| 1. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 2. |
- Bellomo, Rinaldo, et al.
(författare)
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Early acid-base and blood pressure effects of continuous renal replacement therapy intensity in patients with metabolic acidosis
- 2013
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 39:3, s. 429-436
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:In acute kidney injury patients, metabolic acidosis is common. Its severity, duration, and associated changes in mean arterial pressure (MAP) and vasopressor therapy may be affected by the intensity of continuous renal replacement therapy (CRRT). We aimed to compare key aspects of acidosis and MAP and vasopressor therapy in patients treated with two different CRRT intensities.METHODS:We studied a nested cohort of 115 patients from two tertiary intensive care units (ICUs) within a large multicenter randomized controlled trial treated with lower intensity (LI) or higher intensity (HI) CRRT.RESULTS:Levels of metabolic acidosis at randomization were similar [base excess (BE) of -8 ± 8 vs. -8 ± 7 mEq/l; p = 0.76]. Speed of BE correction did not differ between the two groups. However, the HI group had a greater increase in MAP from baseline to 24 h (7 ± 3 vs. 0 ± 3 mmHg; p < 0.01) and a greater decrease in norepinephrine dose (from 12.5 to 3.5 vs. 5 to 2.5 μg/min; p < 0.05). The correlation (r) coefficients between absolute change in MAP and norepinephrine (NE) dose versus change in BE were 0.05 and -0.37, respectively.CONCLUSIONS:Overall, LI and HI CRRT have similar acid-base effects in patients with acidosis. However, HI was associated with greater improvements in MAP and vasopressor requirements (clinical trial no. NCT00221013).
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| 3. |
- Bernal, Esteban, et al.
(författare)
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Friction-Slip Curves - The Pathway From Twin-Disc Tribo Measurements To Full-Scale Locomotive Multibody Simulations
- 2022
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Ingår i: PROCEEDINGS OF 2022 JOINT RAIL CONFERENCE (JRC2022). - : AMER SOC MECHANICAL ENGINEERS.
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Konferensbidrag (refereegranskat)abstract
- Locomotive multibody simulations are commonly used as a cost-effective tool to study, energy efficiency, wheel-rail wear, rolling contact fatigue, etc. The accuracy of the wheel-rail contact forces from multibody simulations depends on the correct modelling of the friction conditions. The friction coefficient is a function of the slip velocity, and it is influenced by several tribological parameters including, for example, material mechanical properties, environmental conditions and the presence of third body layers that vary spatially and temporally along the track. In most cases, generic friction-slip curves obtained from publications and public reports are used as inputs to the wheel-rail contact model in the locomotive simulations, as direct friction measurements using full-scale experimental set-ups are generally cost-prohibitive. A pathway to produce friction-slip curves from tribo-machine friction measurements is proposed in this paper. The pathway involves manufacturing discs from actual wheel and rail material samples to measure the traction coefficient at a spectrum of slip set points using a twin-disc tribo-machine. The tribo-machine results are scaled to be used in a locomotive multibody model that uses the modified Fastsim and a traction system co-simulation approach. Two friction curves for wet and dry conditions are processed and exemplified in a dynamic model.
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| 4. |
- Bernal, Esteban, et al.
(författare)
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Prediction of rail surface damage in locomotive traction operations using laboratory-field measured and calibrated data
- 2022
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Ingår i: Engineering Failure Analysis. - : Elsevier BV. - 1350-6307 .- 1873-1961. ; 135
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Tidskriftsartikel (refereegranskat)abstract
- Rail damage prediction is a complex task because it depends on numerous tribological parameters and the dynamic conditions produced by the vehicles operating at different speeds and configurations. Shakedown maps and Whole-Life-Rail-Model/T-Gamma have been used to predict rail damage, but they involve assumptions that may reduce their accuracy. This paper proposes a simulation modelling method to predict rail surface damage based on a locomotive digital twin, calibrated shakedown maps and friction measurements. The method improves the accuracy of rail damage predictions by including slip-dependent friction characteristics, co-simulation of locomotive traction mechatronic system and the mechanical properties of the wheel and rail materials measured through tensile tests. A set of operating conditions are simulated on a high-performance computing cluster, with stress results being post processed into calibrated shakedown heatmaps. The method clearly indicated the influences of the different operating conditions on rail damage for specific combinations of wheel-rail materials and vehicle-track configurations.
