| 1. |
- Gregers, Jannie, et al.
(författare)
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Polymorphisms in the ABCB1 gene affect outcome and toxicity in Childhood Acute Lymphoblastic Leukemia
- 2012
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences pharmacokinetics in several anti-cancer drugs. We hypothesized that 1199G>A, 1236C>T, 2677G>A/T and 3435C>T variants of ABCB1 could affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL), since treatment includes known P-glycoprotein substrates and 3435C/T may affect methotrexate therapy. We studied 522 Danish children with ALL treated according to NOPHO ALL92 and ALL2000 protocols, 93% of all those eligible during 1992-2007. Risk of relapse was 2.9-fold increased for 41 patients with the 1199GA variant compared to 477 with 1199GG (p=0.001), and reduced by 61% and 40%, respectively for 421 patients with the 3435CT or 3435TT variants compared to 96 with 3435CC (overall p=0.02). Degree of bone marrow toxicity during doxorubicin, vincristine and prednisolone induction therapy was higher in 71 patients with 3435TT variant (median nadirs: hemoglobin 3% and platelets 34/37% lower in3435CT/3435CC) compared to 160 patients with 3435CT/3435CC (Hemoglobin p=0.01 and platelets p<0.0001). We observed more liver toxicity after high-dose methotrexate in 109 patients with 3435CC variant versus 3435CT/TT (Median max alanineaminotransferase: 280 versus 142/111 U/L, p=0.03). In conclusion, there is a statistically significant association between ABCB1 polymorphisms and efficacy and toxicity in childhood ALL.
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| 2. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 3. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 4. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 5. |
- Arridge, Christopher S., et al.
(författare)
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Uranus Pathfinder : exploring the origins and evolution of Ice Giant planets
- 2012
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 753-791
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Tidskriftsartikel (refereegranskat)abstract
- The "Ice Giants" Uranus and Neptune are a different class of planet compared to Jupiter and Saturn. Studying these objects is important for furthering our understanding of the formation and evolution of the planets, and unravelling the fundamental physical and chemical processes in the Solar System. The importance of filling these gaps in our knowledge of the Solar System is particularly acute when trying to apply our understanding to the numerous planetary systems that have been discovered around other stars. The Uranus Pathfinder (UP) mission thus represents the quintessential aspects of the objectives of the European planetary community as expressed in ESA's Cosmic Vision 2015-2025. UP was proposed to the European Space Agency's M3 call for medium-class missions in 2010 and proposed to be the first orbiter of an Ice Giant planet. As the most accessible Ice Giant within the M-class mission envelope Uranus was identified as the mission target. Although not selected for this call the UP mission concept provides a baseline framework for the exploration of Uranus with existing low-cost platforms and underlines the need to develop power sources suitable for the outer Solar System. The UP science case is based around exploring the origins, evolution, and processes at work in Ice Giant planetary systems. Three broad themes were identified: (1) Uranus as an Ice Giant, (2) An Ice Giant planetary system, and (3) An asymmetric magnetosphere. Due to the long interplanetary transfer from Earth to Uranus a significant cruise-phase science theme was also developed. The UP mission concept calls for the use of a Mars Express/Rosetta-type platform to launch on a Soyuz-Fregat in 2021 and entering into an eccentric polar orbit around Uranus in the 2036-2037 timeframe. The science payload has a strong heritage in Europe and beyond and requires no significant technology developments.
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| 6. |
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| 7. |
- Boll, Rebecca, et al.
(författare)
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Imaging molecular structure through femtosecond photoelectron diffraction on aligned and oriented gas-phase molecules
- 2014
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Ingår i: Faraday Discussions. - : Royal Society of Chemistry (RSC). - 1364-5498. ; 171, s. 57-80
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Tidskriftsartikel (refereegranskat)abstract
- This paper gives an account of our progress towards performing femtosecond time-resolved photoelectron diffraction on gas-phase molecules in a pump-probe setup combining optical lasers and an X-ray free-electron laser. We present results of two experiments aimed at measuring photoelectron angular distributions of laser-aligned 1-ethynyl-4-fluorobenzene (C8H5F) and dissociating, laser-aligned 1,4-dibromobenzene (C6H4Br2) molecules and discuss them in the larger context of photoelectron diffraction on gas-phase molecules. We also show how the strong nanosecond laser pulse used for adiabatically laser-aligning the molecules influences the measured electron and ion spectra and angular distributions, and discuss how this may affect the outcome of future time-resolved photoelectron diffraction experiments.
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| 8. |
- Callaghan, Terry, et al.
(författare)
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Multi-Decadal Changes in Tundra Environments and Ecosystems : Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF)
- 2011
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40:6, s. 705-716
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the responses of tundra systemsto global change has global implications. Most tundraregions lack sustained environmental monitoring and oneof the only ways to document multi-decadal change is toresample historic research sites. The International PolarYear (IPY) provided a unique opportunity for such researchthrough the Back to the Future (BTF) project (IPY project#512). This article synthesizes the results from 13 paperswithin this Ambio Special Issue. Abiotic changes includeglacial recession in the Altai Mountains, Russia; increasedsnow depth and hardness, permafrost warming, andincreased growing season length in sub-arctic Sweden;drying of ponds in Greenland; increased nutrient availabilityin Alaskan tundra ponds, and warming at mostlocations studied. Biotic changes ranged from relativelyminor plant community change at two sites in Greenland tomoderate change in the Yukon, and to dramatic increasesin shrub and tree density on Herschel Island, and in subarcticSweden. The population of geese tripled at one sitein northeast Greenland where biomass in non-grazed plotsdoubled. A model parameterized using results from a BTFstudy forecasts substantial declines in all snowbeds andincreases in shrub tundra on Niwot Ridge, Colorado overthe next century. In general, results support and provideimproved capacities for validating experimental manipulation,remote sensing, and modeling studies.
