| 1. |
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| 2. |
- Burisch, Johan, et al.
(author)
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Disease course of inflammatory bowel disease unclassified in a European population-based inception cohort : an Epi-IBD study
- 2019
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In: Journal of Gastroenterology and Hepatology. - : John Wiley & Sons. - 0815-9319 .- 1440-1746. ; 34:6, s. 996-1003
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Journal article (peer-reviewed)abstract
- BACKGROUND: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following five years.METHODS: The Epi-IBD study is a prospective population-based cohort of 1,289 IBD patients diagnosed in centres across Europe. Clinical data were captured prospectively throughout the follow-up period.RESULTS: Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n=20, 71%) or CD (n=8, 29%) after a median of six months (IQR: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n=6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n=107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU.CONCLUSIONS: In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after five years of follow-up. One in four patients with IBDU eventually were classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.
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| 3. |
- Burisch, Johan, et al.
(author)
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Natural Disease Course of Ulcerative Colitis During the First Five Years of Follow-up in a European Population-based Inception Cohort-An Epi-IBD Study
- 2019
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In: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 13:2, s. 198-208
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Journal article (peer-reviewed)abstract
- Background and Aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort.Methods: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.Results: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8].Conclusions: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation.
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| 4. |
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- 2019
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Journal article (peer-reviewed)
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| 5. |
- Andersen, Vibeke, et al.
(author)
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Colorectal cancer in patients with inflammatory bowel disease : can we predict risk?
- 2012
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In: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 18:31, s. 4091-4094
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Journal article (peer-reviewed)abstract
- The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), may be complicated by colorectal cancer (CRC). In a recent population-based cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed CRC during 30 years of observation. The overall risk of CRC among patients with UC and CD was comparable with that of the general population. However, patients diagnosed with UC during childhood or as adolescents, patients with long duration of disease and those with concomitant primary sclerosing cholangitis were at increased risk. In this commentary, we discuss the mechanisms underlying carcinogenesis in IBD and current investigations of genetic susceptibility in IBD patients. Further advances will depend on the cooperative work by epidemiologist and molecular geneticists in order to identify genetic polymorphisms involved in IBD-associated CRC. The ultimate goal is to incorporate genotypes and clinical parameters into a predictive model that will refine the prediction of risk for CRC in colonic IBD. The challenge will be to translate these new findings into clinical practice and to determine appropriate preventive strategies in order to avoid CRC in IBD patients. The achieved knowledge may also be relevant for other inflammation-associated cancers.
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| 6. |
- Andersen, Vibeke, et al.
(author)
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Fibre intake and the development of inflammatory bowel disease : A European prospective multi-centre cohort study (EPIC-IBD)
- 2018
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In: Journal of Crohn's & Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 12:2, s. 129-136
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Journal article (peer-reviewed)abstract
- 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.
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| 7. |
- Berge, Tone, et al.
(author)
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T cell specific adapter protein (TSAd) interacts with Tec kinase ITK to promote CXCL12 induced migration of human and murine T cells
- 2010
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:3, s. e9761-
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Journal article (peer-reviewed)abstract
- BACKGROUND: The chemokine CXCL12/SDF-1alpha interacts with its G-protein coupled receptor CXCR4 to induce migration of lymphoid and endothelial cells. T cell specific adapter protein (TSAd) has been found to promote migration of Jurkat T cells through interaction with the G protein beta subunit. However, the molecular mechanisms for how TSAd influences cellular migration have not been characterized in detail. PRINCIPAL FINDINGS: We show that TSAd is required for tyrosine phosphorylation of the Lck substrate IL2-inducible T cell kinase (Itk). Presence of Itk Y511 was necessary to boost TSAd's effect on CXCL12 induced migration of Jurkat T cells. In addition, TSAd's ability to promote CXCL12-induced actin polymerization and migration of Jurkat T lymphocytes was dependent on the Itk-interaction site in the proline-rich region of TSAd. Furthermore, TSAd-deficient murine thymocytes failed to respond to CXCL12 with increased Itk phosphorylation, and displayed reduced actin polymerization and cell migration responses. CONCLUSION: We propose that TSAd, through its interaction with both Itk and Lck, primes Itk for Lck mediated phosphorylation and thereby regulates CXCL12 induced T cell migration and actin cytoskeleton rearrangements.
