El sujeto liviano: una restricción de tipo funcional

El objetivo de esta investigación es confirmar o refutar para el español una restricción observada por Chafe (1994) en el inglés conversacional, y que el autor denomina "la restricción del sujeto liviano " (the light subject contraint). Dicha restricción predice que un sujeto gramatical será pragmáticamente adecuado solo si transmite información dada o accesible, o bien si transmite infonnación nueva pero trivial, es decir, poco importante para el discurso que se está desarrollando. El Corpus para el presente estudio está constituido por 1.800 sujetos extraídos de seis grabaciones de habla del "Estudio sociolingüístico del habla de Caracas, 1987". Las variables consideradas son tres: i) tipo de sujeto; ii) tipo de infonnaciónde los sujetos léxicos; iii) relevancia pragmática de los sujetos léxicos que transmiten información nueva. bs resultados de la investigación no solo confirman en español la restricción establecida por Chafe sino que aportan datos importantes sobre las características del sujeto gramatical

Clinical and genetic characteristics of late-onset Huntington's disease in a large European cohort

Background and purpose Huntington's disease (HD) is an autosomal dominant condition caused by CAG-triplet repeat expansions. CAG-triplet repeat expansion is inversely correlated with age of onset in HD and largely determines the clinical features. The aim of this study was to examine the phenotypic and genotypic correlates of late-onset HD (LoHD) and to determine whether LoHD is a more benign expression of HD. Methods This was a retrospective observational study of 5053 White European HD patients from the ENROLL-HD database. Sociodemographic, genetic and phenotypic variables at baseline evaluation of subjects with LoHD, common-onset HD (CoHD) and young-onset HD (YoHD) were compared. LoHD subjects were compared with healthy subjects (HS) aged >= 60 years. Differences between the CoHD and LoHD groups were also explored in subjects with 41 CAG triplets, a repeat number in the lower pathological expansion range associated with wide variability in age at onset. Results Late-onset HD presented predominantly as motor-onset disease, with a lower prevalence of both psychiatric history and current symptomatology. Absent/unknown HD family history was significantly more common in the LoHD group (31.2%) than in the other groups. The LoHD group had more severe motor and cognitive deficits than the HS group. Subjects with LoHD and CoHD with 41 triplets in the larger allele were comparable with regard to cognitive impairment, but those with LoHD had more severe motor disorders, less problematic behaviors and more often an unknown HD family history. Conclusions It is likely that cognitive disorders and motor symptoms of LoHD are at least partly age-related and not a direct expression of the disease. In addition to CAG-triplet repeat expansion, future studies should investigate the role of other genetic and environmental factors in determining age of onset

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Orden de palabras en español: un análisis sintáctico-semántico-pragmático del sujeto

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Orden de palabras en español: un análisis sintáctico-semántico-pragmático del sujeto

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Ausencia y presencia de la preposición de antes cláusulas encabezadas por que en el español de Caracas: un análisis variacionista

A partir del artículo seminal de Rabanales 1974, el fenómeno del queísmo (ausencia de una proposición delante de una cláusula sustantiva encabezada por que) ha sido estudiado en varios dealectos del español, en la mayoría de los casos conjuntamente con el fenómeno del dequeísmo. Nuestra investigación se centra solamente en la variación presentada por la presencia o ausenca de la preposición de ante que + cláusula en una muestra de 728 casos procedentes de hablantes caraqueños estratificados por edad, sexo y nivel socioeconómico. Se comprueba la hipótesis de que la variación se debe al defecto conjunto de factores tanto lingüísticos como sociolingüísticos y que la variante más frecuente es la queísta (58%). Los factores que favorecen esta variante son: el contexto gramatical (especialmente los verbos pronominales), la similitud fonogramaticas y el nivel socioeconómico (el nivel bajo es más queísta que los niveles de alto y medio). La aplicación de la metodología variacionista a este problema ha permitido determinar cuáles de los factores empleados inciden en la tendencia hacia el queísmo, así como poner a prueba el efecto de algunos de ellos (por ej., la similitud fonogramatical) no utilizados aún en análisis previos sobre el español