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Hultdin, Johan
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Publications (10 of 62) Show all publications
Widbom, L., Schneede, J., Karling, P. & Hultdin, J. (2019). Higher plasma cotinine is associated with an increased risk for later developing IBD, especially among users of combusted tobacco. Journal of Crohn's & Colitis, 13, S508-S508
Open this publication in new window or tab >>Higher plasma cotinine is associated with an increased risk for later developing IBD, especially among users of combusted tobacco
2019 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 13, p. S508-S508Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2019
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-157520 (URN)10.1093/ecco-jcc/jjy222.898 (DOI)000460544503018 ()
Note

Supplement: 1

Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-04-05Bibliographically approved
Späth, F., Wibom, C., Krop, E. J., Izarra Santamaria, A., Johansson, A. S., Bergdahl, I., . . . Melin, B. S. (2019). Immune marker changes and risk of multiple myeloma: a nested case-control study using repeated prediagnostic blood samples.. Haematologica, Article ID haematol.2019.216895.
Open this publication in new window or tab >>Immune marker changes and risk of multiple myeloma: a nested case-control study using repeated prediagnostic blood samples.
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2019 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, article id haematol.2019.216895Article in journal (Refereed) Epub ahead of print
Abstract [en]

Biomarkers reliably predicting progression to multiple myeloma are lacking. Myeloma risk has been associated with low blood levels of monocyte chemotactic protein 3, macrophage inflammatory protein 1 alpha, vascular endothelial growth factor, fibroblast growth factor 2, fractalkine, and transforming growth factor alpha. In this study, we aimed to replicate these findings and study the individual dynamics of each marker in a prospective longitudinal cohort, thereby examining their potential as markers of myeloma progression. For this purpose, we identified 65 myeloma cases and 65 matched cancer-free controls each with two donated blood samples within the Northern Sweden Health and Disease Study. Samples from myeloma cases were donated in median 13 and 4 years before myeloma diagnosis. Known risk factors of progression were determined by protein-, and immunofixation electrophoresis, and free light chain assays. We observed lower levels of monocyte chemotactic protein 3, vascular endothelial growth factor, fibroblast growth factor 2, fractalkine, and transforming growth factor alpha in myeloma patients than controls, consistent with previous data. We also observed that these markers decreased among future myeloma patients while remaining stable in controls. Decreasing trajectories were marked for transforming growth factor alpha (P = 2.5 x 10-4) indicating progression to multiple myeloma. Investigating this, we found that low levels of transforming growth factor alpha assessed at time of the repeated sample were independently associated with risk of progression in a multivariable model (hazard ratio = 3.5; P = 0.003). Transforming growth factor alpha can potentially improve early detection of multiple myeloma. .

Keywords
Immune marker change, Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, Progression, prospective longitudinal study
Identifiers
urn:nbn:se:umu:diva-158803 (URN)10.3324/haematol.2019.216895 (DOI)30948485 (PubMedID)
Available from: 2019-05-09 Created: 2019-05-09 Last updated: 2019-05-10
Karling, P., Lundgren, D., Eklöf, V., Palmqvist, R. & Hultdin, J. (2019). Improved monitoring of inflammatory activity in patients with ulcerative colitis by combination of faecal tests for haemoglobin and calprotectin. Scandinavian Journal of Clinical and Laboratory Investigation
Open this publication in new window or tab >>Improved monitoring of inflammatory activity in patients with ulcerative colitis by combination of faecal tests for haemoglobin and calprotectin
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2019 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Article in journal (Refereed) Epub ahead of print
Abstract [en]

