| 1. |
- Zhou, Wei, et al.
(författare)
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Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
- 2022
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Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
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| 2. |
- Allahvirdizadeh, Reza
(författare)
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Reliability-Based Assessment and Optimization of High-Speed Railway Bridges
- 2021
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Increasing the operational speed of trains has attracted a lot of interest in the last decades and has brought new challenges, especially in terms of infrastructure design methodology, as it may induce excessive vibrations. Such demands can damage bridges, which in turn increases maintenance costs, endangers the safety of passing trains and disrupts passenger comfort. Conventional design provisions should therefore be evaluated in the light of modern concerns; nevertheless, several previous studies have highlighted some of their shortcomings. It should be emphasized that most of these studies have neglected the uncertainties involved, which preventsthe reported results from representing a complete picture of the problem. In this respect, the present thesis is dedicated to evaluating the performance of conventional design methods, especially those related to running safety and passenger comfort, using probabilistic approaches. To achieve this objective, a preliminary study was carried out using the first-order reliability method for short/medium span bridges passed by trains at a wide range of operating speeds. Comparison of these results with the corresponding deterministic responses showed that applying a constant safety factor to the running safety threshold does not guarantee that the safety index will be identical for all bridges. It also shows that the conventional design approaches result in failure probabilities that are higher than the target values. This conclusion highlights the need to update the design methodology for running safety. However, it would be essential to determine whether running safety is the predominant design criterion before conducting further analysis. Therefore, a stochastic comparison between this criterion and passenger comfort was performed. Due to the significant computational cost of such investigations, subset simulation and crude Monte-Carlo (MC) simulation using meta-models based on polynomial chaos expansion were employed. Both methods were found to perform well, with running safety almost always dominating the passenger comfort limit state. Subsequently, classification-based meta-models, e.g. support vector machines, k-nearest neighbours and decision trees, were combined using ensemble techniques to investigate the influence of soil-structure interaction on the evaluated reliability of running safety. The obtained results showed a significant influence, highlighting the need for detailed investigations in further studies. Finally, a reliability-based design optimization was conducted to update the conventional design method of running safety by proposing minimum requirements for the mass per length and moment of inertia of bridges. It is worth mentioning that the inner loop of the method was solved by a crude MC simulation using adaptively trained Kriging meta-models.
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| 3. |
- Bismut, Elizabeth, et al.
(författare)
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Optimal adaptive decision rules in geotechnical construction considering uncertainty
- 2023
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Ingår i: Geotechnique. - : Emerald. - 0016-8505 .- 1751-7656.
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Tidskriftsartikel (refereegranskat)abstract
- To optimally design a geotechnical engineering structure, an iterative decision-making process is required due to the prevailing uncertainty of the ground conditions. At present, these decisions are taken based on simple deterministic rules and models. This paper proposes a risk-based decision-theoretic framework to the optimal planning for geotechnical construction. This framework combines geotechnical probabilistic models, cost analysis using Monte Carlo simulation and the observational method. The framework is illustrated on the design of the surcharge for an embankment on soft soil, whereby the optimal preloading sequence of added surcharge is adapted to the observed settlement. The approach balances the cost of surcharge material against financial penalties related to project delays and insufficient overconsolidation, which causes damage due to residual settlement. The result is a preloading strategy that optimally accounts for information obtained from settlement measurements under uncertain ground conditions. The findings highlight the potential of using risk-based decision planning in geotechnical engineering, in particular in combination with the observational method. For the investigated case-study, we observe a reduction in the expected cost in the order of 25%.
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| 4. |
- Botterweg-Paredes, Esther, et al.
(författare)
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Light affects tissue patterning of the hypocotyl in the shade-avoidance response
- 2020
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Plants have evolved strategies to avoid shade and optimize the capture of sunlight. While some species are tolerant to shade, plants such as Arabidopsis thaliana are shade-intolerant and induce elongation of their hypocotyl to outcompete neighboring plants. We report the identification of a developmental module acting downstream of shade perception controlling vascular patterning. We show that Arabidopsis plants react to shade by increasing the number and types of water-conducting tracheary elements in the vascular cylinder to maintain vascular density constant. Mutations in genes affecting vascular patterning impair the production of additional xylem and also show defects in the shade-induced hypocotyl elongation response. Comparative analysis of the shade-induced transcriptomes revealed differences between wild type and vascular patterning mutants and it appears that the latter mutants fail to induce sets of genes encoding biosynthetic and cell wall modifying enzymes. Our results thus set the stage for a deeper understanding of how growth and patterning are coordinated in a dynamic environment.
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| 5. |
- Cotoarbă, Dafydd, et al.
(författare)
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Data-driven uncertainty reduction in geotechnical engineering : Optimal preloading of a road embankment
- 2023
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Ingår i: 14th International Conference on Applications of Statistics and Probability in Civil Engineering (ICASP14).
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Konferensbidrag (refereegranskat)abstract
- Decision making in geotechnical engineering is characterized by considerable uncertainty. To find optimal solutions in such an environment, an iterative decision-making process, which includes new information as it becomes available, is required. In this contribution we extend the risk-based framework of Bismut et al. (2023) for optimal planning of a geotechnical construction to include predictions, which are based on a linear regression analysis of monitoring data. This approach is illustrated for the design of a surcharge on an embankment in clayey soil, as the optimal preloading sequence is searched. We demonstrate that by increasing the amount of information considered more cost efficient strategies can be identified and outcome uncertainties can be reduced.
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| 6. |
- Koenig, Julian, et al.
