Speculations About Early Syntax : the Production of Wh-questions by Normally Developing French Children and French Children with SLI

This paper examines the spontaneous (and elicited) production of questions in 3 typically developing French children (1;8-2;10) and 11 French children with SLI (3;10-9;1). French has three types of constituent questions (Wh-in-situ, fronted Wh without inversion, fronted Wh with inversion) graded in syntactic complexity, allowing detailed investigation of syntactic competence. The results show that both groups of children greatly prefer Wh-in-situ over fronted Wh and avoid inversion. Infinitives are extremely rare in all questions, whereas null subjects are rare in fronted Wh-questions but occur in in-situ questions in typically developing children. SLI children do not produce infinitives in Wh-questions, but allow null subjects in all question types. The elicitation experiment confirmed these trends, though the SLI children had significantly more difficulties with movement than the normal children. A tentative account uses the truncation approach and the assumption that young children avoid movement by deriving in-situ questions with a Q-element in the head position of an Interrogative Phrase entering into an Agree relation with the element left in-situ. SLI children might extend this economic analysis to all Wh-questions

The WASCAL high-resolution regional climate simulation ensemble for West Africa: concept, dissemination and assessment

Climate change and constant population growth pose severe challenges to 21st century rural Africa. Within the framework of the West African Science Service Center on Climate Change and Adapted Land Use (WASCAL), an ensemble of high-resolution regional climate change scenarios for the greater West African region is provided to support the development of effective adaptation and mitigation measures. This contribution presents the overall concept of the WASCAL regional climate simulations, as well as detailed information on the experimental design, and provides information on the format and dissemination of the available data. All data are made available to the public at the CERA long-term archive of the German Climate Computing Center (DKRZ) with a subset available at the PANGAEA Data Publisher for Earth & Environmental Science portal (https://doi.pangaea.de/10.1594/PANGAEA.880512). A brief assessment of the data are presented to provide guidance for future users. Regional climate projections are generated at high (12 km) and intermediate (60 km) resolution using the Weather Research and Forecasting Model (WRF). The simulations cover the validation period 1980–2010 and the two future periods 2020–2050 and 2070–2100. A brief comparison to observations and two climate change scenarios from the Coordinated Regional Downscaling Experiment (CORDEX) initiative is presented to provide guidance on the data set to future users and to assess their climate change signal. Under the RCP4.5 (Representative Concentration Pathway 4.5) scenario, the results suggest an increase in temperature by 1.5 °C at the coast of Guinea and by up to 3 °C in the northern Sahel by the end of the 21st century, in line with existing climate projections for the region. They also project an increase in precipitation by up to 300 mm per year along the coast of Guinea, by up to 150 mm per year in the Soudano region adjacent in the north and almost no change in precipitation in the Sahel. This stands in contrast to existing regional climate projections, which predict increasingly drier conditions. The high spatial and temporal resolution of the data, the extensive list of output variables, the large computational domain and the long time periods covered make this data set a unique resource for follow-up analyses and impact modelling studies over the greater West African region. The comprehensive documentation and standardisation of the data facilitate and encourage their use within and outside of the WASCAL community

The acquisition of pronouns by French children: A parallel study of production and comprehension

This study examines syntactic and morphological aspects of the production and comprehension of pronouns by 99 typically developing French-speaking children aged 3 years, 5 months to 6 years, 5 months. A fine structural analysis of subject, object, and reflexive clitics suggests that whereas the object clitic chain crosses the subject chain, the reflexive clitic chain is nested within it. We argue that this structural difference introduces differences in processing complexity, chain crossing being more complex than nesting. In support of this analysis, both production and comprehension experiments show that children have more difficulty with object than with reflexive clitics (with more omissions in production and more erroneous judgments in sentences involving Principle B in comprehension). Concerning the morphological aspect, French subject and object pronouns agree in gender with their referent. We report serious difficulties with pronoun gender both in production and comprehension in children around the age of 4 (with nearly 30% errors in production and chance level judgments in comprehension), which tend to disappear by age 6. The distribution of errors further suggests that the masculine gender is processed as the default value. These findings provide further insights into the relationship between comprehension and production in the acquisition proces

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline