| 1. |
- Iacobelli, M., et al.
(author)
-
Studying Galactic interstellar turbulence through fluctuations in synchrotron emission: First LOFAR Galactic foreground detection
- 2013
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 558, s. 721-
-
Journal article (peer-reviewed)abstract
- Aims. The characteristic outer scale of turbulence (i.e. the scale at which the dominant source of turbulence injects energy to the interstellar medium) and the ratio of the random to ordered components of the magnetic field are key parameters to characterise magnetic turbulence in the interstellar gas, which affects the propagation of cosmic rays within the Galaxy. We provide new constraints to those two parameters. Methods. We use the LOw Frequency ARray (LOFAR) to image the diffuse continuum emission in the Fan region at (l,b) ∼ (137.0, +7.0) at 80′′ × 70′′ resolution in the range [146, 174] MHz. We detect multi-scale fluctuations in the Galactic synchrotron emission and compute their power spectrum. Applying theoretical estimates and derivations from the literature for the first time, we derive the outer scale of turbulence and the ratio of random to ordered magnetic field from the characteristics of these fluctuations. Results. We obtain the deepest image of the Fan region to date and find diffuse continuum emission within the primary beam. The power spectrum displays a power law behaviour for scales between 100 and 8 arcmin with a slope α =-1.84 ± 0.19. We find an upper limit of ∼20 pc for the outer scale of the magnetic interstellar turbulence toward the Fan region, which is in agreement with previous estimates in literature. We also find a variation of the ratio of random to ordered field as a function of Galactic coordinates, supporting different turbulent regimes. Conclusions. We present the first LOFAR detection and imaging of the Galactic diffuse synchrotron emission around 160 MHz from the highly polarized Fan region. The power spectrum of the foreground synchrotron fluctuations is approximately a power law with a slope α ≈-1.84 up to angular multipoles of ≤1300, corresponding to an angular scale of ∼8 arcmin. We use power spectra fluctuations from LOFAR as well as earlier GMRT and WSRT observations to constrain the outer scale of turbulence (Lout) of the Galactic synchrotron foreground, finding a range of plausible values of 10-20 pc. Then, we use this information to deduce lower limits of the ratio of ordered to random magnetic field strength. These are found to be 0.3, 0.3, and 0.5 for the LOFAR, WSRT and GMRT fields considered respectively. Both these constraints are in agreement with previous estimates. © 2013 ESO.
|
|
| 2. |
- Oonk, J. B. R., et al.
(author)
-
Discovery of carbon radio recombination lines in absorption towards Cygnus A
- 2014
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 437:4, s. 3506-3515
-
Journal article (peer-reviewed)abstract
- We present the first detection of carbon radio recombination line absorption along the line of sight to Cygnus A. The observations were carried out with the Low Frequency Array in the 33–57 MHz range. These low-frequency radio observations provide us with a new line of sight to study the diffuse, neutral gas in our Galaxy. To our knowledge this is the first time that foreground Milky Way recombination line absorption has been observed against a bright extragalactic background source. By stacking 48 carbon α lines in the observed frequency range we detect carbon absorption with a signal-to-noise ratio of about 5. The average carbon absorption has a peak optical depth of 2 × 10−4, a line width of 10 km s−1 and a velocity of +4 km s−1 with respect to the local standard of rest. The associated gas is found to have an electron temperature Te ∼ 110 K and density ne ∼ 0.06 cm−3. These properties imply that the observed carbon α absorption likely arises in the cold neutral medium of the Orion arm of the Milky Way. Hydrogen and helium lines were not detected to a 3σ peak optical depth limit of 1.5 × 10−4 for a 4 km s−1 channel width. Radio recombination lines associated with Cygnus A itself were also searched for, but are not detected. We set a 3σ upper limit of 1.5 × 10−4 for the peak optical depth of these lines for a 4 km s−1 channel width.
|
|
| 3. |
- Adlarson, Patrik, et al.
(author)
-
Abashian-Booth-Crowe Effect in Basic Double-Pionic Fusion : A New Resonance?
