Saxon and Medieval Settlement on the Northern Edge of Wimborne Minster, Dorset

An excavation on the northern edge of Wimborne Minster revealed elements of a middle to late Saxon and medieval rural settlement fronting onto the west side of the road that leads north out of the town. The Saxon phase comprised a number of rectangular enclosures flanking the road, within and to the west of which were numerous pits and postholes as well as a number of features probably related to industrial activity, including iron smelting. Although no clear structures were identified, the material recovered from the features include Saxon pottery, animal bone, and charred crop remains indicative of settlement within a mixed agricultural economy. Radiocarbon dating of cereal grain from four features gave date ranges in the early/middle and middle/late Saxon periods. The enclosures were subsequently extended during the late Saxon/medieval period, with pottery indicating occupation possibly continuing into the 13th–14th centuries. The site also produced very limited evidence of prehistoric and Romano-British activity

Hepatic carcinoma-associated fibroblasts promote an adaptative response in colorectal cancer cells that inhibit proliferation and apoptosis: nonresistant cells die by nonapoptotic cell death

Carcinoma-associated fibroblasts (CAFs) are important contributors of microenvironment in determining the tumor's fate. This study aimed to compare the influence of liver microenvironment and primary tumor microenvironment on the behavior of colorectal carcinoma. Conditioned medium (CM) from normal colonic fibroblasts (NCFs), CAFs from primary tumor (CAF-PT) or liver metastasis (CAF-LM) were obtained. We performed functional assays to test the influence of each CM on colorectal cell lines. Microarray and gene set enrichment analysis (GSEA) were performed in DLD1 cells cultured in matched CM. In DLD1 cells, CAF-LM CM compared with CAF-PT CM and NCF led to a more aggressive phenotype, induced the features of an epithelial-to-mesenchymal transition more efficiently, and stimulated migration and invasion to a greater extent. Sustained stimulation with CAF-LM CM evoked a transient G(2)/M cell cycle arrest accompanied by a reduction of apoptosis, inhibition of proliferation, and decreased viability of SW1116, SW620, SW480, DLD1, HT-29, and Caco-2 cells and provoked nonapoptotic cell death in those cells carrying KRAS mutations. Cells resistant to CAF-LM CM completely changed their morphology in an extracellular signal-regulated protein kinase-dependent process and depicted an increased stemness capacity alongside the Wnt pathway stimulation. The transcriptomic profile of DLD1 cells treated with CAF-LM CM was associated with Wnt and mitogen-activated protein kinase pathways activation in GSEA. Therefore, the liver micro-environment induces more efficiently the aggressiveness of colorectal cancer cells than other matched micro-environments do but secondarily evokes cell death. Resistant cells displayed higher stemness capacity

Mutanome and expression of immune response genes in microsatellite stable colon cancer

The aim of this study was to analyze the impact of the mutanome in the prognosis of microsatellite stable stage II CRC tumors. The exome of 42 stage II, microsatellite stable, colon tumors (21 of them relapse) and their paired mucosa were sequenced and analyzed. Although some pathways accumulated more mutations in patients exhibiting good or poor prognosis, no single somatic mutation was associated with prognosis. Exome sequencing data is also valuable to infer tumor neoantigens able to elicit a host immune response. Hence, putative neoantigens were identified by combining information about missense mutations in each tumor and HLAs genotypes of the patients. Under the hypothesis that neoantigens should be correctly presented in order to activate the immune response, expression levels of genes involved in the antigen presentation machinery were also assessed. In addition, CD8A level (as a marker of T-cell infiltration) was measured. We found that tumors with better prognosis showed a tendency to generate a higher number of immunogenic epitopes, and up-regulated genes involved in the antigen processing machinery. Moreover, tumors with higher T-cell infiltration also showed better prognosis. Stratifying by consensus molecular subtype, CMS4 tumors showed the highest association of expression levels of genes involved in the antigen presentation machinery with prognosis. Thus, we hypothesize that a subset of stage II microsatellite stable CRC tumors are able to generate an immune response in the host via MHC class I antigen presentation, directly related with a better prognosis

Exploring the Role of Mutations in Fanconi Anemia Genes in Hereditary Cancer Patients