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| 8. |
- Burisch, Johan, et al.
(author)
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Construction and validation of a web-based epidemiological database for inflammatory bowel diseases in Europe An EpiCom study
- 2011
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In: JOURNAL OF CROHNS and COLITIS. - : Elsevier Science B.v; Amsterdam. - 1873-9946 .- 1876-4479. ; 5:4, s. 342-349
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Journal article (peer-reviewed)abstract
- Background: The EpiCom-study investigates a possible East-West-gradient in Europe in the incidence of IBD and the association with environmental factors. A secured web-based database is used to facilitate and centralize data registration. Aim: To construct and validate a web-based inception cohort database available in both English and Russian language. Method: The EpiCom database has been constructed in collaboration with all 34 participating centers. The database was translated into Russian using forward translation, patient questionnaires were translated by simplified forward-backward translation. Data insertion implies fulfillment of international diagnostic criteria, disease activity, medical therapy, quality of life, work productivity and activity impairment, outcome of pregnancy, surgery, cancer and death. Data is secured by the WinLog3 System, developed in cooperation with the Danish Data Protection Agency. Validation of the database has been performed in two consecutive rounds, each followed by corrections in accordance with comments. Results: The EpiCom database fulfills the requirements of the participating countries local data security agencies by being stored at a single location. The database was found overall to be "good" or "very good" by 81% of the participants after the second validation round and the general applicability of the database was evaluated as "good" or "very good" by 77%. In the inclusion period January 1st -December 31st 2010 1336 IBD patients have been included in the database. Conclusion: A user-friendly, tailor-made and secure web-based inception cohort database has been successfully constructed, facilitating remote data input. The incidence of IBD in 23 European countries can be found at www.epicom-ecco.eu. (C) 2011 European Crohns and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
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| 9. |
- Burisch, Johan, et al.
(author)
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Costs and resource utilization for diagnosis and treatment during the initial year in a European inflammatory bowel disease inception cohort : an ECCO-EpiCom Study
- 2015
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In: Inflammatory Bowel Diseases. - 1078-0998 .- 1536-4844. ; 21:1, s. 121-131
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Journal article (peer-reviewed)abstract
- BACKGROUND: No direct comparison of health care cost in patients with inflammatory bowel disease across the European continent exists. The aim of this study was to assess the costs of investigations and treatment for diagnostics and during the first year after diagnosis in Europe.METHODS: The EpiCom cohort is a prospective population-based inception cohort of unselected inflammatory bowel disease patients from 31 Western and Eastern European centers. Patients were followed every third month from diagnosis, and clinical data regarding treatment and investigations were collected. Costs were calculated in euros (&OV0556;) using the Danish Health Costs Register.RESULTS: One thousand three hundred sixty-seven patients were followed, 710 with ulcerative colitis, 509 with Crohn's disease, and 148 with inflammatory bowel disease unclassified. Total expenditure for the cohort was &OV0556;5,408,174 (investigations: &OV0556;2,042,990 [38%], surgery: &OV0556;1,427,648 [26%], biologicals: &OV0556;781,089 [14%], and standard treatment: &OV0556;1,156,520 [22%)]). Mean crude expenditure per patient in Western Europe (Eastern Europe) with Crohn's disease: investigations &OV0556;1803 (&OV0556;2160) (P = 0.44), surgery &OV0556;11,489 (&OV0556;13,973) (P = 0.14), standard treatment &OV0556;1027 (&OV0556;824) (P = 0.51), and biologicals &OV0556;7376 (&OV0556;8307) (P = 0.31). Mean crude expenditure per patient in Western Europe (Eastern Europe) with ulcerative colitis: investigations &OV0556;1189 (&OV0556;1518) (P < 0.01), surgery &OV0556;18,414 (&OV0556;12,395) (P = 0.18), standard treatment &OV0556;896 (&OV0556;798) (P < 0.05), and biologicals &OV0556;5681 (&OV0556;72) (P = 0.51).CONCLUSIONS: In this population-based unselected cohort, costs during the first year of disease were mainly incurred by investigative procedures and surgeries. However, biologicals accounted for >15% of costs. Long-term follow-up of the cohort is needed to assess the cost-effectiveness of biological agents.