- 2011
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 106:24, s. 242302-
-
Journal article (peer-reviewed)abstract
- We report on an exclusive and kinematically complete high-statistics measurement of the basic double-pionic fusion reaction pn -> d pi(0)pi(0) over the full energy region of the ABC effect, a pronounced low-mass enhancement in the pi pi-invariant mass spectrum. The measurements, which cover also the transition region to the conventional t- channel Delta Delta process, were performed with the upgraded WASA detector setup at COSY. The data reveal the Abashian-Booth-Crowe effect to be uniquely correlated with a Lorentzian energy dependence in the integral cross section. The observables are consistent with a narrow resonance with m = 2.37 GeV, Gamma approximate to 70 MeV and I(J(P)) = 0(3(+)) in both pn and Delta Delta systems. Necessary further tests of the resonance interpretation are discussed.
|
|
| 4. |
- Adlarson, Patrik, et al.
(author)
-
Exclusive measurement of the eta -> pi(+) pi(-) gamma decay
- 2012
-
In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 707:2, s. 243-249
-
Journal article (peer-reviewed)abstract
- An exclusive measurement of the decay eta -> pi(+) pi(-) gamma has been performed at the WASA facility at COSY. The eta mesons were produced in the fusion reaction pd -> He-3 X at a proton beam momentum of 1.7 GeV/c. Efficiency corrected differential distributions have been extracted based on 13 960 +/- 140 events after background subtraction. The measured pion angular distribution is consistent with a relative p-wave of the two-pion system, whereas the measured photon energy spectrum was found at variance with the simplest gauge invariant matrix element of eta -> pi(+) pi(-) gamma. A parameterization of the data can be achieved by the additional inclusion of the empirical pion vector form factor multiplied by a first-order polynomial in the squared invariant mass of the pi(+) pi(-) system.
|
|
| 5. |
- Jelic, V., et al.
(author)
-
Initial LOFAR observations of epoch of reionization windows II. Diffuse polarized emission in the ELAIS-N1 field
- 2014
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 568, s. A101-
-
Journal article (peer-reviewed)abstract
- Aims. This study aims to characterise the polarized foreground emission in the ELAIS-N1 field and to address its possible implications or extracting of the cosmological 21 cm signal from the LOw-Frequency ARray - Epoch of Reionization (LOFAR-EoR) data Methods. We used the high band antennas of LOFAR to image this region and RM-synthesis to unravel structures of polarized emission at high Galactic latitudes. Results. The brightness temperature of the detected Galactic emission is on average similar to 4 K in polarized intensity and covers the range from -10 to +13 rad m(-2) in Faraday depth, The total polarized intensity and polarization angle show a wide range of morphological features. We have also used the Westerbork Synthesis Radio Telescope (WSRT) at 350 MHz to image the same region. The LOFAR and WSRT images show a similar complex morphology at comparable brightness levels, but their spatial correlation is very low. The fractional polarization at 150 MHz, expressed as a percentage of the total intensity, amounts to approximate to 1.5%. There is no indication of diffuse emission in total intensity in the interferometric data. in line with results at higher frequencies Conclusions. The wide frequency range. high angular resolution, and high sensitivity make LOFAR an exquisite instrument for studying Galactic polarized emission at a resolution of similar to 1-2 rad m(-2) in Faraday depth. The different polarized patterns observed at 150 MHz and 350 MHz are consistent with different source distributions along the line of sight wring in a variety of Faraday thin regions of emission. The presence of polarized foregrounds is a serious complication for epoch of reionization experiments. To avoid the leakage of polarized emission into total intensity, which can depend on frequency, we need to calibrate the instrumental polarization across the field of view to a small fraction of 1%.
|
|
| 6. |
- Morosan, D. E., et al.
(author)
-
LOFAR tied-array imaging of Type III solar radio bursts
- 2014
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 568, s. articl no. A67-
-
Journal article (peer-reviewed)abstract
- Context. The Sun is an active source of radio emission which is often associated with energetic phenomena such as solar flares and coronal mass ejections (CMEs). At low radio frequencies (
|
|
| 7. |
- van Weeren, R. J., et al.
(author)
-
Lofar low-band antenna observations of the 3C 295 and boötes fields: Source counts and ultra-steep spectrum sources
- 2014
-
In: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 793:2, s. art. 82-
-
Journal article (peer-reviewed)abstract
- We present Low Frequency Array (LOFAR) Low Band observations of the Bootes and 3C 295 fields. Our images made at 34, 46, and 62 MHz reach noise levels of 12, 8, and 5 mJy beam(-1), making them the deepest images ever obtained in this frequency range. In total, we detect between 300 and 400 sources in each of these images, covering an area of 17-52 deg(2). From the observations, we derive Euclidean-normalized differential source counts. The 62 MHz source counts agree with previous GMRT 153 MHz and Very Large Array 74 MHz differential source counts, scaling with a spectral index of -0.7. We find that a spectral index scaling of -0.5 is required to match up the LOFAR 34 MHz source counts. This result is also in agreement with source counts from the 38 MHz 8C survey, indicating that the average spectral index of radio sources flattens toward lower frequencies. We also find evidence for spectral flattening using the individual flux measurements of sources between 34 and 1400 MHz and by calculating the spectral index averaged over the source population. To select ultra-steep spectrum (alpha
|
|
| 8. |
- Adlarson, Patrik, et al.
