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Sample records for random phase approximations

  1. Nonlinear higher quasiparticle random phase approximation

    Science.gov (United States)

    Smetana, Adam; Šimkovic, Fedor; Štefánik, Dušan; Krivoruchenko, Mikhail

    2017-10-01

    We develop a new approach to describe nuclear states of multiphonon origin, motivated by the necessity for a more accurate description of matrix elements of neutrinoless double-beta decay. Our approach is an extension of the Quasiparticle Random Phase Approximation (QRPA), in which nonlinear phonon operators play an essential role. Before applying the nonlinear higher QRPA (nhQRPA) to realistic problems, we test its efficiency with exactly solvable models. The first considered model is equivalent to a harmonic oscillator. The nhQRPA solutions follow from the standard QRPA equation, but for nonlinear phonon operators defined for each individual excited state separately. The second exactly solvable model is the proton-neutron Lipkin model that describes successfully not only energy spectrum of nuclei, but also beta-decay transitions. Again, we reproduce exactly the numerical solutions in the nhQRPA framework. We show in particular that truncation of the nonlinear phonon operators leads to an approximation similar to the self-consistent second QRPA, given the phonon operators are defined with a constant term. The test results demonstrate that the proposed nhQRPA is a promising tool for a realistic calculation of energy spectra and nuclear transitions.

  2. Static correlation beyond the random phase approximation

    DEFF Research Database (Denmark)

    Olsen, Thomas; Thygesen, Kristian Sommer

    2014-01-01

    We investigate various approximations to the correlation energy of a H2 molecule in the dissociation limit, where the ground state is poorly described by a single Slater determinant. The correlation energies are derived from the density response function and it is shown that response functions de...

  3. Relativistic Quasiparticle Random Phase Approximation in Deformed Nuclei

    OpenAIRE

    Pena Arteaga, Daniel

    2008-01-01

    Covariant density functional theory is used to study the influence of electromagnetic radiation on deformed superfluid nuclei. The relativistic Hartree-Bogoliubov equations and the resulting diagonalization problem of the quasiparticle random phase approximation are solved for axially symmetric systems in a fully self-consistent way by a newly developed parallel code. Three different kinds of high precision energy functionals are investigated and special care is taken for the decoupling of th...

  4. Analytic interatomic forces in the random phase approximation

    CERN Document Server

    Ramberger, Benjamin; Kresse, Georg

    2016-01-01

    We discuss that in the random phase approximation (RPA) the first derivative of the energy with respect to the Green's function is the self-energy in the GW approximation. This relationship allows to derive compact equations for the RPA interatomic forces. We also show that position dependent overlap operators are elegantly incorporated in the present framework. The RPA force equations have been implemented in the projector augmented wave formalism, and we present illustrative applications, including ab initio molecular dynamics simulations, the calculation of phonon dispersion relations for diamond and graphite, as well as structural relaxations for water on boron nitride. The present derivation establishes a concise framework for forces within perturbative approaches and is also applicable to more involved approximations for the correlation energy.

  5. Relativistic quasiparticle random phase approximation in deformed nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Pena Arteaga, D.

    2007-06-25

    Covariant density functional theory is used to study the influence of electromagnetic radiation on deformed superfluid nuclei. The relativistic Hartree-Bogolyubov equations and the resulting diagonalization problem of the quasiparticle random phase approximation are solved for axially symmetric systems in a fully self-consistent way by a newly developed parallel code. Three different kinds of high precision energy functionals are investigated and special care is taken for the decoupling of the Goldstone modes. This allows the microscopic investigation of Pygmy and scissor resonances in electric and magnetic dipole fields. Excellent agreement with recent experiments is found and new types of modes are predicted for deformed systems with large neutron excess. (orig.)

  6. Relativistic continuum random phase approximation in spherical nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Daoutidis, Ioannis

    2009-10-01

    Covariant density functional theory is used to analyze the nuclear response in the external multipole fields. The investigations are based on modern functionals with zero range and density dependent coupling constants. After a self-consistent solution of the Relativistic Mean Field (RMF) equations for the nuclear ground states multipole giant resonances are studied within the Relativistic Random Phase Approximation (RRPA), the small amplitude limit of the time-dependent RMF. The coupling to the continuum is treated precisely by calculating the single particle Greens-function of the corresponding Dirac equation. In conventional methods based on a discretization of the continuum this was not possible. The residual interaction is derived from the same RMF Lagrangian. This guarantees current conservation and a precise decoupling of the Goldstone modes. For nuclei with open shells pairing correlations are taken into account in the framework of BCS theory and relativistic quasiparticle RPA. Continuum RPA (CRPA) presents a robust method connected with an astonishing reduction of the numerical effort as compared to conventional methods. Modes of various multipolarities and isospin are investigated, in particular also the newly discovered Pygmy modes in the vicinity of the neutron evaporation threshold. The results are compared with conventional discrete RPA calculations as well as with experimental data. We find that the full treatment of the continuum is essential for light nuclei and the study of resonances in the neighborhood of the threshold. (orig.)

  7. Restricted second random phase approximations and Tamm-Dancoff approximations for electronic excitation energy calculations

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Degao; Yang, Yang; Zhang, Peng [Department of Chemistry, Duke University, Durham, North Carolina 27708 (United States); Yang, Weitao, E-mail: weitao.yang@duke.edu [Department of Chemistry and Department of Physics, Duke University, Durham, North Carolina 27708 (United States)

    2014-12-07

    In this article, we develop systematically second random phase approximations (RPA) and Tamm-Dancoff approximations (TDA) of particle-hole and particle-particle channels for calculating molecular excitation energies. The second particle-hole RPA/TDA can capture double excitations missed by the particle-hole RPA/TDA and time-dependent density-functional theory (TDDFT), while the second particle-particle RPA/TDA recovers non-highest-occupied-molecular-orbital excitations missed by the particle-particle RPA/TDA. With proper orbital restrictions, these restricted second RPAs and TDAs have a formal scaling of only O(N{sup 4}). The restricted versions of second RPAs and TDAs are tested with various small molecules to show some positive results. Data suggest that the restricted second particle-hole TDA (r2ph-TDA) has the best overall performance with a correlation coefficient similar to TDDFT, but with a larger negative bias. The negative bias of the r2ph-TDA may be induced by the unaccounted ground state correlation energy to be investigated further. Overall, the r2ph-TDA is recommended to study systems with both single and some low-lying double excitations with a moderate accuracy. Some expressions on excited state property evaluations, such as 〈S{sup ^2}〉 are also developed and tested.

  8. Restricted second random phase approximations and Tamm-Dancoff approximations for electronic excitation energy calculations

    Science.gov (United States)

    Peng, Degao; Yang, Yang; Zhang, Peng; Yang, Weitao

    2014-12-01

    In this article, we develop systematically second random phase approximations (RPA) and Tamm-Dancoff approximations (TDA) of particle-hole and particle-particle channels for calculating molecular excitation energies. The second particle-hole RPA/TDA can capture double excitations missed by the particle-hole RPA/TDA and time-dependent density-functional theory (TDDFT), while the second particle-particle RPA/TDA recovers non-highest-occupied-molecular-orbital excitations missed by the particle-particle RPA/TDA. With proper orbital restrictions, these restricted second RPAs and TDAs have a formal scaling of only O(N4). The restricted versions of second RPAs and TDAs are tested with various small molecules to show some positive results. Data suggest that the restricted second particle-hole TDA (r2ph-TDA) has the best overall performance with a correlation coefficient similar to TDDFT, but with a larger negative bias. The negative bias of the r2ph-TDA may be induced by the unaccounted ground state correlation energy to be investigated further. Overall, the r2ph-TDA is recommended to study systems with both single and some low-lying double excitations with a moderate accuracy. Some expressions on excited state property evaluations, such as < hat{S}2rangle are also developed and tested.

  9. Correlations in two-dimensional electron gas: Random-phase approximation with exchange and ladder results

    Science.gov (United States)

    Pederiva, F.; Lipparini, E.; Takayanagi, K.

    1997-12-01

    We have evaluated the density-density response of the two-dimensional electron gas at zero temperature by solving the Dyson equation for the particle-hole Green's function, including exchange Coulomb matrix elements and short-range contributions in the ladder approximation. We study the effect of these correlations on the total energy, compressibility per particle, local field factor G(q), static structure factor and pair-correlation function. Results are compared with the normal random-phase approximation, local field theories and quantum Monte Carlo calculations.

  10. Restoring the Pauli principle in the random phase approximation ground state

    Science.gov (United States)

    Kosov, D. S.

    2017-12-01

    Random phase approximation ground state contains electronic configurations where two (and more) identical electrons can occupy the same molecular spin-orbital violating the Pauli exclusion principle. This overcounting of electronic configurations happens due to quasiboson approximation in the treatment of electron-hole pair operators. We describe the method to restore the Pauli principle in the RPA wavefunction. The proposed theory is illustrated by the calculations of molecular dipole moments and electronic kinetic energies. The Hartree-Fock based RPA, which is corrected for the Pauli principle, gives the results of comparable accuracy with Møller-Plesset second order perturbation theory and coupled-cluster singles and doubles method.

  11. Insight into organic reactions from the direct random phase approximation and its corrections

    Energy Technology Data Exchange (ETDEWEB)

    Ruzsinszky, Adrienn [Department of Physics, Temple University, Philadelphia, Pennsylvania 19122 (United States); Zhang, Igor Ying; Scheffler, Matthias [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, 14195 Berlin (Germany)

    2015-10-14

    The performance of the random phase approximation (RPA) and beyond-RPA approximations for the treatment of electron correlation is benchmarked on three different molecular test sets. The test sets are chosen to represent three typical sources of error which can contribute to the failure of most density functional approximations in chemical reactions. The first test set (atomization and n-homodesmotic reactions) offers a gradually increasing balance of error from the chemical environment. The second test set (Diels-Alder reaction cycloaddition = DARC) reflects more the effect of weak dispersion interactions in chemical reactions. Finally, the third test set (self-interaction error 11 = SIE11) represents reactions which are exposed to noticeable self-interaction errors. This work seeks to answer whether any one of the many-body approximations considered here successfully addresses all these challenges.

  12. Dielectric matrix formulation of correlation energies in the Random Phase Approximation (RPA): inclusion of exchange effects

    CERN Document Server

    Mussard, Bastien; Jansen, Georg; Angyan, Janos

    2016-01-01

    Starting from the general expression for the ground state correlation energy in the adiabatic connection fluctuation dissipation theorem (ACFDT) framework, it is shown that the dielectric matrix formulation, which is usually applied to calculate the direct random phase approximation (dRPA) correlation energy, can be used for alternative RPA expressions including exchange effects. Within this famework, the ACFDT analog of the second order screened exchange (SOSEX) approximation leads to a logarithmic formula for the correlation energy similar to the direct RPA expression. Alternatively, the contribution of the exchange can be included in the kernel used to evaluate the response functions. In this case the use of an approximate kernel is crucial to simplify the formalism and to obtain a correlation energy in logarithmic form. Technical details of the implementation of these methods are discussed and it is shown that one can take advantage of density fitting or Cholesky decomposition techniques to improve the co...

  13. Core polarization effects in the Hartree--Fock--random phase approximation schemes

    Energy Technology Data Exchange (ETDEWEB)

    Lipparini, E.; Stringari, S.

    1987-02-01

    Core polarization effects in odd nuclei are investigated in the framework of the Hartree--Fock and random phase approximation schemes. The results of the particle vibration coupling model are recovered by linearizing the equations of motion in the interaction Hamiltonian between the external and the core particles. The formalism is used to study the renormalization of diagonal and off-diagonal M1 matrix elements. It is found that M1 polarization effects exhibit a very strong dependence on the range of the force. Copyright 1987 Academic Press, Inc.

  14. Role of small-norm components in extended random-phase approximation

    Science.gov (United States)

    Tohyama, Mitsuru

    2017-09-01

    The role of the small-norm amplitudes in extended random-phase approximation (RPA) theories such as the particle-particle and hole-hole components of one-body amplitudes and the two-body amplitudes other than two-particle/two-hole components are investigated for the one-dimensional Hubbard model using an extended RPA derived from the time-dependent density matrix theory. It is found that these amplitudes cannot be neglected in strongly interacting regions where the effects of ground-state correlations are significant.

  15. Self-consistent random phase approximation - application to systems of strongly correlated fermions; Approximation des phases aleatoires self-consistante - applications a des systemes de fermions fortement correles

    Energy Technology Data Exchange (ETDEWEB)

    Jemai, M

    2004-07-01

    In the present thesis we have applied the self consistent random phase approximation (SCRPA) to the Hubbard model with a small number of sites (a chain of 2, 4, 6,... sites). Earlier SCRPA had produced very good results in other models like the pairing model of Richardson. It was therefore interesting to see what kind of results the method is able to produce in the case of a more complex model like the Hubbard model. To our great satisfaction the case of two sites with two electrons (half-filling) is solved exactly by the SCRPA. This may seem a little trivial but the fact is that other respectable approximations like 'GW' or the approach with the Gutzwiller wave function yield results still far from exact. With this promising starting point, the case of 6 sites at half filling was considered next. For that case, evidently, SCRPA does not any longer give exact results. However, they are still excellent for a wide range of values of the coupling constant U, covering for instance the phase transition region towards a state with non zero magnetisation. We consider this as a good success of the theory. Non the less the case of 4 sites (a plaquette), as indeed all cases with 4n sites at half filling, turned out to have a problem because of degeneracies at the Hartree Fock level. A generalisation of the present method, including in addition to the pairs, quadruples of Fermions operators (called second RPA) is proposed to also include exactly the plaquette case in our approach. This is therefore a very interesting perspective of the present work. (author)

  16. Thermochemistry and Geometries for Transition-Metal Chemistry from the Random Phase Approximation.

    Science.gov (United States)

    Waitt, Craig; Ferrara, Nashali M; Eshuis, Henk

    2016-11-08

    Performance of the random phase approximation (RPA) is tested for thermochemistry and geometries of transition-metal chemistry using various benchmarks obtained either computationally or experimentally. Comparison is made to popular (semi)local meta- and hybrid density functionals as well as to the second-order Møller-Plesset perturbation theory (MP2) and its spin-component-scaled derivatives. The benchmark sets include reaction energies, barrier heights, and dissociation energies of prototype bond-activation reactions, dissociation energies for a set of large transition-metal complexes, bond lengths and dissociation energies of metal hydride ions, and bond lengths and angles of a set of closed-shell first-row transition-metal complexes. The emphasis is on first-row transition-metal chemistry, though for energies, elements beyond the first-row are included. Attention is paid to the basis set convergence of RPA. For thermochemistry, RPA performs on par or better than the density functional theory (DFT) functionals presented and is significantly more accurate than MP2. The largest errors are observed in dissociation energies where the electronic environment is altered substantially. For structural parameters, very good results were obtained, and RPA meets the high quality of structures from DFT. In most cases, well-converged structures are obtained with basis sets of triple-zeta quality. MP2 optimized values can often not be obtained and are on average of inferior quality. Though chemical accuracy is not reached, the RPA method is a step forward toward a systematic, parameter-free, all-round method to describe transition-metal chemistry.

  17. Quasiparticle random phase approximation predictions of the gamma-ray strength functions using the Gogny force

    Science.gov (United States)

    Hilaire, Stéphane; Goriely, Stéphane; Péru, Sophie; Lechaftois, François; Deloncle, Isabelle; Martini, Marco

    2017-09-01

    Dipole excitations of nuclei are crucial since they play an important role in nuclear reaction modeling in connection with the photoabsorption and the radiative capture processes. We present here results for the gamma-ray strength function obtained in large-scale axially-symmetric deformed quasiparticle (qp) random phase approximations approach using the finite-range Gogny force, with a particular emphasis on the E1 mode. The convergence with respect to the number of harmonic oscillator shells adopted and the cut-off introduced in the 2-quasiparticle excitation energy space is analyzed. The microscopic nature of our self-consistent Hartree-Fock-Bogoliubov plus QRPA (HFB+QRPA) calculation has unfortunately to be broken, some phenomenological corrections being needed to take into account effects beyond the standard 2-qp QRPA excitations and the coupling between the single-particle and low-lying collective phonon degrees of freedom. The corresponding phenomenological parameters are adjusted on experimental photoabsorption data. In such a procedure, a rather satisfactory description of experimental data is obtained. To study the sensitivity of these phenomenological corrections on the extrapolation, both at low energies and towards exotic neutron-rich nuclei, three different prescriptions are considered. They are shown to lead to rather similar predictions of the E1 strength at low energies as well as for exotic neutron-rich nuclei. The Gogny-HFB+QRPA strength is finally applied to the calculation of radiative neutron capture cross sections and the predictions compared with those obtained with more traditional Lorentzian-type approaches.

  18. Dynamic response of a two-dimensional electron gas: Exact treatment of Coulomb exchange in the random-phase approximation

    Science.gov (United States)

    Takayanagi, K.; Lipparini, E.

    1995-07-01

    The Dyson equation for the particle-hole Green's function, including Coulomb exchange matrix elements, has been solved exactly for a two-dimensional electron gas. Static and dynamic dielectric functions have been calculated and compared with normal random-phase-approximation and recent quantum Monte Carlo results.

  19. Double, Rydberg and charge transfer excitations from pairing matrix fluctuation and particle-particle random phase approximation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yang [Department of Chemistry, Duke University, Durham, North Carolina 27708 (United States); Aggelen, Helen van [Department of Chemistry, Duke University, Durham, North Carolina 27708 (United States); Department of Inorganic and Physical Chemistry, Ghent University, 9000 Ghent (Belgium); Yang, Weitao, E-mail: weitao.yang@duke.edu [Department of Chemistry and Department of Physics, Duke University, Durham, North Carolina 27708 (United States)

    2013-12-14

    Double, Rydberg, and charge transfer (CT) excitations have been great challenges for time-dependent density functional theory (TDDFT). Starting from an (N ± 2)-electron single-determinant reference, we investigate excitations for the N-electron system through the pairing matrix fluctuation, which contains information on two-electron addition/removal processes. We adopt the particle-particle random phase approximation (pp-RPA) and the particle-particle Tamm-Dancoff approximation (pp-TDA) to approximate the pairing matrix fluctuation and then determine excitation energies by the differences of two-electron addition/removal energies. This approach captures all types of interesting excitations: single and double excitations are described accurately, Rydberg excitations are in good agreement with experimental data and CT excitations display correct 1/R dependence. Furthermore, the pp-RPA and the pp-TDA have a computational cost similar to TDDFT and consequently are promising for practical calculations.

  20. Application of an extended random-phase approximation to giant resonances in light-, medium-, and heavy-mass nuclei

    Science.gov (United States)

    Tselyaev, V.; Lyutorovich, N.; Speth, J.; Krewald, S.; Reinhard, P.-G.

    2016-09-01

    We present results of the time blocking approximation (TBA) for giant resonances in light-, medium-, and heavy-mass nuclei. The TBA is an extension of the widely used random-phase approximation (RPA) adding complex configurations by coupling to phonon excitations. A new method for handling the single-particle continuum is developed and applied in the present calculations. We investigate in detail the dependence of the numerical results on the size of the single-particle space and the number of phonons as well as on nuclear matter properties. Our approach is self-consistent, based on an energy-density functional of Skyrme type where we used seven different parameter sets. The numerical results are compared with experimental data.

  1. Random phase approximation applied to solids, molecules, and graphene-metal interfaces

    DEFF Research Database (Denmark)

    Olsen, Thomas; Thygesen, Kristian S.

    2013-01-01

    to semilocal and hybrid functionals in systems dominated by weak van der Waals or mixed covalent-dispersive interactions. In this work, we present plane-wave-based RPA calculations for a broad collection of systems with bond types ranging from strong covalent to van der Waals. Our main result is the RPA...... potential energy surfaces of graphene on the Cu(111), Ni(111), Co(0001), Pd(111), Pt(111), Ag(111), Au(111), and Al(111) metal surfaces, which represent archetypical examples of metal-organic interfaces. Comparison with semilocal density approximations and a nonlocal van der Waals functional show that only...

  2. Electric dipole strength and dipole polarizability in 48Ca within a fully self-consistent second random-phase approximation

    Science.gov (United States)

    Gambacurta, D.; Grasso, M.; Vasseur, O.

    2018-02-01

    The second random-phase-approximation model corrected by a subtraction procedure designed to cure double counting, instabilities, and ultraviolet divergences, is employed for the first time to analyze the dipole strength and polarizability in 48Ca. All the terms of the residual interaction are included, leading to a fully self-consistent scheme. Results are illustrated with two Skyrme parametrizations, SGII and SLy4. Those obtained with the SGII interaction are particularly satisfactory. In this case, the low-lying strength below the neutron threshold is well reproduced and the giant dipole resonance is described in a very satisfactory way especially in its spreading and fragmentation. Spreading and fragmentation are produced in a natural way within such a theoretical model by the coupling of 1 particle-1 hole and 2 particle-2 hole configurations. Owing to this feature, we may provide for the electric polarizability as a function of the excitation energy a curve with a similar slope around the centroid energy of the giant resonance compared to the corresponding experimental results. This represents a considerable improvement with respect to previous theoretical predictions obtained with the random-phase approximation or with several ab-initio models. In such cases, the spreading width of the excitation cannot be reproduced and the polarizability as a function of the excitation energy displays a stiff increase around the predicted centroid energy of the giant resonance.

  3. Spin {ital M}1 excitations in deformed nuclei from self-consistent Hartree-Fock plus random-phase approximation

    Energy Technology Data Exchange (ETDEWEB)

    Sarriguren, P.; Moya de Guerra, E.; Nojarov, R. [Instituto de Estructura de la Materia, Consejo Superior de Investigaciones Cientificas, Serrano 119, E-28006 Madrid (Spain)

    1996-08-01

    We present a method to study spin magnetic dipole excitations in deformed nuclei within the quasiparticle random phase approximation based on self-consistent Hartree-Fock mean fields and residual interactions derived from the same effective two-body force. We perform a comprehensive study covering different Skyrme forces and various mass regions, and discussing the role of the mean field and of the residual interaction. An overall agreement with experimental data is obtained with the SG2 force. We study the systematics and the deformation dependence of the spin {ital M}1 strength distributions of {ital K}{sup {pi}}=1{sup +} excitations. It is found for the first time that the summed spin {ital M}1 strength obeys a quadratic dependence on deformation in the two isotope chains studied, {sup 142,146,148,150}Nd and {sup 144,148,150,152,154}Sm. {copyright} {ital 1996 The American Physical Society.}

  4. Hubbard-U corrected Hamiltonians for non-self-consistent random-phase approximation total-energy calculations

    DEFF Research Database (Denmark)

    Patrick, Christopher; Thygesen, Kristian Sommer

    2016-01-01

    In non-self-consistent calculations of the total energy within the random-phase approximation (RPA) for electronic correlation, it is necessary to choose a single-particle Hamiltonian whose solutions are used to construct the electronic density and noninteracting response function. Here we...... investigate the effect of including a Hubbard-U term in this single-particle Hamiltonian, to better describe the on-site correlation of 3d electrons in the transitionmetal compounds ZnS, TiO2, and NiO.We find that the RPA lattice constants are essentially independent of U, despite large changes...... and qualitatively different from that found from calculations employingU-corrected (semi)local functionals.However we also find that the+U term cannot be used to correct the RPA’s poor description of the heat of formation of NiO....

  5. A block variational procedure for the iterative diagonalization of non-Hermitian random-phase approximation matrices.

    Science.gov (United States)

    Rocca, Dario; Bai, Zhaojun; Li, Ren-Cang; Galli, Giulia

    2012-01-21

    We present a technique for the iterative diagonalization of random-phase approximation (RPA) matrices, which are encountered in the framework of time-dependent density-functional theory (TDDFT) and the Bethe-Salpeter equation. The non-Hermitian character of these matrices does not permit a straightforward application of standard iterative techniques used, i.e., for the diagonalization of ground state Hamiltonians. We first introduce a new block variational principle for RPA matrices. We then develop an algorithm for the simultaneous calculation of multiple eigenvalues and eigenvectors, with convergence and stability properties similar to techniques used to iteratively diagonalize Hermitian matrices. The algorithm is validated for simple systems (Na(2) and Na(4)) and then used to compute multiple low-lying TDDFT excitation energies of the benzene molecule. © 2012 American Institute of Physics

  6. Spin-unrestricted random-phase approximation with range separation: Benchmark on atomization energies and reaction barrier heights

    CERN Document Server

    Mussard, Bastien; Angyan, Janos; Toulouse, Julien

    2015-01-01

    We consider several spin-unrestricted random-phase approximation (RPA) variants for calculating correlation energies, with and without range separation, and test them on datasets of atomization energies and reaction barrier heights. We show that range separation greatly improves the accuracy of all RPA variants for these properties. Moreover, we show that a RPA variant with exchange, hereafter referred to as RPAx-SO2, first proposed by Sz-abo and Ostlund [A. Szabo and N. S. Ostlund, J. Chem. Phys. 67, 4351 (1977)] in a spin-restricted closed-shell formalism, and extended here to a spin-unrestricted formalism, provides on average the most accurate range-separated RPA variant for atomization energies and reaction barrier heights. Since this range-separated RPAx-SO2 method had already been shown to be among the most accurate range-separated RPA variants for weak intermolecular interactions [J. Toulouse, W. Zhu, A. Savin, G. Jansen, and J. G. {\\'A}ngy{\\'a}n, J. Chem. Phys. 135, 084119 (2011)], this works confirms...

  7. Spin-adapted open-shell random phase approximation and time-dependent density functional theory. I. Theory.

    Science.gov (United States)

    Li, Zhendong; Liu, Wenjian

    2010-08-14

    The spin-adaptation of single-reference quantum chemical methods for excited states of open-shell systems has been nontrivial. The primary reason is that the configuration space, generated by a truncated rank of excitations from only one component of a reference multiplet, is spin-incomplete. Those "missing" configurations are of higher ranks and can, in principle, be recaptured by a particular class of excitation operators. However, the resulting formalisms are then quite involved and there are situations [e.g., time-dependent density functional theory (TD-DFT) under the adiabatic approximation] that prevent one from doing so. To solve this issue, we propose here a tensor-coupling scheme that invokes all the components of a reference multiplet (i.e., a tensor reference) rather than increases the excitation ranks. A minimal spin-adapted n-tuply excited configuration space can readily be constructed by tensor products between the n-tuple tensor excitation operators and the chosen tensor reference. Further combined with the tensor equation-of-motion formalism, very compact expressions for excitation energies can be obtained. As a first application of this general idea, a spin-adapted open-shell random phase approximation is first developed. The so-called "translation rule" is then adopted to formulate a spin-adapted, restricted open-shell Kohn-Sham (ROKS)-based TD-DFT (ROKS-TD-DFT). Here, a particular symmetry structure has to be imposed on the exchange-correlation kernel. While the standard ROKS-TD-DFT can access only excited states due to singlet-coupled single excitations, i.e., only some of the singly excited states of the same spin (S(i)) as the reference, the new scheme can capture all the excited states of spin S(i)-1, S(i), or S(i)+1 due to both singlet- and triplet-coupled single excitations. The actual implementation and computation are very much like the (spin-contaminated) unrestricted Kohn-Sham-based TD-DFT. It is also shown that spin-contaminated spin

  8. M1 (e, e') excitations in {sup 30}Si and {sup 31}S from the quasiparticle random-phase approximation

    Energy Technology Data Exchange (ETDEWEB)

    Udias, J.M.; Faessler, Amand [Institut fuer Theoretische Physik, Universitaet Tuebingen, Auf der Morgenstelle 14, D-72076, Tuebingen (Germany); Nojarov, R. [Institute of Nuclear Research and Nuclear Energy, Bulgarian Academy of Sciences, BG-1784, Sofia (Bulgaria)

    1997-11-01

    We apply the QRPA formalism developed in previous works to study the excitation of the M1 mode through (e, e') scattering on {sup 30}Si and {sup 32}S. The agreement with experiment is comparable with that of the shell model for sd-shell nuclei. Having in view previous works for heavy and medium nuclei, one could conclude that the quasiparticle random-phase approximation (QRPA) is applicable to nuclei from a wide range of masses. (author)

  9. Beyond the random phase approximation

    DEFF Research Database (Denmark)

    Olsen, Thomas; Thygesen, Kristian S.

    2013-01-01

    , and metals. For molecular atomization energies, the rALDA is a factor of 7 better than RPA and a factor of 4 better than the Perdew-Burke-Ernzerhof (PBE) functional when compared to experiments, and a factor of 3 (1.5) better than RPA (PBE) for cohesive energies of solids. For transition metals......, the inclusion of full shell semicore states is found to be crucial for both RPA and rALDA calculations and can improve the cohesive energies by up to 0shell semicore states.4 eV. Finally, we discuss straightforward generalizations of the method, which might improve results even further....

  10. Partial restoration of spin-isospin SU(4) symmetry and the one-quasiparticle random-phase approximation method in double-β decay

    Science.gov (United States)

    Ferreira, V. dos S.; Krmpotić, F.; Barbero, C. A.; Samana, A. R.

    2017-10-01

    The one-quasiparticle random-phase approximation (one-QRPA) method is used to describe simultaneously both double-β -decay modes, giving special attention to the partial restoration of spin-isospin SU(4 ) symmetry. To implement this restoration and to fix the model parameters, we resort to the energetics of Gamow-Teller resonances and to the minima of the single-β+-decay strengths. This makes the theory predictive regarding the β β2 ν decay, producing the 2 ν moments in 48Ca, 76Ge, 82Se, 96Zr, 100Mo, Te,130128, and 150Nd, that are of the same order of magnitude as the experimental ones; however, the agreement with β β2 ν data is only modest. To include contributions coming from induced nuclear weak currents, we extend the β β0 ν -decay formalism employed previously in C. Barbero et al., Nucl. Phys. A 628, 170 (1998), 10.1016/S0375-9474(97)00614-3, which is based on the Fourier-Bessel expansion. The numerical results for the β β0 ν moments in the above mentioned nuclei are similar to those obtained in other theoretical studies although smaller on average by ˜40 % . We attribute this difference basically to the one-QRPA method, employed here for the first time, instead of the currently used two-QRPA method. The difference is partially due also to the way of carrying out the restoration of the spin-isospin symmetry. It is hard to say which is the best way to make this restoration, since the β β0 ν moments are not experimentally measurable. The recipe proposed here is based on physically robust arguments. The numerical uncertainties in the β β moments, related to (i) their strong dependence on the residual interaction in the particle-particle channel when evaluated within the QRPA, and (ii) lack of proper knowledge of single-particle energies, have been quantified. It is concluded that the partial restoration of the SU(4 ) symmetry, generated by the residual interaction, is crucial in the description of the β β decays, regardless of the nuclear

  11. Manifolds in random media: beyond the variational approximation

    Science.gov (United States)

    Goldschmidt, Yadin Y.

    1994-01-01

    In this paper we give a closed form expression for the 1/d corrections to the selfenergy characterizing the correlation function of a manifold in random media. This amounts to the first confection beyond the variational approximation. At this time we were able to evaluate these corrections in the high temperature "phase" of the notorious toy-model describing a classical particle subject to the influence of both a harmonic potential and a random potential. Although in this phase the correct solution is replica symmetric the calculation is non-trivial. The outcome is compared with previous analytical and numerical results. The corrections diverge at the "transition" temperature.

  12. Numerical approximation of random periodic solutions of stochastic differential equations

    Science.gov (United States)

    Feng, Chunrong; Liu, Yu; Zhao, Huaizhong

    2017-10-01

    In this paper, we discuss the numerical approximation of random periodic solutions of stochastic differential equations (SDEs) with multiplicative noise. We prove the existence of the random periodic solution as the limit of the pull-back flow when the starting time tends to -∞ along the multiple integrals of the period. As the random periodic solution is not explicitly constructible, it is useful to study the numerical approximation. We discretise the SDE using the Euler-Maruyama scheme and modified Milstein scheme. Subsequently, we obtain the existence of the random periodic solution as the limit of the pull-back of the discretised SDE. We prove that the latter is an approximated random periodic solution with an error to the exact one at the rate of √{Δ t} in the mean square sense in Euler-Maruyama method and Δ t in the Milstein method. We also obtain the weak convergence result for the approximation of the periodic measure.

  13. Efficient approximation of random fields for numerical applications

    KAUST Repository

    Harbrecht, Helmut

    2015-01-07

    We consider the rapid computation of separable expansions for the approximation of random fields. We compare approaches based on techniques from the approximation of non-local operators on the one hand and based on the pivoted Cholesky decomposition on the other hand. We provide an a-posteriori error estimate for the pivoted Cholesky decomposition in terms of the trace. Numerical examples validate and quantify the considered methods.

  14. Finitely approximable random sets and their evolution via differential equations

    Science.gov (United States)

    Ananyev, B. I.

    2016-12-01

    In this paper, random closed sets (RCS) in Euclidean space are considered along with their distributions and approximation. Distributions of RCS may be used for the calculation of expectation and other characteristics. Reachable sets on initial data and some ways of their approximate evolutionary description are investigated for stochastic differential equations (SDE) with initial state in some RCS. Markov property of random reachable sets is proved in the space of closed sets. For approximate calculus, the initial RCS is replaced by a finite set on the integer multidimensional grid and the multistage Markov chain is substituted for SDE. The Markov chain is constructed by methods of SDE numerical integration. Some examples are also given.

  15. Phase Error Correction for Approximated Observation-Based Compressed Sensing Radar Imaging

    Directory of Open Access Journals (Sweden)

    Bo Li

    2017-03-01

    Full Text Available Defocus of the reconstructed image of synthetic aperture radar (SAR occurs in the presence of the phase error. In this work, a phase error correction method is proposed for compressed sensing (CS radar imaging based on approximated observation. The proposed method has better image focusing ability with much less memory cost, compared to the conventional approaches, due to the inherent low memory requirement of the approximated observation operator. The one-dimensional (1D phase error correction for approximated observation-based CS-SAR imaging is first carried out and it can be conveniently applied to the cases of random-frequency waveform and linear frequency modulated (LFM waveform without any a priori knowledge. The approximated observation operators are obtained by calculating the inverse of Omega-K and chirp scaling algorithms for random-frequency and LFM waveforms, respectively. Furthermore, the 1D phase error model is modified by incorporating a priori knowledge and then a weighted 1D phase error model is proposed, which is capable of correcting two-dimensional (2D phase error in some cases, where the estimation can be simplified to a 1D problem. Simulation and experimental results validate the effectiveness of the proposed method in the presence of 1D phase error or weighted 1D phase error.

  16. Exactness of the Bogoliubov approximation in random external potentials

    Science.gov (United States)

    Jaeck, Thomas; Zagrebnov, Valentin A.

    2010-12-01

    We investigate the validity of the Bogoliubov c-number approximation in the case of interacting Bose-gas in a homogeneous random media. To take into account the possible occurence of type III generalized Bose-Einstein condensation (i.e., the occurrence of condensation in an infinitesimal band of low kinetic energy modes without macroscopic occupation of any of them) we generalize the c-number substitution procedure to this band of modes with low momentum. We show that, as in the case of the one-mode condensation for translation-invariant interacting systems, this procedure has no effect on the exact value of the pressure in the thermodynamic limit, assuming that the c-numbers are chosen according to a suitable variational principle. We then discuss the relation between these c-numbers and the (total) density of the condensate.

  17. Intensity approximation of random fluctuation in complex systems

    Science.gov (United States)

    Yulmetyev, R. M.; Gafarov, F. M.; Yulmetyeva, D. G.; Emeljanova, N. A.

    2002-01-01

    The Markov and non-Markov processes in complex systems are examined with the help of dynamical information Shannon entropy method. Here we consider the essential role of two mutually independent channels of entropy involving creation of correlation and annihilation of correlation. The developed method has been used to analyze the intensity fluctuation of the complex systems of various nature: in psychology (to analyze numerical and pattern short-time human memory, to study the effect of stress on the parameters of the dynamical taping-test) and in cardiology (to analyze the random dynamics of RR-intervals in human ECG's and to diagnose various diseases of human cardiovascular systems). The received results show that the application of intensity approximation allows to improve essentially the diagnostics of parameters in the evolution of human dynamic states.

  18. Effective medium approximation for effective propagation constant calculation in a dense random medium. [electromagnetic wave scattering

    Science.gov (United States)

    Zhu, P. Y.; Fung, A. K.

    1986-01-01

    The effective medium approximation (EMA) formalism developed for scalar wave calculations in solid state physics is generalized to electromagnetic wave scattering in a dense random medium. Results are applied to compute the effective propagation constant in a dense medium involving discrete spherical scatterers. When compared with a common quasicrystalline approximation (QCA), it is found that EMA accounts for backward scattering and the effect of correlation among three scatterers which are not available in QCA. It is also found that there is not much difference in the calculated normalized phase velocity between the use of these two approximations. However, there is a significant difference in the computed effective loss tangent in a nonabsorptive random medium. The computed effective loss tangent using EMA and measurements from a snow medium are compared, showing good agreement.

  19. Convergence analysis of two-phase methods for approximating the Edgeworth-Pareto hull in nonlinear multicriteria optimization problems

    Science.gov (United States)

    Berezkin, V. E.; Kamenev, G. K.

    2012-06-01

    The convergence of two-phase methods for approximating the Edgeworth-Pareto hull (EPH) in nonlinear multicriteria optimization problems is analyzed. The methods are based on the iterative supplement of the finite set of feasible criteria vectors (approximation basis) whose EPH approximates the desired set. A feature of two-phase methods is that the criteria images of randomly generated points of the decision space approach the Pareto frontier via local optimization of adaptively chosen convolutions of criteria. The convergence of two-phase methods is proved for both an abstract form of the algorithm and for a two-phase method based on the Germeier convolution.

  20. Discrete least squares polynomial approximation with random evaluations - application to PDEs with Random parameters

    KAUST Repository

    Nobile, Fabio

    2015-01-07

    We consider a general problem F(u, y) = 0 where u is the unknown solution, possibly Hilbert space valued, and y a set of uncertain parameters. We specifically address the situation in which the parameterto-solution map u(y) is smooth, however y could be very high (or even infinite) dimensional. In particular, we are interested in cases in which F is a differential operator, u a Hilbert space valued function and y a distributed, space and/or time varying, random field. We aim at reconstructing the parameter-to-solution map u(y) from random noise-free or noisy observations in random points by discrete least squares on polynomial spaces. The noise-free case is relevant whenever the technique is used to construct metamodels, based on polynomial expansions, for the output of computer experiments. In the case of PDEs with random parameters, the metamodel is then used to approximate statistics of the output quantity. We discuss the stability of discrete least squares on random points show convergence estimates both in expectation and probability. We also present possible strategies to select, either a-priori or by adaptive algorithms, sequences of approximating polynomial spaces that allow to reduce, and in some cases break, the curse of dimensionality

  1. Finite volume approximation of two phase-fluid flows based on an approximate Roe-Type Riemann solver

    Energy Technology Data Exchange (ETDEWEB)

    Sainsaulieu, L. [C.E.R.M.I.C.S., E.N.P.C., Noisy-le-Grand (France)]|[Centre de Mathematiques Appliquees, Palaiseau (France)

    1995-10-01

    We introduce an approximate Roe type Riemann solver for the numerical simulation of two-phase fluid flows composed of liquid droplets suspended in gas. We compute a Roe linearization of some well-conditioned approximate Rankine-Hugoniot relations in nonconservation form. The computed solutions are found to be in good agreement with the exact solution in one dimension slab geometry. We extend this solver to two-dimensional geometries using a fininte volume formulation. 24 refs., 15 figs., 2 tabs.

  2. Diffusion in random networks: Asymptotic properties, and numerical and engineering approximations

    Science.gov (United States)

    Padrino, Juan C.; Zhang, Duan Z.

    2016-11-01

    The ensemble phase averaging technique is applied to model mass transport by diffusion in random networks. The system consists of an ensemble of random networks, where each network is made of a set of pockets connected by tortuous channels. Inside a channel, we assume that fluid transport is governed by the one-dimensional diffusion equation. Mass balance leads to an integro-differential equation for the pores mass density. The so-called dual porosity model is found to be equivalent to the leading order approximation of the integration kernel when the diffusion time scale inside the channels is small compared to the macroscopic time scale. As a test problem, we consider the one-dimensional mass diffusion in a semi-infinite domain, whose solution is sought numerically. Because of the required time to establish the linear concentration profile inside a channel, for early times the similarity variable is xt- 1 / 4 rather than xt- 1 / 2 as in the traditional theory. This early time sub-diffusive similarity can be explained by random walk theory through the network. In addition, by applying concepts of fractional calculus, we show that, for small time, the governing equation reduces to a fractional diffusion equation with known solution. We recast this solution in terms of special functions easier to compute. Comparison of the numerical and exact solutions shows excellent agreement.

  3. On bounds in Poisson approximation for distributions of independent negative-binomial distributed random variables.

    Science.gov (United States)

    Hung, Tran Loc; Giang, Le Truong

    2016-01-01

    Using the Stein-Chen method some upper bounds in Poisson approximation for distributions of row-wise triangular arrays of independent negative-binomial distributed random variables are established in this note.

  4. Exponential ratio-product type estimators under second order approximation in stratified random sampling

    OpenAIRE

    Singh, Rajesh; Sharma, Prayas; Smarandache, Florentin

    2014-01-01

    Singh et al (20009) introduced a family of exponential ratio and product type estimators in stratified random sampling. Under stratified random sampling without replacement scheme, the expressions of bias and mean square error (MSE) of Singh et al (2009) and some other estimators, up to the first- and second-order approximations are derived. Also, the theoretical findings are supported by a numerical example.

  5. Measuring edge importance: a quantitative analysis of the stochastic shielding approximation for random processes on graphs.

    Science.gov (United States)

    Schmidt, Deena R; Thomas, Peter J

    2014-04-17

    Mathematical models of cellular physiological mechanisms often involve random walks on graphs representing transitions within networks of functional states. Schmandt and Galán recently introduced a novel stochastic shielding approximation as a fast, accurate method for generating approximate sample paths from a finite state Markov process in which only a subset of states are observable. For example, in ion-channel models, such as the Hodgkin-Huxley or other conductance-based neural models, a nerve cell has a population of ion channels whose states comprise the nodes of a graph, only some of which allow a transmembrane current to pass. The stochastic shielding approximation consists of neglecting fluctuations in the dynamics associated with edges in the graph not directly affecting the observable states. We consider the problem of finding the optimal complexity reducing mapping from a stochastic process on a graph to an approximate process on a smaller sample space, as determined by the choice of a particular linear measurement functional on the graph. The partitioning of ion-channel states into conducting versus nonconducting states provides a case in point. In addition to establishing that Schmandt and Galán's approximation is in fact optimal in a specific sense, we use recent results from random matrix theory to provide heuristic error estimates for the accuracy of the stochastic shielding approximation for an ensemble of random graphs. Moreover, we provide a novel quantitative measure of the contribution of individual transitions within the reaction graph to the accuracy of the approximate process.

  6. Linear-phase approximation in the triangular facet near-field physical optics computer program

    Science.gov (United States)

    Imbriale, W. A.; Hodges, R. E.

    1990-01-01

    Analyses of reflector antenna surfaces use a computer program based on a discrete approximation of the radiation integral. The calculation replaces the actual surface with a triangular facet representation; the physical optics current is assumed to be constant over each facet. Described here is a method of calculation using linear-phase approximation of the surface currents of parabolas, ellipses, and shaped subreflectors and compares results with a previous program that used a constant-phase approximation of the triangular facets. The results show that the linear-phase approximation is a significant improvement over the constant-phase approximation, and enables computation of 100 to 1,000 lambda reflectors within a reasonable time on a Cray computer.

  7. RCS estimation of linear and planar dipole phased arrays approximate model

    CERN Document Server

    Singh, Hema; Jha, Rakesh Mohan

    2016-01-01

    In this book, the RCS of a parallel-fed linear and planar dipole array is derived using an approximate method. The signal propagation within the phased array system determines the radar cross section (RCS) of phased array. The reflection and transmission coefficients for a signal at different levels of the phased-in scattering array system depend on the impedance mismatch and the design parameters. Moreover the mutual coupling effect in between the antenna elements is an important factor. A phased array system comprises of radiating elements followed by phase shifters, couplers, and terminating load impedance. These components lead to respective impedances towards the incoming signal that travels through them before reaching receive port of the array system. In this book, the RCS is approximated in terms of array factor, neglecting the phase terms. The mutual coupling effect is taken into account. The dependence of the RCS pattern on the design parameters is analyzed. The approximate model is established as a...

  8. Saddlepoint approximations for the sum of independent non-identically distributed binomial random variables

    NARCIS (Netherlands)

    Eisinga, R.N.; Grotenhuis, H.F. te; Pelzer, B.J.

    2013-01-01

    We discuss saddlepoint approximations to the distribution of the sum of independent non-identically distributed binomial random variables. We examine the accuracy of the saddlepoint methods for a sum of 10 binomials with different sets of parameter values. The numerical results indicate that the

  9. Fractional White-Noise Limit and Paraxial Approximation for Waves in Random Media

    Science.gov (United States)

    Gomez, Christophe; Pinaud, Olivier

    2017-12-01

    This work is devoted to the asymptotic analysis of high frequency wave propagation in random media with long-range dependence. We are interested in two asymptotic regimes, that we investigate simultaneously: the paraxial approximation, where the wave is collimated and propagates along a privileged direction of propagation, and the white-noise limit, where random fluctuations in the background are well approximated in a statistical sense by a fractional white noise. The fractional nature of the fluctuations is reminiscent of the long-range correlations in the underlying random medium. A typical physical setting is laser beam propagation in turbulent atmosphere. Starting from the high frequency wave equation with fast non-Gaussian random oscillations in the velocity field, we derive the fractional Itô-Schrödinger equation, that is, a Schrödinger equation with potential equal to a fractional white noise. The proof involves a fine analysis of the backscattering and of the coupling between the propagating and evanescent modes. Because of the long-range dependence, classical diffusion-approximation theorems for equations with random coefficients do not apply, and we therefore use moment techniques to study the convergence.

  10. Fractional White-Noise Limit and Paraxial Approximation for Waves in Random Media

    Science.gov (United States)

    Gomez, Christophe; Pinaud, Olivier

    2017-07-01

    This work is devoted to the asymptotic analysis of high frequency wave propagation in random media with long-range dependence. We are interested in two asymptotic regimes, that we investigate simultaneously: the paraxial approximation, where the wave is collimated and propagates along a privileged direction of propagation, and the white-noise limit, where random fluctuations in the background are well approximated in a statistical sense by a fractional white noise. The fractional nature of the fluctuations is reminiscent of the long-range correlations in the underlying random medium. A typical physical setting is laser beam propagation in turbulent atmosphere. Starting from the high frequency wave equation with fast non-Gaussian random oscillations in the velocity field, we derive the fractional Itô-Schrödinger equation, that is, a Schrödinger equation with potential equal to a fractional white noise. The proof involves a fine analysis of the backscattering and of the coupling between the propagating and evanescent modes. Because of the long-range dependence, classical diffusion-approximation theorems for equations with random coefficients do not apply, and we therefore use moment techniques to study the convergence.

  11. Coded diffraction system in X-ray crystallography using a boolean phase coded aperture approximation

    Science.gov (United States)

    Pinilla, Samuel; Poveda, Juan; Arguello, Henry

    2018-03-01

    Phase retrieval is a problem present in many applications such as optics, astronomical imaging, computational biology and X-ray crystallography. Recent work has shown that the phase can be better recovered when the acquisition architecture includes a coded aperture, which modulates the signal before diffraction, such that the underlying signal is recovered from coded diffraction patterns. Moreover, this type of modulation effect, before the diffraction operation, can be obtained using a phase coded aperture, just after the sample under study. However, a practical implementation of a phase coded aperture in an X-ray application is not feasible, because it is computationally modeled as a matrix with complex entries which requires changing the phase of the diffracted beams. In fact, changing the phase implies finding a material that allows to deviate the direction of an X-ray beam, which can considerably increase the implementation costs. Hence, this paper describes a low cost coded X-ray diffraction system based on block-unblock coded apertures that enables phase reconstruction. The proposed system approximates the phase coded aperture with a block-unblock coded aperture by using the detour-phase method. Moreover, the SAXS/WAXS X-ray crystallography software was used to simulate the diffraction patterns of a real crystal structure called Rhombic Dodecahedron. Additionally, several simulations were carried out to analyze the performance of block-unblock approximations in recovering the phase, using the simulated diffraction patterns. Furthermore, the quality of the reconstructions was measured in terms of the Peak Signal to Noise Ratio (PSNR). Results show that the performance of the block-unblock phase coded apertures approximation decreases at most 12.5% compared with the phase coded apertures. Moreover, the quality of the reconstructions using the boolean approximations is up to 2.5 dB of PSNR less with respect to the phase coded aperture reconstructions.

  12. Measuring Edge Importance: A Quantitative Analysis of the Stochastic Shielding Approximation for Random Processes on Graphs

    Science.gov (United States)

    2014-01-01

    Mathematical models of cellular physiological mechanisms often involve random walks on graphs representing transitions within networks of functional states. Schmandt and Galán recently introduced a novel stochastic shielding approximation as a fast, accurate method for generating approximate sample paths from a finite state Markov process in which only a subset of states are observable. For example, in ion-channel models, such as the Hodgkin–Huxley or other conductance-based neural models, a nerve cell has a population of ion channels whose states comprise the nodes of a graph, only some of which allow a transmembrane current to pass. The stochastic shielding approximation consists of neglecting fluctuations in the dynamics associated with edges in the graph not directly affecting the observable states. We consider the problem of finding the optimal complexity reducing mapping from a stochastic process on a graph to an approximate process on a smaller sample space, as determined by the choice of a particular linear measurement functional on the graph. The partitioning of ion-channel states into conducting versus nonconducting states provides a case in point. In addition to establishing that Schmandt and Galán’s approximation is in fact optimal in a specific sense, we use recent results from random matrix theory to provide heuristic error estimates for the accuracy of the stochastic shielding approximation for an ensemble of random graphs. Moreover, we provide a novel quantitative measure of the contribution of individual transitions within the reaction graph to the accuracy of the approximate process. PMID:24742077

  13. Approximations to the Probability of Failure in Random Vibration by Integral Equation Methods

    DEFF Research Database (Denmark)

    Nielsen, Søren R.K.; Sørensen, John Dalsgaard

    Close approximations to the first passage probability of failure in random vibration can be obtained by integral equation methods. A simple relation exists between the first passage probability density function and the distribution function for the time interval spent below a barrier before...... outcrossing. An integral equation for the probability density function of the time interval is formulated, and adequate approximations for the kernel are suggested. The kernel approximation results in approximate solutions for the probability density function of the time interval, and hence for the first...... passage probability density. The results of the theory agree well with simulation results for narrow banded processes dominated by a single frequency, as well as for bimodal processes with 2 dominating frequencies in the structural response....

  14. Matrix model approximations of fuzzy scalar field theories and their phase diagrams

    Energy Technology Data Exchange (ETDEWEB)

    Tekel, Juraj [Department of Theoretical Physics, Faculty of Mathematics, Physics and Informatics, Comenius University, Mlynska Dolina, Bratislava, 842 48 (Slovakia)

    2015-12-29

    We present an analysis of two different approximations to the scalar field theory on the fuzzy sphere, a nonperturbative and a perturbative one, which are both multitrace matrix models. We show that the former reproduces a phase diagram with correct features in a qualitative agreement with the previous numerical studies and that the latter gives a phase diagram with features not expected in the phase diagram of the field theory.

  15. Phase Transitions on Random Lattices: How Random is Topological Disorder?

    Science.gov (United States)

    Barghathi, Hatem; Vojta, Thomas

    2015-03-01

    We study the effects of topological (connectivity) disorder on phase transitions. We identify a broad class of random lattices whose disorder fluctuations decay much faster with increasing length scale than those of generic random systems, yielding a wandering exponent of ω = (d - 1) / (2 d) in d dimensions. The stability of clean critical points is thus governed by the criterion (d + 1) ν > 2 rather than the usual Harris criterion dν > 2 , making topological disorder less relevant than generic randomness. The Imry-Ma criterion is also modified, allowing first-order transitions to survive in all dimensions d > 1 . These results explain a host of puzzling violations of the original criteria for equilibrium and nonequilibrium phase transitions on random lattices. We discuss applications, and we illustrate our theory by computer simulations of random Voronoi and other lattices. This work was supported by the NSF under Grant Nos. DMR-1205803 and PHYS-1066293. We acknowledge the hospitality of the Aspen Center for Physics.

  16. Random-phase metasurfaces at optical wavelengths

    DEFF Research Database (Denmark)

    Pors, Anders; Ding, Fei; Chen, Yiting

    2016-01-01

    of an optically thick gold film overlaid by a subwavelength thin glass spacer and an array of gold nanobricks, we design and realize random-phase metasurfaces at a wavelength of 800 nm. Optical characterisation of the fabricated samples convincingly demonstrates the diffuse scattering of reflected light...

  17. APPROXIMATION TO OPTIMAL STOPPING RULES FOR GUMBEL RANDOM VARIABLES WITH UNKNOWN LOCATION AND SCALE PARAMETERS

    OpenAIRE

    Yeh, Tzu-Sheng; Lee, Shen-Ming

    2006-01-01

    An optimal stopping rule is a rule that stops the sampling process at a sample size n that maximizes the expected reward. In this paper we will study the approximation to optimal stopping rule for Gumbel random variables, because the Gumbel-type distribution is the most commonly referred to in discussions of extreme values. Let $X_1, X_2,\\cdots X_n,\\cdots$ be independent, identically distributed Gumbel random variables with unknown location and scale parameters,$\\alpha$ and $\\beta$. If we def...

  18. When to use the projection assumption and the weak-phase object approximation in phase contrast cryo-EM

    Energy Technology Data Exchange (ETDEWEB)

    Vulović, Miloš [Quantitative Imaging Group, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft (Netherlands); Electron Microscopy Section, Molecular Cell Biology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands); Voortman, Lenard M.; Vliet, Lucas J. van [Quantitative Imaging Group, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft (Netherlands); Rieger, Bernd, E-mail: b.rieger@tudelft.nl [Quantitative Imaging Group, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft (Netherlands)

    2014-01-15

    The projection assumption (PA) and the weak-phase object approximation (WPOA) are commonly used to model image formation in cryo-electron microscopy. For simulating the next step in resolution improvement we show that it is important to revisit these two approximations as well as their limitations. Here we start off by inspecting both approximations separately to derive their respective conditions of applicability. The thick-phase grating approximation (TPGA) imposes less strict conditions on the interaction potential than PA or WPOA and gives comparable exit waves as a multislice calculation. We suggest the ranges of applicability for four models (PA, PA+WPOA, WPOA, and TPGA) given different interaction potentials using exit wave simulations. The conditions of applicability for the models are based on two measures, a worst-case (safest) and an average criterion. This allows us to present a practical guideline for when to use each image formation model depending on the spatial frequency, thickness and strength of the interaction potential of a macromolecular complex. - Highlights: • Show applicability of projection assumption and weak-phase object approximation. • PA and WPOA are satisfied in cryo-EM tomograms at >30 AA resolution. • At ∼5 AA resolution PA and WPOA fail for typical macromolecules. • Thick phase grating approximation is an excellent substitute to multi-slice computation for life sciences.

  19. An accurate two-phase approximate solution to the acute viral infection model

    Energy Technology Data Exchange (ETDEWEB)

    Perelson, Alan S [Los Alamos National Laboratory

    2009-01-01

    During an acute viral infection, virus levels rise, reach a peak and then decline. Data and numerical solutions suggest the growth and decay phases are linear on a log scale. While viral dynamic models are typically nonlinear with analytical solutions difficult to obtain, the exponential nature of the solutions suggests approximations can be found. We derive a two-phase approximate solution to the target cell limited influenza model and illustrate the accuracy using data and previously established parameter values of six patients infected with influenza A. For one patient, the subsequent fall in virus concentration was not consistent with our predictions during the decay phase and an alternate approximation is derived. We find expressions for the rate and length of initial viral growth in terms of the parameters, the extent each parameter is involved in viral peaks, and the single parameter responsible for virus decay. We discuss applications of this analysis in antiviral treatments and investigating host and virus heterogeneities.

  20. Analysis and implementation issues for the numerical approximation of parabolic equations with random coefficients

    KAUST Repository

    Nobile, Fabio

    2009-11-05

    We consider the problem of numerically approximating statistical moments of the solution of a time- dependent linear parabolic partial differential equation (PDE), whose coefficients and/or forcing terms are spatially correlated random fields. The stochastic coefficients of the PDE are approximated by truncated Karhunen-Loève expansions driven by a finite number of uncorrelated random variables. After approxi- mating the stochastic coefficients, the original stochastic PDE turns into a new deterministic parametric PDE of the same type, the dimension of the parameter set being equal to the number of random variables introduced. After proving that the solution of the parametric PDE problem is analytic with respect to the parameters, we consider global polynomial approximations based on tensor product, total degree or sparse polynomial spaces and constructed by either a Stochastic Galerkin or a Stochastic Collocation approach. We derive convergence rates for the different cases and present numerical results that show how these approaches are a valid alternative to the more traditional Monte Carlo Method for this class of problems. © 2009 John Wiley & Sons, Ltd.

  1. Dual Dynamically Orthogonal approximation of incompressible Navier Stokes equations with random boundary conditions

    Science.gov (United States)

    Musharbash, Eleonora; Nobile, Fabio

    2018-02-01

    In this paper we propose a method for the strong imposition of random Dirichlet boundary conditions in the Dynamical Low Rank (DLR) approximation of parabolic PDEs and, in particular, incompressible Navier Stokes equations. We show that the DLR variational principle can be set in the constrained manifold of all S rank random fields with a prescribed value on the boundary, expressed in low rank format, with rank smaller then S. We characterize the tangent space to the constrained manifold by means of a Dual Dynamically Orthogonal (Dual DO) formulation, in which the stochastic modes are kept orthonormal and the deterministic modes satisfy suitable boundary conditions, consistent with the original problem. The Dual DO formulation is also convenient to include the incompressibility constraint, when dealing with incompressible Navier Stokes equations. We show the performance of the proposed Dual DO approximation on two numerical test cases: the classical benchmark of a laminar flow around a cylinder with random inflow velocity, and a biomedical application for simulating blood flow in realistic carotid artery reconstructed from MRI data with random inflow conditions coming from Doppler measurements.

  2. Analytic regularity and collocation approximation for elliptic PDEs with random domain deformations

    KAUST Repository

    Castrillon, Julio

    2016-03-02

    In this work we consider the problem of approximating the statistics of a given Quantity of Interest (QoI) that depends on the solution of a linear elliptic PDE defined over a random domain parameterized by N random variables. The elliptic problem is remapped onto a corresponding PDE with a fixed deterministic domain. We show that the solution can be analytically extended to a well defined region in CN with respect to the random variables. A sparse grid stochastic collocation method is then used to compute the mean and variance of the QoI. Finally, convergence rates for the mean and variance of the QoI are derived and compared to those obtained in numerical experiments.

  3. Random phase textures: theory and synthesis.

    Science.gov (United States)

    Galerne, Bruno; Gousseau, Yann; Morel, Jean-Michel

    2011-01-01

    This paper explores the mathematical and algorithmic properties of two sample-based texture models: random phase noise (RPN) and asymptotic discrete spot noise (ADSN). These models permit to synthesize random phase textures. They arguably derive from linearized versions of two early Julesz texture discrimination theories. The ensuing mathematical analysis shows that, contrarily to some statements in the literature, RPN and ADSN are different stochastic processes. Nevertheless, numerous experiments also suggest that the textures obtained by these algorithms from identical samples are perceptually similar. The relevance of this study is enhanced by three technical contributions providing solutions to obstacles that prevented the use of RPN or ADSN to emulate textures. First, RPN and ADSN algorithms are extended to color images. Second, a preprocessing is proposed to avoid artifacts due to the nonperiodicity of real-world texture samples. Finally, the method is extended to synthesize textures with arbitrary size from a given sample.

  4. Validity of the mean-field approximation for diffusion on a random comb

    Science.gov (United States)

    Revathi, S.; Balakrishnan, V.; Lakshmibala, S.; Murthy, K. P. N.