(författare)
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Cortical thickness and resting-state cardiac function across the lifespan : A cross-sectional pooled mega-analysis
- 2021
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Ingår i: Psychophysiology. - : Wiley. - 0048-5772 .- 1469-8986 .- 1540-5958. ; 58:7
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12–87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS—or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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| 7. |
- Lo Faro, Valeria, Postdoc, et al.
(författare)
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Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation
- 2024
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Ingår i: Cell Reports Medicine. - : Elsevier. - 2666-3791. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Primary open -angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta -analysis across 15 biobanks (of the Global Biobank Meta -analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multiancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene -enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related. We perform an extensive statistical analysis of SIX6 and CDKN2B-AS1 loci in human GTEx data and across large electronic health records showing interaction between SIX6 gene and causal variants in the chr9p21.3 locus, with expression effect on CDKN2A/B. Our results suggest that some POAG risk variants may be ancestry specific, sex specific, or both, and support the contribution of genes involved in programmed cell death in POAG pathogenesis.
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| 8. |
- Lu, Lu, et al.
(författare)
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Rhamnolipid Biosurfactants Enhance Microbial Oil Biodegradation in Surface Seawater from the North Sea
- 2023
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Ingår i: ACS - ES & T Water. - : American Chemical Society (ACS). - 2690-0637. ; 3:8, s. 2255-2266
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Tidskriftsartikel (refereegranskat)abstract
- This study provides strong evidence thatthe biosurfactantrhamnolipid is more efficient than the widely used chemical dispersantsCorexit 9500 and Slickgone NS in stimulating oil biodegradation innatural seawater. Biosurfactants arepromising alternatives to chemical dispersantsfor combating marine oil spills; however, the impacts of biosurfactantson microbial community composition and oil biodegradation activitiesremain largely unknown. Here, we conducted a time-course microcosmexperiment mimicking oil spill scenarios with surface seawater fromthe North Sea, amended with either the biosurfactant rhamnolipid ora dispersant (Corexit 9500 or Slickgone NS). Radioactive tracer assaysto track hexadecane and naphthalene oxidation as well as bacterialproduction revealed the highest hydrocarbon oxidation rates and generalmicrobial activities in the rhamnolipid-amended oil microcosms, followedby oil microcosms with Slickgone and Corexit. Impacts on the microbialcommunity composition differed among treatments, and growth of oil-degrading Colwellia was stimulated remarkably in Corexit-amended oiland oil-only microcosms, while potential oil-degrading Oleispira were highly enriched in the presence of oil in combination withrhamnolipid or Slickgone. Furthermore, increased abundances of Colwellia and Oleispira, and stimulatedbacterial production in microcosms with only rhamnolipid, Corexit,or Slickgone, indicated their involvement in biosurfactant/dispersantbiodegradation. Our findings highlight varying microbial impacts resultingfrom rhamnolipid and chemical dispersants and suggest great promisefor the application of biosurfactants in future marine oil spills.
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| 9. |
- Maljaars, Johan, et al.
(författare)
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Models and methods for probabilistic safety assessment of steel structures subject to fatigue
- 2024
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Ingår i: Structural Safety. - : Elsevier BV. - 0167-4730 .- 1879-3355. ; , s. 102446-102446
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Tidskriftsartikel (refereegranskat)abstract
- We review of the state of the art in probabilistic modelling for fatigue reliability of civil engineering and offshore structures. The modeling of randomness and uncertainty in fatigue resistance and fatigue load variables are presented in some detail. This is followed by a review of the specifics of reliability analysis for fatigue limit states and a background on the semi-probabilistic treatment of fatigue safety. We discuss the different life-cycle reliability concepts and give an overview on probabilistic inspection planning. We describe the choices made in the Probabilistic Model Code of the Joint Committee of Structural Safety, present alternatives to these choices and suggest areas of future research.
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| 10. |
- Spross, Johan, 1986-
(författare)
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Beslutsteori i geotekniken : Förstudie
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Byggande av geotekniska konstruktioner innebär ofta stora investeringar av samhällets resurser, ofta i form av skattemedel. Myndigheter som bygger och förvaltar stora geotekniska anläggningar har därför ett ansvar att fatta genomtänkta beslut avseende utformning, byggande och förvaltning. Med ett riskbaserat beslutsfattande kan kostnaderna över tid minimeras. I praktiken kräver detta att man kan ta fram modeller dels för sannolikheten för olika framtida scenarier, dels för de kostnader som de olika scenarierna medför. Detta blir ofta avancerade beslutsteoretiska problem, vars lösning dock sällan studerats inom geotekniken.Denna förstudie syftar till att undersöka potentialen i bayesiansk beslutsteori för att lösa praktiska geotekniska dimensioneringsfrågor. Förstudien ger dels en översikt över hur bayesiansk beslutsteori principiellt kan tillämpas på geoteknisk dimensionering, dels ett omfattande praktiskt beräkningsexempel för optimeringen av en överlast för en bank på lera. Författarnas bedömning är att den beslutsteoretiska analysmetoden som användes i exemplet är generellt tillämpbar på liknande problem där många beslut fattas i sekvens, givet att det finns en probabilistisk modell av den geotekniska konstruktionen. Slutligen noteras att det inte föreligger något större behov av att utveckla själva de beslutsteoretiska modellerna. Forskningsarbetet bör därför framöver riktas mot att försöka beskriva vanligen förekommande geotekniska frågeställningar som beslutsteoretiska problem och därefter utveckla probabilistiska geotekniska modeller som möjliggör deras lösning.
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