| 1. |
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| 2. |
- Bouyoucef, S E, et al.
(författare)
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Poster Session 2 : Monday 4 May 2015, 08
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
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| 5. |
- Porcu, E, et al.
(författare)
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Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3300-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs, indicating their potential involvement in regulation of gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and multiple gene expression traits as exposures, simultaneously. Applied to 43 human phenotypes, it uncovers 3,913 putatively causal gene–trait associations, 36% of which have no genome-wide significant SNP nearby in previous GWAS. Using independent association summary statistics, we find that the majority of these loci were missed by GWAS due to power issues. Noteworthy among these links is educational attainment-associated BSCL2, known to carry mutations leading to a Mendelian form of encephalopathy. We also find pleiotropic causal effects suggestive of mechanistic connections. TWMR better accounts for pleiotropy and has the potential to identify biological mechanisms underlying complex traits.
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| 6. |
- Ferreira, Mjv, et al.
(författare)
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Poster Session 3 : Tuesday 5 May 2015, 08
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Arias, M., et al.
(författare)
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Low-frequency radio absorption in Cassiopeia A
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
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Tidskriftsartikel (refereegranskat)abstract
- Context. Cassiopeia A is one of the best-studied supernova remnants. Its bright radio and X-ray emission is due to shocked ejecta. Cas A is rather unique in that the unshocked ejecta can also be studied: through emission in the infrared, the radio-active decay of Ti-44, and the low-frequency free-free absorption caused by cold ionised gas, which is the topic of this paper. Aims. Free-free absorption processes are affected by the mass, geometry, temperature, and ionisation conditions in the absorbing gas. Observations at the lowest radio frequencies can constrain a combination of these properties. Methods. We used Low Frequency Array (LOFAR) Low Band Antenna observations at 30-77 MHz and Very Large Array (VLA) L-band observations at 1-2 GHz to fit for internal absorption as parametrised by the emission measure. We simultaneously fit multiple UV-matched images with a common resolution of 17 '' (this corresponds to 0.25 pc for a source at the distance of Cas A). The ample frequency coverage allows us separate the relative contributions from the absorbing gas, the unabsorbed front of the shell, and the absorbed back of the shell to the emission spectrum. We explored the effects that a temperature lower than the similar to 100-500 K proposed from infrared observations and a high degree of clumping can have on the derived physical properties of the unshocked material, such as its mass and density. We also compiled integrated radio flux density measurements, fit for the absorption processes that occur in the radio band, and considered their effect on the secular decline of the source. Results. We find a mass in the unshocked ejecta of M = 2.95 +/- 0.48 M-circle dot for an assumed gas temperature of T = 100 K. This estimate is reduced for colder gas temperatures and, most significantly, if the ejecta are clumped. We measure the reverse shock to have a radius of 114 '' +/- 6 '' and be centred at 23:23:26, +58:48:54 (J2000). We also find that a decrease in the amount of mass in the unshocked ejecta (as more and more material meets the reverse shock and heats up) cannot account for the observed low-frequency behaviour of the secular decline rate. Conclusions. To reconcile our low-frequency absorption measurements with models that reproduce much of the observed behaviour in Cas A and predict little mass in the unshocked ejecta, the ejecta need to be very clumped or the temperature in the cold gas needs to be low (similar to 10 K). Both of these options are plausible and can together contribute to the high absorption value that we find.
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| 8. |
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| 9. |
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| 11. |
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| 12. |
- Valentim, Felipe Leal, et al.
