Contribuciones al diagnóstico del trastorno específico del lenguaje por medio de la repetición de pseudopalabras

Se presentan dos listas de pseudopalabras para la evaluación de la memoria fonológica de trabajo para el diagnóstico del trastorno específico del lenguaje. Una lista está constituida por pseudopalabras compuestas de sílabas frecuentes, y la otra por sílabas no frecuentes. Se acompañan de las instrucciones para su administración y de un baremo provisional realizado con niños de 5 y 7 años. La importancia de la tarea de repetición de pseudopalabras para el diagnóstico del trastorno específico del lenguaje se basa, por una parte, en que se ha comprobado que es la mejor forma de medir la capacidad del almacén fonológico de la memoria de trabajo, ya que se deben llevar a cabo tareas de discriminación de la señal acústica, transformación de la secuencia acústico-fonética en sus fonemas constituyentes, codificación de la información acústica en una representación fonológica, mantenimiento del orden de esta representación en la memoria de trabajo, y planificación y ejecución de la respuesta, sin que se pongan en marcha procesos de arriba abajo desde el significado. Y por otra parte, parece comprobado que el origen del trastorno específico del lenguaje está en la limitación de la capacidad del mencionado almacén fonológico que afecta, en primer lugar, a la adquisición de vocabulario, y, en segundo lugar, al desarrollo de la morfosintaxis.------------------Two lists of nonwords are proposed to evaluate the phonological working memory for diagnostic of specific language impairment. One list is made up of nonwords whose syllables are frequent and the other of nonwords whose syllables are not frequent. These lists are accompanied by instructions for their performance and by provisional norms carried out on 5- and 7-year-old children. On one hand, the importance of the task of nonword repetition for diagnostic of specific language impairment is based on works which reliably prove that it is the best tool to measure the capacity of phonological store of working memory, because it is necessary to implement tasks like discriminating the acoustic signal, converting the acoustic-phonetic sequence into phonemes, encoding acoustic information into a phonological representation, keeping the order of this representation in working memory, and planning and implementing the response; and these psycholinguistic activities must be carried out without activating top-down processes from the meaning. On the other hand, it seems proved that the origin of specific language impairment lies in the limitation of capacity of phonological store which affects, firstly, vocabulary acquisition, and, secondly, morphosyntax development

La concepción simple de la lectura en educación primaria: una revisión sistemática

La concepción simple de la lectura (CSL) es un modelo que trata de explicar la comprensión lectora (L) a partir de dos componentes básicos: la descodificación (D) y la comprensión del lenguaje (C). En los últimos años este modelo ha sido utilizado como base teórica para la toma de decisiones sobre el aprendizaje de la lectura en el sistema educativo de países como Reino Unido o Francia. La CSL ha sido criticada por distintos motivos. El primero, y más importante, es que D y C dejan sin explicar una parte importante de la varianza de los resultados de L. Esta parte podría ser del 50% o más, lo que indicaría que el modelo es incompleto y existe la posibilidad de que personas con una descodificación y comprensión del lenguaje normales obtengan malos resultados en comprensión lectora. También se ha señalado que los componentes del modelo están vagamente definidos, especialmente C, y que distintos autores los evalúan de formas diferentes. Otras críticas son que la relación entre sus componentes cambia con la edad y que no ha inspirado intervenciones pedagógicas de consideración. A pesar de estas observaciones, se considera que la CSL puede ser útil en educación ya que tiene características poco habituales en los modelos de comprensión lectora como su carácter evolutivo, el énfasis en la descodificación y su sencillez.The simple view of reading (SVR) is a model to explain reading comprehension (R) using two basic components: decoding (D) and language comprehension (C). In recent years this model has been employed as a theoretical base for decision making in the education system in countries such as United Kingdom or France. The SVR has been criticized for several reasons. The first, and most important, is that D and C cannot explain a substantial part of the variance of R results. This unexplained part could be 50% or even higher, which could mean that the model is not complete and that there is a possibility that people with normal decodification and language comprehension skills could perform badly in reading comprehension tasks. It has also been pointed out that the components of the model are loosely defined, particularly C, and that different researchers evaluate those components in different ways. Other criticisms are that the relation between the components of the model changes with age, and that it has not produced any relevant pedagogical interventions. In spite of these points, the SVR can be useful in educational work. It has some characteristics that are unusual in reading comprehension models: it is evolutionary, it places emphasis on decoding, and it is an easy to understand model

