357 research outputs found

    Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel

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    (1) Background: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3-0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4-0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2-0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1-3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1-2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2-2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2-1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1-3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX

    Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology.

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    Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose-concentration-effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future

    Study of Tau-pair Production in Photon-Photon Collisions at LEP and Limits on the Anomalous Electromagnetic Moments of the Tau Lepton

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    Tau-pair production in the process e+e- -> e+e-tau+tau- was studied using data collected by the DELPHI experiment at LEP2 during the years 1997 - 2000. The corresponding integrated luminosity is 650 pb^{-1}. The values of the cross-section obtained are found to be in agreement with QED predictions. Limits on the anomalous magnetic and electric dipole moments of the tau lepton are deduced.Comment: 20 pages, 9 figures, Accepted by Eur. Phys. J.

    Energy dependence of Cronin momentum in saturation model for p+Ap+A and A+AA+A collisions

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    We calculate s\sqrt{s} dependence of Cronin momentum for p+Ap+A and A+AA+A collisions in saturation model. We show that this dependence is consistent with expectation from formula which was obtained using simple dimentional consideration. This can be used to test validity of saturation model (and distinguish among its variants) and measure xx dependence of saturation momentum from experimental data.Comment: LaTeX2e, 12 pages, 8 figure

    Measurement and Interpretation of Fermion-Pair Production at LEP energies above the Z Resonance

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    This paper presents DELPHI measurements and interpretations of cross-sections, forward-backward asymmetries, and angular distributions, for the e+e- -> ffbar process for centre-of-mass energies above the Z resonance, from sqrt(s) ~ 130 - 207 GeV at the LEP collider. The measurements are consistent with the predictions of the Standard Model and are used to study a variety of models including the S-Matrix ansatz for e+e- -> ffbar scattering and several models which include physics beyond the Standard Model: the exchange of Z' bosons, contact interactions between fermions, the exchange of gravitons in large extra dimensions and the exchange of sneutrino in R-parity violating supersymmetry.Comment: 79 pages, 16 figures, Accepted by Eur. Phys. J.

    A Determination of the Centre-of-Mass Energy at LEP2 using Radiative 2-fermion Events

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    Using e+e- -> mu+mu-(gamma) and e+e- -> qqbar(gamma) events radiative to the Z pole, DELPHI has determined the centre-of-mass energy, sqrt{s}, using energy and momentum constraint methods. The results are expressed as deviations from the nominal LEP centre-of-mass energy, measured using other techniques. The results are found to be compatible with the LEP Energy Working Group estimates for a combination of the 1997 to 2000 data sets.Comment: 20 pages, 6 figures, Accepted by Eur. Phys. J.

    Determination of the b quark mass at the M_Z scale with the DELPHI detector at LEP

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    An experimental study of the normalized three-jet rate of b quark events with respect to light quarks events (light= \ell \equiv u,d,s) has been performed using the CAMBRIDGE and DURHAM jet algorithms. The data used were collected by the DELPHI experiment at LEP on the Z peak from 1994 to 2000. The results are found to agree with theoretical predictions treating mass corrections at next-to-leading order. Measurements of the b quark mass have also been performed for both the b pole mass: M_b and the b running mass: m_b(M_Z). Data are found to be better described when using the running mass. The measurement yields: m_b(M_Z) = 2.85 +/- 0.18 (stat) +/- 0.13 (exp) +/- 0.19 (had) +/- 0.12 (theo) GeV/c^2 for the CAMBRIDGE algorithm. This result is the most precise measurement of the b mass derived from a high energy process. When compared to other b mass determinations by experiments at lower energy scales, this value agrees with the prediction of Quantum Chromodynamics for the energy evolution of the running mass. The mass measurement is equivalent to a test of the flavour independence of the strong coupling constant with an accuracy of 7 permil.Comment: 24 pages, 10 figures, Accepted by Eur. Phys. J.

    Study of Inclusive J/psi Production in Two-Photon Collisions at LEP II with the DELPHI Detector

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    Inclusive J/psi production in photon-photon collisions has been observed at LEP II beam energies. A clear signal from the reaction gamma gamma -> J/psi+X is seen. The number of observed N(J/psi -> mu+mu-) events is 36 +/- 7 for an integrated luminosity of 617 pb^{-1}, yielding a cross-section of sigma(J/psi+X) = 45 +/- 9 (stat) +/- 17 (syst) pb. Based on a study of the event shapes of different types of gamma gamma processes in the PYTHIA program, we conclude that (74 +/- 22)% of the observed J/psi events are due to `resolved' photons, the dominant contribution of which is most probably due to the gluon content of the photon.Comment: 13 pages, 8 figures, Accepted by Phys. Lett.

    CP asymmetry in BϕKSB \to \phi K_S in a general two-Higgs-doublet model with fourth-generation quarks

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    We discuss the time-dependent CP asymmetry of decay BϕKSB \to \phi K_S in an extension of the Standard Model with both two Higgs doublets and additional fourth-generation quarks. We show that although the Standard Model with two-Higgs-doublet and the Standard model with fourth generation quarks alone are not likely to largely change the effective sin2β\sin 2 \beta from the decay of BϕKSB \to \phi K_S , the model with both additional Higgs doublet and fourth-generation quarks can easily account for the possible large negative value of sin2β\sin 2 \beta without conflicting with other experimental constraints. In this model, additional large CP violating effects may arise from the flavor changing Yukawa interactions between neutral Higgs bosons and the heavy fourth generation down type quark, which can modify the QCD penguin contributions. With the constraints obtained from bssˉsb \to s \bar{s} s processes such as BXsγB \to X_s \gamma and ΔmBs0\Delta m_{B_s^0}, this model can lead to the effective sin2β\sin 2 \beta to be as large as 0.4- 0.4 in the CP asymmetry of BϕKSB \to \phi K_S.Comment: 13 pages, 5 figures, references added, to appear in Eur.Phys.J.
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