| 1. |
- Munch Roager, Henrik, et al.
(författare)
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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: A randomised cross-over trial
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:1, s. 83-93
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Tidskriftsartikel (refereegranskat)abstract
- Objective T o investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of =6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Conclusion C ompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic lowgrade inflammation.
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| 2. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 3. |
- Christensen, Robin, et al.
(författare)
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Effect of Weight Maintenance on Symptoms of Knee Osteoarthritis in Obese Patients: A Twelve-Month Randomized Controlled Trial 1
- 2015
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 67:5, s. 640-650
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To compare results of obese patients with knee osteoarthritis (OA) who, after an intensive weight loss regimen, received 1 year of either dietary support (D), a knee-exercise program (E), or "no attention" (C; control group). Methods. We conducted a randomized, 2-phase, parallel-group trial. A total of 192 obese participants with knee OA were enrolled; the mean age was 62.5 years and 81% were women with a mean entry weight of 103.2 kg. In phase 1, all participants were randomly assigned to 1 of 3 groups and began a dietary regimen of 400-810 and 1,250 kcal/day for 16 weeks (2 8-week phases) to achieve a major weight loss. Phase 2 consisted of 52 weeks' maintenance in either group D, E, or C. Outcomes were changes from randomization in pain on a 100-mm visual analog scale, weight, and response according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria. Results. Mean weight loss for phase 1 was 12.8 kg. After 1 year on maintenance therapy, the D group sustained a lower weight (11.0 kg, 95% confidence interval [95% CI] 9.0, 12.8 kg) than those in the E (6.2, 95% CI 4.4, 8.1 kg) and C (8.2, 95% CI 6.4, 10.1 kg) groups (P = 0.002 by analysis of covariance [ANCOVA]). Adherence was low in the E group. All groups had statistically significant pain reduction (D: 6.1; E: 5.6; and C: 5.5 mm) with no difference between groups (P = 0.98 by ANCOVA). In each group 32 (50%), 26 (41%), and 33 (52%) participants responded to treatment in the D, E, and C groups, respectively, with no statistically significant difference in the number of responders (P = 0.41). Conclusion. A significant weight reduction with a 1-year maintenance program improves knee OA symptoms irrespective of maintenance program.
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| 4. |
- Hansen, Lea B.S., et al.
(författare)
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A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2018, The Author(s). Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.
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| 5. |
- Jørgensen, Tanja Schjødt, et al.
(författare)
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Protocol for evaluating and implementing a pragmatic value-based healthcare management model for patients with inflammatory arthritis : A Danish population-based regional cohort and qualitative implementation study
- 2018
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The provision of healthcare for patients with inflammatory arthritis occurs in the context of somewhat conflicting targets, values and drivers. Therefore, there is a need for introducing 'value-based healthcare' defined as the value of patient relevant health outcomes in relation to costs. This term is a central part of tomorrow's healthcare sector, especially for rheumatic diseases, yet the transition is a huge challenge, as it will impact the development, delivery and assessment of healthcare. Aims The aim of this study is to compare medical and patient evaluated impact of the traditional settlement and financing production (DAGS) controlled healthcare setting with a value-based and patient-centred adjunctive to standard care. Methods and analysis Patients with inflammatory arthritis receiving treatment in routine care at the outpatient clinics in the Capital Region of Denmark will prospectively and consecutively be enrolled in a Non-Intervention-Study framework providing a pragmatic value-based management model. A Danish reference cohort, used for comparison will be collected as part of routine clinical care. The enrolment period will be from 1 June 2018 until 31December 2023. Baseline and follow-up visits will be according to routine clinical care. Registry data will be obtained directly from patients and include personal, clinical and outcomes information. The study results will be reported in accordance with the STROBE statement. Ethics and dissemination The study has been notified to the Danish Data Protection Agency and granted authorisation for the period June 2018 to January 2025 (pending). Informed consent will be obtained from all patients before enrolment in the study. The study is approved by the ethics committee, Capital Region of Denmark (H-18013158). Results of the study will be disseminated through publication in international peer-reviewed journals.
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| 6. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Ahluwalia, Tarunveer S., et al.
(författare)
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A novel rare CUBN variant and three additional genes identified in Europeans with and without diabetes : results from an exome-wide association study of albuminuria
- 2019
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 62:2, s. 292-305
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Identifying rare coding variants associated with albuminuria may open new avenues for preventing chronic kidney disease and end-stage renal disease, which are highly prevalent in individuals with diabetes. Efforts to identify genetic susceptibility variants for albuminuria have so far been limited, with the majority of studies focusing on common variants. Methods: We performed an exome-wide association study to identify coding variants in a two-stage (discovery and replication) approach. Data from 33,985 individuals of European ancestry (15,872 with and 18,113 without diabetes) and 2605 Greenlanders were included. Results: We identified a rare (minor allele frequency [MAF]: 0.8%) missense (A1690V) variant in CUBN (rs141640975, β = 0.27, p = 1.3 × 10−11) associated with albuminuria as a continuous measure in the combined European meta-analysis. The presence of each rare allele of the variant was associated with a 6.4% increase in albuminuria. The rare CUBN variant had an effect that was three times stronger in individuals with type 2 diabetes compared with those without (pinteraction = 7.0 × 10−4, β with diabetes = 0.69, β without diabetes = 0.20) in the discovery meta-analysis. Gene-aggregate tests based on rare and common variants identified three additional genes associated with albuminuria (HES1, CDC73 and GRM5) after multiple testing correction (pBonferroni < 2.7 × 10−6). Conclusions/interpretation: The current study identifies a rare coding variant in the CUBN locus and other potential genes associated with albuminuria in individuals with and without diabetes. These genes have been implicated in renal and cardiovascular dysfunction. The findings provide new insights into the genetic architecture of albuminuria and highlight target genes and pathways for the prevention of diabetes-related kidney disease.
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| 8. |
- Amini, Kasra, et al.