RNA-seq based transcriptome analysis of the type I interferon host response upon vaccinia virus infection of mouse cells

Vaccinia virus (VACV) encodes the soluble type I interferon (IFN) binding protein B18 that is secreted from infected cells and also attaches to the cell surface, as an immunomodulatory strategy to inhibit the host IFN response. By using next generation sequencing technologies, we performed a detailed RNA-seq study to dissect at the transcriptional level the modulation of the IFN based host response by VACV and B18. Transcriptome profiling of L929 cells after incubation with purified recombinant B18 protein showed that attachment of B18 to the cell surface does not trigger cell signalling leading to transcriptional activation. Consistent with its ability to bind type I IFN, B18 completely inhibited the IFN-mediated modulation of host gene expression. Addition of UV-inactivated virus particles to cell cultures altered the expression of a set of 53 cellular genes, including genes involved in innate immunity. Differential gene expression analyses of cells infected with replication competent VACV identified the activation of a broad range of host genes involved in multiple cellular pathways. Interestingly, we did not detect an IFN-mediated response among the transcriptional changes induced by VACV, even after the addition of IFN to cells infected with a mutant VACV lacking B18. This is consistent with additional viral mechanisms acting at different levels to block IFN responses during VACV infection

Análisis de la batería de inicio a la lectura (BIL 3-6) para la predicción de las dificultades del aprendizaje del lenguaje escrito

Esta es la primera parte de un estudio cuyo objetivo es mostrar si la Batería de Inicio a la lectura (BIL 3-6) de Sellés, Martínez, Vidal-Abarca y Gilabert (2008) puede ser considerada como una batería predictiva en lo que se refiere a las dificultades de la adquisición de la lectura. El objetivo presente es conocer la relación de las distintas variables que componen la batería, de manera que se conozca su idoneidad para el fin que se propone. Método: la batería fue aplicada a 87 niños de 2º de Educación Infantil. Resultados: las pruebas que miden los factores Conocimiento Fonológico y Habilidades Lingüísticas correlacionan de forma parcial. Las pruebas que evalúan el Conocimiento Metalingüístico y las pruebas que miden Procesos Cognitivos no presentan correlación que determine la idoneidad de la puntuación global de los factores. La relación entre las pruebas de los factores Conocimiento Fonológico y Habilidades Lingüísticas y Conocimiento Fonológico y Conocimiento Alfabético no presentan correlación de manera absoluta. La puntuación de las profesoras es útil para valorar el aprendizaje de la lectura. Pasados dos años se confirmará si los resultados obtenidos en la batería pueden llegar a predecir las dificultades de aprendizaje de la lectura.This is the first part of a research which purpose is to demonstrate if la Batería de Inicio a la lectura (BIL 3-6) by Sellés, Martínez, Vidal-Abarca y Gilabert (2008) can be considered a predictive test of reading difficulties. The main aim of this study is to evaluate the relationship between the test’s variables to know if it’s suitable for the intended purpose. Method: The test battery was applied to 87 children, students of 2nd Early Childhood Education. Results: The tests that evaluate the factors phonological knowledge and linguistic abilities correlate partially. The tests that evaluate metalinguistic knowledge and the tests that evaluate cognitive processes do not show a correlation that could determine the suitability of the global score of the factors. The tests of the factors phonological 8 knowledge and linguistic abilities and phonological knowledge and literacy skills do not correlate in an absolute way. It was found that the teacher’s evaluation is useful to assess the process of learning to read. After 2 years, it will be confirmed if the obtained result could predict difficulties learning to read

Valoración de un test para la predicción de dificultades en el aprendizaje de la lectura