(författare)
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A Quantitative and Dynamic Model of the Arabidopsis Flowering Time Gene Regulatory Network
- 2015
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Various environmental signals integrate into a network of floral regulatory genes leading to the final decision on when to flower. Although a wealth of qualitative knowledge is available on how flowering time genes regulate each other, only a few studies incorporated this knowledge into predictive models. Such models are invaluable as they enable to investigate how various types of inputs are combined to give a quantitative readout. To investigate the effect of gene expression disturbances on flowering time, we developed a dynamic model for the regulation of flowering time in Arabidopsis thaliana. Model parameters were estimated based on expression time-courses for relevant genes, and a consistent set of flowering times for plants of various genetic backgrounds. Validation was performed by predicting changes in expression level in mutant backgrounds and comparing these predictions with independent expression data, and by comparison of predicted and experimental flowering times for several double mutants. Remarkably, the model predicts that a disturbance in a particular gene has not necessarily the largest impact on directly connected genes. For example, the model predicts that SUPPRESSOR OF OVEREXPRESSION OF CONSTANS (SOC1) mutation has a larger impact on APETALA1 (AP1), which is not directly regulated by SOC1, compared to its effect on LEAFY (LFY) which is under direct control of SOC1. This was confirmed by expression data. Another model prediction involves the importance of cooperativity in the regulation of APETALA1 (AP1) by LFY, a prediction supported by experimental evidence. Concluding, our model for flowering time gene regulation enables to address how different quantitative inputs are combined into one quantitative output, flowering time.
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| 13. |
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| 14. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 15. |
- dos Remedios, C. G., et al.
(författare)
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The Sydney Heart Bank : improving translational research while eliminating or reducing the use of animal models of human heart disease
- 2017
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Ingår i: Biophysical Reviews. - : Springer Nature. - 1867-2450 .- 1867-2469. ; 9:4, s. 431-441
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Tidskriftsartikel (refereegranskat)abstract
- The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5–10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy organ donors whose hearts, for a variety of reasons (mainly tissue-type incompatibility with waiting heart transplant recipients), could not be used for transplantation. Donor hearts were collected by the St Vincent’s Hospital Heart and Lung transplantation team from local hospitals or within a 4-h jet flight from Sydney. They were flushed with chilled cardioplegic solution and transported to Sydney where they were quickly cryopreserved in small samples. Failing and/or donor samples have been used by more than 60 research teams around the world, and have resulted in more than 100 research papers. The tissues most commonly requested are from donor left ventricles, but right ventricles, atria, interventricular system, and coronary arteries vessels have also been reported. All tissues are stored for long-term use in liquid N or vapor (170–180 °C), and are shipped under nitrogen vapor to avoid degradation of sensitive molecules such as RNAs and giant proteins. We present evidence that the availability of these human heart samples has contributed to a reduction in the use of animal models of human heart failure.
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| 16. |
- Farzan, N, et al.
(författare)
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Rationale and design of the multiethnic Pharmacogenomics in Childhood Asthma consortium
- 2017
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Ingår i: Pharmacogenomics. - : Future Medicine Ltd. - 1744-8042 .- 1462-2416. ; 18:10, s. 931-943
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Tidskriftsartikel (refereegranskat)abstract
- Aim: International collaboration is needed to enable large-scale pharmacogenomics studies in childhood asthma. Here, we describe the design of the Pharmacogenomics in Childhood Asthma (PiCA) consortium. Materials & methods: Investigators of each study participating in PiCA provided data on the study characteristics by answering an online questionnaire. Results: A total of 21 studies, including 14,227 children/young persons (58% male), from 12 different countries are currently enrolled in the PiCA consortium. Fifty six percent of the patients are Caucasians. In total, 7619 were inhaled corticosteroid users. Among patients from 13 studies with available data on asthma exacerbations, a third reported exacerbations despite inhaled corticosteroid use. In the future pharmacogenomics studies within the consortium, the pharmacogenomics analyses will be performed separately in each center and the results will be meta-analyzed. Conclusion: PiCA is a valuable platform to perform pharmacogenetics studies within a multiethnic pediatric asthma population.
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| 17. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 18. |
- Loeffen, Erik A. H., et al.
(författare)
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Reducing pain in children with cancer : Methodology for the development of a clinical practice guideline
- 2019
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 66:6
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Tidskriftsartikel (refereegranskat)abstract
- Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand.
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| 19. |
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| 20. |
- Van Dijk, H. A. J., et al.
