| 1. |
- Banerjee, A, et al.
(författare)
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Subtypes of atrial fibrillation with concomitant valvular heart disease derived from electronic health records: phenotypes, population prevalence, trends and prognosis
- 2019
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Ingår i: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. - : Oxford University Press (OUP). - 1532-2092. ; 21:12, s. 1776-1784
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo evaluate population-based electronic health record (EHR) definitions of atrial fibrillation (AF) and valvular heart disease (VHD) subtypes, time trends in prevalence and prognosis.Methods and resultsA total of 76 019 individuals with AF were identified in England in 1998–2010 in the CALIBER resource, linking primary and secondary care EHR. An algorithm was created, implemented, and refined to identify 18 VHD subtypes using 406 diagnosis, procedure, and prescription codes. Cox models were used to investigate associations with a composite endpoint of incident stroke (ischaemic, haemorrhagic, and unspecified), systemic embolism (SSE), and all-cause mortality. Among individuals with AF, the prevalence of AF with concomitant VHD increased from 11.4% (527/4613) in 1998 to 17.6% (7014/39 868) in 2010 and also in individuals aged over 65 years. Those with mechanical valves, mitral stenosis (MS), or aortic stenosis had highest risk of clinical events compared to AF patients with no VHD, in relative [hazard ratio (95% confidence interval): 1.13 (1.02–1.24), 1.20 (1.05–1.36), and 1.27 (1.19–1.37), respectively] and absolute (excess risk: 2.04, 4.20, and 6.37 per 100 person-years, respectively) terms. Of the 95.2% of individuals with indication for warfarin (men and women with CHA2DS2-VASc ≥1 and ≥2, respectively), only 21.8% had a prescription 90 days prior to the study.ConclusionPrevalence of VHD among individuals with AF increased from 1998 to 2010. Atrial fibrillation associated with aortic stenosis, MS, or mechanical valves (compared to AF without VHD) was associated with an excess absolute risk of stroke, SSE, and mortality, but anticoagulation was underused in the pre-direct oral anticoagulant (DOAC) era, highlighting need for urgent clarity regarding DOACs in AF and concomitant VHD.
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| 2. |
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| 3. |
- Hansen, Michael Adsetts Edberg, et al.
(författare)
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State Estimation of the Performance of Gravity Tables Using Multispectral Image Analysis
- 2017
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Ingår i: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783319591285 ; 10270 LNCS, s. 471-480
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Konferensbidrag (refereegranskat)abstract
- Gravity tables are important machinery that separate dense(healthy) grains from lighter (low yielding varieties) aiding in improving the overall quality of seed and grain processing. This paper aims at evaluating the operating states of such tables, which is a critical criterionrequired for the design and automation of the next generation of gravity separators. We present a method capable of detecting differences in grain densities, that as an elementary step forms the basis for a related optimization of gravity tables. The method is based on a multispectral imaging technology, capable of capturing differences in the surface chemistry of the kernels. The relevant micro-properties of the grains are estimated using a Canonical Discriminant Analysis (CDA) that segments the captured grains into individual kernels and we show that for wheat, our method correlates well with control measurements (R 2 = 0.93).
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| 4. |
- Jacobsen, Carsten Suhr, et al.
(författare)
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Inter-laboratory testing of the effect of DNA blocking reagent G2 on DNA extraction from low-biomass clay samples
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Here we show that a commercial blocking reagent (G2) based on modified eukaryotic DNA significantly improved DNA extraction efficiency. We subjected G2 to an inter-laboratory testing, where DNA was extracted from the same clay subsoil using the same batch of kits. The inter-laboratory extraction campaign revealed large variation among the participating laboratories, but the reagent increased the number of PCR-amplified16S rRNA genes recovered from biomass naturally present in the soils by one log unit. An extensive sequencing approach demonstrated that the blocking reagent was free of contaminating DNA, and may therefore also be used in metagenomics studies that require direct sequencing.
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| 5. |
- Kannan, Ananda Subramani, 1989, et al.
