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| 2. |
- Arndt, D. S., et al.
(author)
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STATE OF THE CLIMATE IN 2017
- 2018
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In: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Research review (peer-reviewed)
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| 3. |
- Attauabi, Mohamed, et al.
(author)
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Influence of Genetics, Immunity and the Microbiome on the Prognosis of Inflammatory Bowel Disease (IBD Prognosis Study) : the protocol for a Copenhagen IBD Inception Cohort Study
- 2022
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:6, s. e055779-e055779
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Journal article (peer-reviewed)abstract
- Introduction: Inflammatory bowel diseases (IBD), encompassing Crohn's disease and ulcerative colitis, are chronic, inflammatory diseases of the gastrointestinal tract. We have initiated a Danish population-based inception cohort study aiming to investigate the underlying mechanisms for the heterogeneous course of IBD, including need for, and response to, treatment.Methods and analysis: IBD Prognosis Study is a prospective, population-based inception cohort study of unselected, newly diagnosed adult, adolescent and paediatric patients with IBD within the uptake area of Hvidovre University Hospital and Herlev University Hospital, Denmark, which covers approximately 1 050 000 inhabitants (~20% of the Danish population). The diagnosis of IBD will be according to the Porto diagnostic criteria in paediatric and adolescent patients or the Copenhagen diagnostic criteria in adult patients. All patients will be followed prospectively with regular clinical examinations including ileocolonoscopies, MRI of the small intestine, validated patient-reported measures and objective examinations with intestinal ultrasound. In addition, intestinal biopsies from ileocolonoscopies, stool, rectal swabs, saliva samples, swabs of the oral cavity and blood samples will be collected systematically for the analysis of biomarkers, microbiome and genetic profiles. Environmental factors and quality of life will be assessed using questionnaires and, when available, automatic registration of purchase data. The occurrence and course of extraintestinal manifestations will be evaluated by rheumatologists, dermatologists and dentists, and assessed by MR cholangiopancreatography, MR of the spine and sacroiliac joints, ultrasonography of peripheral joints and entheses, clinical oral examination, as well as panoramic radiograph of the jaws. Fibroscans and dual-energy X-ray absorptiometry scans will be performed to monitor occurrence and course of chronic liver diseases, osteopenia and osteoporosis.Ethics and dissemination: This study has been approved by Ethics Committee of the Capital Region of Denmark (approval number: H-20065831). Study results will be disseminated through publication in international scientific journals and presentation at (inter)national conferences.
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| 4. |
- Auer, Renate, et al.
(author)
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Measuring the Signs of H-1(alpha) Chemical Shift Differences Between Ground and Excited Protein States by Off-Resonance Spin-Lock R-1 rho NMR Spectroscopy
- 2009
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In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 131:31, s. 10832-10833
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Journal article (peer-reviewed)abstract
- Analysis of Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR profiles provides the kinetics and thermodynamics of millisecond-time-scale exchange processes involving the interconversion of populated ground and invisible excited states. In addition, the absolute values of chemical, shift differences between NMR probes in the exchanging states, vertical bar Delta(pi)vertical bar, are also extracted. Herein, we present a simple experiment for obtaining the sign of H-1(alpha) Delta(pi) values by measuring off-resonance H-1(alpha) decay rates, R-1 rho, using weak proton spin-lock fields. A pair of R-1 rho values is measured with a spin-lock field applied vertical bar Delta omega vertical bar downfield and upfield of the major-state peak. In many cases, these two relaxation rates differ substantially, with the larger one corresponding to the case where the spin-lock field coincides with the resonance frequency of the probe in the minor state. The utility of the methodology is demonstrated first on a system involving protein ligand exchange and subsequently on an SH3 domain exchanging between a folded state and its on-pathway folding intermediate. With this experiment, it thus becomes possible to determine H-1(alpha) chemical shifts of the invisible excited state, which can be used as powerful restraints in defining the structural properties of these elusive conformers.
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| 6. |
- Brorsson, C., et al.