(författare)
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Cost Effective CO2 Reduction in the Iron & Steel Industry by Means of the SEWGS Technology : STEPWISE Project
- 2017
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Ingår i: Energy Procedia. - : Elsevier BV. - 1876-6102. ; , s. 6256-6265
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Konferensbidrag (refereegranskat)abstract
- In the STEPWISE project, the Sorption Enhanced Water-Gas Shift (SEWGS) technology for CO2 capture is brought to TRL6 by means of design, construction, operation and modelling a pilot installation in the Iron and Steel industry using Blast Furnace Gas (BFG). This advanced CO2 removal technology makes use of regenerative solid adsorbents. The STEPWISE project represents the essential demonstration step within the research, development and demonstration trajectory of the SEWGS technology. This project will further reduce the risks associated with scaling up the process.
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| 21. |
- van Dijk, P. A. D., et al.
(författare)
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Post-treatment Follow-up, Imaging, and Outcome Scores: Proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle
- 2018
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Ingår i: Foot & Ankle International. - : SAGE Publications. - 1071-1007 .- 1944-7876. ; 39:S1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The evidence supporting best practice guidelines in the field of cartilage repair of the ankle are based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on Post-treatment Follow-up, Imaging and Outcome Scores developed at the 2017 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Seventy-five international experts in cartilage repair of the ankle representing 25 countries and 1 territory were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within 11 working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterized as follows: consensus, 51% to 74%; strong consensus, 75% to 99%; unanimous, 100%. Results: A total of 12 statements on Post-treatment Follow-up, Imaging, and Outcome Scores reached consensus during the 2017 International Consensus Meeting on Cartilage Repair of the Ankle. All 12 statements reached strong consensus (greater than 75% agreement). Conclusions: This international consensus derived from leaders in the field will assist clinicians with post-treatment follow-up, imaging, and outcome scores after management of a cartilage injury of the ankle in the general population. Moreover, healing, rehabilitation, and final outcomes can be optimized for the individual patient.
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| 22. |
- Bouter, K. E. C., et al.
(författare)
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Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects article
- 2018
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Ingår i: Clinical and Translational Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 2155-384X. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gut microbiota-derived short-chain fatty acids (SCFAs) have been associated with beneficial metabolic effects. However, the direct effect of oral butyrate on metabolic parameters in humans has never been studied. In this first in men pilot study, we thus treated both lean and metabolic syndrome male subjects with oral sodium butyrate and investigated the effect on metabolism. Methods: Healthy lean males (n = 9) and metabolic syndrome males (n = 10) were treated with oral 4 g of sodium butyrate daily for 4 weeks. Before and after treatment, insulin sensitivity was determined by a two-step hyperinsulinemic euglycemic clamp using [6,6-2H2]-glucose. Brown adipose tissue (BAT) uptake of glucose was visualized using 18F-FDG PET-CT. Fecal SCFA and bile acid concentrations as well as microbiota composition were determined before and after treatment. Results: Oral butyrate had no effect on plasma and fecal butyrate levels after treatment, but did alter other SCFAs in both plasma and feces. Moreover, only in healthy lean subjects a significant improvement was observed in both peripheral (median Rd: from 71 to 82 μmol/kg min, p < 0.05) and hepatic insulin sensitivity (EGP suppression from 75 to 82% p < 0.05). Although BAT activity was significantly higher at baseline in lean (SUVmax: 12.4 ± 1.8) compared with metabolic syndrome subjects (SUVmax: 0.3 ± 0.8, p < 0.01), no significant effect following butyrate treatment on BAT was observed in either group (SUVmax lean to 13.3 ± 2.4 versus metabolic syndrome subjects to 1.2 ± 4.1). Conclusions: Oral butyrate treatment beneficially affects glucose metabolism in lean but not metabolic syndrome subjects, presumably due to an altered SCFA handling in insulin-resistant subjects. Although preliminary, these first in men findings argue against oral butyrate supplementation as treatment for glucose regulation in human subjects with type 2 diabetes mellitus. © 2018 The Author(s).
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| 23. |
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| 24. |
- Dijk, FN, et al.