(författare)
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Alignment, orientation, and Coulomb explosion of difluoroiodobenzene studied with the pixel imaging mass spectrometry (PImMS) camera
- 2017
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 147:1
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Tidskriftsartikel (refereegranskat)abstract
- Laser-induced adiabatic alignment and mixed-field orientation of 2,6-difluoroiodobenzene (C6H3F2I) molecules are probed by Coulomb explosion imaging following either near-infrared strong-field ionization or extreme-ultraviolet multi-photon inner-shell ionization using free-electron laser pulses. The resulting photoelectrons and fragment ions are captured by a double-sided velocity map imaging spectrometer and projected onto two position-sensitive detectors. The ion side of the spectrometer is equipped with a pixel imaging mass spectrometry camera, a time-stamping pixelated detector that can record the hit positions and arrival times of up to four ions per pixel per acquisition cycle. Thus, the time-of-flight trace and ion momentum distributions for all fragments can be recorded simultaneously. We show that we can obtain a high degree of one-and three-dimensional alignment and mixed-field orientation and compare the Coulomb explosion process induced at both wavelengths.
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| 9. |
- Amini, Kasra, et al.
(författare)
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Photodissociation of aligned CH3I and C6H3F2I molecules probed with time-resolved Coulomb explosion imaging by site-selective extreme ultraviolet ionization
- 2018
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Ingår i: Structural Dynamics. - : AIP Publishing. - 2329-7778. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- We explore time-resolved Coulomb explosion induced by intense, extreme ultraviolet (XUV) femtosecond pulses from a free-electron laser as a method to image photo-induced molecular dynamics in two molecules, iodomethane and 2,6-difluoroiodobenzene. At an excitation wavelength of 267 nm, the dominant reaction pathway in both molecules is neutral dissociation via cleavage of the carbon-iodine bond. This allows investigating the influence of the molecular environment on the absorption of an intense, femtosecond XUV pulse and the subsequent Coulomb explosion process. We find that the XUV probe pulse induces local inner-shell ionization of atomic iodine in dissociating iodomethane, in contrast to non-selective ionization of all photofragments in difluoroiodobenzene. The results reveal evidence of electron transfer from methyl and phenyl moieties to a multiply charged iodine ion. In addition, indications for ultrafast charge rearrangement on the phenyl radical are found, suggesting that time-resolved Coulomb explosion imaging is sensitive to the localization of charge in extended molecules.
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| 10. |
- Bengtsson, Åsa, 1973-, et al.
(författare)
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Ideals and Actions : Do Citizens’ Patterns of Political Participation Correspond to their Conceptions of Democracy?
- 2016
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Ingår i: Government and Opposition. - : Cambridge University Press (CUP). - 0017-257X .- 1477-7053. ; 51:2, s. 234-260
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Tidskriftsartikel (refereegranskat)abstract
- The interest in procedures for political decision-making has grown tremendously during recent decades. Given the intense scholarly debate and the implementation of greater opportunities for citizen participation in many democracies, there has been surprisingly little interest in citizens’ conceptions of democracy understood as their preferences concerning the processes by which the political system works. Some recent attempts do, however, suggest that it is important to expand the study of public opinion from policy output to decision-making processes, and that there are coherent patterns in citizens’ expectations of the way in which political decisions come about. What is not clear, though, is whether citizens’ different conceptions of democracy have repercussions for how they engage in politics. Using the Finnish National Election Study of 2011 (Borg and Grönlund 2011), this article explores the relationship between citizens’ conceptions of democracy and patterns of political participation. Results demonstrate a distinct association between citizens’ ideals and the actions they take.
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| 11. |
- Biasin, Elisa, et al.
(författare)
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Femtosecond X-Ray Scattering Study of Ultrafast Photoinduced Structural Dynamics in Solvated[Co(terpy)2]2$
- 2016
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Ingår i: Physical Review Letters. - : American Physical Society (APS). - 1079-7114 .- 0031-9007. ; 117:1
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Tidskriftsartikel (refereegranskat)abstract
- We study the structural dynamics of photoexcited [Co(terpy)2]2+ in an aqueous solution with ultrafast x-ray diffuse scattering experiments conducted at the Linac Coherent Light Source. Through direct comparisons with density functional theory calculations, our analysis shows that the photoexcitation event leads to elongation of the Co-N bonds, followed by coherent Co-N bond length oscillations arising from the impulsive excitation of a vibrational mode dominated by the symmetrical stretch of all six Co-N bonds. This mode has a period of 0.33 ps and decays on a subpicosecond time scale. We find that the equilibrium bond-elongated structure of the high spin state is established on a single-picosecond time scale and that this state has a lifetime of ∼7 ps.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Christensen-Nugues, Charlotte, et al.
(författare)
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Ediktet i Nantes och Nicolas ko : En reformert prästs anteckningar i det sena 1500-talets La Rochelle
- 2018
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Ingår i: Vetenskapssocieteten i Lund. Årsbok 2018. - 0349-053X. - 9789198055191 ; , s. 15-28
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Under slutet av 1500-talet och början av 1600-talet utgjorde La Rochelle den viktigaste reformerta enklaven i Frankrike. I denna artikel studerar jag hur religionsstriderna, både de faktiska händelserna och de olika rykten som cirkulerade, framträdde i den reformerta prästen Jacques Merlins anteckningar från 1589 till 1620.
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| 16. |
- Denk, Thomas, 1971-, et al.
(författare)
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How to classify political cultures? : A comparison of three methods of classification
- 2016
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Ingår i: Quality and quantity. - : Springer. - 0033-5177 .- 1573-7845. ; 50:1, s. 177-191
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Tidskriftsartikel (refereegranskat)abstract
- To study the composition of political cultures, it is necessary to classify citizens according to a theoretical typology of political subcultures. Different methods of classification have been used for confronting this challenge, but the choice of method is rarely discussed in any detail because most studies apply a method without considering implications or possible alternatives. This is unfortunate because the choice of method has important consequences for the ensuing results. With this article, we aim to determine the implications of different methods for classification and hereby call attention to the importance of this choice for comparative research on political culture. We compare three commonly used methods of classification: critical thresholds, factor analysis and cluster analysis. These methods are used for classifying respondents from the 2008 European Social Survey according to a typology of political subcultures. Based on empirical analyses, we conclude that: (a) the choice of method of classification affects the outcome of the analysis, (b) cluster analysis and factor analysis may result in classifications that do not adequately reflect the theoretical typology, and (c) cluster analysis and factor analysis provide classifications that differ depending on analytical level. While the results do not show that either method is inherently superior, they clearly demonstrate that the choice of method should be recognized as a critical part of the research process.
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| 17. |
- Denk, Thomas, 1971-, et al.
(författare)
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The Composition of Political Culture : A Study of 25 European Democracies
- 2015
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Ingår i: Studies in comparative international development. - New York : Springer Science+Business Media B.V.. - 0039-3606 .- 1936-6167. ; 50:3, s. 358-377
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Tidskriftsartikel (refereegranskat)abstract
- The Civic Culture by Gabriel Almond and Sidney Verba is a path-breaking work within political science. Although The Civic Culture still provides inspiration for studies, new approaches to political culture have identified alternative citizen orientations that may be replacing the value orientations identified at the time. The more recent studies have examined specific attitudes such as political trust, party identification, and political efficacy or types of political subcultures such as critical citizens, stealth citizens or disenchanted citizens. These studies provide insights into the developments of specific attitudinal orientations, but do not discern the mix of political orientations among the population, which The Civic Culture suggests is central for democratic stability. The implications of these changes for the composition of political cultures are therefore still unknown. In this article, we, as suggested by The Civic Culture, examine the composition of political cultures to shed new light on the differences in political culture between old and new democracies. We use the fourth round of the European Social Survey to examine this question in 25 European democracies. The results suggest that there is a need to revise some of the main conclusions of The Civic Culture when it comes to the connection between political culture and democratic stability. Although civic citizens are widespread in old democracies, there is no single political culture sustaining a stable democracy. We also find considerable heterogeneity in the composition of the political cultures within old and new democracies alike, suggesting that there may be considerable variation in the cultural conditions for creating a stable democracy.
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| 18. |
- Engstrøm, Thomas, et al.
(författare)
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Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients : A phase 2 randomised clinical trial
- 2018
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 104:19, s. 1593-1599
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Reperfusion immediately after reopening of the infarct-related artery in ST-segment elevation myocardial infarction (STEMI) may cause myocardial damage in addition to the ischaemic insult (reperfusion injury). The gap junction modulating peptide danegaptide has in animal models reduced this injury. We evaluated the effect of danegaptide on myocardial salvage in patients with STEMI. Methods: In addition to primary percutaneous coronary intervention in STEMI patients with thrombolysis in myocardial infarction flow 0-1, single vessel disease and ischaemia time less than 6 hours, we tested, in a clinical proof-of-concept study, the therapeutic potential of danegaptide at two-dose levels. Primary outcome was myocardial salvage evaluated by cardiac MRI after 3 months. Results: From November 2013 to August 2015, a total of 585 patients were randomly enrolled in the trial. Imaging criteria were fulfilled for 79 (high dose), 80 (low dose) and 84 (placebo) patients eligible for the per-protocol analysis. Danegaptide did not affect the myocardial salvage index (danegaptide high (63.9±14.9), danegaptide low (65.6±15.6) and control (66.7±11.7), P=0.40), final infarct size (danegaptide high (19.6±11.4 g), danegaptide low (18.6±9.6 g) and control (21.4±15.0 g), P=0.88) or left ventricular ejection fraction (danegaptide high (53.9%±9.5%), danegaptide low (52.7%±10.3%) and control (52.1%±10.9%), P=0.64). There was no difference between groups with regard to clinical outcome. Conclusions: Administration of danegaptide to patients with STEMI did not improve myocardial salvage. Trial registration number: NCT01977755; Pre-results.
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| 19. |
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| 20. |
- Gregers, Jannie, et al.
(författare)
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Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia
- 2015
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Ingår i: The Pharmacogenomics Journal. - : Nature Publishing Group: Open Access Hybrid Model Option B. - 1470-269X .- 1473-1150. ; 15:4, s. 372-379
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Tidskriftsartikel (refereegranskat)abstract
- The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those eligible. Risk of relapse was increased 2.9-fold for patients with the 1199GA variant versus 1199GG (P = 0.001), and reduced 61% and 40%, respectively, for patients with the 3435CT or 3435TT variants versus 3435CC (overall P = 0.02). The degree of bone marrow toxicity during doxorubicin, vincristine and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P = 0.01/P less than 0.0001). We observed more liver toxicity after high-dose methotrexate in patients with 3435CC variant versus 3435CT/TT ( P = 0.03). In conclusion, there is a statistically significant association between ABCB1 polymorphisms, efficacy and toxicity in the treatment of ALL, and ABCB1 1199G greater than A may be a new possible predictive marker for outcome in childhood ALL.
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| 21. |
- Haldrup, Kristoffer, et al.
(författare)
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Ultrafast X-Ray Scattering Measurements of Coherent Structural Dynamics on the Ground-State Potential Energy Surface of a Diplatinum Molecule
- 2019
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Ingår i: Physical Review Letters. - 0031-9007. ; 122:6
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Tidskriftsartikel (refereegranskat)abstract
- We report x-ray free electron laser experiments addressing ground-state structural dynamics of the diplatinum anion Pt2POP4 following photoexcitation. The structural dynamics are tracked with <100 fs time resolution by x-ray scattering, utilizing the anisotropic component to suppress contributions from the bulk solvent. The x-ray data exhibit a strong oscillatory component with period 0.28 ps and decay time 2.2 ps, and structural analysis of the difference signal directly shows this as arising from ground-state dynamics along the PtPt coordinate. These results are compared with multiscale Born-Oppenheimer molecular dynamics simulations and demonstrate how off-resonance excitation can be used to prepare a vibrationally cold excited-state population complemented by a structure-dependent depletion of the ground-state population which subsequently evolves in time, allowing direct tracking of ground-state structural dynamics.
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| 22. |
- Hedegaard, Sofie Fogh, et al.
(författare)
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Fluorophore labeling of a cell-penetrating peptide significantly alters the mode and degree of biomembrane interaction
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The demand for highly efficient macromolecular drugs, used in the treatment of many severe diseases, is continuously increasing. However, the hydrophilic character and large molecular size of these drugs significantly limit their ability to permeate across cellular membranes and thus impede the drugs in reaching their target sites in the body. Cell-penetrating peptides (CPP) have gained attention as promising drug excipients, since they can facilitate drug permeation across cell membranes constituting a major biological barrier. Fluorophores are frequently covalently conjugated to CPPs to improve detection, however, the ensuing change in physico-chemical properties of the CPPs may alter their biological properties. With complementary biophysical techniques, we show that the mode of biomembrane interaction may change considerably upon labeling of the CPP penetratin (PEN) with a fluorophore. Fluorophore-PEN conjugates display altered modes of membrane interaction with increased insertion into the core of model cell membranes thereby exerting membrane-thinning effects. This is in contrast to PEN, which localizes along the head groups of the lipid bilayer, without affecting the thickness of the lipid tails. Particularly high membrane disturbance is observed for the two most hydrophobic PEN conjugates; rhodamine B or 1-pyrene butyric acid, as compared to the four other tested fluorophore-PEN conjugates.
