Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk

Social economy, youth and employment

Organizations of the Social Economy in Spain accounted for 13% of employment and 12% of GDP in 2013, according to the Spanish Confederation fo Social Economy. Also, according to various institutions and studies, the role of Social Economy has become relevant due to they represent a model promoting the creation of collective business projects with greater sustainability and potential than models of individual self-employment. However, despite all this, there are few academic studies or sectoral reports analyzing employment in this sector, especially in the case of youth employment. This study aims to fill this gap in the literature analyzing the scared available data in order to show the numbers and characteristics of youth employment in this sector. Results show the weight of youth employment in the Social Economy is higher than the economy overall.

Effects of a positive emotion-based adjuvant psychological therapy in colorectal cancer patients: a pilot study

Objective: To examine the effectiveness of an “Enhancing Positive Emotions Procedure” (EPEP) based on positive psychology and cognitive behavioral therapy in relieving distress at the time of adjuvant chemotherapy treatment in colorectal cancer patients (CRC). It is expected that EPEP will increase quality of life and positive affect in CRC patients during chemotherapy treatment intervention and at 1 month follow-up.Method: A group of 24 CRC patients received the EPEP procedure (intervention group), whereas another group of 20 CRC patients did not receive the EPEP (control group). Quality of life (EORTC-QLQC30), and mood (PANAS) were assessed in three moments: prior to enter the study (T1), at the end of the time required to apply the EPEP (T2, 6 weeks after T1), and, at follow-up (T3, one-month after T2). Patient’s assessments of the EPEP (improving in mood states, and significance of the attention received) were assessed with Lickert scales.Results: Insomnia was reduced in the intervention group. Treatment group had better scores on positive affect although there were no significantly differences between groups and over time. There was a trend to better scores at T2 and T3 for the intervention group on global health status, physical, role, and social functioning scales. Patients stated that positive mood was enhanced and that EPEP was an important resource.Conclusions: CRC patients receiving EPEP during chemotherapy believed that this intervention was important. Furthermore, EPEP seems to improve positive affect and quality of life. EPEP has potential benefits, and its implementation to CRC patients should be considered.

Concept maps as a tool to analyze the ideas of teacher training students regarding what to teach on human nutrition in Primary Education

Concept maps are a technique used to obtain a visual representation of a person's ideas about a concept or a set of related concepts. Specifically, in this paper, through a qualitative methodology, we analyze the concept maps proposed by 52 groups of teacher training students in order to find out the characteristics of the maps and the degree of adequacy of the contents with regard to the teaching of human nutrition in the 3rd cycle of primary education. The participants were enrolled in the Teacher Training Degree majoring in Primary Education, and the data collection was carried out through a training activity under the theme of what to teach about Science in Primary School? The results show that the maps are a useful tool for working in teacher education as they allow organizing, synthesizing, and communicating what students know. Moreover, through this work, it has been possible to see that future teachers have acceptable skills for representing the concepts/ideas in a concept map, although the level of adequacy of concepts/ideas about human nutrition and its relations is usually medium or low. These results are a wake-up call for teacher training, both initial and ongoing, because they shows the inability to change priorities as far as the selection of content is concerned.

Auditoría integrada de Información + Conocimiento: aplicación en un caso de estudio

Se presentan los resultados de la aplicación de una metodología integradora de auditoría de información y conocimiento, llevada a cabo en un Centro de Investigación del Ministerio de Ciencia, Tecnología y Medio Ambiente de la provincia de Holguín, Cuba, conformada por siete etapas con un enfoque híbrido dirigida a revisar la estrategia y la política de gestión de información y conocimiento, identificar e inventariar y mapear los recursos de I+C y sus flujos, y valorar los procesos asociados a su gestión. La alta dirección de este centro, sus especialistas e investigadores manifestaron la efectividad de la metodología aplicada cuyos resultados propiciaron reajustar la proyección estratégica en relación con la gestión de la I+C, rediseñar los flujos informativos de los procesos claves, disponer de un directorio de sus expertos por áreas y planificar el futuro aprendizaje y desarrollo profesional.

