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- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 2. |
- Saarela, Svetlana, et al.
(författare)
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Comparing frameworks for biomass prediction for the Global Ecosystem Dynamics Investigation
- 2022
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Ingår i: Remote Sensing of Environment. - : Elsevier. - 0034-4257 .- 1879-0704. ; 278
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Tidskriftsartikel (refereegranskat)abstract
- NASA's Global Ecosystem Dynamics Investigation (GEDI) mission offers data for temperate and pan-tropical estimates of aboveground forest biomass (AGB). The spaceborne, full-waveform LiDAR from GEDI provides sample footprints of canopy structure, expected to cover about 4% of the land area following two years of operation. Several options are available for estimating AGB at different geographical scales. Using GEDI sample data alone, gridded biomass predictions are based on hybrid inference which correctly propagates errors due to the modeling and accounts for sampling variability, but this method requires at least two GEDI tracks in the area of interest. However, there are significant gaps in GEDI coverage and in some areas of interest GEDI data may need to be combined with other wall-to-wall remotely sensed (RS) data, such as those from multispectral or SAR sensors. In these cases, we may employ hierarchical model-based (HMB) inference that correctly considers the additional model errors that result from relating GEDI data to the wall-to-wall data. Where predictions are possible from both hybrid and HMB inference the question arises which framework to choose, and under what circumstances? In this paper, we make progress towards answering these questions by comparing the performance of the two prediction frameworks under conditions relevant for the GEDI mission. Conventional model-based (MB) inference with wall-to-wall TanDEM-X data was applied as a baseline prediction framework, which does not involve GEDI data at all. An important feature of the study was the comparison of AGB predictors in terms of both standard deviation (SD: the square root of variance) and root mean square error (RMSE: the square root of mean square error – MSE). Since, in model-based inference, the true AGB in an area of interest is a random variable, comparisons of the performance of prediction frameworks should preferably be made in terms of their RMSEs. However, in practice only the SD can be estimated based on empirical survey data, and thus it is important also to study whether or not the difference between the two uncertainty measures is small or large under conditions relevant for the GEDI mission. Our main findings were that: (i) hybrid and HMB prediction typically resulted in smaller RMSEs than conventional MB prediction although the difference between the three frameworks in terms of SD often was small; (ii) in most cases the difference between hybrid and HMB inference was small in terms of both RMSE and SD; (iii) the RMSEs for all frameworks was substantially larger than the SDs in small study areas whereas the two uncertainty measures were similar in large study areas, and; (iv) spatial autocorrelation of model residual errors had a large effect on the RMSEs of AGB predictors, especially in small study areas. We conclude that hybrid inference is suitable in most GEDI applications for AGB assessment, due to its simplicity compared to HMB inference. However, where GEDI data are sparse HMB inference should be preferred.
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