723 research outputs found

    Relationship of imatinib-free plasma levels and target genotype with efficacy and tolerability

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    Imatinib has revolutionised the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GIST). Using a nonlinear mixed effects population model, individual estimates of pharmacokinetic parameters were derived and used to estimate imatinib exposure (area under the curve, AUC) in 58 patients. Plasma-free concentration was deduced from a model incorporating plasma levels of alpha1-acid glycoprotein. Associations between AUC (or clearance) and response or incidence of side effects were explored by logistic regression analysis. Influence of KIT genotype was also assessed in GIST patients. Both total (in GIST) and free drug exposure (in CML and GIST) correlated with the occurrence and number of side effects (e.g. odds ratio 2.7±0.6 for a two-fold free AUC increase in GIST; P<0.001). Higher free AUC also predicted a higher probability of therapeutic response in GIST (odds ratio 2.6±1.1; P=0.026) when taking into account tumour KIT genotype (strongest association in patients harbouring exon 9 mutation or wild-type KIT, known to decrease tumour sensitivity towards imatinib). In CML, no straightforward concentration–response relationships were obtained. Our findings represent additional arguments to further evaluate the usefulness of individualising imatinib prescription based on a therapeutic drug monitoring programme, possibly associated with target genotype profiling of patients

    Prediction studies of environment-friendly biodegradable polymeric packaging based on PLA. Influence of specimens’ thickness on the hydrolytic degradation profile

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    Application of new biodegradable polymer packaging based on polylactide (PLA), susceptible to organic recycling, can help in the waste reduction in landfills. In this paper, the results of the study on abiotic degradation of PLA and its blend containing 15 mol% of poly[(R,S)-3-hydroxybutyrate], as a model for the first step of organic recycling were presented. The samples used for this study have different shapes and thicknesses: rigid films and cuboid-bars. Particular emphasis was placed on determining the pattern of degradation products released into the medium. Originally, the results of present study revealed that the application of electrospray ionization mass spectrometry supported by high performance liquid chromatography allowed envisaging the differences in the degradation products pattern released from the studied PLA-based samples differing in thickness. The significant differences in degradation products pattern were predominately observed in the first steps of incubation process and are caused by an autocatalytic effect, which occurs mainly during degradation of the large size PLA samples. Although, the thickness of PLA-based packaging changes the degradation product patterns, however this does not increase the total amounts of acids released to the medium. Thus, it may be concluded that thickness should not affect significantly organic recycling of the packaging

    Measurement of the charged-pion polarisability

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    The COMPASS collaboration at CERN has investigated pion Compton scattering, πγπγ\pi^-\gamma\rightarrow \pi^-\gamma, at centre-of-mass energy below 3.5 pion masses. The process is embedded in the reaction πNiπγ  Ni\pi^-\mathrm{Ni}\rightarrow\pi^-\gamma\;\mathrm{Ni}, which is initiated by 190\,GeV pions impinging on a nickel target. The exchange of quasi-real photons is selected by isolating the sharp Coulomb peak observed at smallest momentum transfers, Q2<0.0015Q^2<0.0015\,(GeV/cc)2^2. From a sample of 63\,000 events the pion electric polarisability is determined to be $\alpha_\pi\ =\ (\,2.0\ \pm\ 0.6_{\mbox{\scriptsize stat}}\ \pm\ 0.7_{\mbox{\scriptsize syst}}\,) \times 10^{-4}\,\mbox{fm}^3undertheassumption under the assumption \alpha_\pi=-\beta_\pi$, which relates the electric and magnetic dipole polarisabilities. It is the most precise measurement of this fundamental low-energy parameter of strong interaction, that has been addressed since long by various methods with conflicting outcomes. While this result is in tension with previous dedicated measurements, it is found in agreement with the expectation from chiral perturbation theory. An additional measurement replacing pions by muons, for which the cross-section behavior is unambigiously known, was performed for an independent estimate of the systematic uncertainty.Comment: Published version: 9 pages, 3 figures, 1 tabl

    Transverse-momentum-dependent Multiplicities of Charged Hadrons in Muon-Deuteron Deep Inelastic Scattering

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    A semi-inclusive measurement of charged hadron multiplicities in deep inelastic muon scattering off an isoscalar target was performed using data collected by the COMPASS Collaboration at CERN. The following kinematic domain is covered by the data: photon virtuality Q2>1Q^{2}>1 (GeV/cc)2^2, invariant mass of the hadronic system W>5W > 5 GeV/c2c^2, Bjorken scaling variable in the range 0.003<x<0.40.003 < x < 0.4, fraction of the virtual photon energy carried by the hadron in the range 0.2<z<0.80.2 < z < 0.8, square of the hadron transverse momentum with respect to the virtual photon direction in the range 0.02 (GeV/c)2<PhT2<3c)^2 < P_{\rm{hT}}^{2} < 3 (GeV/cc)2^2. The multiplicities are presented as a function of PhT2P_{\rm{hT}}^{2} in three-dimensional bins of xx, Q2Q^2, zz and compared to previous semi-inclusive measurements. We explore the small-PhT2P_{\rm{hT}}^{2} region, i.e. PhT2<1P_{\rm{hT}}^{2} < 1 (GeV/cc)2^2, where hadron transverse momenta are expected to arise from non-perturbative effects, and also the domain of larger PhT2P_{\rm{hT}}^{2}, where contributions from higher-order perturbative QCD are expected to dominate. The multiplicities are fitted using a single-exponential function at small PhT2P_{\rm{hT}}^{2} to study the dependence of the average transverse momentum PhT2\langle P_{\rm{hT}}^{2}\rangle on xx, Q2Q^2 and zz. The power-law behaviour of the multiplicities at large PhT2P_{\rm{hT}}^{2} is investigated using various functional forms. The fits describe the data reasonably well over the full measured range.Comment: 28 pages, 20 figure

    Longitudinal double spin asymmetries in single hadron quasi-real photoproduction at high pTp_T

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    We measured the longitudinal double spin asymmetries ALLA_{LL} for single hadron muo-production off protons and deuterons at photon virtuality Q2Q^2 < 1(GeV/c\it c)2^2 for transverse hadron momenta pTp_T in the range 0.7 GeV/c\it c to 4 GeV/c\it c . They were determined using COMPASS data taken with a polarised muon beam of 160 GeV/c\it c or 200 GeV/c\it c impinging on polarised 6LiD\mathrm{{}^6LiD} or NH3\mathrm{NH_3} targets. The experimental asymmetries are compared to next-to-leading order pQCD calculations, and are sensitive to the gluon polarisation ΔG\Delta G inside the nucleon in the range of the nucleon momentum fraction carried by gluons 0.05<xg<0.20.05 < x_g < 0.2
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