    1996-09-01

    We consider unbiased diffusion on a random comb structure (an infinitely long backbone with loopless branches of arbitrary length emanating from it). If w=T0 is the mean time (averaged over all random walks) for first passage from an arbitrary origin 0 on the backbone to either of the sites +j or -j on it in a given realization of the structure, the exact diffusion constant for the problem is defined as K=limj-->∞j2c, where c stands for the configuration average over the realizations of the random comb. The diffusion constant in the mean-field approximation is given by KMF=limj-->∞j2/c. We compute T0 exactly for an arbitrary realization of the comb and then show rigorously that, owing to the suppression of the relative fluctuations in T0 in the ``thermodynamic limit'' j-->∞, we have KMF=K whenever the moments of certain random variables Γ(L,α,β) are finite; here the site-dependent random variables L, α, and β are, respectively, the branch length, stay probability at the tip of a branch, and the backbone-to-branch jump probability. Finally, we discuss different situations in which K will not be equal to KMF, although the transport remains diffusive, as opposed to those in which anomalous diffusion occurs.

  5. Analytic approximations for the elastic moduli of two-phase materials

    DEFF Research Database (Denmark)

    Zhu, Y. K.; Zhang, P.; Zhang, Y. Y.

    2017-01-01

    Based on the models of series and parallel connections of the two phases in a composite, analytic approximations are derived for the elastic constants (Young's modulus, shear modulus, and Poisson's ratio) of elastically isotropic two-phase composites containing second phases of various volume...... fractions, shapes, and regular distributions. Comparison with a plentitude of finite element simulations and numerous previous experimental investigations shows a large consistency between the results and the analytic expressions derived, confirming the adequacy of the present approach. Compared...... with previous classical models, the present model has several advantages, including its simplicity, accuracy of prediction, and universal applicability....

  6. Approximate Analytic Solutions for the Two-Phase Stefan Problem Using the Adomian Decomposition Method

    Directory of Open Access Journals (Sweden)

    Xiao-Ying Qin

    2014-01-01

    Full Text Available An Adomian decomposition method (ADM is applied to solve a two-phase Stefan problem that describes the pure metal solidification process. In contrast to traditional analytical methods, ADM avoids complex mathematical derivations and does not require coordinate transformation for elimination of the unknown moving boundary. Based on polynomial approximations for some known and unknown boundary functions, approximate analytic solutions for the model with undetermined coefficients are obtained using ADM. Substitution of these expressions into other equations and boundary conditions of the model generates some function identities with the undetermined coefficients. By determining these coefficients, approximate analytic solutions for the model are obtained. A concrete example of the solution shows that this method can easily be implemented in MATLAB and has a fast convergence rate. This is an efficient method for finding approximate analytic solutions for the Stefan and the inverse Stefan problems.

  7. Madelung energy for random metallic alloys in the coherent potential approximation

    DEFF Research Database (Denmark)

    Korzhavyi, P. A.; Ruban, Andrei; Abrikosov, I. A.

    1995-01-01

    Within the conventional single-site coherent potential approximation (CPA) used to calculate thermodynamic properties of random alloys, the effect of charge transfer is neglected. We discuss a number of recent models based on the same mathematical form but with a different prefactor β which allow...... one to include charge-transfer effects in the framework of the CPA. We show how the models work in actual calculations for selected metallic alloy systems, Al-Li, Li-Mg, and Ni-Pt, which exhibit charge transfer. We find that the so-called screened impurity model (β=1), which is derived completely...... within the mean-field single-site approximation, leads to the best agreement with experimental lattice parameter and mixing energy data for Al-Li and Li-Mg alloys. However, for the Ni-Pt system exhibiting strong ordering tendency this model seems to overestimate the Madelung energy of the completely...

  8. Random matrix theory and acoustic resonances in plates with an approximate symmetry

    DEFF Research Database (Denmark)

    Andersen, Anders Peter; Ellegaard, C.; Jackson, A.D.

    2001-01-01

    We discuss a random matrix model of systems with an approximate symmetry and present the spectral fluctuation statistics and eigenvector characteristics for the model. An acoustic resonator like, e.g., an aluminum plate may have an approximate symmetry. We have measured the frequency spectrum...... and the widths for acoustic resonances in thin aluminum plates, cut in the shape of the so-called three-leaf clover. Due to the mirror symmetry through the middle plane of the plate, each resonance of the plate belongs to one of two mode classes and we show how to separate the modes into these two classes using...... their measured widths. We compare the spectral statistics of each mode class with results for the Gaussian orthogonal ensemble. By cutting a slit of increasing depth on one face of the plate, we gradually break the mirror symmetry and study the transition that takes place as the two classes are mixed. Presenting...

  9. The application of random phase filter in the image recognition

    Science.gov (United States)

    Yang, Xiujuan; Zhong, Mei; Shao, Zhufeng

    2016-03-01

    We define one kind of new correlation, i.e. random phase correlation, which based on the Random Fourier Transform (RFT). An optical pattern recognition system, random phase filtering, is given according to random phase correlation. Furthermore its electro-optical setup is given for the application in image recognition. By the numerical simulation on computer, when the, we have found the proposed random phase filter can recognize the small change of object image and has higher recognition capability comparing of other three conventional correlators, the classical marched filter, the phase-only filter and the pure phase correlator.

  10. Discrete least squares polynomial approximation with random evaluations − application to parametric and stochastic elliptic PDEs

    KAUST Repository

    Chkifa, Abdellah

    2015-04-08

    Motivated by the numerical treatment of parametric and stochastic PDEs, we analyze the least-squares method for polynomial approximation of multivariate functions based on random sampling according to a given probability measure. Recent work has shown that in the univariate case, the least-squares method is quasi-optimal in expectation in [A. Cohen, M A. Davenport and D. Leviatan. Found. Comput. Math. 13 (2013) 819–834] and in probability in [G. Migliorati, F. Nobile, E. von Schwerin, R. Tempone, Found. Comput. Math. 14 (2014) 419–456], under suitable conditions that relate the number of samples with respect to the dimension of the polynomial space. Here “quasi-optimal” means that the accuracy of the least-squares approximation is comparable with that of the best approximation in the given polynomial space. In this paper, we discuss the quasi-optimality of the polynomial least-squares method in arbitrary dimension. Our analysis applies to any arbitrary multivariate polynomial space (including tensor product, total degree or hyperbolic crosses), under the minimal requirement that its associated index set is downward closed. The optimality criterion only involves the relation between the number of samples and the dimension of the polynomial space, independently of the anisotropic shape and of the number of variables. We extend our results to the approximation of Hilbert space-valued functions in order to apply them to the approximation of parametric and stochastic elliptic PDEs. As a particular case, we discuss “inclusion type” elliptic PDE models, and derive an exponential convergence estimate for the least-squares method. Numerical results confirm our estimate, yet pointing out a gap between the condition necessary to achieve optimality in the theory, and the condition that in practice yields the optimal convergence rate.

  11. Random matrix theory and acoustic resonances in plates with an approximate symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, A.; Ellegaard, C.; Jackson, A. D.; Schaadt, K.

    2001-06-01

    We discuss a random matrix model of systems with an approximate symmetry and present the spectral fluctuation statistics and eigenvector characteristics for the model. An acoustic resonator like, e.g., an aluminum plate may have an approximate symmetry. We have measured the frequency spectrum and the widths for acoustic resonances in thin aluminum plates, cut in the shape of the so-called three-leaf clover. Due to the mirror symmetry through the middle plane of the plate, each resonance of the plate belongs to one of two mode classes and we show how to separate the modes into these two classes using their measured widths. We compare the spectral statistics of each mode class with results for the Gaussian orthogonal ensemble. By cutting a slit of increasing depth on one face of the plate, we gradually break the mirror symmetry and study the transition that takes place as the two classes are mixed. Presenting the spectral fluctuation statistics and the distribution of widths for the resonances, we find that this transition is well described by the random matrix model.

  12. Quantum Monte Carlo with variable spins: Fixed-phase and fixed-node approximations

    Science.gov (United States)

    Melton, Cody A.; Mitas, Lubos

    2017-10-01

    We study several aspects of the recently introduced fixed-phase spinor diffusion Monte Carlo method, in particular, its relation to the fixed-node method and its potential use as a general approach for electronic structure calculations. We illustrate constructions of spinor-based wave functions with the full space-spin symmetry without assigning up or down spin labels to particular electrons, effectively "complexifying" even ordinary real-valued wave functions for Hamiltonians without spin terms. Interestingly, with proper choice of the simulation parameters and spin variables, such fixed-phase calculations enable one to reach also the fixed-node limit. The fixed-phase approximation has several desirable properties when compared to the fixed-node approximation. The fixed-phase solution provides a straightforward interpretation as the lowest bosonic state in a given effective potential generated by the many-body approximate phase, whereas nodal boundary conditions are defined through less intuitive and complicated hypersurfaces with one dimension less than the original configuration space. In addition, the divergences of the local energy and drift at real wave function nodes are smoothed out to lower dimensionality when the wave function is complexified, thus decreasing the variation of sampled quantities and eliminating artificial nodal domain issues that can occur in the fixed-node formalism. We illustrate some of these properties on calculations of selected first-row systems that recover the fixed-node results with quantitatively similar levels of the corresponding biases. At the same time, the fixed-phase approach opens new possibilities for more general trial wave functions with further opportunities for increasing accuracy in practical calculations.

  13. Analysis of half-band approximately linear phase IIR filter realization structure in MATLAB

    OpenAIRE

    Radonjić, Aleksandar D.; Certić, Jelena

    2015-01-01

    In this paper a detailed analysis of an atypical filter structure in MATLAB Filter Design and Analysis (FDA) Tool is presented. As an example of atypical filter structure, the IIR half-band filter with approximately linear phase realized as a parallel connection of two all-pass branches was examined. We compare two types of those filters obtained by two different design algorithms. FDA tool was used for the experiment because different effects of the fixed point implementation can be simulate...

  14. Gaussian phase distribution approximations for oscillating gradient spin echo diffusion MRI.

    Science.gov (United States)

    Ianuş, Andrada; Siow, Bernard; Drobnjak, Ivana; Zhang, Hui; Alexander, Daniel C

    2013-02-01

    Oscillating gradients provide an optimal probe of small pore sizes in diffusion MRI. While sinusoidal oscillations have been popular for some time, recent work suggests additional benefits of square or trapezoidal oscillating waveforms. This paper presents analytical expressions of the free and restricted diffusion signal for trapezoidal and square oscillating gradient spin echo (OGSE) sequences using the Gaussian phase distribution (GPD) approximation and generalises existing similar expressions for sinusoidal OGSE. Accurate analytical models are necessary for exploitation of these pulse sequences in imaging studies, as they allow model fitting and parameter estimation in reasonable computation times. We evaluate the accuracy of the approximation against synthesised data from the Monte Carlo (MC) diffusion simulator in Camino and Callaghan's matrix method and we show that the accuracy of the approximation is within a few percent of the signal, while providing several orders of magnitude faster computation. Moreover, since the expressions for trapezoidal wave are complex, we test sine and square wave approximations to the trapezoidal OGSE signal. The best approximations depend on the gradient amplitude and the oscillation frequency and are accurate to within a few percent. Finally, we explore broader applications of trapezoidal OGSE, in particular for non-model based applications, such as apparent diffusion coefficient estimation, where only sinusoidal waveforms have been considered previously. We show that with the right apodisation, trapezoidal waves also have benefits by virtue of the higher diffusion weighting they provide compared to sinusoidal gradients. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. A Randomized Exchange Algorithm for Computing Optimal Approximate Designs of Experiments

    KAUST Repository

    Harman, Radoslav

    2018-01-17

    We propose a class of subspace ascent methods for computing optimal approximate designs that covers both existing as well as new and more efficient algorithms. Within this class of methods, we construct a simple, randomized exchange algorithm (REX). Numerical comparisons suggest that the performance of REX is comparable or superior to the performance of state-of-the-art methods across a broad range of problem structures and sizes. We focus on the most commonly used criterion of D-optimality that also has applications beyond experimental design, such as the construction of the minimum volume ellipsoid containing a given set of data-points. For D-optimality, we prove that the proposed algorithm converges to the optimum. We also provide formulas for the optimal exchange of weights in the case of the criterion of A-optimality. These formulas enable one to use REX for computing A-optimal and I-optimal designs.

  16. Sparse Estimation Based on a New Random Regularized Matching Pursuit Generalized Approximate Message Passing Algorithm

    Directory of Open Access Journals (Sweden)

    Yongjie Luo

    2016-05-01

    Full Text Available Approximate Message Passing (AMP and Generalized AMP (GAMP algorithms usually suffer from serious convergence issues when the elements of the sensing matrix do not exactly match the zero-mean Gaussian assumption. To stabilize AMP/GAMP in these contexts, we have proposed a new sparse reconstruction algorithm, termed the Random regularized Matching pursuit GAMP (RrMpGAMP. It utilizes a random splitting support operation and some dropout/replacement support operations to make the matching pursuit steps regularized and uses a new GAMP-like algorithm to estimate the non-zero elements in a sparse vector. Moreover, our proposed algorithm can save much memory, be equipped with a comparable computational complexity as GAMP and support parallel computing in some steps. We have analyzed the convergence of this GAMP-like algorithm by the replica method and provided the convergence conditions of it. The analysis also gives an explanation about the broader variance range of the elements of the sensing matrix for this GAMP-like algorithm. Experiments using simulation data and real-world synthetic aperture radar tomography (TomoSAR data show that our method provides the expected performance for scenarios where AMP/GAMP diverges.

  17. Phases and approximations of baryonic popcorn in a low-dimensional analogue of holographic QCD

    Science.gov (United States)

    Elliot-Ripley, Matthew

    2015-07-01

    The Sakai-Sugimoto model is the most pre-eminent model of holographic QCD, in which baryons correspond to topological solitons in a five-dimensional bulk spacetime. Recently it has been shown that a single soliton in this model can be well approximated by a flat-space self-dual Yang-Mills instanton with a small size, although studies of multi-solitons and solitons at finite density are currently beyond numerical computations. A lower-dimensional analogue of the model has also been studied in which the Sakai-Sugimoto soliton is replaced by a baby Skyrmion in three spacetime dimensions with a warped metric. The lower dimensionality of this model means that full numerical field calculations are possible, and static multi-solitons and solitons at finite density were both investigated, in particular the baryonic popcorn phase transitions at high densities. Here we present and investigate an alternative lower-dimensional analogue of the Sakai-Sugimoto model in which the Sakai-Sugimoto soliton is replaced by an O(3)-sigma model instanton in a warped three-dimensional spacetime stabilized by a massive vector meson. A more detailed range of baryonic popcorn phase transitions are found, and the low-dimensional model is used as a testing ground to check the validity of common approximations made in the full five-dimensional model, namely approximating fields using their flat-space equations of motion, and performing a leading order expansion in the metric.

  18. Phase-field approach to implicit solvation of biomolecules with Coulomb-field approximation.

    Science.gov (United States)

    Zhao, Yanxiang; Kwan, Yuen-Yick; Che, Jianwei; Li, Bo; McCammon, J Andrew

    2013-07-14

    A phase-field variational implicit-solvent approach is developed for the solvation of charged molecules. The starting point of such an approach is the representation of a solute-solvent interface by a phase field that takes one value in the solute region and another in the solvent region, with a smooth transition from one to the other on a small transition layer. The minimization of an effective free-energy functional of all possible phase fields determines the equilibrium conformations and free energies of an underlying molecular system. All the surface energy, the solute-solvent van der Waals interaction, and the electrostatic interaction are coupled together self-consistently through a phase field. The surface energy results from the minimization of a double-well potential and the gradient of a field. The electrostatic interaction is described by the Coulomb-field approximation. Accurate and efficient methods are designed and implemented to numerically relax an underlying charged molecular system. Applications to single ions, a two-plate system, and a two-domain protein reveal that the new theory and methods can capture capillary evaporation in hydrophobic confinement and corresponding multiple equilibrium states as found in molecular dynamics simulations. Comparisons of the phase-field and the original sharp-interface variational approaches are discussed.

  19. Mathematical analysis of approximate biological effective dose (BED calculation for multi-phase radiotherapy treatment plans

    Directory of Open Access Journals (Sweden)

    Kevin I Kauweloa

    2014-03-01

    Full Text Available Purpose: There is growing interest about biological effective dose (BED and its application in treatment plan evaluation due to its stronger correlation with treatment outcome. An approximate biological effective dose (BEDA equation was introduced in order to simplify BED calculations by treatment planning systems in multi-phase treatments. The purpose of this work is to reveal its mathematical properties relative to the true, multi-phase BED (BEDT equation.Methods: The BEDT equation was derived and used to reveal the mathematical properties of BEDA. MATLAB (MathWorks, Natick, MA was used to simulate and analyze common and extreme clinical multi-phase cases. In those cases, percent error and Bland-Altman analysis were used to study the significance of the inaccuracies of BEDA for different combinations of total doses, numbers of fractions, doses per fractions and α/β values. All the calculations were performed on a voxel-basis in order to study how dose distributions would affect the accuracy of BEDA.Results: When the voxel dose-per-fractions (DPF delivered by both phases are equal, BEDA and BEDT are equal (0% error. In heterogeneous dose distributions, which significantly vary between the phases, there are fewer occurrences of equal DPFs and hence the imprecision of BEDA is greater. It was shown that as the α/β ratio increased the accuracy of BEDA would improve. Examining twenty-four cases, it was shown that the range of DPF ratios for 3% Perror varied from 0.32 to 7.50Gy, whereas for Perror of 1% the range varied from 0.50 to 2.96Gy.Conclusion: The DPF between the different phases should be equal in order to render BEDA accurate. OARs typically receive heterogeneous dose distributions hence the probability of equal DPFs is low. Consequently, the BEDA equation should only be used for targets or OARs that receive uniform or very similar dose distributions by the different treatment phases.---------------------------Cite this article as

  20. Structurally Complex Frank–Kasper Phases and Quasicrystal Approximants: Electronic Origin of Stability

    Directory of Open Access Journals (Sweden)

    Valentina F. Degtyareva

    2017-12-01

    Full Text Available Metal crystals with tetrahedral packing are known as Frank–Kasper phases, with large unit cells with the number of atoms numbering from hundreds to thousands. The main factors of the formation and stability of these phases are the atomic size ratio and the number of valence electrons per atom. The significance of the electronic energy contribution is analyzed within the Fermi sphere–Brillouin zone interaction model for several typical examples: Cu4Cd3, Mg2Al3 with over a thousand atoms per cell, and for icosahedral quasicrystal approximants with 146–168 atoms per cell. Our analysis shows that to minimize the crystal energy, it is important that the Fermi sphere (FS is in contact with the Brillouin zones that are related to the strong diffraction peaks: the zones either inscribe the FS or are circumscribed by the FS creating contact at edges or vertices.

  1. Phase diagram in two-dimensional Hubbard model: variational cluster approximation

    Science.gov (United States)

    Kocharian, Armen; Fang, Kun; Fernando, Gayanath; Balatsky, Alexander; Palandage, Kalum

    2014-03-01

    The Variational Cluster Approximation (VCA) is used to rigorously calculate the intrinsic phase diagram in bipartite two-dimensional (2d) Hubbard structures such as square and honeycomb lattice geometries with attraction and repulsion of electrons. The Mott-Hubbard gap, manifested as a smooth metal-insulator transition at finite U > 0 in both square and honeycomb lattices at half filling (n = 1), is in agreement with the generic 2d phase diagram. However, a density variation with the chemical potential displays their distinct structural differences away from half filling. Near n = 1 at equilibrium we found discontinuous transition in square lattices signaling a phase separation instability into an inhomogeneous state with hole rich (metallic) and hole poor (n = 1 -insulating) regions. In contrast, a smooth density transition in honeycomb geometry describes a continuous evolution of homogenous (metallic) state. Incorporation of long-range input in VCA using U >0 and U topological insulators as well as comparison to other studies is discussed. The VCA provides strong support for spontaneous phase separation instability found in our quantum cluster calculations. The authors acknowledge the BNL and LANL computing facilities supported by the U.S. DOE, Office of Basic Energy Sciences, under Contracts No.DE-AC02-98CH10886, No.DE-AC52-06NA25396 and Sandia National Laboratories (Contract DE-AC04-94AL85000).

  2. Variance of phase fluctuations of waves propagating through a random medium

    Science.gov (United States)

    Chu, Nelson C.; Kong, Jin AU; Yueh, Simon H.; Nghiem, Son V.; Fleischman, Jack G.; Ayasli, Serpil; Shin, Robert T.

    1992-01-01

    As an electromagnetic wave propagates through a random scattering medium, such as a forest, its energy is attenuated and random phase fluctuations are induced. The magnitude of the random phase fluctuations induced is important in estimating how well a Synthetic Aperture Radar (SAR) can image objects within the scattering medium. The two-layer random medium model, consisting of a scattering layer between free space and ground, is used to calculate the variance of the phase fluctuations induced between a transmitter located above the random medium and a receiver located below the random medium. The scattering properties of the random medium are characterized by a correlation function of the random permittivity fluctuations. The effective permittivity of the random medium is first calculated using the strong fluctuation theory, which accounts for large permittivity fluctuations of the scatterers. The distorted Born approximation is used to calculate the first-order scattered field. A perturbation series for the phase of the received field in the Rytov approximation is then introduced and the variance of the phase fluctuations is also calculated assuming that the transmitter and receiver are in the paraxial limit of the random medium, which allows an analytic solution to be obtained. Results are compared using the paraxial approximation, scalar Green's function formulation, and dyadic Green's function formulation. The effects studied are the dependence of the variance of the phase fluctuations on receiver location in lossy and lossless regions, medium thickness, correlation length and fractional volume of scatterers, depolarization of the incident wave, ground layer permittivity, angle of incidence, and polarization.

  3. Phase-conjugated mirror-induced oscillations outside the rotating-wave approximation

    Energy Technology Data Exchange (ETDEWEB)

    Hassan, S S [Ain Shams University, Faculty of Science, Mathematics Department, Cairo (Egypt); Frege, O [Ain Shams University, Faculty of Education, Mathematics Department, Cairo (Egypt)

    2002-06-01

    Dynamical behaviour of a single harmonic oscillator (HO) and of a single and two cooperative atoms in front of a phase-conjugated mirror is investigated without using the rotating-wave approximation. The mean photon number of the HO shows transient oscillation of frequency (2{omega}{sub 0}) and O({gamma}/{omega}{sub 0}), the ratio of the free-space decay rate to the oscillation frequency, and the fluorescent spectrum becomes asymmetric due to additional resonant and non-resonant dispersive terms. In the single-two-level-atom case, the mean atomic inversion and the fluorescent intensity show steady oscillation O({gamma}{sub 0}/{omega}{sub 0}), the ratio of the A-coefficient to the atomic transition frequency. The amplitude of this steady oscillation at frequency (2{omega}{sub 0}) is larger in the case of two cooperative atoms.

  4. Phase change material solidification in a finned cylindrical shell thermal energy storage: An approximate analytical approach

    Directory of Open Access Journals (Sweden)

    Mosaffa Amirhossein

    2013-01-01

    Full Text Available Results are reported of an investigation of the solidification of a phase change material (PCM in a cylindrical shell thermal energy storage with radial internal fins. An approximate analytical solution is presented for two cases. In case 1, the inner wall is kept at a constant temperature and, in case 2, a constant heat flux is imposed on the inner wall. In both cases, the outer wall is insulated. The results are compared to those for a numerical approach based on an enthalpy method. The results show that the analytical model satisfactory estimates the solid-liquid interface. In addition, a comparative study is reported of the solidified fraction of encapsulated PCM for different geometric configurations of finned storage having the same volume and surface area of heat transfer.

  5. Constrained low-rank matrix estimation: phase transitions, approximate message passing and applications

    Science.gov (United States)

    Lesieur, Thibault; Krzakala, Florent; Zdeborová, Lenka

    2017-07-01

    This article is an extended version of previous work of Lesieur et al (2015 IEEE Int. Symp. on Information Theory Proc. pp 1635-9 and 2015 53rd Annual Allerton Conf. on Communication, Control and Computing (IEEE) pp 680-7) on low-rank matrix estimation in the presence of constraints on the factors into which the matrix is factorized. Low-rank matrix factorization is one of the basic methods used in data analysis for unsupervised learning of relevant features and other types of dimensionality reduction. We present a framework to study the constrained low-rank matrix estimation for a general prior on the factors, and a general output channel through which the matrix is observed. We draw a parallel with the study of vector-spin glass models—presenting a unifying way to study a number of problems considered previously in separate statistical physics works. We present a number of applications for the problem in data analysis. We derive in detail a general form of the low-rank approximate message passing (Low-RAMP) algorithm, that is known in statistical physics as the TAP equations. We thus unify the derivation of the TAP equations for models as different as the Sherrington-Kirkpatrick model, the restricted Boltzmann machine, the Hopfield model or vector (xy, Heisenberg and other) spin glasses. The state evolution of the Low-RAMP algorithm is also derived, and is equivalent to the replica symmetric solution for the large class of vector-spin glass models. In the section devoted to result we study in detail phase diagrams and phase transitions for the Bayes-optimal inference in low-rank matrix estimation. We present a typology of phase transitions and their relation to performance of algorithms such as the Low-RAMP or commonly used spectral methods.

  6. Spatially distributed successive approximation register (SDSAR) photonic ADCs based on phase-domain quantization.

    Science.gov (United States)

    Nazarathy, Moshe; Shaham, Oded

    2012-03-26

    We explore photonic ADC architectures based on encoding voltage-under-test into phase. The first step is to identify two basic optical building blocks: the optical phase comparator (1-bit ADC), based on interferometric comparison of phases in the well-known balanced photo-detection configuration, and the optical 1-bit DAC, namely electro-optic modulation with a bipolar electrical pulse. Equipped with these fundamental building blocks, we proceed to systematically port and adapt known ADC quantization architectures to photonic ADC, conceiving a hybrid between the Successive Approximation Register (SAR) and the Pipeline classic ADC architectures, referred to here as Spatially Distributed SAR (SDSAR). This novel photonic ADC, constructed out of B 1-bit ADCs and B-2 1-bit DACs, with B the number of bits, is not equivalent to any of the previous photonic ADCs in the literature, but appears superior to prior schemes in both optical power efficiency and electro-optic modulation complexity. We derive upper bounds on resolution, Effective Number of Bits (ENOB) performance as a function of average optical power for the new SDSAR device, developing analytic and numeric Monte-Carlo statistical models, comprising quantization, shot, thermal and DAC voltage noise sources. Our findings indicate that SDSAR is limited to ~11.5 ENOBs, assuming state-of-the-art mode-locked-lasers providing ~250 mW of average power (assuming ~7 dB excess losses). However, this upper bound is not tight, due to various physical impairments. In particular, the mode locked laser jitter is shown to have negligible impact on overall performance for RMS jitter < 20 fsec.

  7. Approximated transport-of-intensity equation for coded-aperture x-ray phase-contrast imaging.

    Science.gov (United States)

    Das, Mini; Liang, Zhihua

    2014-09-15

    Transport-of-intensity equations (TIEs) allow better understanding of image formation and assist in simplifying the "phase problem" associated with phase-sensitive x-ray measurements. In this Letter, we present for the first time to our knowledge a simplified form of TIE that models x-ray differential phase-contrast (DPC) imaging with coded-aperture (CA) geometry. The validity of our approximation is demonstrated through comparison with an exact TIE in numerical simulations. The relative contributions of absorption, phase, and differential phase to the acquired phase-sensitive intensity images are made readily apparent with the approximate TIE, which may prove useful for solving the inverse phase-retrieval problem associated with these CA geometry based DPC.

  8. Approximation of Quantities of Interest in Stochastic PDEs by the Random Discrete L^2 Projection on Polynomial Spaces

    KAUST Repository

    Migliorati, G.

    2013-05-30

    In this work we consider the random discrete L^2 projection on polynomial spaces (hereafter RDP) for the approximation of scalar quantities of interest (QOIs) related to the solution of a partial differential equation model with random input parameters. In the RDP technique the QOI is first computed for independent samples of the random input parameters, as in a standard Monte Carlo approach, and then the QOI is approximated by a multivariate polynomial function of the input parameters using a discrete least squares approach. We consider several examples including the Darcy equations with random permeability, the linear elasticity equations with random elastic coefficient, and the Navier--Stokes equations in random geometries and with random fluid viscosity. We show that the RDP technique is well suited to QOIs that depend smoothly on a moderate number of random parameters. Our numerical tests confirm the theoretical findings in [G. Migliorati, F. Nobile, E. von Schwerin, and R. Tempone, Analysis of the Discrete $L^2$ Projection on Polynomial Spaces with Random Evaluations, MOX report 46-2011, Politecnico di Milano, Milano, Italy, submitted], which have shown that, in the case of a single uniformly distributed random parameter, the RDP technique is stable and optimally convergent if the number of sampling points is proportional to the square of the dimension of the polynomial space. Here optimality means that the weighted $L^2$ norm of the RDP error is bounded from above by the best $L^\\\\infty$ error achievable in the given polynomial space, up to logarithmic factors. In the case of several random input parameters, the numerical evidence indicates that the condition on quadratic growth of the number of sampling points could be relaxed to a linear growth and still achieve stable and optimal convergence. This makes the RDP technique very promising for moderately high dimensional uncertainty quantification.

  9. Comparison of Clenshaw–Curtis and Leja Quasi-Optimal Sparse Grids for the Approximation of Random PDEs

    KAUST Repository

    Nobile, Fabio

    2015-11-26

    In this work we compare different families of nested quadrature points, i.e. the classic Clenshaw–Curtis and various kinds of Leja points, in the context of the quasi-optimal sparse grid approximation of random elliptic PDEs. Numerical evidence suggests that both families perform comparably within such framework.

  10. Review of Random Phase Encoding in Volume Holographic Storage

    Directory of Open Access Journals (Sweden)

    Wei-Chia Su

    2012-09-01

    Full Text Available Random phase encoding is a unique technique for volume hologram which can be applied to various applications such as holographic multiplexing storage, image encryption, and optical sensing. In this review article, we first review and discuss diffraction selectivity of random phase encoding in volume holograms, which is the most important parameter related to multiplexing capacity of volume holographic storage. We then review an image encryption system based on random phase encoding. The alignment of phase key for decryption of the encoded image stored in holographic memory is analyzed and discussed. In the latter part of the review, an all-optical sensing system implemented by random phase encoding and holographic interconnection is presented.

  11. Ordering and phase transitions in random-field Ising systems

    Science.gov (United States)

    Maritan, Amos; Swift, Michael R.; Cieplak, Marek; Chan, Moses H. W.; Cole, Milton W.; Banavar, Jayanth R.

    1991-01-01

    An exact analysis of the Ising model with infinite-range interactions in a random field and a local mean-field theory in three dimensions is carried out leading to a phase diagram with several coexistence surfaces and lines of critical points. The results show that the phase diagram depends crucially on whether the distribution of random fields is symmetric or not. Thus, Ising-like phase transitions in a porous medium (the asymmetric case) are in a different universality class from the conventional random-field model (symmetric case).

  12. A tool for modelling of microsegregation: an approximation method for partition coefficients in experimentally determined multicomponent phase diagrams

    Energy Technology Data Exchange (ETDEWEB)

    Roosz, A.; Szoeke, J. [Miskolc Univ. (Hungary). Dept. of Materials Science; Rettenmayr, M. [Darmstadt Univ. of Technology (Germany). Materials Science Dept.

    2000-12-01

    A complete set of partition coefficients of all alloying elements in multicomponent systems is an essential input for solidification models. An approximation method for partition coefficients in experimentally determined phase diagrams has been developed. The equilibria of the binary boundary systems and the eutectic valleys are used as a basis for the approximation in ternary systems. The method has been verified by a comparison of approximated and known (calculated by the CALPHAD method) partition coefficients in the Al-Cu-Si system. The ratio of the end points of calculated tie-lines is in excellent agreement with approximated partition coefficients. In the empirical Al-Cu-Si phase diagram, the approximated partition coefficients yield solid concentrations that are close to the measured solidus surface. (orig.)

  13. Extension of an Itô-based general approximation technique for random vibration of a BBW general hysteris model part II: Non-Gaussian analysis

    Science.gov (United States)

    Davoodi, H.; Noori, M.

    1990-07-01

    The work presented in this paper constitutes the second phase of on-going research aimed at developing mathematical models for representing general hysteretic behavior of structures and approximation techniques for the computation and analysis of the response of hysteretic systems to random excitations. In this second part, the technique previously developed by the authors for the Gaussian response analysis of non-linear systems with general hysteretic behavior is extended for the non-Gaussian analysis of these systems. This approximation technique is based on the approach proposed independently by Ibrahim and Wu-Lin. In this work up to fourth order moments of the response co-ordinates are obtained for the Bouc-Baber-Wen smooth hysteresis model. These higher order statistics previously have not been made available for general hysteresis models by using existing approximation methods. Second order moments obtained for the model by this non-Gaussian closure scheme are compared with equivalent linearization and Gaussian closure results via Monte Carlo simulation (MCS). Higher order moments are compared with the simulation results. The study performed for a wide range of degradation parameters and input power spectral density ( PSD) levels shows that the non-Gaussian responses obtained by this approach are in better agreement with the MCS results than the linearized and Gaussian ones. This approximation technique can provide information on higher order moments for general hysteretic systems. This information is valuable in random vibration and the reliability analysis of hysteretically yielding structures.

  14. Analyzing Signal Attenuation in PFG Anomalous Diffusion via a Modified Gaussian Phase Distribution Approximation Based on Fractal Derivative Model

    CERN Document Server

    Lin, Guoxing

    2016-01-01

    Pulsed field gradient (PFG) has been increasingly employed to study anomalous diffusions in Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI). However, the analysis of PFG anomalous diffusion is complicated. In this paper, a fractal derivative model based modified Gaussian phase distribution method is proposed to describe PFG anomalous diffusion. By using the phase distribution obtained from the effective phase shift diffusion method based on fractal derivatives, and employing some of the traditional Gaussian phase distribution approximation techniques, a general signal attenuation expression for free fractional diffusion is derived. This expression describes a stretched exponential function based attenuation, which is distinct from both the exponential attenuation for normal diffusion obtained from conventional Gaussian phase distribution approximation, and the Mittag-Leffler function based attenuation for anomalous diffusion obtained from fractional derivative. The obtained signal attenu...

  15. Synthesis of a scalar wavelet intensity propagating through von Kármán-type random media: joint use of the radiative transfer equation with the Born approximation and the Markov approximation

    Science.gov (United States)

    Sato, Haruo; Emoto, Kentaro

    2017-10-01

    In high-frequency seismograms of small earthquakes, we clearly see the excitation of long lasting coda waves and the envelope broadening of an S-wavelet with travel distance increasing. We can interpret those phenomena resulting from scattering by random inhomogeneities distributed in the earth medium. Those phenomena have been theoretically studied by stochastic methods, which deal with velocity inhomogeneities as random media. As a simple mathematical model, we study the propagation of a scalar wavelet for the spherical radiation from a point source in 3-D von Kármán-type random media, of which the power spectral density function (PSDF) decreases according to a power-law higher than the corner wavenumber. Our objective is to propose a method to synthesize the wavelet intensity time trace, the mean square amplitude trace, at a given travel distance by using statistical parameters characterizing the PSDF and the centre wavenumber of the wavelet. When the phase shift is small, we can use the Born approximation to calculate the non-isotropic scattering coefficient representing the scattering power per unit volume. Using the scattering coefficient in the radiative transfer equation (RTE), we are able to synthesize the wavelet intensity time trace. When the centre wavenumber increases in the power-law spectral range, however, we often face the situation of a large phase shift, where the Born approximation is inapplicable, but we are able to use the Markov approximation based on the parabolic approximation. It well explains the intensity time traces showing envelope broadening with peak delay due to multiple scattering around the forward direction and the wandering effect caused by travel time fluctuations; however, it fails to explain rich coda waves composed of scattered waves in wide angles. In such a case, here, we newly propose the spectrum division method as follows: at first, taking the centre wavenumber with a tuning parameter as a reference, we divide the

  16. Implementation of optimal Galerkin and Collocation approximations of PDEs with Random Coefficients

    KAUST Repository

    Beck, Joakim

    2011-12-22

    In this work we first focus on the Stochastic Galerkin approximation of the solution u of an elliptic stochastic PDE. We rely on sharp estimates for the decay of the coefficients of the spectral expansion of u on orthogonal polynomials to build a sequence of polynomial subspaces that features better convergence properties compared to standard polynomial subspaces such as Total Degree or Tensor Product. We consider then the Stochastic Collocation method, and use the previous estimates to introduce a new effective class of Sparse Grids, based on the idea of selecting a priori the most profitable hierarchical surpluses, that, again, features better convergence properties compared to standard Smolyak or tensor product grids.

  17. Implementation of optimal Galerkin and Collocation approximations of PDEs with Random Coefficients⋆⋆⋆

    Directory of Open Access Journals (Sweden)

    Tempone R.

    2011-12-01

    Full Text Available In this work we first focus on the Stochastic Galerkin approximation of the solution u of an elliptic stochastic PDE. We rely on sharp estimates for the decay of the coefficients of the spectral expansion of u on orthogonal polynomials to build a sequence of polynomial subspaces that features better convergence properties compared to standard polynomial subspaces such as Total Degree or Tensor Product. We consider then the Stochastic Collocation method, and use the previous estimates to introduce a new effective class of Sparse Grids, based on the idea of selecting a priori the most profitable hierarchical surpluses, that, again, features better convergence properties compared to standard Smolyak or tensor product grids.

  18. Phase diagram of the Blume-Emery-Griffiths model on the simple cubic lattice calculated by the linear chain approximation

    CERN Document Server

    Albayrak, E

    2000-01-01

    The linear chain approximation is used to study the temperature dependence of the order parameters and the phase diagrams of the Blume-Emery-Griffiths model on the simple cubic lattice with dipole-dipole, quadrupole-quadrupole coupling strengths and a crystal-field interaction. The problem is approached introducing first a trial one-dimensional Hamiltonian whose free energy can be calculated exactly by the transfer matrix method. Then using the Bogoliubov variational principle, the free energy of the model is determined. It is assumed that the dipolar and quadrupolar intrachain coupling constants are much stronger than the corresponding interchain constants and confined the attention to the case of nearest-neighbor interactions. The phase transitions are examined and the phase diagrams are obtained for several values of the coupling strengths in the three different planes. A comparison with other approximate techniques is also made.

  19. Analyzing signal attenuation in PFG anomalous diffusion via a non-Gaussian phase distribution approximation approach by fractional derivatives

    CERN Document Server

    Lin, Guoxing

    2016-01-01

    Anomalous diffusion exists widely in polymer and biological systems. Pulsed field gradient (PFG) techniques have been increasingly used to study anomalous diffusion in NMR and MRI. However, the interpretation of PFG anomalous diffusion is complicated. Moreover, there is not an exact signal attenuation expression based on fractional derivatives for PFG anomalous diffusion, which includes the finite gradient pulse width effect. In this paper, a new method, a Mainardi-Luchko-Pagnini (MLP) phase distribution approximation, is proposed to describe PFG fractional diffusion. MLP phase distribution is a non-Gaussian phase distribution. From the fractional diffusion equation based on fractional derivatives in both real space and phase space, the obtained probability distribution function is a MLP distribution. The MLP distribution leads to a Mittag-Leffler function based PFG signal attenuation rather than the exponential or stretched exponential attenuation that is obtained from a Gaussian phase distribution (GPD) und...

  20. Phase transitions for information diffusion in random clustered networks

    Science.gov (United States)

    Lim, Sungsu; Shin, Joongbo; Kwak, Namju; Jung, Kyomin

    2016-09-01

    We study the conditions for the phase transitions of information diffusion in complex networks. Using the random clustered network model, a generalisation of the Chung-Lu random network model incorporating clustering, we examine the effect of clustering under the Susceptible-Infected-Recovered (SIR) epidemic diffusion model with heterogeneous contact rates. For this purpose, we exploit the branching process to analyse information diffusion in random unclustered networks with arbitrary contact rates, and provide novel iterative algorithms for estimating the conditions and sizes of global cascades, respectively. Showing that a random clustered network can be mapped into a factor graph, which is a locally tree-like structure, we successfully extend our analysis to random clustered networks with heterogeneous contact rates. We then identify the conditions for phase transitions of information diffusion using our method. Interestingly, for various contact rates, we prove that random clustered networks with higher clustering coefficients have strictly lower phase transition points for any given degree sequence. Finally, we confirm our analytical results with numerical simulations of both synthetically-generated and real-world networks.

  1. Bilayer technique and nano-filled coating increase success of approximal ART restorations: a randomized clinical trial.

    Science.gov (United States)

    Hesse, Daniela; Bonifácio, Clarissa Calil; Guglielmi, Camila de Almeida Brandão; Bönecker, Marcelo; van Amerongen, Willem Evert; Raggio, Daniela Prócida

    2016-05-01

    The high-viscosity consistency of glass ionomer cement (GIC) may lead to its incorrect adaptation into the cavity and therefore to restoration failure. To compare two different insertion techniques for GIC in approximal atraumatic restorative treatment (ART) restorations and two different surface protection materials. Approximal caries lesion in primary molars from 208 schoolchildren was randomly assigned into four groups: G1, conventional GIC insertion protected with petroleum jelly (PJ); G2, bilayer technique protected with PJ; G3 conventional GIC insertion protected with nano-filled particles coating for GIC (NPC); G4, bilayer technique protected with NPC. Restorations were evaluated after 1, 6, 12, 18, 24, and 36 months. Kaplan-Meier survival analysis and log-rank test were performed. Cox regression analysis (α = 5%) was used to verify the influence of clinical factors. Restoration survival was 52.8%. Log-rank test indicated a better survival of the bilayer technique restorations, compared to conventional restorations (P = 0.005), whereas the coated conventional restorations presented higher survival than the uncoated ones (P = 0.035). Cox regression analysis showed no influence of any clinical tested variables. The survival rate of the approximal ART restorations is positively influenced by the bilayer technique, and the application of nano-filled coating increases the longevity of the conventional approximal ART restorations. © 2015 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. On the relation between phase-field crack approximation and gradient damage modelling

    Science.gov (United States)

    Steinke, Christian; Zreid, Imadeddin; Kaliske, Michael

    2017-05-01

    The finite element implementation of a gradient enhanced microplane damage model is compared to a phase-field model for brittle fracture. Phase-field models and implicit gradient damage models share many similarities despite being conceived from very different standpoints. In both approaches, an additional differential equation and a length scale are introduced. However, while the phase-field method is formulated starting from the description of a crack in fracture mechanics, the gradient method starts from a continuum mechanics point of view. At first, the scope of application for both models is discussed to point out intersections. Then, the analysis of the employed mathematical methods and their rigorous comparison are presented. Finally, numerical examples are introduced to illustrate the findings of the comparison which are summarized in a conclusion at the end of the paper.

  3. Single-random-phase holographic encryption of images

    Science.gov (United States)

    Tsang, P. W. M.

    2017-02-01

    In this paper, a method is proposed for encrypting an optical image onto a phase-only hologram, utilizing a single random phase mask as the private encryption key. The encryption process can be divided into 3 stages. First the source image to be encrypted is scaled in size, and pasted onto an arbitrary position in a larger global image. The remaining areas of the global image that are not occupied by the source image could be filled with randomly generated contents. As such, the global image as a whole is very different from the source image, but at the same time the visual quality of the source image is preserved. Second, a digital Fresnel hologram is generated from the new image, and converted into a phase-only hologram based on bi-directional error diffusion. In the final stage, a fixed random phase mask is added to the phase-only hologram as the private encryption key. In the decryption process, the global image together with the source image it contained, can be reconstructed from the phase-only hologram if it is overlaid with the correct decryption key. The proposed method is highly resistant to different forms of Plain-Text-Attacks, which are commonly used to deduce the encryption key in existing holographic encryption process. In addition, both the encryption and the decryption processes are simple and easy to implement.

  4. Analyzing signal attenuation in PFG anomalous diffusion via a modified Gaussian phase distribution approximation based on fractal derivative model

    Science.gov (United States)

    Lin, Guoxing

    2017-02-01

    Pulsed field gradient (PFG) technique is a noninvasive tool, and has been increasingly employed to study anomalous diffusions in Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI). However, the analysis of PFG anomalous diffusion is much more complicated than normal diffusion. In this paper, a fractal derivative model based modified Gaussian phase distribution method is proposed to describe PFG anomalous diffusion. By using the phase distribution obtained from the effective phase shift diffusion method based on fractal derivatives, and employing some of the traditional Gaussian phase distribution approximation techniques, a general signal attenuation expression for free fractional diffusion is derived. This expression describes a stretched exponential function based attenuation, which is distinct from both the exponential attenuation for normal diffusion obtained from conventional Gaussian phase distribution approximation, and the Mittag-Leffler function based attenuation for anomalous diffusion obtained from fractional derivative. The obtained signal attenuation expression can analyze the finite gradient pulse width (FGPW) effect. Additionally, it can generally be applied to all three types of PFG fractional diffusions classified based on time derivative order α and space derivative order β. These three types of fractional diffusions include time-fractional diffusion with { 0 < α ≤ 2 , β = 2 } , space-fractional diffusion with { α = 1 , 0 < β ≤ 2 } , and general fractional diffusion with { 0 < α , β ≤ 2 } . The results in this paper are consistent with reported results based on effective phase shift diffusion equation method and instantaneous signal attenuation method. This method provides a new, convenient approximation formalism for analyzing PFG anomalous diffusion experiments. The expression that can simultaneously interpret general fractional diffusion and FGPW effect could be especially important in PFG MRI, where the narrow

  5. Random phase-free computer-generated hologram

    CERN Document Server

    Shimobaba, Tomoyoshi

    2015-01-01

    Addition of random phase to the object light is required in computer-generated holograms (CGHs) to widely diffuse the object light and to avoid its concentration on the CGH; however, this addition causes considerable speckle noise in the reconstructed image. For improving the speckle noise problem, techniques such as iterative phase retrieval algorithms and multi-random phase method are used; however, they are time consuming and are of limited effectiveness. Herein, we present a simple and computationally inexpensive method that drastically improves the image quality and reduces the speckle noise by multiplying the object light with the virtual convergence light. Feasibility of the proposed method is shown using simulations and optical reconstructions; moreover, we apply it to lens-less zoom-able holographic projection. The proposed method is useful for the speckle problems in holographic applications.

  6. Enhanced wavefront reconstruction by random phase modulation with a phase diffuser

    DEFF Research Database (Denmark)

    Almoro, Percival F; Pedrini, Giancarlo; Gundu, Phanindra Narayan

    2011-01-01

    propagation in free space. The presentation of this technique is carried out using two setups. In the first setup, a diffuser plate is placed at the image plane of a metallic test object. The benefit of randomizing the phase of the object wave is the enhanced intensity recording due to high dynamic range...... of the diffusely scattered beam. The use of demagnification optics will also allow the investigations of relatively large objects. In the second setup, a transparent object is illuminated using a wavefront with random phase and constant amplitude by positioning the phase diffuser close to the object. The benefit...

  7. Phase shifting interferometry from two normalized interferograms with random tilt phase-shift.

    Science.gov (United States)

    Liu, Fengwei; Wu, Yongqian; Wu, Fan

    2015-07-27

    We propose a novel phase shifting interferometry from two normalized interferograms with random tilt phase-shift. The determination of tilt phase-shift is performed by extracting the tilted phase-shift plane from the phase difference of two normalized interferograms, and with the calculated tilt phase-shift value the phase distribution can be retrieved from the two normalized frames. By analyzing the distribution of phase difference and utilizing special points fitting method, the tilted phase-shift plane is extracted in three different cases, which relate to different magnitudes of tilts. Proposed method has been applied to simulations and experiments successfully and the satisfactory results manifest that proposed method is of high accuracy and high speed compared with the three step iterative method. Additionally, both open and closed fringe can be analyzed with proposed method. What's more, it cannot only eliminate the small tilt-shift error caused by slight vibration in phase-shifting interferometry, but also detect the large tilt phase-shift in phase-tilting interferometry. Thus, it will relaxes the requirements on the accuracy of phase shifter, and the costly phase shifter may even be useless by applying proposed method in high amplitude vibrated circumstance to achieve high-precision analysis.

  8. Analyzing signal attenuation in PFG anomalous diffusion via a non-Gaussian phase distribution approximation approach by fractional derivatives.

    Science.gov (United States)

    Lin, Guoxing

    2016-11-21

    Anomalous diffusion exists widely in polymer and biological systems. Pulsed-field gradient (PFG) techniques have been increasingly used to study anomalous diffusion in nuclear magnetic resonance and magnetic resonance imaging. However, the interpretation of PFG anomalous diffusion is complicated. Moreover, the exact signal attenuation expression including the finite gradient pulse width effect has not been obtained based on fractional derivatives for PFG anomalous diffusion. In this paper, a new method, a Mainardi-Luchko-Pagnini (MLP) phase distribution approximation, is proposed to describe PFG fractional diffusion. MLP phase distribution is a non-Gaussian phase distribution. From the fractional derivative model, both the probability density function (PDF) of a spin in real space and the PDF of the spin's accumulating phase shift in virtual phase space are MLP distributions. The MLP phase distribution leads to a Mittag-Leffler function based PFG signal attenuation, which differs significantly from the exponential attenuation for normal diffusion and from the stretched exponential attenuation for fractional diffusion based on the fractal derivative model. A complete signal attenuation expression Eα(-Dfbα,β(*)) including the finite gradient pulse width effect was obtained and it can handle all three types of PFG fractional diffusions. The result was also extended in a straightforward way to give a signal attenuation expression of fractional diffusion in PFG intramolecular multiple quantum coherence experiments, which has an n(β) dependence upon the order of coherence which is different from the familiar n(2) dependence in normal diffusion. The results obtained in this study are in agreement with the results from the literature. The results in this paper provide a set of new, convenient approximation formalisms to interpret complex PFG fractional diffusion experiments.

  9. Analyzing signal attenuation in PFG anomalous diffusion via a non-Gaussian phase distribution approximation approach by fractional derivatives

    Science.gov (United States)

    Lin, Guoxing

    2016-11-01

    Anomalous diffusion exists widely in polymer and biological systems. Pulsed-field gradient (PFG) techniques have been increasingly used to study anomalous diffusion in nuclear magnetic resonance and magnetic resonance imaging. However, the interpretation of PFG anomalous diffusion is complicated. Moreover, the exact signal attenuation expression including the finite gradient pulse width effect has not been obtained based on fractional derivatives for PFG anomalous diffusion. In this paper, a new method, a Mainardi-Luchko-Pagnini (MLP) phase distribution approximation, is proposed to describe PFG fractional diffusion. MLP phase distribution is a non-Gaussian phase distribution. From the fractional derivative model, both the probability density function (PDF) of a spin in real space and the PDF of the spin's accumulating phase shift in virtual phase space are MLP distributions. The MLP phase distribution leads to a Mittag-Leffler function based PFG signal attenuation, which differs significantly from the exponential attenuation for normal diffusion and from the stretched exponential attenuation for fractional diffusion based on the fractal derivative model. A complete signal attenuation expression Eα(-Dfbα,β * ) including the finite gradient pulse width effect was obtained and it can handle all three types of PFG fractional diffusions. The result was also extended in a straightforward way to give a signal attenuation expression of fractional diffusion in PFG intramolecular multiple quantum coherence experiments, which has an nβ dependence upon the order of coherence which is different from the familiar n2 dependence in normal diffusion. The results obtained in this study are in agreement with the results from the literature. The results in this paper provide a set of new, convenient approximation formalisms to interpret complex PFG fractional diffusion experiments.

  10. Structure of Sn1−xGex random alloys as obtained from the coherent potential approximation

    KAUST Repository

    Pulikkotil, J. J.

    2011-08-09

    The structure of the Sn1−xGex random alloys is studied using density functional theory and the coherent potential approximation. We report on the deviation of the Sn1−xGex alloys from Vegard’s law, addressing their full compositional range. The findings are compared to the related Si1−xGex alloys and to experimental results. Interestingly, the deviation from Vegard’s law is quantitatively and qualitatively different between the Sn1−xGex and Si1−xGex alloys. An almost linear dependence of the bulk modulus as a function of composition is found for Si1−xGex, whereas for Sn1−xGex the dependence is strongly nonlinear.

  11. Dispersive and Covalent Interactions between Graphene and Metal Surfaces from the Random Phase Approximation

    DEFF Research Database (Denmark)

    Olsen, Thomas; Yan, Jun; Mortensen, Jens Jørgen

    2011-01-01

    for exchange-correlation functionals give inadequate descriptions of either van der Waals or chemical bonds, RPA accounts accurately for both. It is found that the adsorption is a delicate competition between a weak chemisorption minimum close to the surface and a physisorption minimum further from the surface....

  12. Dispersive SH waves in a cylindrical multiferroic composite with interfacial irregularity: Approximate analysis on coordinate-dependent phase velocity

    Science.gov (United States)

    Li, Yong-Dong; Liu, Shi-Lun; Jin, Ying; Wei, Hong-Xing; Guan, Yong

    2017-09-01

    Irregular interfaces may be formed between the neighboring ferromagnetic and ferroelectric layers of multiferroic composites during the hot-pressing process. They undoubtedly affects the mechanical behavior of multiferroic composites and this is a scientific problem deserving studying. In addition, phase velocity will be a function of coordinate if the interface is irregular, and this makes the governing equation so complicated that direct analytical solution is unobtainable. The present article proposes an approximate approach for analyzing SH waves in a cylindrical multiferroic composite with interfacial irregularity. The dispersion equation is analytically derived and numerically solved. After the validity range of the approximate treatment is clarified, parametric studies reveals that interfacial corrugations can give rise to an oscillatory distribution of phase velocity along the propagation direction. Because such oscillation can lead to unstable signal transmission, it should be avoided in engineering. Further discussion suggests three possible ways for suppressing the oscillation of phase velocity. The research results can provide references for optimizing the design, manufacture and application of multiferroic devices.

  13. Diffusely scattered and transmitted elastic waves by random rough solid-solid interfaces using an elastodynamic Kirchhoff approximation

    Science.gov (United States)

    Shi, Fan; Lowe, Mike; Craster, Richard

    2017-06-01

    Elastic waves scattered by random rough interfaces separating two distinct media play an important role in modeling phonon scattering and impact upon thermal transport models, and are also integral to ultrasonic inspection. We introduce theoretical formulas for the diffuse field of elastic waves scattered by, and transmitted across, random rough solid-solid interfaces using the elastodynamic Kirchhoff approximation. The new formulas are validated by comparison with numerical Monte Carlo simulations, for a wide range of roughness (rms σ ≤λ /3 , correlation length λ0≥ wavelength λ ), demonstrating a significant improvement over the widely used small-perturbation approach, which is valid only for surfaces with small rms values. Physical analysis using the theoretical formulas derived here demonstrates that increasing the rms value leads to a considerable change of the scattering patterns for each mode. The roughness has different effects on the reflection and the transmission, with a strong dependence on the material properties. In the special case of a perfect match of the wave speed of the two solid media, the transmission is the same as the case for a flat interface. We pay particular attention to scattering in the specular direction, often used as an observable quantity, in terms of the roughness parameters, showing a peak at an intermediate value of rms; this rms value coincides with that predicted by the Rayleigh parameter.

  14. Reconstruction of a random phase dynamics network from observations

    Science.gov (United States)

    Pikovsky, A.

    2018-01-01

    We consider networks of coupled phase oscillators of different complexity: Kuramoto-Daido-type networks, generalized Winfree networks, and hypernetworks with triple interactions. For these setups an inverse problem of reconstruction of the network connections and of the coupling function from the observations of the phase dynamics is addressed. We show how a reconstruction based on the minimization of the squared error can be implemented in all these cases. Examples include random networks with full disorder both in the connections and in the coupling functions, as well as networks where the coupling functions are taken from experimental data of electrochemical oscillators. The method can be directly applied to asynchronous dynamics of units, while in the case of synchrony, additional phase resettings are necessary for reconstruction.

  15. Quantum phase fluctuations of coherent and thermal light coupled to a non-degenerate parametric oscillator beyond rotating wave approximation

    Science.gov (United States)

    Alam, Mohosin; Mandal, Swapan; Wahiddin, Mohamed Ridza

    2017-09-01

    The essence of the rotating wave approximation (RWA) is to eliminate the non-conserving energy terms from the interaction Hamiltonian. The cost of using RWA is heavy if the frequency of the input radiation field is low (e.g. below optical region). The well known Bloch-Siegert effect is the out come of the inclusion of the terms which are normally neglected under RWA. We investigate the fluctuations of the quantum phase of the coherent light and the thermal light coupled to a nondegenerate parametric oscillator (NDPO). The Hamiltonian and hence the equations of motion involving the signal and idler modes are framed by using the strong (classical) pump condition. These differential equations are nonlinear in nature and are found coupled to each other. Without using the RWA, we obtain the analytical solutions for the signal and idler fields. These solutions are obtained up to the second orders in dimensionless coupling constants. The analytical expressions for the quantum phase fluctuation parameters due to Carruther's and Nieto are obtained in terms of the coupling constants and the initial photon numbers of the input radiation field. Moreover, we keep ourselves confined to the Pegg-Barnett formalism for measured phase operators. With and without using the RWA, we compare the quantum phase fluctuations for coherent and thermal light coupled to the NDPO. In spite of the significant departures (quantitative), the qualitative features of the phase fluctuation parameters for the input thermal light are identical for NDPO with and without RWA. On the other hand, we report some interesting results of input coherent light coupled to the NDPO which are substantially different from their RWA counterpart. In spite of the various quantum optical phenomena in a NDPO, we claim that it is the first effort where the complete analytical approach towards the solutions and hence the quantum phase fluctuations of input radiation fields coupled to it are obtained beyond rotating wave

  16. Calculation Of Effective Fluid Permeability In Porous Media With Quenched Random Disorder Using The Coherent Potential Approximation

    Science.gov (United States)

    Hristopulos, Dionissios

    2001-03-01

    Quenched random disorder models represent the heterogeneity of the saturated fluid permeability of porous media in steady-state flow conditions. The effective permeability is based on the stochastic average of local fluctuations and measures large-scale effects of the disorder. Explicit calculations of effective permeability require various restrictive assumptions on the disorder distribution, and numerical methods are computationally intensive. We propose a semianalytical approach based on the coherent potential approximation (CPA), used for electronic band structure calculations in disordered semiconductors. The PCPA does not require the restrictions of explicit methods and admits efficient numerical solutions. The PCPA equations yield the exact effective permeability (the harmonic mean), in one spatial dimension. The leading order solution in higher dimensions agrees with the standard perturbation expansion. It is known that the effective permeability of a two-dimensional medium with lognormal disorder is given exactly by the geometric mean. We show that the numerical solutions of the PCPA are in good agreement with the exact expression.

  17. Optical double image security using random phase fractional Fourier domain encoding and phase-retrieval algorithm

    Science.gov (United States)

    Rajput, Sudheesh K.; Nishchal, Naveen K.

    2017-04-01

    We propose a novel security scheme based on the double random phase fractional domain encoding (DRPE) and modified Gerchberg-Saxton (G-S) phase retrieval algorithm for securing two images simultaneously. Any one of the images to be encrypted is converted into a phase-only image using modified G-S algorithm and this function is used as a key for encrypting another image. The original images are retrieved employing the concept of known-plaintext attack and following the DRPE decryption steps with all correct keys. The proposed scheme is also used for encryption of two color images with the help of convolution theorem and phase-truncated fractional Fourier transform. With some modification, the scheme is extended for simultaneous encryption of gray-scale and color images. As a proof-of-concept, simulation results have been presented for securing two gray-scale images, two color images, and simultaneous gray-scale and color images.

  18. Fast conjugate phase image reconstruction based on a Chebyshev approximation to correct for B0 field inhomogeneity and concomitant gradients.