(author)
-
Abashian-Booth-Crowe resonance structure in the double pionic fusion to He-4
- 2012
-
In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 86:3, s. 032201-
-
Journal article (peer-reviewed)abstract
- Exclusive and kinematically complete high-statistics measurements of the double pionic fusion reaction dd -> He-4 pi(0)pi(0) have been performed in the energy range 0.8-1.4 GeV covering thus the region of the Abashian-Booth-Crowe effect, which denotes a pronounced low-mass enhancement in the pi pi invariant mass spectrum. The experiments were carried out with the WASA detector setup at the cooler synchrotron at Forshungszentrum Julich GmbH. Similar to the observation in the basic pn -> d pi(0)pi(0) reaction, the data reveal a correlation between the ABC effect and a resonancelike energy dependence in the total cross section. The maximum occurs at m = 2.37 GeV + 2m(N), i.e., at the same position as in the basic reaction. The observed resonance width Gamma approximate to 160 MeV can be understood from broadening due to Fermi motion of the nucleons in initial and final nuclei together with collision damping. Differential cross sections are described equally well by the hypothesis of a pn resonance formation during the reaction process.
|
|
| 9. |
- Adlarson, Patrik, et al.
(author)
-
Investigation of the dd -> (3)Hen pi(0) reaction with the FZ Julich WASA-at-COSY facility
- 2013
-
In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 88:1, s. 014004-
-
Journal article (peer-reviewed)abstract
- An exclusive measurement of the dd -> (3)Hen pi(0) reaction was carried out at a beam momentum of p(d) = 1.2 GeV/c using the WASA-at-COSY facility. Information on the total cross section as well as differential distributions was obtained. The data are described by a phenomenological approach based on a combination of a quasifree model and a partial wave expansion for the three-body reaction. The total cross section is found to be sigma(tot) = ( 2.89 +/- 0.01(stat) +/- 0.06(sys) +/- 0.29(norm)) mu b. The contribution of the quasifree processes ( with the beam or target neutron being a spectator) accounts for 38% of the total cross section and dominates the differential distributions in specific regions of phase space. The remaining part of the cross section can be described by a partial wave decomposition indicating the significance of p-wave contributions in the final state.
|
|
| 10. |
- Adlarson, Patrik, et al.
(author)
-
pi(0)pi(0) Production in proton-proton collisions at T-p=1.4 GeV The WASA-at-COSY Collaboration
- 2012
-
In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 706:4-5, s. 256-262
-
Journal article (peer-reviewed)abstract
- The reaction pp -> pp pi(0)pi(0) has been investigated at a beam energy of 1.4 GeV using the WASA-at-COSY facility. The total cross section is found to be (324 +/- 21(systematic) +/- 58(normalization)) mu b. In order to study the production mechanism, differential kinematic distributions have been evaluated. The differential distributions indicate that both initial state protons are excited into intermediate Delta(1232) resonances, each decaying into a proton and a single pion, thereby producing the pion pair in the final state. No significant contribution of the Roper resonance N*(1440) via its decay into a proton and two pions is found.
|
|
| 11. |
- Adlarson, Patrik, et al.
(author)
-
Charge symmetry breaking in dd -> He-4 pi(0) with WASA-at-COSY
- 2014
-
In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 739, s. 44-49
-
Journal article (peer-reviewed)abstract
- Charge symmetry breaking (CSB) observables are a suitable experimental tool to examine effects induced by quark masses on the nuclear level. Previous high precision data from TRIUMF and IUCF are currently used to develop a consistent description of CSB within the framework of chiral perturbation theory. In this work the experimental studies on the reaction dd -> He-4 pi(0) have been extended towards higher excess energies in order to provide information on the contribution of p-waves in the final state. For this, an exclusive measurement has been carried out at a beam momentum of p(d) = 1.2GeV/c using the WASA-at-COSY facility. The total cross section amounts to sigma(tot) =(118 +/- 18(stat) +/- 13(sys) +/- 8(ext)) p band first data on the differential cross section are consistent with s-wave pion production.
|
|
| 12. |
- Adlarson, P., et al.