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| 9. |
- Callaghan, Terry V., et al.
(författare)
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Ecosystem change and stability over multiple decades in the Swedish subarctic : complex processes and multiple drivers
- 2013
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Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 368:1624
-
Tidskriftsartikel (refereegranskat)abstract
- The subarctic environment of northernmost Sweden has changed over the past century, particularly elements of climate and cryosphere. This paper presents a unique geo-referenced record of environmental and ecosystem observations from the area since 1913. Abiotic changes have been substantial. Vegetation changes include not only increases in growth and range extension but also counterintuitive decreases, and stability: all three possible responses. Changes in species composition within the major plant communities have ranged between almost no changes to almost a 50 per cent increase in the number of species. Changes in plant species abundance also vary with particularly large increases in trees and shrubs (up to 600%). There has been an increase in abundance of aspen and large changes in other plant communities responding to wetland area increases resulting from permafrost thaw. Populations of herbivores have responded to varying management practices and climate regimes, particularly changing snow conditions. While it is difficult to generalize and scale-up the site-specific changes in ecosystems, this very site-specificity, combined with projections of change, is of immediate relevance to local stakeholders who need to adapt to new opportunities and to respond to challenges. Furthermore, the relatively small area and its unique datasets are a microcosm of the complexity of Arctic landscapes in transition that remains to be documented.
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| 10. |
- Canton, Sophie, et al.
(författare)
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Toward Highlighting the Ultrafast Electron Transfer Dynamics at the Optically Dark Sites of Photocatalysts
- 2013
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Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 4:11, s. 1972-1976
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Tidskriftsartikel (refereegranskat)abstract
- Building a detailed understanding of the structure function relationship is a crucial step in the optimization of molecular photocatalysts employed in water splitting schemes. The optically dark nature of their active sites usually prevents a complete mapping of the photoinduced dynamics. In this work, transient X-ray absorption spectroscopy highlights the electronic and geometric changes that affect such a center in a bimetallic model complex. Upon selective excitation of the ruthenium chromophore, the cobalt moiety is reduced through intramolecular electron transfer and undergoes a spin flip accompanied by an average bond elongation of 0.20 +/- 0.03 angstrom. The analysis is supported by simulations based on density functional theory structures (B3LYP*/TZVP) and FEFF 9.0 multiple scattering calculations. More generally, these results exemplify the large potential of the technique for tracking elusive intermediates that impart unique functionalities in photochemical devices.
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| 11. |
- Christensen, G Bryce, et al.
(författare)
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Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses.
- 2010
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 70, s. 735-744
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS: Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS: Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate (c) 2010 Wiley-Liss, Inc.
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| 12. |
- Christensen, Mette M H, et al.
(författare)
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The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c
- 2011
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Ingår i: Pharmacogenetics & Genomics. - : Lippincott, Williams and Wilkins. - 1744-6872 .- 1744-6880. ; 21:12, s. 837-850
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to evaluate the effect of genetic variations in OCT1, OCT2, MATE1, MATE 2, and PMAT on the trough steady-state plasma concentration of metformin and hemoglobin A1c (Hb1Ac). less thanbrgreater than less thanbrgreater thanMethod The South Danish Diabetes Study was a 2 x 2 x 2 factorial, prospective, randomized, double-blind, placebo-controlled, multicentre study. One hundred and fifty-nine patients received 1 g of metformin, twice daily continuously, and 415 repeated plasma metformin measurements were obtained after 3, 6, and 9 months of treatment. less thanbrgreater than less thanbrgreater thanResults The mean trough steady-state metformin plasma concentration was estimated to be 576 ng/ml (range, 54-4133 ng/ml, rho = 0.55) and correlated to the number of reduced function alleles in OCT1 (none, one or two: 642, 542, 397 ng/ml; P = 0.001). The absolute decrease in Hb1Ac both initially and long term was also correlated to the number of reduced function alleles in OCT1 resulting in diminished pharmacodynamic effect of metformin after 6 and 24 months. less thanbrgreater than less thanbrgreater thanConclusion In a large cohort of type 2 diabetics, we either confirm or show for the first time: (a) an enormous 80-fold) variability in trough steady-state metformin plasma concentration, (b) OCT1 activity affects metformin steady-state pharmacokinetics, and (c) OCT1 genotype has a bearing on HbA1c during metformin treatment.
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| 13. |
- Christensen, Steffen, et al.