Fanconi anemia (FA) is caused by biallelic mutations in FA genes. Monoallelic mutations in five of these genes (BRCA1, BRCA2, PALB2, BRIP1 and RAD51C) increase the susceptibility to breast/ovarian cancer and are used in clinical diagnostics as bona-fide hereditary cancer genes. Increasing evidence suggests that monoallelic mutations in other FA genes could predispose to tumor development, especially breast cancer. The objective of this study is to assess the mutational spectrum of 14 additional FA genes (FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FANCP, FANCQ, FANCR and FANCU) in a cohort of hereditary cancer patients, to compare with local cancer-free controls as well as GnomAD. A total of 1021 hereditary cancer patients and 194 controls were analyzed using our next generation custom sequencing panel. We identified 35 pathogenic variants in eight genes. A significant association with the risk of breast cancer/breast and ovarian cancer was found for carriers of FANCA mutations (odds ratio (OR) = 3.14 95% confidence interval (CI) 1.4-6.17, p = 0.003). Two patients with early-onset cancer showed a pathogenic FA variant in addition to another germline mutation, suggesting a modifier role for FA variants. Our results encourage a comprehensive analysis of FA genes in larger studies to better assess their role in cancer risk

Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer

Next generation sequencing panels have been developed for hereditary cancer, although there is some debate about their cost-effectiveness compared to exome sequencing. The performance of two panels is compared to exome sequencing. Twenty-four patients were selected: ten with identified mutations (control set) and fourteen suspicious of hereditary cancer but with no mutation (discovery set). TruSight Cancer (94 genes) and a custom panel (122 genes) were assessed alongside exome sequencing. Eightythree genes were targeted by the two panels and exome sequencing. More than 99% of bases had a read depth of over 30x in the panels, whereas exome sequencing covered 94%. Variant calling with standard settings identified the 10 mutations in the control set, with the exception of MSH6 c.255dupC using TruSight Cancer. In the discovery set, 240 unique non-silent coding and canonic splice-site variants were identified in the panel genes, 7 of them putatively pathogenic (in ATM, BARD1, CHEK2, ERCC3, FANCL, FANCM, MSH2). The three approaches identified a similar number of variants in the shared genes. Exomes were more expensive than panels but provided additional data. In terms of cost and depth, panels are a suitable option for genetic diagnostics, although exomes also identify variants in non-targeted genes

Impact of sea-level rise on the tourist-carrying capacity of Catalan beaches

Tourism provides about 11% of Catalonia's GDP, with most accommodations placed being associated with the “sun-and-sand” model. Since beaches are the main resource to be exploited, it is important to assess how their future evolution can affect this economic sector. Accordingly, we present a methodology to assess the effect of shoreline evolution on beach recreational carrying capacity (BCC) at different territorial scales considering different climate change scenarios. Our results suggest that by 2050, in the absence of climate change, tourist BCC will decrease down to 83% of current values due to the dominant erosive behaviour of the Catalan coast. When sea-level rise is considered, BCC will decrease further, with expected values ranging from 74% to 53% of current capacity for the tested scenarios (RCP4.5 and High-end respectively). Hence, current erosional trends are adverse for future development of coastal tourism in Catalonia, and accelerated sea-level rise exacerbates this adverse situation. The adopted methodology permits to locate hotspots along the territory where local BCC values collapse as well as to predict when this will occur under a given climatic scenario. Moreover, the use of different spatial scales to integrate BCC permits to test management strategies to sustaining the recreational use of beaches.</p