(författare)
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Genetic regulation of IL1RL1 methylation and IL1RL1-a protein levels in asthma
- 2018
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 51:3
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-1 receptor–like 1 (IL1RL1) is an important asthma gene. (Epi)genetic regulation of IL1RL1 protein expression has not been established. We assessed the association between IL1RL1 single nucleotide polymorphisms (SNPs), IL1RL1 methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma.Associations of IL1RL1 SNPs with asthma were determined in the Dutch Asthma Genome-wide Association Study cohort and three European birth cohorts, BAMSE (Children/Barn, Allergy, Milieu, Stockholm, an Epidemiological survey), INMA (Infancia y Medio Ambiente) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy), participating in the Mechanisms of the Development of Allergy study. We performed blood DNA IL1RL1 methylation quantitative trait locus (QTL) analysis (n=496) and (epi)genome-wide protein QTL analysis on serum IL1RL1-a levels (n=1462). We investigated the association of IL1RL1 CpG methylation with asthma (n=632) and IL1RL1-a levels (n=548), with subsequent causal inference testing. Finally, we determined the association of IL1RL1-a levels with asthma and its clinical characteristics (n=1101).IL1RL1 asthma-risk SNPs strongly associated with IL1RL1 methylation (rs1420101; p=3.7×10−16) and serum IL1RL1-a levels (p=2.8×10−56). IL1RL1 methylation was not associated with asthma or IL1RL1-a levels. IL1RL1-a levels negatively correlated with blood eosinophil counts, whereas there was no association between IL1RL1-a levels and asthma.In conclusion, asthma-associated IL1RL1 SNPs strongly regulate IL1RL1 methylation and serum IL1RL1-a levels, yet neither these IL1RL1-methylation CpG sites nor IL1RL1-a levels are associated with asthma.
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| 25. |
- Dijk, M., et al.
(författare)
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Sustainability assessment as problem structuring: three typical ways
- 2017
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Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4057 .- 1862-4065. ; 12:2, s. 305-317
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Tidskriftsartikel (refereegranskat)abstract
- Sustainability assessment (SA) is an increasingly popular term referring to a broad range of approaches to align decision-making with the principles of sustainability. Nevertheless, in public and private sectors sustainability results are still disappointing, and this paper reflects on this problem and proposes a way forward. We argue that, because sustainability issues are generally wicked problems (i.e. a ‘complex of interconnected factors in a pluralistic context’), effective assessments need to be reflexive about the definition of the issue and about the criteria for sustainable solutions. Based on a distinction of policy problems, we characterize SA as a form of problem structuring, and we distinguish three typical ways of problem structuring, corresponding to three different ways of integrating reflexivity in the assessment. We illustrate these routes in three examples. We discuss the way reflexivity is integrated in each example by discussing the mix of methods, SA process and epistemological balance. Rather than merely calling for more st akeholder participation, our aim is to call for more reflexivity integrated into the SA approach, and we conclude by proposing a process map for reflexive sustainability assessment to support this.
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| 26. |
- Dijk, Wieneke, et al.
(författare)
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ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure
- 2015
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Ingår i: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Brown adipose tissue (BAT) activation via cold exposure is increasingly scrutinized as a potential approach to ameliorate cardio-metabolic risk. Transition to cold temperatures requires changes in the partitioning of energy substrates, re-routing fatty acids to BAT to fuel non-shivering thermogenesis. However, the mechanisms behind the redistribution of energy substrates to BAT remain largely unknown. Angiopoietin-like 4 (ANGPTL4), a protein that inhibits lipoprotein lipase (LPL) activity, is highly expressed in BAT. Here, we demonstrate that ANGPTL4 is part of a shuttling mechanism that directs fatty acids derived from circulating triglyceride-rich lipoproteins to BAT during cold. Specifically, we show that cold markedly down-regulates ANGPTL4 in BAT, likely via activation of AMPK, enhancing LPL activity and uptake of plasma triglyceride-derived fatty acids. In contrast, cold up-regulates ANGPTL4 in WAT, abolishing a cold-induced increase in LPL activity. Together, our data indicate that ANGPTL4 is an important regulator of plasma lipid partitioning during sustained cold.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Jaasma, Philemonne, et al.