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| 10. |
- Burisch, Johan, et al.
(author)
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Initial Disease Course and Treatment in an Inflammatory Bowel Disease Inception Cohort in Europe : The ECCO-EpiCom Cohort
- 2014
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In: Inflammatory Bowel Diseases. - : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 20:1, s. 36-46
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Journal article (peer-reviewed)abstract
- Background:The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort.Methods:Patients were followed-up every third month during the first 12 (3) months, and clinical data, demographics, disease activity, medical therapy, surgery, cancers, and deaths were collected and entered in a Web-based database (www.epicom-ecco.eu).Results:In total, 1367 patients were included in the 1-year follow-up. In western Europe, 65 Crohn's disease (CD) (16%), 20 ulcerative colitis (UC) (4%), and 4 IBD unclassified (4%) patients underwent surgery, and in eastern Europe, 12 CD (12%) and 2 UC (1%) patients underwent surgery. Eighty-one CD (20%), 80 UC (14%), and 13 (9%) IBD unclassified patients were hospitalized in western Europe compared with 17 CD (16%) and 12 UC (8%) patients in eastern Europe. The cumulative probability of receiving immunomodulators was 57% for CD in western (median time to treatment 2 months) and 44% (1 month) in eastern Europe, and 21% (5 months) and 5% (6 months) for biological therapy, respectively. For UC patients, the cumulative probability was 22% (4 months) and 15% (3 months) for immunomodulators and 6% (3 months) and 1% (12 months) for biological therapy, respectively in the western and eastern Europe.Discussion:In this cohort, immunological therapy was initiated within the first months of disease. Surgery and hospitalization rates did not differ between patients from eastern and western Europe, although more western European patients received biological agents and were comparable to previous population-based inception cohorts.
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| 11. |
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| 12. |
- Burisch, Johan, et al.
(author)
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Occurrence of anaemia in the first year of inflammatory bowel disease in a European population-based inception cohort : An ECCO-EpiCom study
- 2017
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In: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 11:10, s. 1213-1222
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Journal article (peer-reviewed)abstract
- Background and aims: Anaemia is an important complication of inflammatory bowel disease (IBD). The aim of this study was to determine the prevalence of anaemia and the practice of anaemia screening during the first year following diagnosis in a European prospective population-based inception cohort.Methods: Newly diagnosed IBD patients were included and followed prospectively for one year in 29 European and 1 Australian centre. Clinical data including demographics, medical therapy, surgery and blood samples were collected. Anaemia was defined according to the World Health Organization.Results: A total of 1,871 patients (CD: 686, 88%; UC: 1,021, 87%; IBDU 164. 81%) were included in the study. The prevalence of anaemia was higher in CD than in UC patients and overall, 49% of CD and 39% of UC patients had at least one instance of anaemia during the first 12 months after diagnosis. UC patients with more extensive disease and those from Eastern European countries, and CD patients with penetrating disease or colonic disease location, had higher risks of anaemia. CD and UC patients in need of none or only mild anti-inflammatory treatment had a lower risk of anaemia. In a significant proportion of patients, anaemia was not assessed until several months after diagnosis, and in almost half of all cases of anaemia a thorough work-up was not performed.Conclusions: Overall, 42% of patients had at least one instance of anaemia during the first year following diagnosis. Most patients were assessed for anaemia regularly; however, a full anaemia work-up was frequently neglected in this community setting.