Anclaje, dinámicas e impactos territoriales de la cadena global de cítricos dulces en el nordeste argentino

El artículo analiza firmas insertas en circuitos globalizados de exportación de frutas frescas, así como la interfase empresas-territorios. Se focaliza en la producción argentina de cítricos dulces y particularmente en un espacio productivo, y se interesa por cómo se traduce la construcción de los circuitos globales en los espacios y actores locales. Para ello, desarrolla una tipología de empresas e indicadores de anclaje y recurre a una combinación de fuentes cuantitativas y cualitativas, con vistas a desentrañar la “caja negra” del comportamiento empresarial. Se concluye que existen diferentes grados de anclaje territorial y combinaciones variables de fijación y movilidad por parte de las empresas. La adopción de una modalidad de agricultura empresarial multilocalizada, orientada al aprovechamiento de las peculiaridades de los diferentes ambientes locales, conduce a la desarticulación de espacios en función de sus características productivas y de sus diversos contextos sociales e institucionales. De esta forma se promueve la conformación de agentes de características flexibles, transformando su reproducción en contingente.

Source Provenance of Pre-Historic Granitic Grindstones: The Case Study of the Cogotas I Archaeological Site of Arroyo Mucientes/San Lázaro (Castronuño, Valladolid) and a Proposal on the General Methodological Flow Process

The occurrence of hand grindstones at the Cogotas I archaeological sites is considered to be a common feature. Given that a distant-provenance raw material is frequently involved, determination of its source is a basic factor in the search for a better understanding of resource management and for any Political Economy approach. To progress in these directions an overall study should be planned, using selected grindstones with a view to covering diverse sub-zones of the Cogotas I dispersal area, especially because of its considerable distance from the granite basement source. Such a study may today includes diverse analytical procedures combining successive geographic, petrographic, mineralogical and geochemical criteria. To check the plausibility of the proposed methodology, a preliminary test has been carried out on two granite grindstones, obtained at the archaeological excavation at the Castronuño (Valladolid) Cogotian site, which is fifty km away from an inferred source area that was presumably located at Peñausende (Zamora). The result obtained validates the proposed operational process, yielding a generalizable knowledge to other similar situations.

"Lancea", Lusitanian Word, and the "Lancienses" Ethnogenesis

Analysis of the word lancea, of Hispanic origin after Varro, and of place names, people´s names and personal names derived from it. It confirms that the spear was the most important weapon in the Bronze Age, belonging to the iuventus and used as heroic and divine symbol. This analysis confirms also the personality of the Lusitanians, a people related to the Celts but with more archaic archaeological, linguistic and cultural characteristics originated in the tradition of the Atlantic Bronze in the II millennium BC. It is also relevant to better know the organisation of Broze and Iron Age societies and the origin of Indo-Europeans peoples in Western Europe and of pre-Roman peoples of Iberia.

¿Fue la crisis política del Occidente musulmán del siglo XIII debida a un cambio climático? Una aproximación histórica al fin del Periodo Cálido Medieval

Durante el siglo XIII se produjo una sucesión de revueltas que supuso la desaparición del Imperio almohade y su sustitución por poderes regionales en al-Andalus, el Magreb y el Magreb al-Aqsà. La historiografía ha presentado el surgimiento y pugna entre estos poderes como un fenómeno social, político e, incluso, cultural y religioso, con el que se ha podido explicar su aniquilación o marginalización. Este trabajo pretende contextualizar los hechos desde una perspectiva medioambiental, de forma que la desintegración del califato almohade, el surgimiento de aquellos poderes y la progresión de los reinos cristianos en la península ibérica puedan entenderse desde una visión global de cambio climático y una posible crisis agrícola.

Piscolabis (‘snack’): etymological proposals, variations and entries

This article focuses on the study of the word piscolabis. A review of the possible etymological origins put forward in the relevant literature is first presented. This evinces that the difficulties to offer one single (and safe) etymology probably stem from the lack of documents that record the word under study and that date back to the time when it was first used. This historical account also shows that piscolabis has had different variant forms before and after the dictionary of the Spanish Academy (DRAE) established the current one. Finally, the semantic development that the word has undergone is also provided, which allows us to question the suitability of the entry the word has been assigned in the current edition of the DRAE.

