| 11. |
- Heap, Graham A., et al.
(författare)
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HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:10, s. 1131-1134
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 x 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the H LA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.
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| 12. |
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| 13. |
- 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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| 14. |
- Toh, Wei Seong, et al.
(författare)
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Cellular senescence in aging and osteoarthritis : implications for cartilage repair
- 2016
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Ingår i: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 87:sup. 363, s. 6-14
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Tidskriftsartikel (refereegranskat)abstract
- - It is well accepted that age is an important contributing factor to poor cartilage repair following injury, and to the development of osteoarthritis. Cellular senescence, the loss of the ability of cells to divide, has been noted as the major factor contributing to age-related changes in cartilage homeostasis, function, and response to injury. The underlying mechanisms of cellular senescence, while not fully understood, have been associated with telomere erosion, DNA damage, oxidative stress, and inflammation. In this review, we discuss the causes and consequences of cellular senescence, and the associated biological challenges in cartilage repair. In addition, we present novel strategies for modulation of cellular senescence that may help to improve cartilage regeneration in an aging population.
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| 15. |
- Vijayakrishnan, Jayaram, et al.
(författare)
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Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10-9, odds ratio (OR) = 1.34) and for ETV6-RUNX1 fusion-positive BCP-ALL at 2q22.3 (rs17481869, P = 3.20 × 10-8, OR = 2.14). Our findings provide further insights into genetic susceptibility to ALL and its biology.
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| 16. |
- Beale, Colin, et al.
(författare)
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Pyrodiversity interacts with rainfall to increase bird andmammal richness in African savannas
- 2018
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 21:4, s. 557-567
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Tidskriftsartikel (refereegranskat)abstract
- Fire is a fundamental process in savannas and is widely used for management. Pyrodiversity, variation in local fire characteristics, has been proposed as a driver of biodiversity although empirical evidence is equivocal. Using a new measure of pyrodiversity (Hempsonet al.), we undertook the first continent-wide assessment of how pyrodiversity affects biodiversity in protected areas across African savannas. The influence of pyrodiversity on bird and mammal species richness varied with rainfall: strongest support for a positive effect occurred in wet savannas (>650 mm/year), where species richness increased by 27% for mammals and 40% for birds in the most pyrodiverse regions. Range-restricted birds were most increased by pyrodiversity, suggesting the diversity of fire regimes increases the availability of rare niches. Our findings are significant because they explain the conflicting results found in previous studies of savannas. We argue that managing savanna landscapes to increase pyrodiversity is especially important in wet savannas.
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| 17. |
- Boyd, Sally, 1949, et al.
(författare)
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Sociolinguistic practice among multilingual youth in Sweden and Canada
- 2011
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Ingår i: International symposium on bilingualism, 15-18 June, Oslo.
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Konferensbidrag (refereegranskat)abstract
- 2.Sociolinguistic Practice Among Multilingual Youth in Sweden and Canada This paper addresses two interrelated questions about the sociolinguistic identity and language use of young people in multilingual urban settings. First, can such speakers be divided into different groups on the basis of their sociolinguistic identity and native-speaker status? Second, to what extent does use of the majority language by multilingual youth differ from that of other majority-language speakers? These questions are of broad sociolinguistic interest, contributing more generally to the question of the extent to which the increasingly multilingual nature of formerly monolingual cities has resulted in relatively new ways of speaking, and what role multilingual speakers play in the local speech community. In this paper, we use quantitative methods to compare and contrast the results of a study of three urban centres in Sweden (Stockholm, Göteborg and Malmö) and one in Canada (Toronto). Findings of the studies in Sweden suggest that it is difficult not only to delineate homogeneous groups of speakers among multilingual urban youth, but also to find regular, cohesive patterns in sociolinguistic variation. Similarly, the Toronto study finds it difficult to delineate homogeneous groups, though speakers do seem to be distinguished on the basis of ethnic identity in their overall rates of use of certain variables. Some of these differences may be attributed to instantiations of and attitudes toward policies advocating multiculturalism in Sweden and Toronto. Taken together, the results of these studies suggest that new ways of speaking may be more fruitfully considered as a style of speech or an array of features selected from a pool of available resources for talk in certain contexts and for certain purposes, rather than as one or more ethnolects in the cities studied. These conclusions indicate that such ways of speaking are part and parcel of contemporary spoken Swedish and English. Summary: This paper compares identity and language use of youth in multilingual cities in Sweden and Canada. Examining speakers by (ethno)linguistic criteria and analysing linguistic variation, we find no homogeneous groupings, though some speakers may use particular styles or features as resources in certain contexts and for certain purposes.
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| 18. |
- Boyd, Sally, 1949, et al.
