| 1. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 2. |
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| 3. |
- Ameen, Carly, et al.
(författare)
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Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic
- 2019
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 286:1916
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Tidskriftsartikel (refereegranskat)abstract
- Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP.
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| 5. |
- Bowes, John, et al.
(författare)
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PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis : evidence for a further PsA-specific risk locus
- 2015
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:10, s. 1882-1885
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis; it has a higher estimated genetic component than psoriasis alone, however most genetic susceptibility loci identified for PsA to date are also shared with psoriasis. Here we attempt to validate novel single nucleotide polymorphisms selected from our recent PsA Immunochip study and determine specificity to PsA. Methods A total of 15 single nucleotide polymorphisms were selected (P-Immunochip <1x10(-4)) for validation genotyping in 1177 cases and 2155 controls using TaqMan. Meta-analysis of Immunochip and validation data sets consisted of 3139 PsA cases and 11 078 controls. Novel PsA susceptibility loci were compared with data from two large psoriasis studies (WTCCC2 and Immunochip) to determine PsA specificity. Results We found genome-wide significant association to rs2476601, mapping to PTPN22 (p=1.49x10(-9), OR=1.32), but no evidence for association in the psoriasis cohort (p=0.34) and the effect estimates were significantly different between PsA and psoriasis (p=3.2x10(-4)). Additionally, we found genome-wide significant association to the previously reported psoriasis risk loci; NOS2 (rs4795067, p=5.27x10(-9)). Conclusions For the first time, we report genome-wide significant association of PTPN22 (rs2476601) to PsA susceptibility, but no evidence for association to psoriasis.
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| 6. |
- Jia, Qi
(författare)
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Estimation of industrial dust using exposure-profiling method
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dust is a primary cause for air quality deterioration, as well as a potential health hazard. Mining and construction sites, in particular, are the most profound in dust generation. The possible source activities are drilling, loading, transporting, dumping, crushing, stockpiles, waste rock and unprotected open surfaces, etc. Dust can be any airborne contaminants occur in the gaseous form or as aerosols. This research dealt with ‘fugitive dust’ which is defined as dust that could not reasonably pass through a stack, chimney, vent, or other functionally equivalent openings, and does not include non-geologic particulate matter emitted directly by internal and external combustion processes. Fugitive dust and dust are used interchangeably in this thesis.In mining areas, construction sites or other industrial areas, fugitive dust is generated through wind erosion of surface materials or application of mechanical forces. The transportation of dust particles is a result of wind direction, velocity, source activities, particles dispersion characteristics, topography, control methods, and so on. A case study on dust fallout from Malmberget Iron Mine showed that the dust generation due to the mining activities in Malmberget Iron Mine influences the down-wind residential areas depending on the weather conditions and the rate of dust generation; the sources of dust generation from Malmberget Iron Mine are haul road transportations, active stockpiles, and the open pit with the loose surface materials. Dust due to wind erosion of the loose material from the open pit is somewhat insignificant as the lab tests showed that the surface material was slightly to moderately erodible and has the soil erosion index of 4.7kg/m2/year.To measure dust generation, three sites were used. They are unpaved roads, road construction and the Aitik tailings dam. This was achieved using an exposure-profiling method with Big Spring Number Eight (BSNE) samplers. Wind erosion prediction system (WEPS) was also used to model the wind erosion process on the Aitik tailings dam. The measurement for the unpaved roads showed that dust generation strongly depends on the driving speed and silt content of road surface materials when the moisture contents are the same. The estimated dust emission rate from the road construction work during the measuring period was 22.87 kg TSP/d, of which 6 kg/d was from construction work and 16.87 kg/d was generated due to traffic on temporary roads. The measured total suspended material from the Aitik tailings dam was 0.475kg/m2 for five days, which had a big difference with simulated value of 4.4559 kg/m2. Many reasons contributed to the disagreement between the simulated value and the measured value. In order to use the model for mining industry more tests are required to validate the modeling result. This could be useful in adjusting the internal coefficients and empirical equations.The research concluded that the exposure-profiling method with BSNEs worked best for the unpaved roads which is a line source, whereas for the road construction and the Aitik tailings dam the method was not robust enough. BSNE sampler is cheap and widely used, but can produce poor accuracy in some cases. Upwind-downwind method with active samplers is recommended for the road construction and the tailings dam which are the non-line sources in the future work. Both of the methods are applicable for development of dust emission factors. WESP is a soil erosion model designed for agriculture land and need to be validated with more field tests in order to be used for the tailings dam.
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| 8. |
- Mitra, Aditee, et al.
