| 1. |
- Aad, G., et al.
(författare)
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Commissioning of the ATLAS Muon Spectrometer with cosmic rays
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 875-916
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS detector at the Large Hadron Collider has collected several hundred million cosmic ray events during 2008 and 2009. These data were used to commission the Muon Spectrometer and to study the performance of the trigger and tracking chambers, their alignment, the detector control system, the data acquisition and the analysis programs. We present the performance in the relevant parameters that determine the quality of the muon measurement. We discuss the single element efficiency, resolution and noise rates, the calibration method of the detector response and of the alignment system, the track reconstruction efficiency and the momentum measurement. The results show that the detector is close to the design performance and that the Muon Spectrometer is ready to detect muons produced in high energy proton-proton collisions.
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| 2. |
- Aad, G., et al.
(författare)
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Studies of the performance of the ATLAS detector using cosmic-ray muons
- 2011
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 71:3
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Tidskriftsartikel (refereegranskat)abstract
- Muons from cosmic-ray interactions in the atmosphere provide a high-statistics source of particles that can be used to study the performance and calibration of the ATLAS detector. Cosmic-ray muons can penetrate to the cavern and deposit energy in all detector subsystems. Such events have played an important role in the commissioning of the detector since the start of the installation phase in 2005 and were particularly important for understanding the detector performance in the time prior to the arrival of the first LHC beams. Global cosmic-ray runs were undertaken in both 2008 and 2009 and these data have been used through to the early phases of collision data-taking as a tool for calibration, alignment and detector monitoring. These large datasets have also been used for detector performance studies, including investigations that rely on the combined performance of different subsystems. This paper presents the results of performance studies related to combined tracking, lepton identification and the reconstruction of jets and missing transverse energy. Results are compared to expectations based on a cosmic-ray event generator and a full simulation of the detector response.
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| 3. |
- Aad, G., et al.
(författare)
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The ATLAS Inner Detector commissioning and calibration
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 787-821
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS Inner Detector is a composite tracking system consisting of silicon pixels, silicon strips and straw tubes in a 2 T magnetic field. Its installation was completed in August 2008 and the detector took part in data-taking with single LHC beams and cosmic rays. The initial detector operation, hardware commissioning and in-situ calibrations are described. Tracking performance has been measured with 7.6 million cosmic-ray events, collected using a tracking trigger and reconstructed with modular pattern-recognition and fitting software. The intrinsic hit efficiency and tracking trigger efficiencies are close to 100%. Lorentz angle measurements for both electrons and holes, specific energy-loss calibration and transition radiation turn-on measurements have been performed. Different alignment techniques have been used to reconstruct the detector geometry. After the initial alignment, a transverse impact parameter resolution of 22.1 +/- 0.9 mu m and a relative momentum resolution sigma (p) /p=(4.83 +/- 0.16)x10(-4) GeV(-1)xp (T) have been measured for high momentum tracks.
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| 4. |
- Aad, G., et al.
(författare)
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The ATLAS Simulation Infrastructure
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 823-874
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Tidskriftsartikel (refereegranskat)abstract
- The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid. This simulation requires many components, from the generators that simulate particle collisions, through packages simulating the response of the various detectors and triggers. All of these components come together under the ATLAS simulation infrastructure. In this paper, that infrastructure is discussed, including that supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors. Also described are the tools allowing the software validation, performance testing, and the validation of the simulated output against known physics processes.
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| 5. |
- Anney, Richard, et al.
(författare)
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Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
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Tidskriftsartikel (refereegranskat)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
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| 6. |
- 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
-
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
-
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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| 7. |
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| 8. |
- Casey, Jillian P, et al.
(författare)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
-
Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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| 9. |
- Dreisig, Karin, et al.
(författare)
-
TPMT polymorphisms and minimal residual disease after 6-mercaptopurine post-remission consolidation therapy of childhood acute lymphoblastic leukaemia
- 2021
-
Ingår i: Pediatric Hematology and Oncology. - : Informa UK Limited. - 0888-0018 .- 1521-0669. ; 38:3, s. 227-238
-
Tidskriftsartikel (refereegranskat)abstract
- © 2020 Taylor & Francis Group, LLC. Bone marrow minimal residual disease (MRD) is the strongest predictor of relapse in children with acute lymphoblastic leukemia (ALL). 6-mercaptopurine (6MP) in ALL therapy has wide inter-individual variation in disposition and is strongly influenced by polymorphisms in the thiopurine methyltransferase (TPMT) gene. In 952 patients treated according to the NOPHO ALL2008 protocol, we explored the association between thiopurine disposition, TPMT genotypes and MRD levels after consolidation therapy with 6MP, high-dose methotrexate (HD-MTX), asparaginase, and vincristine. The levels of the cytotoxic DNA-incorporated thioguanine were significantly higher on day 70-79 in G460A/A719G TPMT heterozygous (TPMT HZ) compared to TPMT wild type (TPMT WT) patients (mean: 230.7 vs. 149.7 fmol/µg DNA, p = 0.002). In contrast, TPMT genotype did not associate with the end of consolidation MRD levels irrespective of randomization of the patients to fixed dose (25 mg/m2/day) or 6MP escalation (up to 50 or 75 mg/m2/day) during consolidation therapy.