(författare)
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Preadmission beta-blocker use and 30-day mortality among patients in intensive care : a cohort study
- 2011
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 15:2, s. R87-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Beta-blockers have cardioprotective, metabolic and immunomodulating effects that may be beneficial to patients in intensive care. We examined the association between preadmission beta-blocker use and 30-day mortality following intensive care. Methods: We identified 8,087 patients over age 45 admitted to one of three multidisciplinary intensive care units (ICUs) between 1999 and 2005. Data on the use of beta-blockers and medications, diagnosis, comorbidities, surgery, markers of socioeconomic status, laboratory tests upon ICU admission, and complete follow-up for mortality were obtained from medical databases. We computed probability of death within 30 days following ICU admission for beta-blocker users and non-users, and the odds ratio (OR) of death as a measure of relative risk using conditional logistic regression and also did a propensity score-matched analysis. Results: Inclusion of all 8,087 ICU patients in a logistic regression analysis yielded an adjusted OR of 0.82 (95% confidence interval (CI): 0.71 to 0.94) for beta-blocker users compared with non-users. In the propensity score-matched analysis we matched all 1,556 beta-blocker users (19.2% of the entire cohort) with 1,556 non-users; the 30-day mortality was 25.7% among beta-blocker users and 31.4% among non-users (OR 0.74 (95% CI: 0.63 to 0.87)]. The OR was 0.69 (95% CI: 0.54 to 0.88) for surgical ICU patients and 0.71 (95% CI: 0.51 to 0.98) for medical ICU patients. The OR was 0.99 (95% CI: 0.67 to 1.47) among users of non-selective beta-blockers, and 0.70 (95% CI: 0.58 to 0.83) among users of cardioselective beta-blockers. Conclusions: Preadmission beta-blocker use is associated with reduced mortality following ICU admission.
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| 14. |
- Christensen, Steffen, et al.
(författare)
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Preadmission statin use and one-year mortality among patients in intensive care : a cohort study
- 2010
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 14:2, s. R29-
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Statins reduce risk of cardiovascular events and have beneficial pleiotropic effects; both may reduce mortality in critically ill patients. We examined whether statin use was associated with risk of death in general intensive care unit (ICU) patients. METHODS: Cohort study of 12,483 critically ill patients > 45 yrs of age with a first-time admission to one of three highly specialized ICUs within the Aarhus University Hospital network, Denmark, between 2001 and 2007. Statin users were identified through population-based prescription databases. We computed cumulative mortality rates 0-30 days and 31-365 days after ICU admission and mortality rate ratios (MRRs), using Cox regression analysis controlling for potential confounding factors (demographics, use of other cardiovascular drugs, comorbidity, markers of social status, diagnosis, and surgery). RESULTS: 1882 (14.3%) ICU patients were current statin users. Statin users had a reduced risk of death within 30 days of ICU admission [users: 22.1% vs. non-users 25.0%; adjusted MRR = 0.76 (95% confidence interval (CI): 0.69 to 0.86)]. Statin users also had a reduced risk of death within one year after admission to the ICU [users: 36.4% vs. non-users 39.9%; adjusted MRR = 0.79 (95% CI: 0.73 to 0.86)]. Reduced risk of death associated with current statin use remained robust in various subanalyses and in an analysis using propensity score matching. Former use of statins and current use of non-statin lipid-lowering drugs were not associated with reduced risk of death. CONCLUSIONS: Preadmission statin use was associated with reduced risk of death following intensive care. The associations seen could be a pharmacological effect of statins, but unmeasured differences in characteristics of statin users and non-users cannot be entirely ruled out.
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| 15. |
- Christensen, Steffen, et al.
(författare)
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Three-year mortality among alcoholic patients after intensive care : a population-based cohort study
- 2012
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 16:1, s. R5-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Alcoholic patients comprise a large proportion of patients in intensive care units (ICUs). However, data are limited on the impact of alcoholism on mortality after intensive care. Methods: We conducted a cohort study among 16,848 first-time ICU patients between 2001 and 2007 to examine 30-day and 3-year mortality among alcoholic patients. Alcoholic patients with and without complications of alcohol misuse (for example, alcoholic liver disease) were identified from previous hospital contacts for alcoholism-related conditions or redemption of a prescription for alcohol deterrents. Data on medication use, demographics, hospital diagnoses, and comorbidity were obtained from medical databases. We computed 30-day and 3-year mortality and mortality rate ratios (MRRs) by using Cox regression analysis, controlling for covariates. Results: In total, 1,229 (7.3%) ICU patients were current alcoholics. Among alcoholic patients without complications of alcoholism (n = 785, 4.7% of the cohort), 30-day mortality was 15.9% compared with 19.7% among nonalcoholic patients. Compared with nonalcoholic patients, the adjusted 30-day MRR was 1.04 (95% confidence interval (CI), 0.87 to 1.25). Three-year mortality was 36.2% compared with 40.9% among nonalcoholic patients, corresponding to an adjusted 3-year MRR of 1.16 (95% CI, 1.03 to 1.31). For alcoholic patients with complications (n = 444, 2.6% of the cohort), 30-day mortality was 33.6%, and 3-year mortality was 64.5%, corresponding to adjusted MRRs, with nonalcoholics as the comparator, of 1.64 (95% CI, 1.38 to 1.95) and 1.67 (95% CI, 1.48 to 1.90), respectively. Conclusions: Alcoholic ICU patients with chronic complications of alcoholism have substantially increased 30-day and 3-year mortality. In contrast, alcoholics without complications have no increased 30-day and only slightly increased 3-year mortality.