Integración de deficientes : actitudes determinantes y canales de actuación

Dentro del ámbito de la Educación Especial y de la integración, y tras un análisis del concepto clave de normalización y/o integración y del concepto de dogmatismo de Rokeach (1960), plantea una aproximación contextualizada al problema de la integración de los deficientes mentales, contemplando el papel desempeñado por psicólogos, profesores, cuidadores, padres y alumnos. Considera los aspectos de grado de implicación, contacto previo con deficientes y dimensiones de personalidad, en concreto dogmatismo. 3 grupos: Niños, 913 entre 7 y 15 años, estudiantes de EGB. Adolescentes, 329 entre 14 y 18 años, estudiantes de BUP y FP. Adultos, 975 con edades que oscilan desde menores de 30 años hasta 60, clasificados según su proximidad o actividad con deficientes. Análisis de la muestra y aplicación de cuestionarios: niños y adolescentes (cuestionario de actitudes hacia la integración), adultos (mismo cuestionario más la escala de actitudes de Rokeach). Los análisis y resultados se exponen en este orden: Niños.- Variables: curso académico (3 niveles), sexo, centro escolar (2 niveles), contacto previo con deficientes (2 niveles) y zona de residencia (2 niveles). Variable criterio, contactos con deficientes. Adolescentes.- Variables: implicación personal, tipo de estudios y sexo. Variable criterio: implicación personal. Adultos.- Variables: edad, sexo, estamento (4 niveles), contacto con deficientes (6 niveles) e implicación personal. Niños: actitud favorable a la integración mayor en los cursos superiores, en las niñas, en alumnos de centros privados, cuando han tenido experiencias previas de contacto y pertenecientes a colegios de la capital. Adolescentes: actitud favorable a la integración mayor en las chicas y en estudiantes de BUP. Aunque en la variable sexo y en la de tipo de estudios, la no implicación reduce las diferencias. Adultos: perfil más favorable a la integración en edad menor de 30 años, mujer, con profesión educativa, en concreto educación especial, en sus niveles inferiores (cuidadores). El contacto con el deficiente origina un cambio de actitudes positivo. Respecto a la relación entre actitudes hacia la integración y componentes de personalidad, dogmatismo y xenofobia implican una actitud más negativa. Aun cuando las conclusiones de este trabajo no pueden extrapolarse a todo el territorio y que las relaciones entre actitudes y conducta no pueden anticiparse con totales garantías, parece claro, que las mujeres y el personal docente tienen una mejor disposición. Los padres son los más resistentes al cambio social, lo que hace necesaria una campaña de concienciación. También es necesario en EGB, donde se realiza la integración en las primeras etapas, y en la que los alumnos tienen peor disposición que en cursos superiores. La implicación, conocimiento y relación con el deficiente mejora la actitud hacia la integración.CantabriaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; Fax +34917748026; [email protected]

Hepatic carcinoma-associated fibroblasts promote an adaptative response in colorectal cancer cells that inhibit proliferation and apoptosis: nonresistant cells die by nonapoptotic cell death

Carcinoma-associated fibroblasts (CAFs) are important contributors of microenvironment in determining the tumor's fate. This study aimed to compare the influence of liver microenvironment and primary tumor microenvironment on the behavior of colorectal carcinoma. Conditioned medium (CM) from normal colonic fibroblasts (NCFs), CAFs from primary tumor (CAF-PT) or liver metastasis (CAF-LM) were obtained. We performed functional assays to test the influence of each CM on colorectal cell lines. Microarray and gene set enrichment analysis (GSEA) were performed in DLD1 cells cultured in matched CM. In DLD1 cells, CAF-LM CM compared with CAF-PT CM and NCF led to a more aggressive phenotype, induced the features of an epithelial-to-mesenchymal transition more efficiently, and stimulated migration and invasion to a greater extent. Sustained stimulation with CAF-LM CM evoked a transient G(2)/M cell cycle arrest accompanied by a reduction of apoptosis, inhibition of proliferation, and decreased viability of SW1116, SW620, SW480, DLD1, HT-29, and Caco-2 cells and provoked nonapoptotic cell death in those cells carrying KRAS mutations. Cells resistant to CAF-LM CM completely changed their morphology in an extracellular signal-regulated protein kinase-dependent process and depicted an increased stemness capacity alongside the Wnt pathway stimulation. The transcriptomic profile of DLD1 cells treated with CAF-LM CM was associated with Wnt and mitogen-activated protein kinase pathways activation in GSEA. Therefore, the liver micro-environment induces more efficiently the aggressiveness of colorectal cancer cells than other matched micro-environments do but secondarily evokes cell death. Resistant cells displayed higher stemness capacity