(författare)
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A study of the performance of pilot scale gravity sorters using a CFD-DEM computational framework
- 2016
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Ingår i: ICMF 2016 International Conference on Multiphase Flow, Firenze, Italy, May 22 - 27, 2016.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Gravity sorters are utilized in the downstream processing of harvested grains in order to clean and enhance the grain quality for human consumption. In this paper, we undertake a detailed assessment into the performance of such sorters using a coupled CFD-DEM framework implemented in the OpenFOAM® environment. We look to establish and characterize the performance of gravity sorters cleaning harvested wheat at different operating conditions such as: deck tilt, fluidization conditions, deck vibrational intensity etc. Our simulations result in the identification of the optimal deck tilt and consequently the corresponding fluidization velocity and deck vibration intensity required for obtaining peak performance. A clear segregation between the light wastes present in the feed and the good product is noted in the virtual sorter, with the separation becoming poorer at steeper deck tilts. Finally, a regression model relating the operating conditions to the performance is developed in order to aid in making qualified guesses during the startup of such sorters.
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| 6. |
- Kannan, Ananda Subramani, 1989, et al.
(författare)
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CFD-DEM studies of grain segregation patterns on a conceptual destoner
- 2015
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Ingår i: The 16th International Conference on Fluid Flow Technologies (CMFF15), Budapest, Hungary.
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Konferensbidrag (refereegranskat)abstract
- Removal of contaminants from ‘food grade’ quality grains is of great importance in food and grain processing operations. A thorough understanding of the inherent granular segregation profiles on this processing equipment is a pivotal step in the design and development of more efficient processes. One such grain cleaning operation is the ‘density-based separation’ using a destoner. This process removes stones and other heavy material from lighter food grains using a vibrating deck and fluidizing air. In this paper we formulate a CFD-DEM framework (set up and implemented in the OpenFOAM® environment) to study granular segregation patterns on a destoner. The scheme is first validated by comparing simulations with experimental data using a gas-solid fluidized-bed test case. A good agreement between the experiments and the simulations is noted. This proposed framework is then used to characterize the combined effects of deck inclination and fluidization velocities on the separation profiles generated from a virtual destoner. We have found these profiles to be highly sensitive to changes in fluidization conditions, with the gradual development of segregation zones at velocities close to the minimum fluidization velocity of the heavier component. A deck inclination of 5 degrees and a fluidization velocity of 2.0 m/s is considered optimal while steeper slopes (inclinations of 15 degrees) and lower air velocities (0 and 1.5 m/s) are deemed unsuitable for segregation.
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| 7. |
- Kannan, Ananda Subramani, 1989, et al.
(författare)
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Segregation phenomena in gravity separators: A combined numerical and experimental study
- 2016
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Ingår i: Powder Technology. - : Elsevier BV. - 1873-328X .- 0032-5910. ; 301, s. 679-693
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we formulate a computational framework for characterizing and optimizing the performance of adestoner, an example of a density-based separation technique. The numerical framework combines ComputationalFluid Dynamics (CFD) simulations with a Discrete Element Method (DEM), implemented in an opensourcecomputation package (OpenFOAM). This framework is validated first by comparing the simulationswith experiments for a standardized test case and further with our experimental study of a pilot-scale destoner.We evaluate the combined effects of process conditions, such as separator deck inclination, vibration speed andfluidization velocities on destoner performance. Our simulations showhowthe heavy product fraction in the discardsstreamincreases over timewith a corresponding accumulation of the ‘valuable’ light product at the base ofthe deck, indicating segregation between the stones (heavy product) and the grains (light product).We also findthat these separation profiles are highly sensitive to changes in deck surface air velocities, with the gradual developmentof segregation zones at velocities close to the minimum fluidization velocity of the heavier component.Optimal separation is seen at a deck inclination of 4° and a fluidization velocity of between 1.75 and2 m/s. Our simulation results also agree well with the experimental findings indicating the usability of the proposedframework for the design and optimization of gravity separators.
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| 8. |
- Kannan, Ananda Subramani, 1989, et al.