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| 23. |
- Hedenås, Henrik, et al.
(författare)
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Changes in vegetation cover and composition in the Swedish mountain region
- 2016
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Ingår i: Environmental Monitoring and Assessment. - : Springer Science and Business Media LLC. - 0167-6369 .- 1573-2959. ; 188
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Tidskriftsartikel (refereegranskat)abstract
- Climate change, higher levels of natural resource demands, and changing land use will likely lead to changes in vegetation configuration in the mountain regions. The aim of this study was to determine if the vegetation cover and composition have changed in the Swedish region of the Scandinavian Mountain Range, based on data from the long-term landscape biodiversity monitoring program NILS (National Inventory of Landscapes in Sweden). Habitat type and vegetation cover were assessed in 1740 systematically distributed permanent field plots grouped into 145 sample units across the mountain range. Horvitz-Thompson estimations were used to estimate the present areal extension of the alpine and the mountain birch forest areas of the mountain range, the cover of trees, shrubs, and plants, and the composition of the bottom layer vegetation. We employed the data from two subsequent 5-year monitoring periods, 2003-2007 and 2008-2012, to determine if there have been any changes in these characteristics. We found that the extension of the alpine and the mountain birch forest areas has not changed between the inventory phases. However, the total tree canopy cover increased in the alpine area, the cover of graminoids and dwarf shrubs and the total cover of field vegetation increased in both the alpine area and the mountain birch forest, the bryophytes decreased in the alpine area, and the foliose lichens decreased in the mountain birch forest. The observed changes in vegetation cover and composition, as assessed by systematic data in a national and regional monitoring scheme, can validate the results of local studies, experimental studies, and models. Through benchmark assessments, monitoring data also contributes to governmental policies and land-management strategies as well as to directed cause and effect analyses.
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| 24. |
- Hedenås, Henrik, et al.
(författare)
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Det föränderliga fjällandskapet
- 2015
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Ingår i: Skog & Mark 2015 : Om tillståndet i svensk landmiljö. - 9789162012984 ; , s. 4-8
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Bokkapitel (populärvet., debatt m.m.)abstract
- Landskapet i fjällen påverkas av klimatförändringar och ändrad markanvändning, inklusive ökad turism. Här presenteras miljöövervakningsresultat från studier av växtligheten och på- verkan av bland annat terrängfordon på kalfjäll och i fjällbjörkskog.
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| 25. |
- Hedenås, Henrik, et al.
(författare)
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Vegetation conditions and changes in the Swedish mountain area
- 2016
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Ingår i: Environmental Monitoring and Assessment. - 0167-6369. ; 188
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Tidskriftsartikel (refereegranskat)abstract
- Climate change, higher levels of natural resource demands, and changing land use will likely lead to changes in vegetation configuration in the mountain regions. The aim of this study was to determine if the vegetation cover and composition have changed in the Swedish region of the Scandinavian Mountain Range, based on data from the long-term landscape biodiversity monitoring program NILS (National Inventory of Landscapes in Sweden). Habitat type and vegetation cover were assessed in 1740 systematically distributed permanent field plots grouped into 145 sample units across the mountain range. Horvitz–Thompson estimations were used to estimate the present areal extension of the alpine and the mountain birch forest areas of the mountain range, the cover of trees, shrubs, and plants, and the composition of the bottom layer vegetation. We employed the data from two subsequent 5-year monitoring periods, 2003–2007 and 2008–2012, to determine if there have been any changes in these characteristics. We found that the extension of the alpine and the mountain birch forest areas has not changed between the inventory phases. However, the total tree canopy cover increased in the alpine area, the cover of graminoids and dwarf shrubs and the total cover of field vegetation increased in both the alpine area and the mountain birch forest, the bryophytes decreased in the alpine area, and the foliose lichens decreased in the mountain birch forest. The observed changes in vegetation cover and composition, as assessed by systematic data in a national and regional monitoring scheme, can validate the results of local studies, experimental studies, and models. Through benchmark assessments, monitoring data also contributes to governmental policies and land-management strategies as well as to directed cause and effect analyses.
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| 26. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
-
Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 27. |
- Kjær, Kasper S., et al.
(författare)
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Finding intersections between electronic excited state potential energy surfaces with simultaneous ultrafast X-ray scattering and spectroscopy
- 2019
-
Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 10:22, s. 5749-5760
-
Tidskriftsartikel (refereegranskat)abstract
- Light-driven molecular reactions are dictated by the excited state potential energy landscape, depending critically on the location of conical intersections and intersystem crossing points between potential surfaces where non-adiabatic effects govern transition probabilities between distinct electronic states. While ultrafast studies have provided significant insight into electronic excited state reaction dynamics, experimental approaches for identifying and characterizing intersections and seams between electronic states remain highly system dependent. Here we show that for 3d transition metal systems simultaneously recorded X-ray diffuse scattering and X-ray emission spectroscopy at sub-70 femtosecond time-resolution provide a solid experimental foundation for determining the mechanistic details of excited state reactions. In modeling the mechanistic information retrieved from such experiments, it becomes possible to identify the dominant trajectory followed during the excited state cascade and to determine the relevant loci of intersections between states. We illustrate our approach by explicitly mapping parts of the potential energy landscape dictating the light driven low-to-high spin-state transition (spin crossover) of [Fe(2,2′-bipyridine)3]2+, where the strongly coupled nuclear and electronic dynamics have been a source of interest and controversy. We anticipate that simultaneous X-ray diffuse scattering and X-ray emission spectroscopy will provide a valuable approach for mapping the reactive trajectories of light-triggered molecular systems involving 3d transition metals.
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| 28. |
- Kjær, Kasper S., et al.