    Science.gov (United States)

    Chen, Weitian; Sica, Christopher T; Meyer, Craig H

    2008-11-01

    Off-resonance effects can cause image blurring in spiral scanning and various forms of image degradation in other MRI methods. Off-resonance effects can be caused by both B0 inhomogeneity and concomitant gradient fields. Previously developed off-resonance correction methods focus on the correction of a single source of off-resonance. This work introduces a computationally efficient method of correcting for B0 inhomogeneity and concomitant gradients simultaneously. The method is a fast alternative to conjugate phase reconstruction, with the off-resonance phase term approximated by Chebyshev polynomials. The proposed algorithm is well suited for semiautomatic off-resonance correction, which works well even with an inaccurate or low-resolution field map. The proposed algorithm is demonstrated using phantom and in vivo data sets acquired by spiral scanning. Semiautomatic off-resonance correction alone is shown to provide a moderate amount of correction for concomitant gradient field effects, in addition to B0 imhomogeneity effects. However, better correction is provided by the proposed combined method. The best results were produced using the semiautomatic version of the proposed combined method.

  19. Improvement of the image quality of random phase--free holography using an iterative method

    CERN Document Server

    Shimobaba, Tomoyoshi; Endo, Yutaka; Hirayama, Ryuji; Hiyama, Daisuke; Hasegawa, Satoki; Nagahama, Yuki; Sano, Marie; Oikawa, Minoru; Sugie, Takashige; Ito, Tomoyoshi

    2015-01-01

    Our proposed method of random phase-free holography using virtual convergence light can obtain large reconstructed images exceeding the size of the hologram, without the assistance of random phase. The reconstructed images have low-speckle noise in the amplitude and phase-only holograms (kinoforms); however, in low-resolution holograms, we obtain a degraded image quality compared to the original image. We propose an iterative random phase-free method with virtual convergence light to address this problem.

  20. Cramer-Rao Bounds for M-PSK Packets with Random Phase

    Science.gov (United States)

    Drake, Jeffrey

    1999-01-01

    In this paper, we derive new Cramer-Rao bounds (CRBs) for the estimation of phase from a block of random M-PSK (M=8) symbols for the case where the phase to be estimated is a random variable(r.v.). Existing bounds for 2 and 4-PSK which model the phase as non-random are extended to obtain a new 8-PSK CRB. The new bound which models the phase as a r.v. is compared to the new 8-PSK bound which models the phase as non-random. With 8-PSK we see clearly that use of the random phase CRB more accurately models the behavior if the phase, as normally happens, is supposed to be constrained to the interval [-pi/M,pi/M).

  1. Bilayer technique and nano-filled coating increase success of approximal ART restorations: a randomized clinical trial

    NARCIS (Netherlands)

    Hesse, D.; Bonifácio, C.C.; de Almeida Brandão Guglielmi, C.; Bönecker, M.; van Amerongen, W.E.; Raggio, D.P.

    2016-01-01

    Background. The high-viscosity consistency of glass ionomer cement (GIC) may lead to its incorrect adaptation into the cavity and therefore to restoration failure. Aim. To compare two different insertion techniques for GIC in approximal atraumatic restorative treatment (ART) restorations and two

  2. Approximate Forward Difference Equations for the Lower Order Non-Stationary Statistics of Geometrically Non-Linear Systems subject to Random Excitation

    DEFF Research Database (Denmark)

    Köylüoglu, H. U.; Nielsen, Søren R. K.; Cakmak, A. S.

    Geometrically non-linear multi-degree-of-freedom (MDOF) systems subject to random excitation are considered. New semi-analytical approximate forward difference equations for the lower order non-stationary statistical moments of the response are derived from the stochastic differential equations...... of motion, and, the accuracy of these equations is numerically investigated. For stationary excitations, the proposed method computes the stationary statistical moments of the response from the solution of non-linear algebraic equations....

  3. Stochastic-shielding approximation of Markov chains and its application to efficiently simulate random ion-channel gating.

    Science.gov (United States)

    Schmandt, Nicolaus T; Galán, Roberto F

    2012-09-14

    Markov chains provide realistic models of numerous stochastic processes in nature. We demonstrate that in any Markov chain, the change in occupation number in state A is correlated to the change in occupation number in state B if and only if A and B are directly connected. This implies that if we are only interested in state A, fluctuations in B may be replaced with their mean if state B is not directly connected to A, which shortens computing time considerably. We show the accuracy and efficacy of our approximation theoretically and in simulations of stochastic ion-channel gating in neurons.

  4. Convergence of quasi-optimal sparse-grid approximation of Hilbert-space-valued functions: application to random elliptic PDEs

    KAUST Repository

    Nobile, F.

    2015-10-30

    In this work we provide a convergence analysis for the quasi-optimal version of the sparse-grids stochastic collocation method we presented in a previous work: “On the optimal polynomial approximation of stochastic PDEs by Galerkin and collocation methods” (Beck et al., Math Models Methods Appl Sci 22(09), 2012). The construction of a sparse grid is recast into a knapsack problem: a profit is assigned to each hierarchical surplus and only the most profitable ones are added to the sparse grid. The convergence rate of the sparse grid approximation error with respect to the number of points in the grid is then shown to depend on weighted summability properties of the sequence of profits. This is a very general argument that can be applied to sparse grids built with any uni-variate family of points, both nested and non-nested. As an example, we apply such quasi-optimal sparse grids to the solution of a particular elliptic PDE with stochastic diffusion coefficients, namely the “inclusions problem”: we detail the convergence estimates obtained in this case using polynomial interpolation on either nested (Clenshaw–Curtis) or non-nested (Gauss–Legendre) abscissas, verify their sharpness numerically, and compare the performance of the resulting quasi-optimal grids with a few alternative sparse-grid construction schemes recently proposed in the literature.

  5. Deep Learning the Quantum Phase Transitions in Random Two-Dimensional Electron Systems

    Science.gov (United States)

    Ohtsuki, Tomoki; Ohtsuki, Tomi

    2016-12-01

    Random electron systems show rich phases such as Anderson insulator, diffusive metal, quantum Hall and quantum anomalous Hall insulators, Weyl semimetal, as well as strong/weak topological insulators. Eigenfunctions of each matter phase have specific features, but owing to the random nature of systems, determining the matter phase from eigenfunctions is difficult. Here, we propose the deep learning algorithm to capture the features of eigenfunctions. Localization-delocalization transition, as well as disordered Chern insulator-Anderson insulator transition, is discussed.

  6. The relationship between multilevel models and non-parametric multilevel mixture models: Discrete approximation of intraclass correlation, random coefficient distributions, and residual heteroscedasticity.

    Science.gov (United States)

    Rights, Jason D; Sterba, Sonya K

    2016-11-01

    Multilevel data structures are common in the social sciences. Often, such nested data are analysed with multilevel models (MLMs) in which heterogeneity between clusters is modelled by continuously distributed random intercepts and/or slopes. Alternatively, the non-parametric multilevel regression mixture model (NPMM) can accommodate the same nested data structures through discrete latent class variation. The purpose of this article is to delineate analytic relationships between NPMM and MLM parameters that are useful for understanding the indirect interpretation of the NPMM as a non-parametric approximation of the MLM, with relaxed distributional assumptions. We define how seven standard and non-standard MLM specifications can be indirectly approximated by particular NPMM specifications. We provide formulas showing how the NPMM can serve as an approximation of the MLM in terms of intraclass correlation, random coefficient means and (co)variances, heteroscedasticity of residuals at level 1, and heteroscedasticity of residuals at level 2. Further, we discuss how these relationships can be useful in practice. The specific relationships are illustrated with simulated graphical demonstrations, and direct and indirect interpretations of NPMM classes are contrasted. We provide an R function to aid in implementing and visualizing an indirect interpretation of NPMM classes. An empirical example is presented and future directions are discussed. © 2016 The British Psychological Society.

  7. NIMROD: a program for inference via a normal approximation of the posterior in models with random effects based on ordinary differential equations.

    Science.gov (United States)

    Prague, Mélanie; Commenges, Daniel; Guedj, Jérémie; Drylewicz, Julia; Thiébaut, Rodolphe

    2013-08-01

    Models based on ordinary differential equations (ODE) are widespread tools for describing dynamical systems. In biomedical sciences, data from each subject can be sparse making difficult to precisely estimate individual parameters by standard non-linear regression but information can often be gained from between-subjects variability. This makes natural the use of mixed-effects models to estimate population parameters. Although the maximum likelihood approach is a valuable option, identifiability issues favour Bayesian approaches which can incorporate prior knowledge in a flexible way. However, the combination of difficulties coming from the ODE system and from the presence of random effects raises a major numerical challenge. Computations can be simplified by making a normal approximation of the posterior to find the maximum of the posterior distribution (MAP). Here we present the NIMROD program (normal approximation inference in models with random effects based on ordinary differential equations) devoted to the MAP estimation in ODE models. We describe the specific implemented features such as convergence criteria and an approximation of the leave-one-out cross-validation to assess the model quality of fit. In pharmacokinetics models, first, we evaluate the properties of this algorithm and compare it with FOCE and MCMC algorithms in simulations. Then, we illustrate NIMROD use on Amprenavir pharmacokinetics data from the PUZZLE clinical trial in HIV infected patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Approximation Clustering

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Approximation Clustering. Clustering within (1+ ε) of the optimum cost. ε is user defined tolerance. For metric spaces even approximating is. hard (below, say 30%). Euclidean k-median in fixed dimension can. be approximated in polynomial time.

  9. Shaping the spectrum of random-phase radar waveforms

    Science.gov (United States)

    Doerry, Armin W.; Marquette, Brandeis

    2017-05-09

    The various technologies presented herein relate to generation of a desired waveform profile in the form of a spectrum of apparently random noise (e.g., white noise or colored noise), but with precise spectral characteristics. Hence, a waveform profile that could be readily determined (e.g., by a spoofing system) is effectively obscured. Obscuration is achieved by dividing the waveform into a series of chips, each with an assigned frequency, wherein the sequence of chips are subsequently randomized. Randomization can be a function of the application of a key to the chip sequence. During processing of the echo pulse, a copy of the randomized transmitted pulse is recovered or regenerated against which the received echo is correlated. Hence, with the echo energy range-compressed in this manner, it is possible to generate a radar image with precise impulse response.

  10. ON THE NUMERICAL APPROXIMATION OF THE NONLINEAR PHASE-FIELD EQUATION SUPPLIED WITH NON-HOMOGENEOUS DYNAMIC BOUNDARY CONDITIONS. CASE 1D

    Directory of Open Access Journals (Sweden)

    Costic˘a Moro¸sanu

    2015-07-01

    Full Text Available The paper is concerned with the numerical analysis of a scheme of fractional steps type, associated to the nonlinear phase-field (AllenCahn equation, endowed with non-homogeneous dynamic boundary conditions (depending both on the time and space variables. To approximate the solution of the linear parabolic equation, introduced by such approximating schemes, a first-order IMplicit Backward Differentiation Formula (1-IMBDF is considered. A conceptual numerical algorithm and numerical experiments in one dimension are performed too.

  11. Accelerated three-dimensional cine phase contrast imaging using randomly undersampled echo planar imaging with compressed sensing reconstruction.

    Science.gov (United States)

    Basha, Tamer A; Akçakaya, Mehmet; Goddu, Beth; Berg, Sophie; Nezafat, Reza

    2015-01-01

    The aim of this study was to implement and evaluate an accelerated three-dimensional (3D) cine phase contrast MRI sequence by combining a randomly sampled 3D k-space acquisition sequence with an echo planar imaging (EPI) readout. An accelerated 3D cine phase contrast MRI sequence was implemented by combining EPI readout with randomly undersampled 3D k-space data suitable for compressed sensing (CS) reconstruction. The undersampled data were then reconstructed using low-dimensional structural self-learning and thresholding (LOST). 3D phase contrast MRI was acquired in 11 healthy adults using an overall acceleration of 7 (EPI factor of 3 and CS rate of 3). For comparison, a single two-dimensional (2D) cine phase contrast scan was also performed with sensitivity encoding (SENSE) rate 2 and approximately at the level of the pulmonary artery bifurcation. The stroke volume and mean velocity in both the ascending and descending aorta were measured and compared between two sequences using Bland-Altman plots. An average scan time of 3 min and 30 s, corresponding to an acceleration rate of 7, was achieved for 3D cine phase contrast scan with one direction flow encoding, voxel size of 2 × 2 × 3 mm(3) , foot-head coverage of 6 cm and temporal resolution of 30 ms. The mean velocity and stroke volume in both the ascending and descending aorta were statistically equivalent between the proposed 3D sequence and the standard 2D cine phase contrast sequence. The combination of EPI with a randomly undersampled 3D k-space sampling sequence using LOST reconstruction allows a seven-fold reduction in scan time of 3D cine phase contrast MRI without compromising blood flow quantification. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Higher-order approximation of the phase transition in the Pb-based perovskite oxide solid-solutions

    Science.gov (United States)

    Li, Lin; Kim, Ilhwan; Jang, Kumok; Ri, Kwangson; Cha, Jongchol

    2013-07-01

    It is shown that the ferroelectric phase transitions in the mixture compounds PbZr1-xTixO3 (PZT), Pb(Mg1/3Nb2/3)1-xTixO3 (PMN-PT), and Pb(Zn1/3Nb2/3)1-xTixO3 (PZN-PT) are described by a twelfth-order expansion of the Landau potential in terms of the phenomenological order parameter. Classical Poincaré transformation is used in constructing the appropriate Landau potential. Our consideration requires two more basic monomials, a 10th-order invariant and a 12th-order one, to be present than the previous model. A phase diagram is calculated in phenomenological parameter space. T-x phase diagrams for the PZT and PZN-PT are estimated. The PbTiO3-concentration dependence of physical properties is calculated in the vicinity of the morphotropic phase boundary.

  13. Study of solid-liquid phase transition using the modified weighted density approximation of inhomogeneous hard sphere systems

    Directory of Open Access Journals (Sweden)

    Mahmood Moradi

    2007-09-01

    Full Text Available  In this article we first introduce the weighted density approximation (WDA to study the classical inhomogeneous system such as inhomogeneous fluids. Then we introduce the modified weighted density approximation (MWDA to calculate the structure and thermodynamical properties of the FCC hard sphere crystal. The MWDA is a self consistent method where the free energy is expressed as an unperturbed expression. Usually the required input is the Percus-Yevick (PY direct correlation function of hard sphere. In addition to this, we use the hard sphere DCF introduced by Roth et al. [ J. Phys. Condense Matter, 14, 12063 (2002. ], here we call it RELK, we also introduce a new expression for the DCF which is a combination of the PY and RELK. This new expression gives the best result for the DCF of hard sphere, as it compared with the Monte Carlo simulation. In our calculation we use all these DCFs to calculate the free energy and freezing parameters of FCC hard sphere crystals. Although we obtained the better results using the PY-RELK DCF but it seems we should improve the MWDA to get better result.

  14. Double blind randomized phase II study with radiation + 5-fluorouracil ± celecoxib for resectable rectal cancer

    National Research Council Canada - National Science Library

    Debucquoy, Annelies; Roels, Sarah; Goethals, Laurence; Libbrecht, Louis; Cutsem, Eric Van; Geboes, Karel; Penninckx, Freddy; D’Hoore, André; McBride, William H; Haustermans, Karin

    2009-01-01

    To assess the feasibility and efficacy of the COX-2 inhibitor celecoxib in conjunction with preoperative chemoradiation for patients with locally advanced rectal cancer in a double blind randomized phase II study...

  15. Optical image transformation and encryption by phase-retrieval-based double random-phase encoding and compressive ghost imaging

    Science.gov (United States)

    Yuan, Sheng; Yang, Yangrui; Liu, Xuemei; Zhou, Xin; Wei, Zhenzhuo

    2018-01-01

    An optical image transformation and encryption scheme is proposed based on double random-phase encoding (DRPE) and compressive ghost imaging (CGI) techniques. In this scheme, a secret image is first transformed into a binary image with the phase-retrieval-based DRPE technique, and then encoded by a series of random amplitude patterns according to the ghost imaging (GI) principle. Compressive sensing, corrosion and expansion operations are implemented to retrieve the secret image in the decryption process. This encryption scheme takes the advantage of complementary capabilities offered by the phase-retrieval-based DRPE and GI-based encryption techniques. That is the phase-retrieval-based DRPE is used to overcome the blurring defect of the decrypted image in the GI-based encryption, and the CGI not only reduces the data amount of the ciphertext, but also enhances the security of DRPE. Computer simulation results are presented to verify the performance of the proposed encryption scheme.

  16. Fractional Fourier domain optical image hiding using phase retrieval algorithm based on iterative nonlinear double random phase encoding.

    Science.gov (United States)

    Wang, Xiaogang; Chen, Wen; Chen, Xudong

    2014-09-22

    We present a novel image hiding method based on phase retrieval algorithm under the framework of nonlinear double random phase encoding in fractional Fourier domain. Two phase-only masks (POMs) are efficiently determined by using the phase retrieval algorithm, in which two cascaded phase-truncated fractional Fourier transforms (FrFTs) are involved. No undesired information disclosure, post-processing of the POMs or digital inverse computation appears in our proposed method. In order to achieve the reduction in key transmission, a modified image hiding method based on the modified phase retrieval algorithm and logistic map is further proposed in this paper, in which the fractional orders and the parameters with respect to the logistic map are regarded as encryption keys. Numerical results have demonstrated the feasibility and effectiveness of the proposed algorithms.

  17. Speeding up image quality improvement in random phase-free holograms using ringing artifact characteristics.

    Science.gov (United States)

    Nagahama, Yuki; Shimobaba, Tomoyoshi; Kakue, Takashi; Masuda, Nobuyuki; Ito, Tomoyoshi

    2017-05-01

    A holographic projector utilizes holography techniques. However, there are several barriers to realizing holographic projections. One is deterioration of hologram image quality caused by speckle noise and ringing artifacts. The combination of the random phase-free method and the Gerchberg-Saxton (GS) algorithm has improved the image quality of holograms. However, the GS algorithm requires significant computation time. We propose faster methods for image quality improvement of random phase-free holograms using the characteristics of ringing artifacts.

  18. Prediction of friction pressure drop for low pressure two-phase flows on the basis of approximate analytical models

    Science.gov (United States)

    Zubov, N. O.; Kaban'kov, O. N.; Yagov, V. V.; Sukomel, L. A.

    2017-12-01

    Wide use of natural circulation loops operating at low redused pressures generates the real need to develop reliable methods for predicting flow regimes and friction pressure drop for two-phase flows in this region of parameters. Although water-air flows at close-to-atmospheric pressures are the most widely studied subject in the field of two-phase hydrodynamics, the problem of reliably calculating friction pressure drop can hardly be regarded to have been fully solved. The specific volumes of liquid differ very much from those of steam (gas) under such conditions, due to which even a small change in flow quality may cause the flow pattern to alter very significantly. Frequently made attempts to use some or another universal approach to calculating friction pressure drop in a wide range of steam quality values do not seem to be justified and yield predicted values that are poorly consistent with experimentally measured data. The article analyzes the existing methods used to calculate friction pressure drop for two-phase flows at low pressures by comparing their results with the experimentally obtained data. The advisability of elaborating calculation procedures for determining the friction pressure drop and void fraction for two-phase flows taking their pattern (flow regime) into account is demonstrated. It is shown that, for flows characterized by low reduced pressures, satisfactory results are obtained from using a homogeneous model for quasi-homogeneous flows, whereas satisfactory results are obtained from using an annular flow model for flows characterized by high values of void fraction. Recommendations for making a shift from one model to another in carrying out engineering calculations are formulated and tested. By using the modified annular flow model, it is possible to obtain reliable predictions for not only the pressure gradient but also for the liquid film thickness; the consideration of droplet entrainment and deposition phenomena allows reasonable

  19. High-resolution STEM imaging with a quadrant detector--conditions for differential phase contrast microscopy in the weak phase object approximation.

    Science.gov (United States)

    Majert, S; Kohl, H

    2015-01-01

    Differential phase contrast is a contrast mechanism that can be utilized in the scanning transmission electron microscope (STEM) to determine the distribution of magnetic or electric fields. In practice, several different detector geometries can be used to obtain differential phase contrast. As recent high resolution differential phase contrast experiments with the STEM are focused on ring quadrant detectors, we evaluate the contrast transfer characteristics of different quadrant detector geometries, namely two ring quadrant detectors with different inner detector angles and a conventional quadrant detector, by calculating the corresponding phase gradient transfer functions. For an ideal microscope and a weak phase object, this can be done analytically. The calculated phase gradient transfer functions indicate that the barely illuminated ring quadrant detector setup used for imaging magnetic fields in the specimen reduces the resolution limit to about 2.5Å for an aberration corrected STEM. Our results show that the resolution can be drastically improved by using a conventional quadrant detector instead. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Is there a spin-glass phase in the random temperature Ising ferromagnet?

    Energy Technology Data Exchange (ETDEWEB)

    Tarjus, Gilles; Dotsenko, Victor [Laboratoire de Physique Theorique des Liquides, UMR 7600, Universite Paris VI, Paris (France)

    2002-02-22

    In this paper we study the phase diagram of the disordered Ising ferromagnet. Within the framework of the Gaussian variational approximation it is shown that in systems with a finite value of the disorder in dimensions D=4 and D<4 the paramagnetic and ferromagnetic phases are separated by a spin-glass phase. The transition from paramagnetic to spin-glass state is continuous (second order), whereas the transition between spin-glass and ferromagnetic states is discontinuous (first order). It is also shown that within the considered approximation there is no replica symmetry breaking in the spin-glass phase. The validity of the Gaussian variational approximation for the present problem is discussed, and we provide a tentative physical interpretation of the results. (author)

  1. Multiple-wavelength double random phase encoding with CCD-plane sparse-phase multiplexing for optical information verification.

    Science.gov (United States)

    Chen, Wen

    2015-12-20

    A novel method is proposed by using multiple-wavelength double random phase encoding (MW-DRPE) with CCD-plane sparse-phase multiplexing for optical information verification. Two different strategies are applied to conduct sparse-phase multiplexing in the CCD plane. The results demonstrate that large capacity can be achieved for optical multiple-image verification. The proposed optical verification strategy is implemented based on optical encoding, and the keys generated by optical encryption can further guarantee the safety of the designed optical multiple-image verification system. The proposed method provides a novel alternative for DRPE-based optical information verification.

  2. Three Phase Power Imbalance Decomposition into Systematic Imbalance and Random Imbalance

    DEFF Research Database (Denmark)

    Kong, Wangwei; Ma, Kang; Wu, Qiuwei

    2017-01-01

    is calculated based on the systematic imbalance component to guide phase swapping. Case studies demonstrate that 72.8% of 782 low voltage substations have systematic imbalance components. The degree of power imbalance results reveal the maximum need for phase swapping and the random imbalance components reveal...

  3. A Randomized Double-Blind Crossover Study of Phase-Shift Sound Therapy for Tinnitus

    NARCIS (Netherlands)

    Heijneman, Karin M.; de Kleine, Emile; van Dijk, Pim

    Objective. The purpose of this study was to compare the efficacy of the treatment of tinnitus with a phase-shifting pure tone to that of the same tone treatment without phase shifting. Study Design. A double-blind crossover randomized controlled trial. Setting. This study was conducted at the

  4. Assessing the performance of the random phase approximation for exchange and superexchange coupling constants in magnetic crystalline solids

    DEFF Research Database (Denmark)

    Olsen, Thomas

    2017-01-01

    . It is found that the RPA can accurately correct the large errors introduced by Hartree- Fock, independent of the input orbitals used for the perturbative expansion. However, in most cases, accuracies similar to RPA can be obtained with DFT+ U, which is significantly simpler from a computational point of view....

  5. Minocycline in Acute Cerebral Hemorrhage: An Early Phase Randomized Trial.

    Science.gov (United States)

    Fouda, Abdelrahman Y; Newsome, Andrea S; Spellicy, Samantha; Waller, Jennifer L; Zhi, Wenbo; Hess, David C; Ergul, Adviye; Edwards, David J; Fagan, Susan C; Switzer, Jeffrey A

    2017-10-01

    Minocycline is under investigation as a neurovascular protective agent for stroke. This study evaluated the pharmacokinetic, anti-inflammatory, and safety profile of minocycline after intracerebral hemorrhage. This study was a single-site, randomized controlled trial of minocycline conducted from 2013 to 2016. Adults ≥18 years with primary intracerebral hemorrhage who could have study drug administered within 24 hours of onset were included. Patients received 400 mg of intravenous minocycline, followed by 400 mg minocycline oral daily for 4 days. Serum concentrations of minocycline after the last oral dose and biomarkers were sampled to determine the peak concentration, half-life, and anti-inflammatory profile. A total of 16 consecutive eligible patients were enrolled, with 8 randomized to minocycline. Although the literature supports a time to peak concentration (Tmax) of 1 hour for oral minocycline, the Tmax was estimated to be at least 6 hours in this cohort. The elimination half-life (available on 7 patients) was 17.5 hours (SD±3.5). No differences were observed in inflammatory biomarkers, hematoma volume, or perihematomal edema. Concentrations remained at neuroprotective levels (>3 mg/L) throughout the dosing interval in 5 of 7 patients. In intracerebral hemorrhage, a 400 mg dose of minocycline was safe and achieved neuroprotective serum concentrations. However, oral administration led to delayed absorption in these critically ill patients and should not be used when rapid, high concentrations are desired. Given the safety and pharmacokinetic profile of minocycline in intracerebral hemorrhage and promising data in the treatment of ischemic stroke, intravenous minocycline is an excellent candidate for a prehospital treatment trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01805895. © 2017 American Heart Association, Inc.

  6. A quantum method for thermal rate constant calculations from stationary phase approximation of the thermal flux-flux correlation function integral.

    Science.gov (United States)

    Aieta, Chiara; Ceotto, Michele

    2017-06-07

    This paper presents a quantum mechanical approximation to the calculation of thermal rate constants. The rate is derived from a suitable stationary phase approximation to the time integral of the thermal flux-flux correlation function. The goal is to obtain an expression that barely depends on the position of the flux operators, i.e., of the dividing surfaces, so that it can be applied also to complex systems by arbitrarily locating the dividing surfaces. The approach is tested on one and two dimensional systems where quantum effects are predominant over a wide range of temperatures. The results are quite accurate, i.e., within a few percent of the exact values for a reasonable range of dividing surface positions.

  7. Equilibrium phase diagram of a randomly pinned glass-former.

    Science.gov (United States)

    Ozawa, Misaki; Kob, Walter; Ikeda, Atsushi; Miyazaki, Kunimasa

    2015-06-02

    We use computer simulations to study the thermodynamic properties of a glass-former in which a fraction c of the particles has been permanently frozen. By thermodynamic integration, we determine the Kauzmann, or ideal glass transition, temperature [Formula: see text] at which the configurational entropy vanishes. This is done without resorting to any kind of extrapolation, i.e., [Formula: see text] is indeed an equilibrium property of the system. We also measure the distribution function of the overlap, i.e., the order parameter that signals the glass state. We find that the transition line obtained from the overlap coincides with that obtained from the thermodynamic integration, thus showing that the two approaches give the same transition line. Finally, we determine the geometrical properties of the potential energy landscape, notably the T- and c dependence of the saddle index, and use these properties to obtain the dynamic transition temperature [Formula: see text]. The two temperatures [Formula: see text] and [Formula: see text] cross at a finite value of c and indicate the point at which the glass transition line ends. These findings are qualitatively consistent with the scenario proposed by the random first-order transition theory.

  8. Phase microscopy of technical and biological samples through random phase modulation with a difuser

    DEFF Research Database (Denmark)

    Almoro, Percival; Pedrini, Giancarlo; Gundu, Phanindra Narayan

    2010-01-01

    A technique for phase microscopy using a phase diffuser and a reconstruction algorithm is proposed. A magnified specimen wavefront is projected on the diffuser plane that modulates the wavefront into a speckle field. The speckle patterns at axially displaced planes are sampled and used in an iter...

  9. Isolobal analogies in intermetallics: the reversed approximation MO approach and applications to CrGa4- and Ir3Ge7-type phases.

    Science.gov (United States)

    Yannello, Vincent J; Kilduff, Brandon J; Fredrickson, Daniel C

    2014-03-03

    Intermetallic phases offer a wealth of unique and unexplained structural features, which pose exciting challenges for the development of new bonding concepts. In this article, we present a straightforward approach to rapidly building bonding descriptions of such compounds: the reversed approximation Molecular Orbital (raMO) method. In this approach, we reverse the usual technique of using linear combinations of simple functions to approximate true wave functions and employ the fully occupied crystal orbitals of a compound as a basis set for the determination of the eigenfunctions of a simple, chemically transparent model Hamiltonian. The solutions fall into two sets: (1) a series of functions representing the best-possible approximations to the model system's eigenstates constructible from the occupied crystal orbitals and (2) a second series of functions that are orthogonal to the bonding picture represented by the model Hamiltonian. The electronic structure of a compound is thus quickly resolved into a series of orthogonal bonding subsystems. We first demonstrate the raMO analysis on a familiar molecule, 1,3-butadiene, and then move to illustrating its use in discovering new bonding phenomena through applications to three intermetallic phases: the PtHg4-type CrGa4 and the Ir3Ge7-type compounds Os3Sn7 and Ir3Sn7. For CrGa4, a density of states (DOS) minimum coinciding with its Fermi energy is traced to 18-electron configurations on the Cr atoms. For Os3Sn7 and Ir3Sn7, 18-electron configurations also underlie DOS pseudogaps. This time, however, the 18-electron counts involve multicenter interactions isolobal with classical Ir-Ir or Os-Os covalent bonds, as well as Sn-Sn single bonds serving as electron reservoirs. Our results are based on DFT-calibrated Hückel calculations, but in principle the raMO analysis can be implemented in any method employing one-electron wave functions.

  10. UA(1) breaking and phase transition in chiral random matrix model

    OpenAIRE

    Sano, T.; Fujii, H.; Ohtani, M

    2009-01-01

    We propose a chiral random matrix model which properly incorporates the flavor-number dependence of the phase transition owing to the \\UA(1) anomaly term. At finite temperature, the model shows the second-order phase transition with mean-field critical exponents for two massless flavors, while in the case of three massless flavors the transition turns out to be of the first order. The topological susceptibility satisfies the anomalous \\UA(1) Ward identity and decreases gradually with the temp...

  11. Approximate Riemann solvers and flux vector splitting schemes for two-phase flow; Solveurs de Riemann approches et schemas de decentrement de flux pour les ecoulements diphasiques

    Energy Technology Data Exchange (ETDEWEB)

    Toumi, I.; Kumbaro, A.; Paillere, H

    1999-07-01

    These course notes, presented at the 30. Von Karman Institute Lecture Series in Computational Fluid Dynamics, give a detailed and through review of upwind differencing methods for two-phase flow models. After recalling some fundamental aspects of two-phase flow modelling, from mixture model to two-fluid models, the mathematical properties of the general 6-equation model are analysed by examining the Eigen-structure of the system, and deriving conditions under which the model can be made hyperbolic. The following chapters are devoted to extensions of state-of-the-art upwind differencing schemes such as Roe's Approximate Riemann Solver or the Characteristic Flux Splitting method to two-phase flow. Non-trivial steps in the construction of such solvers include the linearization, the treatment of non-conservative terms and the construction of a Roe-type matrix on which the numerical dissipation of the schemes is based. Extension of the 1-D models to multi-dimensions in an unstructured finite volume formulation is also described; Finally, numerical results for a variety of test-cases are shown to illustrate the accuracy and robustness of the methods. (authors)

  12. Deterministic matrices matching the compressed sensing phase transitions of Gaussian random matrices

    Science.gov (United States)

    Monajemi, Hatef; Jafarpour, Sina; Gavish, Matan; Donoho, David L.; Ambikasaran, Sivaram; Bacallado, Sergio; Bharadia, Dinesh; Chen, Yuxin; Choi, Young; Chowdhury, Mainak; Chowdhury, Soham; Damle, Anil; Fithian, Will; Goetz, Georges; Grosenick, Logan; Gross, Sam; Hills, Gage; Hornstein, Michael; Lakkam, Milinda; Lee, Jason; Li, Jian; Liu, Linxi; Sing-Long, Carlos; Marx, Mike; Mittal, Akshay; Monajemi, Hatef; No, Albert; Omrani, Reza; Pekelis, Leonid; Qin, Junjie; Raines, Kevin; Ryu, Ernest; Saxe, Andrew; Shi, Dai; Siilats, Keith; Strauss, David; Tang, Gary; Wang, Chaojun; Zhou, Zoey; Zhu, Zhen

    2013-01-01

    In compressed sensing, one takes samples of an N-dimensional vector using an matrix A, obtaining undersampled measurements . For random matrices with independent standard Gaussian entries, it is known that, when is k-sparse, there is a precisely determined phase transition: for a certain region in the (,)-phase diagram, convex optimization typically finds the sparsest solution, whereas outside that region, it typically fails. It has been shown empirically that the same property—with the same phase transition location—holds for a wide range of non-Gaussian random matrix ensembles. We report extensive experiments showing that the Gaussian phase transition also describes numerous deterministic matrices, including Spikes and Sines, Spikes and Noiselets, Paley Frames, Delsarte-Goethals Frames, Chirp Sensing Matrices, and Grassmannian Frames. Namely, for each of these deterministic matrices in turn, for a typical k-sparse object, we observe that convex optimization is successful over a region of the phase diagram that coincides with the region known for Gaussian random matrices. Our experiments considered coefficients constrained to for four different sets , and the results establish our finding for each of the four associated phase transitions. PMID:23277588

  13. Approximate Likelihood

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    Most physics results at the LHC end in a likelihood ratio test. This includes discovery and exclusion for searches as well as mass, cross-section, and coupling measurements. The use of Machine Learning (multivariate) algorithms in HEP is mainly restricted to searches, which can be reduced to classification between two fixed distributions: signal vs. background. I will show how we can extend the use of ML classifiers to distributions parameterized by physical quantities like masses and couplings as well as nuisance parameters associated to systematic uncertainties. This allows for one to approximate the likelihood ratio while still using a high dimensional feature vector for the data. Both the MEM and ABC approaches mentioned above aim to provide inference on model parameters (like cross-sections, masses, couplings, etc.). ABC is fundamentally tied Bayesian inference and focuses on the “likelihood free” setting where only a simulator is available and one cannot directly compute the likelihood for the dat...

  14. Methadone induction in primary care (ANRS-Methaville: a phase III randomized intervention trial

    Directory of Open Access Journals (Sweden)

    Roux Perrine

    2012-06-01

    Full Text Available Abstract Background In France, the rapid scale-up of buprenorphine, an opioid maintenance treatment (OMT, in primary care for drug users has led to an impressive reduction in HIV prevalence among injecting drug users (IDU but has had no major effect on Hepatitis C incidence. To date, patients willing to start methadone can only do so in a methadone clinic (a medical centre for drug and alcohol dependence (CSAPA or a hospital setting and are referred to primary care physicians after dose stabilization. This study aims to assess the effectiveness of methadone in patients who initiated treatment in primary care compared with those who initiated it in a CSAPA, by measuring abstinence from street opioid use after one year of treatment. Methods/Design The ANRS-Methaville study is a randomized multicenter non-inferiority control trial comparing methadone induction (lasting approximately 2 weeks in primary care and in CSAPA. The model of care chosen for methadone induction in primary care was based on study-specific pre-training of all physicians, exclusion criteria and daily supervision of methadone during the initiation phase. Between January 2009 and January 2011, 10 sites each having one CSAPA and several primary care physicians, were identified to recruit patients to be randomized into two groups, one starting methadone in primary care (n = 147, the other in CSAPA (n = 48. The primary outcome of the study is the proportion of participants abstinent from street opioids after 1 year of treatment i.e. non-inferiority of primary care model in terms of the proportion of patients not using street opioids compared with the proportion observed in those starting methadone in a CSAPA. Discussion The ANRS-Methaville study is the first in France to use an interventional trial to improve access to OMT for drug users. Once the non-inferiority results become available, the Ministry of Health and agency for the safety of health products may change the the

  15. Fractional Fourier transform-based optical encryption with treble random phase-encoding

    Science.gov (United States)

    Xin, Yi; Tao, Ran; Wang, Yue

    2008-03-01

    We propose a new architecture of optical encryption technique using the fractional Fourier transform with three statistically independent random phase masks. Compared with the existing double-phase encoding method in the fractional Fourier-domain, the proposed extra phase mask in the last fractional Fourier domain makes the architecture symmetrical, and additive processing to the encrypted image can be turned into complex stationary white noise after decryption, and enlarge the key space without any degradation of its robustness to blind decryption. This property can be utilized to improve the quality of the recover image. Simulation results have verified the validity.

  16. Generation of sound by Alfven waves with random phases in the solar atmosphere

    Energy Technology Data Exchange (ETDEWEB)

    Petrukhin, N.S.; Fainshtein, S.M.

    1976-11-01

    The problem of the excitation of sound by Alfven waves meeting in the solar plasma is discussed. Kinetic equations for the interacting waves are derived and analyzed on the assumption that the Alfven waves have random phases. Estimates are given which show the possibility of the generation of LF-pulsations in the solar atmosphere.

  17. Nanostructure-property relations for phase-change random access memory (PCRAM) line cells

    NARCIS (Netherlands)

    Kooi, B. J.; Oosthoek, J. L. M.; Verheijen, M. A.; Kaiser, M.; Jedema, F. J.; Gravesteijn, D. J.

    2012-01-01

    Phase-change random access memory (PCRAM) cells have been studied extensively using electrical characterization and rather limited by detailed structure characterization. The combination of these two characterization techniques has hardly been exploited and it is the focus of the present work.

  18. 3D Multisource Full‐Waveform Inversion using Dynamic Random Phase Encoding

    KAUST Repository

    Boonyasiriwat, Chaiwoot

    2010-10-17

    We have developed a multisource full‐waveform inversion algorithm using a dynamic phase encoding strategy with dual‐randomization—both the position and polarity of simultaneous sources are randomized and changed every iteration. The dynamic dual‐randomization is used to promote the destructive interference of crosstalk noise resulting from blending a large number of common shot gathers into a supergather. We compare our multisource algorithm with various algorithms in a numerical experiment using the 3D SEG/EAGE overthrust model and show that our algorithm provides a higher‐quality velocity tomogram than the other methods that use only monorandomization. This suggests that increasing the degree of randomness in phase encoding should improve the quality of the inversion result.

  19. Security enhanced optical encryption system by random phase key and permutation key.

    Science.gov (United States)

    He, Mingzhao; Tan, Qiaofeng; Cao, Liangcai; He, Qingsheng; Jin, Guofan

    2009-12-07

    Conventional double random phase encoding (DRPE) encrypts plaintext to white noise-like ciphertext which may attract attention of eavesdroppers, and recent research reported that DRPE is vulnerable to various attacks. Here we propose a security enhanced optical encryption system that can hide the existence of secret information by watermarking. The plaintext is encrypted using iterative fractional Fourier transform with random phase key, and ciphertext is randomly permuted with permutation key before watermarking. Cryptanalysis shows that linearity of the security system has been broken and the permutation key prevent the attacker from accessing the ciphertext in various attacks. A series of simulations have shown the effectiveness of this system and the security strength is enhanced for invisibility, nonlinearity and resistance against attacks.

  20. Second-order structural phase transitions, free energy curvature, and temperature-dependent anharmonic phonons in the self-consistent harmonic approximation: Theory and stochastic implementation

    Science.gov (United States)

    Bianco, Raffaello; Errea, Ion; Paulatto, Lorenzo; Calandra, Matteo; Mauri, Francesco

    2017-07-01

    The self-consistent harmonic approximation is an effective harmonic theory to calculate the free energy of systems with strongly anharmonic atomic vibrations, and its stochastic implementation has proved to be an efficient method to study, from first-principles, the anharmonic properties of solids. The free energy as a function of average atomic positions (centroids) can be used to study quantum or thermal lattice instability. In particular the centroids are order parameters in second-order structural phase transitions such as, e.g., charge-density-waves or ferroelectric instabilities. According to Landau's theory, the knowledge of the second derivative of the free energy (i.e., the curvature) with respect to the centroids in a high-symmetry configuration allows the identification of the phase-transition and of the instability modes. In this work we derive the exact analytic formula for the second derivative of the free energy in the self-consistent harmonic approximation for a generic atomic configuration. The analytic derivative is expressed in terms of the atomic displacements and forces in a form that can be evaluated by a stochastic technique using importance sampling. Our approach is particularly suitable for applications based on first-principles density-functional-theory calculations, where the forces on atoms can be obtained with a negligible computational effort compared to total energy determination. Finally, we propose a dynamical extension of the theory to calculate spectral properties of strongly anharmonic phonons, as probed by inelastic scattering processes. We illustrate our method with a numerical application on a toy model that mimics the ferroelectric transition in rock-salt crystals such as SnTe or GeTe.

  1. Deep Learning the Quantum Phase Transitions in Random Electron Systems: Applications to Three Dimensions

    Science.gov (United States)

    Ohtsuki, Tomi; Ohtsuki, Tomoki

    2017-04-01

    Three-dimensional random electron systems undergo quantum phase transitions and show rich phase diagrams. Examples of the phases are the band gap insulator, Anderson insulator, strong and weak topological insulators, Weyl semimetal, and diffusive metal. As in the previous paper on two-dimensional quantum phase transitions [J. Phys. Soc. Jpn. 85, 123706 (2016)], we use an image recognition algorithm based on a multilayered convolutional neural network to identify which phase the eigenfunction belongs to. The Anderson model for localization-delocalization transition, the Wilson-Dirac model for topological insulators, and the layered Chern insulator model for Weyl semimetal are studied. The situation where the standard transfer matrix approach is not applicable is also treated by this method.

  2. Stochastic modeling for starting-time of phase evolution of random seismic ground motions

    Directory of Open Access Journals (Sweden)

    Yongbo Peng

    2014-01-01

    Full Text Available In response to the challenge inherent in classical high-dimensional models of random ground motions, a family of simulation methods for non-stationary seismic ground motions was developed previously through employing a wave-group propagation formulation with phase spectrum model built up on the frequency components' starting-time of phase evolution. The present paper aims at extending the formulation to the simulation of non-stationary random seismic ground motions. The ground motion records associated with N—S component of Northridge Earthquake at the type-II site are investigated. The frequency components' starting-time of phase evolution of is identified from the ground motion records, and is proved to admit the Gamma distribution through data fitting. Numerical results indicate that the simulated random ground motion features zero-mean, non-stationary, and non-Gaussian behaviors, and the phase spectrum model with only a few starting-times of phase evolution could come up with a sound contribution to the simulation.

  3. Double image encryption based on random phase encoding in the fractional Fourier domain.

    Science.gov (United States)

    Tao, Ran; Xin, Yi; Wang, Yue

    2007-11-26

    A novel image encryption method is proposed by utilizing random phase encoding in the fractional Fourier domain to encrypt two images into one encrypted image with stationary white distribution. By applying the correct keys which consist of the fractional orders, the random phase masks and the pixel scrambling operator, the two primary images can be recovered without cross-talk. The decryption process is robust against the loss of data. The phase-based image with a larger key space is more sensitive to keys and disturbances than the amplitude-based image. The pixel scrambling operation improves the quality of the decrypted image when noise perturbation occurs. The novel approach is verified by simulations.

  4. Hacking on decoy-state quantum key distribution system with partial phase randomization

    Science.gov (United States)

    Sun, Shi-Hai; Jiang, Mu-Sheng; Ma, Xiang-Chun; Li, Chun-Yan; Liang, Lin-Mei

    2014-04-01

    Quantum key distribution (QKD) provides means for unconditional secure key transmission between two distant parties. However, in practical implementations, it suffers from quantum hacking due to device imperfections. Here we propose a hybrid measurement attack, with only linear optics, homodyne detection, and single photon detection, to the widely used vacuum + weak decoy state QKD system when the phase of source is partially randomized. Our analysis shows that, in some parameter regimes, the proposed attack would result in an entanglement breaking channel but still be able to trick the legitimate users to believe they have transmitted secure keys. That is, the eavesdropper is able to steal all the key information without discovered by the users. Thus, our proposal reveals that partial phase randomization is not sufficient to guarantee the security of phase-encoding QKD systems with weak coherent states.

  5. Phase-Image Encryption Based on 3D-Lorenz Chaotic System and Double Random Phase Encoding

    Science.gov (United States)

    Sharma, Neha; Saini, Indu; Yadav, AK; Singh, Phool

    2017-12-01

    In this paper, an encryption scheme for phase-images based on 3D-Lorenz chaotic system in Fourier domain under the 4f optical system is presented. The encryption scheme uses a random amplitude mask in the spatial domain and a random phase mask in the frequency domain. Its inputs are phase-images, which are relatively more secure as compared to the intensity images because of non-linearity. The proposed scheme further derives its strength from the use of 3D-Lorenz transform in the frequency domain. Although the experimental setup for optical realization of the proposed scheme has been provided, the results presented here are based on simulations on MATLAB. It has been validated for grayscale images, and is found to be sensitive to the encryption parameters of the Lorenz system. The attacks analysis shows that the key-space is large enough to resist brute-force attack, and the scheme is also resistant to the noise and occlusion attacks. Statistical analysis and the analysis based on correlation distribution of adjacent pixels have been performed to test the efficacy of the encryption scheme. The results have indicated that the proposed encryption scheme possesses a high level of security.

  6. Bayesian phase II adaptive randomization by jointly modeling time-to-event efficacy and binary toxicity.

    Science.gov (United States)

    Lei, Xiudong; Yuan, Ying; Yin, Guosheng

    2011-01-01

    In oncology, toxicity is typically observable shortly after a chemotherapy treatment, whereas efficacy, often characterized by tumor shrinkage, is observable after a relatively long period of time. In a phase II clinical trial design, we propose a Bayesian adaptive randomization procedure that accounts for both efficacy and toxicity outcomes. We model efficacy as a time-to-event endpoint and toxicity as a binary endpoint, sharing common random effects in order to induce dependence between the bivariate outcomes. More generally, we allow the randomization probability to depend on patients' specific covariates, such as prognostic factors. Early stopping boundaries are constructed for toxicity and futility, and a superior treatment arm is recommended at the end of the trial. Following the setup of a recent renal cancer clinical trial at M. D. Anderson Cancer Center, we conduct extensive simulation studies under various scenarios to investigate the performance of the proposed method, and compare it with available Bayesian adaptive randomization procedures.

  7. Role of an encapsulating layer for reducing resistance drift in phase change random access memory

    Directory of Open Access Journals (Sweden)

    Bo Jin

    2014-12-01

    Full Text Available Phase change random access memory (PCRAM devices exhibit a steady increase in resistance in the amorphous phase upon aging and this resistance drift phenomenon directly affects the device reliability. A stress relaxation model is used here to study the effect of a device encapsulating layer material in addressing the resistance drift phenomenon in PCRAM. The resistance drift can be increased or decreased depending on the biaxial moduli of the phase change material (YPCM and the encapsulating layer material (YELM according to the stress relationship between them in the drift regime. The proposed model suggests that the resistance drift can be effectively reduced by selecting a proper material as an encapsulating layer. Moreover, our model explains that reducing the size of the phase change material (PCM while fully reset and reducing the amorphous/crystalline ratio in PCM help to improve the resistance drift, and thus opens an avenue for highly reliable multilevel PCRAM applications.

  8. What makes a phase transition? Analysis of the random satisfiability problem

    Science.gov (United States)

    Zweig, Katharina A.; Palla, Gergely; Vicsek, Tamás

    2010-04-01

    In the last 30 years it was found that many combinatorial systems undergo phase transitions. One of the most important examples of these can be found among the random k-satisfiability problems (often referred to as k-SAT), asking whether there exists an assignment of Boolean values satisfying a Boolean formula composed of clauses with k random variables each. The random 3-SAT problem is reported to show various phase transitions at different critical values of the ratio of the number of clauses to the number of variables. The most famous of these occurs when the probability of finding a satisfiable instance suddenly drops from 1 to 0. This transition is associated with a rise in the hardness of the problem, but until now the correlation between any of the proposed phase transitions and the hardness is not totally clear. In this paper we will first show numerically that the number of solutions universally follows a lognormal distribution, thereby explaining the puzzling question of why the number of solutions is still exponential at the critical point. Moreover we provide evidence that the hardness of the closely related problem of counting the total number of solutions does not show any phase transition-like behavior. This raises the question of whether the probability of finding a satisfiable instance is really an order parameter of a phase transition or whether it is more likely to just show a simple sharp threshold phenomenon. More generally, this paper aims at starting a discussion where a simple sharp threshold phenomenon turns into a genuine phase transition.

  9. Information hiding based on double random-phase encoding and public-key cryptography.

    Science.gov (United States)

    Sheng, Yuan; Xin, Zhou; Alam, Mohammed S; Xi, Lu; Xiao-Feng, Li

    2009-03-02

    A novel information hiding method based on double random-phase encoding (DRPE) and Rivest-Shamir-Adleman (RSA) public-key cryptosystem is proposed. In the proposed technique, the inherent diffusion property of DRPE is cleverly utilized to make up the diffusion insufficiency of RSA public-key cryptography, while the RSA cryptosystem is utilized for simultaneous transmission of the cipher text and the two phase-masks, which is not possible under the DRPE technique. This technique combines the complementary advantages of the DPRE and RSA encryption techniques and brings security and convenience for efficient information transmission. Extensive numerical simulation results are presented to verify the performance of the proposed technique.

  10. Phase-space representation and polarization domains of random electromagnetic fields.

    Science.gov (United States)

    Castaneda, Roman; Betancur, Rafael; Herrera, Jorge; Carrasquilla, Juan

    2008-08-01

    The phase-space representation of stationary random electromagnetic fields is developed by using electromagnetic spatial coherence wavelets. The propagation of the field's power and states of spatial coherence and polarization results from correlations between the components of the field vectors at pairs of points in space. Polarization domains are theoretically predicted as the structure of the field polarization at the observation plane. In addition, the phase-space representation provides a generalization of the Poynting theorem. Theoretical predictions are examined by numerically simulating the Young experiment with electromagnetic waves. The experimental implementation of these results is a current subject of research.

  11. Viterbi Tracking of Randomly Phase-Modulated Data (and Related Topics).

    Science.gov (United States)

    1982-08-10

    space I-ir, vr). were a random sequence on the unit circle C or equiva- Discretization of this bounded interval leads to a finite-state lently on the...and the symbol phase, arg ak. Also, of Recall ’k is defined on the circle C . Therefore, for clarity course, for PSK symbol sets only one symbol...x)) on [-V,w] g,(R(x)) Wropped on M-4 the Circle C . M*4 (c) (d) Fig. 5. Density functions of phase increment before and after folding. dix). It

  12. Security authentication with a three-dimensional optical phase code using random forest classifier: an overview

    Science.gov (United States)

    Markman, Adam; Carnicer, Artur; Javidi, Bahram

    2017-05-01

    We overview our recent work [1] on utilizing three-dimensional (3D) optical phase codes for object authentication using the random forest classifier. A simple 3D optical phase code (OPC) is generated by combining multiple diffusers and glass slides. This tag is then placed on a quick-response (QR) code, which is a barcode capable of storing information and can be scanned under non-uniform illumination conditions, rotation, and slight degradation. A coherent light source illuminates the OPC and the transmitted light is captured by a CCD to record the unique signature. Feature extraction on the signature is performed and inputted into a pre-trained random-forest classifier for authentication.

  13. A randomized double-blind crossover study of phase-shift sound therapy for tinnitus.

    Science.gov (United States)

    Heijneman, Karin M; de Kleine, Emile; van Dijk, Pim

    2012-08-01

    The purpose of this study was to compare the efficacy of the treatment of tinnitus with a phase-shifting pure tone to that of the same tone treatment without phase shifting. A double-blind crossover randomized controlled trial. This study was conducted at the University Medical Center Groningen. Twenty-two patients with predominantly tonal tinnitus underwent both intervention and control treatments. Each treatment consisted of three 30-minute sessions in 1 week. The control treatment was identical to the intervention treatment, except that the stimulus was a pure tone without phase shifting. Questionnaires, tinnitus loudness match, and annoyance and loudness ratings were used to measure treatment effects. Pure-tone treatment and phase-shift treatment had no significant effect on tinnitus according to questionnaires (Tinnitus Handicap Index, Tinnitus Reaction Questionnaire, Hospital Anxiety and Depression Scale, and Maastricht Questionnaire), audiological matching procedures, and loudness and annoyance ratings of tinnitus. Furthermore, phase-shift treatment showed no additional significant improvement in comparison with pure-tone treatment. Changes in questionnaire scores due to pure-tone and the phase-shift treatment were correlated. On average across the group, both treatments failed to demonstrate a significant effect. Both treatments were beneficial for some patients. However, a positive effect was not demonstrated that could be attributed to the periodic shifting of the phase of the stimulus tone.

  14. Luteal Phase Support in the Intrauterine Insemination (IUI) Cycles: A Randomized Double Blind, Placebo Controlled Study.

    OpenAIRE

    Batool Hossein Rashidi; Fatemeh Davari Tanha; Haleh Rahmanpour; Mahya Ghazizadeh

    2014-01-01

    Objective: To evaluate the impact of luteal phase support with vaginal progesterone on pregnancy rates in the intrauterine insemination (IUI) cycles, stimulated with clomiphene citrate and human menopausal gonadotropin (hMG), in sub fertile couples. Materials and methods: This prospective, randomized, double blind study was performed in a tertiary infertility center from March 2011 to January 2012. It consisted of 253 sub fertile couples undergoing ovarian stimulation for IUI cycles. They und...

  15. Implementation of the direct evaluation of strains using a phase analysis code for random patterns

    CERN Document Server

    Molimard, Jérôme

    2011-01-01

    A new approach for decoding directly strains from surfaces encoded with random patterns has been developed and validated. It is based on phase analysis of small region of interest. Here we adapt to random patterns new concepts proposed by Badulescu (2009) on the grid method. First metrological results are encouraging: resolution is proportional to strain level, being 9% of the nominal value, for a spatial resolution of 9 pixels (ZOI 64 \\times 64 pixels2). Random noise has to be carefully controlled. A numerical example shows the relevance of the approach. Then, first application on a carbon fiber reinforced composite is developed. Fabric intertwining is studied using a tensile test. Over-strains are clearly visible, and results connect well with the previous studies

  16. On the incorporation of the geometric phase in general single potential energy surface dynamics: A removable approximation to ab initio data.

    Science.gov (United States)

    Malbon, Christopher L; Zhu, Xiaolei; Guo, Hua; Yarkony, David R

    2016-12-21

    For two electronic states coupled by conical intersections, the line integral of the derivative coupling can be used to construct a complex-valued multiplicative phase factor that makes the real-valued adiabatic electronic wave function single-valued, provided that the curl of the derivative coupling is zero. Unfortunately for ab initio determined wave functions, the curl is never rigorously zero. However, when the wave functions are determined from a coupled two diabatic state Hamiltonian H(d) (fit to ab initio data), the resulting derivative couplings are by construction curl free, except at points of conical intersection. In this work we focus on a recently introduced diabatization scheme that produces the H(d) by fitting ab initio determined energies, energy gradients, and derivative couplings to the corresponding H(d) determined quantities in a least squares sense, producing a removable approximation to the ab initio determined derivative coupling. This approach and related numerical issues associated with the nonremovable ab initio derivative couplings are illustrated using a full 33-dimensional representation of phenol photodissociation. The use of this approach to provide a general framework for treating the molecular Aharonov Bohm effect is demonstrated.

  17. Induction chemotherapy before chemoradiotherapy and surgery for locally advanced rectal cancer. Is it time for a randomized phase III trial?

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, Claus [Frankfurt Univ. (Germany). Klinik fuer Strahlentherapie und Onkologie; Arnold, Dirk [Halle Univ. (Germany). Klinik und Poliklinik fuer Innere Medizin IV; Becker, Heinz; Ghadimi, Michael; Liersch, Torsten [Goettingen Univ. (Germany). Klinik fuer Allgemein- und Visceralchirurgie; Fietkau, Rainer; Sauer, Rolf [Erlangen Univ. (Germany). Strahlenklinik; Graeven, Ullrich [Kliniken Maria Hilf GmbH, Moenchengladbach (Germany). Klinik fuer Haematologie, Onkologie und Gastroenterologie; Hess, Clemens [Goettingen Univ. (Germany). Klinik fuer Strahlentherapie und Radioonkologie; Hofheinz, Ralf [Universitaetsmedizin Mannheim (Germany). III. Medizinische Klinik Haematologie und Internistische Onkologie; Hohenberger, Werner [Erlangen Univ. (Germany). Chirurgische Klinik; Post, Stefan [Universitaetsmedizin Mannheim (Germany). Chirurgische Klinik; Raab, Rudolf [Klinikum Oldenburg (Germany). Klinik fuer Allgemein- und Visceralchirurgie; Wenz, Frederick [Universitaetsmedizin Mannheim (Germany). Klinik fuer Strahlentherapie und Radioonkologie

    2010-12-15

    Background: In the era of preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), the development of distant metastases is the predominant mode of failure in rectal cancer patients today. Integrating more effective systemic therapy into combined modality programs is the challenge. The question that needs to be addressed is how and when to apply systemic treatment with adequate dose and intensity. Material and Methods: This review article focuses on phase II-III trials designed to improve 5-fluorouracil (5-FU)-based combined modality treatment for rectal cancer patients through the inclusion of concurrent, adjuvant or, most recently, induction combination chemotherapy. Computerized bibliographic searches of PubMed were supplemented with hand searches of reference lists and abstracts of ASCO/ASTRO/ESTRO meetings. Results: After preoperative CRT and surgical resection, approximately one third of patients do not receive adjuvant chemotherapy, mainly due to surgical complications, patients' refusal, or investigator's discretion. In order to be able to apply chemotherapy with sufficient dose and intensity, an innovative approach is to deliver systemic therapy prior to preoperative CRT rather than adjuvant chemotherapy. Emerging evidence from several phase II trials and, recently, randomized phase II trials indicate that induction chemotherapy is feasible, does not compromise CRT or surgical resection, and enables the delivery of chemotherapy in adequate dose and intensity. Although this approach did not increase local efficacy in recent trials (e.g., pathological complete response rates, tumor regression, R0 resection rates, local control), it may help to improve control of distant disease. Conclusion: Whether this improvement in applicability and dose density of chemotherapy will ultimately translate into improved disease-free survival will have to be tested in a larger phase III trial. (orig.)

  18. High-vs low-dose cytarabine combined with interferon alfa in patients with first chronic phase chronic myeloid leukemia. A prospective randomized phase III study

    NARCIS (Netherlands)

    Deenik, W.; van der Holt, B.; Verhoef, G. E. G.; Schattenberg, A. V. M. B.; Verdonck, L. F.; Daenen, S. M. G. J.; Zachee, P.; Westveer, P. H. M.; Smit, W. M.; Wittebol, S.; Schouten, H. C.; Lowenberg, B.; Ossenkoppele, G. J.; Cornelissen, J. J.

    A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase

  19. High-vs low-dose cytarabine combined with interferon alfa in patients with first chronic phase chronic myeloid leukemia : A prospective randomized phase III study

    NARCIS (Netherlands)

    Deenik, W.; Holt, B. van der; Verhoef, G.E.; Schattenberg, A.V.M.B.; Verdonck, L.F.; Daenen, S.M.G.J.; Zachee, P.; Westveer, P.H.; Smit, W.M.; Wittebol, S.; Schouten, H.C.; Lowenberg, B.; Ossenkoppele, G.J.; Cornelissen, J.J.L.M.

    2007-01-01

    A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase

  20. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia : 2-year follow-up from a randomized phase 3 trial (DASISION)

    NARCIS (Netherlands)

    Kantarjian, Hagop M.; Shah, Neil P.; Cortes, Jorge E.; Baccarani, Michele; Agarwal, Mohan B.; Soledad Undurraga, Maria; Wang, Jianxiang; Kassack Ipina, Juan Julio; Kim, Dong-Wook; Ogura, Michinori; Pavlovsky, Carolina; Junghanss, Christian; Milone, Jorge H.; Nicolini, Franck E.; Robak, Tadeusz; Van Droogenbroeck, Jan; Vellenga, Edo; Bradley-Garelik, M. Brigid; Zhu, Chao; Hochhaus, Andreas

    2012-01-01

    Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronic-phase (CP) CML were randomized to receive dasatinib 100 mg (n =

  1. Dynamical Cluster Approximation

    Science.gov (United States)

    Fotso, H.; Yang, S.; Chen, K.; Pathak, S.; Moreno, J.; Jarrell, M.; Mikelsons, K.; Khatami, E.; Galanakis, D.