Faecal calprotectin (FC) tests and faecal immunological tests (FIT) for haemoglobin have been used to monitor disease activity in patients with ulcerative colitis (UC) but used alone they have some limitation concerning the predictive ability. We aimed to test if an FC test used in combination with FIT could improve the predictive ability. Consecutive out-patients with UC (n = 93) who were admitted for colonoscopy completed a single faecal sample before the start of bowel preparation. A quantitative CALPRO (R) calprotectin ELISA test and a qualitative FIT (cut-off < 40 ng/mL) were analyzed. An estimated Mayo score and a score of histological inflammation was performed blinded to the result of the faecal tests. The sensitivity, specificity, negative predictive value and positive predictive value for endoscopic inflammation (Mayo score > 1) was for FIT 85%, 83%, 96%, 57% and for FC > 186 mu g/g 73%, 87%, 87%, 54%. Corresponding results for FIT*FC > 186 mu g/g (at least one test positive) were 92%, 69%, 97%, 43%. For detecting moderate/severe histological inflammation the results were for FIT 69%, 79%, 92%, 43%, for FC > 75 mu g/g 95%, 62%, 98%, 41%, and for FIT*FC > 75 mu g/g 100%, 60%, 100%, 36%. None of the markers alone or in combination were useful to predict deep remission (Mayo score = 0 and no histological inflammation). We conclude that using the combination of an FC test and FIT shows minor improvement in predictive ability for inflammatory activity and remission in patients with UC.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Faecal calprotectin, faecal immunochemical haemoglobin tests, inflammatory bowel disease, ulcerative colitis
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-161714 (URN)10.1080/00365513.2019.1622148 (DOI)000473803200001 ()31164011 (PubMedID)
Funder
Västerbotten County Council
Available from: 2019-08-05 Created: 2019-08-05 Last updated: 2019-08-05Bibliographically approved
Lundgren, D., Eklöf, V., Palmqvist, R., Hultdin, J. & Karling, P. (2019). Proton pump inhibitor use is associated with elevated faecal calprotectin levels. A cross-sectional study on subjects referred for colonoscopy. Scandinavian Journal of Gastroenterology, 54(2), 152-157
Open this publication in new window or tab >>Proton pump inhibitor use is associated with elevated faecal calprotectin levels. A cross-sectional study on subjects referred for colonoscopy
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2019 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 2, p. 152-157Article in journal (Refereed) Published
Abstract [en]

Objectives: Faecal Calprotectin (FC) is a sensitive marker for gut inflammation. However, slightly elevated FC levels are also common in subjects without inflammation. We investigated the association between FC and clinical factors including concomitant use of medical therapy in patients with a normal colonoscopy.Material and methods: Out-patients (n=1263) referred for colonoscopy, performed FC test (CALPRO) the day before the start of bowel preparation. All subjects answered questionnaires that included questions on the present and past health history, concomitant medical treatment and gastrointestinal symptoms (GSRS). A medical record chart review was performed to check for concomitant disease, cause of referral and the result of the colonoscopy including biopsies. Inclusion criteria were a normal colonoscopy. Exclusion criteria were inflammatory bowel disease, colon cancer and high-grade dysplasia.Results: Five hundred ninety subjects fulfilled the inclusion criteria and completed the study. Thirty-six per cent of the subjects had a FC >50 mu g/g. In a logistic regression analysis, age (adjusted OR: 1.051; CI: 1.032-1.071), and the use of proton pump inhibitors (adjusted OR: 3.843; CI: 2.338-6.316), non-steroid anti-inflammatory drugs (adjusted OR: 2.411; CI: 1.162-5.002) and acetylsalicylic acid (adjusted OR: 2.934; CI: 1.085-3.448) were significantly associated with an elevated FC (>50 mu g/g).Conclusions: More than one-third of the patients with a normal colonoscopy performed in clinical routine had a slightly elevated FC level. Our results emphasise the need for attention to age, the use of proton pump inhibitors, non-steroid anti-inflammatory drugs and acetylsalicylic acid in the interpretation of FC tests in clinical practice.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Faecal calprotectin, colonoscopy, non-steroidal inflammatory drugs, proton pump inhibitors
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-160629 (URN)10.1080/00365521.2019.1566493 (DOI)000468463000004 ()30676120 (PubMedID)
Funder
Västerbotten County Council
Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-06-20Bibliographically approved
Zuo, H., Ueland, P. M., Midttun, O., Tell, G. S., Fanidi, A., Zheng, W., . . . Ulvik, A. (2019). Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3). Annals of Oncology, 30(3), 478-485
Open this publication in new window or tab >>Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3)
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2019 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 30, no 3, p. 478-485Article in journal (Refereed) Published
Abstract [en]

Background: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known.

Materials and methods: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models.

Results: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3years of blood draw (OR: 1.73, 95% CI: 1.34-2.23).

Conclusion: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.