(författare)
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Solvent control of charge transfer excited state relaxation pathways in [Fe(2,2′-bipyridine)(CN)4]2-
- 2018
-
Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 20:6, s. 4238-4249
-
Tidskriftsartikel (refereegranskat)abstract
- The excited state dynamics of solvated [Fe(bpy)(CN)4]2-, where bpy = 2,2′-bipyridine, show significant sensitivity to the solvent Lewis acidity. Using a combination of optical absorption and X-ray emission transient spectroscopies, we have previously shown that the metal to ligand charge transfer (MLCT) excited state of [Fe(bpy)(CN)4]2- has a 19 picosecond lifetime and no discernable contribution from metal centered (MC) states in weak Lewis acid solvents, such as dimethyl sulfoxide and acetonitrile.1,2 In the present work, we use the same combination of spectroscopic techniques to measure the MLCT excited state relaxation dynamics of [Fe(bpy)(CN)4]2- in water, a strong Lewis acid solvent. The charge-transfer excited state is now found to decay in less than 100 femtoseconds, forming a quasi-stable metal centered excited state with a 13 picosecond lifetime. We find that this MC excited state has triplet (3MC) character, unlike other reported six-coordinate Fe(ii)-centered coordination compounds, which form MC quintet (5MC) states. The solvent dependent changes in excited state non-radiative relaxation for [Fe(bpy)(CN)4]2- allows us to infer the influence of the solvent on the electronic structure of the complex. Furthermore, the robust characterization of the dynamics and optical spectral signatures of the isolated 3MC intermediate provides a strong foundation for identifying 3MC intermediates in the electronic excited state relaxation mechanisms of similar Fe-centered systems being developed for solar applications.
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| 29. |
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| 30. |
- Laursen, Peter Nørkjær, et al.
(författare)
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Comparison between patients included in randomized controlled trials of ischemic heart disease and real-world data. A nationwide study
- 2018
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 204, s. 128-138
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The objective was to compare patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) who were included in randomized controlled trials (RCTs) (trial participants) with patients who were not included (nonparticipants) on a trial-by-trial basis and according to indication for PCI. Methods: In this cohort study, we compared patients with IHD who were randomized in RCTs in relation to undergoing PCI in Denmark between 2011 and 2015 were considered as RCT-participants in this study. The RCT-participants were compared with contemporary nonparticipants with IHD undergoing PCI in the same period, and they were identified using unselected national registry data. The primary end point was all-cause mortality. Results: A total of 10,317 (30%) patients were included in 10 relevant RCTs (trial participants), and a total of 23,644 (70%) contemporary patients did not participate (nonparticipants). In all the included RCTs, nonparticipants had higher hazard ratios for mortality compared to trial participants (P <.001). Among all patients treated with PCI, the pooled estimates showed a significantly higher mortality rate for nonparticipants compared to trial participants (hazard ratio: 2.03, 95% CI: 1.88-2.19) (P <.001). When patients were stratified according to indication for PCI, the pooled estimates showed a significantly lower mortality rate for trial participants compared to nonparticipants in all strata (P for all <.001). Conclusions: Trial participants in recently performed RCTs including patients undergoing PCI were not representative of the general population of patients with IHD treated with PCI according to clinical characteristics and mortality. The difference in mortality was found irrespective of the indication for PCI. Thus, results from RCTs including patients undergoing PCI should be extrapolated with caution to the general patient population.
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| 31. |
- Li, Jingmei, et al.
(författare)
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Prevalence of BRCA1 and BRCA2 pathogenic variants in a large, unselected breast cancer cohort
- 2019
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 144:5, s. 1195-1204
-
Tidskriftsartikel (refereegranskat)abstract
- Breast cancer patients with BRCA1/2-driven tumors may benefit from targeted therapy. It is not clear whether current BRCA screening guidelines are effective at identifying these patients. The purpose of our study was to evaluate the prevalence of inherited BRCA1/2 pathogenic variants in a large, clinically representative breast cancer cohort and to estimate the proportion of BRCA1/2 carriers not detected by selectively screening individuals with the highest probability of being carriers according to current clinical guidelines. The study included 5,122 unselected Swedish breast cancer patients diagnosed from 2001 to 2008. Target sequence enrichment (48.48 Fluidigm Access Arrays) and sequencing were performed (Illumina Hi-Seq 2,500 instrument, v4 chemistry). Differences in patient and tumor characteristics of BRCA1/2 carriers who were already identified as part of clinical BRCA1/2 testing routines and additional BRCA1/2 carriers found by sequencing the entire study population were compared using logistic regression models. Ninety-two of 5,099 patients with valid variant calls were identified as BRCA1/2 carriers by screening all study participants (1.8%). Only 416 study participants (8.2%) were screened as part of clinical practice, but this identified 35 out of 92 carriers (38.0%). Clinically identified carriers were younger, less likely postmenopausal and more likely to be associated with familiar ovarian cancer compared to the additional carriers identified by screening all patients. More BRCA2 (34/42, 81.0%) than BRCA1 carriers (23/50, 46%) were missed by clinical screening. In conclusion, BRCA1/2 mutation prevalence in unselected breast cancer patients was 1.8%. Six in ten BRCA carriers were not detected by selective clinical screening of individuals.
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| 32. |
- Lundby, Knut, et al.
(författare)
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Religion and the Media : Continuity, Complexity, and Mediatization
- 2018
-
Ingår i: Religious Complexity in the Public Sphere. - Basingstoke : Palgrave Macmillan. - 9783319556772 - 9783319556789 ; , s. 137-191
-
Bokkapitel (refereegranskat)abstract
- This chapter begins with a presentation of the particular features of the Nordic media systems and their transformations since 1980. The following analyzes three forms of mediatized religion: journalism on religion (in major newspapers), religion in popular media (popular magazines and films), and religious media (religious programs in the public service broadcasting and the Internet presentations by the Nordic majority churches). The conclusions show no simple pattern of a decline or resurgence of the visibility of religion in the media. This chapter also asks what the media do to religion (mediatization theory), and concludes that the media genre has a profound impact on the representation of religion, which results in a complex pattern of increased diversity of topics and perspectives.
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| 33. |
- Lövheim, Mia, 1968-, et al.