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| 5. |
- Cole, John W, et al.
(författare)
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Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke.
- 2018
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-stage design of discovery and replication.Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 15-49 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms (SNPs) in THBD and 22 SNPs in PROCR were evaluated. Following LD pruning (r2≥0.8), we advanced uncorrelated SNPs forward for association analyses. Associated SNPs were evaluated for replication in an early-onset ischemic stroke population (onset-age<60 years) consisting of 3676 cases and 21118 non-stroke controls from 6 case-control studies. Lastly, we determined if the replicated SNPs also associated with older-onset ischemic stroke in the METASTROKE data-base.Among GEOS Caucasians, PROCR rs9574, which was in strong LD with 8 other SNPs, and one additional independent SNP rs2069951, were significantly associated with ischemic stroke (rs9574, OR = 1.33, p = 0.003; rs2069951, OR = 1.80, p = 0.006) using an additive-model adjusting for age, gender and population-structure. Adjusting for risk factors did not change the associations; however, associations were strengthened among those without risk factors. PROCR rs9574 also associated with early-onset ischemic stroke in the replication sample (OR = 1.08, p = 0.015), but not older-onset stroke. There were no PROCR associations in African-Americans, nor were there any THBD associations in either ethnicity.PROCR polymorphisms are associated with early-onset ischemic stroke in Caucasians.
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| 6. |
- Cole, J. W., et al.
(författare)
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The copy number variation and stroke (CaNVAS) risk and outcome study
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap. Methods Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and exome arrays, with case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome it is planned to: 1) perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and Extension to determine whether the identified stroke-associated CNVs replicate in other ethnically diverse datasets and use biomarker data (e.g. methylation, proteomic, RNA, miRNA, etc.) to evaluate how the identified CNVs exert their effects on stroke risk, and lastly; 3) perform outcome-based Replication and Extension analyses of recent findings demonstrating an inverse relationship between CNV burden and stroke outcome at 3 months (mRS), and then determine the key CNV drivers responsible for these associations using existing biomarker data. Results The results of an initial CNV evaluation of 50 samples from each participating dataset are presented demonstrating that the existing GWAS and exome chip data are excellent for the planned CNV analyses. Further, some samples will require additional considerations for analysis, however such samples can readily be identified, as demonstrated by a sample demonstrating clonal mosaicism. Conclusion The CaNVAS study will cost-effectively leverage the numerous advantages of using existing case-control data sets, exploring the relationships between CNV and IS and its subtypes, and outcome at 3 months, in both men and women, in those of African and European-Caucasian descent, this, across the entire adult-age spectrum. Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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| 7. |
- Cole, Theresa, et al.
(författare)
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Ancient DNA of crested penguins: Testing for temporal genetic shifts in the world's most diverse penguin clade
- 2018
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Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1055-7903 .- 1095-9513. ; 131, s. 72-79
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Tidskriftsartikel (refereegranskat)abstract
- Human impacts have substantially reduced avian biodiversity in many parts of the world, particularly on isolated islands of the Pacific Ocean. The New Zealand archipelago, including its five subantarctic island groups, holds breeding grounds for a third of the world's penguin species, including several representatives of the diverse crested penguin genus Eudyptes. While this species-rich genus has been little studied genetically, recent population estimates indicate that several Eudyptes taxa are experiencing demographic declines. Although crested penguins are currently limited to southern regions of the New Zealand archipelago, prehistoric fossil and archaeological deposits suggest a wider distribution during prehistoric times, with breeding ranges perhaps extending to the North Island. Here, we analyse ancient, historic and modern DNA sequences to explore two hypotheses regarding the recent history of Eudyptes in New Zealand, testing for (1) human-driven extinction of Eudyptes lineages; and (2) reduced genetic diversity in surviving lineages. From 83 prehistoric bone samples, each tentatively identified as ‘Eudyptes spp.’, we genetically identified six prehistoric penguin taxa from mainland New Zealand, including one previously undescribed genetic lineage. Moreover, our Bayesian coalescent analyses indicated that, while the range of Fiordland crested penguin (E. pachyrhynchus) may have contracted markedly over the last millennium, genetic DNA diversity within this lineage has remained relatively constant. This result contrasts with human-driven biodiversity reductions previously detected in several New Zealand coastal vertebrate taxa.