Place, publisher, year, edition, pages
Oxford University Press, 2019
Keywords
PAr, vitamin B6, lung cancer, Lung Cancer Cohort Consortium, inflammation, nested case-control study
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-158604 (URN)10.1093/annonc/mdz002 (DOI)000465084000023 ()30698666 (PubMedID)
Available from: 2019-05-08 Created: 2019-05-08 Last updated: 2019-05-08Bibliographically approved
Andersen, V., Chan, S., Luben, R., Khaw, K.-T., Olsen, A., Tjonneland, A., . . . Hart, A. (2018). Fibre intake and the development of inflammatory bowel disease: A European prospective multi-centre cohort study (EPIC-IBD). Journal of Crohn's & Colitis, 12(2), 129-136
Open this publication in new window or tab >>Fibre intake and the development of inflammatory bowel disease: A European prospective multi-centre cohort study (EPIC-IBD)
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2018 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no 2, p. 129-136Article in journal (Refereed) Published
Abstract [en]

Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn's disease [CD] and ulcerative colitis [UC] in a large European population.

Methods: In total, 401 326 participants, aged 20-80 years, were recruited in eight countries in Europe between 1991 and 1998. At baseline, fibre intake [total fibres, fibres from fruit, vegetables and cereals] was recorded using food frequency questionnaires. The cohort was monitored for the development of inflammatory bowel disease. Each case was matched with four controls and odds ratios [ORs] for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed.

Results: In total, 104 and 221 participants developed incident CD and UC, respectively. For both CD and UC, there were no statistically significant associations with either quartiles, or trends across quartiles, for total fibre or any of the individual sources. The associations were not affected by adjusting for smoking and energy intake. Stratification according to smoking status showed null findings apart from an inverse association with cereal fibre and CD in non-smokers [Quartile 4 vs 1 OR = 0.12, 95% confidence interval = 0.02-0.75, p = 0.023, OR trend across quartiles = 0.50, 95% confidence interval = 0.29-0.86, p = 0.017].

Conclusion: The results do not support the hypothesis that dietary fibre is involved in the aetiology of UC, although future work should investigate whether there may be a protective effect of specific types of fibre according to smoking status in CD.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
Keywords
Dietary fibre, diet, epidemiology, fibre food, inflammatory bowel disease, prospective study
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-144945 (URN)10.1093/ecco-jcc/jjx136 (DOI)000423703000001 ()29373726 (PubMedID)
Available from: 2018-02-22 Created: 2018-02-22 Last updated: 2019-05-20Bibliographically approved
Theofylaktopoulou, D., Midttun, O., Ueland, P. M., Meyer, K., Fanidi, A., Zheng, W., . . . Ulvik, A. (2018). Impaired functional vitamin B6 status is associated with increased risk of lung cancer. International Journal of Cancer, 142(12), 2425-2434
Open this publication in new window or tab >>Impaired functional vitamin B6 status is associated with increased risk of lung cancer
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 12, p. 2425-2434Article in journal (Refereed) Published
Abstract [en]

Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4th vs. 1st) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.

Keywords
pyridoxal 5 '-phosphate, functional vitamin B6 marker, 3-hydroxykynurenine:xanthurenic acid, Lung ncer Cohort Consortium
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-147424 (URN)10.1002/ijc.31215 (DOI)000430390800002 ()29238985 (PubMedID)
Available from: 2018-07-19 Created: 2018-07-19 Last updated: 2019-05-10Bibliographically approved
Muller, D. C., Hodge, A. M., Fanidi, A., Albanes, D., Mai, X. M., Shu, X. O., . . . Brennan, P. (2018). No association between circulating concentrations of vitamin D and risk of lung cancer: an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3). Annals of Oncology, 29(6), 1468-1475
Open this publication in new window or tab >>No association between circulating concentrations of vitamin D and risk of lung cancer: an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3)
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2018 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 29, no 6, p. 1468-1475Article in journal (Refereed) Published
Abstract [en]

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3).

Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables.

Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology.

Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
serum 25-hydroxyvitamin D, vitamin D, lung cancer, case control, prospective, consortium
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-150392 (URN)10.1093/annonc/mdy104 (DOI)000438508100024 ()29617726 (PubMedID)2-s2.0-85050815132 (Scopus ID)
Available from: 2018-08-06 Created: 2018-08-06 Last updated: 2018-08-06Bibliographically approved
Ljungberg, J., Janiec, M., Bergdahl, I., Holmgren, A., Hultdin, J., Johansson, B., . . . Söderberg, S. (2018). Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement. Circulation, 138(6)
Open this publication in new window or tab >>Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement
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2018 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 138, no 6Article in journal (Refereed) Published
Abstract [en]