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| 10. |
- Hansen, Michael Adsetts Edberg, et al.
(författare)
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State Estimation of the Performance of Gravity Tables Using Multispectral Image Analysis
- 2017
-
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
-
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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| 11. |
- 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
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
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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| 12. |
- 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
-
Ingår i: ICMF 2016 International Conference on Multiphase Flow, Firenze, Italy, May 22 - 27, 2016.
-
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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| 13. |
- Kannan, Ananda Subramani, 1989, et al.
(författare)
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CFD-DEM studies of grain segregation patterns on a conceptual destoner
- 2015
-
Ingår i: The 16th International Conference on Fluid Flow Technologies (CMFF15), Budapest, Hungary.
-
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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| 14. |
- Kannan, Ananda Subramani, 1989, et al.
(författare)
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Segregation phenomena in gravity separators: A combined numerical and experimental study
- 2016
-
Ingår i: Powder Technology. - : Elsevier BV. - 1873-328X .- 0032-5910. ; 301, s. 679-693
-
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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| 15. |
- Kannan, Ananda Subramani, 1989, et al.
(författare)
-
Studies of grain segregation patterns on a Destoner using a CFD-DEM approach
- 2015
-
Ingår i: WIT Transactions on Engineering Sciences. - 1743-3533. ; 89, s. 287 - 298
-
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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| 16. |
- 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
-
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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| 17. |
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| 18. |
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| 19. |
- Lund, Jacob, et al.
(författare)
-
Introduction
- 2018
-
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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| 20. |
- 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
-
Ingår i: JACC: Basic to Translational Science. - : Elsevier BV. - 2452-302X. ; 3:4, s. 464-480
-
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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| 21. |
- Nersting, Jacob, et al.
(författare)
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Methotrexate polyglutamate levels and co-distributions in childhood acute lymphoblastic leukemia maintenance therapy.
- 2019
-
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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| 22. |
- 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
-
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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| 23. |
- 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
-
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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| 24. |
- Nyegaard, Mette, et al.
(författare)
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Mutations in Calmodulin Cause Ventricular Tachycardia and Sudden Cardiac Death
- 2012
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:4, s. 703-712
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Tidskriftsartikel (refereegranskat)abstract
- Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion in individuals without structural cardiac abnormalities. Although rare, CPVT is suspected to cause a substantial part of sudden cardiac deaths in young individuals. Mutations in RYR2, encoding the cardiac sarcoplasmic calcium channel, have been identified as causative in approximately half of all dominantly inherited CPVT cases. Applying a genome-wide linkage analysis in a large Swedish family with a severe dominantly inherited form of CPVT-like arrhythmias, we mapped the disease locus to chromosome 14q31-32. Sequencing CALM1 encoding calmodulin revealed a heterozygous missense mutation (c.161A>T [p.Asn53Ile]) segregating with the disease. A second, de novo, missense mutation (c.293A>G [p.Asn97Ser]) was subsequently identified in an individual of Iraqi origin; this individual was diagnosed with CPVT from a screening of 61 arrhythmia samples with no identified RYR2 mutations. Both CALM1 substitutions demonstrated compromised calcium binding, and p.Asn97Ser displayed an aberrant interaction with the RYR2 calmodulin-binding-domain peptide at low calcium concentrations. We conclude that calmodulin mutations can cause severe cardiac arrhythmia and that the calmodulin genes are candidates for genetic screening of individual cases and families with idiopathic ventricular tachycardia and unexplained sudden cardiac death.
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| 25. |
- Riisager, K., et al.
(författare)
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Search for beta-delayed proton emission from 11 Be
- 2020
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-601X .- 1434-6001. ; 56:3
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Tidskriftsartikel (refereegranskat)abstract
- We report on an attempt to reproduce the observation of β--delayed proton emission from 11Be through detection of the final state nucleus 10Be with accelerator mass spectrometry. Twelve samples were collected at the ISOLDE facility at CERN at different separator settings, allowing tests of different sources of contamination to be carried out. The observed amounts of 10Be per collected 11Be rule out several contamination sources, but do not agree internally. Formation of BeH molecular ions in the ion source may explain our data, in which case an upper limit of the βp branching ratio of 2.2 × 10 - 6 can be derived.