(författare)
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Studies of grain segregation patterns on a Destoner using a CFD-DEM approach
- 2015
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Ingår i: WIT Transactions on Engineering Sciences. - 1743-3533. ; 89, s. 287 - 298
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Konferensbidrag (refereegranskat)abstract
- Removal of contaminants from ‘food grade’ quality grains is of great importance in food and grain processing operations. A thorough understanding of the inherent granular segregation profiles on this processing equipment is a pivotal step in the design and development of more efficient processes. One such grain cleaning operation is the ‘density-based separation’ using a destoner. This process removes stones and other heavy material from lighter food grains using a vibrating deck and fluidizing air. In this paper we formulate a CFD-DEM framework (set up and implemented in the OpenFOAM® environment) to study granular segregation patterns on a destoner. The scheme is first validated by comparing simulations with experimental data using a gas-solid fluidized-bed test case. A good agreement between the experiments and the simulations is noted. This proposed framework is then used to characterize the combined effects of deck inclination and fluidization velocities on the separation profiles generated from a virtual destoner. We have found these profiles to be highly sensitive to changes in fluidization conditions, with the gradual development of segregation zones at velocities close to the minimum fluidization velocity of the heavier component. A deck inclination of 5 degrees and a fluidization velocity of 2.0 m/s is considered optimal while steeper slopes (inclinations of 15 degrees) and lower air velocities (0 and 1.5 m/s) are deemed unsuitable for segregation.
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| 9. |
- Kjellström, Erik, et al.
(författare)
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European climate change at global mean temperature increases of 1.5 and 2 degrees C above pre-industrial conditions as simulated by the EURO-CORDEX regional climate models
- 2018
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Ingår i: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 9:2, s. 459-478
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Tidskriftsartikel (refereegranskat)abstract
- We investigate European regional climate change for time periods when the global mean temperature has increased by 1.5 and 2 degrees C compared to pre-industrial conditions. Results are based on regional downscaling of transient climate change simulations for the 21st century with global climate models (GCMs) from the fifth-phase Coupled Model Intercomparison Project (CMIP5). We use an ensemble of EURO-CORDEX high-resolution regional climate model (RCM) simulations undertaken at a computational grid of 12.5 km horizontal resolution covering Europe. The ensemble consists of a range of RCMs that have been used for downscaling different GCMs under the RCP8.5 forcing scenario. The results indicate considerable near-surface warming already at the lower 1.5 degrees C of warming. Regional warming exceeds that of the global mean in most parts of Europe, being the strongest in the northernmost parts of Europe in winter and in the southernmost parts of Europe together with parts of Scandinavia in summer. Changes in precipitation, which are less robust than the ones in temperature, include increases in the north and decreases in the south with a borderline that migrates from a northerly position in summer to a southerly one in winter. Some of these changes are already seen at 1.5 degrees C of warming but are larger and more robust at 2 degrees C. Changes in near-surface wind speed are associated with a large spread among individual ensemble members at both warming levels. Relatively large areas over the North Atlantic and some parts of the continent show decreasing wind speed while some ocean areas in the far north show increasing wind speed. The changes in temperature, precipitation and wind speed are shown to be modified by changes in mean sea level pressure, indicating a strong relationship with the large-scale circulation and its internal variability on decade-long timescales. By comparing to a larger ensemble of CMIP5 GCMs we find that the RCMs can alter the results, leading either to attenuation or amplification of the climate change signal in the underlying GCMs. We find that the RCMs tend to produce less warming and more precipitation (or less drying) in many areas in both winter and summer.
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| 10. |
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| 11. |
- Lund, Jacob, et al.
(författare)
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Introduction
- 2018
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Ingår i: Nordic Journal of Aesthetics. - 2000-1452 .- 2000-9607. ; 27:55-56, s. 5-7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Matic, L. P., et al.
(författare)
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Novel Multiomics Profiling of Human Carotid Atherosclerotic Plaques and Plasma Reveals Biliverdin Reductase B as a Marker of Intraplaque Hemorrhage
- 2018
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Ingår i: JACC: Basic to Translational Science. - : Elsevier BV. - 2452-302X. ; 3:4, s. 464-480
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Tidskriftsartikel (refereegranskat)abstract
- Clinical tools to identify individuals with unstable atherosclerotic lesions are required to improve prevention of myocardial infarction and ischemic stroke. Here, a systems-based analysis of atherosclerotic plaques and plasma from patients undergoing carotid endarterectomy for stroke prevention was used to identify molecular signatures with a causal relationship to disease. Local plasma collected in the lesion proximity following clamping prior to arteriotomy was profiled together with matched peripheral plasma. This translational workflow identified biliverdin reductase B as a novel marker of intraplaque hemorrhage and unstable carotid atherosclerosis, which should be investigated as a potential predictive biomarker for cardiovascular events in larger cohorts.