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| 13. |
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| 14. |
- Cleynen, Isabelle, et al.
(author)
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Inherited determinants of Crohn's disease and ulcerative colitis phenotypes : a genetic association study
- 2016
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In: The Lancet. - New York, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 387:10014, s. 156-167
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Journal article (peer-reviewed)abstract
- Background: Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases.Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile.Findings: After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65 × 10(-78)), even after exclusion of NOD2, MHC, and 3p21 (p=9·23 × 10(-18)). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8 × 10(-4)).Interpretation: Our data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time.Funding: International Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list).
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| 15. |
- Dueholm, Morten Kam Dahl, et al.
(author)
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MiDAS 5 : Global diversity of bacteria and archaea in anaerobic digesters
- 2024
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In: Nature Communications. - 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- Anaerobic digestion of organic waste into methane and carbon dioxide (biogas) is carried out by complex microbial communities. Here, we use full-length 16S rRNA gene sequencing of 285 full-scale anaerobic digesters (ADs) to expand our knowledge about diversity and function of the bacteria and archaea in ADs worldwide. The sequences are processed into full-length 16S rRNA amplicon sequence variants (FL-ASVs) and are used to expand the MiDAS 4 database for bacteria and archaea in wastewater treatment systems, creating MiDAS 5. The expansion of the MiDAS database increases the coverage for bacteria and archaea in ADs worldwide, leading to improved genus- and species-level classification. Using MiDAS 5, we carry out an amplicon-based, global-scale microbial community profiling of the sampled ADs using three common sets of primers targeting different regions of the 16S rRNA gene in bacteria and/or archaea. We reveal how environmental conditions and biogeography shape the AD microbiota. We also identify core and conditionally rare or abundant taxa, encompassing 692 genera and 1013 species. These represent 84–99% and 18–61% of the accumulated read abundance, respectively, across samples depending on the amplicon primers used. Finally, we examine the global diversity of functional groups with known importance for the anaerobic digestion process.
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| 16. |
- Ellinghaus, David, et al.
(author)
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Association between variants of PRDM1 and NDP52 and Crohn's disease, based on exome sequencing and functional studies
- 2013
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In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 145:2, s. 339-347
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Genome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD through detailed sequencing, genetic association, expression, and functional studies.METHODS: We sequenced whole exomes of 42 unrelated subjects with CD and 5 healthy subjects (controls) and then filtered single nucleotide variants by incorporating association results from meta-analyses of CD GWAS and in silico mutation effect prediction algorithms. We then genotyped 9348 subjects with CD, 2868 subjects with ulcerative colitis, and 14,567 control subjects and associated variants analyzed in functional studies using materials from subjects and controls and in vitro model systems.RESULTS: We identified rare missense mutations in PR domain-containing 1 (PRDM1) and associated these with CD. These mutations increased proliferation of T cells and secretion of cytokines on activation and increased expression of the adhesion molecule L-selectin. A common CD risk allele, identified in GWAS, correlated with reduced expression of PRDM1 in ileal biopsy specimens and peripheral blood mononuclear cells (combined P = 1.6 x 10(-8)). We identified an association between CD and a common missense variant, Val248Ala, in nuclear domain 10 protein 52 (NDP52) (P = 4.83 x 10(-9)). We found that this variant impairs the regulatory functions of NDP52 to inhibit nuclear factor kappa B activation of genes that regulate inflammation and affect the stability of proteins in Toll-like receptor pathways.CONCLUSIONS: We have extended the results of GWAS and provide evidence that variants in PRDM1 and NDP52 determine susceptibility to CD. PRDM1 maps adjacent to a CD interval identified in GWAS and encodes a transcription factor expressed by T and B cells. NDP52 is an adaptor protein that functions in selective autophagy of intracellular bacteria and signaling molecules, supporting the role of autophagy in the pathogenesis of CD.
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| 17. |
- Fejrskov, Anja, et al.
