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Marklund, M., Wu, J. H., Imamura, F., Del Gobbo, L. C., Fretts, A., de Goede, J., . . . Risérus, U. (2019). Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies. Circulation, 139(21), 2422-2436
Open this publication in new window or tab >>Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies
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2019 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 21, p. 2422-2436Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease (CHD), ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytical plan. Levels of LA and AA, measured as % of total fatty acids, were evaluated linearly according to their interquintile range (i.e., the range between the mid-point of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15,198 incident cardiovascular events occurred among 68,659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI: 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower CHD risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; comparing extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

Place, publisher, year, edition, pages
American Heart Association, 2019
Keywords
Arachidonic acid, Linoleic acid, Pooled analysis, diet and nutrition
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-158789 (URN)10.1161/CIRCULATIONAHA.118.038908 (DOI)000469018300011 ()30971107 (PubMedID)
Available from: 2019-05-08 Created: 2019-05-08 Last updated: 2019-06-17Bibliographically approved
Johansson, I., Esberg, A., Nilsson, L. M., Jansson, J.-H., Wennberg, P. & Winkvist, A. (2019). Dairy Product Intake and Cardiometabolic Diseases in Northern Sweden: A 33-Year Prospective Cohort Study. Nutrients, 11(284)
Open this publication in new window or tab >>Dairy Product Intake and Cardiometabolic Diseases in Northern Sweden: A 33-Year Prospective Cohort Study
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2019 (English)In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, no 284Article in journal (Refereed) Published
Abstract [en]

Dairy products are important constituents of most diets, and their association with adverse health outcomes remains a focus. We characterized dairy food intake and examined associations with the incidence of type 2 diabetes (T2D), myocardial infarction (MI) or stroke among 108,065 Swedish men and women. Hazard ratios (HRs) and 95% CIs were estimated using the multivariable Cox proportional hazards models in a population characterized by high milk tolerance. During a mean follow-up of 14.2 years, 11,641 first-time events occurred. Non-fermented milk intake decreased, whereas butter intake increased over the period. For high intake of non-fermented milk, the HR (95% CI) for developing T2D and MI was 1.17 (1.03, 1.34) and 1.23 (1.10, 1.37), respectively, in men. A greater intake of butter, fermented milk, and cheese tended to be associated with a reduced risk of T2D and/or MI. Non-consumers and those who chose low-fat variants of the targeted dairy products had increased risk for T2D, MI, or stroke compared to those in the non-case group. Generally, effect-sizes were small. This prospective study found that non-fermented milk was associated with an increased risk for developing T2D and MI and that subjects abstaining from dairy products or choosing low-fat variants were at greater risk. However, the overall cardiometabolic risk of non-fermented milk intake was judged as low, since the effect sizes were small.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
dairy products, milk, cardiovascular disease, myocardial infarction, stroke, type 2 diabetes
National Category
Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-156027 (URN)10.3390/nu11020284 (DOI)000460829700075 ()30696081 (PubMedID)2-s2.0-85060813708 (Scopus ID)
Available from: 2019-02-01 Created: 2019-02-01 Last updated: 2019-04-04Bibliographically approved
Nilsson, L. M., Winkvist, A., Esberg, A., Jansson, J.-H., Wennberg, P., van Guelpen, B. & Johansson, I. (2019). Dairy Products and Cancer Risk in a Northern Sweden Population. Nutrition and Cancer
Open this publication in new window or tab >>Dairy Products and Cancer Risk in a Northern Sweden Population
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2019 (English)In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914Article in journal (Refereed) Epub ahead of print
Abstract [en]