(författare)
-
Religion on the political agenda
- 2018. - 1
-
Ingår i: Religious Complexity in the Public Sphere. - Basingstoke : Palgrave Macmillan. - 9783319556772 ; , s. 137-191
-
Bokkapitel (refereegranskat)abstract
- Nordic politics on religion has historically been formed by the close relationship between the state and the Lutheran majority churches. There has been a consensus on religious tolerance and the value of an inclusive majority church. This chapter asks whether the growing religious diversity during the past thirty years has implied a shift in the role of religion in political opinions and debates. ISSP survey data on political and religious views from 1991-2008 shows continuity as well as change across the Nordic countries. The growing religious diversity does not seem to have changed previous patterns of connections between individual religiosity and political party preferences. However, people in Denmark, Norway and Sweden have become more tolerant towards religious minorities and their rights. Nordic political party platforms and parliamentary debates is a rich source of information to changes in the role of religion in political discourse. Christianity and the majority churches are still used as references to national identity in party platforms, in particular in Denmark and Norway. The analysis of the parliamentary debates shows that there is a growing invocation of religion in the parliamentary debates in all the Nordic countries. This tendency is most obvious in Denmark and Norway and weakest in Sweden. In particular, issues that connect religion to Islam and to human rights have increased, particularly in Denmark, Norway and Sweden, where levels of immigration are higher than in Finland and Iceland. In conclusion, religion has become more diversified and more contested as a political issue during the period studied, both in terms of the issues to which it is connected, and in terms of the range of religious traditions that are addressed. This development can be seen as a politicization of religion in a process of renegotiating social and cultural identities and values in the Nordic countries.
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| 34. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 35. |
- Martínez-Gómez, Jesus, et al.
(författare)
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Where Are We After Five Editions? : Robot Vision Challenge, a Competition that Evaluates Solutions for the Visual Place Classification Problem
- 2015
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Ingår i: IEEE robotics & automation magazine. - : IEEE. - 1070-9932 .- 1558-223X. ; 22:4, s. 147-156
-
Tidskriftsartikel (refereegranskat)abstract
- This article describes the Robot Vision challenge, a competition that evaluates solutions for the visual place classification problem. Since its origin, this challenge has been proposed as a common benchmark where worldwide proposals are measured using a common overall score. Each new edition of the competition introduced novelties, both for the type of input data and sub-objectives of the challenge. All the techniques used by the participants have been gathered up and published to make it accessible for future developments. The legacy of the Robot Vision challenge includes data sets, benchmarking techniques, and a wide experience in the place classification research that is reflected in this article.
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| 36. |
- Mirza, Mansoor Raza, et al.
(författare)
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A phase I study of the PARP inhibitor niraparib in combination with bevacizumab in platinum-sensitive epithelial ovarian cancer: NSGO AVANOVA1/ENGOT-OV24
- 2019
-
Ingår i: Cancer Chemotherapy and Pharmacology. - : SPRINGER. - 0344-5704 .- 1432-0843. ; 84:4, s. 791-798
-
Tidskriftsartikel (refereegranskat)abstract
- Background Combining poly(ADP-ribose) polymerase (PARP) inhibitors with antiangiogenic agents appeared to enhance activity vs PARP inhibitors alone in a randomized phase II trial. Materials and methods In AVANOVA (NCT02354131) part 1, patients with measurable/evaluable high-grade serous/endometrioid platinum-sensitive ovarian cancer received bevacizumab 15 mg/kg every 21 days with escalating doses of niraparib capsules (100, 200, or 300 mg daily) in a 3 + 3 dose-escalation design. Primary objectives were to evaluate safety and tolerability and to determine the recommended phase II dose (RP2D). Results Three of 12 enrolled patients had germline BRCA2 mutations. In cycle 1, nine patients experienced grade 3 toxicities: five with hypertension, three with anemia, and one with thrombocytopenia. There was one dose-limiting toxicity (grade 4 thrombocytopenia with niraparib 300 mg), thus the RP2D was bevacizumab 15 mg/kg with niraparib 300 mg. The response rate was 50%; disease was stabilized in a further 42%. Median progression-free survival was 11.6 (95% confidence interval 8.4-20.1) months. Niraparib pharmacokinetics were consistent with historical single-agent data. Overlapping exposure was observed across the dose ranges tested on days 1 and 21. Conclusions There was one dose-limiting toxicity; other adverse events were typical PARP inhibitor and antiangiogenic class effects. Niraparib-bevacizumab showed promising activity; Part 2 (vs bevacizumab) was recently reported and phase III comparison with standard-of-care therapy is planned.
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| 37. |
- Mirza, Mansoor Raza, et al.
(författare)
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Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial
- 2019
-
Ingår i: The Lancet Oncology. - : ELSEVIER SCIENCE INC. - 1470-2045 .- 1474-5488. ; 20:10, s. 1409-1419
-
Tidskriftsartikel (refereegranskat)abstract
- Background Platinum-based chemotherapy is the foundation of treatment for platinum-sensitive recurrent ovarian cancer, but has substantial toxicity. Bevacizumab and maintenance poly(ADP-ribose) polymerase (PARP) inhibitors both significantly improve efficacy versus standard therapy, primarily in terms of progression-free survival, and offer the potential for chemotherapy-free treatment. AVANOVA2 compared niraparib and bevacizumab versus niraparib alone as definitive treatment for platinum-sensitive recurrent ovarian cancer. Methods This open-label, randomised, phase 2, superiority trial in 15 university hospitals in Denmark, Sweden, Finland, Norway, and the USA enrolled women aged 18 years or older with measurable or evaluable high-grade serous or endometrioid platinum-sensitive recurrent ovarian cancer. Patients had to have an Eastern Cooperative Oncology Group performance status of 0-2, and had to have previously received platinum-containing therapy for primary disease but amp;lt;= 1 prior non-platinum-containing regimen for recurrent disease. Previous treatment with bevacizumab or first-line maintenance PARP inhibitors was permitted. Eligible patients were randomly assigned 1:1 (by random permuted blocks with block sizes of two and four, no masking), stratified by homologous recombination deficiency status and chemotherapy-free interval, to receive once-daily oral niraparib 300 mg alone or with intravenous bevacizumab 15 mg/kg once every 3 weeks until disease progression. The primary endpoint was progression-free survival, assessed by the investigators in the intention-to-treat population after events in at least 62 patients. Safety was analysed in all patients who received at least one dose of study drug. This ongoing trial is registered with ClinicalTrials.gov , number NCT02354131. Findings Between May 23,2016, and March 6,2017,97 patients were enrolled and randomly assigned: 48 to niraparib plus bevacizumab and 49 to single-agent niraparib. Median follow-up was 16.9 months (IQR 15.4-20.9). Niraparib plus bevacizumab significantly improved progression-free survival compared with niraparib alone (median progression-free survival 11.9 months [95% CI 8.5-16.7] vs 5.5 months [3.8-6.3], respectively; adjusted hazard ratio [HR] 0.35 [95% CI 0.21-0.57], pamp;lt;0.0001). Grade 3 or worse adverse events occurred in 31 (65%) of 48 patients who received niraparib plus bevacizumab and 22 (45%) of 49 who received single-agent niraparib. The most common grade 3 or worse adverse events in both groups were anaemia (7 [15%] of 48 vs 9 [18%] of 49) and thrombocytopenia (5 [10%] vs 6 [12%]), and hypertension in the combination group (10 [21%] vs 0). Niraparib plus bevacizumab was associated with increased incidences of any-grade proteinuria (10 [21%] of 48 patients vs 0) and hypertension (27[56%] of 48 vs 11 [22%] of 49) compared with niraparib alone. No treatment-related deaths occurred. Interpretation The efficacy observed with this chemotherapy-free combination of approved agents in women with platinum-sensitive recurrent ovarian cancer warrants further evaluation. A randomised phase 3 trial investigating niraparib plus bevacizumab versus chemotherapy plus bevacizumab in platinum-sensitive recurrent ovarian cancer is planned. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 38. |
- Munch, Henrik K, et al.