Este trabajo es la primera parte de un estudio cuya finalidad es comprobar si la BIL 3- 6 elaborada por Sellés, Martínez, Vidal-Abarca y Gilabert (2008), tiene la capacidad de predecir las dificultades del aprendizaje en la lectura. El objetivo es recoger los resultados de la administración de esta prueba para conocer la correlación existente entre las diferentes variables que lo componen. Participantes: 53 niños, de los cuales 40 cursan Kínder (Chile), 4 niños de Pre-Kínder en un jardín infantil (Chile) y 9 niños que cursan Pre-Kínder en un colegio en Puerto Rico. Resultados: las pruebas que evalúan Conocimiento Fonológico correlacionan sólo en parte y en su totalidad correlacionan con Conocimiento Alfabético. Las variables que miden el Conocimiento Metalingüístico no correlacionan. Sólo dos variables correlacionan en el factor Habilidades Lingüísticas cuya prueba Conceptos Básicos, es la que más correlaciona con Conocimiento Fonológico. Procesos Cognitivos correlaciona entre sí. La valoración de las profesoras, sobre el nivel de aprendizaje coincide con los resultados obtenidos sólo al considerar habilidades prelectoras. Tras dos años se comprobará si los resultados obtenidos en este test tienen la capacidad de predecir las dificultades en el aprendizaje de la lectura.This is the first part of a study which purpose is to demostrate if BIL 3-6, elaborated by Sellés, Martínez, Vidal-Abarca and Gilabert (2008) has the capacity to predict difficulties in learning to read. The aim of this study is to collect data from the test application to know the existence correlation between the variables. Participants: 53 children’s, of which 40 were student of Kindergarten (Chile), 4 students of Pre-kinder (Chile) and, 9 were students of Pre-Kinder in a school in Puerto Rico. Results: The tests that evaluate Phonological Knowledge correlate partially between them, and correlate totally with Literacy Skills. The variables that evaluate Metalinguistic Knowledge do not correlate. Only two variables correlate on the Linguistic Abilities factor, whose test Basic Concepts correlate the most with Phonological Knowledge. Cognitive Processes factor correlates between them. The teacher’s evaluation about the academic performance concurs with the results obtained in the test, taking into account pre-reading skills. After two years, it will be confirmed if the results obtained in this test have the capacity to predict difficulties in the learning to read process

Reading Comprehension Improvement for Spanish Students: A Meta- Analysis

Se realizó una revisión sistemática de intervenciones para la mejora de la comprensión lectora en español. Se incluyeron estudios realizados con alumnado en edad escolar con diseños experimentales o diseños cuasi-experimentales, que habían controlado la equivalencia de los grupos en comprensión lectora antes de la intervención. Se localizaron 39 estudios con los que se hizo un meta-análisis de efectos aleatorios obteniendo una estimación combinada del tamaño del efecto de 0.71. Se muestra la eficacia de las intervenciones basadas en estrategias de comprensión, como la identificación de ideas principales o la construcción de inferencias, y de las que combinan la enseñanza de estrategias con otros métodos como la motivación o la mejora de la descodificación. Solo dos estudios proporcionaron información sobre cómo se mantenían los resultados tiempo después de finalizar la intervención por lo que se considera que ése tendría que ser uno de los puntos a tener en cuenta en futuras investigaciones

Bringing Machine-Learning Enhanced Quantum Chemistry and Microwave Spectroscopy to Conformational Landscape Exploration: the Paradigmatic Case of 4-Fluoro-Threonine

A combined experimental and theoretical study has been carried out on 4-fluoro-threonine, the only naturally occurring fluorinated amino acid. Fluorination of the methyl group significantly increases the conformational complexity with respect to the parent amino acid threonine. The conformational landscape has been characterized in great detail, with special attention given to the inter-conversion pathways between different conformers. This led to the identification of 13 stable low-energy minima. The equilibrium population of so many conformers produces a very complicated and congested rotational spectrum that could be assigned through a strategy that combines several levels of quantum chemical calculations with the principles of machine learning. Twelve conformers out of 13 could be experimentally characterized. The results obtained from the analysis of the intra-molecular interactions can be exploited to accurately model fluorine-substitution effects in biomolecules

NTHL1 biallelic mutations seldom cause colorectal cancer, serrated polyposis or a multi-tumor phenotype, in absence of colorectal adenomas