Programas de tertulia política en Twitter: un modelo neurocomunicativo de análisis del discurso

En este trabajo aplicamos a la red social Twitter un modelo de análisis del discurso político y mediático desarrollado en publicaciones previas, que permite hacer compatible el estudio de los datos discursivos con propuestas explicativas surgidas a propósito de la comunicación política (neurocomunicación) y de la comunicación digital (la red como quinto estado, convergencia, inteligencia colectiva). Asumimos que hay categorías del encuadre discursivo (frame) que pueden ser tratadas como indicadores de habilidades cognitivas y comunicativas. Analizamos estas categorías agrupándolas en tres dimensiones fundamentales: la intencional (ilocutividad del tuit, encuadre interpretativo de las etiquetas), referencial (temas, protagonistas), e interactiva (alineamiento estructural, predictibilidad; marcas de intertextualidad y dialogismo; afiliación partidista). El corpus consta de 4116 tuits: 3000 tuits pertenecientes a los programas Al Rojo Vivo (La Sexta: A3 Media), Las Mañanas Cuatro (Cuatro: Mediaset) y Los Desayunos de TVE (RTVE), 1116 tuits de seguidores de los programas, que corresponden a 45 tuits de cada programa. Los resultados confirman que el modelo permite establecer diferentes perfiles de subjetividad política en las cuentas de Twitter.

Buenas prácticas de los centros de rehabilitación laboral (CRL) para personas con enfermedad mental grave de la Comunidad de Madrid a tener en cuenta para el diseño de un nuevo modelo de gestión de los servicios de empleo

El presente artículo tiene como objetivo principal identificar las variables que explican por qué los Centros de Rehabilitación Laboral (CRL) para personas con enfermedad mental grave y duradera de la Comunidad de Madrid consiguen tasas de inserción sociolaboral cercanas al 50%, siendo un colectivo que presenta unas tasas de desempleo superiores al 80%. La metodología empleada en la investigación del recurso (documental, cualitativa y cuantitativa) demuestra que estos resultados son posibles gracias a la conjunción de varios elementos: financiación sostenible, método de trabajo, fuerte liderazgo político, trabajo con el tejido empresarial (presentando a las empresas, perfiles profesionales basados en un certero análisis de las competencias), trabajo en red, plazo de intervención marcado por la persona y la composición de los equipos multiprofesionales, entre otros factores.

Gelsolin-mediated activation of PI3K/Akt pathway is crucial for hepatocyte growth factor-induced cell scattering in gastric carcinoma

In gastric cancer (GC), the main subtypes (diffuse and intestinal types) differ in pathological characteristics, with diffuse GC exhibiting early disseminative and invasive behaviour. A distinctive feature of diffuse GC is loss of intercellular adhesion. Although widely attributed to mutations in the CDH1 gene encoding E-cadherin, a significant percentage of diffuse GC do not harbor CDH1 mutations. We found that the expression of the actin-modulating cytoskeletal protein, gelsolin, is significantly higher in diffuse-type compared to intestinal-type GCs, using immunohistochemical and microarray analysis. Furthermore, in GCs with wild-type CDH1, gelsolin expression correlated inversely with CDH1 gene expression. Downregulating gelsolin using siRNA in GC cells enhanced intercellular adhesion and E-cadherin expression, and reduced invasive capacity. Interestingly, hepatocyte growth factor (HGF) induced increased gelsolin expression, and gelsolin was essential for HGF-medicated cell scattering and E-cadherin transcriptional repression through Snail, Twist and Zeb2. The HGF-dependent effect on E-cadherin was found to be mediated by interactions between gelsolin and PI3K-Akt signaling. This study reveals for the first time a function of gelsolin in the HGF/cMet oncogenic pathway, which leads to E-cadherin repression and cell scattering in gastric cancer. Our study highlights gelsolin as an important pro-disseminative factor contributing to the aggressive phenotype of diffuse GC.

Manual práctico de evaluación para políticas públicas en el ámbito de la discapacidad

Este manual es una herramienta que guía la evaluación de las intervenciones sociales en el ámbito de la discapacidad. Intervenciones que pueden realizar el sector público, el sector privado o ambos de manera conjunta. Si bien se trata de una herramienta pragmática, el usuario del manual o herramienta está acompañado de una teoría potente que ilumina el proceso de evaluación dándole sentido y orientación, pues de lo que se trata es de mejorar las condiciones generales de accesibilidad de las personas con discapacidad a la educación, al empleo, a los servicios colectivos y, en general, a los recursos de la sociedad.