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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Mullins, Niamh, et al.
(författare)
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GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
- 2019
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 176:8, s. 651-660
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Tidskriftsartikel (refereegranskat)abstract
- Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.
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| 3. |
- Pascal, Mathilde M.V., et al.
(författare)
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DOLORisk : Study protocol for a multi-centre observational study to understand the risk factors and determinants of neuropathic pain [version 2; referees: 2 approved]
- 2019
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Ingår i: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuropathic pain is an increasingly prevalent condition and has a major impact on health and quality of life. However, the risk factors for the development and maintenance of neuropathic pain are poorly understood. Clinical, genetic and psychosocial factors all contribute to chronic pain, but their interactions have not been studied in large cohorts. The DOLORisk study aims to study these factors. Protocol: Multicentre cross-sectional and longitudinal cohorts covering the main causes leading to neuropathic pain (e.g. diabetes, surgery, chemotherapy, traumatic injury), as well as rare conditions, follow a common protocol for phenotyping of the participants. This core protocol correlates answers given by the participants on a set of questionnaires with the results of protocol for phenotyping of the participants. This core protocol correlates answers given by the participants on a set of questionnaires with the results of their genetic analyses. A smaller number of participants undergo deeper phenotyping procedures, including neurological examination, nerve conduction studies, threshold tracking, quantitative sensory testing, conditioned pain modulation and electroencephalography. Ethics and dissemination: All studies have been approved by their regional ethics committees as required by national law. Results are disseminated through the DOLORisk website, scientific meetings, open-access publications, and in partnership with patient organisations. Strengths and limitations: • Large cohorts covering many possible triggers for neuropathic pain • Multi-disciplinary approach to study the interaction of clinical, psychosocial and genetic risk factors • High comparability of the data across centres thanks to harmonised protocols • One limitation is that the length of the questionnaires might reduce the response rate and quality of responses of participants.
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| 4. |
- Bansal, A., et al.
(författare)
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Pion-less effective field theory for atomic nuclei and lattice nuclei
- 2018
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Ingår i: Physical Review C. - 2469-9993 .- 2469-9985. ; 98:5
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Tidskriftsartikel (refereegranskat)abstract
- We compute the medium-mass nuclei 16O and 40Ca using pion-less effective field theory (EFT) at next-to-leading order (NLO). The low-energy coefficients of the EFT Hamiltonian are adjusted to experimental data for nuclei with mass numbers A=2 and 3, or alternatively to results from lattice quantum chromodynamics at an unphysical pion mass of 806 MeV. The EFT is implemented through a discrete variable representation in the harmonic oscillator basis. This approach ensures rapid convergence with respect to the size of the model space and facilitates the computation of medium-mass nuclei. At NLO the nuclei 16O and 40Ca are bound with respect to decay into alpha particles. Binding energies per nucleon are 9–10 MeV and 21–40 MeV at pion masses of 140 and 806 MeV, respectively.
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| 5. |
- Binder, Christian, 1988-, et al.
(författare)
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Experimental Determination of the Heat Transfer Coefficient in Piston Cooling Galleries
- 2018
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Ingår i: SAE Technical Papers. - Heidelberg, Germanay : SAE International. - 0148-7191.
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Tidskriftsartikel (refereegranskat)abstract
- Piston cooling galleries are critical for the pistons’ capability to handle increasing power density while maintaining the same level of durability. However, piston cooling also accounts for a considerable amount of heat rejection and parasitic losses. Knowing the distribution of the heat transfer coefficient (HTC) inside the cooling gallery could enable new designs which ensure effective cooling of areas decisive for durability while minimizing parasitic losses and overall heat rejection. In this study, an inverse heat transfer method is presented to determine the spatial HTC distribution inside the cooling gallery based on surface temperature measurements with an infrared (IR) camera. The method utilizes a piston specially machined so it only has a thin sheet of material of a known thickness left between the cooling gallery and the piston bowl. The piston - initially at room temperature - is heated up with warm oil injected into the cooling gallery. The transient of the piston’s outer surface temperature is captured with an IR camera from the top. Combining the temperature transient of each pixel, the HTC is later obtained through an inverse heat transfer solver based on one-dimensional heat conduction inside the piston material. To the authors’ knowledge, the current study presents the first application of an inverse heat transfer method for spatially resolved and experimentally determined heat transfer coefficients inside a piston cooling gallery. Preliminary measurements at standstill to demonstrate the method display an area of increased heat transfer where the entering oil jet impinges onto the wall of the cooling gallery.