(författare)
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Defining Planktonic Protist Functional Groups on Mechanisms for Energy and Nutrient Acquisition : Incorporation of Diverse Mixotrophic Strategies
- 2016
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Ingår i: Protist. - : Elsevier BV. - 1434-4610 .- 1618-0941. ; 167:2, s. 106-120
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Tidskriftsartikel (refereegranskat)abstract
- Arranging organisms into functional groups aids ecological research by grouping organisms (irrespective of phylogenetic origin) that interact with environmental factors in similar ways. Planktonic protists traditionally have been split between photoautotrophic "phytoplankton" and phagotrophic "microzooplankton". However, there is a growing recognition of the importance of mixotrophy in euphotic aquatic systems, where many protists often combine photoautotrophic and phagotrophic modes of nutrition. Such organisms do not align with the traditional dichotomy of phytoplankton and microzooplankton. To reflect this understanding, we propose a new functional grouping of planktonic protists in an ecophysiological context: (i) phagoheterotrophs lacking phototrophic capacity, (ii) photoautotrophs lacking phagotrophic capacity, (iii) constitutive mixotrophs (CMs) as phagotrophs with an inherent capacity for phototrophy, and (iv) non-constitutive mixotrophs (NCMs) that acquire their phototrophic capacity by ingesting specific (SNCM) or general non-specific (GNCM) prey. For the first time, we incorporate these functional groups within a foodweb structure and show, using model outputs, that there is scope for significant changes in trophic dynamics depending on the protist functional type description. Accordingly, to better reflect the role of mixotrophy, we recommend that as important tools for explanatory and predictive research, aquatic food-web and biogeochemical models need to redefine the protist groups within their frameworks. (C) 2016 The Authors. Published by Elsevier GmbH.
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| 9. |
- Scown, Murray, et al.
(författare)
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Improving Predictive Models of In-Stream Phosphorus Concentration Based on Nationally-Available Spatial Data Coverages
- 2017
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Ingår i: Journal of the American Water Resources Association. - : Wiley. - 1752-1688 .- 1093-474X. ; 53:4, s. 944-960
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Tidskriftsartikel (refereegranskat)abstract
- Spatial data are playing an increasingly important role in watershed science and management. Large investments have been made by government agencies to provide nationally-available spatial databases; however, their relevance and suitability for local watershed applications is largely unscrutinized. We investigated how goodness of fit and predictive accuracy of total phosphorus (TP) concentration models developed from nationally-available spatial data could be improved by including local watershed-specific data in the East Fork of the Little Miami River, Ohio, a 1,290 km2 watershed. We also determined whether a spatial stream network (SSN) modeling approach improved on multiple linear regression (nonspatial) models. Goodness of fit and predictive accuracy were highest for the SSN model that included local covariates, and lowest for the nonspatial model developed from national data. Septic systems and point source TP loads were significant covariates in the local models. These local data not only improved the models but enabled a more explicit interpretation of the processes affecting TP concentrations than more generic national covariates. The results suggest SSN modeling greatly improves prediction and should be applied when using national covariates. Including local covariates further increases the accuracy of TP predictions throughout the studied watershed; such variables should be included in future national databases, particularly the locations of septic systems.
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| 10. |
- Zafari, Zafar, et al.
(författare)
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Individualized prediction of lung-function decline in chronic obstructive pulmonary disease
- 2016
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Ingår i: CMAJ. - : CMA Joule Inc.. - 0820-3946. ; 188:14, s. 1004-1010
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Tidskriftsartikel (refereegranskat)abstract
- Background: The rate of lung-function decline in chronic obstructive pulmonary disease (COPD) varies substantially among individuals. We sought to develop and validate an individualized prediction model for forced expiratory volume at 1 second (FEV1) in current smokers with mild-to-moderate COPD. Methods: Using data from a large long-term clinical trial (the Lung Health Study), we derived mixed-effects regression models to predict future FEV1 values over 11 years according to clinical traits. We modelled heterogeneity by allowing regression coefficients to vary across individuals. Two independent cohorts with COPD were used for validating the equations. Results: We used data from 5594 patients (mean age 48.4 yr, 63% men, mean baseline FEV1 2.75 L) to create the individualized prediction equations. There was significant between-individual variability in the rate of FEV1 decline, with the interval for the annual rate of decline that contained 95% of individuals being -124 to -15 mL/yr for smokers and -83 to 15 mL/yr for sustained quitters. Clinical variables in the final model explained 88% of variation around follow-up FEV1. The C statistic for predicting severity grades was 0.90. Prediction equations performed robustly in the 2 external data sets. Interpretation: A substantial part of individual variation in FEV1 decline can be explained by easily measured clinical variables. The model developed in this work can be used for prediction of future lung health in patients with mild-to-moderate COPD.
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