RESUMO
Substantial evidence suggests that priming can co-occur at different syntactic and nonsyntactic levels. In this study, we further explore two loci of priming concerned with hierarchical configuration and thematic information using relative clause (RC) constructions. In a comprehension-to-production task, Persian speakers (42 adults and 42 children) described pictures after hearing extraposed subject or center-embedded object RCs containing the same or different verbs. We ask whether priming the object RC mitigates the computational cost of center-embedding and thus increases the subsequent production of this infrequent structure. We also measured persistence effects associated with the assignment of emphasis to thematic roles, examining whether a particular portrayal of an event is captured and reproduced (e.g., foregrounding the patient). Although this study could not establish any significant priming effects in the production of the center-embedded object RC, we observed that adults used this construction more in the same verbs condition. The overall results instead revealed strong evidence for thematic emphasis persistence, such that patient-emphasis object relatives further elicited functionally equivalent RC constructions. We discuss priming of hierarchical configuration as a candidate locus and explain the activation of functional information from the speaker's perspective.
Assuntos
Compreensão , Idioma , Adulto , Criança , Humanos , AudiçãoRESUMO
BACKGROUND: Inhibitors of the sodium-glucose cotransporter 2 (SGLT2) slow the progression of diabetic kidney disease, possibly by reducing the proximal tubule transport workload with subsequent improvement of renal oxygenation. We aimed to test this hypothesis in individuals with type 1 diabetes and albuminuria. METHODS: A randomised, double-blind, placebo-controlled, crossover trial with a single 50 mg dose of the SGLT2 inhibitor dapagliflozin and placebo in random order, separated by a two-week washout period. Magnetic resonance imaging (MRI) was used to assess renal R2* (a low value corresponds to a high tissue oxygenation), renal perfusion (arterial spin labelling) and renal artery flow (phase contrast imaging) at baseline, three- and six hours from tablet ingestion. Exploratory outcomes, including baroreflex sensitivity, peripheral blood oxygen saturation, peripheral blood mononuclear cell mitochondrial oxygen consumption rate, and biomarkers of inflammation were evaluated at baseline and 12 h from medication. The study is registered in the EU Clinical Trials Register (EudraCT 2019-004,557-92), on ClinicalTrials.gov (NCT04193566), and is completed. FINDINGS: Between February 3, 2020 and October 23, 2020, 31 individuals were screened, and 19 eligible individuals were randomised. Three dropped out before receiving any of the interventions and one dropped out after receiving only placebo. We included 15 individuals (33% female) in the per-protocol analysis with a mean age of 58 (SD 14) years, median urinary albumin creatinine ratio of 46 [IQR 21-58] mg/g and an eGFR of 73 (32) ml/min/1·73m2. The mean changes in renal cortical R2* from baseline to six hours were for dapagliflozin -1·1 (SD 0·7) s-1 and for placebo +1·3 (0·7) s-1, resulting in a difference between interventions of -2·3 s-1 [95% CI -4·0 to -0·6]; p = 0·012. No between-intervention differences were found in any other MRI outcomes, physiological parameters or exploratory outcomes. There were no adverse events. INTERPRETATION: A single dose of 50 mg dapagliflozin acutely improved renal cortical R2* without changing renal perfusion or blood flow. This suggests improved renal cortical oxygenation due to a reduced tubular transport workload in the proximal tubules. Such improved oxygenation may in part explain the long-term beneficial renal effects seen with SGLT2 inhibitors, but it remains to be determined whether the observed effects can be achieved with lower doses, with chronic treatment and if they occur in type 2 diabetes as well.