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| 8. |
- Sandholm, Niina, et al.
(författare)
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Genome-wide meta-analysis and omics integration identifies novel genes associated with diabetic kidney disease
- 2022
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 65:9, s. 1495-1509
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Diabetic kidney disease (DKD) is the leading cause of kidney failure and has a substantial genetic component. Our aim was to identify novel genetic factors and genes contributing to DKD by performing meta-analysis of previous genome-wide association studies (GWAS) on DKD and by integrating the results with renal transcriptomics datasets. Methods: We performed GWAS meta-analyses using ten phenotypic definitions of DKD, including nearly 27,000 individuals with diabetes. Meta-analysis results were integrated with estimated quantitative trait locus data from human glomerular (N=119) and tubular (N=121) samples to perform transcriptome-wide association study. We also performed gene aggregate tests to jointly test all available common genetic markers within a gene, and combined the results with various kidney omics datasets. Results: The meta-analysis identified a novel intronic variant (rs72831309) in the TENM2 gene associated with a lower risk of the combined chronic kidney disease (eGFR<60 ml/min per 1.73 m2) and DKD (microalbuminuria or worse) phenotype (p=9.8×10−9; although not withstanding correction for multiple testing, p>9.3×10−9). Gene-level analysis identified ten genes associated with DKD (COL20A1, DCLK1, EIF4E, PTPRN–RESP18, GPR158, INIP–SNX30, LSM14A and MFF; p<2.7×10−6). Integration of GWAS with human glomerular and tubular expression data demonstrated higher tubular AKIRIN2 gene expression in individuals with vs without DKD (p=1.1×10−6). The lead SNPs within six loci significantly altered DNA methylation of a nearby CpG site in kidneys (p<1.5×10−11). Expression of lead genes in kidney tubules or glomeruli correlated with relevant pathological phenotypes (e.g. TENM2 expression correlated positively with eGFR [p=1.6×10−8] and negatively with tubulointerstitial fibrosis [p=2.0×10−9], tubular DCLK1 expression correlated positively with fibrosis [p=7.4×10−16], and SNX30 expression correlated positively with eGFR [p=5.8×10−14] and negatively with fibrosis [p<2.0×10−16]). Conclusions/interpretation: Altogether, the results point to novel genes contributing to the pathogenesis of DKD. Data availability: The GWAS meta-analysis results can be accessed via the type 1 and type 2 diabetes (T1D and T2D, respectively) and Common Metabolic Diseases (CMD) Knowledge Portals, and downloaded on their respective download pages (https://t1d.hugeamp.org/downloads.html; https://t2d.hugeamp.org/downloads.html; https://hugeamp.org/downloads.html). Graphical abstract: [Figure not available: see fulltext.]
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| 9. |
- Sovio, Ulla, et al.
(författare)
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Association between Common Variation at the FTO Locus and Changes in Body Mass Index from Infancy to Late Childhood : The Complex Nature of Genetic Association through Growth and Development
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:2, s. e1001307-
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Tidskriftsartikel (refereegranskat)abstract
- An age-dependent association between variation at the FTO locus and BMI in children has been suggested. We meta-analyzed associations between the FTO locus (rs9939609) and BMI in samples, aged from early infancy to 13 years, from 8 cohorts of European ancestry. We found a positive association between additional minor (A) alleles and BMI from 5.5 years onwards, but an inverse association below age 2.5 years. Modelling median BMI curves for each genotype using the LMS method, we found that carriers of minor alleles showed lower BMI in infancy, earlier adiposity rebound (AR), and higher BMI later in childhood. Differences by allele were consistent with two independent processes: earlier AR equivalent to accelerating developmental age by 2.37% (95% CI 1.87, 2.87, p = 10−20) per A allele and a positive age by genotype interaction such that BMI increased faster with age (p = 10−23). We also fitted a linear mixed effects model to relate genotype to the BMI curve inflection points adiposity peak (AP) in infancy and AR. Carriage of two minor alleles at rs9939609 was associated with lower BMI at AP (−0.40% (95% CI: −0.74, −0.06), p = 0.02), higher BMI at AR (0.93% (95% CI: 0.22, 1.64), p = 0.01), and earlier AR (−4.72% (−5.81, −3.63), p = 10−17), supporting cross-sectional results. Overall, we confirm the expected association between variation at rs9939609 and BMI in childhood, but only after an inverse association between the same variant and BMI in infancy. Patterns are consistent with a shift on the developmental scale, which is reflected in association with the timing of AR rather than just a global increase in BMI. Results provide important information about longitudinal gene effects and about the role of FTO in adiposity. The associated shifts in developmental timing have clinical importance with respect to known relationships between AR and both later-life BMI and metabolic disease risk.