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| 16. |
- Elfwing, Stefan, et al.
(författare)
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Darwinian Embodied Evolution of the Learning Ability for Survival
- 2011
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Ingår i: Adaptive Behavior. - : SAGE Publications. - 1059-7123 .- 1741-2633. ; 19:2, s. 101-102
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Tidskriftsartikel (refereegranskat)abstract
- In this article we propose a framework for performing embodied evolution with a limited number of robots, by utilizing time-sharing in subpopulations of virtual agents hosted in each robot. Within this framework, we explore the combination of within-generation learning of basic survival behaviors by reinforcement learning, and evolutionary adaptations over the generations of the basic behavior selection policy, the reward functions, and metaparameters for reinforcement learning. We apply a biologically inspired selection scheme, in which there is no explicit communication of the individuals' fitness information. The individuals can only reproduce offspring by mating-a pair-wise exchange of genotypes-and the probability that an individual reproduces offspring in its own subpopulation is dependent on the individual's "health," that is, energy level, at the mating occasion. We validate the proposed method by comparing it with evolution using standard centralized selection, in simulation, and by transferring the obtained solutions to hardware using two real robots.
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| 17. |
- Gregers, Jannie, et al.
(författare)
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Pharmacogenetic polymorphisms in folate metabolism affect toxicity after high dose methotrexate in childhood acute lymphoblastic leukemia
- 2012
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We hypothesized that polymorphisms in folate metabolism would affect treatment effects of the folate antagonist methotrexate (MTX). We studied whether ATIC347C>T, MTHFR677C>T, MTHFR1298C>A and SHMT1-1420C>T polymorphisms influence risk of disease or efficacy and toxicity of MTX in a large population of children with acute lymphoblastic leukaemia (ALL). The children were treated after standardized Nordic protocols with 5-8 g/m2 high-dose MTX courses and long term oral maintenance therapy with weekly MTX. Ninety-four percent (n=533) of the children diagnosed during a 16 year time period were included. The study showed that the polymorphisms had no effect on risk of ALL, MTX pharmacokinetics or outcome. However after high-dose MTX treatment, patients with MTHFR677TT/MTHFR677CT had more liver toxicity than patients with MTHFR677CC (alanine transferase: 174/154 versus 115U/L, p=0.049). Patients with MTHFR1298AA had more liver toxicity than patients with MTHFR1298CC (alanine transferase: 144 versus 108 U/L, p=0.04). More bone marrow toxicity was found in patients with MTHFR1298CC compared to MTHFR1298CT / MTHFR1298AA (Nadir means: Platelets 72 versus 109/93*109/L, p=0.0001). In conclusion this study supports that MTHFR1298C>A and MTHFR677C>T are associated with toxicity in MTX treatment and the MTHFR variants should be considered as markers for individualization of treatment in childhood ALL in combination with other pharmacogenetic markers.
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| 18. |
- Gregers, Jannie, et al.
(författare)
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The association of reduced folate carrier 80G greater than A polymorphism to outcome in childhood acute lymphoblastic leukemia interacts with chromosome 21 copy number
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:23, s. 4671-4677
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Tidskriftsartikel (refereegranskat)abstract
- The reduced folate carrier (RFC) is involved in the transport of methotrexate (MTX) across the cell membrane. The RFC gene (SLC19A1) is located on chromosome 21, and we hypothesized that the RFC80 G greater than A polymorphism would affect outcome and toxicity in childhood leukemia and that this could interact with chromosome 21 copy number in the leukemic clone. A total of 500 children with acute lymphoblastic leukemia treated according to the common Nordic treatment protocols were included, and we found that the RFC AA variant was associated with a 50% better chance of staying in remission compared with GG or GA variants (P = .046). Increased copy numbers of chromosome 21 appear to improve outcome also in children with GA or GG variant. In a subset of 182 children receiving 608 high-dose MTX courses, we observed higher degree of bone marrow toxicity in patients with the RFC AA variant compared with GA/GG variants (platelet 73 vs 99/105 x 10(9)/L, P = .004, hemoglobin 5.6 vs 5.9/6.0 mmol/L, P = .004) and a higher degree of liver toxicity in patients with RFC GG variant (alanine aminotransferase 167 vs 127/124 U/L, P = .05). In conclusion, the RFC 80G greater than A polymorphism interacts with chromosome 21 copy numbers and affects both efficacy and toxicity of MTX.
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| 19. |
- Gupta, Shashank, et al.
(författare)
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Global and 3D Spatial Assessment of Neuroinflammation in Rodent Models of Multiple Sclerosis.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Multiple Sclerosis (MS) is a progressive autoimmune inflammatory and demyelinating disease of the central nervous system (CNS). T cells play a key role in the progression of neuroinflammation in MS and also in the experimental autoimmune encephalomyelitis (EAE) animal models for the disease. A technology for quantitative and 3 dimensional (3D) spatial assessment of inflammation in this and other CNS inflammatory conditions is much needed. Here we present a procedure for 3D spatial assessment and global quantification of the development of neuroinflammation based on Optical Projection Tomography (OPT). Applying this approach to the analysis of rodent models of MS, we provide global quantitative data of the major inflammatory component as a function of the clinical course. Our data demonstrates a strong correlation between the development and progression of neuroinflammation and clinical disease in several mouse and a rat model of MS refining the information regarding the spatial dynamics of the inflammatory component in EAE. This method provides a powerful tool to investigate the effect of environmental and genetic forces and for assessing the therapeutic effects of drug therapy in animal models of MS and other neuroinflammatory/neurodegenerative disorders.