    The dynamical cluster approximation (DCA) is a method which systematically incorporates nonlocal corrections to the dynamical mean-field approximation. Here we present a pedagogical discussion of the DCA by describing it as a Φ-derivable coarse-graining approximation in k-space, which maps an infinite lattice problem onto a periodic finite-sized cluster embedded in a self-consistently determined effective medium. We demonstrate the method by applying it to the two-dimensional Hubbard model. From this application, we show evidences of the presence of a quantum critical point (QCP) at a finite doping underneath the superconducting dome. The QCP is associated with the second-order terminus of a line of first order phase separation transitions. This critical point is driven to zero temperature by varying the band parameters, generating the QCP. The effect of the proximity of the QCP to the superconducting dome is also discussed.

  2. Equilibrium phase behavior and maximally random jammed state of truncated tetrahedra.

    Science.gov (United States)

    Chen, Duyu; Jiao, Yang; Torquato, Salvatore

    2014-07-17

    Numerous recent investigations have been devoted to the determination of the equilibrium phase behavior and packing characteristics of hard nonspherical particles, including ellipsoids, superballs, and polyhedra, to name but just a few shapes. Systems of hard nonspherical particles exhibit a variety of stable phases with different degrees of translational and orientational order, including isotropic liquid, solid crystal, rotator and a variety of liquid crystal phases. In this paper, we employ a Monte Carlo implementation of the adaptive-shrinking-cell (ASC) numerical scheme and free-energy calculations to ascertain with high precision the equilibrium phase behavior of systems of congruent Archimedean truncated tetrahedra over the entire range of possible densities up to the maximal nearly space-filling density. In particular, we find that the system undergoes two first-order phase transitions as the density increases: first a liquid-solid transition and then a solid-solid transition. The isotropic liquid phase coexists with the Conway-Torquato (CT) crystal phase at intermediate densities, verifying the result of a previous qualitative study [ J. Chem. Phys. 2011 , 135 , 151101 ]. The freezing- and melting-point packing fractions for this transition are respectively ϕF = 0.496 ± 0.006 and ϕM = 0.591 ± 0.005. At higher densities, we find that the CT phase undergoes another first-order phase transition to one associated with the densest-known crystal, with coexistence densities in the range ϕ ∈ [0.780 ± 0.002, 0.802 ± 0.003]. We find no evidence for stable rotator (or plastic) or nematic phases. We also generate the maximally random jammed (MRJ) packings of truncated tetrahedra, which may be regarded to be the glassy end state of a rapid compression of the liquid. Specifically, we systematically study the structural characteristics of the MRJ packings, including the centroidal pair correlation function, structure factor and orientational pair correlation

  3. Securing image information using double random phase encoding and parallel compressive sensing with updated sampling processes

    Science.gov (United States)

    Hu, Guiqiang; Xiao, Di; Wang, Yong; Xiang, Tao; Zhou, Qing

    2017-11-01

    Recently, a new kind of image encryption approach using compressive sensing (CS) and double random phase encoding has received much attention due to the advantages such as compressibility and robustness. However, this approach is found to be vulnerable to chosen plaintext attack (CPA) if the CS measurement matrix is re-used. Therefore, designing an efficient measurement matrix updating mechanism that ensures resistance to CPA is of practical significance. In this paper, we provide a novel solution to update the CS measurement matrix by altering the secret sparse basis with the help of counter mode operation. Particularly, the secret sparse basis is implemented by a reality-preserving fractional cosine transform matrix. Compared with the conventional CS-based cryptosystem that totally generates all the random entries of measurement matrix, our scheme owns efficiency superiority while guaranteeing resistance to CPA. Experimental and analysis results show that the proposed scheme has a good security performance and has robustness against noise and occlusion.

  4. Optical information authentication via compressed sensing and double random phase encoding

    Science.gov (United States)

    Chen, Junxin; Bao, Nan; Zhu, Zhi-liang

    2017-10-01

    This paper presents a novel information authentication scheme via compressed sensing and double random phase encoding. Two alternative architectures have been investigated, in which significantly compressed data with micro percentage is sufficient for authentication. At the decoder end, a noise-like image with no leakage of the plaintext is recovered and subsequently authenticated using a nonlinear optical correlation approach. The authentication effectiveness, noise resistance and security performance of the proposed scheme have been experimentally validated. This work was supported by the Fundamental Research Funds for the Central Universities (N162410002-4, N151904002), the National Natural Science Foundation of China (No. 61374178).

  5. Cryptographic salting for security enhancement of double random phase encryption schemes

    Science.gov (United States)

    Velez Zea, Alejandro; Fredy Barrera, John; Torroba, Roberto

    2017-10-01

    Security in optical encryption techniques is a subject of great importance, especially in light of recent reports of successful attacks. We propose a new procedure to reinforce the ciphertexts generated in double random phase encrypting experimental setups. This ciphertext is protected by multiplexing with a ‘salt’ ciphertext coded with the same setup. We present an experimental implementation of the ‘salting’ technique. Thereafter, we analyze the resistance of the ‘salted’ ciphertext under some of the commonly known attacks reported in the literature, demonstrating the validity of our proposal.

  6. Phase transitions of Ising mixed spin 1 and 3/2 with random crystal field distribution

    Science.gov (United States)

    Sabri, S.; EL Falaki, M.; EL Yadari, M.; Benyoussef, A.; EL Kenz, A.

    2016-10-01

    The thermal and magnetic properties of the mixed spin-1 and spin-3/2 in the presence of the random crystal field are studied within the mean field approach based on the Bogoliubov inequality for the Gibbs free energy. The model exhibits first, second order transitions, a tricritical point, triple point and an isolated critical end point. It is found that the system displays simple and double compensation temperatures, five topologies of the phase diagrams. A re-entrant phenomenon is also discussed and the thermal dependences of total magnetization according to extended Neel classification have been also given.

  7. High energy X-ray phase and dark-field imaging using a random absorption mask.

    Science.gov (United States)

    Wang, Hongchang; Kashyap, Yogesh; Cai, Biao; Sawhney, Kawal

    2016-07-28

    High energy X-ray imaging has unique advantage over conventional X-ray imaging, since it enables higher penetration into materials with significantly reduced radiation damage. However, the absorption contrast in high energy region is considerably low due to the reduced X-ray absorption cross section for most materials. Even though the X-ray phase and dark-field imaging techniques can provide substantially increased contrast and complementary information, fabricating dedicated optics for high energies still remain a challenge. To address this issue, we present an alternative X-ray imaging approach to produce transmission, phase and scattering signals at high X-ray energies by using a random absorption mask. Importantly, in addition to the synchrotron radiation source, this approach has been demonstrated for practical imaging application with a laboratory-based microfocus X-ray source. This new imaging method could be potentially useful for studying thick samples or heavy materials for advanced research in materials science.

  8. Workshop on Strategic Behavior and Phase Transitions in Random and Complex Combinatorial Structures : Extended Abstracts

    CERN Document Server

    Kirousis, Lefteris; Ortiz-Gracia, Luis; Serna, Maria

    2017-01-01

    This book is divided into two parts, the first of which seeks to connect the phase transitions of various disciplines, including game theory, and to explore the synergies between statistical physics and combinatorics. Phase Transitions has been an active multidisciplinary field of research, bringing together physicists, computer scientists and mathematicians. The main research theme explores how atomic agents that act locally and microscopically lead to discontinuous macroscopic changes. Adopting this perspective has proven to be especially useful in studying the evolution of random and usually complex or large combinatorial objects (like networks or logic formulas) with respect to discontinuous changes in global parameters like connectivity, satisfiability etc. There is, of course, an obvious strategic element in the formation of a transition: the atomic agents “selfishly” seek to optimize a local parameter. However, up to now this game-theoretic aspect of abrupt, locally triggered changes had not been e...

  9. A random phased array device for delivery of high intensity focused ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Hand, J W [Radiological Sciences Unit, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London W12 0HS (United Kingdom); Shaw, A; Sadhoo, N; Rajagopal, S [Acoustics Group, National Physical Laboratory, Teddington TW11 0LW (United Kingdom); Dickinson, R J [Department of Bioengineering, Imperial College London, London SW7 2AZ (United Kingdom); Gavrilov, L R [N.N. Andreev Acoustics Institute, 117036 Moscow (Russian Federation)], E-mail: j.hand@imperial.ac.uk

    2009-10-07

    Randomized phased arrays can offer electronic steering of a single focus and simultaneous multiple foci concomitant with low levels of secondary maxima and are potentially useful as sources of high intensity focused ultrasound (HIFU). This work describes laboratory testing of a 1 MHz random phased array consisting of 254 elements on a spherical shell of radius of curvature 130 mm and diameter 170 mm. Acoustic output power and efficiency are measured for a range of input electrical powers, and field distributions for various single- and multiple-focus conditions are evaluated by a novel technique using an infrared camera to provide rapid imaging of temperature changes on the surface of an absorbing target. Experimental results show that the array can steer a single focus laterally to at least {+-}15 mm off axis and axially to more than {+-}15 mm from the centre of curvature of the array and patterns of four and five simultaneous foci {+-}10 mm laterally and axially whilst maintaining low intensity levels in secondary maxima away from the targeted area in good agreement with linear theoretical predictions. Experiments in which pork meat was thermally ablated indicate that contiguous lesions several cm{sup 3} in volume can be produced using the patterns of multiple foci.

  10. Affine cryptosystem of double-random-phase encryption based on the fractional Fourier transform.

    Science.gov (United States)

    Xin, Zhou; Sheng, Yuan; Sheng-wei, Wang; Jian, Xie

    2006-11-20

    An affine mapping mathematical expression of the double-random-phase encryption technique has been deduced utilizing the matrix form of discrete fractional Fourier transforms. This expression clearly describes the encryption laws of the double-random-phase encoding techniques based on both the fractional Fourier transform and the ordinary Fourier transform. The encryption process may be regarded as a substantial optical realization of the affine cryptosystem. It has been illustrated that the encryption process converts the original image into a white Gaussian noise with a zero-mean value. Also, the decryption process converts the data deviations of the encrypted image into white Gaussian noises, regardless of the type of data deviations. These noises superimpose on the decrypted image and degrade the signal-to-noise ratio. Numerical simulations have been implemented for the different types of noises introduced into the encrypted image, such as the white noise with uniform distribution probability, the white noise with Gaussian distribution probability, colored noise, and the partial occlusion of the encrypted image.

  11. Band-phase-randomized Surrogates to assess nonlinearity in non-stationary time series

    CERN Document Server

    Guarin, Diego; Orozco, Alvaro

    2011-01-01

    Testing for nonlinearity is one of the most important preprocessing steps in nonlinear time series analysis. Typically, this is done by means of the linear surrogate data methods. But it is a known fact that the validity of the results heavily depends on the stationarity of the time series. Since most physiological signals are non-stationary, it is easy to falsely detect nonlinearity using the linear surrogate data methods. In this document, we propose a methodology to extend the procedure for generating constrained surrogate time series in order to assess nonlinearity in non-stationary data. The method is based on the band-phase-randomized surrogates, which consists (contrary to the linear surrogate data methods) in randomizing only a portion of the Fourier phases in the high frequency band. Analysis of simulated time series showed that in comparison to the linear surrogate data method, our method is able to discriminate between linear stationarity, linear non-stationary and nonlinear time series. When apply...

  12. Effect of Mo on the phase stability and elastic mechanical properties of Ti-Mo random alloys from ab initio calculations

    Science.gov (United States)

    Cao, Peiyu; Tian, Fuyang; Wang, Yandong

    2017-11-01

    Ti-Mo alloys are promising materials for shape memory alloys and biomedical materials. Whereas, the appearance of metastable ω phase can cause embrittlement and destroy the shape memory effect. In order to avoid the ω phase, the effect of Mo on the temperature dependent lattice parameters, phase stability and elastic mechanical properties of β, α, and ω Ti1-x Mo x (x  =  0-2.0) random alloys was systematically investigated by using the exact muffin-tin orbitals method in combination with the coherent potential approximation. The theoretical predictions for the lattice parameters are in good agreement with the available experiments. Results show that β Ti0.96Mo0.04 can almost transform to ω phase without lattice deformation and volume change, which suggests that the athermal ω phase is easier to precipitate and grow near 4 at.% Mo content in the β Ti1-x Mo x alloys. The critical content of Mo for the competed stabilization of β phase at T  =  300 K is ~11.2 at.%. Its valence electron concentration of 4.224 is viewed as a necessary criterion for the competed phase stability. The calculations of formation energy are used to explain successfully why the partitioning of Mo can be found in Ti0.91Mo0.09 alloy after annealing. Through the analysis of formation energy, both Mo addition and increasing temperature can stabilize the β phase. The calculated Cauchy pressure, Pugh’s ratio, Poisson ratio, and Young’s modulus suggests that ω phase is intrinsically brittle and has large Young’s modulus compared with β and α phases.

  13. Random sampler M-estimator algorithm with sequential probability ratio test for robust function approximation via feed-forward neural networks.

    Science.gov (United States)

    El-Melegy, Moumen T

    2013-07-01

    This paper addresses the problem of fitting a functional model to data corrupted with outliers using a multilayered feed-forward neural network. Although it is of high importance in practical applications, this problem has not received careful attention from the neural network research community. One recent approach to solving this problem is to use a neural network training algorithm based on the random sample consensus (RANSAC) framework. This paper proposes a new algorithm that offers two enhancements over the original RANSAC algorithm. The first one improves the algorithm accuracy and robustness by employing an M-estimator cost function to decide on the best estimated model from the randomly selected samples. The other one improves the time performance of the algorithm by utilizing a statistical pretest based on Wald's sequential probability ratio test. The proposed algorithm is successfully evaluated on synthetic and real data, contaminated with varying degrees of outliers, and compared with existing neural network training algorithms.

  14. Robustness of double random phase encoding spread-space spread-spectrum image watermarking technique

    Science.gov (United States)

    Liu, Shi; Hennelly, Bryan M.; Sheridan, John T.

    2013-09-01

    In this paper the robustness of a recently proposed image watermarking scheme is investigated, namely the Double Random Phase Encoding spread-space spread-spectrum watermarking (DRPE SS-SS) technique. In the DRPE SS-SS method, the watermark is in the form of a digital barcode image which is numerically encrypted using a simulation of the optical DRPE process. This produces a random complex image, which is then processed to form a real valued random image with a low number of quantization levels. This signal is added to the host image. Extraction of the barcode, involves applying an inverse DRPE process to the watermarked image followed by a low pass filter. This algorithm is designed to utilize the capability of the DRPE to reversibly spread the energy of the watermarking information in both the space and spatial frequency domains, and the energy of the watermark in any spatial or spatial frequency bin is very small. The common geometric transformations and signal processing operations are performed using both the informed and the blind detections for different barcode widths and different quantization levels. The results presented indicate that the DRPE SS-SS method is robust to scaling, JPEG compression distortion, cropping, low pass and high pass filtering. It is also demonstrated that the bigger the barcode width is, the lower the false positive rate will be.

  15. Influence of liquid crystalline phases on the tunability of a random laser

    Science.gov (United States)

    Trull, José; Salud, Josep; Diez-Berart, Sergio; López, David O.

    2017-05-01

    In this paper, we report the temperature behavior of an optimized disordered photonic system-based liquid crystal by means of heat capacity and refractive index measurements. The scattering system is formed by a porous borosilicate glass random matrix (about 60%) infiltrated with a smectogenic liquid crystal (about 16%) and a small amount of laser dye (0.1%). The rest of the scattering system is about 24% air, giving rise to a high refractive index contrast scattering system. Such a system has the functionality to change the refractive index contrast with temperature due to the liquid crystal temperature behavior. The system, optically pumped by the second harmonic of a Q -switched Nd:YAG pulsed laser working at 532 nm, exhibits random laser action, the threshold of which depends upon the liquid crystalline mesophase. Temperatures of existence of the smectic-B phase correspond to the most optimized random laser. In such a mesophase, the transport mean free path has been determined as about 16 μm in a coherent backscattering experiment.

  16. Critical points of quadratic renormalizations of random variables and phase transitions of disordered polymer models on diamond lattices.

    Science.gov (United States)

    Monthus, Cécile; Garel, Thomas

    2008-02-01

    We study the wetting transition and the directed polymer delocalization transition on diamond hierarchical lattices. These two phase transitions with frozen disorder correspond to the critical points of quadratic renormalizations of the partition function. (These exact renormalizations on diamond lattices can also be considered as approximate Migdal-Kadanoff renormalizations for hypercubic lattices.) In terms of the rescaled partition function z=Z/Z(typ) , we find that the critical point corresponds to a fixed point distribution with a power-law tail P(c)(z) ~ Phi(ln z)/z(1+mu) as z-->+infinity [up to some subleading logarithmic correction Phi(ln z)], so that all moments z(n) with n>mu diverge. For the wetting transition, the first moment diverges z=+infinity (case 0infinity (case 1fixed point distribution coincides with the transfer matrix describing a directed polymer on the Cayley tree, but the random weights determined by the fixed point distribution P(c)(z) are broadly distributed. This induces some changes in the traveling wave solutions with respect to the usual case of more narrow distributions.

  17. Comparison between amniotomy, oxytocin or both for augmentation of labor in prolonged latent phase: a randomized controlled trial

    OpenAIRE

    Shalev Eliezer; Zafran Noah; Kadan Yfat; Garmi Gali; Nachum Zohar; Salim Raed

    2010-01-01

    Abstract Background A prolonged latent phase is independently associated with an increased incidence of subsequent labor abnormalities. We aimed to compare between oxytocin augmentation, amniotomy and a combination of both on the duration of labor among women with a prolonged latent phase. Methods Women with a singleton fetus in cephalic presentation who have a prolonged latent phase, were randomly allocated to amniotomy (group 1), oxytocin (group 2) or both (group 3). A group of women who pr...

  18. Particle–particle Tamm–Dancoff approximation and particle–particle ...

    Indian Academy of Sciences (India)

    –particle Tamm–. Dancoff approximation (pp TDA) and particle–particle random phase approximation (pp RPA). All possible single-particle states of the allowed angular momenta are considered in the 0p and 1s–. 0d shells. The Hamiltonian is ...

  19. Particle–particle Tamm–Dancoff approximation and particle–particle ...

    Indian Academy of Sciences (India)

    Nuclear structure; collective excitations and transition strength. Abstract. The nuclear structures of 18O and 18F nuclei are studied using particle–particle Tamm–Dancoff approximation (pp TDA) and particle–particle random phase approximation (pp ... Physics Department, College of Science, Kirkuk University, Kirkuk, Iraq ...

  20. Multicenter, randomized, placebo-controlled phase III study of pyridoxalated hemoglobin polyoxyethylene in distributive shock (PHOENIX).

    Science.gov (United States)

    Vincent, Jean-Louis; Privalle, Christopher T; Singer, Mervyn; Lorente, José A; Boehm, Erwin; Meier-Hellmann, Andreas; Darius, Harald; Ferrer, Ricard; Sirvent, Josep-Maria; Marx, Gernot; DeAngelo, Joseph

    2015-01-01

    To compare the effectiveness and safety of the hemoglobin-based nitric oxide scavenger, pyridoxalated hemoglobin polyoxyethylene, against placebo in patients with vasopressor-dependent distributive shock. Multicenter, randomized, placebo-controlled, open-label study. Sixty-one participating ICUs in six European countries (Austria, Belgium, Germany, the Netherlands, Spain, and United Kingdom). All patients admitted with distributive shock, defined as the presence of at least two systemic inflammatory response syndrome criteria, persisting norepinephrine dependence and evidence of organ dysfunction/hypoperfusion despite adequate fluid resuscitation. Patients were randomized to receive 0.25 mL/kg/hr pyridoxalated hemoglobin polyoxyethylene (20 mg Hb/kg/hr) or an equal volume of placebo, infused for up to 150 hours, in addition to conventional vasopressor therapy. The study was stopped after interim analysis showed higher mortality in the pyridoxalated hemoglobin polyoxyethylene group and an increased prevalence of adverse events. At this time, 377 patients had been randomized to pyridoxalated hemoglobin polyoxyethylene (n = 183) or placebo (n = 194). Age, gender, type of patient (medical/surgical), and Acute Physiology and Chronic Health Evaluation II scores were similar between groups. Twenty-eight-day mortality rate was 44.3% in the pyridoxalated hemoglobin polyoxyethylene group versus 37.6% in the placebo group (OR, 1.29; 95% CI, 0.85-1.95; p = 0.227). In patients with higher organ dysfunction scores (Sepsis-related Organ Failure Assessment > 13), mortality rates were significantly higher in the pyridoxalated hemoglobin polyoxyethylene group when compared with those in placebo-treated patients (60.9% vs 39.2%; p = 0.014). Survivors who received pyridoxalated hemoglobin polyoxyethylene had a longer vasopressor-free time (21.3 vs 19.7 d; p = 0.035). In this randomized, controlled phase III trial in patients with vasopressor-dependent distributive shock

  1. Luteal Phase Support in the Intrauterine Insemination (IUI Cycles: A Randomized Double Blind, Placebo Controlled Study.

    Directory of Open Access Journals (Sweden)

    Batool Hossein Rashidi

    2014-12-01

    Full Text Available To evaluate the impact of luteal phase support with vaginal progesterone on pregnancy rates in the intrauterine insemination (IUI cycles, stimulated with clomiphene citrate and human menopausal gonadotropin (hMG, in sub fertile couples.This prospective, randomized, double blind study was performed in a tertiary infertility center from March 2011 to January 2012. It consisted of 253 sub fertile couples undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with clomiphene citrate (100 mg and hMG (75 IU in preparation for the IUI cycle. Study group (n = 127 received luteal phase support in the form of vaginal progesterone (400 mg twice a day, and control group (n = 126 received placebo. Clinical pregnancy and abortion rates were assessed and compared between the two groups.The clinical pregnancy rate was not significantly higher for supported cycles than that for the unsupported ones (15.75% vs. 12.69%, p = 0.3. The abortion rate in the patients with progesterone luteal support compared to placebo group was not statistically different (10% vs. 18.75%, p = 0.45.It seems that luteal phase support with vaginal progesterone was not enhanced the success of IUI cycles outcomes, when clomiphene citrate and hMG were used for ovulation stimulation.

  2. Luteal Phase Support in the Intrauterine Insemination (IUI) Cycles: A Randomized Double Blind, Placebo Controlled Study.

    Science.gov (United States)

    Hossein Rashidi, Batool; Davari Tanha, Fatemeh; Rahmanpour, Haleh; Ghazizadeh, Mahya

    2014-12-01

    To evaluate the impact of luteal phase support with vaginal progesterone on pregnancy rates in the intrauterine insemination (IUI) cycles, stimulated with clomiphene citrate and human menopausal gonadotropin (hMG), in sub fertile couples. This prospective, randomized, double blind study was performed in a tertiary infertility center from March 2011 to January 2012. It consisted of 253 sub fertile couples undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with clomiphene citrate (100 mg) and hMG (75 IU) in preparation for the IUI cycle. Study group (n = 127) received luteal phase support in the form of vaginal progesterone (400 mg twice a day), and control group (n = 126) received placebo. Clinical pregnancy and abortion rates were assessed and compared between the two groups. The clinical pregnancy rate was not significantly higher for supported cycles than that for the unsupported ones (15.75% vs. 12.69%, p = 0.3). The abortion rate in the patients with progesterone luteal support compared to placebo group was not statistically different (10% vs. 18.75%, p = 0.45). It seems that luteal phase support with vaginal progesterone was not enhanced the success of IUI cycles outcomes, when clomiphene citrate and hMG were used for ovulation stimulation.

  3. Statistical mechanics of random geometric graphs: Geometry-induced first-order phase transition.

    Science.gov (United States)

    Ostilli, Massimo; Bianconi, Ginestra

    2015-04-01

    Random geometric graphs (RGGs) can be formalized as hidden-variables models where the hidden variables are the coordinates of the nodes. Here we develop a general approach to extract the typical configurations of a generic hidden-variables model and apply the resulting equations to RGGs. For any RGG, defined through a rigid or a soft geometric rule, the method reduces to a nontrivial satisfaction problem: Given N nodes, a domain D, and a desired average connectivity 〈k〉, find, if any, the distribution of nodes having support in D and average connectivity 〈k〉. We find out that, in the thermodynamic limit, nodes are either uniformly distributed or highly condensed in a small region, the two regimes being separated by a first-order phase transition characterized by a O(N) jump of 〈k〉. Other intermediate values of 〈k〉 correspond to very rare graph realizations. The phase transition is observed as a function of a parameter a∈[0,1] that tunes the underlying geometry. In particular, a=1 indicates a rigid geometry where only close nodes are connected, while a=0 indicates a rigid antigeometry where only distant nodes are connected. Consistently, when a=1/2 there is no geometry and no phase transition. After discussing the numerical analysis, we provide a combinatorial argument to fully explain the mechanism inducing this phase transition and recognize it as an easy-hard-easy transition. Our result shows that, in general, ad hoc optimized networks can hardly be designed, unless to rely to specific heterogeneous constructions, not necessarily scale free.

  4. An Approximate Treatment of Reflection Coefficient in the Phased Beam Tracing Method for the Simulation of Enclosed Sound Fields at Medium Frequencies

    DEFF Research Database (Denmark)

    Jeong, Cheol-Ho; Ih, Jeong-Guon; Rindel, Jens Holger

    2008-01-01

    of a surface and the complex wave number for describing the propagation characteristics. In this study, two types of approximate real reflection coefficients derived from the measured absorption coefficient were tested for a practical applicability. As a test example, pressure impulse responses and energy...

  5. Pseudo-random-bit-sequence phase modulation for reduced errors in a fiber optic gyroscope.

    Science.gov (United States)

    Chamoun, Jacob; Digonnet, Michel J F

    2016-12-15

    Low noise and drift in a laser-driven fiber optic gyroscope (FOG) are demonstrated by interrogating the sensor with a low-coherence laser. The laser coherence was reduced by broadening its optical spectrum using an external electro-optic phase modulator driven by either a sinusoidal or a pseudo-random bit sequence (PRBS) waveform. The noise reduction measured in a FOG driven by a modulated laser agrees with the calculations based on the broadened laser spectrum. Using PRBS modulation, the linewidth of a laser was broadened from 10 MHz to more than 10 GHz, leading to a measured FOG noise of only 0.00073  deg/√h and a drift of 0.023  deg/h. To the best of our knowledge, these are the lowest noise and drift reported in a laser-driven FOG, and this noise is below the requirement for the inertial navigation of aircraft.

  6. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial

    Science.gov (United States)

    Motzer, Robert J.; Rini, Brian I.; McDermott, David F.; Redman, Bruce G.; Kuzel, Timothy M.; Harrison, Michael R.; Vaishampayan, Ulka N.; Drabkin, Harry A.; George, Saby; Logan, Theodore F.; Margolin, Kim A.; Plimack, Elizabeth R.; Lambert, Alexandre M.; Waxman, Ian M.; Hammers, Hans J.

    2015-01-01

    Purpose Nivolumab is a fully human immunoglobulin G4 programmed death–1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) to nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was to evaluate the dose-response relationship as measured by progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), and safety. Results A total of 168 patients were randomly assigned to the nivolumab 0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54) cohorts. One hundred eighteen patients (70%) had received more than one prior systemic regimen. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Respective ORRs were 20%, 22%, and 20%. Median OS was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively. The most common treatment-related adverse event (AE) was fatigue (24%, 22%, and 35%, respectively). Nineteen patients (11%) experienced grade 3 to 4 treatment-related AEs. Conclusion Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS. These efficacy and safety results in mRCC support study in the phase III setting. PMID:25452452

  7. Asymmetric multiple information cryptosystem based on chaotic spiral phase mask and random spectrum decomposition

    Science.gov (United States)

    Rafiq Abuturab, Muhammad

    2018-01-01

    A new asymmetric multiple information cryptosystem based on chaotic spiral phase mask (CSPM) and random spectrum decomposition is put forwarded. In the proposed system, each channel of secret color image is first modulated with a CSPM and then gyrator transformed. The gyrator spectrum is randomly divided into two complex-valued masks. The same procedure is applied to multiple secret images to get their corresponding first and second complex-valued masks. Finally, first and second masks of each channel are independently added to produce first and second complex ciphertexts, respectively. The main feature of the proposed method is the different secret images encrypted by different CSPMs using different parameters as the sensitive decryption/private keys which are completely unknown to unauthorized users. Consequently, the proposed system would be resistant to potential attacks. Moreover, the CSPMs are easier to position in the decoding process owing to their own centering mark on axis focal ring. The retrieved secret images are free from cross-talk noise effects. The decryption process can be implemented by optical experiment. Numerical simulation results demonstrate the viability and security of the proposed method.

  8. Mavoglurant in Parkinson's patients with l-Dopa-induced dyskinesias: Two randomized phase 2 studies.

    Science.gov (United States)

    Trenkwalder, Claudia; Stocchi, Fabrizio; Poewe, Werner; Dronamraju, Nalina; Kenney, Chris; Shah, Amy; von Raison, Florian; Graf, Ana

    2016-07-01

    Two phase 2 randomized, double-blind studies were designed to evaluate efficacy and safety of immediate-release (study 1) and modified-release (study 2) mavoglurant formulations in PD l-dopa-induced dyskinesia. Patients were randomized to mavoglurant 100-mg or placebo (4:3) groups (study 1) and mavoglurant 200-mg, mavoglurant 150-mg, or placebo (2:1:1) groups (study 2). Primary outcome was antidyskinetic efficacy, as measured by change from baseline to week 12 in modified Abnormal Involuntary Movement Scale total score. Differences in least-squares mean (standard error) change in modified Abnormal Involuntary Movement Scale total score in week 12 did not reach statistical significance in either study (study 1: mavoglurant 100 mg twice a day versus placebo, 1.7 [1.31]; study 2: mavoglurant 150 mg twice a day (-1.3 [1.16]) and 200 mg twice a day (-0.2 [1.03]) versus placebo). Adverse events incidence was higher with mavoglurant than with placebo. Both studies failed to meet the primary objective of demonstrating improvement of dyskinesia with mavoglurant treatment. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  9. A Multispectral Photon-Counting Double Random Phase Encoding Scheme for Image Authentication

    Directory of Open Access Journals (Sweden)

    Faliu Yi

    2014-05-01

    Full Text Available In this paper, we propose a new method for color image-based authentication that combines multispectral photon-counting imaging (MPCI and double random phase encoding (DRPE schemes. The sparsely distributed information from MPCI and the stationary white noise signal from DRPE make intruder attacks difficult. In this authentication method, the original multispectral RGB color image is down-sampled into a Bayer image. The three types of color samples (red, green and blue color in the Bayer image are encrypted with DRPE and the amplitude part of the resulting image is photon counted. The corresponding phase information that has nonzero amplitude after photon counting is then kept for decryption. Experimental results show that the retrieved images from the proposed method do not visually resemble their original counterparts. Nevertheless, the original color image can be efficiently verified with statistical nonlinear correlations. Our experimental results also show that different interpolation algorithms applied to Bayer images result in different verification effects for multispectral RGB color images.

  10. Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial

    Science.gov (United States)

    Van Coevorden, Frits; Punt, Cornelis J. A.; Pierie, Jean-Pierre E. N.; Borel-Rinkes, Inne; Ledermann, Jonathan A.; Poston, Graeme; Bechstein, Wolf; Lentz, Marie-Ange; Mauer, Murielle; Folprecht, Gunnar; Van Cutsem, Eric; Ducreux, Michel; Nordlinger, Bernard

    2017-01-01

    Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n  38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases. PMID:28376151

  11. A Locust Phase Change Model with Multiple Switching States and Random Perturbation

    Science.gov (United States)

    Xiang, Changcheng; Tang, Sanyi; Cheke, Robert A.; Qin, Wenjie

    2016-12-01

    Insects such as locusts and some moths can transform from a solitarious phase when they remain in loose populations and a gregarious phase, when they may swarm. Therefore, the key to effective management of outbreaks of species such as the desert locust Schistocercagregaria is early detection of when they are in the threshold state between the two phases, followed by timely control of their hopper stages before they fledge because the control of flying adult swarms is costly and often ineffective. Definitions of gregarization thresholds should assist preventive control measures and avoid treatment of areas that might not lead to gregarization. In order to better understand the effects of the threshold density which represents the gregarization threshold on the outbreak of a locust population, we developed a model of a discrete switching system. The proposed model allows us to address: (1) How frequently switching occurs from solitarious to gregarious phases and vice versa; (2) When do stable switching transients occur, the existence of which indicate that solutions with larger amplitudes can switch to a stable attractor with a value less than the switching threshold density?; and (3) How does random perturbation influence the switching pattern? Our results show that both subsystems have refuge equilibrium points, outbreak equilibrium points and bistable equilibria. Further, the outbreak equilibrium points and bistable equilibria can coexist for a wide range of parameters and can switch from one to another. This type of switching is sensitive to the intrinsic growth rate and the initial values of the locust population, and may result in locust population outbreaks and phase switching once a small perturbation occurs. Moreover, the simulation results indicate that the switching transient patterns become identical after some generations, suggesting that the evolving process of the perturbation system is not related to the initial value after some fixed number of

  12. Long-Term Improvements After Multimodal Rehabilitation in Late Phase After Stroke: A Randomized Controlled Trial.

    Science.gov (United States)

    Bunketorp-Käll, Lina; Lundgren-Nilsson, Åsa; Samuelsson, Hans; Pekny, Tulen; Blomvé, Karin; Pekna, Marcela; Pekny, Milos; Blomstrand, Christian; Nilsson, Michael

    2017-07-01

    Treatments that improve function in late phase after stroke are urgently needed. We assessed whether multimodal interventions based on rhythm-and-music therapy or horse-riding therapy could lead to increased perceived recovery and functional improvement in a mixed population of individuals in late phase after stroke. Participants were assigned to rhythm-and-music therapy, horse-riding therapy, or control using concealed randomization, stratified with respect to sex and stroke laterality. Therapy was given twice a week for 12 weeks. The primary outcome was change in participants' perception of stroke recovery as assessed by the Stroke Impact Scale with an intention-to-treat analysis. Secondary objective outcome measures were changes in balance, gait, grip strength, and cognition. Blinded assessments were performed at baseline, postintervention, and at 3- and 6-month follow-up. One hundred twenty-three participants were assigned to rhythm-and-music therapy (n=41), horse-riding therapy (n=41), or control (n=41). Post-intervention, the perception of stroke recovery (mean change from baseline on a scale ranging from 1 to 100) was higher among rhythm-and-music therapy (5.2 [95% confidence interval, 0.79-9.61]) and horse-riding therapy participants (9.8 [95% confidence interval, 6.00-13.66]), compared with controls (-0.5 [-3.20 to 2.28]); P =0.001 (1-way ANOVA). The improvements were sustained in both intervention groups 6 months later, and corresponding gains were observed for the secondary outcomes. Multimodal interventions can improve long-term perception of recovery, as well as balance, gait, grip strength, and working memory in a mixed population of individuals in late phase after stroke. URL: http//www.ClinicalTrials.gov. Unique identifier: NCT01372059. © 2017 American Heart Association, Inc.

  13. A stochastic study of electron transfer kinetics in nano-particulate photocatalysis: a comparison of the quasi-equilibrium approximation with a random walking model.

    Science.gov (United States)

    Liu, Baoshun; Zhao, Xiujian; Yu, Jiaguo; Fujishima, Akira; Nakata, Kazuya

    2016-11-23

    In the photocatalysis of porous nano-crystalline materials, the transfer of electrons to O 2 plays an important role, which includes the electron transport to photocatalytic active centers and successive interfacial transfer to O 2 . The slowest of them will determine the overall speed of electron transfer in the photocatalysis reaction. Considering the photocatalysis of porous nano-crystalline TiO 2 as an example, although some experimental results have shown that the electron kinetics are limited by the interfacial transfer, we still lack the depth of understanding the microscopic mechanism from a theoretical viewpoint. In the present research, a stochastic quasi-equilibrium (QE) theoretical model and a stochastic random walking (RW) model were established to discuss the electron transport and electron interfacial transfer by taking the electron multi-trapping transport and electron interfacial transfer from the photocatalytic active centers to O 2 into consideration. By carefully investigating the effect of the electron Fermi level (E F ) and the photocatalytic center number on electron transport, we showed that the time taken for an electron to transport to a photocatalytic center predicated by the stochastic RW model was much lower than that predicted by the stochastic QE model, indicating that the electrons cannot reach a QE state during their transport to photocatalytic centers. The stochastic QE model predicted that the electron kinetics of a real photocatalysis for porous nano-crystalline TiO 2 should be limited by electron transport, whereas the stochastic RW model showed that the electron kinetics of a real photocatalysis can be limited by the interfacial transfer. Our simulation results show that the stochastic RW model was more in line with the real electron kinetics that have been observed in experiments, therefore it is concluded that the photoinduced electrons cannot reach a QE state before transferring to O 2 .

  14. A Phase Ib open label, randomized, safety study of SANGUINATE™ in patients with sickle cell anemia.

    Science.gov (United States)

    Misra, Hemant; Bainbridge, James; Berryman, John; Abuchowski, Abraham; Galvez, Kenneth Mauricio; Uribe, Luis Fernando; Hernandez, Angel Luis; Sosa, Nestor Rodolfo

    Treatment of sickle cell anemia is a challenging task and despite the well understood genetic and biochemical pathway of sickle hemoglobin, current therapy continues to be limited to the symptomatic treatment of pain, supplemental oxygen, antibiotics, red blood cell transfusions and hydroxyurea. SANGUINATE is a carbon monoxide releasing molecule and oxygen transfer agent under clinical development for the treatment of sickle cell anemia and comorbidities. An open-label randomized Phase Ib study was performed in adult sickle cell anemia patients. Two dose levels of SANGUINATE were compared to hydroxyurea in 24 homozygotes for Hb SS. Twelve subjects received either a low dose (160mg/kg) of SANGUINATE or 15mg/kg hydroxyurea. Another 12 subjects received either a high dose (320mg/kg) of SANGUINATE or 15mg/kg hydroxyurea. The primary endpoint was the safety of SANGUINATE versus hydroxyurea in sickle cell anemia patients. Secondary endpoints included determination of the plasma pharmacokinetics and assessment of hematologic measurements. Musculoskeletal related adverse events were the most common. Transient troponin I levels increased in three patients, one of whom had an increase in tricuspid regurgitant velocity; however, no clinical signs were noted. Following an assessment of vital signs, tricuspid regurgitant velocity, electrocardiogram, serum biochemistry, hematology, urinalysis, and analysis of reported adverse events, SANGUINATE was found to be safe in stable sickle cell anemia patients. The clinical trial met its primary objective of demonstrating an acceptable safety profile for SANGUINATE in patients with sickle cell anemia. This trial established the safety of SANGUINATE at both dose levels and permitted its advance to Phase II trials. Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

  15. Validation of the k-filtering technique for a signal composed of random-phase plane waves and non-random coherent structures

    Directory of Open Access Journals (Sweden)

    O. W. Roberts

    2014-12-01

    Full Text Available Recent observations of astrophysical magnetic fields have shown the presence of fluctuations being wave-like (propagating in the plasma frame and those described as being structure-like (advected by the plasma bulk velocity. Typically with single-spacecraft missions it is impossible to differentiate between these two fluctuations, due to the inherent spatio-temporal ambiguity associated with a single point measurement. However missions such as Cluster which contain multiple spacecraft have allowed for temporal and spatial changes to be resolved, using techniques such as k filtering. While this technique does not assume Taylor's hypothesis it requires both weak stationarity of the time series and that the fluctuations can be described by a superposition of plane waves with random phases. In this paper we test whether the method can cope with a synthetic signal which is composed of a combination of non-random-phase coherent structures with a mean radius d and a mean separation λ, as well as plane waves with random phase.

  16. Approximation by Penultimate Stable Laws

    NARCIS (Netherlands)

    L.F.M. de Haan (Laurens); L. Peng (Liang); H. Iglesias Pereira

    1997-01-01

    textabstractIn certain cases partial sums of i.i.d. random variables with finite variance are better approximated by a sequence of stable distributions with indices \\\\alpha_n \\\\to 2 than by a normal distribution. We discuss when this happens and how much the convergence rate can be improved by using

  17. Alpha-galactosylceramide in chronic hepatitis B infection: results from a randomized placebo-controlled Phase I/II trial.

    NARCIS (Netherlands)

    Woltman, A.M.; Borg, M.J. Ter; Binda, R.S.; Sprengers, D.; Blomberg, B.M.E. von; Scheper, R.J.; Hayashi, K.; Nishi, N.; Boonstra, A.; Molen, R.G. van der; Janssen, H.L.

    2009-01-01

    BACKGROUND: The glycosphingolipid alpha-galactosylceramide (alpha-GalCer) is known to stimulate invariant natural killer T-cells (iNKTs) and is able to induce powerful antiviral immune responses. The present dose-escalating randomized placebo-controlled Phase I/II trial aimed to investigate

  18. Double random phase spread spectrum spread space technique for secure parallel optical multiplexing with individual encryption key

    Science.gov (United States)

    Hennelly, B. M.; Javidi, B.; Sheridan, J. T.

    2005-09-01

    A number of methods have been recently proposed in the literature for the encryption of 2-D information using linear optical systems. In particular the double random phase encoding system has received widespread attention. This system uses two Random Phase Keys (RPK) positioned in the input spatial domain and the spatial frequency domain and if these random phases are described by statistically independent white noises then the encrypted image can be shown to be a white noise. Decryption only requires knowledge of the RPK in the frequency domain. The RPK may be implemented using a Spatial Light Modulators (SLM). In this paper we propose and investigate the use of SLMs for secure optical multiplexing. We show that in this case it is possible to encrypt multiple images in parallel and multiplex them for transmission or storage. The signal energy is effectively spread in the spatial frequency domain. As expected the number of images that can be multiplexed together and recovered without loss is proportional to the ratio of the input image and the SLM resolution. Many more images may be multiplexed with some loss in recovery. Furthermore each individual encryption is more robust than traditional double random phase encoding since decryption requires knowledge of both RPK and a lowpass filter in order to despread the spectrum and decrypt the image. Numerical simulations are presented and discussed.

  19. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial.

    Science.gov (United States)

    Rush, A John; Marangell, Lauren B; Sackeim, Harold A; George, Mark S; Brannan, Stephen K; Davis, Sonia M; Howland, Robert; Kling, Mitchel A; Rittberg, Barry R; Burke, William J; Rapaport, Mark H; Zajecka, John; Nierenberg, Andrew A; Husain, Mustafa M; Ginsberg, David; Cooke, Robert G

    2005-09-01

    Vagus nerve stimulation (VNS) alters both concentrations of neurotransmitters or their metabolites and functional activity of central nervous system regions dysregulated in mood disorders. An open trial has suggested efficacy. This 10-week, acute, randomized, controlled, masked trial compared adjunctive VNS with sham treatment in 235 outpatients with nonpsychotic major depressive disorder (n = 210) or nonpsychotic, depressed phase, bipolar disorder (n = 25). In the current episode, participants had not responded adequately to between two and six research-qualified medication trials. A two-week, single-blind recovery period (no stimulation) and then 10 weeks of masked active or sham VNS followed implantation. Medications were kept stable. Primary efficacy outcome among 222 evaluable participants was based on response rates (>/=50% reduction from baseline on the 24-item Hamilton Rating Scale for Depression [HRSD(24)]). At 10-weeks, HRSD(24) response rates were 15.2% for the active (n = 112) and 10.0% for the sham (n = 110) groups (p = .251, last observation carried forward [LOCF]). Response rates with a secondary outcome, the Inventory of Depressive Symptomatology - Self-Report (IDS-SR(30)), were 17.0% (active) and 7.3% (sham) (p = .032, LOCF). VNS was well tolerated; 1% (3/235) left the study because of adverse events. This study did not yield definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression.

  20. Broadband diffuse terahertz wave scattering by flexible metasurface with randomized phase distribution.

    Science.gov (United States)

    Zhang, Yin; Liang, Lanju; Yang, Jing; Feng, Yijun; Zhu, Bo; Zhao, Junming; Jiang, Tian; Jin, Biaobing; Liu, Weiwei

    2016-05-26

    Suppressing specular electromagnetic wave reflection or backward radar cross section is important and of broad interests in practical electromagnetic engineering. Here, we present a scheme to achieve broadband backward scattering reduction through diffuse terahertz wave reflection by a flexible metasurface. The diffuse scattering of terahertz wave is caused by the randomized reflection phase distribution on the metasurface, which consists of meta-particles of differently sized metallic patches arranged on top of a grounded polyimide substrate simply through a certain computer generated pseudorandom sequence. Both numerical simulations and experimental results demonstrate the ultralow specular reflection over a broad frequency band and wide angle of incidence due to the re-distribution of the incident energy into various directions. The diffuse scattering property is also polarization insensitive and can be well preserved when the flexible metasurface is conformably wrapped on a curved reflective object. The proposed design opens up a new route for specular reflection suppression, and may be applicable in stealth and other technology in the terahertz spectrum.

  1. Combining double random phase encoding for color image watermarking in quaternion gyrator domain

    Science.gov (United States)

    Shao, Zhuhong; Duan, Yuping; Coatrieux, Gouenou; Wu, Jiasong; Meng, Jinyu; Shu, Huazhong

    2015-05-01

    Quaternion representation of color image has attracted great attention due to its capability to treat holistically the three color channels. In a more general way, it has successfully been used in multi-channel signal processing applications over the past few decades. In this study, a joint encryption/watermarking system with more security based on double random phase encoding (DRPE) in quaternion gyrator transform domain is addressed. In the proposed scheme, an RGB-scale watermark image together with a grayscale watermark image or not is encoded into a quaternion matrix and encrypted through the DRPE, the encrypted data is then fused into the middle coefficients of the quaternion gyrator-transformed host image. In the process of extracting watermarks, it is impossible to retrieve them without authorized keys. Compared with the three channels independently processing approach implemented in fractional Fourier domain, the proposed algorithm achieves lower complexity by reason of avoiding repetitive operations. Experimental results have demonstrated the feasibility of the proposed algorithm and its superior performance in terms of noise robustness.

  2. A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis

    DEFF Research Database (Denmark)

    Vollmer, T L; Sorensen, P S; Selmaj, K

    2014-01-01

    using EDSS was -31 % [hazard ratio (HR) 0.69, p = 0.063], and using Multiple Sclerosis Functional Composite (MSFC) z-score was -77 % (p = 0.150), vs. placebo. IFNβ-1a reduced ARR 26 % (RR = 0.74, 95 % CI 0.60-0.92, p = 0.007), showed no effect on PBVC loss (+11 %, p = 0.14), and changes in disability......The phase III placebo-controlled BRAVO study assessed laquinimod effects in patients with relapsing-remitting MS (RRMS), and descriptively compared laquinimod with interferon beta (IFNβ)-1a (Avonex(®) reference arm). RRMS patients age 18-55 years with Expanded Disability Status Scale (EDSS) scores...... months. The primary endpoint was annualized relapse rate (ARR); secondary endpoints included percent brain volume change (PBVC) and 3-month confirmed disability worsening. In all, 1,331 patients were randomized: laquinimod (n = 434), placebo (n = 450), and IFNβ-1a (n = 447). ARR was not significantly...

  3. Biometrics based key management of double random phase encoding scheme using error control codes

    Science.gov (United States)

    Saini, Nirmala; Sinha, Aloka

    2013-08-01

    In this paper, an optical security system has been proposed in which key of the double random phase encoding technique is linked to the biometrics of the user to make it user specific. The error in recognition due to the biometric variation is corrected by encoding the key using the BCH code. A user specific shuffling key is used to increase the separation between genuine and impostor Hamming distance distribution. This shuffling key is then further secured using the RSA public key encryption to enhance the security of the system. XOR operation is performed between the encoded key and the feature vector obtained from the biometrics. The RSA encoded shuffling key and the data obtained from the XOR operation are stored into a token. The main advantage of the present technique is that the key retrieval is possible only in the simultaneous presence of the token and the biometrics of the user which not only authenticates the presence of the original input but also secures the key of the system. Computational experiments showed the effectiveness of the proposed technique for key retrieval in the decryption process by using the live biometrics of the user.

  4. Innovative measurement of parallelism for parallel transparent plate based on optical scanning holography by using a random-phase pupil.

    Science.gov (United States)

    Luo-Zhi, Zhang; Jian-Ping, Hu; Dao-Ming, Wan; Xing, Zeng; Chun-Miao, Li; Xin, Zhou

    2015-03-20

    A potential method is proposed to measure the parallelism of parallel transparent plate with an advanced lower limit and a convenient process by optical scanning holography (OSH) using a random-phase pupil, which is largely distinct from traditional methods. As a new possible application of OSH, this promising method is demonstrated theoretically and numerical simulations are carried out on a 2  cm×2  cm parallel plate. Discussions are also made on the quality of reconstructed image as well as local mean square error (MSE), which are closely related with the parallelism of sample. These amounts may become the judgments of parallelism, while in most interference methods judgments are paces between two interference fringes. In addition, randomness of random-phase pupil also affects the quality of reconstructed image and local MSE. According to the simulation results, high parallelism usually brings about distinguishable reconstructed information and suppressed local MSE.

  5. Nature of the spin-glass phase in dense packings of Ising dipoles with random anisotropy axes

    Science.gov (United States)

    Alonso, Juan J.; Allés, B.

    2017-09-01

    Using tempered Monte Carlo simulations, we study the the spin-glass phase of dense packings of Ising dipoles pointing along random axes. We consider systems of dipoles (i) placed on the sites of a simple cubic lattice with lattice constant d, and (ii) placed at the center of random close packed spheres of diameter d that occupy 64% of the volume. For both cases, we find a spin-glass phase below a certain temperature T sg. By analysing the data obtained for the overlap parameter, the associated correlation length, as well as the statistics of the overlap distributions of individual samples, we find a behavior consistent with quasi-long-range order in the spin-glass phase, similar to the one previously found in strongly diluted dipolar systems.

  6. Nature of the spin-glass phase in dense packings of Ising dipoles with random anisotropy axes.

    Science.gov (United States)

    Alonso, Juan J; Allés, B

    2017-09-06

    Using tempered Monte Carlo simulations, we study the the spin-glass phase of dense packings of Ising dipoles pointing along random axes. We consider systems of dipoles (i) placed on the sites of a simple cubic lattice with lattice constant d, and (ii) placed at the center of random close packed spheres of diameter d that occupy 64% of the volume. For both cases, we find a spin-glass phase below a certain temperature T sg. By analysing the data obtained for the overlap parameter, the associated correlation length, as well as the statistics of the overlap distributions of individual samples, we find a behavior consistent with quasi-long-range order in the spin-glass phase, similar to the one previously found in strongly diluted dipolar systems.

  7. Trunk Exercises Improve Gait Symmetry in Parkinson Disease: A Blind Phase II Randomized Controlled Trial.

    Science.gov (United States)

    Hubble, Ryan P; Naughton, Geraldine; Silburn, Peter A; Cole, Michael H

    2018-03-01

    Deficits in step-to-step symmetry and trunk muscle activations have been linked to falls in Parkinson disease. Given such symptoms are poorly managed with anti-parkinsonian medications, alternate therapies are needed. This blind phase II randomized controlled trial sought to establish whether exercise can improve step-to-step symmetry in Parkinson disease. Twenty-four Parkinson disease patients with a falls history completed baseline assessments of symptom severity, balance confidence, mobility, and quality of life. Step-to-step symmetry was assessed by deriving harmonic ratios from three-dimensional accelerations collected for the head and trunk. Patients were randomly assigned to either 12 wks of exercise and falls prevention education or falls prevention education only. Both groups repeated the baseline tests 12 and 24 wks after the initial assessment. The Australian and New Zealand Clinical Trials Registry number is ACTRN12613001175763. At 12 wks, the exercise group had statistically significant and clinically relevant improvements in anterior-posterior step-to-step trunk symmetry. In contrast, the education group recorded statistically significant and clinically meaningful reductions in medial-lateral and vertical step-to-step trunk symmetry at 12 wks. Given that step-to-step symmetry improved for the exercise group and declined for the education group after intervention, active interventions seem more suited to increasing independence and quality of life for people with Parkinson disease. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to do the following: (1) Describe the effect deficits in trunk muscle function have on gait in individuals with Parkinson disease; (2) Identify the benefits of targeted trunk exercises on step-to-step symmetry; and (3) Discuss the benefits of improving step-to-step symmetry in individuals with Parkinson

  8. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention.

    Science.gov (United States)

    Chen, Andrew C; Martin, Andrew J; Choy, Bonita; Fernández-Peñas, Pablo; Dalziell, Robyn A; McKenzie, Catriona A; Scolyer, Richard A; Dhillon, Haryana M; Vardy, Janette L; Kricker, Anne; St George, Gayathri; Chinniah, Niranthari; Halliday, Gary M; Damian, Diona L

    2015-10-22

    Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses. In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months. The primary end point was the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included the number of new squamous-cell carcinomas and basal-cell carcinomas and the number of actinic keratoses during the 12-month intervention period, the number of nonmelanoma skin cancers in the 6-month postintervention period, and the safety of nicotinamide. At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39] lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (Pnicotinamide was discontinued. Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. (Funded by the National Health and Medical Research Council; ONTRAC Australian New Zealand Clinical Trials

  9. Bicomponent Block Copolymers Derived from One or More Random Copolymers as an Alternative Route to Controllable Phase Behavior

    Energy Technology Data Exchange (ETDEWEB)

    Ashraf, Arman R. [Corporate Research and Development, The Procter and Gamble Company, Cincinnati OH 45224 USA; Ryan, Justin J. [Department of Materials Science and Engineering, North Carolina State University, Raleigh NC 27695 USA; Satkowski, Michael M. [Corporate Research and Development, The Procter and Gamble Company, Cincinnati OH 45224 USA; Lee, Byeongdu [Advanced Photon Source, Argonne National Laboratory, Argonne IL 60439 USA; Smith, Steven D. [Corporate Research and Development, The Procter and Gamble Company, Cincinnati OH 45224 USA; Spontak, Richard J. [Department of Materials Science and Engineering, North Carolina State University, Raleigh NC 27695 USA; Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh NC 27695 USA

    2017-06-29

    Block copolymers have been extensively studied due to their ability to spontaneously self-organize into a wide variety of morphologies that are valuable in energy-, medical- and conservation-related (nano)technologies. While the phase behavior of bicomponent diblock and triblock copolymers is conventionally governed by temperature and individual block masses, we demonstrate that their phase behavior can alternatively be controlled through the use of blocks with random monomer sequencing. Block random copolymers (BRCs), i.e., diblock copolymers wherein one or both blocks is a random copolymer comprised of A and B repeat units, have been synthesized, and their phase behavior, expressed in terms of the order-disorder transition (ODT), has been investigated. Our results establish that, depending on the block composition contrast and molecular weight, BRCs can microphase-separate. We also report that the predicted ODT can be generated at relatively constant molecular weight and temperature with these new soft materials. This sequence-controlled synthetic strategy is extended to thermoplastic elastomeric triblock copolymers differing in chemistry and possessing a random-copolymer midblock.

  10. ATX-101 for reduction of submental fat: A phase III randomized controlled trial.

    Science.gov (United States)

    Humphrey, Shannon; Sykes, Jonathan; Kantor, Jonathan; Bertucci, Vince; Walker, Patricia; Lee, Daniel R; Lizzul, Paul F; Gross, Todd M; Beddingfield, Frederick C

    2016-10-01

    ATX-101, an injectable form of deoxycholic acid, causes adipocytolysis when injected subcutaneously into fat. We sought to evaluate the efficacy and safety of ATX-101. In this phase III trial (REFINE-2), adults dissatisfied with their moderate or severe submental fat (SMF) were randomized to ATX-101 or placebo. Coprimary end points, evaluated at 12 weeks after last treatment, were composite improvements of 1 or more grades and 2 or more grades in SMF observed on both the validated Clinician- and Patient-Reported SMF Rating Scales. Other end points included magnetic resonance imaging-based assessment of submental volume, assessment of psychological impact of SMF, and additional patient-reported outcomes. Among those treated with ATX-101 or placebo (n = 258/treatment group), 66.5% versus 22.2%, respectively, achieved a composite improvement of 1 or more grades (Mantel-Haenszel risk ratio 2.98; 95% confidence interval 2.31-3.85) and 18.6% versus 3.0% achieved a composite improvement of 2 or more grades in SMF (Mantel-Haenszel risk ratio 6.27; 95% confidence interval 2.91-13.52; P ATX-101 were more likely to achieve submental volume reduction confirmed by magnetic resonance imaging, greater reduction in psychological impact of SMF, and satisfaction with treatment (P ATX-101 group and 76.9% in the placebo group were localized to the injection site. Follow-up was limited to 44 weeks. ATX-101 is an alternative treatment for SMF reduction. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  11. Early Aqueous Suppressant Therapy on Hypertensive Phase Following Glaucoma Drainage Device Procedure: A Randomized Prospective Trial.

    Science.gov (United States)

    Law, Simon K; Kornmann, Helen L; Giaconi, JoAnn A; Kwong, Allen; Tran, Eric; Caprioli, Joseph

    2016-03-01

    To prospectively evaluate the effect of early aqueous suppression (therapy) on hypertensive phase (HP) and intraocular pressure (IOP) control after implantation of silicone Ahmed glaucoma valve (AGV). Patients who underwent AGV implantation were randomized to initiate therapy (including β-blockers, α-agonists, or carbonic anhydrase inhibitors) when postoperative IOP>10 mm Hg (low-IOP initiation group) or >17 mm Hg (moderate-IOP initiation group). HP was defined as an IOP>21 mm Hg during the first 6 postoperative months, after an initial IOP reduction to measures included the occurrence of HP and IOP control. Fifty-two eyes (50 patients) underwent AGV implantation. Average follow-up was 21.9±10.7 months. HP was observed in 21 eyes (40.4%) with average peak IOP of 30±8 mm Hg, onset at 32±30 days, and duration of 15±32 days. One year postoperatively, those eyes with HP had higher IOP than eyes that did not develop HP (15.1±5.2, 11.4±4.3, respectively; P=0.021) and required more additional glaucoma surgeries (28.6%, 3.2%, respectively; P=0.013). The peak IOP at week 3 postoperatively in the low-IOP initiation group (26 eyes) was significantly lower than in the moderate-IOP initiation group (26 eyes; 15.7±3.6, 20.6±8.9, respectively; P=0.012). Eyes with therapy started after HP onset had significantly higher postoperative IOP from 2 to 4 months. Therapy initiated before the development of HP was not associated with a higher complication rate. Aqueous suppression initiated in the early postoperative period while IOPs were still in the low-teens and was able to reduce the incidence of IOP spike associated with the HP without an increased complication rate.

  12. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia.

    Science.gov (United States)

    Byrd, John C; Flynn, Joseph M; Kipps, Thomas J; Boxer, Michael; Kolibaba, Kathryn S; Carlile, David J; Fingerle-Rowson, Guenter; Tyson, Nicola; Hirata, Jamie; Sharman, Jeff P

    2016-01-07

    Obinutuzumab is a glycoengineered, type 2 anti-CD20 humanized antibody with single-agent activity in relapsed chronic lymphocytic leukemia (CLL). With other CD20 antibodies, a dose-response relationship has been shown. We therefore performed a randomized phase 2 study in symptomatic, untreated CLL patients to evaluate if an obinutuzumab dose response exists. Obinutuzumab was given at a dose of 1000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 8 and day 15 of cycle 1; 1000 mg day 1 of cycles 2-8) or 2000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 3, 2000 mg day 8 and day 15 of cycle 1; 2000 mg day 1 of cycles 2-8). The primary end point was overall response rate (ORR). Eighty patients were enrolled with similar demographics: median age 67 years, 41% high-risk Rai disease, and 10% del(17p)(13.1). ORR (67% vs 49%, P = .08) and complete response (CR) or CR with incomplete cytopenia response (20% vs 5%) favored 2000 mg obinutuzumab. Overall, therapy was well tolerated, and infusion events were manageable. This study demonstrates significant efficacy of obinutuzumab monotherapy, for 1000 mg as well as for 2000 mg, in untreated CLL patients with acceptable toxicity. Although exploratory, a dose-response relationship may exist, but its relevance to improving progression-free survival is uncertain and will require further follow-up. This trial was registered at www.clinicaltrials.gov as #NCT01414205. © 2016 by The American Society of Hematology.

