Patrones de variación y cambio en la sintaxis del Siglo de Oro: un estudio variacionista de dos perífrasis modales en textos de inmediatez comunicativa

Using the hermeneutic tools of variationism in a corpus of a million and a half words, taken from texts approaching the pole of ‘language immediacy’ (private letters, diaries, etc.), this article analyzes the evolution of constraint factor conditioning the variability between deber & deber de + infi nitive periphrasis in the XVI and XVII centuries. The empirical research shows that deber has a prominent role in Golden Age Spanish, as well as in other moments in its history. However, unlike what has been observed in other periods, deber de has an important vitality in this period, with uses increasing signifi cantly from the second half of the sixteenth century onwards. This vitality is further strengthened in some linguistic contexts, either in isolation (epistemic contexts, modalized utterances –especially, emphasized ones–, negative sentences) or in interaction among them. Furthermore, the fact that these linguistic contexts are much more occasional in discourse than their opposing ones (deontic contexts, non modalized utterances, affi rmative sentences), could explain the secular disadvantage of this periphrasis versus its rival variant. Mediante las herramientas del variacionismo  lingüístico, y a partir de un corpus de un  millón y medio de palabras integrado por textos  cercanos al polo de la inmediatez comunicativa  (cartas privadas, diarios, etc.), en este artículo se  analiza la evolución de los factores que condicionan  la alternancia entre las perífrasis modales deber  y deber de + infinitivo durante el periodo del español  clásico. De la investigación empírica se desprende  que la variante no prepositiva ocupa una posición  predominante en el Siglo de Oro, al igual que en  otros momentos de la historia del español. Ahora  bien, a diferencia de lo que se ha observado en otras  épocas, deber de posee una aceptable vitalidad en  el periodo clásico, con usos que se incrementan significativamente a partir de la segunda mitad del  siglo XVI. Esta vitalidad se ve reforzada además en  algunos contextos lingüísticos, bien aisladamente  (contextos epistémicos, enunciados modalizados  –especialmente, enfáticos–, oraciones negativas),  bien en interacción entre sí. De paso, el hecho de  que estos entornos sean minoritarios en el discurso  con respecto a otros alternativos (contextos  deónticos, enunciados no modalizados, oraciones  afi rmativas) podría explicar la desventaja secular de  esta perífrasis frente a su competidora

The scope of language contact as a constraint factor in language change: The periphrasis haber de plus infinitive in a corpus of language immediacy in modern Spanish

In this work an empirical study grounded in the principles and methods of the comparative variationist framework is conducted to measure the scope of language contact as a factor constraining some potentially diverging uses of a Spanish verbal periphrasis that has undergone a sharp decline over the last century (haber de plus infinitive). The analysis is based on three independent samples of text that correspond to three dialectal areas of peninsular Spanish (monolingual zones, Catalan-speaking linguistic territories and the north-western linguistic area). These samples, extracted from a corpus made up of texts of communicative immediacy from the 19th and the first half of the 20th centuries, confirm the existence of a certain linguistic convergence in the expressive habits of the speakers in the bilingual communities. In each region, however, the outcomes are different, due to parallel differences in the structural position of the periphrasis in each language. However, a thorough analysis of the variable context that surrounds the periphrasis shows that the observed differences do not affect the essence of the underlying grammar of this variant, whose decline (which favours tener que plus infinitive and becomes faster as the 20th century advances) is constrained by identical linguistic and extralinguistic conditioning factors in all the dialectal areas

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

Patrones de variación y cambio en la sintaxis del Siglo de Oro: un estudio variacionista de dos perífrasis modales en textos de inmediatez comunicativa

Using the hermeneutic tools of variationism in a corpus of a million and a half words, taken from texts approaching the pole of ‘language immediacy’ (private letters, diaries, etc.), this article analyzes the evolution of constraint factor conditioning the variability between deber & deber de + infi nitive periphrasis in the XVI and XVII centuries. The empirical research shows that deber has a prominent role in Golden Age Spanish, as well as in other moments in its history. However, unlike what has been observed in other periods, deber de has an important vitality in this period, with uses increasing signifi cantly from the second half of the sixteenth century onwards. This vitality is further strengthened in some linguistic contexts, either in isolation (epistemic contexts, modalized utterances –especially, emphasized ones–, negative sentences) or in interaction among them. Furthermore, the fact that these linguistic contexts are much more occasional in discourse than their opposing ones (deontic contexts, non modalized utterances, affi rmative sentences), could explain the secular disadvantage of this periphrasis versus its rival variant. Mediante las herramientas del variacionismo  lingüístico, y a partir de un corpus de un  millón y medio de palabras integrado por textos  cercanos al polo de la inmediatez comunicativa  (cartas privadas, diarios, etc.), en este artículo se  analiza la evolución de los factores que condicionan  la alternancia entre las perífrasis modales deber  y deber de + infinitivo durante el periodo del español  clásico. De la investigación empírica se desprende  que la variante no prepositiva ocupa una posición  predominante en el Siglo de Oro, al igual que en  otros momentos de la historia del español. Ahora  bien, a diferencia de lo que se ha observado en otras  épocas, deber de posee una aceptable vitalidad en  el periodo clásico, con usos que se incrementan significativamente a partir de la segunda mitad del  siglo XVI. Esta vitalidad se ve reforzada además en  algunos contextos lingüísticos, bien aisladamente  (contextos epistémicos, enunciados modalizados  –especialmente, enfáticos–, oraciones negativas),  bien en interacción entre sí. De paso, el hecho de  que estos entornos sean minoritarios en el discurso  con respecto a otros alternativos (contextos  deónticos, enunciados no modalizados, oraciones  afi rmativas) podría explicar la desventaja secular de  esta perífrasis frente a su competidora