Hepatic carcinoma-associated fibroblasts promote an adaptative response in colorectal cancer cells that inhibit proliferation and apoptosis: nonresistant cells die by nonapoptotic cell death

Carcinoma-associated fibroblasts (CAFs) are important contributors of microenvironment in determining the tumor's fate. This study aimed to compare the influence of liver microenvironment and primary tumor microenvironment on the behavior of colorectal carcinoma. Conditioned medium (CM) from normal colonic fibroblasts (NCFs), CAFs from primary tumor (CAF-PT) or liver metastasis (CAF-LM) were obtained. We performed functional assays to test the influence of each CM on colorectal cell lines. Microarray and gene set enrichment analysis (GSEA) were performed in DLD1 cells cultured in matched CM. In DLD1 cells, CAF-LM CM compared with CAF-PT CM and NCF led to a more aggressive phenotype, induced the features of an epithelial-to-mesenchymal transition more efficiently, and stimulated migration and invasion to a greater extent. Sustained stimulation with CAF-LM CM evoked a transient G(2)/M cell cycle arrest accompanied by a reduction of apoptosis, inhibition of proliferation, and decreased viability of SW1116, SW620, SW480, DLD1, HT-29, and Caco-2 cells and provoked nonapoptotic cell death in those cells carrying KRAS mutations. Cells resistant to CAF-LM CM completely changed their morphology in an extracellular signal-regulated protein kinase-dependent process and depicted an increased stemness capacity alongside the Wnt pathway stimulation. The transcriptomic profile of DLD1 cells treated with CAF-LM CM was associated with Wnt and mitogen-activated protein kinase pathways activation in GSEA. Therefore, the liver micro-environment induces more efficiently the aggressiveness of colorectal cancer cells than other matched micro-environments do but secondarily evokes cell death. Resistant cells displayed higher stemness capacity

Programa Comunitario de Educación Especial en Cantabria

Promover estrategias que comprometan a todas aquellas personas que están comprometidas con la deficiencia mental. Llevar a cabo un acercamiento contextual e interdisciplinar al mundo de la deficiencia mental referido a la población en edad escolarizable. El objeto del trabajo es conseguir un reciclaje de los profesionales y que los padres aprendan no solamente a resolver y aliviar los problemas actuales sino los principios generales de solución que les posibilite la solución de problemas futuros. Para los técnicos se han celebrado actividades en forma de cursos de contenido académico e impartidos usualmente por profesorado universitario. En el caso de seminarios realizados con padres se han seguido una serie de modelos gestados y desarrollados por el director del programa y llevados a cabo por colaboradores universitarios del mismo y posteriormente miembros del equipo técnico. Además para cada uno de los niveles se ofrece la posibilidad de contar con una asistencia individual. Cursos para técnicos. Cursos para profesores. Cursos para cuidadores y educadores. Cursos para padres. Cuestionario de evaluación de centros escolares. Cuestionario de motivación y ansiedad externa. Cuestionario de locus de control. Cuestionario de extraversión neuroticismo. Análisis factorial: lógica, características de una matriz de intercorrelaciones. Interpretación de la matriz factorial. Procedimientos de rotación. Puntos operativos de decisión: el número de factores, significación estadística de los factores, incorporación de comunalidades, varianza explicada, eficacia de la rotación. La familia de soluciones factoriales. Descripción y confirmación de factores, factores ortogonales y factores oblicuos. Método factorial dinámico: programación interactiva coloquial, los puntos lógicos de decisión, técnicas de correspondencia factorial. Existen tres tipos de resultados: En el primero se presentan los cursos realizados; reciclaje de personal, que ya está trabajando, y charlas de sensibilización a los padres. En el segundo se presentan los modos de actuación directa a base de seminarios de pequeño grupo y asistencia individualizada. En el tercero se recogen una serie de áreas de investigación ilustrativas del modo de hacer del equipo. A lo largo del primer año de trabajo la acción del grupo de trabajo ha insistido en los centros de Educación Especial. La diversificación de los servicios prestados y el régimen de voluntariedad propuesto en cuanto a participación, ha permitido que no se haya colapsado el modelo funcional. Se ha demostrado que el modelo es viable y puede ponerse en funcionamiento en Cantabria.CantabriaES