  13. Lowest excited 2+ and 3- states in even-A N =82 and N =126 isotones from relativistic quasiparticle random-phase approximation

    Science.gov (United States)

    Ansari, A.

    2017-05-01

    Excitation energy, reduced transition rates, and g factors of the lowest 2+ and 3- states of even-even N =82 and N =126 isotones are studied in relativistic QRPA formalism. These values are compared to available experimental data and some of the recent theoretical results. In the following the obtained results are presented first for N =82 isotones with Z =36 -72 , that is very neutron-rich to neutron-deficient nuclei with N /Z varying from 2.28 to 1.14 and then for N =126 isotones with Z =76 -92 . These calculations are performed employing NL3, as well as its recently revised version NL 3* set of the RMF Lagrangian parameters. It is found that both the interaction sets produce almost similar results. The agreement with available data is rather satisfactory in view of such a wide range of nuclei considered here, though there are serious disagreements like in the case of 140Ce and properties of 3- states of N =126 isotones.

  14. Hybrid random walk-linear discriminant analysis method for unwrapping quantitative phase microscopy images of biological samples

    Science.gov (United States)

    Kim, Diane N. H.; Teitell, Michael A.; Reed, Jason; Zangle, Thomas A.

    2015-11-01

    Standard algorithms for phase unwrapping often fail for interferometric quantitative phase imaging (QPI) of biological samples due to the variable morphology of these samples and the requirement to image at low light intensities to avoid phototoxicity. We describe a new algorithm combining random walk-based image segmentation with linear discriminant analysis (LDA)-based feature detection, using assumptions about the morphology of biological samples to account for phase ambiguities when standard methods have failed. We present three versions of our method: first, a method for LDA image segmentation based on a manually compiled training dataset; second, a method using a random walker (RW) algorithm informed by the assumed properties of a biological phase image; and third, an algorithm which combines LDA-based edge detection with an efficient RW algorithm. We show that the combination of LDA plus the RW algorithm gives the best overall performance with little speed penalty compared to LDA alone, and that this algorithm can be further optimized using a genetic algorithm to yield superior performance for phase unwrapping of QPI data from biological samples.

  15. Comparison between amniotomy, oxytocin or both for augmentation of labor in prolonged latent phase: a randomized controlled trial.

    Science.gov (United States)

    Nachum, Zohar; Garmi, Gali; Kadan, Yfat; Zafran, Noah; Shalev, Eliezer; Salim, Raed

    2010-11-07

    A prolonged latent phase is independently associated with an increased incidence of subsequent labor abnormalities. We aimed to compare between oxytocin augmentation, amniotomy and a combination of both on the duration of labor among women with a prolonged latent phase. Women with a singleton fetus in cephalic presentation who have a prolonged latent phase, were randomly allocated to amniotomy (group 1), oxytocin (group 2) or both (group 3). A group of women who progressed spontaneously without intervention composed the control group (group 4). The primary outcome was the duration of time from initiation of augmentation until delivery. A total of 213 women were consented and randomized to group 1 (70 women), group 2 (72 women) and group 3 (71 women). Group 4 was composed from additional 70 women. A mean reduction of 120 minutes in labor duration was observed among group 3 compared to group 1 (p = 0.08) and 180 minutes compared to group 2 and 4 (p = 0.001). Women in group 3 had a shorter length of time from augmentation until the beginning of the active phase and a shorter first stage of labor than group 1 (p = 0.03), group 2 (p = 0.001) and group 4 (p = 0.001). Satisfaction was greater among group 3 and 4. Mode of delivery and neonatal outcome were comparable between the groups. Labor augmentation by combined amniotomy and oxytocin among women with a prolonged latent phase at term seems superior compared to either of them alone.

  16. Computing approximate diagnoses by using approximate entailment

    NARCIS (Netherlands)

    Teije, A. ten; Harmelen, van F.A.H.

    1996-01-01

    The most widely accepted models of diagnostic reasoning are all phrased in terms of the logical consequence relations. In work in recent years, Schaerf and Cadoli have proposed efficient approximations of the classical consequence relation. The central idea of this paper is to parameterise the

  17. Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis

    OpenAIRE

    Constantinescu, Cris S.; Asher, Aliya; Fryze, Waldemar; Kozubski, Wojciech; Wagner, Frank; Aram, Jehan; Tanasescu, Radu; Korolkiewicz, Roman P.; Dirnberger-Hertweck, Maren; Steidl, Stefan; Libretto, Susan E.; Sprenger, Till; Radue, Ernst W.

    2015-01-01

    Objectives: To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity. Methods: In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infu...

  18. Approximation of Laws

    Science.gov (United States)

    Niiniluoto, Ilkka

    2014-03-01

    Approximation of laws is an important theme in the philosophy of science. If we can make sense of the idea that two scientific laws are "close" to each other, then we can also analyze such methodological notions as approximate explanation of laws, approximate reduction of theories, approximate empirical success of theories, and approximate truth of laws. Proposals for measuring the distance between quantitative scientific laws were given in Niiniluoto (1982, 1987). In this paper, these definitions are reconsidered as a response to the interesting critical remarks by Liu (1999).

  19. Omeprazole-Domperidone Fixed Dose Combination vs Omeprazole Monotherapy: A Phase 4, Open-Label, Comparative, Parallel Randomized Controlled Study in Mild to Moderate Gastroesophageal Reflux Disease

    Directory of Open Access Journals (Sweden)

    KY Marakhouski

    2017-05-01

    Full Text Available Aim: To compare the efficacy and safety of omeprazole-domperidone combination vs omeprazole monotherapy in gastroesophageal reflux disease (GERD. Methods: In a comparative, randomized controlled, phase 4 study, outpatients with GERD were randomly allocated to either group 1 (omeprazole 20 mg + domperidone 30 mg or group 2 (omeprazole 20 mg in an equal ratio; 2 capsules daily in the morning were administered for 8 weeks. Results: Sixty patients were enrolled. Esophagitis reversal was observed in 92% patients in group 1 vs 65.2% in group 2. Approximately, 83.3% patients in group 1 vs 43.3% patients in group 2 demonstrated full cupping of reflux symptoms at 8 weeks. Combined therapy resulted in significantly longer period of heartburn-free days (23 vs 12 days on omeprazole. There were no safety concerns. Conclusions: Omeprazole-domperidone combination was more effective than omeprazole alone in providing complete cupping of reflux symptoms and healing of esophagitis in patients with GERD. Both the treatments were well tolerated with few reports of adverse events. Trial registration: This trial is registered with http://clinicaltrials.gov , number NCT02140073.

  20. Diophantine approximation and Dirichlet series

    CERN Document Server

    Queffélec, Hervé

    2013-01-01

    This self-contained book will benefit beginners as well as researchers. It is devoted to Diophantine approximation, the analytic theory of Dirichlet series, and some connections between these two domains, which often occur through the Kronecker approximation theorem. Accordingly, the book is divided into seven chapters, the first three of which present tools from commutative harmonic analysis, including a sharp form of the uncertainty principle, ergodic theory and Diophantine approximation to be used in the sequel. A presentation of continued fraction expansions, including the mixing property of the Gauss map, is given. Chapters four and five present the general theory of Dirichlet series, with classes of examples connected to continued fractions, the famous Bohr point of view, and then the use of random Dirichlet series to produce non-trivial extremal examples, including sharp forms of the Bohnenblust-Hille theorem. Chapter six deals with Hardy-Dirichlet spaces, which are new and useful Banach spaces of anal...

  1. Sparse approximation with bases

    CERN Document Server

    2015-01-01

    This book systematically presents recent fundamental results on greedy approximation with respect to bases. Motivated by numerous applications, the last decade has seen great successes in studying nonlinear sparse approximation. Recent findings have established that greedy-type algorithms are suitable methods of nonlinear approximation in both sparse approximation with respect to bases and sparse approximation with respect to redundant systems. These insights, combined with some previous fundamental results, form the basis for constructing the theory of greedy approximation. Taking into account the theoretical and practical demand for this kind of theory, the book systematically elaborates a theoretical framework for greedy approximation and its applications.  The book addresses the needs of researchers working in numerical mathematics, harmonic analysis, and functional analysis. It quickly takes the reader from classical results to the latest frontier, but is written at the level of a graduate course and do...

  2. Driven interfaces in random media at finite temperature: existence of an anomalous zero-velocity phase at small external force.

    Science.gov (United States)

    Monthus, Cécile; Garel, Thomas

    2008-10-01

    The motion of driven interfaces in random media at finite temperature T and small external force F is usually described by a linear displacement h{G}(t) approximately V(F,T)t at large times, where the velocity vanishes according to the creep formula as V(F,T) approximately e;{-K(T)F;{mu}} for F-->0 . In this paper, we question this picture on the specific example of the directed polymer in a two-dimensional random medium. We have recently shown [C. Monthus and T. Garel, J. Phys. A 41, 255002 (2008)] that its dynamics for F=0 can be analyzed in terms of a strong disorder renormalization procedure, where the distribution of renormalized barriers flows towards some "infinite disorder fixed point." In the present paper, we obtain that for small F , this "infinite disorder fixed point" becomes a "strong disorder fixed point" with an exponential distribution of renormalized barriers. The corresponding distribution of trapping times then only decays as a power law P(tau) approximately 1tau;{1+alpha} , where the exponent alpha(F,T) vanishes as alpha(F,T) proportional, variant F micro as F-->0 . Our conclusion is that in the small force region alpha(F,T)infinity induces strong non-self-averaging effects that invalidate the usual creep formula obtained by replacing all trapping times by the typical value. We find instead that the motion is only sublinearly in time h{G}(t) approximately t;{alpha(F,T)} , i.e., the asymptotic velocity vanishes V=0 . This analysis is confirmed by numerical simulations of a directed polymer with a metric constraint driven in a traps landscape. We moreover obtain that the roughness exponent, which is governed by the equilibrium value zeta{eq}=23 up to some large scale, becomes equal to zeta=1 at the largest scales.

  3. Approximate Loop Unrolling

    OpenAIRE

    Rodriguez-Cancio, Marcelino; Combemale, Benoit; Baudry, Benoit

    2016-01-01

    We introduce Approximate Unrolling, a loop optimization that reduces execution time and energy consumption, exploiting the existence of code regions that can endure some degree of approximation while still producing acceptable results. This work focuses on a specific kind of forgiving region: counted loops that map a given functions over the elements of an array. Approximate Unrolling transforms loops in a similar way Loop Unrolling does. However, unlike its exact counterpart, our optimizatio...

  4. Safety, Tolerability and Pharmacokinetics of Single Doses of Oxytocin Administered via an Inhaled Route in Healthy Females: Randomized, Single-blind, Phase 1 Study.

    Science.gov (United States)

    Fernando, Disala; Siederer, Sarah; Singh, Sunita; Schneider, Ian; Gupta, Ashutosh; Powell, Marcy; Richards, Duncan; McIntosh, Michelle P; Lambert, Peter; Fowles, Susan

    2017-08-01

    The utility of intramuscular (IM) oxytocin for the prevention of postpartum hemorrhage in resource-poor settings is limited by the requirement for temperature-controlled storage and skilled staff to administer the injection. We evaluated the safety, tolerability and pharmacokinetics (PK) of a heat-stable, inhaled (IH) oxytocin formulation. This phase 1, randomized, single-center, single-blind, dose-escalation, fixed-sequence study (NCT02542813) was conducted in healthy, premenopausal, non-pregnant, non-lactating women aged 18-45years. Subjects initially received IM oxytocin 10 international units (IU) on day 1, IH placebo on day 2, and IH oxytocin 50μg on day 3. Subjects were then randomized 4:1 using validated GSK internal software to IH placebo or ascending doses of IH oxytocin (200, 400, 600μg). PK was assessed by comparing systemic exposure (maximum observed plasma concentration, area under the concentration-time curve, and plasma concentrations at 10 and 30min post dose) for IH versus IM oxytocin. Adverse events (AEs), spirometry, laboratory tests, vital signs, electrocardiograms, physical examinations, and cardiac telemetry were assessed. Subjects were recruited between September 14, 2015 and October 12, 2015. Of the 16 subjects randomized following initial dosing, 15 (IH placebo n=3; IH oxytocin n=12) completed the study. IH (all doses) and IM oxytocin PK profiles were comparable in shape. However, systemic exposure with IH oxytocin 400μg most closely matched IM oxytocin 10IU. Systemic exposure was approximately dose proportional for IH oxytocin. No serious AEs were reported. No clinically significant findings were observed for any safety parameters. These data suggest that similar oxytocin systemic exposure can be achieved with IM and IH administration routes, and no safety concerns were identified with either route. The inhalation route may offer the opportunity to increase access to oxytocin for women giving birth in resource-poor settings. Copyright

  5. Comparison between amniotomy, oxytocin or both for augmentation of labor in prolonged latent phase: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Shalev Eliezer

    2010-11-01

    Full Text Available Abstract Background A prolonged latent phase is independently associated with an increased incidence of subsequent labor abnormalities. We aimed to compare between oxytocin augmentation, amniotomy and a combination of both on the duration of labor among women with a prolonged latent phase. Methods Women with a singleton fetus in cephalic presentation who have a prolonged latent phase, were randomly allocated to amniotomy (group 1, oxytocin (group 2 or both (group 3. A group of women who progressed spontaneously without intervention composed the control group (group 4. The primary outcome was the duration of time from initiation of augmentation until delivery. Results A total of 213 women were consented and randomized to group 1 (70 women, group 2 (72 women and group 3 (71 women. Group 4 was composed from additional 70 women. A mean reduction of 120 minutes in labor duration was observed among group 3 compared to group 1 (p = 0.08 and 180 minutes compared to group 2 and 4 (p = 0.001. Women in group 3 had a shorter length of time from augmentation until the beginning of the active phase and a shorter first stage of labor than group 1 (p = 0.03, group 2 (p = 0.001 and group 4 (p = 0.001. Satisfaction was greater among group 3 and 4. Mode of delivery and neonatal outcome were comparable between the groups. Conclusion Labor augmentation by combined amniotomy and oxytocin among women with a prolonged latent phase at term seems superior compared to either of them alone.

  6. Orlistat in clozapine- or olanzapine-treated patients with overweight or obesity: a 16-week open-label extension phase and both phases of a randomized controlled trial.

    Science.gov (United States)

    Tchoukhine, Evgueni; Takala, Pirjo; Hakko, Helinä; Raidma, Mirjam; Putkonen, Hanna; Räsänen, Pirkko; Terevnikov, Viacheslav; Stenberg, Jan-Henry; Eronen, Markku; Joffe, Grigori

    2011-03-01

    To explore long-term effects of orlistat in adult clozapine- or olanzapine-treated patients with DSM-IV-diagnosed schizophrenia and overweight or obesity who tolerate orlistat. Orlistat or placebo was added to clozapine or olanzapine in stable doses in a 16-week randomized controlled trial. Open-label orlistat was added to the antipsychotics during a 16-week extension phase for those completing the double-blind phase. No low-calorie diet or participation in behavioral programs was required. Body weight (primary outcome) and some metabolic parameters were measured prospectively. Analyses were performed for those completing both phases (ie, population differing from that reported earlier). The study was conducted from 2004 through 2005. During the open-label phase, the 44 patients experienced mean ± SD body weight loss of -1.29 ± 3.04 kg, P = .007. During both phases, men (but not women) showed a weight loss of -2.39 ± 5.45 kg, P = .023. Some subgroups showed desirable changes in several metabolic parameters. Prolonged (32 weeks) orlistat treatment yielded no additional benefits as compared to short (16 weeks) treatment. In clozapine- or olanzapine-treated overweight or obese patients able to take orlistat on a long-term basis, the drug, with no concomitant hypocaloric diet or behavioral interventions, caused moderate weight loss only in men. However, some metabolic benefits may be achieved independently of weight changes. In patients who do not respond to orlistat within the first 16 weeks, continuation treatment may provide no additional benefits. controlled-trials.com Identifier: ISRCTN65731856. © Copyright 2011 Physicians Postgraduate Press, Inc.

  7. Expectation Consistent Approximate Inference

    DEFF Research Database (Denmark)

    Opper, Manfred; Winther, Ole

    2005-01-01

    We propose a novel framework for approximations to intractable probabilistic models which is based on a free energy formulation. The approximation can be understood from replacing an average over the original intractable distribution with a tractable one. It requires two tractable probability dis...

  8. Phase structure of the O(n) model on a random lattice for n > 2

    DEFF Research Database (Denmark)

    Durhuus, B.; Kristjansen, C.

    1997-01-01

    We show that coarse graining arguments invented for the analysis of multi-spin systems on a randomly triangulated surface apply also to the O(n) model on a random lattice. These arguments imply that if the model has a critical point with diverging string susceptibility, then either γ = +1...... by (γ̃, γ) = (-1/m, 1/m+1), m = 2, 3, . . . We also show that at the critical points with positive string susceptibility exponent the average number of loops on the surface diverges while the average length of a single loop stays finite....

  9. Quasi-Coherent Noise Jamming to LFM Radar Based on Pseudo-random Sequence Phase-modulation

    Directory of Open Access Journals (Sweden)

    N. Tai

    2015-12-01

    Full Text Available A novel quasi-coherent noise jamming method is proposed against linear frequency modulation (LFM signal and pulse compression radar. Based on the structure of digital radio frequency memory (DRFM, the jamming signal is acquired by the pseudo-random sequence phase-modulation of sampled radar signal. The characteristic of jamming signal in time domain and frequency domain is analyzed in detail. Results of ambiguity function indicate that the blanket jamming effect along the range direction will be formed when jamming signal passes through the matched filter. By flexible controlling the parameters of interrupted-sampling pulse and pseudo-random sequence, different covering distances and jamming effects will be achieved. When the jamming power is equivalent, this jamming obtains higher process gain compared with non-coherent jamming. The jamming signal enhances the detection threshold and the real target avoids being detected. Simulation results and circuit engineering implementation validate that the jamming signal covers real target effectively.

  10. On approximating multi-criteria TSP

    NARCIS (Netherlands)

    Manthey, Bodo; Albers, S.; Marion, J.-Y.

    2009-01-01

    We present approximation algorithms for almost all variants of the multi-criteria traveling salesman problem (TSP), whose performances are independent of the number $k$ of criteria and come close to the approximation ratios obtained for TSP with a single objective function. We present randomized

  11. On approximating multi-criteria TSP

    NARCIS (Netherlands)

    Manthey, Bodo

    We present approximation algorithms for almost all variants of the multicriteria traveling salesman problem (TSP). First, we devise randomized approximation algorithms for multicriteria maximum traveling salesman problems (Max-TSP). For multicriteria Max-STSP where the edge weights have to be

  12. Parenteral nutrition at the palliative phase of advanced cancer: the ALIM-K study protocol for a randomized controlled trial.

    Science.gov (United States)

    Pazart, Lionel; Cretin, Elodie; Grodard, Ghislain; Cornet, Cecile; Mathieu-Nicot, Florence; Bonnetain, Franck; Mercier, Mariette; Cuynet, Patrice; Bouleuc, Carole; Aubry, Regis

    2014-09-24

    Malnutrition is a common complication in patients at the palliative stage of cancer. During the curative phase of cancer, optimal enteral or parenteral nutrition intake can reduce morbidity and mortality, and improve quality of life. When the main goal of treatment becomes palliative, introduction of artificial nutrition is controversial. Although scientific societies do not recommend the introduction of artificial nutrition in all cases of malnutrition, especially in hypophagic patients if their life expectancy is shorter than 2 months, considerable differences in the use of parenteral nutrition in nonsurgical oncology practice are noted around the world. One explanation is a paucity of well-conducted randomized controlled trials in these situations, and consequently, the risk/benefit ratio of parenteral nutrition and its impact on quality of life in palliative care remains uncertain. The ALIM-K study is a French national multicenter randomized controlled trial designed to evaluate the effectiveness of parenteral nutrition, versus an exclusive oral-feeding supply, on the quality of life of malnourished patients who have a functional digestive tube and who are at the palliative phase of advanced cancer with a life expectancy of more than 2 months. This article presents the methodologic options chosen for our study, and in particular, the choice of the Zelen method of randomization, the definition of the main end point (quality of life), the choice of comparator (oral feeding), and the inclusion criteria (life expectancy of more than 2 months), which are all critical points in building a randomized controlled trial in the setting of palliative care. This study was registered with the clinical trials database ClinicalTrials.gov on May 27, 2014, under the number NCT02151214.

  13. Empirical forward scattering phase functions from 0.08 to 16 deg. for randomly shaped terrigenous 1-21 microm sediment grains.

    Science.gov (United States)

    Agrawal, Y C; Mikkelsen, Ole A

    2009-05-25

    We present in-water forward scattering phase functions covering the angle range 0.08 to 16 degrees for 19 narrow-sized dispersions of randomly shaped sediment grains. These dispersions cover particle size range from 1 to 20 microns. These phase functions offer a realistic alternative to Mie theory. Qualitatively, (i) the magnitude of phase functions at the smallest angles for equal size spheres and randomly shaped particles are nearly equal; (ii) the oscillations predicted by Mie theory for spheres disappear for random shaped grains, and (iii) the tendency of phase functions of large spheres to merge at large angles is also seen with randomly shaped grains. The data are also provided in tabulated form.

  14. Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: Crossover extension to a randomized, double-blind, Phase III study

    NARCIS (Netherlands)

    M.D. Bronstein (Marcello); Fleseriu, M. (Maria); S.J.C.M.M. Neggers (Bas); A. Colao (Annamaria); Sheppard, M. (Michael); Gu, F. (Feng); Shen, C.-C. (Chiung-Chyi); M.R. Gadelha (Mônica R.); Farrall, A.J. (Andrew J.); Reséndiz, K.H. (Karina Hermosillo); Ruffin, M. (Matthieu); Chen, Y. (YinMiao); P.U. Freda (Pamela)

    2016-01-01

    markdownabstractBackground Many patients with acromegaly do not achieve biochemical control with first-generation somatostatin analogues. A large, multicenter, randomized, Phase III core study demonstrated that pasireotide LAR had significantly superior efficacy over octreotide LAR. This analysis

  15. W-Band Millimeter-Wave Vector Signal Generation Based on Precoding-Assisted Random Photonic Frequency Tripling Scheme Enabled by Phase Modulator

    National Research Council Canada - National Science Library

    Li, Xinying; Xu, Yuming; Xiao, Jiangnan; Yu, Jianjun

    2016-01-01

    We propose W-band photonic millimeter-wave (mm-wave) vector signal generation employing a precoding-assisted random frequency tripling scheme enabled by a single phase modulator cascaded with a wavelength selective switch (WSS...

  16. Mathematics of Approximation

    CERN Document Server

    de Villiers, Johan

    2012-01-01

    The approximation of a continuous function by either an algebraic polynomial, a trigonometric polynomial, or a spline, is an important issue in application areas like computer-aided geometric design and signal analysis. This book is an introduction to the mathematical analysis of such approximation, and, with the prerequisites of only calculus and linear algebra, the material is targeted at senior undergraduate level, with a treatment that is both rigorous and self-contained. The topics include polynomial interpolation; Bernstein polynomials and the Weierstrass theorem; best approximations in

  17. Approximate calculation of integrals

    CERN Document Server

    Krylov, V I

    2006-01-01

    A systematic introduction to the principal ideas and results of the contemporary theory of approximate integration, this volume approaches its subject from the viewpoint of functional analysis. In addition, it offers a useful reference for practical computations. Its primary focus lies in the problem of approximate integration of functions of a single variable, rather than the more difficult problem of approximate integration of functions of more than one variable.The three-part treatment begins with concepts and theorems encountered in the theory of quadrature. The second part is devoted to t

  18. Generalized optimal design for two-arm, randomized phase II clinical trials with endpoints from the exponential dispersion family.

    Science.gov (United States)

    Jiang, Wei; Mahnken, Jonathan D; He, Jianghua; Mayo, Matthew S

    2016-11-01

    For two-arm randomized phase II clinical trials, previous literature proposed an optimal design that minimizes the total sample sizes subject to multiple constraints on the standard errors of the estimated event rates and their difference. The original design is limited to trials with dichotomous endpoints. This paper extends the original approach to be applicable to phase II clinical trials with endpoints from the exponential dispersion family distributions. The proposed optimal design minimizes the total sample sizes needed to provide estimates of population means of both arms and their difference with pre-specified precision. Its applications on data from specific distribution families are discussed under multiple design considerations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. TMB: Automatic differentiation and laplace approximation

    DEFF Research Database (Denmark)

    Kristensen, Kasper; Nielsen, Anders; Berg, Casper Willestofte

    2016-01-01

    computations. The user defines the joint likelihood for the data and the random effects as a C++ template function, while all the other operations are done in R; e.g., reading in the data. The package evaluates and maximizes the Laplace approximation of the marginal likelihood where the random effects...

  20. Multiple-image authentication with a cascaded multilevel architecture based on amplitude field random sampling and phase information multiplexing.

    Science.gov (United States)

    Fan, Desheng; Meng, Xiangfeng; Wang, Yurong; Yang, Xiulun; Pan, Xuemei; Peng, Xiang; He, Wenqi; Dong, Guoyan; Chen, Hongyi

    2015-04-10

    A multiple-image authentication method with a cascaded multilevel architecture in the Fresnel domain is proposed, in which a synthetic encoded complex amplitude is first fabricated, and its real amplitude component is generated by iterative amplitude encoding, random sampling, and space multiplexing for the low-level certification images, while the phase component of the synthetic encoded complex amplitude is constructed by iterative phase information encoding and multiplexing for the high-level certification images. Then the synthetic encoded complex amplitude is iteratively encoded into two phase-type ciphertexts located in two different transform planes. During high-level authentication, when the two phase-type ciphertexts and the high-level decryption key are presented to the system and then the Fresnel transform is carried out, a meaningful image with good quality and a high correlation coefficient with the original certification image can be recovered in the output plane. Similar to the procedure of high-level authentication, in the case of low-level authentication with the aid of a low-level decryption key, no significant or meaningful information is retrieved, but it can result in a remarkable peak output in the nonlinear correlation coefficient of the output image and the corresponding original certification image. Therefore, the method realizes different levels of accessibility to the original certification image for different authority levels with the same cascaded multilevel architecture.

  1. Approximation Behooves Calibration

    DEFF Research Database (Denmark)

    da Silva Ribeiro, André Manuel; Poulsen, Rolf

    2013-01-01

    Calibration based on an expansion approximation for option prices in the Heston stochastic volatility model gives stable, accurate, and fast results for S&P500-index option data over the period 2005–2009....

  2. Approximation by mediants

    Science.gov (United States)

    Bosma, Wieb

    1990-01-01

    The distribution is determined of some sequences that measure how well a number is approximated by its mediants (or intermediate continued fraction convergents). The connection with a theorem of Fatou, as well as a new proof of this, is given.

  3. Vernakalant hydrochloride for rapid conversion of atrial fibrillation - A phase 3, randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Roy, D.; Pratt, C.M.; Torp-Pedersen, C.

    2008-01-01

    .6%; P complete atrioventricular block, and cardiogenic shock) occurred in 3 patients. Conclusion - Vernakalant......Background - The present study assessed the efficacy and safety of vernakalant hydrochloride ( RSD1235), a novel compound, for the conversion of atrial fibrillation ( AF). Methods and Results - Patients were randomized in a 2: 1 ratio to receive vernakalant or placebo and were stratified by AF...... was conversion of AF to sinus rhythm for at least 1 minute within 90 minutes of the start of drug infusion in the short-duration AF group. A total of 336 patients were randomized and received treatment (short duration, n = 220; long duration, n = 116). Of the 145 vernakalant patients, 75 (51.7%) in the short...

  4. Approximation and Computation

    CERN Document Server

    Gautschi, Walter; Rassias, Themistocles M

    2011-01-01

    Approximation theory and numerical analysis are central to the creation of accurate computer simulations and mathematical models. Research in these areas can influence the computational techniques used in a variety of mathematical and computational sciences. This collection of contributed chapters, dedicated to renowned mathematician Gradimir V. Milovanovia, represent the recent work of experts in the fields of approximation theory and numerical analysis. These invited contributions describe new trends in these important areas of research including theoretic developments, new computational alg

  5. Phase I Randomized Safety Study of Twice Daily Dosing of Acidform Vaginal Gel: Candidate Antimicrobial Contraceptive

    OpenAIRE

    Keller, Marla J.; Carpenter, Colleen A.; Yungtai Lo; Einstein, Mark H.; Congzhou Liu; David N Fredricks; Herold, Betsy C.

    2012-01-01

    Background Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. Methods Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety ...

  6. Phase-space diffusion in turbulent plasmas: The random acceleration problem revisited

    DEFF Research Database (Denmark)

    Pécseli, H.L.; Trulsen, J.

    1991-01-01

    Phase-space diffusion of test particles in turbulent plasmas is studied by an approach based on a conditional statistical analysis of fluctuating electrostatic fields. Analytical relations between relevant conditional averages and higher-order correlations, , and trip...

  7. Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting.

    Science.gov (United States)

    Uc, Ergun Y; Doerschug, Kevin C; Magnotta, Vincent; Dawson, Jeffrey D; Thomsen, Teri R; Kline, Joel N; Rizzo, Matthew; Newman, Sara R; Mehta, Sonya; Grabowski, Thomas J; Bruss, Joel; Blanchette, Derek R; Anderson, Steven W; Voss, Michelle W; Kramer, Arthur F; Darling, Warren G

    2014-07-29

    To (1) investigate effects of aerobic walking on motor function, cognition, and quality of life in Parkinson disease (PD), and (2) compare safety, tolerability, and fitness benefits of different forms of exercise intervention: continuous/moderate intensity vs interval/alternating between low and vigorous intensity, and individual/neighborhood vs group/facility setting. Initial design was a 6-month, 2 × 2 randomized trial of different exercise regimens in independently ambulatory patients with PD. All arms were required to exercise 3 times per week, 45 minutes per session. Randomization to group/facility setting was not feasible because of logistical factors. Over the first 2 years, we randomized 43 participants to continuous or interval training. Because preliminary analyses suggested higher musculoskeletal adverse events in the interval group and lack of difference between training methods in improving fitness, the next 17 participants were allocated only to continuous training. Eighty-one percent of 60 participants completed the study with a mean attendance of 83.3% (95% confidence interval: 77.5%-89.0%), exercising at 46.8% (44.0%-49.7%) of their heart rate reserve. There were no serious adverse events. Across all completers, we observed improvements in maximum oxygen consumption, gait speed, Unified Parkinson's Disease Rating Scale sections I and III scores (particularly axial functions and rigidity), fatigue, depression, quality of life (e.g., psychological outlook), and flanker task scores (p exercise program improves aerobic fitness, motor function, fatigue, mood, and cognition. © 2014 American Academy of Neurology.

  8. The gated integration technique for the accurate measurement of the autocorrelation function of speckle intensities scattered from random phase screens

    Science.gov (United States)

    Zhang, Ningyu; Cheng, Chuanfu; Teng, Shuyun; Chen, Xiaoyi; Xu, Zhizhan

    2007-09-01

    A new approach based on the gated integration technique is proposed for the accurate measurement of the autocorrelation function of speckle intensities scattered from a random phase screen. The Boxcar used for this technique in the acquisition of the speckle intensity data integrates the photoelectric signal during its sampling gate open, and it repeats the sampling by a preset number, m. The average analog of the m samplings output by the Boxcar enhances the signal-to-noise ratio by √{m}, because the repeated sampling and the average make the useful speckle signals stable, while the randomly varied photoelectric noise is suppressed by 1/√{m}. In the experiment, we use an analog-to-digital converter module to synchronize all the actions such as the stepped movement of the phase screen, the repeated sampling, the readout of the averaged output of the Boxcar, etc. The experimental results show that speckle signals are better recovered from contaminated signals, and the autocorrelation function with the secondary maximum is obtained, indicating that the accuracy of the measurement of the autocorrelation function is greatly improved by the gated integration technique.

  9. A phase-synchronization and random-matrix based approach to multichannel time-series analysis with application to epilepsy

    Science.gov (United States)

    Osorio, Ivan; Lai, Ying-Cheng

    2011-09-01

    We present a general method to analyze multichannel time series that are becoming increasingly common in many areas of science and engineering. Of particular interest is the degree of synchrony among various channels, motivated by the recognition that characterization of synchrony in a system consisting of many interacting components can provide insights into its fundamental dynamics. Often such a system is complex, high-dimensional, nonlinear, nonstationary, and noisy, rendering unlikely complete synchronization in which the dynamical variables from individual components approach each other asymptotically. Nonetheless, a weaker type of synchrony that lasts for a finite amount of time, namely, phase synchronization, can be expected. Our idea is to calculate the average phase-synchronization times from all available pairs of channels and then to construct a matrix. Due to nonlinearity and stochasticity, the matrix is effectively random. Moreover, since the diagonal elements of the matrix can be arbitrarily large, the matrix can be singular. To overcome this difficulty, we develop a random-matrix based criterion for proper choosing of the diagonal matrix elements. Monitoring of the eigenvalues and the determinant provides a powerful way to assess changes in synchrony. The method is tested using a prototype nonstationary noisy dynamical system, electroencephalogram (scalp) data from absence seizures for which enhanced cortico-thalamic synchrony is presumed, and electrocorticogram (intracranial) data from subjects having partial seizures with secondary generalization for which enhanced local synchrony is similarly presumed.

  10. "HEATPAC" - a phase II randomized study of concurrent thermochemoradiotherapy versus chemoradiotherapy alone in locally advanced pancreatic cancer.

    Science.gov (United States)

    Datta, Niloy Ranjan; Pestalozzi, Bernhard; Clavien, Pierre-Alain; Siebenhüner, Alexander; Puric, Emsad; Khan, Shaka; Mamot, Christoph; Riesterer, Oliver; Knuchel, Jürg; Reiner, Cäcilia Sophie; Bodis, Stephan

    2017-11-21

    Pancreatic cancer has a dismal prognosis with 5-year overall survival rate of around 5%. Although surgery is still the best option in operable cases, majority of the patients who present in locally advanced stages are deemed inoperable. Novel approaches are therefore needed for the management of around 80% of these inoperable locally advanced pancreatic cancers (LAPC). Hyperthermia (39-43 °C) is a potent radiosensitizer and further enhances the action of gemcitabine, also a known radiosensitizer. Thus through triple sensitization, a combination of hyperthermia, radiotherapy and gemcitabine could be expected to improve the therapeutic outcomes in LAPC. This phase II randomized trial, HEATPAC in unresectable LAPC, explores the feasibility and efficacy of concurrent thermochemoradiotherapy (HTCTRT) over chemoradiotherapy (CTRT) alone with pre- and post-intervention FOLFIRINOX at standard dosage and schedule. Following 4 cycles of neoadjuvant FOLFIRINOX, patients with no metastasis and absence of gross peritoneal carcinomatosis would be randomized to either (a) control arm: concurrent CTRT with gemcitabine (400 mg/m2, weekly ×6) or (b) study arm: locoregional hyperthermia (weekly ×6 during radiotherapy) with concurrent CTRT (same as in control arm). All patients would receive simultaneous-integrated boost intensity-modulated radiation therapy to doses of 56Gy and 50.4Gy to the gross and clinical target volumes respectively delivered in 28 fractions over 5.5 weeks. Deep locoregional hyperthermia would be administered weekly and monitored with real-time intraduodenal multisensor thermometry probe. A temperature of 40-43 °C for 60 min would be aimed for each hyperthermia session. On completion of CTRT/HTCTRT, patients of both groups would receive an additional 8 cycles of FOLFIRINOX. The expected 1-year baseline overall survival with CTRT alone is considered as 40%. With HTCTRT, a survival advantage of +20% is expected. Considering α = 0.05 and β = 0

  11. Efficacy of dignity therapy on depression and anxiety in Portuguese terminally ill patients: a phase II randomized controlled trial.

    Science.gov (United States)

    Julião, Miguel; Oliveira, Fátima; Nunes, Baltazar; Vaz Carneiro, António; Barbosa, António

    2014-06-01

    Dignity therapy is a brief psychotherapy developed for patients living with a life-limiting illness. To determine the influence of dignity therapy on depression and anxiety in inpatients with a terminal illness and experiencing a high level of distress in a palliative care unit. A nonblinded phase II randomized controlled trial of 80 patients who were randomly assigned to one of two groups: intervention group (dignity therapy+standard palliative care [SPC]) or control group (SPC alone). The main outcomes were depression and anxiety scores, as measured with the Hospital Anxiety and Depression Scale, and assessed at baseline (T1), day 4 (T2), day 15 (T3), and day 30 (T4) of follow-up. This study is registered with www.controlled-trials.com/ISRCTN34354086. Of the final 80 participants, 41 were randomly assigned to SPC and 39 to dignity therapy. Baseline characteristics were similar between the two groups. Dignity therapy was associated with a decrease in depression scores (median, 95% confidence interval [CI]: -4.00, -6.00 to -2.00, pdepression and anxiety symptoms in end-of-life care. The therapeutic benefit of dignity therapy was sustained over a 30-day period. Having established its efficacy, future trials of dignity therapy may now begin, comparing it with other psychotherapeutic approaches within the context of terminal illness.

  12. Safety and immunogenicity of the recombinant BCG vaccine VPM1002 in a phase 1 open-label randomized clinical trial.

    Science.gov (United States)

    Grode, Leander; Ganoza, Christian A; Brohm, Christiane; Weiner, January; Eisele, Bernd; Kaufmann, Stefan H E

    2013-02-18

    Current vaccination using Mycobacterium bovis bacillus Calmette-Guérin (BCG), fails to prevent pulmonary tuberculosis (TB). New vaccination strategies are essential for reducing the global incidence of TB. We assessed the safety and immunogenicity of VPM1002, a recombinant BCG vaccine candidate. EudraCT (2007-002789-37) and ClinicalTrials.gov (NCT00749034). Healthy volunteers were enrolled in a phase 1 open-label, dose escalation randomized clinical trial, and received one intradermal dose of VPM1002 (Mycobacterium bovis BCG ΔureC::hly Hm(R)) or BCG. Immunogenicity was assessed by interferon-gamma (IFN-γ) production, cellular immune response markers by flow cytometry and serum antibodies against mycobacterial antigens. Eighty volunteers were randomized into two groups according to previous BCG vaccination and mycobacterial exposure (BCG-naïve, n=40 and BCG-immune, n=40). In each group, 30 individuals were vaccinated with VPM1002 (randomized to three escalating doses) and 10 with BCG. VPM1002 was safe and stimulated IFN-γ-producing and multifunctional T cells, as well as antibody-producing B cells in BCG-naïve and BCG-immune individuals. VPM1002 was safe and immunogenic for B-cell and T-cell responses and hence will be brought forward through the clinical trial pipeline. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Phase IV: randomized controlled trial to evaluate lot consistency of trivalent split influenza vaccines in healthy adults.

    Science.gov (United States)

    Song, Joon Young; Cheong, Hee Jin; Lee, Jacob; Wie, Seong-Heon; Park, Kyung-Hwa; Kee, Sae Yoon; Jeong, Hye Won; Kim, Yeon-Sook; Noh, Ji Yun; Choi, Won Suk; Park, Dae Won; Sohn, Jang Wook; Kim, Woo Joo

    2014-01-01

    Influenza vaccines are the primary method for preventing influenza and its complications. Considering the increasing demand for influenza vaccines, vaccine manufacturers are required to establish large-scale production systems. This phase IV randomized trial was conducted to evaluate the lot consistency of trivalent split influenza vaccines regarding immunogenicity and safety. A total of 1,023 healthy adults aged 18-64 y were enrolled in the study. Subjects were randomly assigned in a 1:1 ratio to receive the GC FLU® Prefilled Syringe or the GC FLU® Injection, and they were further randomized to one of 3 lots of each vaccine in a 1:1:1 ratio. In both GC FLU® Injection and GC FLU® Prefilled Syringe groups, immune responses were equivalent between lots for each of the 3 vaccine strains on day 21. The 2-sided 95% CI of GMT ratios between pairs of lots were between 0.67 and 1.5, meeting the equivalence criteria. After vaccination, all 3 criteria of the European Medicines Agency were met in both GC FLU® Injection and GC FLU® Prefilled Syringe groups. The vaccines showed tolerable safety profiles without serious adverse events. The demonstration of lot consistency, robust immunogenic responses and favorable safety profiles support the reliability of mass-manufacturing systems for the GC FLU® Injection and GC FLU® Prefilled Syringe.

  14. Periodically driven random quantum spin chains: real-space renormalization for Floquet localized phases

    Science.gov (United States)

    Monthus, Cécile

    2017-07-01

    When random quantum spin chains are submitted to some periodic Floquet driving, the eigenstates of the time-evolution operator over one period can be localized in real space. For the case of periodic quenches between two Hamiltonians (or periodic kicks), where the time-evolution operator over one period reduces to the product of two simple transfer matrices, we propose a block-self-dual renormalization procedure to construct the localized eigenstates of the Floquet dynamics. We also discuss the corresponding strong disorder renormalization procedure, that generalizes the RSRG-X procedure to construct the localized eigenstates of time-independent Hamiltonians.

  15. Thermodynamics of Phase Transitions and Bipolar Filamentary Switching in Resistive Random-Access Memory

    Science.gov (United States)

    Karpov, V. G.; Niraula, D.; Karpov, I. V.; Kotlyar, R.

    2017-08-01

    We present a phenomenological theory of bipolar filamentary resistive random-access memory describing the commonly observed features of their current-voltage characteristics. Our approach follows the approach of a thermodynamic theory developed earlier for chalcogenide memory and threshold switches and largely independent of their microscopic details. It explains, without adjustable parameters, such features as the domains of filament formation and switching, voltage-independent current in set and current-independent voltage in reset regimes, the relation between the set and reset voltages, filament resistance independent of its length, etc. Furthermore, it expresses the observed features through the material and circuitry parameters, thus paving the way to device improvements.

  16. Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: a randomized multicenter Phase III trial.

    Science.gov (United States)

    Scheller, Christian; Wienke, Andreas; Tatagiba, Marcos; Gharabaghi, Alireza; Ramina, Kristofer F; Ganslandt, Oliver; Bischoff, Barbara; Zenk, Johannes; Engelhorn, Tobias; Matthies, Cordula; Westermaier, Thomas; Antoniadis, Gregor; Pedro, Maria Teresa; Rohde, Veit; von Eckardstein, Kajetan; Kretschmer, Thomas; Kornhuber, Malte; Steighardt, Jörg; Richter, Michael; Barker, Fred G; Strauss, Christian

    2016-03-01

    A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1-2 mg/hr) and hydroxyethyl starch (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34-3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18-1.30], p = 0.15). Apart from dose-dependent hypotension (p nimodipine can be recommended in VS surgery.

  17. Randomized phase II study of TJ-54 (Yokukansan) for postoperative delirium in gastrointestinal and lung malignancy patients.

    Science.gov (United States)

    Sugano, Nobuhiro; Aoyama, Toru; Sato, Tsutomu; Kamiya, Mariko; Amano, Shinya; Yamamoto, Naoto; Nagashima, Takuya; Ishikawa, Yoshihiro; Masudo, Katsuhiko; Taguri, Masataka; Yamanaka, Takeharu; Yamamoto, Yuji; Matsukawa, Hiroshi; Shiraisi, Ryuji; Oshima, Takashi; Yukawa, Norio; Rino, Yasushi; Masuda, Munetaka

    2017-10-01

    The present study evaluated the efficacy and safety of TJ-54 (Yokukansan; a traditional Japanese medicine) for the prevention and/or treatment of postoperative delirium in a randomized phase II trial of patients receiving surgery for gastrointestinal and lung malignancies. Patients ≥70 years of age who underwent surgery for gastrointestinal or lung malignancy were eligible for participation in the study. The 186 eligible patients were randomly assigned at a 1:1 ratio to receive TJ-54 or control during their peri-operative care (between 7 days prior to surgery and 4 days following surgery, except for the operation day). The signs and symptoms of delirium were assessed using the Diagnostic and Statistical Manual of Mental Disorders-IV by the investigator during the peri-operative period. A total of 186 eligible gastrointestinal or lung malignancy patients were analyzed (93, TJ-54; 93, control). There were no marked differences between the two randomized groups. The incidence of delirium was 6.5% (6 patients) in the TJ-54 group and 9.7% (9 patients) in the control group, with no significant difference (P=0.419). However, of the patients categorized with a mini-mental state examination (MMSE) score of ≤26, the incidence of postoperative delirium was 9.1% in the TJ-54 group and 26.9% in the control group [risk ratio, 0.338; 95% confidence interval (0.078-1.462), P=0.115]. Treatment with TJ-54 reduced the incidence of postoperative delirium compared with the control group. Although TJ-54 did not demonstrate any contribution to preventing or treating postoperative delirium in patients following surgery for gastrointestinal or lung malignancy, TJ-54 reduced the risk of postoperative delirium in the patients who were classified as MMSE ≤26. Further phase III studies with a larger sample size are required in order to clarify the effects of TJ-54 against postoperative delirium.

  18. Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET: Study protocol for a randomized phase II trial

    Directory of Open Access Journals (Sweden)

    Palma David A

    2012-07-01

    Full Text Available Abstract Background Stereotactic ablative radiotherapy (SABR has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control. Survival outcomes for patients with oligometastatic disease treated with SABR appear promising, but conclusions are limited by patient selection, and the lack of adequate controls in most studies. The goal of this multicenter randomized phase II trial is to assess the impact of a comprehensive oligometastatic SABR treatment program on overall survival and quality of life in patients with up to 5 metastatic cancer lesions, compared to patients who receive standard of care treatment alone. Methods After stratification by the number of metastases (1-3 vs. 4-5, patients will be randomized between Arm 1: current standard of care treatment, and Arm 2: standard of care treatment + SABR to all sites of known disease. Patients will be randomized in a 1:2 ratio to Arm 1:Arm 2, respectively. For patients receiving SABR, radiotherapy dose and fractionation depends on the site of metastasis and the proximity to critical normal structures. This study aims to accrue a total of 99 patients within four years. The primary endpoint is overall survival, and secondary endpoints include quality of life, toxicity, progression-free survival, lesion control rate, and number of cycles of further chemotherapy/systemic therapy. Discussion This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with oligometastatic disease, and will inform the design of a possible phase III study. Trial registration Clinicaltrials.gov identifier: NCT01446744

  19. Tapentadol immediate-release for acute postbunionectomy pain: a phase 3, randomized, double-blind, placebo-controlled, parallel-group study in Taiwan.

    Science.gov (United States)

    Chen, Yeung-Jen; Chiang, Chao-Ching; Huang, Peng-Ju; Huang, Jason; Karcher, Keith; Li, Honglan

    2015-11-01

    To evaluate the efficacy and safety of tapentadol immediate-release (IR) for treating acute pain following orthopedic bunionectomy surgery in a Taiwanese population. This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group bridging study in which Taiwanese patients (N = 60) with moderate-to-severe pain following bunionectomy were randomized (1:1:1) to receive tapentadol IR 50 or 75 mg or placebo orally every 4-6 hours over a 72 hour period. The primary endpoint was the sum of pain intensity difference over 48 hours (SPID48), analyzed using analysis of variance. Out of 60 patients randomized (mainly women [96.7%]; median age 44 years), 41 (68.3%) completed the treatment. Mean SPID48 values were significantly higher for tapentadol IR (p ≤ 0.006: 50 mg, p ≤ 0.004: 75 mg) compared with placebo. Between-group differences in LS means of SPID48 (vs. placebo) were tapentadol IR 50 mg: 105.6 (95% CI: 32.0; 179.2); tapentadol IR 75 mg: 126.6 (95% CI: 49.5; 203.7). Secondary endpoints including SPID at 12, 24, and 72 hours, time to first use of rescue medication, cumulative distribution of responder rates, total pain relief and sum of total pain relief and sum of pain intensity difference at 12, 24, 48, and 72 hours, and patient global impression of change showed numerically better results supporting that tapentadol IR (50 and 75 mg) was more efficacious than placebo in relieving acute pain. The most frequent treatment emergent adverse events reported in ≥ 10% patients in either group were dizziness, nausea, and vomiting. A limitation of this study may possibly include more controlled patient monitoring through 4-6 hour dosing intervals, which reflects optimal conditions and thus may not approximate real-world clinical practice. However, all treatment groups would be equally affected by such bias of frequent monitoring, if any, since it was a randomized and double-blind study. Tapentadol IR treatment significantly relieved acute postoperative

  20. Covariant approximation averaging

    CERN Document Server

    Shintani, Eigo; Blum, Thomas; Izubuchi, Taku; Jung, Chulwoo; Lehner, Christoph

    2014-01-01

    We present a new class of statistical error reduction techniques for Monte-Carlo simulations. Using covariant symmetries, we show that correlation functions can be constructed from inexpensive approximations without introducing any systematic bias in the final result. We introduce a new class of covariant approximation averaging techniques, known as all-mode averaging (AMA), in which the approximation takes account of contributions of all eigenmodes through the inverse of the Dirac operator computed from the conjugate gradient method with a relaxed stopping condition. In this paper we compare the performance and computational cost of our new method with traditional methods using correlation functions and masses of the pion, nucleon, and vector meson in $N_f=2+1$ lattice QCD using domain-wall fermions. This comparison indicates that AMA significantly reduces statistical errors in Monte-Carlo calculations over conventional methods for the same cost.

  1. Covariant approximation averaging

    Science.gov (United States)

    Shintani, Eigo; Arthur, Rudy; Blum, Thomas; Izubuchi, Taku; Jung, Chulwoo; Lehner, Christoph

    2015-06-01

    We present a new class of statistical error reduction techniques for Monte Carlo simulations. Using covariant symmetries, we show that correlation functions can be constructed from inexpensive approximations without introducing any systematic bias in the final result. We introduce a new class of covariant approximation averaging techniques, known as all-mode averaging (AMA), in which the approximation takes account of contributions of all eigenmodes through the inverse of the Dirac operator computed from the conjugate gradient method with a relaxed stopping condition. In this paper we compare the performance and computational cost of our new method with traditional methods using correlation functions and masses of the pion, nucleon, and vector meson in Nf=2 +1 lattice QCD using domain-wall fermions. This comparison indicates that AMA significantly reduces statistical errors in Monte Carlo calculations over conventional methods for the same cost.

  2. A randomized, phase 2, dose-ranging study in the treatment of moderate to severe inflammatory facial acne vulgaris with doxycycline calcium.

    Science.gov (United States)

    Leyden, James J; Bruce, Suzanne; Lee, Chai Sue; Ling, Mark; Sheth, Pranav B; Stewart, Daniel M; Werschler, William P; Gilbert, Richard D; Kircik, Leon

    2013-06-01

    Doxycycline calcium (WC2055) is a drug substance with a possible role in the treatment of acne. The objective of this study was to evaluate the safety and efficacy of three doses of doxycycline calcium tablets compared with placebo in the treatment of moderate to severe inflammatory facial acne vulgaris. This was a randomized, double-blind, phase 2 dose-ranging study in subjects with moderate to severe inflammatory acne aged 12 years to 45 years. Subjects were randomized to receive doxycycline calcium tablets 0.6, 1.2, or 2.4 mg/kg/day or placebo, and instructed to take their tablets once daily for 12 weeks, in the evening at least 1 hour before or 2 hours after mealtime. The primary efficacy variables were the dichotomized Investigator's Global Assessment score (success or failure) at week 12 (success defined as ≥ 2 score decrease from baseline) and the absolute change from baseline to week 12 in inflammatory lesion count. A dose-response effect was seen with doxycycline calcium formulation in subjects with moderate to severe inflammatory acne. The highest dose-group (corresponding to approximately 2.4 mg/kg/day) showed a statistically significant difference from placebo. The dose-response effect was confirmed by logistic regression analysis for both treatment success and incidence of gastrointestinal adverse events. A limitation of this study is that safety and efficacy were only studied on moderate to severe inflammatory acne. Also, the study was not prospectively powered to show efficacy differences. Doxycycline calcium shows a dose-response effect in reducing inflammatory lesions in subjects with moderate to severe inflammatory acne.

  3. Introduction to Diophantine Approximation

    Directory of Open Access Journals (Sweden)

    Watase Yasushige

    2015-06-01

    Full Text Available In this article we formalize some results of Diophantine approximation, i.e. the approximation of an irrational number by rationals. A typical example is finding an integer solution (x, y of the inequality |xθ − y| ≤ 1/x, where 0 is a real number. First, we formalize some lemmas about continued fractions. Then we prove that the inequality has infinitely many solutions by continued fractions. Finally, we formalize Dirichlet’s proof (1842 of existence of the solution [12], [1].

  4. More evidence on additive antipsychotic effect of adjunctive mirtazapine in schizophrenia: an extension phase of a randomized controlled trial.

    Science.gov (United States)

    Terevnikov, Viacheslav; Stenberg, Jan-Henry; Joffe, Marina; Tiihonen, Jari; Burkin, Mark; Tchoukhine, Evgueni; Joffe, Grigori

    2010-08-01

    Adjunctive mirtazapine improved negative symptoms of schizophrenia in several studies. Recently, we found an improvement also in positive symptoms when mirtazapine was added to first generation antipsychotics (FGAs) in a 6 week randomized controlled trial (RCT). The short duration of that trial was its limitation. This study aimed to explore whether longer treatment is worthwhile. Completers of the RCT (n = 39) received open-label add-on mirtazapine for additional 6 weeks. The Positive and Negative Syndrome Scale (PANSS) total score (primary outcome) and several other clinical parameters were measured prospectively. During the open-label phase, significant improvement was achieved in all parameters, with an effect size of 0.94 (CI 95% = 0.45-1.43) on the primary outcome and an impressive additive antipsychotic effect. Patients who received mirtazapine during both phases demonstrated greater improvement in positive symptoms (29.6% versus 21.2%, p = 0.027) than those who received mirtazapine during open-label extension phase only. These findings support our previous data on the additive antipsychotic effect of mirtazapine in FGAs-treated schizophrenia. Mirtazapine may be effective in other symptom domains, too. Longer duration of mirtazapine treatment may yield additional benefits. If these results will be confirmed in larger studies, add-on mirtazapine may become a feasible option in difficult-to-treat schizophrenia. Copyright 2010 John Wiley & Sons, Ltd.

  5. Second harmonic generation in gallium phosphide microdisks on silicon: from strict \\bar{4} to random quasi-phase matching

    Science.gov (United States)

    Guillemé, P.; Dumeige, Y.; Stodolna, J.; Vallet, M.; Rohel, T.; Létoublon, A.; Cornet, C.; Ponchet, A.; Durand, O.; Léger, Y.

    2017-06-01

    The convergence of nonlinear optical devices and silicon photonics is a key milestone for the practical development of photonic integrated circuits. The associated technological issues often stem from material incompatibility. This is the case of second order nonlinear processes in monolithically integrated III-V semiconductor devices on silicon, where structural defects called antiphase domains strongly impact the optical properties of the material. We theoretically investigate the influence of antiphase domains on second harmonic generation in III-V whispering gallery mode microresonators on silicon and focus on the effects of the antiphase domains’ mean size (i.e. the correlation length of the distribution). We demonstrate that the domain distributions can have opposite effects depending on the nonlinear process under consideration: while antiphase domains negatively impact second harmonic generation under \\bar{4} quasi-phase matching conditions (independent of the correlation length), large conversion efficiencies can arise far from \\bar{4}-quasi-phase matching provided that the APD correlation length remains within an appropriate range, and is still compatible with the spontaneous emergence of such defects in the usual III-V on Si epilayers. Such a build-up can be explained by the occurrence of random quasi-phase matching in the system.

  6. Looking for phase transitions of strongly interacting matter applying new method on basic of Random Matrix Theory

    Energy Technology Data Exchange (ETDEWEB)

    Suleymanov, Mais [CIIT, Islamabad (Pakistan); Shahaliev, Ehtiram [HEPL, JINR, Dubna (Russian Federation)

    2009-07-01

    Over the last 25 years a lot of efforts have been made to search for new phases of strongly interacting matter. Heavy ion collisions are of great importance since they open a way to reproduce these phases in the Earth laboratory. But in this case the volume of information increases sharply as well as the background information. A method was introduced a method on the basic of Random Matrix Theory to study the fluctuations of neutron resonances in compound nuclei which doesn't depend on the background of measurements. To analyze the energetic levels of compound nuclei the function of distances between two energetic levels p(s{sub i}) is defined as the general distributions for probability of all kinds of ensembles. At values of the index of universality {nu}=0 it will change to Poisson type distributions pointing to absence of any correlations in the system and at the values of {nu}=1 it will change to Wigner type behavior directing to some correlation in the studying ensemble. We discuss that the experimental study of the behavior of p(s{sub i}) distribution for secondary particles could give a signal on the phase transitions.

  7. A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children

    DEFF Research Database (Denmark)

    Bélard, Sabine; Issifou, Saadou; Hounkpatin, Aurore B

    2011-01-01

    GMZ2 is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP) that mediates an immune response against the blood stage of the parasite. Two previous phase I clinical trials, one in naïve European adults and one in malaria-exposed Gabonese ...... adults showed that GMZ2 was well tolerated and immunogenic. Here, we present data on safety and immunogenicity of GMZ2 in one to five year old Gabonese children, a target population for future malaria vaccine efficacy trials....

  8. Prestack wavefield approximations

    KAUST Repository

    Alkhalifah, Tariq

    2013-09-01

    The double-square-root (DSR) relation offers a platform to perform prestack imaging using an extended single wavefield that honors the geometrical configuration between sources, receivers, and the image point, or in other words, prestack wavefields. Extrapolating such wavefields, nevertheless, suffers from limitations. Chief among them is the singularity associated with horizontally propagating waves. I have devised highly accurate approximations free of such singularities which are highly accurate. Specifically, I use Padé expansions with denominators given by a power series that is an order lower than that of the numerator, and thus, introduce a free variable to balance the series order and normalize the singularity. For the higher-order Padé approximation, the errors are negligible. Additional simplifications, like recasting the DSR formula as a function of scattering angle, allow for a singularity free form that is useful for constant-angle-gather imaging. A dynamic form of this DSR formula can be supported by kinematic evaluations of the scattering angle to provide efficient prestack wavefield construction. Applying a similar approximation to the dip angle yields an efficient 1D wave equation with the scattering and dip angles extracted from, for example, DSR ray tracing. Application to the complex Marmousi data set demonstrates that these approximations, although they may provide less than optimal results, allow for efficient and flexible implementations. © 2013 Society of Exploration Geophysicists.

  9. Approximate and Incomplete Factorizations

    NARCIS (Netherlands)

    Chan, T.F.; Vorst, H.A. van der

    1997-01-01

    In this chapter, we give a brief overview of a particular class of preconditioners known as incomplete factorizations. They can be thought of as approximating the exact LU factorization of a given matrix A (e.g. computed via Gaussian elimination) by disallowing certain ll-ins. As opposed to other

  10. Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial.

    Science.gov (United States)

    Butchart, Joseph; Brook, Laura; Hopkins, Vivienne; Teeling, Jessica; Püntener, Ursula; Culliford, David; Sharples, Richard; Sharif, Saif; McFarlane, Brady; Raybould, Rachel; Thomas, Rhodri; Passmore, Peter; Perry, V Hugh; Holmes, Clive

    2015-05-26

    To determine whether the tumor necrosis factor α inhibitor etanercept is well tolerated and obtain preliminary data on its safety in Alzheimer disease dementia. In a double-blind study, patients with mild to moderate Alzheimer disease dementia were randomized (1:1) to subcutaneous etanercept (50 mg) once weekly or identical placebo over a 24-week period. Tolerability and safety of this medication was recorded including secondary outcomes of cognition, global function, behavior, and systemic cytokine levels at baseline, 12 weeks, 24 weeks, and following a 4-week washout period. This trial is registered with EudraCT (2009-013400-31) and ClinicalTrials.gov (NCT01068353). Forty-one participants (mean age 72.4 years; 61% men) were randomized to etanercept (n = 20) or placebo (n = 21). Etanercept was well tolerated; 90% of participants (18/20) completed the study compared with 71% (15/21) in the placebo group. Although infections were more common in the etanercept group, there were no serious adverse events or new safety concerns. While there were some interesting trends that favored etanercept, there were no statistically significant changes in cognition, behavior, or global function. This study showed that subcutaneous etanercept (50 mg/wk) was well tolerated in this small group of patients with Alzheimer disease dementia, but a larger more heterogeneous group needs to be tested before recommending its use for broader groups of patients. This study shows Class I evidence that weekly subcutaneous etanercept is well tolerated in Alzheimer disease dementia. © 2015 American Academy of Neurology.

