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- Loza, M. J., et al.
(författare)
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Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
- 2016
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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| 2. |
- Vega Mendoza, Mariana, et al.
(författare)
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Lexically-specific syntactic restrictions in second-language speakers
- 2024
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Ingår i: Journal of memory and language (Print). - : Elsevier. - 0749-596X .- 1096-0821. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- In two structural priming experiments, we investigated the representations of lexically-specific syntactic restrictions of English verbs for highly proficient and immersed second language (L2) speakers of English. We considered the interplay of two possible mechanisms: generalization from the first language (L1) and statistical learning within the L2 (both of abstract structure and of lexically-specific information). In both experiments, L2 speakers with either Germanic or Romance languages as L1 were primed to produce dispreferred double-object structures involving non-alternating dative verbs. Priming occurred from ungrammatical double-object primes involving different non-alternating verbs (Experiment 1) and from grammatical primes involving alternating verbs (Experiment 2), supporting abstract statistical learning within the L2. However, we found no differences between L1-Germanic speakers (who have the double-object structure in their L1) and L1-Romance speakers (who do not), inconsistent with the prediction for between-group differences of the L1-generalization account. Additionally, L2 speakers in Experiment 2 showed a lexical boost: There was stronger priming after (dispreferred) non-alternating same-verb double-object primes than after (grammatical) alternating different-verb primes. Such lexically-driven persistence was also shown by L1 English speakers (Ivanova, Pickering, McLean, Costa, & Branigan, 2012) and may underlie statistical learning of lexically-dependent structural regularities. We conclude that lexically-specific syntactic restrictions in highly proficient and immersed L2 speakers are shaped by statistical learning (both abstract and lexically-specific) within the L2, but not by generalization from the L1.
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