(author)
-
Isospin decomposition of the basic double-pionic fusion in the region of the ABC effect
- 2013
-
In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 721:4-5, s. 229-236
-
Journal article (peer-reviewed)abstract
- Exclusive and kinematically complete high-statistics measurements of the basic double-pionic fusion reactions pn -> d pi(0)pi(0), pn -> d pi(+)pi(-) and pp -> d pi(+)pi(0) have been carried out simultaneously over the energy region of the ABC effect using the WASA detector setup at COSY. Whereas the isoscalar reaction part given by the d pi(0)pi(0) channel exhibits the ABC effect, i.e. a low-mass enhancement in the pi pi-invariant mass distribution, as well as the associated resonance structure in the total cross section, the isovector part given by the d pi(+)pi(0) channel shows a smooth behavior consistent with the conventional t-channel Delta Delta process. The d pi(+)pi(-) data are very well reproduced by combining the data for isovector and isoscalar contributions, if the kinematical consequences of the isospin violation due to different masses for charged and neutral pions are taken into account.
|
|
| 13. |
- Adlarson, Patrik, et al.
(author)
-
Measurement of the eta -> pi(+)pi(-)pi(0) Dalitz plot distribution
- 2014
-
In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 90:4, s. 045207-
-
Journal article (peer-reviewed)abstract
- The Dalitz plot distribution of the eta -> pi(+)pi(-)pi(0) decay is determined by using a data sample of 1.2 x 10(7) eta mesons from the pd -> He-3 eta reaction at 1 GeV collected by the WASA detector at COSY.
|
|
| 14. |
- Adlarson, Patrik, et al.
(author)
-
Measurement of the pn -> pp pi(0)pi(-) reaction in search for the recently observed resonance structure in d pi(0)pi(0) and d pi(+)pi(-) systems
- 2013
-
In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 88:5, s. 055208-
-
Journal article (peer-reviewed)abstract
- Exclusive measurements of the quasifree pn -> pp pi(0)pi(-) reaction have been performed by means of pd collisions at T-p = 1.2 GeV using the wide angle shower apparatus (WASA) detector setup at the cooler synchrotron COSY (Institut fur Kernphysik, Julich). Total and differential cross sections have been obtained covering the energy region root s = (2.35-2.46) GeV, which includes the region of the ABC effect and its associated resonance structure. NoABCeffect, i.e., low-mass enhancement is found in the pi(0)pi(-) -invariant mass spectrum, in agreement with the constraint from Bose statistics that the isovector pion pair can not be in relative s wave. At the upper end of the covered energy region t-channel processes for Roper, Delta(1600) and Delta Delta excitations provide a reasonable description of the data, but at low energies the measured cross sections are much larger than predicted by such processes. Adding a resonance amplitude for the resonance at m = 2.37 GeV with Gamma = 70 MeV and I (J(P)) = 0(3(+)) observed recently in pn -> d pi(0)pi(0) and pn -> d pi(+)pi(-) reactions leads to an agreement with the data also at low energies.
|
|
| 15. |
- Adlarson, Patrik, et al.
(author)
-
Search for eta-mesic He-4 with the WASA-at-COSY detector
- 2013
-
In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 87:3, s. 035204-
-
Journal article (peer-reviewed)abstract
- An exclusive measurement of the excitation function for the dd -> (3)Hep pi(-) reaction was performed at the Cooler Synchrotron COSY-Julich with the WASA-at-COSY detection system. The data were taken during a slow acceleration of the beam from 2.185 to 2.400 GeV/c crossing the kinematic threshold for the eta-meson production in the dd -> He-4 eta reaction at 2.336 GeV/c. The corresponding excess energy with respect to the He-4-eta system varied from -51.4 to 22 MeV. The integrated luminosity in the experiment was determined using the dd -> (3)Hen reaction. The shape of the excitation function for the dd -> (3)Hep pi(-) reaction was examined. No signal of the He-4-eta bound state was observed. An upper limit for the cross section for the bound state formation and decay in the process dd -> (He-4-eta)(bound) -> (3)Hep pi(-) was determined on the 90% confidence level and it varies from 20 to 27 nb for the bound state width ranging from 5 to 35 MeV, respectively.
|
|
| 16. |
- Spinelli, L., et al.