(författare)
-
Construction of Insulin 18-mer Nanoassemblies Driven by Coordination to Iron(II) and Zinc(II) Ions at Distinct Sites.
- 2016
-
Ingår i: Angewandte Chemie (International edition). - : Wiley. - 1521-3773. ; 55:7, s. 2378-2381
-
Tidskriftsartikel (refereegranskat)abstract
- Controlled self-assembly (SA) of proteins offers the possibility to tune their properties or to create new materials. Herein, we present the synthesis of a modified human insulin (HI) with two distinct metal-ion binding sites, one native, the other abiotic, enabling hierarchical SA through coordination with two different metal ions. Selective attachment of an abiotic 2,2'-bipyridine (bipy) ligand to HI, yielding HI-bipy, enabled Zn(II) -binding hexamers to SA into trimers of hexamers, [[HI-bipy]6 ]3 , driven by octahedral coordination to a Fe(II) ion. The structures were studied in solution by small-angle X-ray scattering and on surfaces with AFM. The abiotic metal ligand had a higher affinity for Fe(II) than Zn(II) ions, enabling control of the hexamer formation with Zn(II) and the formation of trimers of hexamers with Fe(II) ions. This precise control of protein SA to give oligomers of oligomers provides nanoscale structures with potential applications in nanomedicine.
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| 39. |
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| 40. |
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| 41. |
- Pehlivan Rhodin, Nils Henrik, et al.
(författare)
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The nature of damped HI absorbers probed by cosmological simulations: satellite accretion and outflows
- 2019
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; , s. 3634-3634
-
Tidskriftsartikel (refereegranskat)abstract
- We use cosmological hydrodynamic zoom simulations to study the neutral gas distributionin and around galaxies that gives rise to high column density HILyαabsorption (dampedLyαsystems (DLAs) and sub-DLAs) in background quasar spectra. Such simulations oftensacrifice numerical resolution for volume that affects the lower density galaxy halo gas,and simulations have difficulties reproducing the span of projected separations (b) betweenabsorbing clouds and their hosts. Our simulations produce (sub-)DLAs over the entire probedparameter space (b50 kpc and metallicity−4[M/H]0.5) at all redshifts (z∼0.4−3.0),enclosing spectroscopically confirmed absorber-galaxy pairs. Recovering (sub-)DLAs atb20−30 kpc from a massive host galaxy requires high numerical resolution and efficientfeedback, and we show that these lines-of-sight are associated with dwarf satellites in the mainhalo, stripped metal-rich gas, and outflows. HIdisc- and halo gas significantly contributesto (sub-)DLAs around galaxies. At large redshifts the halo plays an increasingly importantrole, while at 0.4
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| 42. |
- Reintoft Christensen, Henrik, et al.
(författare)
-
Rooms of Silence at Three Universities in Scandinavia
- 2019
-
Ingår i: Sociology of Religion. - : Oxford University Press (OUP). - 1069-4404 .- 1759-8818. ; 80:3, s. 299-322
-
Tidskriftsartikel (refereegranskat)abstract
- In recent decades, a new type of room has been established in public institutions in Europe: the rooms of silence. In this article, rooms of silence at three Scandinavian universities are analyzed with focus on intention, materiality, and use in relation to increased religious diversity in the student population, individualization, and ongoing secularization. This is done by using a typology which distinguishes between individual and collective use and use associated with religious, spiritual, and secular practices. The analyses show that plans and policies for the rooms emphasize stress-reduction and spiritual or secular reflection. The chaplains actively facilitate the shift from collective to more individual use of the rooms. The analyses also show that the restricted materiality of the rooms shapes practices in ways that either hinder collective Muslim prayer or force students to perform prayer as an individual “silent” action.
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| 43. |
- Rodrigues, Letícia, et al.
(författare)
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Immune responses induced by nano-self-assembled lipid adjuvants based on a monomycoloyl glycerol analogue after vaccination with the Chlamydia trachomatis major outer membrane protein.
- 2018
-
Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 285, s. 12-22
-
Tidskriftsartikel (refereegranskat)abstract
- Nanocarriers based on inverse hexagonal liquid crystalline phases (hexosomes) show promising potential as vaccine delivery systems. Their unique internal structure, composed of both lipophilic domains and water-containing channels, renders them capable of accommodating immunopotentiating compounds and antigens. However, their adjuvant properties are poorly understood. We hypothesized that the supramolecular structure of the lyotropic liquid crystalline phase influences the immunostimulatory activity of lipid-based nanocarriers. To test this, hexosomes were designed containing the lipid phytantriol (Phy) and the immunopotentiator monomycoloyl glycerol-1 (MMG-1). Self-assembly of Phy and MMG-1 into nanocarriers featuring an internal hexagonal phase was confirmed by small-angle X-ray scattering and cryogenic transmission electron microscopy. The effect of the nanostructure on the adjuvant activity was studied by comparing the immunogenicity of Phy/MMG-1 hexosomes with MMG-1-containing lamellar liquid crystalline nanoparticles (liposomes, CAF04). The quality and magnitude of the elicited immune responses were determined after vaccination of CB6/F1 mice using the Chlamydia trachomatis major outer membrane protein (MOMP) as antigen. MMG-1-based hexosomes potentiated significantly stronger MOMP-specific humoral responses than CAF04 liposomes. The liposome-based vaccine formulation induced a much stronger MOMP-specific cell-mediated immune response compared to hexosome-adjuvanted MOMP, which elicited minimal MOMP-specific T-cell stimulation after vaccination. Hence, our data demonstrates that hexosomal and liposomal adjuvants activate the immune system via different mechanisms. Our work provides valuable insights into the adjuvant potential of hexosomes and emphasizes that engineering of the supramolecular structure can be used to design adjuvants with customized immunological properties.