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| 26. |
- Rundle, Andrew, et al.
(författare)
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Physical activity and lung cancer among non-smokers : a pilot molecular epidemiological study within EPIC
- 2010
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Ingår i: Biomarkers. - : Taylor & Francis. - 1354-750X .- 1366-5804. ; 15:1, s. 20-30
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Tidskriftsartikel (refereegranskat)abstract
- The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by 32P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35-0.90), higher GSH levels (+1.87 μmol GSH g-1 haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38-2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84-1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.
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| 27. |
- 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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| 28. |
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| 29. |
- Vineis, Paolo, et al.
(författare)
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Lung cancers attributable to environmental tobacco smoke and air pollution in non-smokers in different European countries: a prospective study
- 2007
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Ingår i: Environmental Health. - 1476-069X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several countries are discussing new legislation on the ban of smoking in public places, and on the acceptable levels of traffic-related air pollutants. It is therefore useful to estimate the burden of disease associated with indoor and outdoor air pollution. Methods: We have estimated exposure to Environmental Tobacco Smoke (ETS) and to air pollution in never smokers and ex-smokers in a large prospective study in 10 European countries (European Prospective Investigation into Cancer and Nutrition)(N = 520,000). We report estimates of the proportion of lung cancers attributable to ETS and air pollution in this population. Results: The proportion of lung cancers in never-and ex-smokers attributable to ETS was estimated as between 16 and 24%, mainly due to the contribution of work-related exposure. We have also estimated that 5-7% of lung cancers in European never smokers and ex-smokers are attributable to high levels of air pollution, as expressed by NO2 or proximity to heavy traffic roads. NO2 is the expression of a mixture of combustion (traffic-related) particles and gases, and is also related to power plants and waste incinerator emissions. Discussion: We have estimated risks of lung cancer attributable to ETS and traffic-related air pollution in a large prospective study in Europe. Information bias can be ruled out due to the prospective design, and we have thoroughly controlled for potential confounders, including restriction to never smokers and long-term ex-smokers. Concerning traffic-related air pollution, the thresholds for indicators of exposure we have used are rather strict, i.e. they correspond to the high levels of exposure that characterize mainly Southern European countries (levels of NO2 in Denmark and Sweden are closer to 10-20 ug/m(3), whereas levels in Italy are around 30 or 40, or higher). Therefore, further reduction in exposure levels below 30 ug/m(3) would correspond to additional lung cancer cases prevented, and our estimate of 5-7% is likely to be an underestimate. Overall, our prospective study draws attention to the need for strict legislation concerning the quality of air in Europe.
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| 30. |
- Wålinder, Göran, et al.
(författare)
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Regional differences in treatment and outcome for myeloma patients in Sweden : A population based Swedish myeloma register study
- 2022
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Ingår i: Cancer Reports. - : Wiley. - 2573-8348. ; 5:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: We wanted to evaluate if health care for multiple myeloma (MM) patients is equal in different regions of Sweden. Aim: To study differences in survival for MM depending on health care region and early use of modern treatment. Methods and results: Data from the Swedish Myeloma Register from patients diagnosed between 2008 and 2017 was used. Cohorts were defined by the six healthcare regions (labeled A–F) in Sweden and modern initial treatment was defined as including certain drug combinations. To adjust for time to treatment bias, survival analyses were performed also for patients alive 6 months after diagnosis. In all treated MM patients (n = 5326), we observed a superior overall survival (OS) for region A compared to all other regions (p <.01 for all respectively). After adjusting for time to treatment there was also a superior survival in the region with highest use of modern initial treatment (region A) compared to the regions defined in the study as having intermediate and low use (p <.01 for both). In patients receiving autologous stem cell transplantation (ASCT) a superior survival was observed for region A compared to all regions besides region B. Similar results were seen when adjusting for a time to treatment bias. In patients not receiving ASCT, 75 years or older and adjusted for time to treatment bias, a difference was noted only between region A and E (log rank p =.04, HR 1.2, CI 1.00–1.44, p =.06). In multivariate analyses including age, international staging system stage and time period of diagnosis, differences in survival remained for patients receiving ASCT between region A versus C, D, E and F (p =.01, p <.01, p <.01, p =.03). Conclusion: We observed a superior survival in region A for patients receiving ASCT. Explanations may be higher usage of modern initial treatment or regional residual confounding. For patients not receiving ASCT, 75 years or older, differences in survival could be adjusted for.
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| 31. |
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