In 2015 Weren et al. described a hereditary cancer syndrome caused by biallelic mutations in the DNA base excision repair gene NTHL1, characterized by attenuated adenomatous polyposis and increased colorectal cancer (CRC) risk, largely resembling the recessive syndrome caused by MUTYH mutations1. To date, 33 homozygous or compound heterozygous NTHL1 mutation carriers have been reported (21 families)1,2,3,4,5,6,7,8. More than 5 colonic adenomas (range: 6 to >50) were identified in 24 of the 28 (85%) mutation carriers who underwent colonoscopy screening, and CRC was diagnosed in 19 (68%) of them. Noteworthy, 17 carriers (57%) were diagnosed with multiple primary malignant tumors in extracolonic locations, being the most recurrently found breast and endometrial tumors, head neck squamous cell carcimomas, meningiomas, and bladder and basal cell carcinomas, suggesting that the NTHL1-associated syndrome is a multi-tumor disease rather than a solely CRC syndrome. On the other hand, the fact that at least ¼ (7/28) of the reported biallelic mutation carriers who underwent colonoscopy screening had ≤10 adenomas, and that ≥5 hyperplastic polyps were detected in five carriers (polyp number range: 5->30), lead us to suspect a possible association of NTHL1 mutations with nonpolyposis CRC and serrated/hyperplastic polyposis. Based on previous evidence and with the aim of refining the phenotypic characteristics of the NTHL1-associated syndrome, here we evaluated the implication of NTHL1 biallelic mutations in the predisposition to personal or familial history of multiple tumor types, familial/early-onset nonpolyposis CRC, and serrated/hyperplastic polyposis

Non-Lynch Familial and Early-Onset Colorectal Cancer Explained by Accumulation of Low-Risk Genetic Variants

A large proportion of familial and/or early-onset cancer patients do not carry pathogenic variants in known cancer predisposing genes. We aimed to assess the contribution of previously validated low-risk colorectal cancer (CRC) alleles to familial/early-onset CRC (fCRC) and to serrated polyposis. We estimated the association of CRC with a 92-variant-based weighted polygenic risk score (wPRS) using 417 fCRC patients, 80 serrated polyposis patients, 1077 hospital-based incident CRC patients, and 1642 controls. The mean wPRS was significantly higher in fCRC than in controls or sporadic CRC patients. fCRC patients in the highest (20th) wPRS quantile were at four-fold greater CRC risk than those in the middle quantile (10th). Compared to low-wPRS fCRC, a higher number of high-wPRS fCRC patients had developed multiple primary CRCs, had CRC family history, and were diagnosed at age ≥50. No association with wPRS was observed for serrated polyposis. In conclusion, a relevant proportion of mismatch repair (MMR)-proficient fCRC cases might be explained by the accumulation of low-risk CRC alleles. Validation in independent cohorts and development of predictive models that include polygenic risk score (PRS) data and other CRC predisposing factors will determine the implementation of PRS into genetic testing and counselling in familial and early-onset CRC

Comprehensive analysis of copy number aberrations in microsatellite stable colon cancer in view of stromal component

Background: Somatic copy number aberrations (CNA) are common acquired changes in cancer cells playing an important role in the progression of colon cancer (CRC). This study aimed to perform a characterization of CNA and their impact in gene expression.Methods: CNA were inferred from SNP array data in a series of 99 CRC. CNA events were calculated and used to assess the association between copy number dosage, clinical and molecular characteristics of the tumours, and gene expression changes. All analyses were adjusted for the quantity of stroma in each sample, that was inferred from gene expression data.Results: High heterogeneity among samples was observed, the proportion of altered genome ranged between 0.04 and 26.6%. Recurrent CNA regions with gains were frequent in chromosomes 7p, 8q, 13q, and 20 while 8p, 17p, and 18 cumulated loses. A significant positive correlation was observed between the number of somatic mutations and total CNA (Spearman r=0.42, P=0.006). Approximately 37% of genes located in CNA regions changed their level of expression, and the average partial correlation (adjusted for stromal content) with copy number was 0.54 (inter-quartile range 0.20 to 0.81). Altered genes showed enrichment in pathways relevant for colorectal cancer. Tumours classified as CMS2 and CMS4 by the consensus molecular subtyping showed higher frequency of CNA. Loses of one small region in 1p36.33, with gene CDK11B, were associated with poor prognosis. More than 66% of the recurrent CNA were validated in the TCGA data when analysed with the same procedure. Also 79% of the genes with altered expression in our data were validated in the TCGA.Conclusion: Though CNA are frequent events in MSS CRC, few focal recurrent regions were found. These aberrations have strong effects on gene expression and contribute to deregulate relevant cancer pathways. Due to the diploid nature of stromal cells, it is important to consider the purity of tumour samples to accurately calculate CNA events in CRC