(författare)
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Storstadsungdomars deltagande i den pågående förändringen av ä-ljudet
- 2013
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Ingår i: Svenskans beskrivning 33, 15-17 maj 2013, Helsingfors.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Forskning om språkkontakt i Skandinaviens storstäder har ofta fokuserat på språkdrag vilka upplevs som nya och framträdande (bl a. Kotsinas 1994, Ganuza 2008, Svendsen & Røyneland 2008, Quist 2008, Källström & Lindberg 2011). I denna studie undersöker vi ett mindre framträdande språkdrag som har konstaterats vara under pågående förändring i svenska, nämligen öppningen av ä-ljudet, för att se om ungdomar med utländsk bakgrund deltar på samma sätt som övriga ungdomar i denna förändring (Leinonen 2010, Gross 2012). Det kan tänkas antingen 1) att språkförändringen påskyndas av språkkontakten, 2) att ungdomarna med utländsk bakgrund inte deltar i förändringsprocessen eller 3) att det inte finns signifikanta skillnader mellan ungdomar med olika bakgrunder vad gäller denna vokal. Vår kvantitativa studie bygger på fonetiska analyser av sociolingvistiska intervjuer med 60 ungdomar från olika stadsdelar i Göteborg och Stockholm; hälften av ungdomarna har svenskfödda mödrar och hälften utlandsfödda. Första och andra formanten av tre långa referensvokaler, /ɛ:/ mättes samt /ɛ:/ i kontexten framför /r/ , normaliserades och analyserades statistiskt. Resultaten visar att den allofoniska alterneringen mellan [ɛ:] och [æ:] framför /r/ och retroflexa konsonanter kan vara på väg att försvinna, åtminstone för vissa talare. Det visar sig också att de som ”leder utvecklingen” och har det öppnaste uttalet är tjejer, ungdomar bosatta i Stockholm och ungdomar med utlandsfödda mödrar. Vår preliminära slutsats är ändå att ungdomar med utländsk bakgrund deltar på samma sätt som övriga ungdomar i förändringsprocessen, eftersom andra bakgrundsvariabler (kön och stad) verkar spela större roll i förändringen än föräldrarnas ursprungsland.
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| 19. |
- Boyd, Sally, 1949, et al.
(författare)
-
Variation and Change in the Vowels of Multilingual Swedish Youth
- 2013
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Ingår i: The 9th International Symposium on Bilingualism, 10-13 June 2013, Singapore. - 9789810767587
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Variation and Change in the Vowels of Multilingual Swedish Youth Sally Boyd 1,a , Johan Gross 1,b , Therese Leinonen 2,c and James Walker 3,d 1 University of Gothenburg, Sweden 2 Society of Swedish Literature in Finland 3 York University, Toronto, Canada a sally.boyd@gu.se, b gusgrosjo@student.gu.se, c therese.leinonen@gmail.com, d jamesw@york.ca Language contact in modern urban Scandinavia is the subject of recent studies (e.g. Kotsinas, 1994, Svendsen & Røyneland, 2008, Quist, 2008, Källström & Lindberg, 2011), which tend to focus on salient majority-language linguistic features used by multilingual youth of non-Scandinavian background in contrast with monolingual Scandinavian youth. However, many such features turn out to be infrequent or show no significant difference between monolingual and multilinguals (author1 et al., in press). In this study, we focus on less salient ongoing variation and change in the Swedish vowel system (author3, author2), to determine the extent to which multilingual urban youth in Sweden participate in ongoing changes. The data for this study come from recorded sociolinguistic interviews with mul- tilingual and monolingual youth in three cities. Using interviews with 60 speakers from Stockholm and Gothenburg, half of whom have Swedish as a second language or coordinate first language, we measured a representative sample of tokens of the first and second formant values for three long vowels, though here we focus on / ä :/. After coding the tokens for a series of linguistic and social factors, we used Rbrul (Johnson, 2009) to conduct regression analyses. Preliminary results show that youth in Stockholm tend to have higher F1 values than those in Gothenburg and a possible merger between allophones of / ä :/ before /r/ and elsewhere. Differences between multilinguals and monolinguals are small but statistically significant: monolinguals tend to produce a slightly more retracted [ Ä :] (i.e. they have a lower F2) than multilinguals. Furthermore, monolinguals with more diverse social networks tend to have values that are intermediate between other monolinguals and multilinguals.These results indicate that monolingual and multilingual Swedish youth participate fully in patterns of variation and change in the contemporary vowel system, though their pattern of participation may serve to identify them with the multicultural urban setting.
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| 20. |
- Bruce, Louise C, et al.
(författare)
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A multi-lake comparative analysis of the General Lake Model (GLM) : Stress-testing across a global observatory network
- 2018
-
Ingår i: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152 .- 1873-6726. ; 102, s. 274-291
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Tidskriftsartikel (refereegranskat)abstract
- The modelling community has identified challenges for the integration and assessment of lake models due to the diversity of modelling approaches and lakes. In this study, we develop and assess a one-dimensional lake model and apply it to 32 lakes from a global observatory network. The data set included lakes over broad ranges in latitude, climatic zones, size, residence time, mixing regime and trophic level. Model performance was evaluated using several error assessment metrics, and a sensitivity analysis was conducted for nine parameters that governed the surface heat exchange and mixing efficiency. There was low correlation between input data uncertainty and model performance and predictions of temperature were less sensitive to model parameters than prediction of thermocline depth and Schmidt stability. The study provides guidance to where the general model approach and associated assumptions work, and cases where adjustments to model parameterisations and/or structure are required.
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