(author)
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Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease : protocol for the Nordic inception cohort study (NORDTREAT)
- 2024
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In: BMJ Open. - : BioMed Central (BMC). - 2044-6055. ; 14:5
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death.METHODS AND ANALYSIS: We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits.ETHICS AND DISSEMINATION: This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.CLINICAL TRIAL REGISTRATION NUMBER: NCT05414578; Pre-results.
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| 18. |
- Hammerling, Ulf, et al.
(author)
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Identifying Food Consumption Patterns among Young Consumers by Unsupervised and Supervised Multivariate Data Analysis
- 2014
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In: European Journal of Nutrition & Food Safety. - 2347-5641. ; 4:4, s. 392-403
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Journal article (peer-reviewed)abstract
- Although computational multivariate data analysis (MDA) already has been employed in the dietary survey area, the results reported are based mainly on classical exploratory (descriptive) techniques. Therefore, data of a Swedish and a Danish dietary survey on young consumers (4 to 5 years of age) were subjected not only to modern exploratory MDA, but also modern predictive MDA that via supervised learning yielded predictive classification models. The exploratory part, also encompassing Swedish 8 or 11-year old Swedish consumers, included new innovative forms of hierarchical clustering and bi-clustering. This resulted in several interesting multi-dimensional dietary patterns (dietary prototypes), including striking difference between those of the age-matched Danish and Swedish children. The predictive MDA disclosed additional multi-dimensional food consumption relationships. For instance, the consumption patterns associated with each of several key foods like bread, milk, potato and sweetened beverages, were found to differ markedly between the Danish and Swedish consumers. In conclusion, the joint application of modern descriptive and predictive MDA to dietary surveys may enable new levels of diet quality evaluation and perhaps also prototype-based toxicology risk assessment.
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| 19. |
- Hertel, Ole, et al.
(author)
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Assessing atmospheric nitrogen deposition to natural and semi-natural ecosystems - Experience from Danish studies using the DAMOS
- 2013
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In: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 66, s. 151-160
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Journal article (peer-reviewed)abstract
- Local agricultural emissions contribute significantly to the atmospheric reactive nitrogen loads of Danish terrestrial ecosystems. In the vicinity of the sources this may be up to 6-8 kg N ha(-1) yr(-1) depending on location and ecosystem type. This contribution arises from dry deposition of gas phase ammonia derived from local livestock production. Long-range transport, however, often constitutes the largest contribution to the overall atmospheric terrestrial reactive nitrogen loadings in Denmark. This is often in the range 10-15 kg N ha(-1) yr(-1) and consists mainly of aerosol phase nitrate and ammonium (reaction products of nitrogen oxides and ammonia), but also dry deposition of other reactive nitrogen compounds (mainly nitrogen oxides in the form of gas phase nitric acid and nitrogen dioxide). In Denmark's environmental management of the sensitive terrestrial ecosystems modelling tools are required that account for both the local and the long-range transported contributions. This motivated development of the Danish Ammonia MOdelling System (DAMOS) that has been successfully applied to the assessment of atmospheric nitrogen loadings to sensitive Danish ecosystems. We present here three different examples of such assessments. Our results show that ecosystems located in Western Denmark (Case 1) receive the highest loads of atmospheric nitrogen depositions which generally exceed the critical load. This part of the country has the highest livestock density. In the Eastern part of the country, the atmospheric loadings are often below or close to the lower end of the interval for critical load values. These lower loads in Eastern Denmark (Case 2) are due to lower density of agricultural activities, as well as, lower precipitation rates, which leads to less wet deposition of reactive nitrogen. In general there is a gradient in atmospheric deposition over the country, with the highest depositions in the South-Western part of Denmark (Case 3) due to long-range transport contributions from North-Western Europe, but also due to local ammonia deposition associated with the high local emission from the high density livestock farming in this area. (c) 2012 Elsevier Ltd. All rights reserved.
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| 20. |
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| 21. |
- Lokkegaard, Sanne, et al.