(author)
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Identification of T1D susceptibility genes within the MHC region by combining protein interaction networks and SNP genotyping data
- 2009
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In: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 11:S1, s. 60-66
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Journal article (peer-reviewed)abstract
- To develop novel methods for identifying new genes that contribute to the risk of developing type 1 diabetes within the Major Histocompatibility Complex (MHC) region on chromosome 6, independently of the known linkage disequilibrium (LD) between human leucocyte antigen (HLA)-DRB1, -DQA1, -DQB1 genes. We have developed a novel method that combines single nucleotide polymorphism (SNP) genotyping data with protein-protein interaction (ppi) networks to identify disease-associated network modules enriched for proteins encoded from the MHC region. Approximately 2500 SNPs located in the 4 Mb MHC region were analysed in 1000 affected offspring trios generated by the Type 1 Diabetes Genetics Consortium (T1DGC). The most associated SNP in each gene was chosen and genes were mapped to ppi networks for identification of interaction partners. The association testing and resulting interacting protein modules were statistically evaluated using permutation. A total of 151 genes could be mapped to nodes within the protein interaction network and their interaction partners were identified. Five protein interaction modules reached statistical significance using this approach. The identified proteins are well known in the pathogenesis of T1D, but the modules also contain additional candidates that have been implicated in beta-cell development and diabetic complications. The extensive LD within the MHC region makes it important to develop new methods for analysing genotyping data for identification of additional risk genes for T1D. Combining genetic data with knowledge about functional pathways provides new insight into mechanisms underlying T1D.
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| 7. |
- Brorsson, Caroline, et al.
(author)
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The Type 1 Diabetes - HLA Susceptibility Interactome - Identification of HLA Genotype-Specific Disease Genes for Type 1 Diabetes
- 2010
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:3
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Journal article (peer-reviewed)abstract
- Background: The individual contribution of genes in the HLA region to the risk of developing type 1 diabetes (T1D) is confounded by the high linkage disequilibrium (LD) in this region. Using a novel approach we have combined genetic association data with information on functional protein-protein interactions to elucidate risk independent of LD and to place the genetic association into a functional context. Methodology/Principal Findings: Genetic association data from 2300 single nucleotide polymorphisms (SNPs) in the HLA region was analysed in 2200 T1D family trios divided into six risk groups based on HLA-DRB1 genotypes. The best SNP signal in each gene was mapped to proteins in a human protein interaction network and their significance of clustering in functional network modules was evaluated. The significant network modules identified through this approach differed between the six HLA risk groups, which could be divided into two groups based on carrying the DRB1*0301 or the DRB1*0401 allele. Proteins identified in networks specific for DRB1*0301 carriers were involved in stress response and inflammation whereas in DRB1*0401 carriers the proteins were involved in antigen processing and presentation. Conclusions/Significance: In this study we were able to hypothesise functional differences between individuals with T1D carrying specific DRB1 alleles. The results point at candidate proteins involved in distinct cellular processes that could not only help the understanding of the pathogenesis of T1D, but also the distinction between individuals at different genetic risk for developing T1D.
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| 8. |
- Byskov, Camilla S., et al.
(author)
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Treatment plan comparison of proton vs photon radiotherapy for lower-grade gliomas
- 2021
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In: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 20, s. 98-104
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Journal article (peer-reviewed)abstract
- Background and purpose: Patients with lower-grade gliomas are long-term survivors after radiotherapy and may benefit from the reduced dose to normal tissue achievable with proton therapy. Here, we aimed to quantify differences in dose to the uninvolved brain and contralateral hippocampus and compare the risk of radiation-induced secondary cancer for photon and proton plans for lower-grade glioma patients. Materials and methods: Twenty-three patients were included in this in-silico planning comparative study and had photon and proton plans calculated (50.4 Gy(RBE = 1.1), 28 Fx) applying similar dose constraints to the target and organs at risk. Automatically calculated photon plans were generated with a 3 mm margin from clinical target volume (CTV) to planning target volume. Manual proton plans were generated using robust optimisation on the CTV. Dose metrics of organs at risk were compared using population mean dose-volume histograms and Wilcoxon signed-rank test. Secondary cancer risk per 10,000 persons per year (PPY) was estimated using dose-volume data and a risk model for secondary cancer induction. Results: CTV coverage (V95%>98%) was similar for the two treatment modalities. Mean dose (D-mean) to the uninvolved brain was significantly reduced from 21.5 Gy (median, IQR 17.1-24.4 Gy) with photons compared to 10.3 Gy(RBE) (8.1-13.9 Gy(RBE)) with protons. D-mean to the contralateral hippocampus was significantly reduced from 6.5 Gy (5.4-11.7 Gy) with photons to 1.5 Gy(RBE) (0.4-6.8 Gy(RBE)) with protons. The estimated secondary cancer risk was reduced from 6.7 PPY (median, range 3.3-10.4 PPY) with photons to 3.0 PPY (1.3-7.5 PPY) with protons. Conclusion: A significant reduction in mean dose to uninvolved brain and contralateral hippocampus was found with proton planning. The estimated secondary cancer risk was reduced with proton therapy.