The role of dairy products in cancer is unclear. We assessed consumption of fermented milk, non-fermented milk, cheese, and butter, estimated from semi-quantitative food frequency questionnaires, in relation to prospective risk of breast, prostate, colorectal, smoking-, and obesity-related cancers in 101,235 subjects, including 12,552 cancer cases, in the population-based Northern Sweden Health and Disease Study. Most analyses (n = 20) rendered null results. In men, we observed an increased prostate cancer risk among high-consumers of cheese (hazard ratio (HR) for highest vs. lowest quintile (Q5-Q1), 1.11; 95% CI, 0.97-1.27; Ptrend = 0.013). In women, high-consumers of cheese had a decreased risk of overall cancer (HR Q5-Q1, 0.95; 95% CI, 0.88-1.04; Ptrend = 0.039), smoking-related (HR Q5-Q1, 0.84; 95% CI, 0.72-0.97; Ptrend ≤ 0.001), and colorectal cancers (HR Q5-Q1, 0.82; 95% CI, 0.63-1.07; Ptrend = 0.048). Butter yielded a weak decreased obesity-related cancer risk in women (HR Q5-Q1, 0.91; 95% CI, 0.81-1.02; Ptrend = 0.049). Fermented milk yielded HRs below zero in women, but with no clear linear associations. In conclusion, this study does not support any major adverse or beneficial effects of fermented milk, non-fermented milk, cheese, and butter in the diet from a cancer risk perspective.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
dairy products, milk, cheese, fermented milk, cancer
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-161682 (URN)10.1080/01635581.2019.1637441 (DOI)000476072800001 ()31298944 (PubMedID)2-s2.0-85068900342 (Scopus ID)
Available from: 2019-07-25 Created: 2019-07-25 Last updated: 2019-08-12
Teixeira Damasceno, N. R., Landfors, F., De Lira Teixeira, L., Fonseca, H., Gidlund, M., Wennberg, P., . . . Nilsson, S. K. (2019). Low Plasma Titer Of Autoantibodies Against Degraded Apob100 Is Independently Associated With Myocardial Infarction. Paper presented at 87th Congress of the European-Atherosclerosis-Society (EAS), MAY 26-29, 2019, Maastricht, Netherlands. Atherosclerosis, 287, E221-E221
Open this publication in new window or tab >>Low Plasma Titer Of Autoantibodies Against Degraded Apob100 Is Independently Associated With Myocardial Infarction
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2019 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 287, p. E221-E221Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-163695 (URN)10.1016/j.atherosclerosis.2019.06.676 (DOI)000482110800674 ()
Conference
87th Congress of the European-Atherosclerosis-Society (EAS), MAY 26-29, 2019, Maastricht, Netherlands
Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2019-10-16Bibliographically approved
Erzurumluoglu, A. M., Liu, M., Jackson, V. E., Barnes, D. R., Datta, G., Melbourne, C. A., . . . Howson, J. M. (2019). Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci. Molecular Psychiatry
Open this publication in new window or tab >>Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
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2019 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578Article in journal (Refereed) Epub ahead of print
Abstract [en]

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-156372 (URN)10.1038/s41380-018-0313-0 (DOI)30617275 (PubMedID)
Available from: 2019-02-13 Created: 2019-02-13 Last updated: 2019-02-27
Ashar, F. N., Mitchell, R. N., Albert, C. M., Newton-Cheh, C., Brody, J. A., Mueller-Nurasyid, M., . . . Sotoodehnia, N. (2018). A comprehensive evaluation of the genetic architecture of sudden cardiac arrest. European Heart Journal, 39(44), 3961-+
Open this publication in new window or tab >>A comprehensive evaluation of the genetic architecture of sudden cardiac arrest
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2018 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 44, p. 3961-+Article in journal (Refereed) Published
Abstract [en]

Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA.

Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk.

Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
Sudden cardiac arrest, Genome-wide association study, Mendelian randomization
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-155117 (URN)10.1093/eurheartj/ehy474 (DOI)000453397900012 ()30169657 (PubMedID)
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved
Ricci, C., Wood, A., Muller, D., Gunter, M. J., Agudo, A., Boeing, H., . . . Ferrari, P. (2018). Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study. BMJ. British Medical Journal, 361, Article ID k934.
Open this publication in new window or tab >>Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study
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2018 (English)In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 361, article id k934Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. DESIGN Multicentre case-cohort study. SETTING A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. PARTICIPANTS 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. MAIN OUTCOME MEASURES Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). RESULTS There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/ day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. CONCLUSIONS Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-150694 (URN)10.1136/bmj.k934 (DOI)000434274800011 ()29844013 (PubMedID)
Available from: 2018-09-06 Created: 2018-09-06 Last updated: 2019-05-17Bibliographically approved
Johansson, I., Nilsson, L. M., Esberg, A., Jansson, J.-H. & Winkvist, A. (2018). Dairy intake revisited - associations between dairy intake and lifestyle related cardio-metabolic risk factors in a high milk consuming population. Nutrition Journal, 17, Article ID 110.
Open this publication in new window or tab >>Dairy intake revisited - associations between dairy intake and lifestyle related cardio-metabolic risk factors in a high milk consuming population
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2018 (English)In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 17, article id 110Article in journal (Refereed) Published
Abstract [en]

Background: The association between milk and dairy intake and the incidence of cardiometabolic diseases, cancer and mortality has been evaluated in many studies, but these studies have had conflicting results with no clear conclusion on causal or confounding associations. The present study aims to further address this association by cross-sectional and longitudinal evaluation of the associations between exposure to various types of dairy products and metabolic risk markers among inhabitants in northern Sweden while taking other lifestyle factors into account.