(författare)
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The Blue Studio : Designing an Interactive Environmentfor Embodied Multi-Stakeholder Ideation Processes
- 2017
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Ingår i: TEI 2017 - Proceedings of the 11th International Conference on Tangible, Embedded, and Embodied Interaction. - New York, NY, USA : Association for Computing Machinery, Inc. - 9781450346764
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Konferensbidrag (refereegranskat)abstract
- This paper describes the process of designing the Blue Studio: An interactive space for embodied multi-stakeholder ideation processes. Inspired by embodied sensemaking - the way people make sense of things through external expression and interaction with other people - we iteratively designed material, interactive and spatial interventions in the Blue Studio and evaluated them with multi-stakeholder participants in various studies. Thereupon, we analyzed the impact of the design interventions, based on the seven principles to design for embodied sensemaking and highlighted opportunities for refining our interactive space for embodied ideation. Based on the insights gained, a final design of the Blue Studio was realized and evaluated on functionality.
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| 31. |
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| 32. |
- Klein, Alison P., et al.
(författare)
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Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 x 10(-8)). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PAN-DoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 x 10(-14)), rs2941471 at 8q21.11 (HNF4G, P = 6.60 x 10(-10)), rs4795218 at 17q12 (HNF1B, P = 1.32 x 10(-8)), and rs1517037 at 18q21.32 (GRP, P = 3.28 x 10(-8)). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.
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| 33. |
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| 34. |
- Meyer, S, et al.
(författare)
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Somatosensory Impairments in the Upper Limb Poststroke: Distribution and Association With Motor Function and Visuospatial Neglect
- 2016
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Ingår i: Neurorehabilitation and neural repair. - : SAGE Publications. - 1552-6844 .- 1545-9683. ; 30:8, s. 731-742
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Tidskriftsartikel (refereegranskat)abstract
- Background. A thorough understanding of the presence of different upper-limb somatosensory deficits poststroke and the relation with motor performance remains unclear. Additionally, knowledge about the relation between somatosensory deficits and visuospatial neglect is limited. Objective. To investigate the distribution of upper-limb somatosensory impairments and the association with unimanual and bimanual motor outcomes and visuospatial neglect. Methods. A cross-sectional observational study was conducted, including 122 patients within 6 months after stroke (median = 82 days; interquartile range = 57-133 days). Somatosensory measurement included the Erasmus MC modification of the (revised) Nottingham Sensory Assessment (Em-NSA), Perceptual Threshold of Touch (PTT), thumb finding test, 2-point discrimination, and stereognosis subscale of the NSA. Upper-limb motor assessment comprised the Fugl-Meyer assessment, motricity index, Action Research Arm Test, and Adult-Assisting Hand Assessment Stroke. Screening for visuospatial neglect was performed using the Star Cancellation Test. Results. Upper-limb somatosensory impairments were common, with prevalence rates ranging from 21% to 54%. Low to moderate Spearman ρ correlations were found between somatosensory and motor deficits ( r = 0.22-0.61), with the strongest associations for PTT ( r = 0.56-0.61) and stereognosis ( r = 0.51-0.60). Visuospatial neglect was present in 27 patients (22%). Between-group analysis revealed somatosensory deficits that occurred significantly more often and more severely in patients with visuospatial neglect ( P < .05). Results showed consistently stronger correlations between motor and somatosensory deficits in patients with visuospatial neglect ( r = 0.44-0.78) compared with patients without neglect ( r = 0.08-0.59). Conclusions. Somatosensory impairments are common in subacute patients poststroke and are related to motor outcome. Visuospatial neglect was associated with more severe upper-limb somatosensory impairments.
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| 35. |
- Miao, X. F., et al.
(författare)
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Short-range magnetic correlations and spin dynamics in the paramagnetic regime of (Mn,Fe)2(P,Si)
- 2016
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Ingår i: PHYSICAL REVIEW B. - 2469-9950. ; 94:1
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Tidskriftsartikel (refereegranskat)abstract
- The spatial and temporal correlations of magnetic moments in the paramagnetic regime of (Mn,Fe)(2)(P,Si) have been investigated by means of polarized neutron diffraction and muon-spin relaxation techniques. Short-range magnetic correlations are present at temperatures far above the ferromagnetic transition temperature (T-C). This leads to deviations of paramagnetic susceptibility from Curie-Weiss behavior. These short-range magnetic correlations extend in space, slow down with decreasing temperature, and finally develop into long-range magnetic order at T-C.