  11. A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy.

    Science.gov (United States)

    Victor, Ronald G; Sweeney, H Lee; Finkel, Richard; McDonald, Craig M; Byrne, Barry; Eagle, Michelle; Goemans, Nathalie; Vandenborne, Krista; Dubrovsky, Alberto L; Topaloglu, Haluk; Miceli, M Carrie; Furlong, Pat; Landry, John; Elashoff, Robert; Cox, David

    2017-10-24

    To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens the decline in ambulatory ability in boys with Duchenne muscular dystrophy (DMD). Three hundred thirty-one participants with DMD 7 to 14 years of age taking glucocorticoids were randomized to tadalafil 0.3 mg·kg(-1)·d(-1), tadalafil 0.6 mg·kg(-1)·d(-1), or placebo. The primary efficacy measure was 6-minute walk distance (6MWD) after 48 weeks. Secondary efficacy measures included North Star Ambulatory Assessment and timed function tests. Performance of Upper Limb (PUL) was a prespecified exploratory outcome. Tadalafil had no effect on the primary outcome: 48-week declines in 6MWD were 51.0 ± 9.3 m with placebo, 64.7 ± 9.8 m with low-dose tadalafil (p = 0.307 vs placebo), and 59.1 ± 9.4 m with high-dose tadalafil (p = 0.538 vs placebo). Tadalafil also had no effect on secondary outcomes. In boys >10 years of age, total PUL score and shoulder subscore declined less with low-dose tadalafil than placebo. Adverse events were consistent with the known safety profile of tadalafil and the DMD disease state. Tadalafil did not lessen the decline in ambulatory ability in boys with DMD. Further studies should be considered to confirm the hypothesis-generating upper limb data and to determine whether ambulatory decline can be slowed by initiation of tadalafil before 7 years of age. NCT01865084. This study provides Class I evidence that tadalafil does not slow ambulatory decline in 7- to 14-year-old boys with Duchenne muscular dystrophy. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  12. Computer Experiments for Function Approximations

    Energy Technology Data Exchange (ETDEWEB)

    Chang, A; Izmailov, I; Rizzo, S; Wynter, S; Alexandrov, O; Tong, C

    2007-10-15

    This research project falls in the domain of response surface methodology, which seeks cost-effective ways to accurately fit an approximate function to experimental data. Modeling and computer simulation are essential tools in modern science and engineering. A computer simulation can be viewed as a function that receives input from a given parameter space and produces an output. Running the simulation repeatedly amounts to an equivalent number of function evaluations, and for complex models, such function evaluations can be very time-consuming. It is then of paramount importance to intelligently choose a relatively small set of sample points in the parameter space at which to evaluate the given function, and then use this information to construct a surrogate function that is close to the original function and takes little time to evaluate. This study was divided into two parts. The first part consisted of comparing four sampling methods and two function approximation methods in terms of efficiency and accuracy for simple test functions. The sampling methods used were Monte Carlo, Quasi-Random LP{sub {tau}}, Maximin Latin Hypercubes, and Orthogonal-Array-Based Latin Hypercubes. The function approximation methods utilized were Multivariate Adaptive Regression Splines (MARS) and Support Vector Machines (SVM). The second part of the study concerned adaptive sampling methods with a focus on creating useful sets of sample points specifically for monotonic functions, functions with a single minimum and functions with a bounded first derivative.

  13. Teriflunomide added to interferon-β in relapsing multiple sclerosis: a randomized phase II trial.

    Science.gov (United States)

    Freedman, M S; Wolinsky, J S; Wamil, B; Confavreux, C; Comi, G; Kappos, L; Olsson, T P; Miller, A; Benzerdjeb, H; Li, H; Simonson, C; O'Connor, P W

    2012-06-05

    To evaluate teriflunomide as add-on therapy to ongoing stable-dosed interferon-β (IFNβ) in patients with relapsing forms of multiple sclerosis (RMS). A total of 118 patients with RMS were randomly assigned 1:1:1 to receive oral placebo or teriflunomide, 7 or 14 mg, once daily for 24 weeks; 86 patients entered the 24-week extension. The primary objective was to evaluate safety; secondary objectives were to evaluate the effects of treatment on disease activity assessed by MRI and relapse rate. Teriflunomide was well tolerated with a low and similar incidence of treatment-emergent adverse events (TEAEs) across the 3 groups; TEAEs led to treatment discontinuation of 4.9%, 8.1%, and 7.9% of patients in the placebo, 7-mg, and 14-mg groups, respectively. The number of gadolinium-enhancing T1 (T1-Gd) lesions was reduced in both teriflunomide groups, with relative risk reductions (RRRs) of 84.6% (p = 0.0005) and 82.8% (p Teriflunomide as add-on therapy to IFNβ had acceptable safety and tolerability and reduced MRI disease activity compared with IFNβ alone. This study provides Class II evidence that teriflunomide, 7 and 14 mg, added to IFNβ, is safe. The T1-Gd lesion burden was significantly reduced with both teriflunomide doses.

  14. Randomized Phase II trial of nintedanib, afatinib and sequential combination in castration-resistant prostate cancer.

    Science.gov (United States)

    Molife, L Rhoda; Omlin, Aurelius; Jones, Rob J; Karavasilis, Vasilios; Bloomfield, David; Lumsden, Graeme; Fong, Peter C; Olmos, David; O'Sullivan, Joe M; Pedley, Ian; Hickish, Tamas; Jenkins, Peter; Thompson, Emilda; Oommen, Nikhil; Wheatley, Duncan; Heath, Catherine; Temple, Graham; Pelling, Katy; de Bono, Johann S

    2014-02-01

    The aim of this article was to evaluate afatinib (BIBW 2992), an ErbB family blocker, and nintedanib (BIBF 1120), a triple angiokinase inhibitor, in castration-resistant prostate cancer patients. Patients were randomized to receive nintedanib (250 mg twice daily), afatinib (40 mg once daily [q.d.]), or alternating sequential 7-day nintedanib (250 mg twice daily) and afatinib (70 mg q.d. [Combi70]), which was reduced to 40 mg q.d. (Combi40) due to adverse events. The primary end point was progression-free rate at 12 weeks. Of the 85 patients treated 46, 20, 16 and three received nintedanib, afatinib, Combi40 and Combi70, respectively. At 12 weeks, the progression-free rate was 26% (seven out of 27 patients) for nintedanib, and 0% for afatinib and Combi40 groups. Two patients had a ≥50% decline in PSA (nintedanib and the Combi40 groups). The most common drug-related adverse events were diarrhea, nausea, vomiting and lethargy. Nintedanib and/or afatinib demonstrated limited anti-tumor activity in unselected advanced castration-resistant prostate cancer patients.

  15. Prestack traveltime approximations

    KAUST Repository

    Alkhalifah, Tariq Ali

    2011-01-01

    Most prestack traveltime relations we tend work with are based on homogeneous (or semi-homogenous, possibly effective) media approximations. This includes the multi-focusing or double square-root (DSR) and the common reflection stack (CRS) equations. Using the DSR equation, I analyze the associated eikonal form in the general source-receiver domain. Like its wave-equation counterpart, it suffers from a critical singularity for horizontally traveling waves. As a result, I derive expansion based solutions of this eikonal based on polynomial expansions in terms of the reflection and dip angles in a generally inhomogenous background medium. These approximate solutions are free of singularities and can be used to estimate travetimes for small to moderate offsets (or reflection angles) in a generally inhomogeneous medium. A Marmousi example demonstrates the usefulness of the approach. © 2011 Society of Exploration Geophysicists.

  16. Topology, calculus and approximation

    CERN Document Server

    Komornik, Vilmos

    2017-01-01

    Presenting basic results of topology, calculus of several variables, and approximation theory which are rarely treated in a single volume, this textbook includes several beautiful, but almost forgotten, classical theorems of Descartes, Erdős, Fejér, Stieltjes, and Turán. The exposition style of Topology, Calculus and Approximation follows the Hungarian mathematical tradition of Paul Erdős and others. In the first part, the classical results of Alexandroff, Cantor, Hausdorff, Helly, Peano, Radon, Tietze and Urysohn illustrate the theories of metric, topological and normed spaces. Following this, the general framework of normed spaces and Carathéodory's definition of the derivative are shown to simplify the statement and proof of various theorems in calculus and ordinary differential equations. The third and final part is devoted to interpolation, orthogonal polynomials, numerical integration, asymptotic expansions and the numerical solution of algebraic and differential equations. Students of both pure an...

  17. Pumping approximately integrable systems

    Science.gov (United States)

    Lange, Florian; Lenarčič, Zala; Rosch, Achim

    2017-06-01

    Weak perturbations can drive an interacting many-particle system far from its initial equilibrium state if one is able to pump into degrees of freedom approximately protected by conservation laws. This concept has for example been used to realize Bose-Einstein condensates of photons, magnons and excitons. Integrable quantum systems, like the one-dimensional Heisenberg model, are characterized by an infinite set of conservation laws. Here, we develop a theory of weakly driven integrable systems and show that pumping can induce large spin or heat currents even in the presence of integrability breaking perturbations, since it activates local and quasi-local approximate conserved quantities. The resulting steady state is qualitatively captured by a truncated generalized Gibbs ensemble with Lagrange parameters that depend on the structure but not on the overall amplitude of perturbations nor the initial state. We suggest to use spin-chain materials driven by terahertz radiation to realize integrability-based spin and heat pumps.

  18. Optimization and approximation

    CERN Document Server

    Pedregal, Pablo

    2017-01-01

    This book provides a basic, initial resource, introducing science and engineering students to the field of optimization. It covers three main areas: mathematical programming, calculus of variations and optimal control, highlighting the ideas and concepts and offering insights into the importance of optimality conditions in each area. It also systematically presents affordable approximation methods. Exercises at various levels have been included to support the learning process.

  19. Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial

    DEFF Research Database (Denmark)

    Ravaud, Alain; Hawkins, Robert; Gardner, Jason P

    2008-01-01

    of metastatic sites--were randomly assigned to lapatinib 1,250 mg daily or HT. The primary end point was time to progression (TTP); secondary end points included overall survival (OS), safety, and biomarker analyses. RESULTS: Four hundred sixteen patients were enrolled onto the study. Median TTP was 15.3 weeks......PURPOSE: Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib...... was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2. PATIENTS AND METHODS: Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy--stratified by Karnofsky performance status and number...

  20. Factors associated with publication of randomized phase iii cancer trials in journals with a high impact factor.

    Science.gov (United States)

    Tang, P A; Pond, G R; Welch, S; Chen, E X

    2014-08-01

    Impact factor (if) is often used as a measure of journal quality. The purpose of the present study was to determine whether trials with positive outcomes are more likely to be published in journals with higher ifs. We reviewed 476 randomized phase iii cancer trials published in 13 journals between 1995 and 2005. Multivariate logistic regression models were used to investigate predictors of publication in journals with high ifs (compared with low and medium ifs). A positive outcome had the strongest association with publication in high-if journals [odds ratio (or): 4.13; 95% confidence interval (ci): 2.67 to 6.37; p impact factor bias," and investigators should be encouraged to submit reports of trials of high methodologic quality to journals with high ifs regardless of study outcomes.

  1. Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

    Directory of Open Access Journals (Sweden)

    Dietlind L. Wahner-Roedler

    2011-01-01

    Full Text Available Most patients with fibromyalgia use complementary and alternative medicine (CAM. Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ and the Center for Epidemiologic Studies Depression Scale (CES-D at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02 and by 18% in the placebo group (P < .001. The difference in change in scores between the groups was not significant (P = .16. With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004 and in the placebo group by 15% (P = .05. The change in scores was similar in the groups (P = .83. Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated.

  2. A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia.

    Science.gov (United States)

    Kuriakose, Moni Abraham; Ramdas, Kunnambath; Dey, Bindu; Iyer, Subramanya; Rajan, Gunaseelan; Elango, Kalavathy K; Suresh, Amritha; Ravindran, Divya; Kumar, Rajneesh R; R, Prathiba; Ramachandran, Surya; Kumar, Nisha Asok; Thomas, Gigi; Somanathan, Thara; Ravindran, Hiran K; Ranganathan, Kannan; Katakam, Sudhakar Babu; Parashuram, Shivashankar; Jayaprakash, Vijayvel; Pillai, M Radhakrishna

    2016-08-01

    Oral leukoplakia is a potentially malignant lesion of the oral cavity, for which no effective treatment is available. We investigated the effectiveness of curcumin, a potent inhibitor of NF-κB/COX-2, molecules perturbed in oral carcinogenesis, to treat leukoplakia. Subjects with oral leukoplakia (n = 223) were randomized (1:1 ratio) to receive orally, either 3.6 g/day of curcumin (n = 111) or placebo (n = 112), for 6 months. The primary endpoint was clinical response obtained by bi-dimensional measurement of leukoplakia size at recruitment and 6 months. Histologic response, combined clinical and histologic response, durability and effect of long-term therapy for an additional six months in partial responders, safety and compliance were the secondary endpoints. Clinical response was observed in 75 (67.5%) subjects [95% confidence interval (CI), 58.4-75.6] in the curcumin and 62 (55.3%; 95% CI, 46.1-64.2) in placebo arm (P = 0.03). This response was durable, with 16 of the 18 (88.9%; 95% CI, 67.2-96.9) subjects with complete response in curcumin and 7 of 8 subjects (87.5%) in placebo arm, demonstrating no relapse after 6 months follow-up. Difference in histologic response between curcumin and placebo was not significant (HR, 0.88, 95% CI, 0.45-1.71; P = 0.71). Combined clinical and histologic response assessment indicated a significantly better response with curcumin (HR, 0.50; 95% CI, 0.27-0.92; P = 0.02). Continued therapy, in subjects with partial response at 6 months, did not yield additional benefit. The treatment did not raise any safety concerns. Treatment of oral leukoplakia with curcumin (3.6 g for six months), thus was well tolerated and demonstrated significant and durable clinical response for 6 months. Cancer Prev Res; 9(8); 683-91. ©2016 AACR. ©2016 American Association for Cancer Research.

  3. Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine.

    Science.gov (United States)

    Delrieu, Isabelle; Leboulleux, Didier; Ivinson, Karen; Gessner, Bradford D

    2015-03-24

    Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Robot-assisted Versus Laparoscopic Surgery for Rectal Cancer: A Phase II Open Label Prospective Randomized Controlled Trial.

    Science.gov (United States)

    Kim, Min Jung; Park, Sung Chan; Park, Ji Won; Chang, Hee Jin; Kim, Dae Yong; Nam, Byung-Ho; Sohn, Dae Kyung; Oh, Jae Hwan

    2018-02-01

    The phase II randomized controlled trial aimed to compare the outcomes of robot-assisted surgery with those of laparoscopic surgery in the patients with rectal cancer. The feasibility of robot-assisted surgery over laparoscopic surgery for rectal cancer has not been established yet. Between February 21, 2012 and March 11, 2015, patients with rectal cancer (cT1-3NxM0) were enrolled. Patients were randomized 1:1 to either robot-assisted or laparoscopic surgery, and stratified per sex and administration of preoperative chemoradiotherapy. The primary outcome was the quality of total mesorectal excision (TME) specimen. Secondary outcomes were the circumferential and distal resection margins, the number of harvested lymph nodes, morbidity, bowel function recovery, and quality of life. A total of 163 patients were randomly assigned to the robot-assisted (n = 81) and laparoscopic (n = 82) surgery groups, and 139 patients were eligible for the analyses (73 vs 66, respectively). One patient (1.2%) in the robot-assisted group was converted to open surgery. The TME quality did not differ between the robot-assisted and laparoscopic groups (80.3% vs 78.1% complete TME, respectively; 18.2% vs 21.9% nearly complete TME, respectively; P = 0.599). The resection margins, number of harvested lymph nodes, morbidity, and bowel function recovery also were not significantly different. On analyzing quality of life, scores of the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C30) and EORTC QLQ CR38 were similar in the 2 groups, but in the EORTC QLQ CR 38 questionnaire, sexual function 12 months postoperatively was better in the robot-assisted group than in the laparoscopic group (P = 0.03). Robot-assisted surgery in rectal cancer showed TME quality comparable with that of laparoscopic surgery, and it demonstrated similar postoperative morbidity, bowel function recovery, and quality of life.

  5. Does magnesium sulfate delay the active phase of labor in women with premature rupture of membranes? A randomized controlled trial.

    Science.gov (United States)

    Mirzamoradi, Masoumeh; Behnam, Marzieh; Jahed, Tayebeh; Saleh-Gargari, Soraya; Bakhtiyari, Mahmood

    2014-09-01

    Administration of many drugs including magnesium sulfate (MS) has considerable influences on pregnancy outcomes. The present study investigates the effects of MS administration on reaching the active phase of labor in women with premature rupture of membrane (PROM) and subsequent fetal complications. A double blind, randomized, placebo-controlled trial was performed among primipara women referred to the PROM center in Tehran, Iran between March 2010 and August 2012. Patients were equally allocated into two groups; the intervention group who received MS (n = 46) and the control (placebo) group (n = 46). Both groups received a corticosteroid, 1g oral azithromycin (oral) and 2 g ampicillin (IV) every 6 hours for 48 hours, followed by amoxicillin (500 mg orally 3 times daily) for an additional 5 days. None of the research staff were aware of the treatment allocation of patients in order for blinding purposes. Administration of MS in intervention group increases this period 2.7 times compared to the control group. In women whose gestational age was magnesium sulfate reduced the risk of respiratory distress syndrome significantly (p = 0 .002), without producing any adverse pregnancy outcomes. Magnesium sulfate increases delay in reaching the active phase of labor in mothers with PROM, without producing adverse birth outcomes. (Registration ID in IRCT; IRCT2012091810876N1). Copyright © 2014. Published by Elsevier B.V.

  6. Phase I randomized safety study of twice daily dosing of acidform vaginal gel: candidate antimicrobial contraceptive.

    Directory of Open Access Journals (Sweden)

    Marla J Keller

    Full Text Available BACKGROUND: Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. METHODS: Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. RESULTS: The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002. While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra, an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08. CONCLUSIONS: Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than

  7. Phase I randomized safety study of twice daily dosing of acidform vaginal gel: candidate antimicrobial contraceptive.

    Science.gov (United States)

    Keller, Marla J; Carpenter, Colleen A; Lo, Yungtai; Einstein, Mark H; Liu, Congzhou; Fredricks, David N; Herold, Betsy C

    2012-01-01

    Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL) at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002). While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08). Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than placebo and lower levels of antimicrobial (lactoferrin) and anti

  8. Randomized phase II clinical trial of chemo-immunotherapy in advanced nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Eduardo Lasalvia-Prisco

    2008-09-01

    Full Text Available Eduardo Lasalvia-Prisco1,4, Emilio Garcia-Giralt2, Jesús Vázquez2,4, Marta Aghazarian4, Eduardo Lasalvia-Galante3,4, Joshemaria Larrañaga3,4, Gonzalo Spera31Interdoctors Medical Procedures, North Miami Beach, FL, USA; 2Centre De Cancérologie Hartmann, Neuilly Sur Seine, France; 3Interdoctors Medical Procedures, Montevideo, Uruguay; 4National Institute of Oncology, Montevideo, Uruguay (initial dataAbstract: The purpose of this study was to compare chemotherapy-naive patients with stage IV nonsmall cell lung cancer patients treated with chemotherapy or chemoimmunotherapy. We tested doxetacel plus cisplatinum as chemotherapy protocol. An immunomodulatory adjuvant system was added as chemoimmunotherapy to the previously mentioned protocol. This system contains three well-known and complementary conditioners of protective immune-responses: cyclophosphamide low-dose, granulocyte macrophage-colony stimulant factor and magnesium silicate granuloma. Eighty-eight patients were randomly assigned to receive every 3-weeks one of the treatments under comparison. Patients received four cycles of treatment unless disease progression or unacceptable toxicity was documented. The maximum follow-up was one year. In each arm, tumor response (rate, duration, median survival time, 1-year overall survival, safety, and immunity modifications were assessed. Immunity was evaluated by submitting peripheral blood mononuclear cells to laboratory tests for nonspecific immunity: a phytohemaglutinin-induced lymphocyte proliferation, b prevalence of T-Regulatory (CD4+CD25+ cells and for specific immunity: a lymphocyte proliferation induced by tumor-associated antigens (TAA contained in a previously described autologous thermostable hemoderivative. The difference (chemotherapy vs. chemoimmunotherapy in response rate induced by the two treatments (39.0% and 35.0% was not statistically significant. However, the response duration (22 and 31 weeks, the median survival time (32

  9. Survival Outcomes With Short-Course Radiation Therapy in Elderly Patients With Glioblastoma: Data From a Randomized Phase 3 Trial.

    Science.gov (United States)

    Guedes de Castro, Douglas; Matiello, Juliana; Roa, Wilson; Ghosh, Sunita; Kepka, Lucyna; Kumar, Narendra; Sinaika, Valery; Lomidze, Darejan; Hentati, Dalenda; Rosenblatt, Eduardo; Fidarova, Elena

    2017-07-15

    To perform a subset analysis of survival outcomes in elderly patients with glioblastoma from a randomized phase 3 trial comparing 2 short-course radiation therapy (RT) regimens in elderly and/or frail patients. The original trial population included elderly and/or frail patients with a diagnosis of glioblastoma. Patients joined the phase 3, randomized, multicenter, prospective, noninferiority trial; were assigned to 1 of 2 groups in a 1:1 ratio, either short-course RT (25 Gy in 5 fractions, arm 1) or commonly used RT (40 Gy in 15 fractions, arm 2); and were stratified by age (elderly and frail patients were defined as patients aged ≥65 years with KPS of 50%-70%; elderly and non-frail patients were defined as patients aged ≥65 years with KPS of 80%-100%); 61 of the 98 initial patients comprised the patient population, with 26 patients randomized to arm 1 and 35 to arm 2. In this unplanned analysis, the short-course RT results were not statistically significantly different from the results of commonly used RT in elderly patients. The median overall survival time was 6.8 months (95% confidence interval [CI], 4.5-9.1 months) in arm 1 and 6.2 months (95% CI, 4.7-7.7 months) in arm 2 (P=.936). The median progression-free survival time was 4.3 months (95% CI, 2.6-5.9 months) in arm 1 and 3.2 months (95% CI, 0.1-6.3 months) in arm 2 (P=.706). A short-course RT regimen of 25 Gy in 5 fractions is an acceptable treatment option for patients aged ≥65 years, mainly those with a poor performance status or contraindication to chemotherapy, which would be indicated in cases of methylated O6 methylguanine-DNA-methyltransferase promoter tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial.

    Directory of Open Access Journals (Sweden)

    Victoria K Snowdon

    2017-02-01

    Full Text Available Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2 is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1 and has been shown to increase renal perfusion in healthy human volunteers. We hypothesized that serelaxin could ameliorate renal vasoconstriction and renal dysfunction in patients with cirrhosis and portal hypertension.To establish preclinical proof of concept, we developed two independent rat models of cirrhosis that were characterized by progressive reduction in renal blood flow and glomerular filtration rate and showed evidence of renal endothelial dysfunction. We then set out to further explore and validate our hypothesis in a phase 2 randomized open-label parallel-group study in male and female patients with alcohol-related cirrhosis and portal hypertension. Forty patients were randomized 1:1 to treatment with serelaxin intravenous (i.v. infusion (for 60 min at 80 μg/kg/d and then 60 min at 30 μg/kg/d or terlipressin (single 2-mg i.v. bolus, and the regional hemodynamic effects were quantified by phase contrast magnetic resonance angiography at baseline and after 120 min. The primary endpoint was the change from baseline in total renal artery blood flow. Therapeutic targeting of renal vasoconstriction with serelaxin in the rat models increased kidney perfusion, oxygenation, and function through reduction in renal vascular resistance, reversal of endothelial dysfunction, and increased activation of the AKT

  11. Finite elements and approximation

    CERN Document Server

    Zienkiewicz, O C

    2006-01-01

    A powerful tool for the approximate solution of differential equations, the finite element is extensively used in industry and research. This book offers students of engineering and physics a comprehensive view of the principles involved, with numerous illustrative examples and exercises.Starting with continuum boundary value problems and the need for numerical discretization, the text examines finite difference methods, weighted residual methods in the context of continuous trial functions, and piecewise defined trial functions and the finite element method. Additional topics include higher o

  12. Approximation and perturbation methods

    CERN Document Server

    Iyer, B R

    1993-01-01

    Few problems in nature are amenable to an exact solution and hence when one proceeds from elegant problems of theory to messy complicated problems of practice one is forced to recourse to methods of approximation and perturbation. The development of such techniques has been natural in attempts to extract physically verifiable consequences from either exact solutions of general relativity or from specific astrophysical systems for which an exact solution is impossible to find. However, this should not be taken to imply giving up of mathematical rigour and an appeal to only physical intuition.

  13. Approximate Bayesian Computation

    Science.gov (United States)

    Sunnåker, Mikael; Corander, Jukka; Foll, Matthieu; Dessimoz, Christophe

    2013-01-01

    Approximate Bayesian computation (ABC) constitutes a class of computational methods rooted in Bayesian statistics. In all model-based statistical inference, the likelihood function is of central importance, since it expresses the probability of the observed data under a particular statistical model, and thus quantifies the support data lend to particular values of parameters and to choices among different models. For simple models, an analytical formula for the likelihood function can typically be derived. However, for more complex models, an analytical formula might be elusive or the likelihood function might be computationally very costly to evaluate. ABC methods bypass the evaluation of the likelihood function. In this way, ABC methods widen the realm of models for which statistical inference can be considered. ABC methods are mathematically well-founded, but they inevitably make assumptions and approximations whose impact needs to be carefully assessed. Furthermore, the wider application domain of ABC exacerbates the challenges of parameter estimation and model selection. ABC has rapidly gained popularity over the last years and in particular for the analysis of complex problems arising in biological sciences (e.g., in population genetics, ecology, epidemiology, and systems biology). PMID:23341757

  14. Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

    Science.gov (United States)

    2013-09-01

    10-1-0699 TITLE: Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after...apoptosis. WT1 protein is highly expressed in malignant pleural mesothelioma (MPM), and is a rational target for immunotherapy. We have developed a...this project is to conduct a multicenter, double-blinded, randomized trial comparing treatment with the WT-1 peptide vaccine + Montanide/GM-CSF to

  15. Priming with r-metHuSCF and filgrastim or chemotherapy and filgrastim in patients with malignant lymphomas: a randomized phase II pilot study of mobilization and engraftment

    DEFF Research Database (Denmark)

    Johnsen, H E; Geisler, C; Juvonen, E

    2011-01-01

    SCF has been shown to synergize with G-CSF to mobilize CD34(+) PBPCs. In this study we report results from this combination after a phase II trial of 32 patients with malignant lymphoma randomized to receive recombinant methionyl human SCF (ancestim, r-metHuSCF) in combination with recombinant...... and thrombocytopenia was documented in arm B. Third, 9/14 (64%) patients in arm A reached the target of 5 million CD34(+) cells/kg body weight (bw) compared with 13/15 (87%) in arm B. The results represent the first randomized trial of growth factor plus chemotherapy priming and indicate that a formal phase III trial...

  16. Approximation by Cylinder Surfaces

    DEFF Research Database (Denmark)

    Randrup, Thomas

    1997-01-01

    We present a new method for approximation of a given surface by a cylinder surface. It is a constructive geometric method, leading to a monorail representation of the cylinder surface. By use of a weighted Gaussian image of the given surface, we determine a projection plane. In the orthogonal...... projection of the surface onto this plane, a reference curve is determined by use of methods for thinning of binary images. Finally, the cylinder surface is constructed as follows: the directrix of the cylinder surface is determined by a least squares method minimizing the distance to the points...... in the projection within a tolerance given by the reference curve, and the rulings are lines perpendicular to the projection plane. Application of the method in ship design is given....

  17. Single blind randomized Phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Lips Irene M

    2011-12-01

    Full Text Available Abstract Background The treatment results of external beam radiotherapy for intermediate and high risk prostate cancer patients are insufficient with five-year biochemical relapse rates of approximately 35%. Several randomized trials have shown that dose escalation to the entire prostate improves biochemical disease free survival. However, further dose escalation to the whole gland is limited due to an unacceptable high risk of acute and late toxicity. Moreover, local recurrences often originate at the location of the macroscopic tumor, so boosting the radiation dose at the macroscopic tumor within the prostate might increase local control. A reduction of distant metastases and improved survival can be expected by reducing local failure. The aim of this study is to investigate the benefit of an ablative microboost to the macroscopic tumor within the prostate in patients treated with external beam radiotherapy for prostate cancer. Methods/Design The FLAME-trial (Focal Lesion Ablative Microboost in prostatE cancer is a single blind randomized controlled phase III trial. We aim to include 566 patients (283 per treatment arm with intermediate or high risk adenocarcinoma of the prostate who are scheduled for external beam radiotherapy using fiducial markers for position verification. With this number of patients, the expected increase in five-year freedom from biochemical failure rate of 10% can be detected with a power of 80%. Patients allocated to the standard arm receive a dose of 77 Gy in 35 fractions to the entire prostate and patients in the experimental arm receive 77 Gy to the entire prostate and an additional integrated microboost to the macroscopic tumor of 95 Gy in 35 fractions. The secondary outcome measures include treatment-related toxicity, quality of life and disease-specific survival. Furthermore, by localizing the recurrent tumors within the prostate during follow-up and correlating this with the delivered dose, we can obtain

  18. Efficacy of an aluminium triformate mouthrinse during the maintenance phase in periodontal patients: a pilot double blind randomized placebo-controlled clinical trial.

    Science.gov (United States)

    Azaripour, Adriano; Weusmann, Jens; Eschig, Carl; Schmidtmann, Irene; Van Noorden, Cornelis J F; Willershausen, Brita

    2016-05-23

    The aim of this prospective placebo-controlled pilot study was to evaluate short-term effects of a mouthrinse containing aluminium triformate (ATF) on gingival inflammation and plaque formation in periodontal patients who are in the maintenance phase. ATF has styptic (astringent) and anti-inflammatory effects. Forty non-smoking periodontal patients with modified sulcus bleeding index (MSBI) ≥40 % were randomly divided into two groups. The participants received a masked mouthrinse (ATF or placebo) and were instructed with the rinsing protocol of 3 daily rinses during 30 s for 7 days. One blinded investigator (CE) performed all clinical examinations. The primary outcome was reduction in gingival inflammation as measured by MSBI. The secondary outcomes were reduction of the amount of plaque as measured by plaque index (PI) and approximal plaque index (API) and the occurrence of side effects. The patients were evaluated at the start and the end of the rinsing period, including the compliance of the patients. MSBI was reduced in both groups compared to baseline, but the ATF group showed significantly more reduction in MSBI compared to the placebo group (ATF: 17.6 %, placebo: 7.6 %, p = 0.035). ATF and placebo had no effects on dental plaque. Patients reported ATF mouthrinse not to have side effects other than oral sensation, whereas compliance of the patients was good. Almost all patients in the ATF group reported reduction of gum bleeding after 1 week of rinsing with ATF. This short-term pilot clinical trial is a firm basis to design a long-term controlled clinical trial to show whether ATF helps to inhibit further periodontal breakdown in maintenance patients with high MSBI. This trial was registered in the WHO International Clinical Trials Registry Platform as DRKS00007672 , date of registration: 21/01/2015.

  19. Survival benefit with capecitabine/docetaxel versus docetaxel alone: analysis of therapy in a randomized phase III trial.

    Science.gov (United States)

    Miles, David; Vukelja, Svetislava; Moiseyenko, Vladimir; Cervantes, Guadalupe; Mauriac, Louis; Van Hazel, Guy; Liu, Wing-Yiu; Ayoub, Jean-Pierre; O'Shaughnessy, Joyce A

    2004-10-01

    In a large phase III trial of 511 patients with anthracycline-pretreated advanced/metastatic breast cancer, capecitabine/docetaxel combination therapy was shown to have significantly superior efficacy compared with single-agent docetaxel, including superior progression-free and overall survival and objective response rate. An updated survival analysis with >/= 27 months follow-up shows that patients receiving combination therapy maintained significantly superior survival (hazard ratio [HR], 0.777 [95% CI, 0.645-0.942]; P < 0.01; median survival, 14.5 months vs. 11.5 months) compared with those receiving single-agent docetaxel. Following the failure of docetaxel monotherapy, 35% of patients did not receive additional cytotoxic chemotherapy. Among patients randomized to single-agent docetaxel, only those given poststudy single-agent capecitabine had significantly prolonged survival compared with those given any other poststudy chemotherapy (HR, 0.500; P = 0.0046; median survival, 21.0 months vs. 12.3 months, respectively). By contrast, poststudy vinorelbine-containing chemotherapy did not affect survival following progression on single-agent docetaxel compared with other poststudy chemotherapy regimens (HR, 1.014; P = 0.94; median survival, 13.5 months vs. 12.6 months, respectively). Among patients randomized to combination therapy, discontinuing docetaxel of capecitabine has a similar effect on survival (HR, 0.720; P = 0.20; median survival, 15.8 months vs. 18.3 months, respectively). Median survival was 18.3 months in patients who discontinued docetaxel and continued to receive capecitabine versus 15.8 months in patients who discontinued capecitabine and continued to receive docetaxel, with a trend toward improved survival in patients continuing to receive capecitabine. Although this is a retrospective analysis, these data suggest that the sequential administration of docetaxel followed by capecitabine is associated with prolonged survival in patients who are

  20. Pharmacokinetics of lacosamide and omeprazole coadministration in healthy volunteers: results from a phase I, randomized, crossover trial.

    Science.gov (United States)

    Cawello, Willi; Mueller-Voessing, Christa; Fichtner, Andreas

    2014-05-01

    The antiepileptic drug lacosamide has a low potential for drug-drug interactions, but is a substrate and moderate inhibitor of the cytochrome P450 (CYP) enzyme CYP2C19. This phase I, randomized, open-label, two-way crossover trial evaluated the pharmacokinetic effects of lacosamide and omeprazole coadministration. Healthy, White, male volunteers (n = 36) who were not poor metabolizers of CYP2C19 were randomized to treatment A (single-dose 40 mg omeprazole on days 1 and 8 together with 6 days of multiple-dose lacosamide [200-600 mg/day] on days 3-8) and treatment B (single doses of 300 mg lacosamide on days 1 and 8 with 7 days of 40 mg/day omeprazole on days 3-9) in pseudorandom order, separated by a ≥ 7-day washout period. Area under the concentration-time curve (AUC) and peak concentration (C(max)) were the primary pharmacokinetic parameters measured for lacosamide or omeprazole administered alone (reference) or in combination (test). Bioequivalence was determined if the 90 % confidence interval (CI) of the ratio (test/reference) fell within the acceptance range of 0.8-1.25. The point estimates (90 % CI) of the ratio of omeprazole + lacosamide coadministered versus omeprazole alone for AUC (1.098 [0.996-1.209]) and C(max) (1.105 [0.979-1.247]) fell within the acceptance range for bioequivalence. The point estimates (90 % CI) of the ratio of lacosamide + omeprazole coadministration versus lacosamide alone also fell within the acceptance range for bioequivalence (AUC 1.133 [1.102-1.165]); C(max) 0.996 (0.947-1.047). Steady-state lacosamide did not influence omeprazole single-dose pharmacokinetics, and multiple-dose omeprazole did not influence lacosamide single-dose pharmacokinetics.

  1. Comparison of Iohexol-380 and Iohexol-350 for coronary CT angiography: A multicenter, randomized, double-blind phase 3 trial

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun Ah; Lee, Whal [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Kang, Doo Kyoung [Dept. of Radiology, Ajou University School of Medicine, Suwon (Korea, Republic of); and others

    2016-06-15

    This multi-center, randomized, double-blind, phase 3 trial was conducted to compare the safety and efficacy of contrast agents iohexol-380 and iohexol-350 for coronary CT angiography in healthy subjects. Volunteers were randomized to receive 420 mgI/kg of either iohexol-350 or iohexol-380 using a flow rate of 4 mL/sec. All adverse events were recorded. Two blinded readers independently reviewed the CT images and conflicting results were resolved by a third reader. Luminal attenuations (ascending aorta, left main coronary artery, and left ventricle) in Hounsfield units (HUs) and image quality on a 4-point scale were calculated. A total of 225 subjects were given contrast media (115 with iohexol-380 and 110 with iohexol-350). There was no difference in number of adverse drug reactions between groups: 75 events in 56 (48.7%) of 115 subjects in the iohexol-380 group vs. 74 events in 51 (46.4%) of 110 subjects in the iohexol-350 group (p = 0.690). No severe adverse drug reactions were recorded. Neither group showed an increase in serum creatinine. Significant differences in mean density between the groups was found in the ascending aorta: 375.8 ± 71.4 HU with iohexol-380 vs. 356.3 ± 61.5 HU with iohexol-350 (p = 0.030). No significant differences in image quality scores between both groups were observed for all three anatomic evaluations (all, p > 0.05). Iohexol-380 provides improved enhancement of the ascending aorta and similar attenuation of the coronary arteries without any increase in adverse drug reactions, as compared with iohexol-350 using an identical amount of total iodine.

  2. Randomized phase 2 trial of regadenoson for treatment of acute vaso-occlusive crises in sickle cell disease.

    Science.gov (United States)

    Field, Joshua J; Majerus, Elaine; Gordeuk, Victor R; Gowhari, Michel; Hoppe, Carolyn; Heeney, Matthew M; Achebe, Maureen; George, Alex; Chu, Hillary; Sheehan, Brian; Puligandla, Maneka; Neuberg, Donna; Lin, Gene; Linden, Joel; Nathan, David G

    2017-09-12

    Adenosine A 2A receptor (A 2A R) agonists have been shown to decrease tissue inflammation induced by hypoxia/reoxygenation in mice with sickle cell disease (SCD). The key mediator of the A 2A R agonist's anti-inflammatory effects is a minor lymphocyte subset, invariant natural killer T (iNKT) cells. We tested the hypothesis that administration of an A 2A R agonist in patients with SCD would decrease iNKT cell activation and dampen the severity of vaso-occlusive (VO) crises. In a phase 2, randomized, placebo-controlled trial, we administered a 48-hour infusion of the A 2A R agonist regadenoson (1.44 μg/kg per hour) to patients with SCD during VO crises to produce a plasma concentration of ∼5 nM, a concentration known from prior studies to suppress iNKT cell activation in SCD. The primary outcome measure was a >30% reduction in the percentage of activated iNKT cells. Ninety-two patients with SCD were randomized to receive a 48-hour infusion of regadenoson or placebo, in addition to standard-of-care treatment, during hospital admission for a VO crisis and had analyzable iNKT cell samples. The proportion of subjects who demonstrated a reduction of >30% in activated iNKT cells was not significantly different between the regadenoson and placebo arms (43% vs 23%; P = .07). There were also no differences between regadenoson and placebo groups in length of hospital stay, mean total opioid use, or pain scores. These data demonstrate that a low-dose infusion of regadenoson intended to reduce the activity of iNKT cells is not sufficient to produce a statistically significant reduction in such activation or in measures of clinical efficacy. This trial was registered at www.clinicaltrials.gov as #NCT01788631.

  3. A Randomized Controlled Trial of Cognitive-Behavior Therapy Plus Bright Light Therapy for Adolescent Delayed Sleep Phase Disorder

    Science.gov (United States)

    Gradisar, Michael; Dohnt, Hayley; Gardner, Greg; Paine, Sarah; Starkey, Karina; Menne, Annemarie; Slater, Amy; Wright, Helen; Hudson, Jennifer L.; Weaver, Edward; Trenowden, Sophie

    2011-01-01

    Objective: To evaluate cognitive-behavior therapy plus bright light therapy (CBT plus BLT) for adolescents diagnosed with delayed sleep phase disorder (DSPD). Design: Randomized controlled trial of CBT plus BLT vs. waitlist (WL) control with comparisons at pre- and post-treatment. There was 6-month follow-up for the CBT plus BLT group only. Setting: Flinders University Child & Adolescent Sleep Clinic, Adelaide, South Australia. Patients: 49 adolescents (mean age 14.6 ± 1.0 y, 53% males) diagnosed with DSPD; mean chronicity 4 y 8 months; 16% not attending school. Eighteen percent of adolescents dropped out of the study (CBT plus BLT: N = 23 vs WL: N = 17). Interventions: CBT plus BLT consisted of 6 individual sessions, including morning bright light therapy to advance adolescents' circadian rhythms, and cognitive restructuring and sleep education to target associated insomnia and sleep hygiene. Measurements and Results: DSPD diagnosis was performed via a clinical interview and 7-day sleep diary. Measurements at each time-point included online sleep diaries and scales measuring sleepiness, fatigue, and depression symptoms. Compared to WL, moderate-to-large improvements (d = 0.65-1.24) were found at post-treatment for CBT plus BLT adolescents, including reduced sleep latency, earlier sleep onset and rise times, total sleep time (school nights), wake after sleep onset, sleepiness, and fatigue. At 6-month follow-up (N = 15), small-to-large improvements (d = 0.24-1.53) continued for CBT plus BLT adolescents, with effects found for all measures. Significantly fewer adolescents receiving CBT plus BLT met DPSD criteria at post-treatment (WL = 82% vs. CBT plus BLT = 13%, P sleep and daytime impairments in the immediate and long-term. Studies evaluating the treatment effectiveness of each treatment component are needed. Clinical Trial Information: Australia – New Zealand Trials Registry Number: ACTRN12610001041044. Citation: Gradisar M; Dohnt H; Gardner G; Paine S; Starkey

  4. Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Mahamadou A Thera

    2008-01-01

    Full Text Available The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria.A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1 based on apical membrane antigen-1 (AMA-1 from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert. Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.

  5. Randomized Phase 2 Trial of S1 and Oxaliplatin-Based Chemoradiotherapy With or Without Induction Chemotherapy for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Dok Hyun [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jang, Geundoo [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Internal Medicine, Hallym Medical Center, Hallym University College of Medicine, Seoul (Korea, Republic of); Kim, Jong Hoon [Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Yong-Hee [Department of Thoracic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Ji Youn [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Hyeong Ryul [Department of Thoracic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jung, Hwoon-Yong; Lee, Gin-Hyug [Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Song, Ho Young [Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Cho, Kyung-Ja [Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Ryu, Jin-Sook [Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Sung-Bae, E-mail: sbkim3@amc.seoul.kr [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2015-03-01

    Purpose: To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer. Patients and Methods: Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m{sup 2} on day 1 and S1 at 40 mg/m{sup 2} twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m{sup 2} on days 1 and 21 and S1 30 mg/m{sup 2} twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate. Results: A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery. Conclusions: Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.

  6. Safety and Activity of UR-1505 in Atopic Dermatitis: A Randomized, Double-blind Phase II Exploratory Trial.

    Science.gov (United States)

    Vives, Roser; Pontes, Caridad; Sarasa, Maria; Millier, Aurelie

    2015-09-01

    UR-1505 is a new small molecule with immune modulator properties intended for the topical treatment of inflammatory skin diseases that has shown anti-inflammatory effects in models of skin inflammation. We compared the activity of UR-1505 ointment against its vehicle in the treatment of atopic dermatitis. Secondary objectives included exploring dose response, safety, and local tolerability of UR-1505. Patients with AD lesions on 2 symmetrical topographic areas (arms, leg, or trunk) were included in this unicenter randomized, double-blind, within-patient, controlled Phase II exploratory trial and received simultaneously 2 different treatments (0.5%, 1%, or 2% UR-1505 and vehicle or 0.1% tacrolimus ointment) once daily during 28 days. The primary efficacy end point was the change from baseline in the Investigator Global Assessment score at Day 28. Secondary end points were percentage of area clearance, local Eczema Area Severity Index (local EASI), and local tolerability. A linear mixed model was used, fitting treatment, body side, and group (treatment at the contralateral side) as fixed factors and the patient as a random effect. Twenty-eight patients were randomized and 25 patients were included in the per protocol analysis, with 50 evaluable lesions (n = 13 for vehicle, n = 8 for UR-1505 0.5%, n = 9 for 1% UR-1505, n=8 for 2% UR-1505, and n=12 for tacrolimus). The mean Investigator Global Assessment score change from baseline at Day 28 was -1.7 for vehicle, -1.0, -1.2, and -1.5 for 0.5%, 1%, and 2% UR-1505, respectively, and -2.6% for tacrolimus (P = 0.002). No serious nor causal adverse reactions were reported in this study, but patients reported numerous local symptoms after product applications, especially itching, tingling, tightness, and heat/burning sensations at frequencies that were similar for vehicle, 1% UR-1505, and 2% UR-1505; more frequent with 0.5% UR-1505; and lowest for tacrolimus. This study found that UR-1505 may not be a suitable option for the

  7. Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis.

    Science.gov (United States)

    Constantinescu, Cris S; Asher, Aliya; Fryze, Waldemar; Kozubski, Wojciech; Wagner, Frank; Aram, Jehan; Tanasescu, Radu; Korolkiewicz, Roman P; Dirnberger-Hertweck, Maren; Steidl, Stefan; Libretto, Susan E; Sprenger, Till; Radue, Ernst W

    2015-08-01

    To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity. In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.0 (n = 8), or 2.0 (n = 9) mg/kg every 2 weeks for 10 weeks. Patients had to have ≤10 gadolinium (Gd)-enhancing brain lesions on T1-weighted MRI at baseline. The primary objective was safety. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most frequent was nasopharyngitis. Between-group differences in TEAE numbers were small. There were no TEAE-related trial discontinuations, infusion-related reactions, or deaths. Nine patients experienced MS exacerbations: 3, 5, 1, and 0 patient(s) in the placebo, 0.5, 1.0, and 2.0 mg/kg groups, respectively. A few T1 Gd-enhancing lesions and/or new or enlarging T2 lesions indicative of inflammation were observed in all treatment groups. No clinically significant changes were observed in other clinical assessments or laboratory safety assessments. No anti-MOR103 antibodies were detected. PK evaluations indicated dose linearity with low/no drug accumulation over time. MOR103 was generally well-tolerated in patients with RRMS or SPMS. No evidence of immunogenicity was found. This phase 1b study provides Class I evidence that MOR103 has acceptable tolerability in patients with MS.

  8. Amino acid supplementation is anabolic during the acute phase of endotoxin-induced inflammation: A human randomized crossover trial.

    Science.gov (United States)

    Rittig, N; Bach, E; Thomsen, H H; Johannsen, M; Jørgensen, J O; Richelsen, B; Jessen, N; Møller, N

    2016-04-01

    Inflammation is catabolic and causes muscle loss. It is unknown if amino acid supplementation reverses these effects during the acute phase of inflammation. The aim was to test whether amino acid supplementation counteracts endotoxin-induced catabolism. Eight young, healthy, lean males were investigated three times in randomized order: (i) normal conditions (Placebo), (ii) endotoxemia (LPS), and (iii) endotoxemia with amino acid supplementation (LPS + A). Protein kinetics were determined using phenylalanine, tyrosine, and urea tracers. Each study day consisted of a four-hour non-insulin stimulated period and a two-hour hyperinsulinemic euglycemic clamp period. Muscle biopsies were collected once each period. Endotoxin administration created a significant inflammatory response (cytokines, hormones, and vital parameters) without significant differences between LPS and LPS + A. Whole body protein breakdown was elevated during LPS compared with Placebo and LPS + A (p translation factor 4E-binding protein 1 (4EBP1) phosphorylation (p = 0.007) without activating AMPK or affecting insulin signaling through Akt. During insulin stimulation net muscle phenylalanine release and protein degradation were further reduced. Amino acid supplementation in the acute phase of inflammation reduces whole body and muscle protein loss, and this effect is associated with activation of mTOR and downstream signaling to protein synthesis through mTORC1, suggesting a therapeutic role for intravenous amino acids in inflammatory states. The Central Denmark Region Ethics Commitee (1-10-71-410-12) www.clinicaltrials.gov (identification number NCT01705782). Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  9. Evaluation of Gaussian approximations for data assimilation in reservoir models

    KAUST Repository

    Iglesias, Marco A.

    2013-07-14

    The Bayesian framework is the standard approach for data assimilation in reservoir modeling. This framework involves characterizing the posterior distribution of geological parameters in terms of a given prior distribution and data from the reservoir dynamics, together with a forward model connecting the space of geological parameters to the data space. Since the posterior distribution quantifies the uncertainty in the geologic parameters of the reservoir, the characterization of the posterior is fundamental for the optimal management of reservoirs. Unfortunately, due to the large-scale highly nonlinear properties of standard reservoir models, characterizing the posterior is computationally prohibitive. Instead, more affordable ad hoc techniques, based on Gaussian approximations, are often used for characterizing the posterior distribution. Evaluating the performance of those Gaussian approximations is typically conducted by assessing their ability at reproducing the truth within the confidence interval provided by the ad hoc technique under consideration. This has the disadvantage of mixing up the approximation properties of the history matching algorithm employed with the information content of the particular observations used, making it hard to evaluate the effect of the ad hoc approximations alone. In this paper, we avoid this disadvantage by comparing the ad hoc techniques with a fully resolved state-of-the-art probing of the Bayesian posterior distribution. The ad hoc techniques whose performance we assess are based on (1) linearization around the maximum a posteriori estimate, (2) randomized maximum likelihood, and (3) ensemble Kalman filter-type methods. In order to fully resolve the posterior distribution, we implement a state-of-the art Markov chain Monte Carlo (MCMC) method that scales well with respect to the dimension of the parameter space, enabling us to study realistic forward models, in two space dimensions, at a high level of grid refinement. Our

  10. Prestack traveltime approximations

    KAUST Repository

    Alkhalifah, Tariq Ali

    2012-05-01

    Many of the explicit prestack traveltime relations used in practice are based on homogeneous (or semi-homogenous, possibly effective) media approximations. This includes the multifocusing, based on the double square-root (DSR) equation, and the common reflection stack (CRS) approaches. Using the DSR equation, I constructed the associated eikonal form in the general source-receiver domain. Like its wave-equation counterpart, it suffers from a critical singularity for horizontally traveling waves. As a result, I recasted the eikonal in terms of the reflection angle, and thus, derived expansion based solutions of this eikonal in terms of the difference between the source and receiver velocities in a generally inhomogenous background medium. The zero-order term solution, corresponding to ignoring the lateral velocity variation in estimating the prestack part, is free of singularities and can be used to estimate traveltimes for small to moderate offsets (or reflection angles) in a generally inhomogeneous medium. The higher-order terms include limitations for horizontally traveling waves, however, we can readily enforce stability constraints to avoid such singularities. In fact, another expansion over reflection angle can help us avoid these singularities by requiring the source and receiver velocities to be different. On the other hand, expansions in terms of reflection angles result in singularity free equations. For a homogenous background medium, as a test, the solutions are reasonably accurate to large reflection and dip angles. A Marmousi example demonstrated the usefulness and versatility of the formulation. © 2012 Society of Exploration Geophysicists.

  11. Approximations in the PE-method

    DEFF Research Database (Denmark)

    Arranz, Marta Galindo

    1996-01-01

    Two differenct sources of errors may occur in the implementation of the PE methods; a phase error introduced in the approximation of a pseudo-differential operator and an amplitude error generated from the starting field. First, the inherent phase errors introduced in the solution are analyzed...... for a case where the normal mode solution to the wave equation is valid, when the sound is propagated in a downward refracting atmosphere. The angular limitations for the different parabolic approximations are deduced, and calculations showing shifts in the starter as the second source of error...

  12. Effect of the gastrointestinal prokinetic agent erythromycin on the pharmacokinetics of pregabalin controlled-release in healthy individuals: a phase I, randomized crossover trial.

    Science.gov (United States)

    Chew, Marci L; Plotka, Anna; Alvey, Christine W; Pitman, Verne W; Alebic-Kolbah, Tanja; Scavone, Joseph M; Bockbrader, Howard N

    2015-05-01

    The controlled-release (CR) formulation of pregabalin is designed to remain in the stomach for a prolonged period while slowly releasing pregabalin for absorption in the small intestine. This study evaluated the effect of the gastrointestinal prokinetic agent, erythromycin, on the pharmacokinetics of a single dose of pregabalin CR 330 mg administered following an evening meal and the safety and tolerability of a single dose of pregabalin CR 330 mg when administered with and without multiple doses of erythromycin 500 mg. This was a phase I, open-label, randomized, two-period, two-treatment crossover study. Participants received (in a randomized sequence) a single oral dose of pregabalin CR 330 mg alone and pregabalin CR 330 mg co-administered with multiple doses of erythromycin 500 mg. The CR formulation was administered immediately following a standardized 600-750 calorie 30 % fat evening meal. Erythromycin 500 mg was administered orally approximately 1 h prior to pregabalin CR, as well as 6 and 12 h following the first erythromycin dose. Blood samples were collected up to 48 h post-pregabalin CR dose. Pharmacokinetic parameters were estimated from concentration-time data using standard noncompartmental methods. Adverse events were monitored throughout. Eighteen healthy participants (aged 19-52 years) received pregabalin CR. Co-administration of pregabalin CR with erythromycin resulted in a 17 % decrease in total exposure [area under the plasma concentration-time curve from zero to infinity (AUC∞)] and a 13 % decrease in peak plasma concentrations (C max) relative to pregabalin CR administered alone. The 90 % CI for the ratio of the adjusted geometric mean AUC∞ was 76.5-89.2 % (outside the 80-125 % range prespecified for bioequivalence). Adverse events were of mild to moderate severity and the adverse event profile was similar for pregabalin CR administered with and without erythromycin. Co-administration of multiple high doses of erythromycin resulted in 17

  13. Ixekizumab treatment improves fingernail psoriasis in patients with moderate-to-severe psoriasis: results from the randomized, controlled and open-label phases of UNCOVER-3

    NARCIS (Netherlands)

    Kerkhof, P. van de; Guenther, L.; Gottlieb, A.B.; Sebastian, M.; Wu, J.J.; Foley, P.; Morita, A.; Goldblum, O.; Zhang, L.; Erickson, J.; Ball, S.; Rich, P.

    2017-01-01

    BACKGROUND: Fingernail psoriasis is difficult to treat. OBJECTIVE: The objective was to evaluate the effect of ixekizumab, a monoclonal antibody selectively targeting IL-17A, on fingernail psoriasis. METHODS: This Phase 3, double-blind trial (UNCOVER-3) randomized patients to placebo, etanercept

  14. CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma

    DEFF Research Database (Denmark)

    Escudier, Bernard; Sharma, Padmanee; McDermott, David F

    2017-01-01

    BACKGROUND: The randomized, phase 3 CheckMate 025 study of nivolumab (n=410) versus everolimus (n=411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). OBJECTIV...

  15. ACUTE TOXICITY PROFILE AND COMPLIANCE TO ACCELERATED RADIOTHERAPY PLUS CARBOGEN AND NICOTINAMIDE FOR CLINICAL STAGE T2-4 LARYNGEAL CANCER : RESULTS OF A PHASE III RANDOMIZED TRIAL

    NARCIS (Netherlands)

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; van den Ende, Piet; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

    2012-01-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with

  16. Acute toxicity profile and compliance to accelerated radiotherapy plus carbogen and nicotinamide for clinical stage T2-4 laryngeal cancer: results of a phase III randomized trial.

    NARCIS (Netherlands)

    Janssens, G.O.R.J.; Terhaard, C.H.J.; Doornaert, P.A.; Bijl, H.P.; Ende, P. van den; Chin, A.; Pop, L.A.M.; Kaanders, J.H.A.M.

    2012-01-01

    PURPOSE: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. METHODS AND MATERIALS: From April 2001 to February 2008, 345 patients with

  17. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma.

    NARCIS (Netherlands)

    Lokhorst, H.M.; Holt, B. van der; Zweegman, S.; Vellenga, E.; Croockewit, S.; Oers, M.H. van; Borne, P. von dem; Wijermans, P.; Schaafsma, R.; Weerdt, O. de; Wittebol, S.; Delforge, M.; Berenschot, H.; Bos, G.M.; Jie, K.S.; Sinnige, H.; Marwijk-Kooy, M. van; Joosten, P.; Minnema, M.C.; Ammerlaan, R. van; Sonneveld, P.

    2010-01-01

    The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and

  18. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma

    NARCIS (Netherlands)

    Lokhorst, Henk M.; van der Holt, Bronno; Zweegman, Sonja; Vellenga, Edo; Croockewit, Sandra; van Oers, Marinus H.; von dem Borne, Peter; Wijermans, Pierre; Schaafsma, Ron; de Weerdt, Okke; Wittebol, Shulamiet; Delforge, Michel; Berenschot, Henriëtte; Bos, Gerard M.; Jie, Kon-Siong G.; Sinnige, Harm; van Marwijk-Kooy, Marinus; Joosten, Peter; Minnema, Monique C.; van Ammerlaan, Rianne; Sonneveld, Pieter

    2010-01-01

    The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and

  19. Randomized double-blind controlled Phase I/IIa trial to assess the efficacy of malaria vaccine PfCS102 to protect against challenge with P. falciparum.

    NARCIS (Netherlands)

    Genton, B.; D'Acremont, V.; Lurati-Ruiz, F.; Verhage, D.F.; Audran, R.; Hermsen, C.C.; Wolters, L.; Reymond, C.; Spertini, F.; Sauerwein, R.W.

    2010-01-01

    The aim of this Phase I/IIa double-blind controlled trial was to test the efficacy of the sporozoite-based malaria vaccine PfCS 282-383 (PfCS102) to protect against Plasmodium falciparum parasitaemia. 16 volunteers were randomized to receive twice 30 mug of PfCS102 formulated in Montanide ISA 720 or

  20. The FINISH-3 Trial : A Phase 3, International, Randomized, Single-Blind, Controlled Trial of Topical Fibrocaps in Intraoperative Surgical Hemostasis

    NARCIS (Netherlands)

    Bochicchio, Grant V.; Gupta, Navyash; Porte, Robert J.; Renkens, Kenneth L.; Pattyn, Piet; Topal, Baki; Troisi, Roberto Ivan; Muir, William; Chetter, Ian; Gillen, Daniel L.; Zuckerman, Linda A.; Frohna, Paul A.

    BACKGROUND: This Phase 3, international, randomized, single-blind, controlled trial (FINISH-3) compared the efficacy and safety of Fibrocaps, a ready-to-use, dry-powder fibrin sealant containing human plasma-derived thrombin and fibrinogen, vs gelatin sponge alone for use as a hemostat for surgical

  1. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma

    NARCIS (Netherlands)

    H.M. Lokhorst (Henk); B. van der Holt (Bronno); S. Zweegman (Sonja); E. Vellenga (Edo); S. Croockewit (Sandra); M.H.J. van Oers (Marinus); P.A. von dem Borne (P. A.); P.W. Wijermans (Pierre); R. Schaafsma (Ron); O. de Weerdt (Okke); S. Wittebol (Shulamit); M. Delforge (Michel); H. Berenschot (Henriëtte); G.M. Bos (Gerard); K.S-G. Jie; H. Sinnige (Harm); M. van Marwijk Kooy (Marinus); P. Joosten (Peter); M.C. Minnema (Monique); R.A.H.M. Ammerlaan (Rianne); P. Sonneveld (Pieter)

    2010-01-01

    textabstractThe phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and

  2. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial

    NARCIS (Netherlands)

    Breugom, A.J.; Gijn, W. van; Muller, E.W.; Berglund, A; Broek, C.B. van den; Fokstuen, T.; Gelderblom, H.; Kapiteijn, E.; Leer, J.W.H.; Marijnen, C.A.; Martijn, H.; Meershoek-Klein Kranenbarg, E.; Nagtegaal, I.D.; Pahlman, L.; Punt, C.J.A.; Putter, H.; Roodvoets, A.G.; Rutten, H.J.; Steup, W.H.; Glimelius, B.; Velde, C.J. van de

    2015-01-01

    BACKGROUND: The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients

  3. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial

    NARCIS (Netherlands)

    Breugom, A. J.; van Gijn, W.; Muller, E. W.; Berglund, Å; van den Broek, C. B. M.; Fokstuen, T.; Gelderblom, H.; Kapiteijn, E.; Leer, J. W. H.; Marijnen, C. A. M.; Martijn, H.; Meershoek-Klein Kranenbarg, E.; Nagtegaal, I. D.; Påhlman, L.; Punt, C. J. A.; Putter, H.; Roodvoets, A. G. H.; Rutten, H. J. T.; Steup, W. H.; Glimelius, B.; van de Velde, C. J. H.