Methods: Respondents in the Vasterbotten Intervention Programme with complete and plausible diet data between 1991 and 2016 were included, yielding 124,934 observations from 90,512 unique subjects. For longitudinal analysis, 27,682 participants with a visit 8-12years after the first visit were identified. All participants completed a validated Food Frequency Questionnaire. Metabolic risk markers, including body mass index (BMI), blood pressure, serum (S) cholesterol and triglycerides, and blood glucose, were measured. Participants were categorized into quintiles by intake of dairy products, and risk (odds ratios, OR) of undesirable levels of metabolic risk markers was assessed in multivariable logistic regression analyses. In longitudinal analyses, intake quintiles were related to desirable levels of metabolic risk markers at both visits or deterioration at follow-up using Cox regression analyses.

Results: The OR of being classified with an undesirable BMI decreased with increasing quintiles of total dairy, cheese and butter intake but increased with increasing non-fermented milk intake. The OR of being classified with an undesirable S-cholesterol level increased with increasing intake of total dairy, butter and high fat (3%) non-fermented milk, whereas an undesirable S-triglyceride level was inversely associated with cheese and butter intake in women. In longitudinal analyses, increasing butter intake was associated with deterioration of S-cholesterol and blood glucose levels, whereas increasing cheese intake was associated with a lower risk of deterioration of S-triglycerides.

Conclusions: Confounding factors likely contribute to the demonstrated association between dairy intake and mortality, and other medical conditions and analyses should be stratified by dairy type.

Place, publisher, year, edition, pages
BioMed Central, 2018
Keywords
Dairy products, Milk, Cheese, Butter, Fermented milk, Non-fermented milk, BMI, Serum lipids, Blood glucose, Blood pressure
National Category
Nutrition and Dietetics Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-154046 (URN)10.1186/s12937-018-0418-y (DOI)000451026300003 ()30466440 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Research Council
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2018-12-19Bibliographically approved
Johansson, K., Jansson, J.-H., Johansson, L., Wiklund, P.-G., Nilsson, T. K. & Lind, M. (2018). D-Dimer is associated with first-ever intracerebral hemorrhage: a nested case-control study. Stroke, 49(9), 2034-2039
Open this publication in new window or tab >>D-Dimer is associated with first-ever intracerebral hemorrhage: a nested case-control study
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2018 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 49, no 9, p. 2034-2039Article in journal (Refereed) Published
Abstract [en]

Background and Purpose - Hypertension is the most important risk factor for intracerebral hemorrhage (ICH), but further characterization is needed for groups at high risk of ICH. One way to predict the risk of developing a disease is with plasma biomarkers. This study aimed to investigate the association between the biomarker, D-dimer, and ICH risk.

Methods - This population-based, nested case-control study was conducted using data from 2 population-based surveys; the Vasterbotten Intervention Programme and MONICA Northern Sweden (Monitoring Trends and Determinants in Cardiovascular Disease). All participants underwent a health examination and blood sampling at baseline before the event. Cases (n=141) were diagnosed with a first-ever ICH between 1985 and March 2007. One or 2 controls (n=255) were matched to each case.

Results - The median age was 60 years; 39% of participants were women; and the median time from blood sampling to ICH was 5.2 years. When D-dimer was evaluated as a continuous variable, it was significantly associated with ICH. After multivariable adjustment (for hypertension, body mass index, cholesterol levels, diabetes mellitus, and smoking), the odds ratio was 1.36 per SD of D-dimcr (95% CI, 1.05-1.77). When participants were stratified in 3 groups according to time from blood sampling at health examination to ICH, we found that the association between D-dimer levels and ICH was most pronounced in individuals with the shortest time from blood sampling to ICH event (<3.5 years; odds ratio, 1.78; 95% CI, 1.05-3.05).

Conclusions - High plasma concentrations of D-dimer were associated with increased risk of a future ICH, after adjusting for cardiovascular risk factors. This association was predominantly driven by the cases with the shortest time from blood sampling to ICH event.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018
Keywords
biomarkers, case-control studies, cerebral hemorrhage, fibrin fragment, fibrinolysis
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-153829 (URN)10.1161/STROKEAHA.118.021751 (DOI)000442858100014 ()30354971 (PubMedID)
Funder
Västerbotten County CouncilNorrbotten County Council
Available from: 2018-12-11 Created: 2018-12-11 Last updated: 2019-08-20Bibliographically approved
Johansson, K., Jansson, J.-H., Johansson, L., Wiklund, P.-G., Nilsson, T. K. & Lind, M. (2018). D-dimer is associated with first-ever intracerebral hemorrhage. A prospective ease-control study. Cerebrovascular Diseases, 45, 213-213
Open this publication in new window or tab >>D-dimer is associated with first-ever intracerebral hemorrhage. A prospective ease-control study
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2018 (English)In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 45, p. 213-213Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
S. Karger, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-151802 (URN)000440013700104 ()
Note

Supplement: 1

Meeting Abstract: P165

Available from: 2018-09-14 Created: 2018-09-14 Last updated: 2019-08-20Bibliographically approved
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