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| 20. |
- Heald, Richard, et al.
(författare)
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Optimering af kirurgi ved rectumcancer : [Optimising surgery for rectal cancer]
- 2011
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Ingår i: Ugeskrift for læger. - 1603-6824. ; 173:14, s. 1044-1047
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Tidskriftsartikel (refereegranskat)abstract
- The crucial aspect of open as well as laparoscopic rectal cancer surgery is to find the correct dissection plane to avoid damage of the nerves and to create a perfect specimen. By doing so, a "specimen oriented" resection will be achieved and the risk of a positive circumferential resection margin minimized. Currently, and for the foreseeable future, open surgery remains optimal for complex cases and in cases where a low difficult restorative resection is needed. Optimal surgery remains a crucial part in the curative treatment of this technically challenging cancer.
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| 21. |
- Hedenås, Henrik, et al.
(författare)
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Utvärdering av NILS data i fjällen
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Målet med denna studie har varit att utreda vilka variabler i NILS – Nationell Inventering av Landskapet i Sverige – som är lämpliga och möjliga att ha med i en regional miljöövervakning av fjällandskapet. Utgångspunkten är miljömålet ”Storslagen fjällmiljö”. De data som använts i denna rapport är från två hela inventeringsvarv i NILS fältinventering (2003-2007 respektive 2008-2012) och från ett inventeringsvarv i NILS flygbildstolkning (2003-2007). För fältdata har både data från provyte- och linjekorsningsinventeringen använts. Alla data analyseras dels för hela fjällkedjan, vilken omfattar all mark ovanför den s.k. gränsen för fjällnära skog, och dels för norra fjällen (Norrbottens län ovanför denna gräns) respektive södra fjällen (Västerbottens, Jämtlands och Dalarnas län ovanför denna gräns). Det finns en lång rad variabler i NILS som är nog vanliga för att det skall vara möjligt att detektera förändringar över tiden och som därmed kan användas som uppföljningsbara indikatorer. Exempel på sådana är total krontäckning; täckning av björk; total busktäckning; täckningen av enbuskar, dvärgbjörk och vissa videarter eller artgrupper; fältskiktets totala täckning; täckning av ris och graminider samt av örter i vissa habitat. När det gäller bottenskiktet behövs det lite mer ingående analyser, men gruppen övriga mossor är utan tvekan en grupp som är nog vanlig för att det skall vara möjligt att använda som indikator på förändringar. Det som i hög grad styr om en variabel är möjlig att använda är hur vanlig den är, d.v.s. i hur många NILS rutor som den har registrerats. I här ej publicerade analyser kan vi konstatera att NILS kan följa förändringar över tiden med en tillräcklig tillförlitlighet för variabler som registerats i 13 eller fler rutor. Men är förändringen stor och distinkt nog så kan även förändringar av något ovanligare variabler detekteras (ex. dvärgbjörk på klimatimpediment i södra delen av fjällkedjan). Data från NILS linjekorsningsinventering ger underlag för analyser av tätheten av linjära element. När det gäller variabler så är vattendragen en grupp som är nog vanlig för att det skall vara möjligt att detektera förändringar. När det gäller transportleder så finns det en potential att detektera förändringar i variablerna djurstigar och fordonsspår. För båda dessa variabler finns det indikationer på förändringar i detta datamaterial. För flygbildstolkade data har vi inte genomfört några förändringsskattningar då vi än så länge enbart har data från perioden 2003-2007. Av de variabler som vi tittat på i denna studie är areal öppen och trädbeklädd mark, med andel busk- och trädtäckning i fjällbarrskogen, fjällbjörkskogen och på kalfjället intressanta att följa med avseende på igenväxning av tidigare mer öppna områden. Våra resultat visar att det inte har skett några signifikanta förändringar i areal fjällbarrskog, fjällbjörkskog och kalfjäll under denna tidsperiod (2003-2007 jämfört med 2008-2012). Att kalfjället växer igen på grund av klimatförändringar är något som diskuteras och det finns forskningsresultat från delar av fjällkedjan som stödjer detta. NILS kan med sitt stickprov följa förändringar över hela fjällkedjan men inom denna relativt korta tidsperiod är det inte förväntat att några större förändringar skall ha hunnit ske. Det är dock viktigt att följa hur dessa arealer och deras utbredning (latitud, longitud, altitud) förändras över tiden över hela fjällkedjan, för att kunna fånga upp storskaliga förändringar och ge underlag för uppföljning av miljömål och mer fördjupade studier. Den totala krontäckningen på kalfjället har ökat i hela fjällkedjan, men det har inte skett någon ökad krontäckning av björk som är den dominerande trädarten. Detta gör att resultaten måste tolkas med viss försiktighet. Den totala busktäckningen på kalfjället är högre i den södra delen av fjällkedjan jämfört med den norra delen Detta kan eventuellt bero på skillnader i klimat och betestryck mellan områdena. En annan orsak som kanske kan förklara skillnaden i busktäckning mellan södra och norra fjällen är att det är relativt mer lågalpina områden (lägre altitud som oftare är buskrika) i södra fjällen jämfört med norra fjällen där de finns relativt mer mellan och högalpina områden (som ofta är buskfattiga). Fältskiktet har ökat i hela fjällkedjan; på kalfjället, i fjällbjörkskogen och i fjällbarrskogen. Framförallt har det skett en ökning av graminider och ris på kalfjället och i fjällbjörkskogen. Denna trend är tydligare i norra delen än i södra. I södra delen är det enbart ris som ökat på kalfjället. För linjeobjekten är den relativa standardavikelsen hög och resultaten måste därför tolkas med försiktighet. Intressant är dock den konstaterade ökningen av fordonsspår i hela fjällkedjan. Ett exploateringsindex, som bygger på den totala tätheten av linjeelement, har tagits fram som är ett mått på total mänsklig påverkan, men visar inte på några skillnader över tiden. Rapporten visar att NILS redan idag kan leverera bra underlag för nationell och regional miljöövervakning och indikatorer till miljömålet ”Storslagen fjällmiljö.” Det finns också stora möjligheter att utveckla miljöövervakningen i fjällkedjan för bättre och mer omfattande landskapsdata som underlag till en långsiktigt hållbar förvaltning av fjällandskapet.