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| 13. |
- Nersting, Jacob, et al.
(författare)
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Methotrexate polyglutamate levels and co-distributions in childhood acute lymphoblastic leukemia maintenance therapy.
- 2019
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Ingår i: Cancer chemotherapy and pharmacology. - : Springer Science and Business Media LLC. - 1432-0843 .- 0344-5704. ; 83:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- Methotrexate polyglutamates (MTXpg) facilitate incorporation of thioguanine nucleotides into DNA (DNA-TG, the primary cytotoxic thiopurine metabolite and outcome determinant in MTX/6-mercaptopurine treatment of childhood ALL). We hypothesized that mapping erythrocyte levels of MTXpg with 1-6 glutamates and their associations with DNA-TG formation would facilitate future guidelines for maintenance therapy dosing.Summed MTX with 1-6 glutamates resolved by LCMS [median (interquartile): 5.47 (3.58-7.69) nmol/mmol hemoglobin] was in agreement with total MTX by radio ligand assay. In 16,389 blood samples from 1426 ALL maintenance therapy patients, MTXpg3 21.0 (15.2-27.4)% was the predominant metabolite, and MTXpg1 (the maternal drug) constituted 38.6 (27.2-50.2)% of MTXpg1-6. All subsets correlated; the strongest associations were between metabolites with similar polyglutamate lengths. Correlations of MTXpg1 with MTXpg2 and MTXpg3,4,5,6 were rs=0.68 and rs=0.25-0.42, respectively. Intercorrelations of MTXpg3,4,5,6 were all rs≥0.51. MTXpg4 accounted for 29.8 (24.7-33.3)% of MTXpg3-6, yet explained 96% of the summed MTXpg3-6 variation. MTXpg1-4, MTXpg1-6, MTXpg2-6 and MTXpg3 were all associated with DNA-TG levels (p<0.00001), but collinearity precluded identification of the most informative subset.Measuring erythrocyte MTXpg4 simplifies and can replace longer chain MTXpg monitoring. Resolving individual MTXpg identifies samples that are unsuitable for dose guidance due to high levels of MTXpg1 remaining in the plasma fraction because of recent MTX intake. All tested MTXpg subsets correlated with DNA-TG and may be used for ALL maintenance therapy dose adjustments, but the most informative subset remains to be identified.
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| 14. |
- Nielsen-Kudsk, Jens Erik, et al.
(författare)
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Left atrial appendage occlusion versus standard medical care in patients with atrial fibrillation and intracerebral haemorrhage : a propensity score-matched follow-up study
- 2017
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Ingår i: EuroIntervention. - : EUROPA EDITION. - 1774-024X .- 1969-6213. ; 13:3, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to investigate the prognosis in patients with atrial fibrillation (AF) and intracerebral haemorrhage (ICH) having a left atrial appendage occlusion (LAAO) versus patients receiving standard medical therapy. Methods and results: A total of 151 patients from the Nordic countries with AF and previous ICH who underwent LAAO using the AMPLATZER Cardiac Plug or the AMPLATZER AMULET were compared to a propensity score-matched group of 151 patients receiving standard medical therapy. The two groups were matched so that their risks for stroke and bleeding were similar (CHA2DS2-VASc and HAS-BLED scores). The standard care patients were identified from the Danish Stroke Registry among 787 patients with AF and ICH. The primary endpoint was a composite of all-cause mortality, ischaemic stroke and major bleeding. Patients with AF and a prior ICH treated with LAAO had a lower risk of the composite outcome as compared to patients treated with standard medical care (events/1,000 years [95% confidence interval]: 53.3 [44.3-64.1] vs. 366.7 [298.2-450.9]; hazard ratio 0.16 [0.07-0.37]). Conclusions: LAAO is suggested to be of major clinical benefit in AF patients having sustained an ICH. These results have to be confirmed in a randomised clinical trial.
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| 15. |
- Nielsen, Stine Nygaard, et al.
(författare)
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DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial.