    2015-01-01

    The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with

  4. A phase II randomized trial comparing radiotherapy with concurrent weekly cisplatin or weekly paclitaxel in patients with advanced cervical cancer

    Directory of Open Access Journals (Sweden)

    Charafeddine Maya

    2010-09-01

    Full Text Available Abstract Purpose/Objective This is a prospective comparison of weekly cisplatin to weekly paclitaxel as concurrent chemotherapy with standard radiotherapy for locally advanced cervical carcinoma. Materials/Methods Between May 2000 and May 2004, 31 women with FIGO stage IB2-IVA cervical cancer or with postsurgical pelvic recurrence were enrolled into this phase II study and randomized to receive on a weekly basis either 40 mg/m2 Cisplatin (group I; 16 patients or 50 mg/m2 paclitaxel (group II; 15 patients concurrently with radiotherapy. Median total dose to point A was 74 Gy (range: 66-92 Gy for group I and 66 Gy (range: 40-98 Gy for group II. Median follow-up time was 46 months. Results Patient and tumor characteristics were similar in both groups. The mean number of chemotherapy cycles was also comparable with 87% and 80% of patients receiving at least 4 doses in groups I and II, respectively. Seven patients (44% of group I and 8 patients (53% of group II developed tumor recurrence. The Median Survival time was not reached for Group I and 53 months for group II. The proportion of patients surviving at 2 and 5 years was 78% and 54% for group I and 73% and 43% for group II respectively. Conclusions This small prospective study shows that weekly paclitaxel does not provide any clinical advantage over weekly cisplatin for concurrent chemoradiation for advanced carcinoma of the cervix.

  5. A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma.

    Science.gov (United States)

    Szefler, Stanley J; Murphy, Kevin; Harper, Thomas; Boner, Attilio; Laki, István; Engel, Michael; El Azzi, Georges; Moroni-Zentgraf, Petra; Finnigan, Helen; Hamelmann, Eckard

    2017-11-01

    Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma. We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma. In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, add-on therapy improved the primary end point, peak FEV 1 within 3 hours after dosing (5 μg, 139 mL [95% CI, 75-203; P add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Effect of dance labor on the management of active phase labor pain & clients' satisfaction: a randomized controlled trial study.

    Science.gov (United States)

    Abdolahian, Somayeh; Ghavi, Fatemeh; Abdollahifard, Sareh; Sheikhan, Fatemeh

    2014-03-30

    There are a wide variety of non- pharmacologic pain relief techniques for labor which include pelvic movement, upright position, back massage and partner support during the first stage of labor. The effectiveness of dance labor- which is a combination of these techniques- has not been evaluated. This study aimed to evaluate the effectiveness of dance labor in pain reduction and woman's satisfaction during the first stage of labor. 60 primiparous women aged 18-35 years old were randomly assigned to dance labor and control groups. In the dance labor group, women were instructed to do standing upright with pelvic tilt and rock their hips back and forth or around in a circle while their partner massaged their back and sacrum for a minimum of 30 minutes. In the control group, the participants received usual care during physiologic labor. Pain and satisfaction scores were measured by Visual Analogue Scale. Data were analyzed by using the t. test and Chi-square. Mean pain score in the dance labor group was significantly lower than the control group (P dance labor group was significantly higher than in the control group (P Dance labor which is a complementary treatment with low risk can reduce the intensity of pain and increase mothers, satisfaction with care during the active phase of labor.

  7. Detection and measurement of fetal abdominal contour in ultrasound images via local phase information and iterative randomized Hough transform.

    Science.gov (United States)

    Wang, Weiming; Qin, Jing; Zhu, Lei; Ni, Dong; Chui, Yim-Pan; Heng, Pheng-Ann

    2014-01-01

    Due to the characteristic artifacts of ultrasound images, e.g., speckle noise, shadows and intensity inhomogeneity, traditional intensity-based methods usually have limited success on the segmentation of fetal abdominal contour. This paper presents a novel approach to detect and measure the abdominal contour from fetal ultrasound images in two steps. First, a local phase-based measure called multiscale feature asymmetry (MSFA) is de ned from the monogenic signal to detect the boundaries of fetal abdomen. The MSFA measure is intensity invariant and provides an absolute measurement for the signi cance of features in the image. Second, in order to detect the ellipse that ts to the abdominal contour, the iterative randomized Hough transform is employed to exclude the interferences of the inner boundaries, after which the detected ellipse gradually converges to the outer boundaries of the abdomen. Experimental results in clinical ultrasound images demonstrate the high agreement between our approach and manual approach on the measurement of abdominal circumference (mean sign difference is 0.42% and correlation coef cient is 0.9973), which indicates that the proposed approach can be used as a reliable and accurate tool for obstetrical care and diagnosis.

  8. Effect of sacrum-perineum heat therapy on active phase labor pain and client satisfaction: a randomized, controlled trial study.

    Science.gov (United States)

    Taavoni, Simin; Abdolahian, Somayeh; Haghani, Hamid

    2013-09-01

    Reduction of labor pain is one of the most important aspects of obstetric care. Heat therapy, typically applied to the woman's back, lower abdomen, groin, and/or perineum during last stage of labor, is an easy pain relief method that does not require highly skilled care. The effectiveness of heat therapy applied to the perineum during the first stage of labor has not been evaluated. This study aimed to evaluate the effectiveness of heat therapy for pain and woman's satisfaction during physiological labor. Sixty primiparous women aged 18-35 years old were randomly assigned to heat therapy and control groups. Pain and satisfaction scores were measured by visual analog scale. The measurements of satisfaction were accomplished after birth. Data were analyzed by using the t-test and chi-square Mean pain scores in the heat therapy group were significantly lower than the control group (P < 0.05). The mean satisfaction score in the heat therapy group was significantly higher than in the control group (P < 0.05). Heat therapy, an inexpensive complementary treatment with low risk, can reduce the intensity of pain and increase mothers' satisfaction with care during the active phase of labor. Wiley Periodicals, Inc.

  9. A large-area ultra-precision 2D geometrical measurement technique based on statistical random phase detection

    Science.gov (United States)

    Ekberg, Peter; Stiblert, Lars; Mattsson, Lars

    2012-03-01

    The manufacturing of high-quality chrome masks used in the display industry for the manufacturing of liquid crystals, organic light emission diodes and other display devices would not be possible without high-precision large-area metrology. In contrast to the semiconductor industry where 6‧ masks are most common, the quartz glass masks for the manufacturing of large area TVs can have sizes of up to 1.6 × 1.8 m2. Besides the large area, there are demands of sub-micrometer accuracy in ‘registration’, i.e. absolute dimensional measurements and nanometer requirements for ‘overlay’, i.e. repeatability. The technique for making such precise measurements on large masks is one of the most challenging tasks in dimensional metrology today. This paper presents a new approach to two-dimensional (2D) ultra-precision measurements based on random sampling. The technique was recently presented for ultra-precise one-dimensional (1D) measurement. The 1D method relies on timing the scanning of a focused laser beam 200 µm in the Y-direction from an interferometrically determined reference position. This microsweep is controlled by an acousto-optical deflector. By letting the microsweep scan from random X-positions, we can build XY-recordings through a time-to-space conversion that gives very precise maps of the feature edges of the masks. The method differs a lot from ordinary image processing methods using CCD or CMOS sensors for capturing images in the spatial domain. We use events grabbed by a single detector in the time domain in both the X- and Y-directions. After a simple scaling, we get precise and repeatable spatial information. Thanks to the extremely linear microsweep and its precise power control, spatial and intensity distortions, common in ordinary image processing systems using 2D optics and 2D sensors, can be practically eliminated. Our 2D method has proved to give a standard deviation in repeatability of less than 4 nm (1σ) in both the X- and Y

  10. Comparison between exact and approximate treatments of the pairing interaction for finite Fermi systems

    CERN Document Server

    Dukelsky, J; Hirsch, J G; Schuck, P

    2003-01-01

    As a model for a deformed nucleus the many level pairing model (picket fence model with 100 levels) is considered in four approximations and compared to the exact solution given by Richardson long time ago. It is found that, as usual, the number projected BCS method improves over standard BCS but that it is much less accurate than the more sophisticated many-body-approaches which are Coupled Cluster Theory (CCT) in its SUB2 version or Self-Consistent Random Phase Approximation (SCRPA).

  11. Comparison between exact and approximate treatments of the pairing interaction for finite Fermi systems

    Energy Technology Data Exchange (ETDEWEB)

    Dukelsky, J. E-mail: dukelsky@iem.cfmac.csic.es; Dussel, G.G.; Hirsch, J.G.; Schuck, P

    2003-02-10

    As a model for a deformed nucleus the many level pairing model (picket fence model with 100 levels) is considered in four approximations and compared to the exact solution given by Richardson long time ago. It is found that, as usual, the number projected BCS method improves over standard BCS but that it is much less accurate than the more sophisticated many-body-approaches which are Coupled Cluster Theory (CCT) in its SUB2 version or Self-Consistent Random Phase Approximation (SCRPA)

  12. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2016-09-01

    statistical  design  was  reviewed  and  approved  from  the DSMB  and  IRB. Please find approved justification listed below: “The  study  is  a  randomized ... Randomization  will be performed by using  a  series of  randomized   blocks  of  6 within  each participating  site/primary  therapy  stratum  (with  a...reported during the conduct of the study. 13. STATISTICAL CONSIDERATIONS 13.1 Study Design /Endpoints The study is a randomized phase 2

  13. Phase 3 Randomized Low-Dose Paclitaxel Chemoradiotherapy Study for Locally Advanced Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Lin, Hongmei; Chen, Yuhchyau; Shi, Anhui; Pandya, Kishan J; Yu, Rong; Yuan, Yannan; Li, Jiancheng; Li, Hang; Wang, Yingjie; Xia, Tingyi; Feng, Linchun; Ma, Huimin; Geng, Jianhao; Zhu, Guangying

    2016-01-01

    Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with poor chest tumor control. Here, we report results of a randomized phase 3 study comparing two CCRT regimens in improving chest tumor control by low-dose paclitaxel chemoradiation for LA-NSCLC. Due to the logistics of local referral pattern, the study was designed to enroll patients with stage III LA-NSCLC who had completed 2-4 cycles of full-dose chemotherapy. One hundred thirty four were randomized to either Arm 1 [paclitaxel at 15 mg/m2, three times per week (Monday, Wednesday, and Friday) for 6 weeks, n = 74] or Arm 2 (weekly paclitaxel at 45 mg/m2 for 6 weeks, n = 60). Chest radiotherapy was 60-70 Gy in standard fractionation. Response rate was the primary endpoint, with recurrence-free survival (RFS) as the secondary endpoint. From March 2006 to February 2013, 71 patients completed Arm 1 treatment and 59 completed Arm 2 treatment. The response rate for Arm 1 was significantly higher (83.1%) than Arm 2 (54.2%) (p=0.001). RFS was superior in Arm 1: median 14.6 vs. 9.4 months, p = 0.005, Hazard ratio (HR) 1.87 [95% confidence interval (CI) 1.20, 2.90]. Overall survival was not significantly different: median 32.6 months in Arm 1 vs. 31.3 months in Arm 2, p = 0.91, HR 0.97 (95% CI 0.55, 1.70). Toxicity was significantly lower in Arm 1 for Grade 3 and 4 leukopenia/neutropenia (p < 0.001). Pulsed low-dose paclitaxel CCRT resulted in significantly better RFS and tumor response rate, and less hematologic toxicities than weekly CCRT for LA-NSCLC.

  14. Testing two different doses of tiotropium Respimat® in cystic fibrosis: phase 2 randomized trial results.

    Directory of Open Access Journals (Sweden)

    Judy M Bradley

    Full Text Available Tiotropium is a once-daily, long-acting anticholinergic bronchodilator with the potential to alleviate airway obstruction in cystic fibrosis. Our objective was to evaluate the efficacy and safety of 2.5 and 5 µg once-daily tiotropium delivered via the Respimat Soft Mist Inhaler vs. placebo in people with cystic fibrosis.This phase 2, 12-week, randomized, double-blind, placebo-controlled parallel-group study of tiotropium Respimat as add-on to usual cystic fibrosis maintenance therapy included people with cystic fibrosis with pre-bronchodilator forced expiratory volume in 1 second (FEV1 ≥ 25% predicted. Co-primary efficacy end points were change from baseline in percent-predicted FEV1 area under the curve from 0 to 4 hours (FEV1 AUC0-4h, and trough FEV1 at the end of week 12.A total of 510 subjects with cystic fibrosis aged 5-69 years were randomized. Both doses of tiotropium resulted in significant improvement compared with placebo in the co-primary efficacy end points at the end of week 12 (change from baseline in percent-predicted FEV1 AUC0-4h: 2.5 µg: 2.94%, 95% confidence interval 1.19-4.70, p = 0.001; 5 µg: 3.39%, 95% confidence interval 1.67-5.12, p = 0.0001; in percent-predicted trough FEV1 ∶ 2.5 µg: 2.24%, p = 0.2; 5 µg: 2.22%, p = 0.02. There was a greater benefit with tiotropium 5 vs. 2.5 µg. No treatment-related adverse events or unexpected safety findings were observed in patients taking tiotropium.Tiotropium significantly improved lung function in people with cystic fibrosis. The improvement was greater with the higher dose than the lower dose, with no difference in adverse events.ClinicalTrials.gov NCT00737100 EudraCT 2008-001156-43.

  15. Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol.

    Science.gov (United States)

    Martinez, Jessica A; Chalasani, Pavani; Thomson, Cynthia A; Roe, Denise; Altbach, Maria; Galons, Jean-Philippe; Stopeck, Alison; Thompson, Patricia A; Villa-Guillen, Diana Evelyn; Chow, H-H Sherry

    2016-07-19

    Two-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk. This is a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have elements of metabolic syndrome. Eligible participants will be randomized to receive metformin 850 mg BID (n = 75) or placebo (n = 75) for 12 months. The primary endpoint is change in breast density, based on magnetic resonance imaging (MRI) acquired fat-water features. Secondary outcomes include changes in serum insulin levels, serum insulin-like growth factor (IGF)-1 to insulin-like growth factor binding protein (IGFBP)-3 ratio, serum IGF-2 levels, serum testosterone levels, serum leptin to adiponectin ratio, body weight, and waist circumference. Exploratory outcomes include changes in metabolomic profiles in plasma and nipple aspirate fluid. Changes in tissue architecture as well as cellular and molecular targets in breast tissue collected in a subgroup of participants will also be explored. The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin

  16. An approximate classical unimolecular reaction rate theory

    Science.gov (United States)

    Zhao, Meishan; Rice, Stuart A.

    1992-05-01

    We describe a classical theory of unimolecular reaction rate which is derived from the analysis of Davis and Gray by use of simplifying approximations. These approximations concern the calculation of the locations of, and the fluxes of phase points across, the bottlenecks to fragmentation and to intramolecular energy transfer. The bottleneck to fragment separation is represented as a vibration-rotation state dependent separatrix, which approximation is similar to but extends and improves the approximations for the separatrix introduced by Gray, Rice, and Davis and by Zhao and Rice. The novel feature in our analysis is the representation of the bottlenecks to intramolecular energy transfer as dividing surfaces in phase space; the locations of these dividing surfaces are determined by the same conditions as locate the remnants of robust tori with frequency ratios related to the golden mean (in a two degree of freedom system these are the cantori). The flux of phase points across each dividing surface is calculated with an analytic representation instead of a stroboscopic mapping. The rate of unimolecular reaction is identified with the net rate at which phase points escape from the region of quasiperiodic bounded motion to the region of free fragment motion by consecutively crossing the dividing surfaces for intramolecular energy exchange and the separatrix. This new theory generates predictions of the rates of predissociation of the van der Waals molecules HeI2, NeI2 and ArI2 which are in very good agreement with available experimental data.

  17. Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic: Phase I single group and phase II randomized placebo-controlled studies.

    Science.gov (United States)

    Lovera, Jesus; Ramos, Alexander; Devier, Deidre; Garrison, Virginia; Kovner, Blake; Reza, Tara; Koop, Dennis; Rooney, William; Foundas, Anne; Bourdette, Dennis

    2015-11-15

    Phase I (PhI): assess the safety of Polyphenon E in people with multiple sclerosis (MS) and determine the futility of Polyphenon E as a neuroprotective agent. Correlate plasma levels of EGCG with neuroprotective effects. Phase II (PhII): Further assess safety and confirm the neuroprotective effects of Polyphenon E. PhI: single group futility study. PhII: parallel group randomized double-blind placebo-controlled study. Recruitment area (both studies): LSU MS Center, New Orleans, LA and general public from surrounding areas. Inclusion criteria (both studies): 1) MS per 2005 McDonald criteria; 2) relapsing remitting or secondary progressive MS; 3) stable for six months prior to enrollment on either no therapy or glatiramer acetate (GA) for the PhI study and on either on GA or Interferon β for the PhII study. Exclusion criteria (both studies): 1) complete bone marrow ablation or alentuzumab use at any time; 2) mitoxantrone, cyclophosphamide, natalizumab or fingolimod use in the prior nine months; 3) liver problems or significant medical problems. PhI: Polyphenon E, a green tea extract containing 50% of the antioxidant Epigallocatechin-gallate (EGCG), two capsules twice daily (200mg of EGCG per capsule; total daily dose 800mg) for six months. PhII: Polyphenon E or matching placebo capsules, same dose for one year. Only the research pharmacist knew treatment assignment and she randomized participants (one-to-one, stratified by GA or Interferon β, blocks of 4 or 6). Outcome evaluators did not discuss side effects with participants. PhI: 1) adverse events (AE); 2) futility: decrease in N-acetyl aspartate (NAA) from baseline to six months of 10% or more; 3) association between EGCG plasma levels and change in NAA. PhII: 1) AEs; 2) difference in the rate of change of NAA-levels over twelve months.We measured NAA using a point resolved magnetic resonance spectroscopic imaging sequence (TE30/TR2000) on a 10cm×10cm×1cm volume of interest (VOI) located just superior to the

  18. Efficacy of 8 Weeks of Sofosbuvir, Velpatasvir, and Voxilaprevir in Patients With Chronic HCV Infection: 2 Phase 3 Randomized Trials.

    Science.gov (United States)

    Jacobson, Ira M; Lawitz, Eric; Gane, Edward J; Willems, Bernard E; Ruane, Peter J; Nahass, Ronald G; Borgia, Sergio M; Shafran, Stephen D; Workowski, Kimberly A; Pearlman, Brian; Hyland, Robert H; Stamm, Luisa M; Svarovskaia, Evguenia; Dvory-Sobol, Hadas; Zhu, Yanni; Subramanian, G Mani; Brainard, Diana M; McHutchison, John G; Bräu, Norbert; Berg, Thomas; Agarwal, Kosh; Bhandari, Bal Raj; Davis, Mitchell; Feld, Jordan J; Dore, Gregory J; Stedman, Catherine A M; Thompson, Alexander J; Asselah, Tarik; Roberts, Stuart K; Foster, Graham R

    2017-07-01

    Patients with chronic hepatitis C virus (HCV) infection have high rates of sustained virologic response (SVR) after 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor velpatasvir. We assessed the efficacy of 8 weeks of treatment with sofosbuvir and velpatasvir plus the pangenotypic NS3/4A protease inhibitor voxilaprevir (sofosbuvir-velpatasvir-voxilaprevir). In 2 phase 3, open-label trials, patients with HCV infection who had not been treated previously with a direct-acting antiviral agent were assigned randomly to groups given sofosbuvir-velpatasvir-voxilaprevir for 8 weeks or sofosbuvir-velpatasvir for 12 weeks. POLARIS-2, which enrolled patients infected with all HCV genotypes with or without cirrhosis, except patients with genotype 3 and cirrhosis, was designed to test the noninferiority of 8 weeks of sofosbuvir-velpatasvir-voxilaprevir to 12 weeks of sofosbuvir-velpatasvir using a noninferiority margin of 5%. POLARIS-3, which enrolled patients infected with HCV genotype 3 who had cirrhosis, compared rates of SVR in both groups with a performance goal of 83%. In POLARIS-2, 95% (95% confidence interval [CI], 93%-97%) of patients had an SVR to 8 weeks of sofosbuvir-velpatasvir-voxilaprevir; this did not meet the criterion to establish noninferiority to 12 weeks of sofosbuvir-velpatasvir, which produced an SVR in 98% of patients (95% CI, 96%-99%; difference in the stratum-adjusted Mantel-Haenszel proportions of -3.2%; 95% CI, -6.0% to -0.4%). The difference in the efficacy was owing primarily to a lower rate of SVR (92%) among patients with HCV genotype 1a infection receiving 8 weeks of sofosbuvir-velpatasvir-voxilaprevir. In POLARIS-3, 96% of patients (95% CI, 91%-99%) achieved an SVR in both treatment groups, which was significantly superior to the performance goal. Overall, the most common adverse events were headache, fatigue, diarrhea, and nausea; diarrhea and nausea were reported more frequently by

  19. Assessment of the therapeutic benefit of dexamethasone cyclophosphamide pulse versus only oral cyclophosphamide in phase II of the dexamethasone cyclophosphamide pulse therapy: A preliminary prospective randomized controlled study

    Directory of Open Access Journals (Sweden)

    Nisha V Parmar

    2013-01-01

    Full Text Available Background: Dexamethasone cyclophosphamide pulse (DCP therapy is an established mode of treatment for pemphigus in India. Aims: To assess the therapeutic benefit of additional DCPs (phase II, consolidation phase versus immediate oral cyclophosphamide, usually used in phase III (maintenance phase, after initial DCP therapy (phase I and to assess which laboratory test (DIF or ELISA will reflect the clinical relapse best. Methods: Nineteen newly recruited patients of pemphigus vulgaris (PV received monthly DCPs in phase I and were then randomized into two groups. Group A (10 patients received monthly DCPs for nine months and Group B (nine patients received only oral cyclophosphamide for nine months. Direct immunofluorescence (DIF and enzyme-linked immunosorbent assay (ELISA were tested before starting DCP regimen, and at 0,3,6,9 months after randomization. Results: Clinical relapse by the end of follow-up period occurred in only one patient in each group. In these cases, DIF became (again positive before the relapse. No statistically significant difference between the two groups was found at three, six and nine months by ELISA indices and DIF grading. Conclusion: Although the DCP regimen is the standard therapy for pemphigus in India, we found no difference in the clinical outcome between patients receiving nine DCPs in phase II and patients shifted directly from phase I to III. Periodic testing using DIF and Dsg ELISA were found to be useful to monitor disease activity and predict a relapse. Further large scale studies are required to assess if patients can be shifted directly from phase I to III and maintained only on oral cyclophosphamide.

  20. Abuse liability assessment of eslicarbazepine acetate in healthy male and female recreational sedative users: A Phase I randomized controlled trial.

    Science.gov (United States)

    Levy-Cooperman, Naama; Schoedel, Kerri A; Chakraborty, Bijan; Blum, David; Cheng, Hailong

    2016-08-01

    Eslicarbazepine acetate (ESL) is a once-daily oral antiepileptic drug for the treatment of partial-onset seizures. Adverse events such as dizziness and somnolence reported in clinical studies suggest that ESL has detectable central nervous system (CNS) effects in addition to its antiepileptic effects. This Phase I study evaluated the abuse liability of ESL compared with that of alprazolam (ALP) and placebo (PBO) in recreational CNS depressant users. In this single-dose, randomized, double-blind, PBO- and active-controlled crossover study, healthy recreational CNS depressant users who could discern between ALP 2mg and PBO received single oral doses of each of the following treatments with a washout interval of ≥7days between each treatment: ESL (800mg, 1600mg, 2000mg, and 2400mg); ALP (1.5mg and 3.0mg); and PBO. Subjective measures, including visual analog scales (VASs) e.g., Drug-Liking (primary endpoint), and Addiction Research Center Inventory (ARCI) Morphine-Benzedrine Group (MBG), Pentobarbital Chlorpromazine Alcohol Group (PCAG), and Lysergic Acid Diethylamide Group scales were evaluated at multiple time points up to 24h postdose. Cognitive effects were evaluated using the Choice Reaction Time (CRT), Divided Attention (DAT) and Hopkins Verbal Learning Task-Revised tests. Peak scores for Drug-Liking VAS (maximum effect [Emax]) were significantly higher for both ALP doses than for PBO (peslicarbazepine, increased with increasing ESL dose. Pharmacokinetic parameters estimated for eslicarbazepine were generally comparable with results from previous studies in healthy volunteers. This study demonstrated that single doses of ESL may have less abuse liability than ALP in recreational sedative users. Although ESL had detectable subjective effects and showed some drug-'liking' at higher doses, the magnitude of these effects was small. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. A randomized controlled trial of cognitive-behavior therapy plus bright light therapy for adolescent delayed sleep phase disorder.

    Science.gov (United States)

    Gradisar, Michael; Dohnt, Hayley; Gardner, Greg; Paine, Sarah; Starkey, Karina; Menne, Annemarie; Slater, Amy; Wright, Helen; Hudson, Jennifer L; Weaver, Edward; Trenowden, Sophie

    2011-12-01

    To evaluate cognitive-behavior therapy plus bright light therapy (CBT plus BLT) for adolescents diagnosed with delayed sleep phase disorder (DSPD). Randomized controlled trial of CBT plus BLT vs. waitlist (WL) control with comparisons at pre- and post-treatment. There was 6-month follow-up for the CBT plus BLT group only. Flinders University Child & Adolescent Sleep Clinic, Adelaide, South Australia. 49 adolescents (mean age 14.6 ± 1.0 y, 53% males) diagnosed with DSPD; mean chronicity 4 y 8 months; 16% not attending school. Eighteen percent of adolescents dropped out of the study (CBT plus BLT: N = 23 vs. WL: N = 17). CBT plus BLT consisted of 6 individual sessions, including morning bright light therapy to advance adolescents' circadian rhythms, and cognitive restructuring and sleep education to target associated insomnia and sleep hygiene. DSPD diagnosis was performed via a clinical interview and 7-day sleep diary. Measurements at each time-point included online sleep diaries and scales measuring sleepiness, fatigue, and depression symptoms. Compared to WL, moderate-to-large improvements (d = 0.65-1.24) were found at post-treatment for CBT plus BLT adolescents, including reduced sleep latency, earlier sleep onset and rise times, total sleep time (school nights), wake after sleep onset, sleepiness, and fatigue. At 6-month follow-up (N = 15), small-to-large improvements (d = 0.24-1.53) continued for CBT plus BLT adolescents, with effects found for all measures. Significantly fewer adolescents receiving CBT plus BLT met DPSD criteria at post-treatment (WL = 82% vs. CBT plus BLT = 13%, P adolescent DSPD is effective for improving multiple sleep and daytime impairments in the immediate and long-term. Studies evaluating the treatment effectiveness of each treatment component are needed. Australia-New Zealand Trials Registry Number: ACTRN12610001041044.

  2. Design and initial results of a multi-phase randomized trial of ceftriaxone in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    James D Berry

    Full Text Available Ceftriaxone increases expression of the astrocytic glutamate transporter, EAAT2, which might protect from glutamate-mediated excitotoxicity. A trial using a novel three stage nonstop design, incorporating Phases I-III, tested ceftriaxone in ALS. Stage 1 determined the cerebrospinal fluid pharmacokinetics of ceftriaxone in subjects with ALS. Stage 2 evaluated safety and tolerability for 20-weeks. Analysis of the pharmacokinetics, tolerability, and safety was used to determine the ceftriaxone dosage for Stage 3 efficacy testing.In Stage 1, 66 subjects at ten clinical sites were enrolled and randomized equally into three study groups receiving intravenous placebo, ceftriaxone 2 grams daily or ceftriaxone 4 grams daily divided BID. Participants provided serum and cerebrospinal fluid for pharmacokinetic analysis on study day 7. Participants continued their assigned treatment in Stage 2. The Data and Safety Monitoring Board (DSMB reviewed the data after the last participants completed 20 weeks on study drug.Stage 1 analysis revealed linear pharmacokinetics, and CSF trough levels for both dosage levels exceeding the pre-specified target trough level of 1 µM (0.55 µg/mL. Tolerability (Stages 1 and 2 results showed that ceftriaxone at dosages up to 4 grams/day was well tolerated at 20 weeks. Biliary adverse events were more common with ceftriaxone but not dose-dependent and improved with ursodeoxycholic (ursodiol therapy.The goals of Stages 1 and 2 of the ceftriaxone trial were successfully achieved. Based on the pre-specified decision rules, the DSMB recommended the use of ceftriaxone 4 g/d (divided BID for Stage 3, which recently closed.ClinicalTrials.gov NCT00349622.

  3. A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in patients with asthma.

    Science.gov (United States)

    Corren, Jonathan; Busse, William; Meltzer, Eli O; Mansfield, Lyndon; Bensch, George; Fahrenholz, John; Wenzel, Sally E; Chon, Yun; Dunn, Meleana; Weng, Haoling H; Lin, Shao-Lee

    2010-04-15

    IL-4 and IL-13 share many biological functions important in the development of allergic airway inflammation and are implicated in the pathogenesis of asthma. AMG 317 is a fully human monoclonal antibody to IL-4Ralpha that blocks both IL-4 and IL-13 pathways. To evaluate efficacy and safety of AMG 317 in patients with moderate to severe asthma. In this phase 2, randomized, double-blind, placebo-controlled study, patients received weekly subcutaneous injections of placebo or AMG 317 (75-300 mg) for 12 weeks, followed by a 4-week follow-up period. The primary endpoint was change from baseline at Week 12 in Asthma Control Questionnaire (ACQ) symptom score. Mean ACQ change (SE) was -0.49 (0.09) in placebo (n = 74), and -0.43 (0.11), -0.58 (0.12), and -0.70 (0.09) in the AMG 317 75 mg (n = 73), 150 mg (n = 73), and 300 mg (n = 74) groups, respectively (treatment effect P = 0.25). No statistically significant differences were observed in the secondary endpoints. Numerical decreases in number of and time to exacerbations were noted in patients receiving AMG 317 150 mg and 300 mg. Preplanned analyses by tertile of baseline ACQ revealed that patients with higher baseline ACQ scores (>or=2.86) were more likely to respond to AMG 317. Serious adverse events were reported in three patients, each noted as not related to study drug. AMG 317 did not demonstrate clinical efficacy across the overall group of patients. Clinically significant improvements were observed in several outcome measures in patients with higher baseline ACQ scores. AMG 317 was safe and well tolerated in this study population. Clinical trial registered with www.clinicaltrials.gov (NCT 00436670).

  4. An interesterified palm olein test meal decreases early-phase postprandial lipemia compared to palm olein: a randomized controlled trial.

    Science.gov (United States)

    Hall, Wendy L; Brito, Marcela Fiuza; Huang, Junlan; Wood, Lucy V; Filippou, Androulla; Sanders, Thomas A B; Berry, Sarah E E

    2014-09-01

    Palm oil that has been interesterified to produce a higher proportion of palmitic acid (16:0) in the sn-2 position reduces postprandial lipemia in young, normolipidemic men and women, but effects in older subjects with higher fasting triacylglycerol (TAG) concentrations are unknown. We tested the hypothesis that high-fat meals rich in interesterified palm olein (IPO) decrease lipemia and alter plasma lipoprotein fraction composition compared to native palm olein (NPO) in men aged 40-70 years with fasting TAG concentrations ≥1.2 mmol/L. Postprandial changes in plasma lipids following meals containing 75 g fat (NPO and IPO) were compared using a randomized, double-blind crossover design (n = 11). Although there were no significant differences in plasma TAG concentrations between meals over the total 6-h postprandial measurement period, IPO resulted in a decreased plasma TAG response during the first 4 h of the postprandial period (iAUC 1.65 mmol/L h, 95% CI 1.01-2.29) compared to NPO (iAUC 2.33 mmol/L h, 95% CI 1.58-3.07); meal effect P = 0.024. Chylomicron fraction TAG concentrations at 4-6 h were slightly reduced following IPO compared to NPO [NPO-IPO mean difference 0.29 mmol/L (95% CI -0.01-0.59), P = 0.055]. There were no differences in IDL fraction TAG, cholesterol or apolipoprotein B48 concentrations following IPO compared with NPO. In conclusion, consuming a meal containing palm olein with a higher proportion of 16:0 in the sn-2 position decreases postprandial lipemia compared to native palm olein during the early phase of the postprandial period in men with higher than optimal fasting triacylglycerol concentrations.

  5. A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel (MTN-007.

    Directory of Open Access Journals (Sweden)

    Ian McGowan

    Full Text Available Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal, adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel.Participants were randomized 1:1:1:1 to receive the reduced glycerin formulation of tenofovir 1% gel, a hydroxyethyl cellulose placebo gel, a 2% nonoxynol-9 gel, or no treatment. Each gel was administered as a single dose followed by 7 daily doses. Mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein, microarrays, flow cytometry of mucosal T cell phenotype, and rectal microflora. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response, respectively.Sixty-five participants (45 men and 20 women were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability was 87% (reduced glycerin formulation of tenofovir 1% gel, 93% (hydroxyethyl cellulose placebo gel, and 63% (nonoxynol-9 gel. Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms.The reduced glycerin formulation of tenofovir 1% gel was safe and well tolerated rectally and should be advanced to Phase 2 development.ClinicalTrials.gov NCT01232803.

  6. Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033.

    Science.gov (United States)

    Tran, Jonathan Q; Rana, Jitesh; Barkhof, Frederik; Melamed, Isaac; Gevorkyan, Hakop; Wattjes, Mike P; de Jong, Remko; Brosofsky, Kristin; Ray, Soma; Xu, Lei; Zhao, Jim; Parr, Edward; Cadavid, Diego

    2014-08-01

    To evaluate the safety, tolerability, and pharmacokinetics (PK) of BIIB033 (anti-LINGO-1 monoclonal antibody) in healthy volunteers and participants with multiple sclerosis (MS). In 2 separate randomized, placebo-controlled studies, single ascending doses (SAD; 0.1-100 mg/kg) of BIIB033 or placebo were administered via IV infusion or subcutaneous injection to 72 healthy volunteers, and multiple ascending doses (MAD; 0.3-100 mg/kg; 2 doses separated by 14 days) of BIIB033 or placebo were administered via IV infusion to 47 participants with relapsing-remitting or secondary progressive MS. Safety assessments included adverse event (AE) monitoring, neurologic examinations, conventional and nonconventional MRI, EEG, optical coherence tomography, retinal examinations, and evoked potentials. Serum and CSF PK as well as the immunogenicity of BIIB033 were also evaluated. All 72 healthy volunteers and 47 participants with MS were included in the safety analyses. BIIB033 infusions were well tolerated. The frequency of AEs was similar between BIIB033 and placebo. There were no serious AEs or deaths. No clinically significant changes in any of the safety measures were observed. BIIB033 PK was similar between healthy volunteers and participants with MS. Doses of ≥10 mg/kg resulted in BIIB033 concentrations similar to or higher than the concentration associated with 90% of the maximum remyelination effect in rat remyelination studies. The incidence of anti-drug antibody production was low. The emerging safety, tolerability, and PK of BIIB033 support advancing BIIB033 into phase II clinical development as a potential treatment for CNS demyelination disorders. This study provides Class I evidence that BIIB033 is well tolerated and safe (serious adverse event rate 0%, 95% confidence interval 0-7.6%).

  7. Phase III, randomized controlled trial to evaluate lot consistency of a trivalent subunit egg-based influenza vaccine in adults.

    Science.gov (United States)

    Rivera, Luis; Mazara, Sonia; Vargas, Maria; Fragapane, Elena; Casula, Daniela; Groth, Nicola

    2012-07-27

    Vaccination is the most effective preventive strategy to control influenza. The demonstration of lot-to-lot consistency to confirm the reliability of the manufacturing process has become a mandatory step in vaccine development. This phase III, observer-blind, controlled trial assessed lot-to-lot consistency, immunogenicity, and safety of a subunit trivalent influenza vaccine (Agrippal®, Novartis Vaccines and Diagnostics) in healthy adults aged 18-49 years. The immunogenicity and safety profile of Agrippal was compared with a control vaccine (Fluvirin®, Novartis Vaccines and Diagnostics). A total of 1507 subjects were randomized 2:2:2:1 to receive one vaccination of one of the three lots of influenza vaccine or control vaccine. Antibody levels were measured by hemagglutination inhibition assay on days 1 and 22. Adverse reactions were solicited via diary cards for 7 days after vaccination, and unsolicited adverse events were collected throughout the study period. Equivalence of day 22 immune responses to the three lots was shown for each of the three strains. Robust immunogenic responses after one dose were observed for all vaccine groups, and both Center for Biologics Evaluation and Research criteria for licensure of influenza vaccines were met for all three virus strains. Both vaccines exhibited a robust safety profile and were well tolerated, with no differences in local and systemic solicited reactions or in unsolicited adverse events. The demonstration of consistency between manufacturing lots confirms for purposes of clinical development the reliability of the production process. The robust immunogenic responses and favorable safety profiles further support the use of trivalent subunit influenza vaccines Agrippal and Fluvirin for active immunization against influenza. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. International Conference Approximation Theory XV

    CERN Document Server

    Schumaker, Larry

    2017-01-01

    These proceedings are based on papers presented at the international conference Approximation Theory XV, which was held May 22–25, 2016 in San Antonio, Texas. The conference was the fifteenth in a series of meetings in Approximation Theory held at various locations in the United States, and was attended by 146 participants. The book contains longer survey papers by some of the invited speakers covering topics such as compressive sensing, isogeometric analysis, and scaling limits of polynomials and entire functions of exponential type. The book also includes papers on a variety of current topics in Approximation Theory drawn from areas such as advances in kernel approximation with applications, approximation theory and algebraic geometry, multivariate splines for applications, practical function approximation, approximation of PDEs, wavelets and framelets with applications, approximation theory in signal processing, compressive sensing, rational interpolation, spline approximation in isogeometric analysis, a...

  9. Multiple Scattering Model for Optical Coherence Tomography with Rytov Approximation

    KAUST Repository

    Li, Muxingzi

    2017-04-24

    Optical Coherence Tomography (OCT) is a coherence-gated, micrometer-resolution imaging technique that focuses a broadband near-infrared laser beam to penetrate into optical scattering media, e.g. biological tissues. The OCT resolution is split into two parts, with the axial resolution defined by half the coherence length, and the depth-dependent lateral resolution determined by the beam geometry, which is well described by a Gaussian beam model. The depth dependence of lateral resolution directly results in the defocusing effect outside the confocal region and restricts current OCT probes to small numerical aperture (NA) at the expense of lateral resolution near the focus. Another limitation on OCT development is the presence of a mixture of speckles due to multiple scatterers within the coherence length, and other random noise. Motivated by the above two challenges, a multiple scattering model based on Rytov approximation and Gaussian beam optics is proposed for the OCT setup. Some previous papers have adopted the first Born approximation with the assumption of small perturbation of the incident field in inhomogeneous media. The Rytov method of the same order with smooth phase perturbation assumption benefits from a wider spatial range of validity. A deconvolution method for solving the inverse problem associated with the first Rytov approximation is developed, significantly reducing the defocusing effect through depth and therefore extending the feasible range of NA.

  10. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy

    DEFF Research Database (Denmark)

    De Santis, Maria; Bellmunt, Joaquim; Mead, Graham

    2012-01-01

    This is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy.......This is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy....

  11. Broadband Approximations for Doubly Curved Reflector Antenna

    Directory of Open Access Journals (Sweden)

    V. Schejbal

    2010-12-01

    Full Text Available The broadband approximations for shaped-beam doubly curved reflector antennas with primary feed (rectangular horn producing uniform amplitude and phase aperture distribution are derived and analyzed. They are very valuable for electromagnetic compatibility analyses both from electromagnetic interference and susceptibility point of view, because specialized more accurate methods such as physical optics are only used by antenna designers. To allow quick EMC analyses, typical values, beamwidth changes, sidelobe levels and aperture efficiencies are given for frequency changes approximately up to four times operating frequency. A comparison of approximated and measured patterns of doubly curved reflector antennas shows that the given approximation could be reliably used for analyses of pattern changes due to very broad frequency changes.

  12. Hierarchical low-rank approximation for high dimensional approximation

    KAUST Repository

    Nouy, Anthony

    2016-01-07

    Tensor methods are among the most prominent tools for the numerical solution of high-dimensional problems where functions of multiple variables have to be approximated. Such high-dimensional approximation problems naturally arise in stochastic analysis and uncertainty quantification. In many practical situations, the approximation of high-dimensional functions is made computationally tractable by using rank-structured approximations. In this talk, we present algorithms for the approximation in hierarchical tensor format using statistical methods. Sparse representations in a given tensor format are obtained with adaptive or convex relaxation methods, with a selection of parameters using crossvalidation methods.

  13. INHOMOGENEOUS DIOPHANTINE APPROXIMATION WITH PRIME ...

    Indian Academy of Sciences (India)

    50

    INHOMOGENEOUS DIOPHANTINE APPROXIMATION WITH PRIME. CONSTRAINTS. STEPHAN BAIER AND ANISH GHOSH. Abstract. We study the problem of ... this area under primality constraints. Indeed, the ...... [7] A. Ghosh, Diophantine approximation on subspaces of Rn and dynamics on homogeneous spaces, to.

  14. Diophantine approximation in prescribed degree

    OpenAIRE

    Schleischitz, Johannes

    2017-01-01

    We investigate approximation to a given real number by algebraic numbers and algebraic integers of prescribed degree. We deal with both best and uniform approximation, and highlight the similarities and differences compared with the intensely studied problem of approximation by algebraic numbers (and integers) of bounded degree. We establish the answer to a question of Bugeaud concerning approximation to transcendental real numbers by quadratic irrational numbers, and thereby we refine a resu...

  15. Results from a pooled analysis of two European, randomized, placebo-controlled, phase 3 studies of ATX-101 for the pharmacologic reduction of excess submental fat.

    Science.gov (United States)

    McDiarmid, James; Ruiz, Jesus Benito; Lee, Daniel; Lippert, Susanne; Hartisch, Claudia; Havlickova, Blanka

    2014-10-01

    The injectable adipocytolytic drug ATX-101 is the first nonsurgical treatment for the reduction of submental fat (SMF) to undergo comprehensive clinical evaluation. This study aimed to confirm the efficacy and safety of ATX-101 for SMF reduction through a post hoc pooled analysis of two large phase 3 studies. Patients with unwanted SMF were randomized to receive 1 or 2 mg/cm(2) of ATX-101 or a placebo injected into their SMF during a maximum of four treatment sessions spaced approximately 28 days apart, with a 12-week follow-up period. The proportions of patients with reductions in SMF of one point or more on the Clinician-Reported SMF Rating Scale (CR-SMFRS) and the proportions of patients satisfied with the appearance of their face and chin [Subject Self-Rating Scale (SSRS) score ≥4] were reported overall and in subgroups. Other efficacy measures included improvements in the Patient-Reported SMF Rating Scale (PR-SMFRS), calliper measurements of SMF thickness, and assessment of skin laxity [Skin Laxity Rating Scale (SLRS)]. Adverse events and laboratory test results were recorded. Significantly greater proportions of the patients had improvements in clinician-reported measures (≥1-point improvement in CR-SMFRS: 58.8 and 63.8 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, and 28.6 % of the placebo recipients; p ATX-101 doses vs. placebo) and patient-reported measures (≥1-point improvement in PR-SMFRS: 60.0 and 63.1 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, vs. 34.3 % of the placebo recipients; p ATX-101 versus placebo. These improvements correlated moderately with patient satisfaction regarding face and chin appearance (SSRS score ≥4: 60.8 and 65.4 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, vs. 29.0 % of the placebo recipients; p ATX-101 was effective irrespective of gender, age, or body mass index. Reduction in SMF with ATX-101 was confirmed by calliper measurements (p ATX-101

  16. Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.

    Science.gov (United States)

    Leroux-Roels, Geert; Maes, Cathy; Clement, Frédéric; van Engelenburg, Frank; van den Dobbelsteen, Marieke; Adler, Michael; Amacker, Mario; Lopalco, Lucia; Bomsel, Morgane; Chalifour, Anick; Fleury, Sylvain

    2013-01-01

    Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101). Participants received placebo or MYM-V101 vaccine at 10 μg/dose or 50 μg/dose intramuscularly at week 0 and 8, and intranasally at week 16 and 24. MYM-V101 was safe and well-tolerated at both doses administered by the intramuscular and intranasal routes, with the majority of subjects remaining free of local and general symptoms. P1-specific serum IgGs and IgAs were induced in all high dose recipients after the first injection. After the last vaccination, vaginal and rectal P1-specific IgGs could be detected in all high dose recipients. Approximately 63% and 43% of the low and high dose recipients were respectively tested positive for vaginal P1-IgAs, while 29% of the subjects from the high dose group tested positive for rectal IgAs. Serum samples had total specific IgG and IgA antibody concentrations ≥ 0.4 μg/mL, while mucosal samples were usually below 0.01 μg/mL. Vaginal secretions from MYM-V101 vaccinated subjects were inhibiting HIV-1 transcytosis but had no detectable neutralizing activity. P1-specific Th1 responses could not be detected on PBMC. This study demonstrates the excellent safety and tolerability of MYM-V101, eliciting systemic and mucosal antibodies in the majority of subjects. Vaccine-induced mucosal anti-gp41 antibodies toward conserved gp41 motifs were harboring HIV-1 transcytosis inhibition activity and may contribute to reduce sexually-transmitted HIV-1. ClinicalTrials.gov NCT01084343.

  17. Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.

    Directory of Open Access Journals (Sweden)

    Geert Leroux-Roels

    Full Text Available Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101. Participants received placebo or MYM-V101 vaccine at 10 μg/dose or 50 μg/dose intramuscularly at week 0 and 8, and intranasally at week 16 and 24. MYM-V101 was safe and well-tolerated at both doses administered by the intramuscular and intranasal routes, with the majority of subjects remaining free of local and general symptoms. P1-specific serum IgGs and IgAs were induced in all high dose recipients after the first injection. After the last vaccination, vaginal and rectal P1-specific IgGs could be detected in all high dose recipients. Approximately 63% and 43% of the low and high dose recipients were respectively tested positive for vaginal P1-IgAs, while 29% of the subjects from the high dose group tested positive for rectal IgAs. Serum samples had total specific IgG and IgA antibody concentrations ≥ 0.4 μg/mL, while mucosal samples were usually below 0.01 μg/mL. Vaginal secretions from MYM-V101 vaccinated subjects were inhibiting HIV-1 transcytosis but had no detectable neutralizing activity. P1-specific Th1 responses could not be detected on PBMC. This study demonstrates the excellent safety and tolerability of MYM-V101, eliciting systemic and mucosal antibodies in the majority of subjects. Vaccine-induced mucosal anti-gp41 antibodies toward conserved gp41 motifs were harboring HIV-1 transcytosis inhibition activity and may contribute to reduce sexually-transmitted HIV-1.ClinicalTrials.gov NCT01084343.

  18. Phase transition and random-field induced domain wall response in quantum ferroelectrics SrTi18O3: review and perspective

    Directory of Open Access Journals (Sweden)

    Mitsuru Itoh, Toshirou Yagi, Yoshiaki Uesu, Wolfgang Kleemann and Robert Blinc

    2004-01-01

    Full Text Available The oxygen isotope exchange of 16O by 18O in SrTiO3 causes a drastic change from paraelectric to ferroelectric, due to the suppression of quantum fluctuation. The phase transition and origin of the huge domain wall response were evaluated by dielectric, magnetic (NMR, and optical measurements (SHG, light scattering. The results obtained corroborate (1 smeared ferroelectric transition at Tc due to quenched random field, (2 a quite large dielectric contribution from domain walls, (3 incomplete softening of the transverse optic mode, and (4 a large contribution from the relaxational mode to the phase transition. Quantitative explanations, given to individual results, may give hints to grasp the mechanism for the evolution of ferroelectricity, in which quantum fluctuation and random fields are dominant perturbations. Finally, some of the news studies on the SrTiO3 were also introduced.

  19. Efficacy of an Ayurvedic Formulation for Mild-to-moderate Osteoarthritis: A Phase 3, Randomized Controlled Study.

    Science.gov (United States)

    Modak, Milind Dattatraya; Barde, Mohini Prajak

    2017-01-01

    Context • Current treatment options offer only symptomatic pain relief for patients with osteoarthritis (OA). Thus, a need exists for effective treatment of the disability-causing disease. The proprietary polyherbal formulation, Nartana, has been used for several years for OA. Objective • The study intended to compare the benefits of the herbal formulation with those of routinely used nonsteroidal anti-inflammatory drugs (NSAIDs) for patients with mild-to-moderate OA. Design • The research team designed a phase 3, double-blind, double-dummy, randomized controlled study. Setting • The study was conducted at 2 hospital sites in Pune, India. Participants • The participants were 80 outpatients with OA at the hospitals. Intervention • The participants were randomly assigned to receive either the intervention (herbal formulation) or the active control (diclofenac) for 12 wk. The herbal formulation group received 450 mg of Nartana capsule and diclofenac-matching placebo. Treatment was given 2 ×/d for first 15 d and then 1 ×/d until the end of the study. The control group received 50 mg of diclofenac tablet 2 ×/d for first 15 d and then 100 mg of diclofenac tablet 1 ×/d and a Nartana-matching placebo until end of the study. Outcome Measures • To measure efficacy, the study used the modified Center for Rheumatic Diseases Pune version of the Western Ontario and McMaster Universities OA index (WOMAC) and the Health Assessment Questionnaire (HAQ). The study also measured overall perceived pain relief. The primary outcome measure was the change in the combined WOMAC score from baseline to postintervention (12 wk). Safety and other efficacy measures were the secondary end points. Results • The herbal formulation and diclofenac groups matched well at baseline for demographic profile, disease status, and WOMAC scores. The combined WOMAC scores were significantly reduced from baseline to postintervention for both groups (P < .01). The earliest significant

  20. Efficacy and safety of bilastine in Japanese patients with perennial allergic rhinitis: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study

    OpenAIRE

    Okubo, Kimihiro; Gotoh, Minoru; Asako, Mikiya; Nomura, Yasuyuki; Togawa, Michinori; Saito, Akihiro; Honda, Takayuki; Ohashi, Yoshihiro

    2016-01-01

    Background: Bilastine, a novel non-sedating second-generation H1 antihistamine, has been approved in most European countries since 2010. This study aimed to evaluate the superiority of bilastine over placebo in Japanese patients with perennial allergic rhinitis (PAR). Methods: This randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexo...

  1. Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies.

    Science.gov (United States)

    Burri, Christian; Yeramian, Patrick D; Allen, James L; Merolle, Ada; Serge, Kazadi Kyanza; Mpanya, Alain; Lutumba, Pascal; Mesu, Victor Kande Betu Ku; Bilenge, Constantin Miaka Mia; Lubaki, Jean-Pierre Fina; Mpoto, Alfred Mpoo; Thompson, Mark; Munungu, Blaise Fungula; Manuel, Francisco; Josenando, Théophilo; Bernhard, Sonja C; Olson, Carol A; Blum, Johannes; Tidwell, Richard R; Pohlig, Gabriele

    2016-02-01

    Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT. The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent. Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.

  2. Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies.

    Directory of Open Access Journals (Sweden)

    Christian Burri

    2016-02-01

    Full Text Available Sleeping sickness (human African trypanosomiasis [HAT] is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC] between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2, where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a or 3 months (Phase 2b after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93% than pafuramidine treatment for 5 days (25% and 10 days (57%. These results support continuation of the development program for pafuramidine into Phase 3.

  3. Exact constants in approximation theory

    CERN Document Server

    Korneichuk, N

    1991-01-01

    This book is intended as a self-contained introduction for non-specialists, or as a reference work for experts, to the particular area of approximation theory that is concerned with exact constants. The results apply mainly to extremal problems in approximation theory, which in turn are closely related to numerical analysis and optimization. The book encompasses a wide range of questions and problems: best approximation by polynomials and splines; linear approximation methods, such as spline-approximation; optimal reconstruction of functions and linear functionals. Many of the results are base

  4. International Conference Approximation Theory XIV

    CERN Document Server

    Schumaker, Larry

    2014-01-01

    This volume developed from papers presented at the international conference Approximation Theory XIV,  held April 7–10, 2013 in San Antonio, Texas. The proceedings contains surveys by invited speakers, covering topics such as splines on non-tensor-product meshes, Wachspress and mean value coordinates, curvelets and shearlets, barycentric interpolation, and polynomial approximation on spheres and balls. Other contributed papers address a variety of current topics in approximation theory, including eigenvalue sequences of positive integral operators, image registration, and support vector machines. This book will be of interest to mathematicians, engineers, and computer scientists working in approximation theory, computer-aided geometric design, numerical analysis, and related approximation areas.

  5. Magnetically induced crystal structure and phase stability in Fe1-cCoc

    DEFF Research Database (Denmark)

    Abrikosov, I.A.; James, P.; Eriksson, O.

    1996-01-01

    diagram. We demonstrate that for the Pe-rich random alloys magnetism-stabilizes the bce phase relative to the close-packed fee and hcp phases. Magnetism also favors the partially ordered alpha' phase relative to the random bce alloy. This unique relation between magnetism and phase stability for the Fe......We present an ab initio determination of the crystallographic phase stability of Fe-Co alloys as a function of concentration, using the coherent potential approximation. A bcc --> hcp phase transition is found at a concentration of 85 at.% of Co, in good agreement with the experimental phase...

  6. A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: THE Randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN).

    Science.gov (United States)

    Van de Werf, Frans; Brueckmann, Martina; Connolly, Stuart J; Friedman, Jeffrey; Granger, Christopher B; Härtter, Sebastian; Harper, Ruth; Kappetein, Arie Pieter; Lehr, Thorsten; Mack, Michael J; Noack, Herbert; Eikelboom, John W

    2012-06-01

    Vitamin K antagonists are the only oral anticoagulants approved for long-term treatment of patients with a cardiac valve replacement. This study aims to test a new dosing regimen for dabigatran etexilate in patients with a mechanical bileaflet valve. Patients aged ≥ 18 years and ≤ 75 years, either undergoing implantation of a mechanical bileaflet valve (aortic or mitral or both) during the current hospital stay or having undergone implantation a mitral bileaflet valve >3 months before randomization, will be randomized between dabigatran etexilate or warfarin (in a ratio of 2:1) in an open-label design. Initial doses of dabigatran will be based on the estimated creatinine clearance, and the doses will be adjusted based on measuring trough dabigatran plasma levels to achieve levels ≥ 50 ng/mL at steady state. Doses will range between 150 mg twice a day and 300 mg twice a day. Warfarin management and target international normalized ratio will be according to current practice guidelines at the discretion of the treating physicians. The plan is to treat 270 patients with dabigatran etexilate for a total study population of approximately 405 patients. Clinical efficacy and safety outcomes will be analyzed in an exploratory manner. RE-ALIGN is the first study to test an alternative to warfarin in patients with mechanical heart valves. A definitive phase III study will be planned based on the results of this study. Copyright © 2012 Mosby, Inc. All rights reserved.

  7. Spin-fluctuation theory beyond Gaussian approximation

    Energy Technology Data Exchange (ETDEWEB)

    Melnikov, N B [Moscow State University, 119992 Moscow (Russian Federation); Reser, B I; Grebennikov, V I, E-mail: melnikov@cs.msu.s, E-mail: reser@imp.uran.r, E-mail: greben@imp.uran.r [Institute of Metal Physics, Ural Branch of the Russian Academy of Sciences, 620041 Ekaterinburg (Russian Federation)

    2010-05-14

    A characteristic feature of the Gaussian approximation in the functional-integral approach to the spin-fluctuation theory is the jump phase transition to the paramagnetic state. We eliminate the jump and obtain a continuous second-order phase transition by taking into account high-order terms in the expansion of the free energy in powers of the fluctuating exchange field. The third-order term of the free energy renormalizes the mean field, and the fourth-order term, responsible for the interaction of the fluctuations, renormalizes the spin susceptibility. The extended theory is applied to the calculation of magnetic properties of Fe-Ni Invar.

  8. Concepts for a theoretical and experimental study of lifting rotor random loads and vibrations. Phase 5B: Analysis of gust alleviation methods and rotor dynamic stability

    Science.gov (United States)

    Hohenemser, K. H.; Yin, S. K.

    1971-01-01

    The effects of various gust alleviation methods on the random blade response in flapping were studied analytically, assuming a rigid rotor support. The analytical model assumes rigid flapping blades with elastic root restraints. Linearized equations which are approximately valid at low lift conditions were used. Because of the interblade coupling from the feedback devices, the method of multiblade generalized coordinates was most convenient and was extended to include coning, differential coning, and warping of the rotor. The numerical examples cover the dynamic stability characteristics as affected by feedback gains of three- to six-bladed rotors. The number of blades had large effects on stability limits and modal time functions at these limits. The random flapping response of the blades to atmospheric turbulence was determined at 1.6 rotor advance ratio using feedback gains below the stability limit. The most effective reduction of the flapping response per unit gain was achieved with a rotor coning angle feedback.

  9. Designing the selenium and bladder cancer trial (SELEBLAT, a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

    Directory of Open Access Journals (Sweden)

    Goossens Maria E

    2012-03-01

    Full Text Available Abstract Background In Belgium, bladder cancer is the fifth most common cancer in males (5.2% and the sixth most frequent cause of death from cancer in males (3.8%. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence. Method The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 μg/day supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study. Design The SELEnium and BLAdder cancer Trial (SELEBLAT is a phase III randomized, placebo-controlled, academic, double-blind superior trial. Discussion This is the first report on a selenium randomized trial in bladder cancer patients. Trial registration ClinicalTrials.gov identifier: NCT00729287

  10. Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma : A Randomized, Multicenter, Open-Label Phase 3 Trial

    NARCIS (Netherlands)

    Geissler, Edward K.; Schnitzbauer, Andreas A.; Zuelke, Carl; Lamby, Philipp E.; Proneth, Andrea; Duvoux, Christophe; Burra, Patrizia; Jauch, Karl-Walter; Rentsch, Markus; Ganten, Tom M.; Schmidt, Jan; Settmacher, Utz; Heise, Michael; Rossi, Giorgio; Cillo, Umberto; Kneteman, Norman; Adam, Rene; van Hoek, Bart; Bachellier, Philippe; Wolf, Philippe; Rostaing, Lionel; Bechstein, Wolf O.; Rizell, Magnus; Powell, James; Hidalgo, Ernest; Gugenheim, Jean; Wolters, Heiner; Brockmann, Jens; Roy, Andre; Mutzbauer, Ingrid; Schlitt, Angela; Beckebaum, Susanne; Graeb, Christian; Nadalin, Silvio; Valente, Umberto; Sanchez Turrion, Victor; Jamieson, Neville; Scholz, Tim; Colledan, Michele; Faendrich, Fred; Becker, Thomas; Soderdahl, Gunnar; Chazouilleres, Olivier; Makisalo, Heikki; Pageaux, Georges-Philippe; Steininger, Rudolf; Soliman, Thomas; de Jong, Koert P.; Pirenne, Jacques; Margreiter, Raimund; Pratschke, Johann; Pinna, Antonio D.; Hauss, Johann; Schreiber, Stefan; Strasser, Simone; Klempnauer, Juergen; Troisi, Roberto I.; Bhoori, Sherrie; Lerut, Jan; Bilbao, Itxarone; Klein, Christian G.; Koenigsrainer, Alfred; Mirza, Darius F.; Otto, Gerd; Mazzaferro, Vincenzo; Neuhaus, Peter; Schlitt, Hans J.

    Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target

  11. Scaled hydrogenic approximation wavefunctions. [Hartree-Fock approximation

    Energy Technology Data Exchange (ETDEWEB)

    Shore, B.W.

    1979-09-01

    Although widespread use of computer codes for the solution of Schrodinger equations makes available numerical Hartree-Fock model radial wave functions, there remains persistant interest in simple analytic expressions for atomic wave functions. One such frequency favored approach employs hydrogenic functions, suitably scaled, as approximate wave functions. The following note displays typical inaccuracies to be expected from such approximations. 13 references.