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| 10. |
- Spiryagin, Maksym, et al.
(författare)
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Influence of AC system design on the realisation of tractive efforts by high adhesion locomotives
- 2017
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Ingår i: Vehicle System Dynamics. - : TAYLOR & FRANCIS LTD. - 0042-3114 .- 1744-5159. ; 55:8, s. 1241-1264
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Tidskriftsartikel (refereegranskat)abstract
- The main task for heavy haul railway operators is to reduce the cost of exported minerals and enhance the long-term viability of rail transport operations through increasing productivity by running longer and heavier trains. The common opinion is that this is achievable by means of implementation of high adhesion locomotives with advanced AC traction technologies. Modern AC high adhesion locomotives are very complex mechatronic systems and can be designed with two alternative traction topologies of either bogie or individual axle controls. This paper describes a modelling approach for these two types of AC traction systems with the application of an advanced co-simulation methodology, where an electrical system and a traction algorithm are modelled in Matlab/Simulink, and a mechanical system is modelled in a multibody software package. Although the paper concentrates on the analysis of the functioning for these two types of traction control systems, the choice of reference slip values also has an influence on the performance of both systems. All these design variations and issues have been simulated for various adhesion conditions at the wheel-rail interface and their influence on the high traction performance of a locomotive equipped with two three-axle bogies has been discussed.
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| 11. |
- Wu, Qing, et al.
(författare)
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Heavy haul rail/wheel wear and RCF assessments using 3D train models and a new wear map
- 2024
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Ingår i: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 538-539
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Tidskriftsartikel (refereegranskat)abstract
- Wear and Rolling Contact Fatigue (RCF) on wheels and rails are influenced by relative motions between the studied rail and wheel pair, and therefore influenced by train dynamics. Wear and RCF assessments using a train dynamics approach provide more accurate and comprehensive results comparing with conventional assessments that often do not consider train dynamics. In addition, considering material property differences, currently available rail wear maps are not able to accurately describe the wear performance of materials that have significantly different properties. This paper presented a method for rail/wheel wear and RCF assessments using 3D train dynamics models. The use of train models allows the consideration of coupler forces, traction, and brakes during the assessment. Wear assessments were conducted by using an in-house rail wear map model developed from the twin disc wear machine at the Centre for Railway Engineering (CRE). The new rail wear map was developed by using the AS 60 rail material (hardness 340 HB). The results indicated that the methods proposed in this paper could be used for rail/wheel wear and RCF assessments. Traction/braking forces and coupler lateral forces had evident influences on wear and RCF assessment. Different wear maps were also shown to have significant influences on the wear rate results.
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| 12. |
- Wu, Qing, et al.
(författare)
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RAIL/WHEEL WEAR AND RCF ASSESSMENTS USING 3D TRAIN MODELS AND A NEW WEAR MAP
- 2022
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Ingår i: CM 2022. - : International Conference on Contact Mechanics of Wheel / Rail Systems. ; , s. 217-222
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Konferensbidrag (refereegranskat)abstract
- Wear and Rolling Contact Fatigue (RCF) on wheels and rails are influenced by relative motions between the studied rail and wheel pair, and therefore influenced by train dynamics as well. Wear and RCF assessments by suing train dynamics provide more accurate and comprehensive results. In addition, considering material property differences, previous rail wear maps may not be able to accurately describe the wear performance of materials that have significantly different properties. This paper presents a method for rail/wheel wear and RCF assessments using 3D train dynamics models. The use of train models allows the consideration of coupler forces, traction, and brakes during the assessment. Wear assessments were conducted by using an in-house rail wear map model developed for a twin disc wear machine at the Centre for Railway Engineering (CRE). The new rail wear map was developed by using the AS 60 rail material. Results show that the older BS11 rail material wear rate regimes and transitions are evidently different to the wear behaviour measured for AS60 rail material.
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