(author)
-
Determination of reference values for optical properties of liquid phantoms based on Intralipid and India ink
- 2014
-
In: Biomedical Optics Express. - : Optical Society of America. - 2156-7085. ; 5:7, s. 2037-2053
-
Journal article (peer-reviewed)abstract
- A multi-center study has been set up to accurately characterize the optical properties of diffusive liquid phantoms based on Intralipid and India ink at near-infrared (NIR) wavelengths. Nine research laboratories from six countries adopting different measurement techniques, instrumental set-ups, and data analysis methods determined at their best the optical properties and relative uncertainties of diffusive dilutions prepared with common samples of the two compounds. By exploiting a suitable statistical model, comprehensive reference values at three NIR wavelengths for the intrinsic absorption coefficient of India ink and the intrinsic reduced scattering coefficient of Intralipid-20% were determined with an uncertainty of about 2% or better, depending on the wavelength considered, and 1%, respectively. Even if in this study we focused on particular batches of India ink and Intralipid, the reference values determined here represent a solid and useful starting point for preparing diffusive liquid phantoms with accurately defined optical properties. Furthermore, due to the ready availability, low cost, long-term stability and batch-to-batch reproducibility of these compounds, they provide a unique fundamental tool for the calibration and performance assessment of diffuse optical spectroscopy instrumentation intended to be used in laboratory or clinical environment. Finally, the collaborative work presented here demonstrates that the accuracy level attained in this work for optical properties of diffusive phantoms is reliable.
|
|
| 17. |
- Adlarson, Patrik, et al.
(author)
-
Cross section ratio and angular distributions of the reaction p + d -> He-3 + eta at 48.8MeV and 59.8MeV excess energy
- 2014
-
In: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 50:6, s. 100-
-
Journal article (peer-reviewed)abstract
- We present new data for angular distributions and on the cross section ratio of the p+d -> He-3+eta reaction at excess energies of Q - 48.8MeV and Q - 59.8 MeV. The data have been obtained at the WASA-at-COSY experiment (Forschungszentrum Julich) using a proton beam and a deuterium pellet target. While the shape of obtained angular distributions show only a slow variation with the energy, the new results indicate a distinct and unexpected total cross section fluctuation between Q = 20MeV and Q = 60 MeV, which might indicate the variation of the production mechanism within this energy interval.
|
|
| 18. |
- Adlarson, Patrik, et al.
(author)
-
Neutron-proton scattering in the context of the d*(2380) resonance
- 2014
-
In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 90:3, s. 035204-
-
Journal article (peer-reviewed)abstract
- New data on quasifree polarized neutron-proton scattering in the region of the recently observed d* resonance structure are obtained by exclusive and kinematically complete high-statistics measurements with WASA at COSY. This paper details the determination of the beam polarization, checks of the quasifree character of the scattering process, on all obtained Ay angular distributions and on the new partial-wave analysis, which includes the new data producing a resonance pole in D-3(3)-(3)G(3) coupled partial waves at (2380 +/- 10 - i40 +/- 5) MeV-in accordance with the d* dibaryon resonance hypothesis. The effect of the new partial-wave solution on the description of total and differential cross-section data as well as specific combinations of spin-correlation and spin-transfer observables available from COSY-ANKE measurements at T-d = 2.27 GeV is discussed.
|
|
| 19. |
- Alerstam, Erik, et al.