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| 9. |
- C-Bergstrand, Ingar, et al.
(author)
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Timolol increased retrobulbar flow velocities in untreated glaucoma eyes but not in ocular hypertension
- 2001
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In: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 79:5, s. 455-461
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Journal article (peer-reviewed)abstract
- PURPOSE: To investigate retrobulbar blood flow velocities and the effects of topical timolol treatment in eyes with newly detected, previously untreated open angle glaucoma or ocular hypertension. METHODS: Fifteen eyes with open angle glaucoma (OAG) and 12 eyes with ocular hypertension (OH), in the same number of patients, all untreated and newly detected, were examined with colour Doppler imaging of retrobulbar vessels before and after 1 month of topical timolol treatment (0.5% Timoptic BID). RESULTS: Baseline central retinal artery end diastolic velocity was lower (48%, p=0.0002) and resistive index higher (7.6%, p=0.018) in the OAG group than in the OH group. In the glaucoma group mean end diastolic velocity increased by 41%, (p=0.006) while resistive index decreased by 5.8%, (p=0.02) on treatment, while no significant changes were seen in the OH group. Blood flow velocities in the ophthalmic artery did not change with treatment. Baseline IOP and IOP reduction did not differ between OAG and OH group. CONCLUSION: Peripheral resistance to blood flow was found to be increased in untreated glaucoma eyes as compared to a similar group of eyes with ocular hypertension. Timolol treatment diminished resistance significantly in the glaucoma group, but not in the ocular hypertension group. Thus the two groups responded differently to timolol treatment. The reaction to IOP lowering treatment could indicate defective autoregulation in the glaucoma group.
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| 10. |
- Christensen-Dalsgaard, Signe, et al.
(author)
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What’s the catch with lumpsuckers? A North Atlantic study of seabird bycatch in lumpsucker gillnet fisheries
- 2019
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In: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 240
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Journal article (peer-reviewed)abstract
- Worldwide, incidental bycatch in fisheries is a conservation threat to many seabird species. Although knowledge on bycatch of seabirds has increased in the last decade, most stems from longline fisheries and the impacts of coastal gillnet fisheries are poorly understood. Gillnet fishing for North Atlantic lumpsucker (Cyclopterus lumpus) is one such fishery. We collated and synthesized the available information on seabird bycatch in lumpsucker gillnet fisheries across the entire geographical range to estimate and infer the magnitude of their impact on the affected seabird populations. Most birds killed were diving ducks, cormorants and auks, and each year locally high numbers of seabirds were taken as bycatch. We found large differences in bycatch rates among countries. The estimated mean bycatch in Iceland was 2.43 birds/trip, while the estimates in Norway was 0.44 and 0.39 birds/trip, respectively. The large disparities between estimates might reflect large spatial differences in bycatch rates, but could partly also arise due to distinctions in data recorded by onboard inspectors (Iceland), self-administered registration (Norway) and direct observations by cameras (Denmark). We show that lumpsucker gillnet fisheries might pose a significant risk to some populations of diving seabirds. However, a distinct data deficiency on seabird bycatch in terms of spatio-temporal coverage and the age and origins of the birds killed, limited our abilities to fully assess the extent and population consequences of the bycatch. Our results highlight the need for a joint effort among countries to standardize monitoring methods to better document the impact of these fisheries on seabirds.
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