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.

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

Subcutaneous fat composition of youthful and mature Canadian beef: emphasis on individual conjugated linoleic acid and trans-18:1 isomers

[EN]A comprehensive evaluation of the fatty acid composition of subcutaneous adipose tissue from beef cattle produced in western Canada was undertaken to determine if the current Canadian grading system is able to distinguish classes of animals with value added potential due to their fatty acid composition. Grades included youthful Canadian Yield Grade 1 A/AA beef, under (YUTM) and over (YOTM) 30 mo of age and the four mature grades (D1, D2, D2 and D4). Subcutaneous fat between the 12th and 13th ribs over the longissimus muscle was obtained from 18_21 animals per grade. Fatty acids were analyzed using a combination of silver-ion HPLC and GC with a highly polar 100 m column. There were no differences in total trans-18:1 content amongst grades, but adipose tissue from grade D1, D2 and D4 had more 11t-18:1 than YUTM (PB0.05), whereas adipose tissue from YUTM carcasses had more 10t-18:1 than all other grades (PB0.05). Adipose tissue from YUTM carcasses also had less total CLA (PB0.05) than the D grades, mainly due to a lower level of 9c,11t-CLA, but they had slightly more 7t,9c-CLA and 10t,12c-CLA (PB0.05). Adipose tissue from YOTM and D grades contained more n-3 fatty acids relative to YUTM (0.56% vs. 0.29%; PB0.05) and lower n-6:n-3 ratios (PB0.05). Overall, older animals (YOTM and D grades) had adipose tissue compositions with higher levels of fatty acids with reported health benefits. Taken together, these higher levels may provide opportunities for value added marketing if regulatory authorities allow claims for their enrichment based on demonstrated health benefits. Higher concentrations of beneficial fatty acids, however, need to be considered within the context of the complete fatty acid profile and it would be important to demonstrate their advantages in the presence of relatively high levels of saturated fatty acids.

Short communication: Rapid separation of cis9, trans11- and trans7,cis9-18:2 (CLA) isomers from ruminant tissue using a 30 m SLB-IL111 ionic column

[EN]Rumenic acid (cis9,trans11-18:2) is the main natural isomer of conjugated linoleic acid (CLA). Rumenic acid has many purported health benefits, but effects of most other CLA isomers are unknown. Typically trans7,cis9-18:2 is the second most abundant CLA isomer, but it co-elutes with rumenic acid on conventional polar gas chromatography (GC) columns, requiring complimentary analysis with silver-ion high performance liquid chromatography (Ag(+)-HPLC). Herein we report a rapid method for analyzing rumenic acid and trans7,cis9-18:2 using a 30 m ionic-liquid GC column. Optimal resolution of the two CLA isomers was at 145 degrees C and analysis of backfat from barley-fed cattle compared well with GC/Ag(+)-HPLC (y =0.978x - 0.031, r =0.985, P <0.001).

Incidencia de la gestión de la calidad en los resultados de las empresas: un estudio para el caso de las empresas vascas

En este artículo se analiza la incidencia y la difusión de la Gestión de la Calidad(GC) en las empresas vascas a lo largo de los últimos años. En primer lugar se realiza una breve introducción donde se analiza la difusión del paradigma de la calidad en el ámbito de la gestión y organización de empresas, para más adelante analizar la incidencia de este movimiento en las empresas vascas. Se analiza, asimismo, cuál ha sido la motivación de las empresas a la hora de implantar estas normas y modelos, así como cuáles han sido sus efectos, conforme a los resultados de sendos estudios de carácter cuantitativo y cualitativo llevados a cabo recientemente.

Monitorización avanzada en el posoperatorio de las cardiopatías congénitas : motorización hemodinámica avanzada en el posoperatorio de cardiopatías congénitas mediante termodilución transpulmonar y espectroscopia cercana al infrarrojo

196 p. : graf.

Avances analíticos en la datación forense de tintas y documentos

380 p. : il., gráf.

Desarrollo y aplicación de técnicas avanzadas de medida de compuestos orgánicos volátiles en la atmósfera

331 p.

La cerámica de la Segunda Edad del Hierro en el País Vasco: Estudio tecnológico, funcional y social

670 p. Capítulos de introducción, metodología, discusión y conclusiones en castellano e inglés.

Some experiments on solving multistage stochastic mixed 0-1 programs with time stochastic dominance constraints

In this work we extend to the multistage case two recent risk averse measures for two-stage stochastic programs based on first- and second-order stochastic dominance constraints induced by mixed-integer linear recourse. Additionally, we consider Time Stochastic Dominance (TSD) along a given horizon. Given the dimensions of medium-sized problems augmented by the new variables and constraints required by those risk measures, it is unrealistic to solve the problem up to optimality by plain use of MIP solvers in a reasonable computing time, at least. Instead of it, decomposition algorithms of some type should be used. We present an extension of our Branch-and-Fix Coordination algorithm, so named BFC-TSD, where a special treatment is given to cross scenario group constraints that link variables from different scenario groups. A broad computational experience is presented by comparing the risk neutral approach and the tested risk averse strategies. The performance of the new version of the BFC algorithm versus the plain use of a state-of-the-artMIP solver is also reported.

Análisis de anfetaminas

Revisión bibliográfica del análisis de anfetaminas en pelo y puesta a punto de un método analítico mediante GC-MS sin derivatización previa para el análisis de anfetaminas en el ámbito forense

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.

Optimization of the pyrolysis process for the production of a biomass derived reducing agent and hydrogen-rich gases

221 p.

LC-MS based methods for phytosterols determination in oenological matrices. Targeted metabolomic study of Rioja grape varieties

221 p.+ anexos