Background: Aortic valve stenosis (AS) is the most common indication for cardiac valve surgery; untreated AS is linked to high mortality. The etiological background of AS is unknown. Previous human studies were typically based on case-control studies. Biomarkers identified in prospective studies could lead to novel mechanistic insights. Methods: Within a large population survey with blood samples obtained at baseline, 334 patients were identified who later underwent surgery for AS (median age [interquartile range], 59.9 [10.4] years at survey and 68.3 [12.7] at surgery; 48% female). For each case, 2 matched referents were allocated. Plasma was analyzed with the multiplex proximity extension assay for screening of 92 cardiovascular candidate proteins. Conditional logistic regression models were used to assess associations between each protein and AS, with correction for multiple testing. A separate set of 106 additional cases with 212 matched referents was used in a validation study. Results: Six proteins (growth differentiation factor 15, galectin-4, von Willebrand factor, interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9) were associated with case status in the discovery cohort; odds ratios ranged from 1.25 to 1.37 per SD increase in the protein signal. Adjusting the multivariable models for classical cardiovascular risk factors at baseline yielded similar results. Subanalyses of case-referent triplets (n=133) who showed no visible coronary artery disease at the time of surgery in the index person supported associations between AS and growth differentiation factor 15 (odds ratio, 1.40; 95% confidence interval, 1.10-1.78) and galectin-4 (odds ratio, 1.27; 95% confidence interval, 1.02-1.59), but these associations were attenuated after excluding individuals who donated blood samples within 5 years before surgery. In triplets (n=201), which included index individuals with concurrent coronary artery disease at the time of surgery, all 6 proteins were robustly associated with case status in all sensitivity analyses. In the validation study, the association of all but 1 (interleukin 17 receptor A) of these proteins were replicated in patients with AS with concurrent coronary artery disease but not in patients with AS without coronary artery disease. Conclusions: We provide evidence that 5 proteins were altered years before AS surgery and that the associations seem to be driven by concurrent atherosclerotic disease.

Keywords
aortic stenosis, aortic valve surgery, prospective study, proteomics, risk markers
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-145712 (URN)10.1161/CIRCULATIONAHA.117.030414 (DOI)000440866500011 ()29487139 (PubMedID)
Available from: 2018-04-09 Created: 2018-04-09 Last updated: 2019-05-24Bibliographically approved
Salih, A., Widbom, L., Hultdin, J. & Karling, P. (2018). Smoking is associated with risk for developing inflammatory bowel disease including late onset ulcerative colitis: a prospective study. Scandinavian Journal of Gastroenterology, 53(2), 173-178
Open this publication in new window or tab >>Smoking is associated with risk for developing inflammatory bowel disease including late onset ulcerative colitis: a prospective study
2018 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 2, p. 173-178Article in journal (Refereed) Published
Abstract [en]

Objectives: Life style factors have been associated with inflammatory bowel disease (IBD) but there is a lack of data on the exposure of life styles factors before the onset of IBD. Our aim was to study the association between lifestyle factors and the development of IBD in a prospective setting.

Materials and methods: We performed a case control study of 72 patients who later developed ulcerative colitis (UC), 26 patients who developed Crohn's disease (CD) and 427 healthy controls from the Vasterbotten intervention project matched for gender, age, year of health survey and area of residence. At recruitment, participants completed validated lifestyle questionnaires including data on alcohol intake. Information from this was used to assess the connection between lifestyle factors and later developing IBD.

Results: For CD and UC, the median age at diagnosis was 53 and 52 years and median time of survey was 4 and 6 years before diagnosis, respectively. Multivariate odds ratio (OR) showed an association between never smoking and not developing IBD, including both UC and CD, OR (95% CI) 0.341 (0.136-0.853) and 0.473 (0.259-0.864), respectively. Marital status, educational level, alcohol consumption, reported physical activity and use of moist smokeless tobacco (snus) did not differ between patients and controls.

Conclusions: Smoking proves to be a risk factor for both CD and UC in this prospective case-control study. No association was seen for snus users, implying a non-nicotine pathogenic mechanism from combusted tobacco.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
alcohol, Crohn's disease, inflammatory bowel disease, tobacco, smoking, ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-144849 (URN)10.1080/00365521.2017.1418904 (DOI)000423621300010 ()29262738 (PubMedID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-06-09Bibliographically approved
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