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| 22. |
- Kragic, Danica, et al.
(författare)
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Robust Visual Servoing
- 2014
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Ingår i: Household Service Robotics. - : Elsevier. - 9780128009437 ; , s. 397-427
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- For service robots operating in domestic environments, it is not enough to consider only control level robustness; it is equally important to consider how image information that serves as input to the control process can be used so as to achieve robust and efficient control. In this chapter we present an effort toward the development of robust visual techniques used to guide robots in various tasks. Given a task at hand, we argue that different levels of complexity should be considered; this also defines the choice of the visual technique used to provide the necessary feedback information. We concentrate on visual feedback estimation where we investigate both two- and three-dimensional techniques. In the former case, we are interested in providing coarse information about the object position/velocity in the image plane. In particular, a set of simple visual features (cues) is employed in an integrated framework where voting is used for fusing the responses from individual cues. The experimental evaluation shows the system performance for three different cases of camera-robot configurations most common for robotic systems. For cases where the robot is supposed to grasp the object, a two-dimensional position estimate is often not enough. Complete pose (position and orientation) of the object may be required. Therefore, we present a model-based system where a wire-frame model of the object is used to estimate its pose. Since a number of similar systems have been proposed in literature, we concentrate on the particular part of the system usually neglected-automatic pose initialization. Finally, we show how a number of existing approaches can successfully be integrated in a system that is able to recognize and grasp fairly textured, everyday objects. One of the examples presented in the experimental section shows a mobile robot performing tasks in a real-word environment-a living room.
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| 23. |
- Laustsen, Søren Ravn, et al.
(författare)
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Præoperativ funktionel magnetisk resonans-billeddannelse hos patienter med hjernetumor
- 2010
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Ingår i: Ugeskrift for læger. - 0041-5782 .- 1603-6824. ; 172:35, s. 2370-2376
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Functional Magnetic Resonance Imaging (fMRI) allows important functions in the brain cortex to be mapped noninvasively. The purpose with this work was to investigate a possible correlation between the distance from the tumour margin to fMRI activity and postoperative neurological deficits by means of a standardised method for measurement of distance. A second purpose was to investigate the influence of preoperative fMRI on the neurosurgical decision-making process. MATERIAL AND METHODS: Retrospective study of 25 patients. The inclusion criteria were surgery or biopsy after fMRI plus a three-month postoperative assessment. A total of 14 patients complied with these requirements (six men and eight women, the mean age was 39 years). fMRI raw data was collected using a three tesla magnetic resonance scanner (Signa HDx R14M5, GE Healthcare). The distance from the tumour margin to fMRI activation was measured using GE-reformat version 4.2 after raw data had been postprocessed using GE BrainwavePA version 1.3.08130. The neurosurgeons valuation of fMRI in the preoperative decision-making process was obtained using a standard questionnaire. RESULTS: There was a trend of association between distance from tumour to eloquent functional areas and the patients' postoperative neurological outcome (Fisher's exact test: distance < 15 mm, p = 0.43; distance < 10 mm, p = 0.14). fMRI proved very useful when deciding whether to operate or not (42%), when deciding the surgical approach (50%) and when deciding the extent of the surgical approach (83%). CONCLUSION: The standardised method for measurement of distance between tumour margin and fMRI activity can contribute to the preoperative risk assessment in patients with brain tumours.
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| 24. |
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| 25. |
- Lund, Morten E., et al.