(author)
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MCM3 upregulation confers endocrine resistance in breast cancer and is a predictive marker of diminished tamoxifen benefit
- 2021
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In: npj Breast Cancer. - : NATURE RESEARCH. - 2374-4677. ; 7:1
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Journal article (peer-reviewed)abstract
- Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser(315,33)), CHK1(Ser(317)), and cdc25b(Ser(323)), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.
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| 22. |
- Lu, Yunxia, et al.
(author)
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Dietary Polyphenols in the Aetiology of Crohn's Disease and Ulcerative Colitis-A Multicenter European Prospective Cohort Study (EPIC)
- 2017
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In: Inflammatory Bowel Diseases. - : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 23:12, s. 2072-2082
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Journal article (peer-reviewed)abstract
- Background: Oxidative stress may be involved in the aetiology of inflammatory bowel disease and whether dietary polyphenols, which possess antioxidants properties, prevent its development is unknown.Methods: A total of 401,326 men and women aged 20 to 80 years from 8 countries were recruited between 1991 and 1998 and at baseline completed validated food frequency questionnaires. Dietary polyphenol intake was measured using Phenol-Explorer, a database with information on the content of 502 polyphenols. Incident cases of Crohn's diseases (CD) and ulcerative colitis (UC) were identified during the follow-up period of up to December 2010. A nested case–control study using conditional logistic regression estimated the odds ratios (ORs), and 95% confidence intervals, for polyphenol intake (categories based on quartiles) and developing CD or UC.Results: In total, 110 CD (73% women) and 244 UC (57% women) cases were identified and matched to 440 and 976 controls, respectively. Total polyphenol intake was not associated with CD ( P trend = 0.17) or UC ( P trend = 0.16). For flavones and CD, there were reduced odds for all quartiles, which were statistically significant for the third (OR 3rd versus 1st quartile = 0.33; 95% confidence interval, 0.15–0.69) and there was an inverse trend across quartiles ( P = 0.03). Similarly, for resveratrol, there was an inverse association with CD (OR 4th versus 1st quartile = 0.40; 95% confidence interval, 0.20–0.82) with an inverse trend across quartiles ( P = 0.02). No significant associations between subtypes of polyphenols and UC were found. Effect modification by smoking in CD was documented with borderline statistical significance.Conclusions: The data supports a potential role of flavones and resveratrol in the risk of developing CD; future aetiological studies should investigate these dietary components and further examine the potential for residual confounding.
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| 23. |
- Lundemann, Michael, et al.
(author)
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Feasibility of multi-parametric PET and MRI for prediction of tumour recurrence in patients with glioblastoma
- 2019
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 46:3, s. 603-613
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Journal article (peer-reviewed)abstract
- Background: Recurrence in glioblastoma patients often occur close to the original tumour and indicates that the current treatment is inadequate for local tumour control. In this study, we explored the feasibility of using multi-modality imaging at the time of radiotherapy planning. Specifically, we aimed to identify parameters from pre-treatment PET and MRI with potential to predict tumour recurrence. Materials and methods: Sixteen patients were prospectively recruited and treated according to established guidelines. Multi-parametric imaging with 18 F-FET PET/CT and 18 F-FDG PET/MR including diffusion and dynamic contrast enhanced perfusion MRI were performed before radiotherapy. Correlations between imaging parameters were calculated. Imaging was related to the voxel-wise outcome at the time of tumour recurrence. Within the radiotherapy target, median differences of imaging parameters in recurring and non-recurring voxels were calculated for contrast-enhancing lesion (CEL), non-enhancing lesion (NEL), and normal appearing grey and white matter. Logistic regression models were created to predict the patient-specific probability of recurrence. The most important parameters were identified using standardized model coefficients. Results: Significant median differences between recurring and non-recurring voxels were observed for FDG, FET, fractional anisotropy, mean diffusivity, mean transit time, extra-vascular, extra-cellular blood volume and permeability derived from scans prior to chemo-radiotherapy. Tissue-specific patterns of voxel-wise correlations were observed. The most pronounced correlations were observed for 18 F-FDG- and 18 F-FET-uptake in CEL and NEL. Voxel-wise modelling of recurrence probability resulted in area under the receiver operating characteristic curve of 0.77 from scans prior to therapy. Overall, FET proved to be the most important parameter for recurrence prediction. Conclusion: Multi-parametric imaging before radiotherapy is feasible and significant differences in imaging parameters between recurring and non-recurring voxels were observed. Combining parameters in a logistic regression model enabled patient-specific maps of recurrence probability, where 18 F-FET proved to be most important. This strategy could enable risk-adapted radiotherapy planning.