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| 44. |
- Savelyev, Evgeny, et al.
(författare)
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Jitter-correction for IR/UV-XUV pump-probe experiments at the FLASH free-electron laser
- 2017
-
Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 19:4
-
Tidskriftsartikel (refereegranskat)abstract
- In pump-probe experiments employing a free-electron laser (FEL) in combination with a synchronized optical femtosecond laser, the arrival-time jitter between the FEL pulse and the optical laser pulse often severely limits the temporal resolution that can be achieved. Here, we present a pump-probe experiment on the UV-induced dissociation of 2,6-difluoroiodobenzene (C6H3F2I) molecules performed at the FLASH FEL that takes advantage of recent upgrades of the FLASH timing and synchronization system to obtain high-quality data that are not limited by the FEL arrival-time jitter. We discuss in detail the necessary data analysis steps and describe the origin of the time-dependent effects in the yields and kinetic energies of the fragment ions that we observe in the experiment.
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| 45. |
- Sigurdsson, Halldor Armann, et al.
(författare)
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Subject Float, Low Subject Trapping, and Case in Icelandic
- 2019
-
Ingår i: The sign of the V : Papers in honour of Sten Vikner - Papers in honour of Sten Vikner. - : Aahus University Library. - 9788791134050 - 9788775074617 ; , s. 591-618
-
Bokkapitel (refereegranskat)abstract
- This article describes and discusses two peculiar sets of (in)defi nitenessfacts applying to subjects in Icelandic, here referred to as Subject Floatand Low Subject Trapping. Indefi nite subjects (commonly quantifi ed) inpresentational sentences and related clause types may either occupy thecomplement position within the predicate phrase or “fl oat” into variouspositions in the middle fi eld. This is Subject Float, yielding variation suchas “There would (many farmers) then (many farmers) probably (manyfarmers) be (?*many farmers) elected (many farmers)”. Conversely, andunexpectedly, defi nite NP subjects of some adjectival and verbal predicatesmust stay in the complement position. This is Low Subject Trapping,yielding orders such as “there is cold radiator-the” and “there cooledradiator-the”. It is shown that the licensing of subject NPs in the variouspositions in Subject Float and in the complement position in Low SubjectTrapping is unrelated to specifi c grammatical cases, thus refuting the widelyadopted case approach to NP licensing. Although Icelandic case markinghas been widely discussed, Subject Float and Low Subject Trapping havenot previously received a detailed scrutiny; these phenomena provideadditional and partly new knockout arguments against the case approach toNP licensing and NP movement. While high NP raising to subject (Spec,IP)is unaffected by case, it seems to involve both Person and Topic matching.
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| 46. |
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| 47. |
- Ström, Henrik, 1981, et al.
(författare)
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Atomizing industrial gas-liquid flows - development of an efficient hybrid VOF-LPT numerical framework
- 2016
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Ingår i: International Journal of Heat and Fluid Flow. - : Elsevier BV. - 0142-727X. ; 62:A, s. 104-113
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Tidskriftsartikel (refereegranskat)abstract
- Atomizing gas-liquid flows are used in industrial applications where high interphase heat and mass transfer rates and good mixing are of primary importance. Today, there is no single mathematical framework available to predict the entire liquid breakup process at an acceptablecomputational cost for a typical problem of industrial size.In this work, we develop a volume-of-fluid (VOF) framework that is combined with Lagrangian particle tracking (LPT) to take advantage of the respective strengths of these two approaches. The two frameworks are coupled via a statistical model that enables a transition from the VOF tothe LPT formulation using input data about the primary breakup process obtained from detailed VOF simulations in dedicated switching zones. LPT-to-VOF transitions are handled directly by analyzing the proximity of LPTparcels to larger VOF structures. The combined framework is specifically designed to accommodate situations where atomization occurs in several locations simultaneously and when separated and dispersed turbulent gas-liquid flows co-exist in the same industrial unit. The procedure in which the statistical model is derived is presented and discussed, its performance is verified and the computational efficiency of the combined VOF-LPT model is assessed.Finally, the application of the coupled framework to the simulation of an industrial gas-liquid mixer with four separate atomization regions is presented.
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| 48. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 49. |
- Van Driel, Tim B., et al.
(författare)
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Atomistic characterization of the active-site solvation dynamics of a model photocatalyst
- 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
- The interactions between the reactive excited state of molecular photocatalysts and surrounding solvent dictate reaction mechanisms and pathways, but are not readily accessible to conventional optical spectroscopic techniques. Here we report an investigation of the structural and solvation dynamics following excitation of a model photocatalytic molecular system [Ir 2 (dimen) 4 ] 2+, where dimen is para-diisocyanomenthane. The time-dependent structural changes in this model photocatalyst, as well as the changes in the solvation shell structure, have been measured with ultrafast diffuse X-ray scattering and simulated with Born-Oppenheimer Molecular Dynamics. Both methods provide direct access to the solute-solvent pair distribution function, enabling the solvation dynamics around the catalytically active iridium sites to be robustly characterized. Our results provide evidence for the coordination of the iridium atoms by the acetonitrile solvent and demonstrate the viability of using diffuse X-ray scattering at free-electron laser sources for studying the dynamics of photocatalysis.
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| 50. |
- Webster, Christopher R., et al.
(författare)
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Background levels of methane in Mars' atmosphere show strong seasonal variations
- 2018
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 360:6393, s. 1093-1096
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Tidskriftsartikel (refereegranskat)abstract
- Variable levels of methane in the martian atmosphere have eluded explanation partly because the measurements are not repeatable in time or location. We report in situ measurements at Gale crater made over a 5-year period by the Tunable Laser Spectrometer on the Curiosity rover. The background levels of methane have a mean value 0.41 ± 0.16 parts per billion by volume (ppbv) (95% confidence interval) and exhibit a strong, repeatable seasonal variation (0.24 to 0.65 ppbv). This variation is greater than that predicted from either ultraviolet degradation of impact-delivered organics on the surface or from the annual surface pressure cycle. The large seasonal variation in the background and occurrences of higher temporary spikes (~7 ppbv) are consistent with small localized sources of methane released from martian surface or subsurface reservoirs.
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