- 2017
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Ingår i: The Lancet. Oncology. - 1474-5488. ; 18:4, s. 515-524
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Tidskriftsartikel (refereegranskat)abstract
- Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to establish whether DNA-TGN concentrations in blood leucocytes during maintenance therapy are associated with relapse-free survival.In this substudy of the NOPHO ALL2008 phase 3 trial done in 23 hospitals in seven European countries (Denmark, Estonia, Finland, Iceland, Lithuania, Norway, and Sweden), we analysed data from centralised and blinded analyses of 6-mercaptopurine and methotrexate metabolites in blood samples from patients with non-high-risk childhood acute lymphoblastic leukaemia. Eligible patients were aged 1·0-17·9 years; had been diagnosed with non-high-risk precursor B-cell or T-cell leukaemia; had been treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol; and had reached maintenance therapy in first remission. Maintenance therapy was (mercaptopurine 75 mg/m(2) once per day and methotrexate 20 mg/m(2) once per week, targeted to a leucocyte count of 1·5-3·0×10(9) cells per L). We measured DNA-TGN and erythrocyte concentrations of TGN nucleotides, methylated mercaptopurine metabolites, and methotrexate polyglutamates. The primary objective was the association of DNA-TGN concentrations and 6-mercaptopurine and methotrexate metabolites with relapse-free survival. The secondary endpoint was the assessment of DNA-TGN concentration and 6-mercaptopurine and methotrexate metabolites during maintenance therapy phase 2.Between Nov 26, 2008 and June 14, 2016, 1509 patients from the NOPHO ALL2008 study were assessed for eligibility in the DNA-TGN substudy, of which 918 (89%) of 1026 eligible patients had at least one DNA-TGN measurement and were included in the analyses. Median follow-up was 4·6 years (IQR 3·1-6·1). Relapse-free survival was significantly associated with DNA-TGN concentration (adjusted hazard ratio 0·81 per 100 fmol/μg DNA increase, 95% CI 0·67-0·98; p=0·029). In patients with at least five blood samples, erythrocyte concentrations of TGN, methylated mercaptopurine metabolites, and methotrexate polyglutamates were associated with DNA-TGN concentration (all p<0·0001).Our results suggest the need for intervention trials to identify clinically applicable strategies for individualised drug dosing to increase DNA-TGN concentration, and randomised studies to investigate whether such strategies improve cure rates compared with current dose adjustments based on white blood cell counts.Danish Cancer Society, Childhood Cancer Foundation (Denmark), Childhood Cancer Foundation (Sweden), Nordic Cancer Union, Otto Christensen Foundation, University Hospital Rigshospitalet, and Novo Nordic Foundation.
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| 16. |
- Sakhnini, Laila I, et al.
(författare)
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Improving the Developability of an Antigen Binding Fragment by Aspartate Substitutions
- 2019
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 58:24, s. 2750-2759
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Tidskriftsartikel (refereegranskat)abstract
- Aggregation can be a major challenge in the development of antibody-based pharmaceuticals as it can compromise the quality of the product during bioprocessing, formulation, and drug administration. To avoid aggregation, developability assessment is often run in parallel with functional optimization in the early screening phases to flag and deselect problematic molecules. As developability assessment can be demanding with regard to time and resources, there is a high focus on the development of molecule design strategies for engineering molecules with a high developability potential. Previously, Dudgeon et al. [(2012) Proc. Natl. Acad. Sci. U. S. A. 109, 10879-10884] demonstrated how Asp substitutions at specific positions in human variable domains and single-chain variable fragments could decrease the aggregation propensity. Here, we have investigated whether these Asp substitutions would improve the developability potential of a murine antigen binding fragment (Fab). A full combinatorial library consisting of 393 Fab variants with single, double, and triple Asp substitutions was first screened in silico with Rosetta; thereafter, 26 variants with the highest predicted thermodynamic stability were selected for production. All variants were subjected to a set of developability studies. Interestingly, most variants had thermodynamic stability on par with or improved relative to that of the wild type. Twenty-five of the variants exhibited improved nonspecificity. Half of the variants exhibited improved aggregation resistance. Strikingly, while we observed remarkable improvement in the developability potential, the Asp substitutions had no substantial effect on the antigenic binding affinity. Altogether, by combining the insertion of negative charges and the in silico screen based on computational models, we were able to improve the developability of the Fab rapidly.
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