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| 24. |
- Matthiessen, Jeppe, et al.
(author)
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Reduction in pedometer-determined physical activity in the adult Danish population from 2007-2012
- 2015
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In: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 43:5, s. 525-533
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Journal article (peer-reviewed)abstract
- Aims: To examine the development in pedometer-determined physical activity from 2007-2008 to 2011-2012 in the adult Danish population. Methods: The study population comprised two random samples of 18-75-year-old individuals who took part in cross-sectional studies in 2007-2008 (n=224) and 2011-2012 (n=1515). Pedometer data (sealed Yamax SW 200) were obtained for seven consecutive days. Data for 1624 participants (48.2% men) were included in the analysis. An overall step-defined activity level was examined based on a graduated step index (sedentary, low active, somewhat active, active, highly active). The pedometer-determined outcomes were analysed using regression models. Results: A borderline significant decline (p=0.077) from 8788 to 8341 steps/day (-446 (95% confidence intervals -50, 943)) was found between 2007-2008 and 2011-2012. Furthermore, a 23.7% (95% confidence intervals -41.7%, -0.1%) lower overall step-defined activity level was observed in 2011-2012 compared to 2007-2008. These changes were primarily due to a reduced level of activity among women. The proportion of individuals taking 10,000 steps/day decreased non-significantly from 34.8% to 29.3%, whereas the proportion taking <5000 steps/day did not differ between survey periods. Conclusions: This nationally representative survey suggests an overall reduction in the physical activity level among Danish adults. The reduction was due to a shift in the population distribution from higher to lower levels of activity. If this shift is true, it is worrying from a public health perspective. Our study result needs, however, to be confirmed by other population studies.
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| 25. |
- Matthiessen, Jeppe, et al.
(author)
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Reduction in pedometer-determined physical activity in the adult Danish population from 2007 to 2012
- 2015
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In: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 43:5, s. 525-533
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Journal article (peer-reviewed)abstract
- Aims: To examine the development in pedometer-determined physical activity from 2007-2008 to 2011-2012 in the adult Danish population. Methods: The study population comprised two random samples of 18-75-year-old individuals who took part in cross-sectional studies in 2007-2008 (n=224) and 2011-2012 (n=1515). Pedometer data (sealed Yamax SW 200) were obtained for seven consecutive days. Data for 1624 participants (48.2% men) were included in the analysis. An overall step-defined activity level was examined based on a graduated step index (sedentary, low active, somewhat active, active, highly active). The pedometer-determined outcomes were analysed using regression models. Results: A borderline significant decline (p=0.077) from 8788 to 8341 steps/day (-446 (95% confidence intervals -50, 943)) was found between 2007-2008 and 2011-2012. Furthermore, a 23.7% (95% confidence intervals -41.7%, -0.1%) lower overall step-defined activity level was observed in 2011-2012 compared to 2007-2008. These changes were primarily due to a reduced level of activity among women. The proportion of individuals taking 10,000 steps/day decreased non-significantly from 34.8% to 29.3%, whereas the proportion taking <5000 steps/day did not differ between survey periods. Conclusions: This nationally representative survey suggests an overall reduction in the physical activity level among Danish adults. The reduction was due to a shift in the population distribution from higher to lower levels of activity. If this shift is true, it is worrying from a public health perspective. Our study result needs, however, to be confirmed by other population studies.
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