(författare)
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Inductive tongue control of powered wheelchairs
- 2010
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Ingår i: International Conference of the IEEE Engineering in Medicine and Biology Society. - 1557-170X. - 9781424441235 ; , s. 3361-3364
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Konferensbidrag (refereegranskat)abstract
- Alternative and effective methods for controlling powered wheelchairs are important to individuals with tetraplegia and similar impairments whom are unable to use the standard joystick. This paper describes a system where tongue movements are used to control a powered wheelchair thus providing users, with high level spinal cord injuries, full control of their wheelchair. The system is based on an inductive tongue control system developed at Center for Sensory-Motor Interaction (SMI), Aalborg University. The system emulates a standard analog joystick in order to interface the wheelchair, thus ensuring that the system works with almost any wheelchair. The total embedment of the tongue interface into the mouth makes the control practically invisible. A fuzzy system combining 8 sensors for directional control allows for multidirectional control of the wheelchair. Preliminary test results show navigation abilities, which are highly competitive when compared to other tongue control system.
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| 26. |
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| 27. |
- Merrie, Andrew, et al.
(författare)
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An ocean of surprises - Trends in human use, unexpected dynamics and governance challenges in areas beyond national jurisdiction
- 2014
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Ingår i: Global Environmental Change. - : Elsevier BV. - 0959-3780 .- 1872-9495. ; 27, s. 19-31
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Tidskriftsartikel (refereegranskat)abstract
- The expanse of ocean which makes up all marine areas beyond national jurisdiction has been characterized as the last frontier of exploitation on the planet, a figurative final Wild West. Existing users of areas beyond national jurisdiction, with the exception of fisheries, currently have a limited footprint there as a consequence, in part, of substantial hurdles in technological development that need to be overcome before many resources can be extracted at a commercially viable scale. However, we argue surprise shifts perpetuated by both established and emerging users could lead to an expansion in actors taking opportunities to chase lucrative resources that they are currently constrained from exploiting. Rapid development could also lead to a crowded ocean due to the multiplication of users which could present a problem given the current lack of a unified institutional framework for governance connecting the different user groups. Here, we have collated trends in human use of areas beyond national jurisdiction and offer a framework for, and examples of, unexpected dynamics relevant to living and non-living marine resources. Such an approach is necessary in order to begin to mobilize an adequate governance response to changing conditions and uses of areas beyond national jurisdiction. This governance response must be able to govern established or potential users, be flexible and adaptive in response to unexpected and unpredictable dynamics and be able to transform in the face of unpredictable future uses of this vast area. Here we present a set of institutional design principles as a first tentative step in this direction.
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| 28. |
- Nygaard, Jesper, et al.
(författare)
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Metal Ion Controlled Self-Assembly of a Chemically Reengineered Protein Drug Studied by Small-Angle X-ray Scattering
- 2012
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 28:33, s. 12159-12170
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Tidskriftsartikel (refereegranskat)abstract
- Precise control of the oligomeric state of proteins is of central importance for biological function and for the properties of biopharmaceutical drugs. Here, the self-assembly of 2,2'-bipyridine conjugated monomeric insulin analogues, induced through coordination to divalent metal ions, was studied. This protein drug system was designed to form non-native homo-oligomers through selective coordination of two divalent metal ions, Fe(II) and Zn(II), respectively. The insulin type chosen for this study is a variant designed for a reduced tendency toward native dimer formation at physiological concentrations. A small-angle X-ray scattering analysis of the bipyridine-modified insulin system confirmed an organization into a novel well-ordered structure based on insulin trimers, as induced by the addition of Fe(II). In contrast, unmodified monomeric insulin formed larger and more randomly structured assemblies upon addition of Fe(II). The addition of Zn(II), on the other hand, led to the formation of small quantities of insulin hexamers for both the bipyridine-modified and the unmodified monomeric insulin. Interestingly, the location of the bipyridine-modification significantly affects the tendency to hexamer formation as compared to the unmodified insulin. Our study shows how combining a structural study and chemical design can be used to obtain molecular understanding and control of the self-assembly of a protein drug. This knowledge may eventually be employed to develop an optimized in vivo drug release profile.
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| 29. |
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| 30. |
- Pronobis, Andrzej, et al.
(författare)
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Overview of the ImageCLEF@ICPR 2010 Robot Vision Track
- 2010
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Ingår i: RECOGNIZING PATTERNS IN SIGNALS, SPEECH, IMAGES, AND VIDEOS. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 9783642177101 ; , s. 171-179
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Konferensbidrag (refereegranskat)abstract
- This paper describes the robot vision track that has been proposed to the ImageCLEF@ICPR2010 participants. The track addressed the problem of visual place classification. Participants were asked to classify rooms and areas of an office environment on the basis of image sequences captured by a stereo camera mounted on a mobile robot, under varying illumination conditions. The algorithms proposed by the participants had to answer the question "where are you?" (I am in the kitchen, in the corridor, etc) when presented with a test sequence imaging rooms seen during training (from different viewpoints and under different conditions), or additional rooms that were not imaged in the training sequence. The participants were asked to solve the problem separately for each test image (obligatory task). Additionally, results could also be reported for algorithms exploiting the temporal continuity of the image sequences (optional task). A total of eight groups participated to the challenge, with 25 runs submitted to the obligatory task, and 5 submitted to the optional task. The best result in the obligatory task was obtained by the Computer Vision and Geometry Laboratory, ETHZ, Switzerland, with, an overall score of 3824.0. The best result in the optional task was obtained by the intelligent Systems and Data Mining Group, University of Castilla-La Mancha, Albacete, Spain, with an overall score of 3881..0.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Storm, Tina, et al.