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| 6. |
- Binder, Christian, 1988-
(författare)
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Experiments on Heat Transfer During Diesel Combustion Using Optical Methods
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Transportation is a crucial part of modern societies. This includes their economies. Trade and the transportation of goods have a great influence on prosperity. Nevertheless, the transportation sector with road transport in particular is heavily dependent on fossil fuels and emits a significant amount of greenhouse gases. One approach to mitigate the negative environmental impact of road transport is to increase the efficiency of its most common propulsion system, that is the internal combustion engine. Due to its dominant role in the road freight transportation sector, this thesis directs its attention to heavy-duty diesel engines. In-cylinder heat losses are one of the main factors that reduce engine efficiency. Therefore, the objective of this thesis is to gain a better understanding of the processes that influence in-cylinder heat losses by resolving them in time and space using optical methods. In diesel engines, most of the in-cylinder heat losses are transferred to the piston. As a result, this thesis focuses specifically on that component.In this research project, the task to determine in-cylinder heat losses to the piston in heavy-duty diesel engines is divided into two parts. The most important part consists of fast surface temperature measurements on the piston using phosphor thermometry. The heat transfer coefficient inside the piston cooling gallery defines an additional steady-state boundary condition.The work presented in this thesis includes therefore efforts to improve in-cylinder surface temperature measurements and an assessment of their accuracy and precision. Furthermore, it comprises of experimental results from measurements on steel pistons and a piston with an insulating thermal barrier coating. Results reveal spatial differences of the heat transfer during diesel combustion. Measurements at the impingement point indicate a strong influence of flame impingement on local heat transfer. A correlation is detected between heat transfer and cycle-to-cycle variations of flame impingement.The thesis also reports efforts to determine the heat transfer coefficient inside the piston cooling gallery. Using an infrared camera a method is presented to spatially resolve convective heat transfer inside this cooling channel.
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| 7. |
- Binder, Christian, 1988-, et al.
(författare)
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Heat Loss Analysis of a Steel Piston and a YSZ Coated Piston in a Heavy-Duty Diesel Engine Using Phosphor Thermometry Measurements
- 2017
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Ingår i: SAE International Journal of Engines. - : SAE International. - 1946-3936 .- 1946-3944. ; 10:4, s. 1954-1968
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Tidskriftsartikel (refereegranskat)abstract
- Diesel engine manufacturers strive towards further efficiency improvements. Thus, reducing in-cylinder heat losses is becoming increasingly important. Understanding how location, thermal insulation, and engine operating conditions affect the heattransfer to the combustion chamber walls is fundamental for the future reduction of in-cylinder heat losses. This study investigates the effect of a 1mm-thick plasma-sprayed yttria-stabilized zirconia (YSZ) coating on a piston. Such a coated piston and a similar steel piston are compared to each other based on experimental data for the heat release, the heat transfer rate to the oil in the piston cooling gallery, the local instantaneous surface temperature, and the local instantaneous surface heat flux. The surface temperature was measured for different crank angle positions using phosphor thermometry. The fuel was chosen to be n-heptane to facilitate surface temperature measurements during non-skip-fire, thermally stabilized operating conditions. Assuming one-dimensional heat transfer inside each piston, the local instantaneous surface heat flux was calculated using the heat transfer rate to the oil in the piston cooling gallery and the surface temperature measurements. The results from this study show that the surface temperature variation is similar for both pistons. The instantaneous heat flux during combustion is however significantly greater for the steel piston than the coated piston. The heat release analysis also indicates that combustion is slower for the piston with the yttria-stabilized zirconia coating.
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| 8. |
- de Vries, Paul S., et al.
(författare)
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Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5x10(-8) is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5x10(-8)), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.
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| 9. |
- Farinotti, Daniel, et al.
(författare)
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How accurate are estimates of glacier ice thickness? Results from ITMIX, the Ice Thickness Models Intercomparison eXperiment
- 2017
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Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 11, s. 949-970
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of the ice thickness distribution of glaciers and ice caps is an important prerequisite for many glaciological and hydrological investigations. A wealth of approaches has recently been presented for inferring ice thickness from characteristics of the surface. With the Ice Thickness Models Intercomparison eXperiment (ITMIX) we performed the first coordinated assessment quantifying individual model performance. A set of 17 different models showed that individual ice thickness estimates can differ considerably – locally by a spread comparable to the observed thickness. Averaging the results of multiple models, however, significantly improved the results: on average over the 21 considered test cases, comparison against direct ice thickness measurements revealed deviations on the order of 10 ± 24 % of the mean ice thickness (1σ estimate). Models relying on multiple data sets – such as surface ice velocity fields, surface mass balance, or rates of ice thickness change – showed high sensitivity to input data quality. Together with the requirement of being able to handle large regions in an automated fashion, the capacity of better accounting for uncertainties in the input data will be a key for an improved next generation of ice thickness estimation approaches.
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| 10. |
- Längin, Matthias, et al.
(författare)
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Consistent success in life-supporting porcine cardiac xenotransplantation
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 564:7736, s. 430-433
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Tidskriftsartikel (refereegranskat)abstract
- Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1–3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.
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