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| 36. |
- Moreira, Xoaquín, et al.
(författare)
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Impacts of urbanization on insect herbivory and plant defences in oak trees
- 2019
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Ingår i: Oikos. - : Wiley. - 0030-1299 .- 1600-0706. ; 128:1, s. 113-123
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Tidskriftsartikel (refereegranskat)abstract
- Systematic comparisons of species interactions in urban versus rural environments can improve our understanding of shifts in ecological processes due to urbanization. However, such studies are relatively uncommon and the mechanisms driving urbanization effects on species interactions (e.g. between plants and insect herbivores) remain elusive. Here we investigated the effects of urbanization on leaf herbivory by insect chewers and miners associated with the English oak Quercus robur by sampling trees in rural and urban areas throughout most of the latitudinal distribution of this species. In performing these comparisons, we also controlled for the size of the urban areas (18 cities) and gathered data on CO2 emissions. In addition, we assessed whether urbanization affected leaf chemical defences (phenolic compounds) and nutritional traits (phosphorus and nitrogen), and whether such changes correlated with herbivory levels. Urbanization significantly reduced leaf chewer damage but did not affect leaf miners. In addition, we found that leaves from urban locations had lower levels of chemical defences (condensed and hydrolysable tannins) and higher levels of nutrients (nitrogen and phosphorus) compared to leaves in rural locations. The magnitude of urbanization effects on herbivory and leaf defences was not contingent upon city size. Importantly, while the effects of urbanization on chemical defences were associated with CO2 emissions, changes in leaf chewer damage were not associated with either leaf traits or CO2 levels. These results suggest that effects of urbanization on herbivory occur through mechanisms other than changes in the plant traits measured here. Overall, our simultaneous assessment of insect herbivory, plant traits and abiotic correlates advances our understanding of the main drivers of urbanization effects on plant-herbivore interactions.
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| 37. |
- Panman, Matthijs R, 1983, et al.
(författare)
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Transient two-dimensional vibrational spectroscopy of an operating molecular machine
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic molecular machines are promising building blocks for future nanoscopic devices. However, the details of their mechanical behaviour are in many cases still largely unknown. A deeper understanding of mechanics at the molecular level is essential for the design and construction of complex nanodevices. Here, we show that transient two-dimensional infrared (T2DIR) spectroscopy makes it possible to monitor the conformational changes of a translational molecular machine during its operation. Translation of a macrocyclic ring from one station to another on a molecular thread is initiated by a UV pulse. The arrival of the shuttling macrocycle at the final station is visible from a newly appearing cross peak between these two moieties. To eliminate spectral congestion in the T2DIR spectra, we use a subtraction method applicable to many other complex molecular systems. The T2DIR spectra indicate that the macrocycle adopts a boat-like conformation at the final station, which contrasts with the chair-like conformation at the initial station. © 2017 The Author(s).
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| 38. |
- Withers, Paul J. A., et al.
(författare)
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Stewardship to tackle global phosphorus inefficiency: The case of Europe
- 2015
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Ingår i: Ambio. - : Springer. - 0044-7447 .- 1654-7209. ; 44:2, s. 193-206
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Tidskriftsartikel (refereegranskat)abstract
- The inefficient use of phosphorus (P) in the food chain is a threat to the global aquatic environment and the health and well-being of citizens, and it is depleting an essential finite natural resource critical for future food security and ecosystem function. We outline a strategic framework of 5R stewardship (Re-align P inputs, Reduce P losses, Recycle P in bioresources, Recover P in wastes, and Redefine P in food systems) to help identify and deliver a range of integrated, cost-effective, and feasible technological innovations to improve P use efficiency in society and reduce Europe’s dependence on P imports. Their combined adoption facilitated by interactive policies, co-operation between upstream and downstream stakeholders (researchers, investors, producers, distributors, and consumers), and more harmonized approaches to P accounting would maximize the resource and environmental benefits and help deliver a more competitive, circular, and sustainable European economy. The case of Europe provides a blueprint for global P stewardship.
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