Playing games with words cultural transfer in David Lynch's Blue Velvet

Eguíluz, Federico; Merino, Raquel; Olsen, Vickie; Pajares, Eterio; Santamaría, José Miguel (eds.)

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.

A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer

12 p.

Failure detectors and communication efficiency in the crash and general omisión failure models

122 p.

An Alternative View of the US Price-Dividend Ratio Dynamics

As a necessary condition for the validity of the present value model, the price-dividend ratio must be stationary. However, significant market episodes seem to provide evidence of prices significantly drifting apart from dividends while other episodes show prices anchoring back to dividends. This paper investigates the stationarity of this ratio in the context of a Markov- switching model à la Hamilton (1989) where an asymmetric speed of adjustment towards a unique attractor is introduced. A three-regime model displays the best regime identification and reveals that the first part of the 90’s boom (1985-1995) and the post-war period are characterized by a stationary state featuring a slow reverting process to a relatively high attractor. Interestingly, the latter part of the 90’s boom (1996-2000), characterized by a growing price-dividend ratio, is entirely attributed to a stationary regime featuring a highly reverting process to the attractor. Finally, the post-Lehman Brothers episode of the subprime crisis can be classified into a temporary nonstationary regime.

Instituciones Microfinancieras y banca tradicional: diferencias en funcionamiento y resultados durante la crisis

Español: A finales del 2007 muchas entidades financieras comenzaron a mostrar cifras negativas en sus balances y tras la quiebra de entidades de gran peso económico como el banco Lehman Brothers en Estados Unidos en septiembre del 2008, el mundo se ha visto envuelto en una crisis económica de la que parece no verse el final. Las entidades financieras tradicionales han centrado sus esfuerzos en obtener las mayores rentabilidades posibles, invirtiendo sus recursos en activos muy arriesgados, que si bien en un principio generaban beneficios muy elevados, a día de hoy han hecho quebrar muchas entidades a nivel mundial y han provocado la pérdida de los ahorros de muchos ciudadanos. Ajenas a esto se encuentran las entidades microfinancieras, que con un enfoque muy diferente al de la banca tradicional, se han centrado en proporcionar financiación a aquellos que dada su situación económica y falta de garantías no podían acudir al sector financiero tradicional. Tras realizar un análisis de los resultados de ambos modelos financieros desde 2006 hasta 2012, se ha podido comprobar como el sector microfinanciero presenta resultados más favorables y muestra una mayor prosperidad de cara al futuro. Por lo general, estas entidades mantienen niveles de solvencia más elevados y emplean todos sus recursos en proporcionar financiación a sus clientes. Finalmente, la solución a los problemas del sistema financiero tradicional se basa en un aumento de los niveles de capital de sus entidades, volviendo a un modelo de banca tradicional centrado en ofrecer financiación al público, con provisiones más liquidas y mayores garantías ante necesidades de liquidez como las retiradas masivas de depósitos recientemente sufridas.

The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals

Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance'', being the c.1852_1853delinsGC (p.K618A) variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls) and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

Rescates de entidades financieras: El caso español

Tras el comienzo de la crisis de las hipotecas subprime en 2007 en Estados Unidos y su agudización tras el default de Lehman Brothers en 2008, sabiéndose la extensión de estas hipotecas a lo largo del planeta, la desconfianza se apoderó de los mercados y el crédito dejó de fluir a las economías. En España no se había invertido en estos activos, pero parte del sistema financiero había incurrido en ciertos desequilibrios que si bien permitieron el crecimiento rápido de la economía, cuando la financiación externa dejó de llegar los problemas afloraron de manera rotunda. El sector financiero, especialmente las cajas de ahorro, tuvo que ser rescatado mediante un proceso que constó de numerosas ayudas económicas, cambios de legislación y donde fue necesaria ayuda de la Unión Europea para finalizar el proceso. Tras esta crisis, el subsector de las cajas de ahorro prácticamente desapareció, dando paso a un nuevo mapa de las entidades financieras españolas, donde se ha reducido la participación de los diferentes estamentos políticos, al haber sido estos señalados en ocasiones como posibles causantes de la mala gestión de las cajas. Esta gestión y sus consecuencias no han sido las mismas en las diferentes zonas del país y serán analizadas desde el punto de vista de los gobiernos autonómicos.