(author)
-
Next-generation acceleration and code optimization for light transport in turbid media using GPUs
- 2010
-
In: Biomedical Optics Express. - 2156-7085. ; 1:2, s. 658-675
-
Journal article (peer-reviewed)abstract
- A highly optimized Monte Carlo (MC) code package for simulating light transport is developed on the latest graphics processing unit (GPU) built for general-purpose computing from NVIDIA - the Fermi GPU. In biomedical optics, the MC method is the gold standard approach for simulating light transport in biological tissue, both due to its accuracy and its flexibility in modelling realistic, heterogeneous tissue geometry in 3-D. However, the widespread use of MC simulations in inverse problems, such as treatment planning for PDT, is limited by their long computation time. Despite its parallel nature, optimizing MC code on the GPU has been shown to be a challenge, particularly when the sharing of simulation result matrices among many parallel threads demands the frequent use of atomic instructions to access the slow GPU global memory. This paper proposes an optimization scheme that utilizes the fast shared memory to resolve the performance bottleneck caused by atomic access, and discusses numerous other optimization techniques needed to harness the full potential of the GPU. Using these techniques, a widely accepted MC code package in biophotonics, called MCML, was successfully accelerated on a Fermi GPU by approximately 600x compared to a state-of-the-art Intel Core i7 CPU. A skin model consisting of 7 layers was used as the standard simulation geometry. To demonstrate the possibility of GPU cluster computing, the same GPU code was executed on four GPUs, showing a linear improvement in performance with an increasing number of GPUs. The GPU-based MCML code package, named GPU-MCML, is compatible with a wide range of graphics cards and is released as an open-source software in two versions: an optimized version tuned for high performance and a simplified version for beginners (http://code.google.com/p/gpumcml).
|
|
| 20. |
- Augustyniak, W., et al.
(author)
-
Polarization of a stored beam by spin-filtering
- 2012
-
In: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 718:1, s. 64-69
-
Journal article (peer-reviewed)abstract
- The PAX Collaboration has successfully performed a spin-filtering experiment with protons at the COSY-ring. The measurement allowed the determination of the spin-dependent polarizing cross section, that compares well with the theoretical prediction from the nucleon-nucleon potential. The test confirms that spin-filtering can be adopted as a method to polarize a stored beam and that the present interpretation of the mechanism in terms of the proton-proton interaction is correct. The outcome of the experiment is of utmost importance in view of the possible application of the method to polarize a beam of stored antiprotons.
|
|
| 21. |
|
|
| 22. |
- de Graan, Anne-Joy M., et al.
(author)
-
CYP3A4*22 Genotype and Systemic Exposure Affect Paclitaxel-Induced Neurotoxicity
- 2013
-
In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:12, s. 3316-3324
-
Journal article (peer-reviewed)abstract
- Purpose: Paclitaxel is used for the treatment of several solid tumors and displays a high interindividual variation in exposure and toxicity. Neurotoxicity is one of the most prominent side effects of paclitaxel. This study explores potential predictive pharmacokinetic and pharmacogenetic determinants for the onset and severity of neurotoxicity. Experimental Design: In an exploratory cohort of patients (n = 261) treated with paclitaxel, neurotoxicity incidence, and severity, pharmacokinetic parameters and pharmacogenetic variants were determined. Paclitaxel plasma concentrations were measured by high-performance liquid chromatography or liquid chromatography/tandem mass spectrometry, and individual pharmacokinetic parameters were estimated from previously developed population pharmacokinetic models by nonlinear mixed effects modeling. Genetic variants of paclitaxel pharmacokinetics tested were CYP3A4*22, CYP2C8*3, CYP2C8*4, and ABCB1 3435 C>T. The association between CYP3A4*22 and neurotoxicity observed in the exploratory cohort was validated in an independent patient cohort (n = 239). Results: Exposure to paclitaxel ((log)AUC) was correlated with severity of neurotoxicity (P < 0.00001). Female CYP3A4*22 carriers were at increased risk of developing neurotoxicity (P = 0.043) in the exploratory cohort. CYP3A4*22 carrier status itself was not associated with pharmacokinetic parameters (CL, AUC, C-max, or T->0.05) of paclitaxel in males or females. Other genetic variants displayed no association with neurotoxicity. In the subsequent independent validation cohort, CYP3A4*22 carriers were at risk of developing grade 3 neurotoxicity (OR = 19.1; P = 0.001). Conclusions: Paclitaxel exposure showed a relationship with the severity of paclitaxel-induced neurotoxicity. In this study, female CYP3A4*22 carriers had increased risk of developing severe neurotoxicity during paclitaxel therapy. These observations may guide future individualization of paclitaxel treatment.
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Oellers, D., et al.
(author)
-
New experimental upper limit of the electron-proton spin-flip cross-section
- 2014
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 759, s. 6-9
-
Journal article (peer-reviewed)abstract
- In a previous publication, measurements of the depolarization of a stored proton beam by interaction with a co-propagating unpolarized electron beam at low relative energy have been presented and an upper limit of about 3 x 10(7) b for the electron-proton spin flip cross-section was determined. A refined analysis presented in this paper reduces the previous upper limit by a factor of three by the introduction of a new procedure that, also makes use of non-identified particles.
|
|
