principal vantagem dos diagramas causais é tornar explícitas as hipóteses adjacentes ao modelo considerado, permitindo que suas implicações possam ser analisadas criticamente, facilitando, desta forma, a identificação de possíveis fontes de viés e incerteza nos resultados de um estudo epidemiológico.

Prawn culture and policy options: technology import and culture through fishermen vis a vis industry

Recent developments in aquaculture has created an awareness that prawn culture is a dollar spinner, in which industry can step in to earn foreign exchange by producing an expensive food iten which has a high market demand abroad. The Government has to take a policy decision whether the prawn culture should be done through small fishermen to improve their socio-economic condition or through private industry with the high technology input and predefined objectives of export trade. Perhaps a simultaneous operation of the two could be allowed best in the interest of India. Perhaps in the interest of quick development and adoption of high production technology, through fishermen organization, the development is encouraged through the implimentation of welfare and area development schemes. In some selected areas private industry may be encoureged to use high production technology to develop prawns.