(författare)
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Renal phenotypic investigations of megalin-deficient patients : novel insights into tubular proteinuria and albumin filtration
- 2013
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 28:3, s. 585-591
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe reabsorption of filtered plasma proteins, hormones and vitamins by the renal proximal tubules is vital for body homeostasis. Studies of megalin-deficient mice suggest that the large multi-ligand endocytic receptor megalin plays an essential role in this process. In humans, dysfunctional megalin causes the extremely rare Donnai-Barrow/Facio-Oculo-Acustico-Renal (DB/FOAR) syndrome characterized by a characteristic and multifaceted phenotype including low-molecular-weight proteinuria. In this study, we examined the role of megalin for tubular protein reabsorption in humans through analysis of proximal tubular function in megalin-deficient patients.MethodsDirect sequencing of the megalin-encoding gene (LRP2) was performed in a family in which three children presented with classical DB/FOAR manifestations. Renal consequences of megalin deficiency were investigated through immunohistochemical analyses of renal biopsy material and immunoblotting of urine samples.ResultsIn the patients, a characteristic urinary protein profile with increased urinary excretion of vitamin D-binding protein, retinol-binding protein and albumin was associated with absence of, or reduced, proximal tubular endocytic uptake as shown by renal immunohistochemistry. In the absence of tubular uptake, urinary albumin excretion was in the micro-albuminuric range suggesting that limited amounts of albumin are filtered in human glomeruli.ConclusionsThis study demonstrated that megalin plays an essential role for human proximal tubular protein reabsorption and suggests that only limited amounts of albumin is normally filtered in the human glomeruli. Finally, we propose that the characteristic urinary protein profile of DB/FOAR patients may be utilized as a diagnostic marker of megalin dysfunction.
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| 35. |
- Topp, Elin A., et al.
(författare)
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Detecting Region Transitions for Human-Augmented Mapping
- 2010
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Ingår i: IEEE TRANS ROBOT. - 1552-3098. ; 26:4, s. 715-720
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we describe a concise method for the feature-based representation of regions in an indoor environment and show how it can also be applied for door-passage-independent detection of transitions between regions to improve communication with a human user.
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| 36. |
- van der Post, Sjoerd, 1981, et al.
(författare)
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Site-specific O-glycosylation on the MUC2 mucin protein inhibits cleavage by the Porphyromonas gingivalis secreted cysteine protease (RgpB).
- 2013
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Ingår i: The Journal of biological chemistry. - 1083-351X. ; 288:20, s. 14636-46
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Tidskriftsartikel (refereegranskat)abstract
- The colonic epithelial surface is protected by an inner mucus layer that the commensal microflora cannot penetrate. We previously demonstrated that Entamoeba histolytica secretes a protease capable of dissolving this layer that is required for parasite penetration. Here, we asked whether there are bacteria that can secrete similar proteases. We screened bacterial culture supernatants for such activity using recombinant fragments of the MUC2 mucin, the major structural component, and the only gel-forming mucin in the colonic mucus. MUC2 has two central heavily O-glycosylated mucin domains that are protease-resistant and has cysteine-rich N and C termini responsible for polymerization. Culture supernatants of Porphyromonas gingivalis, a bacterium that secretes proteases responsible for periodontitis, cleaved the MUC2 C-terminal region, whereas the N-terminal region was unaffected. The active enzyme was isolated and identified as Arg-gingipain B (RgpB). Two cleavage sites were localized to IR↓TT and NR↓QA. IR↓TT cleavage will disrupt the MUC2 polymers. Because this site has two potential O-glycosylation sites, we tested whether recombinant GalNAc-transferases (GalNAc-Ts) could glycosylate a synthetic peptide covering the IRTT sequence. Only GalNAc-T3 was able to glycosylate the second Thr in IRTT, rendering the sequence resistant to cleavage by RgpB. Furthermore, when GalNAc-T3 was expressed in CHO cells expressing the MUC2 C terminus, the second threonine was glycosylated, and the protein became resistant to RgpB cleavage. These findings suggest that bacteria can produce proteases capable of dissolving the inner protective mucus layer by specific cleavages in the MUC2 mucin and that this cleavage can be modulated by site-specific O-glycosylation.
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| 37. |
- Österblom, Henrik, et al.
(författare)
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Modeling Social—Ecological Scenarios in Marine Systems
- 2013
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Ingår i: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 63:9, s. 735-744
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Tidskriftsartikel (refereegranskat)abstract
- Human activities have substantial impacts on marine ecosystems, including rapid regime shifts with large consequences for human well-being. We highlight the use of model-based scenarios as a scientific tool for adaptive stewardship in the face of such consequences. The natural sciences have a long history of developing scenarios but rarely with an in-depth understanding of factors influencing human actions. Social scientists have traditionally investigated human behavior, but scholars often argue that behavior is too complex to be repre-ented by broad generalizations useful for models and scenarios. We address this scientific divide with a framework for integrated marine social ecological scenarios, combining quantitative process-based models from the biogeochemical and ecological disciplines with qualitative studies on governance and social change. The aim is to develop policy-relevant scenarios based on an in-depth empirical understanding from both the natural and the social sciences, thereby contributing to adaptive stewardship of marine social-ecological systems.
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