  12. Truthful approximations to range voting

    DEFF Research Database (Denmark)

    Filos-Ratsika, Aris; Miltersen, Peter Bro

    We consider the fundamental mechanism design problem of approximate social welfare maximization under general cardinal preferences on a finite number of alternatives and without money. The well-known range voting scheme can be thought of as a non-truthful mechanism for exact social welfare......-unilateral has an approximation ratio between 0.610 and 0.611, the best ordinal mechanism has an approximation ratio between 0.616 and 0.641, while the best mixed-unilateral mechanism has an approximation ratio bigger than 0.660. In particular, the best mixed-unilateral non-ordinal (i.e., cardinal) mechanism...

  13. Approximation for limit cycles and their isochrons.

    Science.gov (United States)

    Demongeot, Jacques; Françoise, Jean-Pierre

    2006-12-01

    Local analysis of trajectories of dynamical systems near an attractive periodic orbit displays the notion of asymptotic phase and isochrons. These notions are quite useful in applications to biosciences. In this note, we give an expression for the first approximation of equations of isochrons in the setting of perturbations of polynomial Hamiltonian systems. This method can be generalized to perturbations of systems that have a polynomial integral factor (like the Lotka-Volterra equation).

  14. Multilevel weighted least squares polynomial approximation

    KAUST Repository

    Haji-Ali, Abdul-Lateef

    2017-06-30

    Weighted least squares polynomial approximation uses random samples to determine projections of functions onto spaces of polynomials. It has been shown that, using an optimal distribution of sample locations, the number of samples required to achieve quasi-optimal approximation in a given polynomial subspace scales, up to a logarithmic factor, linearly in the dimension of this space. However, in many applications, the computation of samples includes a numerical discretization error. Thus, obtaining polynomial approximations with a single level method can become prohibitively expensive, as it requires a sufficiently large number of samples, each computed with a sufficiently small discretization error. As a solution to this problem, we propose a multilevel method that utilizes samples computed with different accuracies and is able to match the accuracy of single-level approximations with reduced computational cost. We derive complexity bounds under certain assumptions about polynomial approximability and sample work. Furthermore, we propose an adaptive algorithm for situations where such assumptions cannot be verified a priori. Finally, we provide an efficient algorithm for the sampling from optimal distributions and an analysis of computationally favorable alternative distributions. Numerical experiments underscore the practical applicability of our method.

  15. Infinite-randomness fixed points for chains of non-Abelian quasiparticles.

    Science.gov (United States)

    Bonesteel, N E; Yang, Kun

    2007-10-05

    One-dimensional chains of non-Abelian quasiparticles described by SU(2)k Chern-Simons-Witten theory can enter random singlet phases analogous to that of a random chain of ordinary spin-1/2 particles (corresponding to k-->infinity). For k=2 this phase provides a random singlet description of the infinite-randomness fixed point of the critical transverse field Ising model. The entanglement entropy of a region of size L in these phases scales as S(L) approximately lnd/3 log(2)L for large L, where d is the quantum dimension of the particles.

  16. GnRH agonist during luteal phase in women undergoing assisted reproductive techniques: systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Martins, W P; Ferriani, R A; Navarro, P A; Nastri, C O

    2016-02-01

    To identify, evaluate and summarize the available evidence regarding the effectiveness and safety of administering a gonadotropin releasing hormone (GnRH) agonist during the luteal phase in women undergoing assisted reproductive techniques. In this systematic review and meta-analysis, we searched for randomized controlled trials (RCTs) comparing the addition of a GnRH agonist during the luteal phase, compared with standard luteal-phase support. We searched seven electronic databases and hand-searched the reference lists of included studies and related reviews. Our primary outcome was live birth or ongoing pregnancy per randomized woman. Our secondary outcomes were clinical pregnancy per randomized woman, miscarriage per clinical pregnancy, adverse perinatal outcome and congenital malformations. The evidence from eight studies examining 2776 women showed a relative risk (RR) for live birth or ongoing pregnancy of 1.26 (95% CI, 1.04-1.53; I(2) = 58%). Sensitivity analysis when excluding the studies that did not report live birth and those at high risk of bias resulted in one study examining 181 women with an RR of 1.07 (95% CI, 0.73-1.58). Subgroup analysis separating the studies by single/multiple doses of GnRH agonists or by ovarian stimulation with GnRH agonist/antagonist was unable to explain the observed heterogeneity. The quality of the evidence was deemed to be very low: it was downgraded because of the limitation of the included studies, imprecision, inconsistency across the studies' results, and suspicion of publication bias. None of the included studies reported adverse perinatal outcomes or congenital malformations. There is evidence that adding GnRH agonist during the luteal phase improves the likelihood of ongoing pregnancy. However, this evidence is of very low quality and there is no evidence for adverse perinatal outcome and congenital malformations. We therefore believe that including this intervention in clinical practice would be premature

  17. Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

    Directory of Open Access Journals (Sweden)

    Nativ Ofer

    2012-11-01

    Full Text Available Abstract Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10, and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC-controlled Phase I/II study (N = 7 in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10: All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7: Hemostatic success at 10 min (primary endpoint was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial

  18. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial

    Science.gov (United States)

    Gimsing, Peter; Hjertner, Oyvind; Lenhoff, Stig; Laane, Edward; Remes, Kari; Steingrimsdottir, Hlif; Abildgaard, Niels; Ahlberg, Lucia; Blimark, Cecilie; Dahl, Inger Marie; Forsberg, Karin; Gedde-Dahl, Tobias; Gregersen, Henrik; Gruber, Astrid; Guldbrandsen, Nina; Haukås, Einar; Carlson, Kristina; Kvam, Ann Kristin; Nahi, Hareth; Lindås, Roald; Andersen, Niels Frost; Turesson, Ingemar; Waage, Anders; Westin, Jan; Gregersen, Henrik; Frost Andersen, Niels; Gimsing, Peter; Toffner-Clausen, Nilsaage; Abildgaard, Niels; Laane, Edward; Silvennoinen, Raija; Remes, Kari; Steingrimsdottir, Hlif; Lindås, Roald; Gedde-Dahl, Tobias; Guldbrandsen, Nina; Kristin Kvam, Ann; Haukås, Einar; Marie Dahl, Inger; Hjertner, Oyvind; Waage, Anders; Blimark, Cecilie; Mellqvist, Ulf-Henrik; Westin, Jan; Ahlberg, Lucia; Lenhoff, Stig; Turesson, Ingemar; Linder, Olle; Gruber, Astrid; Nahi, Hareth; Forsberg, Karin; Carlson, Kristina

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370 patients were centrally randomly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation. The hypothesis was that consolidation therapy would prolong progression-free survival (PFS). The PFS after randomization was 27 months for the bortezomib group compared with 20 months for the control group (P = .05). Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after randomization (P = .007). No difference in overall survival was seen. Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality-of-life (QOL) questionnaires, whereas no other major differences in QOL were recorded between the groups. Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response (VGPR) but not for patients in the ≥ VGPR category at randomization. Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL. This trial was registered at www.clinicaltrials.gov as #NCT00417911. PMID:23616624

  19. The phase diagrams of the mixed-spin ternary-alloy consisting of half-integer spins: Standard-random approach

    Science.gov (United States)

    Albayrak, Erhan

    2018-02-01

    The ternary-alloy in the form ABpC1-p is investigated on the Bethe lattice with the odd numbered shells containing only A atoms (spin-1/2), while the even shells randomly containing either B (spin-3/2) or C (spin-5/2) atoms with different concentrations p and 1 - p, respectively. The phase diagrams are calculated on the (p ,kTc /JAB) and (R = |JAC | /JAB ,kTc /JAB) planes for given values of R and p, respectively, with the coordination numbers z = 3 , 4 , 5 and 6 by studying the thermal variations of the order-parameters. It is found that there exist a critical value of R, i.e. Rc ≅ 0.653, which is independent of z. In addition, the critical temperatures increase as z increases. The present work is an extension of the previous work [1] and it only differs from it by the implementation technique of randomness into the model. The obtained phase diagrams are in agreement with the site-dependent random case [1] except at low temperatures. On the other hand, there is an overall agreement with the literature.

  20. Bit error rate analysis of Gaussian, annular Gaussian, cos Gaussian, and cosh Gaussian beams with the help of random phase screens.

    Science.gov (United States)

    Eyyuboğlu, Halil T

    2014-06-10

    Using the random phase screen approach, we carry out a simulation analysis of the probability of error performance of Gaussian, annular Gaussian, cos Gaussian, and cosh Gaussian beams. In our scenario, these beams are intensity-modulated by the randomly generated binary symbols of an electrical message signal and then launched from the transmitter plane in equal powers. They propagate through a turbulent atmosphere modeled by a series of random phase screens. Upon arriving at the receiver plane, detection is performed in a circuitry consisting of a pin photodiode and a matched filter. The symbols detected are compared with the transmitted ones, errors are counted, and from there the probability of error is evaluated numerically. Within the range of source and propagation parameters tested, the lowest probability of error is obtained for the annular Gaussian beam. Our investigation reveals that there is hardly any difference between the aperture-averaged scintillations of the beams used, and the distinctive advantage of the annular Gaussian beam lies in the fact that the receiver aperture captures the maximum amount of power when this particular beam is launched from the transmitter plane.

  1. A shoe sole-based apparatus and method for randomly perturbing the stance phase of gait: test-retest reliability in young adults.

    Science.gov (United States)

    Kim, Hogene; Ashton-Miller, James A

    2012-06-26

    Walking on an irregular surface is associated with an elevated risk for a fall at any age. Yet, relatively little is known about how a human responds to an unexpected underfoot perturbation during gait. This is partly due to the difficulty of generating an intermittent but repeatable, unexpected, underfoot perturbation whose size and location are precisely known. So we developed a shoe sole-embedded apparatus for randomly perturbing the stance phase of gait. Medial and lateral flaps were concealed in the soles of pairs of sandals, along with their actuators. Either flap could be deployed within 400ms in the parasagittal plane under a swing foot; this altered the resulting sagittal and frontal plane orientations of the foot during the next stance phase, whereafter the flap was retracted following toe-off for the rest of that gait trial. We tested six healthy young subjects by randomly presenting a single medial or lateral perturbation in 12 of 30 gait trials. Traditional step kinematic measures were used to evaluate the test-retest reliability of the response to the stimulus at two different walking speeds in 60 randomized trials conducted 1 week apart. The method was effective in systematically inducing an alteration in gait, reproducible across visits, as evidenced by acceptable intraclass correlation coefficients for step width, time and length. We conclude that the apparatus and method has potential for measuring the ability of humans to reject one or more unexpected underfoot perturbations during gait. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Approximate circuits for increased reliability

    Science.gov (United States)

    Hamlet, Jason R.; Mayo, Jackson R.

    2015-08-18

    Embodiments of the invention describe a Boolean circuit having a voter circuit and a plurality of approximate circuits each based, at least in part, on a reference circuit. The approximate circuits are each to generate one or more output signals based on values of received input signals. The voter circuit is to receive the one or more output signals generated by each of the approximate circuits, and is to output one or more signals corresponding to a majority value of the received signals. At least some of the approximate circuits are to generate an output value different than the reference circuit for one or more input signal values; however, for each possible input signal value, the majority values of the one or more output signals generated by the approximate circuits and received by the voter circuit correspond to output signal result values of the reference circuit.

  3. Approximate circuits for increased reliability

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, Jason R.; Mayo, Jackson R.

    2015-12-22

    Embodiments of the invention describe a Boolean circuit having a voter circuit and a plurality of approximate circuits each based, at least in part, on a reference circuit. The approximate circuits are each to generate one or more output signals based on values of received input signals. The voter circuit is to receive the one or more output signals generated by each of the approximate circuits, and is to output one or more signals corresponding to a majority value of the received signals. At least some of the approximate circuits are to generate an output value different than the reference circuit for one or more input signal values; however, for each possible input signal value, the majority values of the one or more output signals generated by the approximate circuits and received by the voter circuit correspond to output signal result values of the reference circuit.

  4. Add-on mirtazapine improves depressive symptoms in schizophrenia: a double-blind randomized placebo-controlled study with an open-label extension phase.

    Science.gov (United States)

    Terevnikov, Viacheslav; Stenberg, Jan-Henry; Tiihonen, Jari; Joffe, Marina; Burkin, Mark; Tchoukhine, Evgueni; Joffe, Grigori

    2011-04-01

    Depression is common in schizophrenia and worsens its course. The role of antidepressants for schizophrenic depression remains unclear. In this study, the efficacy of add-on mirtazapine on depression in schizophrenia was explored in a subsidiary arm of a recent randomized controlled trial. Patients (n = 41) with chronic but stable schizophrenia and inadequate response to stable doses of different first-generation antipsychotics were treated with add-on mirtazapine 30 mg or placebo during a 6-week double-blind phase and with open-label add-on mirtazapine during a 6-week extension phase. Efficacy measures were the Calgary Depression Scale for Schizophrenia (CDSS) and the Positive and Negative Syndrome Scale depression item. During the double-blind phase, both measures' scores decreased significantly in the mirtazapine group but not in the placebo group (for the CDSS, 52.0% vs 19.6%, respectively). During the open‐label phase, both groups demonstrated significant improvements. In between‐group comparison, a trend favoring mirtazapine did not reach statistical significance. The changes in the CDSS correlated positively with those in the Positive and Negative Syndrome Scale negative, positive and total (sub)scales for mirtazapine‐treated patients during the double‐blind phase. Depressed patients with schizophrenia may benefit from mirtazapine–first‐generation antipsychotics combination, with no increased risk for psychosis. However, more studies are needed.

  5. Semiclassical initial value approximation for Green's function.

    Science.gov (United States)

    Kay, Kenneth G

    2010-06-28

    A semiclassical initial value approximation is obtained for the energy-dependent Green's function. For a system with f degrees of freedom the Green's function expression has the form of a (2f-1)-dimensional integral over points on the energy surface and an integral over time along classical trajectories initiated from these points. This approximation is derived by requiring an integral ansatz for Green's function to reduce to Gutzwiller's semiclassical formula when the integrations are performed by the stationary phase method. A simpler approximation is also derived involving only an (f-1)-dimensional integral over momentum variables on a Poincare surface and an integral over time. The relationship between the present expressions and an earlier initial value approximation for energy eigenfunctions is explored. Numerical tests for two-dimensional systems indicate that good accuracy can be obtained from the initial value Green's function for calculations of autocorrelation spectra and time-independent wave functions. The relative advantages of initial value approximations for the energy-dependent Green's function and the time-dependent propagator are discussed.

  6. Biological 18[F]-FDG-PET image-guided dose painting by numbers for painful uncomplicated bone metastases: A 3-arm randomized phase II trial.

    Science.gov (United States)

    Berwouts, Dieter; De Wolf, Katrien; Lambert, Bieke; Bultijnck, Renée; De Neve, Wilfried; De Lobel, Lizzy; Jans, Lennart; Goetghebeur, Els; Speleers, Bruno; Olteanu, Luiza A M; Madani, Indira; Goethals, Ingeborg; Ost, Piet

    2015-05-01

    Antalgic radiotherapy for bone metastases might be improved by implementing biological information in the radiotherapy planning using (18)F-FDG-PET-CT based dose painting by numbers (DPBN). Patients with uncomplicated painful bone metastases were randomized (1:1:1) and blinded to receive either 8Gy in a single fraction with conventionally planned radiotherapy (arm A) or 8Gy in a single fraction with DPBN (dose range between 610Gy and 10Gy) (arm B) or 16Gy in a single fraction with DPBN (dose range between 1410Gy and 18Gy) (arm C). The primary endpoint was overall pain response at 1month. The phase II trial was designed to select the experimental arm with sufficient promise of efficacy to continue to a phase III trial. Forty-five patients were randomized. Eight (53%), 12 (80%) and 9 patients (60%) had an overall response to treatment in arm A, B and C, respectively. The estimated odds ratio of overall response for arm B vs. A is 3.5 (95% CI: 0.44-17.71, p=0.12). The estimated odds ratio of arm C vs. A is 1.31 (95% CI: 0.31-5.58, p=0.71). A single fraction of 8Gy with DPBN will be further evaluated in a phase III-trial. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Effects of motive-oriented therapeutic relationship in early-phase treatment of borderline personality disorder: a pilot study of a randomized trial.

    Science.gov (United States)

    Kramer, Ueli; Berger, Thomas; Kolly, Stéphane; Marquet, Pierre; Preisig, Martin; de Roten, Yves; Despland, Jean-Nicolas; Caspar, Franz

    2011-04-01

    Motive-oriented therapeutic relationship (MOTR, also called complementary therapeutic relationship) was postulated to be a particularly helpful therapeutic ingredient in the early-phase treatment of patients with personality disorders, in particular borderline personality disorder (BPD). The present pilot study of randomized controlled trial using an add-on design aims to investigate the effects of MOTR in early-phase treatment (up to session 10), with BPD patients on therapeutic alliance, session impact, and outcome. In total, N = 25 patients participated in the study. BPD patients were randomly allocated to a manual-based investigation process in 10 sessions or to the same investigation process infused with MOTR. Adherence ratings were performed and yielded satisfactory results. The results suggested a specific effectiveness of MOTR on the interpersonal problem area, on the quality of the therapeutic alliance and the quality of the therapeutic relationship, as rated by the patient. These results may have important clinical implications for the early-phase treatment of patients presenting with BPD.

  8. Saddlepoint Approximations for Expectations and an Application to CDO Pricing

    NARCIS (Netherlands)

    Huang, X.; Oosterlee, C.W.

    2011-01-01

    We derive two types of saddlepoint approximations for expectations in the form of E[(X - K)+], where X is the sum of n independent random variables and K is a known constant. We establish error convergence rates for both types of approximations in the independently and identically distributed case.

  9. Prediction and prevention of thromboembolic events with enoxaparin in cancer patients with elevated tissue factor-bearing microparticles: a randomized-controlled phase II trial (the Microtec study).

    Science.gov (United States)

    Zwicker, Jeffrey I; Liebman, Howard A; Bauer, Kenneth A; Caughey, Thomas; Campigotto, Federico; Rosovsky, Rachel; Mantha, Simon; Kessler, Craig M; Eneman, Jonathan; Raghavan, Vidya; Lenz, Heinz-Joseph; Bullock, Andrea; Buchbinder, Elizabeth; Neuberg, Donna; Furie, Bruce

    2013-02-01

    Elevated levels of circulating tissue factor-bearing microparticles (TFMP) have been associated with an increased risk of developing venous thromboembolism (VTE) in cancer patients. We performed a randomized phase II study to evaluate the cumulative incidence of VTE in advanced cancer patients with lower levels of TFMP not receiving thromboprophylaxis and those with higher levels of circulating TFMP randomized to enoxaparin or observation. The cumulative incidence of VTE at 2 months in the higher TFMP group randomized to enoxaparin (N = 23) was 5·6% while the higher TFMP group observation arm (N = 11) was 27·3% (Gray test P = 0·06). The cumulative incidence of VTE in the low TFMP was 7·2% (N = 32). No major haemorrhages were observed in the enoxaparin arm. The median survival for patients with higher levels of TFMP followed by observation was 11·8 months compared with 17·8 months on enoxaparin (P = 0·58). In a prospective randomized trial, increased numbers of circulating TFMP detected by impedance flow cytometry identified cancer patients with a high incidence of VTE. Enoxaparin demonstrated a clear trend towards reducing the rate of VTE in patients with elevated levels of TFMP, with an overall rate of VTE similar in magnitude to the lower TFMP group. © 2012 Blackwell Publishing Ltd.

  10. Random fixed points and random differential inclusions

    Directory of Open Access Journals (Sweden)

    Nikolaos S. Papageorgiou

    1988-01-01

    Full Text Available In this paper, first, we study random best approximations to random sets, using fixed point techniques, obtaining this way stochastic analogues of earlier deterministic results by Browder-Petryshyn, KyFan and Reich. Then we prove two fixed point theorems for random multifunctions with stochastic domain that satisfy certain tangential conditions. Finally we consider a random differential inclusion with upper semicontinuous orientor field and establish the existence of random solutions.

  11. Motor Recovery and Cortical Reorganization After Mirror Therapy in Chronic Stroke Patients : A Phase II Randomized Controlled Trial

    NARCIS (Netherlands)

    Michielsen, Marian E.; Selles, Ruud W.; van der Geest, Jos N.; Eckhardt, Martine; Yavuzer, Gunes; Stam, Henk J.; Smits, Marion; Ribbers, Gerard M.; Bussmann, Johannes B. J.

    2011-01-01

    Objective. To evaluate for any clinical effects of home-based mirror therapy and subsequent cortical reorganization in patients with chronic stroke with moderate upper extremity paresis. Methods. A total of 40 chronic stroke patients (mean time post. onset, 3.9 years) were randomly assigned to the

  12. Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma : Randomized phase III EORTC study

    NARCIS (Netherlands)

    Kluin-Nelemans, HC; Zagonel, [No Value; Anastasopoulou, A; Bron, D; Roozendaal, KJ; Noordijk, EM; Musson, H; Teodorovic, [No Value; Maes, B; Carbone, A; Carde, P

    2001-01-01

    Background: The long-term outcome for patients with aggressive non-Hodgkin's lymphoma (NHL) is poor. Consequently; the European Organization for Research and Treatment of Cancer Lymphoma Group designed a prospective randomized trial to investigate whether high-dose chemotherapy plus autologous bone

  13. A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia

    DEFF Research Database (Denmark)

    Birgens, Henrik; Frederiksen, Henrik; Hasselbalch, Hans Carl

    2013-01-01

    The impact of first-line treatment with the anti-CD 20 chimeric monoclonal antibody rituximab in patients with warm-antibody reactive autoimmune haemolytic anaemia (WAIHA) is unknown. We report the first randomized study of 64 patients with newly diagnosed WAIHA who received prednisolone and ritu...

  14. Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the treatment of patients with advanced pancreatic cancer: results of a phase II randomized, double-blind, placebo-controlled, multicenter study.

    NARCIS (Netherlands)

    Richards, D.A.; Boehm, K.A.; Waterhouse, D.M.; Wagener, D.J.T.; Krishnamurthi, S.S.; Rosemurgy, A.; Grove, W.; Macdonald, K.; Gulyas, S.; Clark, M.; Dasse, K.D.

    2006-01-01

    BACKGROUND: CI-994, an oral histone deacetylase inhibitor, has antineoplastic activity and synergism with gemcitabine preclinically. This randomized phase II trial explored whether CI-994 plus gemcitabine improves overall survival, objective response, duration of response, time to treatment failure

  15. Up-front fludarabine impairs stem cell harvest in multiple myeloma: report from an interim analysis of the NMSG 13/03 randomized placebo controlled phase II trial

    DEFF Research Database (Denmark)

    Johnsen, Hans Erik; Knudsen, Lene Meldgaard; Mylin, Anne Kærsgaard

    2009-01-01

    toxicity and safety analysis, the trial was stopped following inclusion of 34 of a planned 80 patients due to a reduced number of patients (4/17) actually harvested in the experimental arm compared to the control arm (11/17; p lower than 0.05). In conclusion, the scheduled fludarabine dosage in 2 cycles......The impact of chemotherapy resistant B cells in multiple myeloma (MM) needs to be evaluated by in vivo targeted therapy. Here we report the conclusions from a phase II randomized, placebo controlled trial adding fludarabine to the induction with cyclophosphamide-dexamethasone. Based on an interim...

  16. Up-front fludarabine impairs stem cell harvest in multiple myeloma: report of the NMSG 13/03 randomized placebo controlled phase II trial

    DEFF Research Database (Denmark)

    Johnsen, Hans E.; Meldgaard Knudsen, Lene; Mylin, Anne K.

    2009-01-01

    toxicity and safety analysis, the trial was stopped following inclusion of 34 of a planned 80 patients due to a reduced number of patients (4/17) actually harvested in the experimental arm compared to the control arm (11/17; p...The impact of chemotherapy resistant B cells in multiple myeloma (MM) needs to be evaluated by in vivo targeted therapy. Here we report the conlusions from a phase II randomized, placebo controlled trial adding fludarabine to the induction with cyclophosphamide-dexamethasone. Based on an interim...

  17. Approximate Implicitization Using Linear Algebra

    Directory of Open Access Journals (Sweden)

    Oliver J. D. Barrowclough

    2012-01-01

    Full Text Available We consider a family of algorithms for approximate implicitization of rational parametric curves and surfaces. The main approximation tool in all of the approaches is the singular value decomposition, and they are therefore well suited to floating-point implementation in computer-aided geometric design (CAGD systems. We unify the approaches under the names of commonly known polynomial basis functions and consider various theoretical and practical aspects of the algorithms. We offer new methods for a least squares approach to approximate implicitization using orthogonal polynomials, which tend to be faster and more numerically stable than some existing algorithms. We propose several simple propositions relating the properties of the polynomial bases to their implicit approximation properties.

  18. Rollout sampling approximate policy iteration

    NARCIS (Netherlands)

    Dimitrakakis, C.; Lagoudakis, M.G.

    2008-01-01

    Several researchers have recently investigated the connection between reinforcement learning and classification. We are motivated by proposals of approximate policy iteration schemes without value functions, which focus on policy representation using classifiers and address policy learning as a

  19. -commuting maps and invariant approximations

    Directory of Open Access Journals (Sweden)

    Rhoades BE

    2006-01-01

    Full Text Available We obtain common fixed point results for generalized -nonexpansive -commuting maps. As applications, various best approximation results for this class of maps are derived in the setup of certain metrizable topological vector spaces.

  20. Some results in Diophantine approximation

    DEFF Research Database (Denmark)

    Pedersen, Steffen Højris

    This thesis consists of three papers in Diophantine approximation, a subbranch of number theory. Preceding these papers is an introduction to various aspects of Diophantine approximation and formal Laurent series over Fq and a summary of each of the three papers. The introduction introduces...... the basic concepts on which the papers build. Among other it introduces metric Diophantine approximation, Mahler’s approach on algebraic approximation, the Hausdorff measure, and properties of the formal Laurent series over Fq. The introduction ends with a discussion on Mahler’s problem when considered....... The first part is about a failed attempt of applying dynamical methods to obtain results and is not part of the paper. It explains the ideas of how the real case works and what goes wrong in the case of the formal Laurent series. The second part contains the results of the paper and sketches of the proofs....

  1. Weighted approximation with varying weight

    CERN Document Server

    Totik, Vilmos

    1994-01-01

    A new construction is given for approximating a logarithmic potential by a discrete one. This yields a new approach to approximation with weighted polynomials of the form w"n"(" "= uppercase)P"n"(" "= uppercase). The new technique settles several open problems, and it leads to a simple proof for the strong asymptotics on some L p(uppercase) extremal problems on the real line with exponential weights, which, for the case p=2, are equivalent to power- type asymptotics for the leading coefficients of the corresponding orthogonal polynomials. The method is also modified toyield (in a sense) uniformly good approximation on the whole support. This allows one to deduce strong asymptotics in some L p(uppercase) extremal problems with varying weights. Applications are given, relating to fast decreasing polynomials, asymptotic behavior of orthogonal polynomials and multipoint Pade approximation. The approach is potential-theoretic, but the text is self-contained.

  2. Shearlets and Optimally Sparse Approximations

    DEFF Research Database (Denmark)

    Kutyniok, Gitta; Lemvig, Jakob; Lim, Wang-Q

    2012-01-01

    Multivariate functions are typically governed by anisotropic features such as edges in images or shock fronts in solutions of transport-dominated equations. One major goal both for the purpose of compression as well as for an efficient analysis is the provision of optimally sparse approximations...... of such functions. Recently, cartoon-like images were introduced in 2D and 3D as a suitable model class, and approximation properties were measured by considering the decay rate of the $L^2$ error of the best $N$-term approximation. Shearlet systems are to date the only representation system, which provide...... optimally sparse approximations of this model class in 2D as well as 3D. Even more, in contrast to all other directional representation systems, a theory for compactly supported shearlet frames was derived which moreover also satisfy this optimality benchmark. This chapter shall serve as an introduction...

  3. Joint genome-wide prediction in several populations accounting for randomness of genotypes: A hierarchical Bayes approach. II: Multivariate spike and slab priors for marker effects and derivation of approximate Bayes and fractional Bayes factors for the complete family of models.

    Science.gov (United States)

    Martínez, Carlos Alberto; Khare, Kshitij; Banerjee, Arunava; Elzo, Mauricio A

    2017-03-21

    This study corresponds to the second part of a companion paper devoted to the development of Bayesian multiple regression models accounting for randomness of genotypes in across population genome-wide prediction. This family of models considers heterogeneous and correlated marker effects and allelic frequencies across populations, and has the ability of considering records from non-genotyped individuals and individuals with missing genotypes in any subset of loci without the need for previous imputation, taking into account uncertainty about imputed genotypes. This paper extends this family of models by considering multivariate spike and slab conditional priors for marker allele substitution effects and contains derivations of approximate Bayes factors and fractional Bayes factors to compare models from part I and those developed here with their null versions. These null versions correspond to simpler models ignoring heterogeneity of populations, but still accounting for randomness of genotypes. For each marker loci, the spike component of priors corresponded to point mass at 0 in R S , where S is the number of populations, and the slab component was a S-variate Gaussian distribution, independent conditional priors were assumed. For the Gaussian components, covariance matrices were assumed to be either the same for all markers or different for each marker. For null models, the priors were simply univariate versions of these finite mixture distributions. Approximate algebraic expressions for Bayes factors and fractional Bayes factors were found using the Laplace approximation. Using the simulated datasets described in part I, these models were implemented and compared with models derived in part I using measures of predictive performance based on squared Pearson correlations, Deviance Information Criterion, Bayes factors, and fractional Bayes factors. The extensions presented here enlarge our family of genome-wide prediction models making it more flexible in the

  4. An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin

    2013-01-01

    This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer.......This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

  5. An Origami Approximation to the Cosmic Web

    Science.gov (United States)

    Neyrinck, Mark C.

    2016-10-01

    The powerful Lagrangian view of structure formation was essentially introduced to cosmology by Zel'dovich. In the current cosmological paradigm, a dark-matter-sheet 3D manifold, inhabiting 6D position-velocity phase space, was flat (with vanishing velocity) at the big bang. Afterward, gravity stretched and bunched the sheet together in different places, forming a cosmic web when projected to the position coordinates. Here, I explain some properties of an origami approximation, in which the sheet does not stretch or contract (an assumption that is false in general), but is allowed to fold. Even without stretching, the sheet can form an idealized cosmic web, with convex polyhedral voids separated by straight walls and filaments, joined by convex polyhedral nodes. The nodes form in `polygonal' or `polyhedral' collapse, somewhat like spherical/ellipsoidal collapse, except incorporating simultaneous filament and wall formation. The origami approximation allows phase-space geometries of nodes, filaments, and walls to be more easily understood, and may aid in understanding spin correlations between nearby galaxies. This contribution explores kinematic origami-approximation models giving velocity fields for the first time.

  6. Ocular comfort assessment of lifitegrast ophthalmic solution 5.0% in OPUS-3, a Phase III randomized controlled trial.

    Science.gov (United States)

    Nichols, Kelly K; Holland, Edward; Toyos, Melissa M; Peace, James H; Majmudar, Parag; Raychaudhuri, Aparna; Hamdani, Mohamed; Roy, Monica; Shojaei, Amir

    2018-01-01

    To evaluate ocular comfort of lifitegrast ophthalmic solution 5.0% among patients with dry eye disease (DED) in the OPUS-3 trial. OPUS-3 was a multicenter, randomized, double-masked, placebo-controlled study. Adults with DED and recent artificial tear use were randomized 1:1 (lifitegrast:placebo) to ophthalmic drops twice daily for 84 days. On days 0 (baseline), 14, 42, and 84, drop comfort score (scale, 0-10; 0 = very comfortable, 10 = very uncomfortable) was measured at 0, 1, 2, and 3 minutes postinstillation. If the score was >3 at 3 minutes, assessment was repeated at 5, 10, and 15 minutes until score ≤3. Ocular treatment-emergent adverse events (TEAEs) were assessed. Overall, 711 participants were randomized (n=357 received lifitegrast; n=354 received placebo). Drop comfort scores for lifitegrast-treated participants improved within 3 minutes of instillation (mean scores on day 84 for both study and fellow eyes: instillation: lifitegrast, 3.4, placebo, 1.0; 3 minutes: lifitegrast, 1.5, placebo, 0.7). The majority (64%-66%) of participants had scores 3 at 3 minutes, the mean score in the lifitegrast group was similar to or better than that in the placebo group at 5, 10, or 15 minutes postinstillation. Lifitegrast appeared to be well tolerated, with ocular TEAEs rarely leading to discontinuation. In OPUS-3, lifitegrast appeared to be well tolerated and drop comfort scores approached placebo levels by 3 minutes postinstillation.

  7. The Second-Order Polarization Propagator Approximation (SOPPA) method coupled to the polarizable continuum model

    DEFF Research Database (Denmark)

    Eriksen, Janus Juul; Solanko, Lukasz Michal; Nåbo, Lina J.

    2014-01-01

    2) wave function coupled to PCM, we introduce dynamical PCM solvent effects only in the Random Phase Approximation (RPA) part of the SOPPA response equations while the static solvent contribution is kept in both the RPA terms as well as in the higher order correlation matrix components of the SOPPA...... response equations. By dynamic terms, we refer to contributions that describe a change in environmental polarization which, in turn, reflects a change in the core molecular charge distribution upon an electronic excitation. This new combination of methods is termed PCM-SOPPA/RPA. We apply this newly...

  8. Fast randomized approximate string matching with succinct hash data structures.

    Science.gov (United States)

    Policriti, Alberto; Prezza, Nicola

    2015-01-01

    The high throughput of modern NGS sequencers coupled with the huge sizes of genomes currently analysed, poses always higher algorithmic challenges to align short reads quickly and accurately against a reference sequence. A crucial, additional, requirement is that the data structures used should be light. The available modern solutions usually are a compromise between the mentioned constraints: in particular, indexes based on the Burrows-Wheeler transform offer reduced memory requirements at the price of lower sensitivity, while hash-based text indexes guarantee high sensitivity at the price of significant memory consumption. In this work we describe a technique that permits to attain the advantages granted by both classes of indexes. This is achieved using Hamming-aware hash functions--hash functions designed to search the entire Hamming sphere in reduced time--which are also homomorphisms on de Bruijn graphs. We show that, using this particular class of hash functions, the corresponding hash index can be represented in linear space introducing only a logarithmic slowdown (in the query length) for the lookup operation. We point out that our data structure reaches its goals without compressing its input: another positive feature, as in biological applications data is often very close to be un-compressible. The new data structure introduced in this work is called dB-hash and we show how its implementation--BW-ERNE--maintains the high sensitivity and speed of its (hash-based) predecessor ERNE, while drastically reducing space consumption. Extensive comparison experiments conducted with several popular alignment tools on both simulated and real NGS data, show, finally, that BW-ERNE is able to attain both the positive features of succinct data structures (that is, small space) and hash indexes (that is, sensitivity). In applications where space and speed are both a concern, standard methods often sacrifice accuracy to obtain competitive throughputs and memory footprints. In this work we show that, combining hashing and succinct indexing techniques, we can attain good performances and accuracy with a memory footprint comparable to that of the most popular compressed indexes.

  9. Fast, Approximate Solutions for 1D Multicomponent Gas Injection Problems

    DEFF Research Database (Denmark)

    Jessen, Kristian; Wang, Yun; Ermakov, Pavel

    2001-01-01

    This paper presents a new approach for constructing approximate analytical solutions for ID, multicomponent gas displacement problems. The solution to mass conservation equations governing ID dispersion-free flow in which components partition between two equilibrium phases is controlled by the ge......This paper presents a new approach for constructing approximate analytical solutions for ID, multicomponent gas displacement problems. The solution to mass conservation equations governing ID dispersion-free flow in which components partition between two equilibrium phases is controlled...

  10. Approximate number sense theory or approximate theory of magnitude?

    Science.gov (United States)

    Content, Alain; Velde, Michael Vande; Adriano, Andrea

    2017-01-01

    Leibovich et al. argue that the evidence in favor of a perceptual mechanism devoted to the extraction of numerosity from visual collections is unsatisfactory and propose to replace it with an unspecific mechanism capturing approximate magnitudes from continuous dimensions. We argue that their representation of the evidence is incomplete and that their theoretical proposal is too vague to be useful.

  11. Approximate entropy of network parameters

    Science.gov (United States)

    West, James; Lacasa, Lucas; Severini, Simone; Teschendorff, Andrew

    2012-04-01

    We study the notion of approximate entropy within the framework of network theory. Approximate entropy is an uncertainty measure originally proposed in the context of dynamical systems and time series. We first define a purely structural entropy obtained by computing the approximate entropy of the so-called slide sequence. This is a surrogate of the degree sequence and it is suggested by the frequency partition of a graph. We examine this quantity for standard scale-free and Erdös-Rényi networks. By using classical results of Pincus, we show that our entropy measure often converges with network size to a certain binary Shannon entropy. As a second step, with specific attention to networks generated by dynamical processes, we investigate approximate entropy of horizontal visibility graphs. Visibility graphs allow us to naturally associate with a network the notion of temporal correlations, therefore providing the measure a dynamical garment. We show that approximate entropy distinguishes visibility graphs generated by processes with different complexity. The result probes to a greater extent these networks for the study of dynamical systems. Applications to certain biological data arising in cancer genomics are finally considered in the light of both approaches.

  12. The second Born approximation of electron–argon elastic scattering ...

    Indian Academy of Sciences (India)

    We evaluate the S-matrix elements numerically. The dependence of differential cross-section on the relative phase between the two laser components is presented. The results obtained in the first and second Born approximations are compared and analysed. Keywords. Second Born approximation; free–free transition; ...

  13. Bioengineered Temporomandibular Joint Disk Implants: Study Protocol for a Two-Phase Exploratory Randomized Preclinical Pilot Trial in 18 Black Merino Sheep (TEMPOJIMS)

    Science.gov (United States)

    Monje, Florencio Gil; González-García, Raúl; Little, Christopher B; Mónico, Lisete; Pinho, Mário; Santos, Fábio Abade; Carrapiço, Belmira; Gonçalves, Sandra Cavaco; Morouço, Pedro; Alves, Nuno; Moura, Carla; Wang, Yadong; Jeffries, Eric; Gao, Jin; Sousa, Rita; Neto, Lia Lucas; Caldeira, Daniel; Salvado, Francisco

    2017-01-01

    Background Preclinical trials are essential to test efficacious options to substitute the temporomandibular joint (TMJ) disk. The contemporary absence of an ideal treatment for patients with severe TMJ disorders can be related to difficulties concerning the appropriate study design to conduct preclinical trials in the TMJ field. These difficulties can be associated with the use of heterogeneous animal models, the use of the contralateral TMJ as control, the absence of rigorous randomized controlled preclinical trials with blinded outcomes assessors, and difficulties involving multidisciplinary teams. Objective This study aims to develop a new, reproducible, and effective study design for preclinical research in the TMJ domain, obtaining rigorous data related to (1) identify the impact of bilateral discectomy in black Merino sheep, (2) identify the impact of bilateral discopexy in black Merino sheep, and (3) identify the impact of three different bioengineering TMJ discs in black Merino sheep. Methods A two-phase exploratory randomized controlled preclinical trial with blinded outcomes is proposed. In the first phase, nine sheep are randomized into three different surgical bilateral procedures: bilateral discectomy, bilateral discopexy, and sham surgery. In the second phase, nine sheep are randomized to bilaterally test three different TMJ bioengineering disk implants. The primary outcome is the histological gradation of TMJ. Secondary outcomes are imaging changes, absolute masticatory time, ruminant time per cycle, ruminant kinetics, ruminant area, and sheep weight. Results Previous preclinical studies in this field have used the contralateral unoperated side as a control, different animal models ranging from mice to a canine model, with nonrandomized, nonblinded and uncontrolled study designs and limited outcomes measures. The main goal of this exploratory preclinical protocol is to set a new standard for future preclinical trials in oromaxillofacial surgery

  14. Approximation methods in probability theory

    CERN Document Server

    Čekanavičius, Vydas

    2016-01-01

    This book presents a wide range of well-known and less common methods used for estimating the accuracy of probabilistic approximations, including the Esseen type inversion formulas, the Stein method as well as the methods of convolutions and triangle function. Emphasising the correct usage of the methods presented, each step required for the proofs is examined in detail. As a result, this textbook provides valuable tools for proving approximation theorems. While Approximation Methods in Probability Theory will appeal to everyone interested in limit theorems of probability theory, the book is particularly aimed at graduate students who have completed a standard intermediate course in probability theory. Furthermore, experienced researchers wanting to enlarge their toolkit will also find this book useful.

  15. Parenteral nutrition at the palliative phase of advanced cancer: the ALIM-K study protocol for a randomized controlled trial

    OpenAIRE

    Pazart, Lionel; Cretin, Elodie; Grodard, Ghislain; Cornet, Cecile; Mathieu-Nicot, Florence; Bonnetain, Franck; Mercier, Mariette; Cuynet, Patrice; Bouleuc, Carole; Aubry, Regis

    2014-01-01

    Background Malnutrition is a common complication in patients at the palliative stage of cancer. During the curative phase of cancer, optimal enteral or parenteral nutrition intake can reduce morbidity and mortality, and improve quality of life. When the main goal of treatment becomes palliative, introduction of artificial nutrition is controversial. Although scientific societies do not recommend the introduction of artificial nutrition in all cases of malnutrition, especially in hypophagic pa...

  16. Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study.

    Science.gov (United States)

    Guttman-Yassky, Emma; Silverberg, Jonathan I; Nemoto, Osamu; Forman, Seth B; Wilke, August; Prescilla, Randy; de la Peña, Amparo; Nunes, Fabio P; Janes, Jonathan; Gamalo, Margaret; Donley, David; Paik, Jim; DeLozier, Amy M; Nickoloff, Brian J; Simpson, Eric L

    2018-02-01

    Baricitinib, an oral selective inhibitor of Janus kinase (JAK)1 and JAK2, modulates pro-inflammatory cytokine signaling. The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD). In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCS) for 4 weeks before randomization to once daily placebo, baricitinib 2 mg, or baricitinib 4 mg for 16 weeks. Use of TCS was permitted during the study. Primary outcome was the proportion of patients achieving ≥50% reduction in the Eczema Area and Severity Index (EASI-50) compared to placebo. Significantly more baricitinib 4-mg patients achieved EASI-50 compared to placebo (61% vs 37%; P=0.027) at 16 weeks. The proportion of baricitinib 2- and 4-mg patients achieving EASI-50 compared to placebo was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 (49%) placebo, 17 (46%) baricitinib 2-mg, and 27 (71%) baricitinib 4-mg patients. A TCS standardization period prior to randomization reduced disease severity, limiting the ability to compare results to baricitinib monotherapy. Longer studies are required to confirm baricitinib efficacy and safety in AD patients. Baricitinib used with TCS reduced inflammation and pruritus in patients with moderate-to-severe atopic dermatitis (AD). Copyright © 2018. Published by Elsevier Inc.

  17. Cubic anisotropy created by defects of "random local anisotropy" type, and phase diagram of the O( n) Model

    Science.gov (United States)

    Berzin, A. A.; Morosov, A. I.; Sigov, A. S.

    2017-12-01

    The expression for the cubic-type-anisotropy constant created by defects of "random local anisotropy" type is derived. It is shown that the Imry-Ma theorem stating that in space dimensions d equilibrium one. At the defect concentration lower than the critical one the long-range order takes place in the system. For a strongly anisotropic distribution of the easy axes, the Imry-Ma state is suppressed completely and the long-range order state takes place at any defect concentration.

  18. Best Approximation in Numerical Radius

    OpenAIRE

    Aksoy, Asuman Guven; Lewicki, Grzegorz

    2010-01-01

    Let $X$ be a reflexive Banach space. In this paper we give a necessary and sufficient condition for an operator $T\\in \\mathcal{K}(X)$ to have the best approximation in numerical radius from the convex subset $\\mathcal{U} \\subset \\mathcal{K}(X),$ where $\\mathcal{K}(X)$ denotes the set of all linear, compact operators from $X$ into $X.$ We will also present an application to minimal extensions with respect to the numerical radius. In particular some results on best approximation in norm will be...

  19. Face Recognition using Approximate Arithmetic

    DEFF Research Database (Denmark)

    Marso, Karol

    Face recognition is image processing technique which aims to identify human faces and found its use in various different fields for example in security. Throughout the years this field evolved and there are many approaches and many different algorithms which aim to make the face recognition as effective...... processing applications the results do not need to be completely precise and use of the approximate arithmetic can lead to reduction in terms of delay, space and power consumption. In this paper we examine possible use of approximate arithmetic in face recognition using Eigenfaces algorithm....

  20. A randomized, placebo controlled, double masked phase IB study evaluating the safety and antiviral activity of aprepitant, a neurokinin-1 receptor antagonist in HIV-1 infected adults.

    Directory of Open Access Journals (Sweden)

    Pablo Tebas

    Full Text Available BACKGROUND: Neurokinin-1 receptor (NK1R antagonists have anti-HIV activity in monocyte-derived macrophages, decrease CCR5 expression and improve natural killer cell function ex vivo. Aprepitant is a NK1R antagonist approved by FDA as an antiemetic. METHODS: We conducted a phase IB randomized, placebo controlled, double masked study to evaluate the safety, antiviral activity, pharmacokinetics and immune-modulatory effects of aprepitant in HIV-infected adults not receiving antiretroviral therapy, with CD4+ cell count ≥350 cells/mm(3 and plasma viral load ≥2,000 copies/ml. Subjects were stratified by viral load (< vs. ≥20,000 copies/ml and randomized within each stratum to receive aprepitant at 125 mg QD(Low, or 250 mg QD(High, or placebo(PL for 14 days, and followed for 42 days. RESULTS: Thirty subjects were randomized and 27 completed treatment (9, 8, 10 subjects in 125 (Low, 250 (High, and PL groups. 63% were male; 37% white; mean (SD age 43 (9.3 years. Geometric mean baseline viral load (copies/ml for Low, High, and PL was 15,709, 33,013, and 19,450, respectively. Mean (95%CI change in log10 viral load at day 14 for Low, High, and PL was -0.02(-0.24,+0.20, -0.05(-0.21,+0.10, and +0.04(-0.08,+0.16, respectively. The number of subjects with AEs was 4(44.4%, 5(62.5%, and 1(10% for Low, High, and PL. No Grade 4 AEs occurred. CONCLUSIONS: Adverse events of aprepitant were more common in the treated groups. At the dose used in this two-week phase IB study, aprepitant showed biological activity, but no significant antiviral activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00428519.

  1. A Phase 2 Randomized, Double-Blind, Multicenter Trial of Imexon Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy-naïve Pancreatic Adenocarcinoma.

    Science.gov (United States)

    Cohen, Steven J; Zalupski, Mark M; Conkling, Paul; Nugent, Francis; Ma, Wen Wee; Modiano, Manuel; Pascual, Rolan; Lee, Fa Chyi; Wong, Lucas; Hersh, Evan

    2015-12-24

    Imexon is a cyanoaziridine-derived iminopyrrolidone which has synergistic cytotoxicity with gemcitabine. A phase 1 study of the combination demonstrated good tolerance with encouraging clinical activity and thus we conducted this randomized phase II study. Patients with measurable, metastatic, treatment-naive pancreatic adenocarcinoma were randomized 1:1 to receive gemcitabine at 1000 mg/m days 1, 8, and 15 with either imexon, 875 mg/m or placebo days 1, 8, and 15 every 28 days. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and response rate. A total of 142 patients were randomized, 72 to the imexon containing arm and 70 to the placebo arm. Patients in the imexon arm received an average of 3.6 cycles (range, 1 to 23) compared with 4.4 (range, 1 to 21) in the placebo arm. There was no increased rate of ≥grade 3 toxicity in the imexon arm. Seven patients had objective responses in the imexon arm (13.7%), whereas 9 did in the placebo arm (17%). In the imexon arm, 23 patients had ≥50% reduction in CA 19-9 from baseline (33%), whereas 22 did in the placebo arm (31.4%). The median progression-free survival was 2.8 months in the imexon arm (95% confidence interval [CI], 2.0-4.1 m) and 3.8 months in the placebo arm (95% CI, 2.2-4.7 m), P=0.504. The median overall survival time in the imexon arm was 5.2 months (95% CI, 4.2-6.7 m) as compared with 6.8 m (95% CI, 4.9-8.5 m) in the placebo arm, P=0.6822. The combination of imexon and gemcitabine does not result in improved outcome as initial therapy of metastatic pancreatic adenocarcinoma.

  2. A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Wun Ted

    2013-02-01

    Full Text Available Abstract Background Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study. Methods The primary endpoint, safety, was measured by hemorrhagic events requiring medical intervention. Patients were randomized to prasugrel 5 mg daily (n = 41 or placebo (n = 21 for 30 days. Platelet function by VerifyNow® P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients. Results There were no hemorrhagic events requiring medical intervention in either study arm. Mean pain rate (percentage of days with pain and intensity in the prasugrel arm were decreased compared with placebo. However, these decreases did not reach statistical significance. Platelet surface P-selectin and plasma soluble P-selectin, biomarkers of in vivo platelet activation, were significantly reduced in SCD patients receiving prasugrel compared with placebo. In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events. Conclusions Despite the small size and short duration of this study, there was a decrease in platelet activation biomarkers and a trend toward decreased pain.

  3. A Phase II Randomized, Double-Blind, Placebo-Controlled Safety and Efficacy Study of Lenalidomide in Lumbar Radicular Pain with a Long-Term Open-Label Extension Phase.

    Science.gov (United States)

    Manning, Donald C; Gimbel, Joseph; Wertz, Robert; Rauck, Richard; Cooper, Alyse; Zeldis, Jerome B; Levinsky, Dale M

    2017-03-01

    This phase II study assessed lenalidomide efficacy and safety. Three-phase core study: 14-day prerandomization, 12-week treatment, and 52-week open-label extension. Fourteen US centers from July 2005 to July 2007. Chronic lumbar radicular pain patients without history of nerve injury or deficit. Subjects were randomized (1:1) to double-blind treatment with lenalidomide 10 mg or placebo once daily for 12 weeks, followed by a 52-week open-label extension. A 12-week, single-center, randomized-withdrawal (1:2, lenalidomide:placebo), exploratory study with open-label extension was undertaken in 12 subjects from the core extension who were naïve to neuropathic medications and with at least a two-point decrease from baseline average daily Pain Intensity-Numerical Rating Scale score. Of 180 subjects enrolled, 176 had at least one postbaseline measure; 132 completed the 12-week treatment phase. In the core study, no statistically significant difference in Pain Intensity-Numerical Rating Scale mean change (-0.02, P  =   0.958) was observed at week 12 between lenalidomide and placebo; proportions achieving pain reduction at week 12 and other secondary measures were comparable between lenalidomide and placebo. In the exploratory study, week 12 mean changes in Pain Intensity-Numerical Rating Scale scores were -0.05 (lenalidomide: N = 3) and 2.11 (placebo: N = 8). Mean changes in Brief Pain Inventory-short form interference scores were -3.33 and 8.38, respectively; scores at six months were maintained or decreased in 10 of 12 subjects. While this study does not support lenalidomide use in an unselected lumbar radicular pain population, an immunomodulating agent may relieve pain in select subjects naïve to neuropathic pain medications. ClinicalTrials.gov identifier: NCT00120120.

  4. Approximate Reanalysis in Topology Optimization

    DEFF Research Database (Denmark)

    Amir, Oded; Bendsøe, Martin P.; Sigmund, Ole

    2009-01-01

    In the nested approach to structural optimization, most of the computational effort is invested in the solution of the finite element analysis equations. In this study, the integration of an approximate reanalysis procedure into the framework of topology optimization of continuum structures...

  5. Ultrafast Approximation for Phylogenetic Bootstrap

    NARCIS (Netherlands)

    Bui Quang Minh, [No Value; Nguyen, Thi; von Haeseler, Arndt

    Nonparametric bootstrap has been a widely used tool in phylogenetic analysis to assess the clade support of phylogenetic trees. However, with the rapidly growing amount of data, this task remains a computational bottleneck. Recently, approximation methods such as the RAxML rapid bootstrap (RBS) and

  6. Approximation properties of haplotype tagging

    Directory of Open Access Journals (Sweden)

    Dreiseitl Stephan

    2006-01-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are locations at which the genomic sequences of population members differ. Since these differences are known to follow patterns, disease association studies are facilitated by identifying SNPs that allow the unique identification of such patterns. This process, known as haplotype tagging, is formulated as a combinatorial optimization problem and analyzed in terms of complexity and approximation properties. Results It is shown that the tagging problem is NP-hard but approximable within 1 + ln((n2 - n/2 for n haplotypes but not approximable within (1 - ε ln(n/2 for any ε > 0 unless NP ⊂ DTIME(nlog log n. A simple, very easily implementable algorithm that exhibits the above upper bound on solution quality is presented. This algorithm has running time O((2m - p + 1 ≤ O(m(n2 - n/2 where p ≤ min(n, m for n haplotypes of size m. As we show that the approximation bound is asymptotically tight, the algorithm presented is optimal with respect to this asymptotic bound. Conclusion The haplotype tagging problem is hard, but approachable with a fast, practical, and surprisingly simple algorithm that cannot be significantly improved upon on a single processor machine. Hence, significant improvement in computatational efforts expended can only be expected if the computational effort is distributed and done in parallel.

  7. APPROXIMATE MODELS FOR FLOOD ROUTING

    African Journals Online (AJOL)

    kinematic model and a nonlinear convection-diffusion model are extracted from a normalized form of the St. Venant equations, and applied to ... normal flow condition is moderate. Keywords: approximate models, nonlinear kinematic ... The concern here is with the movement of an abnormal amount of water along a river or ...

  8. Approximation for Bayesian Ability Estimation.

    Science.gov (United States)

    1987-02-18

    two-way contingency tables. Journal of Educational Statistics, 11, 33-56. Lindley, D.V. (1980). Approximate Bayesian methods. Trabajos Estadistica , 31...Sloan-Kettering Cancer Center 1275 York Avenue New York, NY 10021 Dr. Wallace Wulfeck, 11 Navy Personnel R&D Center San Diego, CA 92152-6800 Dr. Wendy

  9. Ranking Support Vector Machine with Kernel Approximation.

    Science.gov (United States)

    Chen, Kai; Li, Rongchun; Dou, Yong; Liang, Zhengfa; Lv, Qi

    2017-01-01

    Learning to rank algorithm has become important in recent years due to its successful application in information retrieval, recommender system, and computational biology, and so forth. Ranking support vector machine (RankSVM) is one of the state-of-art ranking models and has been favorably used. Nonlinear RankSVM (RankSVM with nonlinear kernels) can give higher accuracy than linear RankSVM (RankSVM with a linear kernel) for complex nonlinear ranking problem. However, the learning methods for nonlinear RankSVM are still time-consuming because of the calculation of kernel matrix. In this paper, we propose a fast ranking algorithm based on kernel approximation to avoid computing the kernel matrix. We explore two types of kernel approximation methods, namely, the Nyström method and random Fourier features. Primal truncated Newton method is used to optimize the pairwise L2-loss (squared Hinge-loss) objective function of the ranking model after the nonlinear kernel approximation. Experimental results demonstrate that our proposed method gets a much faster training speed than kernel RankSVM and achieves comparable or better performance over state-of-the-art ranking algorithms.

  10. Treatment efficacy of sacral nerve stimulation in slow transit constipation: a two-phase, double-blind randomized controlled crossover study.

    Science.gov (United States)

    Dinning, Phil G; Hunt, Linda; Patton, Vicki; Zhang, Teng; Szczesniak, Michal; Gebski, Val; Jones, Mike; Stewart, Peter; Lubowski, David Z; Cook, Ian J

    2015-05-01

    Sacral nerve stimulation (SNS) is a potential treatment for constipation refractory to standard therapies. However, there have been no randomized controlled studies examining its efficacy. In patients with slow transit constipation, we evaluated the efficacy of suprasensory and subsensory SNS compared with sham, in a prospective, 18-week randomized, double-blind, placebo-controlled, two-phase crossover study. The primary outcome measure was the proportion of patients who, on more than 2 days/week for at least 2 of 3 weeks, reported a bowel movement associated with a feeling of complete evacuation. After 3 weeks of temporary peripheral nerve evaluation (PNE), all patients had permanent implantation and were randomized to subsensory/sham (3 weeks each) and then re-randomized to suprasensory/sham (3 weeks each) with a 2-week washout period between each arm. Daily stool dairies were kept, and quality of life (QoL; SF36) was measured at the end of each arm. Between November 2006 and March 2012, 234 constipated patients were assessed, of whom 59 were willing and deemed eligible to participate (4 male; median age 42 years). Of the 59 patients, 16 (28%) responded to PNE. Fifty-five patients went on to permanent SNS implantation. The proportion of patients satisfying the primary outcome measure did not differ between suprasensory (30%) and sham (21%) stimulations, nor between subsensory (25%) and sham (25%) stimulations. There were no significant changes in QoL scores. In patients with refractory slow transit constipation, SNS did not improve the frequency of complete bowel movements over the 3-week active period.

  11. Comparison of antiplatelet effect and safety of clopidogrel napadisilate with clopidogrel bisulfate in stroke patients: multicenter, randomized, open-label, phase 4, non-inferiority clinical trial.

    Science.gov (United States)

    Kang, Kyusik; Lee, Se-Jin; Kim, Hee-Jin; Koh, Seong-Ho; Kim, Byung Kun

    2016-01-01

    Clopidogrel napadisilate has better chemical stability than clopidogrel bisulfate. Our trial's objective was to compare the efficacy and safety of clopidogrel napadisilate with clopidogrel bisulfate in participants with ischemic stroke. The study was a phase 4, 4 week, randomized, parallel-group, non-inferiority trial. Patients with ischemic stroke were randomized to receive either clopidogrel napadisilate 75 mg or clopidogrel bisulfate 75 mg. The primary study endpoint was change from baseline in P2Y12 percentage inhibition at week 4. The primary analysis was conducted in the per-protocol population. Non-inferiority was confirmed if the lower limit of the 95% confidence interval (CI) of the treatment difference was greater than or equal to -9.0% points. Sixty-one participants were randomly assigned clopidogrel napadisilate and 60 were randomly assigned clopidogrel bisulfate. Thirty-nine participants in the clopidogrel napadisilate group and 39 in the clopidogrel bisulfate group were analyzed for the primary endpoint. At 4 weeks, mean P2Y12 percentage inhibition had increased in both treatment groups. The estimated mean change from baseline was 22.3% with clopidogrel napadisilate and 21.4% with clopidogrel bisulfate; the estimated treatment difference of 0.9% (95% CI, -8.6 to 10.4) confirmed the non-inferiority of clopidogrel napadisilate to clopidogrel bisulfate. Clopidogrel napadisilate was non-inferior to clopidogrel bisulfate as assessed by change in P2Y12 percentage inhibition. Rates of adverse events were similar between the two groups. Therefore, clopidogrel napadisilate is a useful alternative option for the dosing of ischemic stroke patient populations.

  12. Hepatic and vascular enhancement at dual-phase helical CT: comparison of Iobitridol 300 and Iohexol 300 in a prospective randomized study

    Energy Technology Data Exchange (ETDEWEB)

    Legmann, P.; Vignaux, O.; Bahurel, H.; Oudjit, A. [Dept. of Radiology, Universite Rene Descartes, Paris (France); Coste, J. [Dept. of Biostatistics and Epidemiology, Universite Rene Descartes, Paris (France)

    2001-11-01

    The purpose of this study was to determine hepatic and vascular enhancement, clinical tolerance, and iconographic quality of Iobitridol (300 mg/ml) at dual-phase helical CT and to compare it with Iohexol (300 mg/ml). One hundred forty-six patients were randomly divided into two groups. Each group received 120 ml of Iohexol (group A) or Iobitridol (group B). Mean enhancement of liver, aorta and portal vein was obtained at the arterial phase and at the portal-venous phase. Overall image quality was assessed by two independent blinded investigators. Adverse reactions were recorded. There were no significant differences in demographic characteristics and distribution of patient intrinsic parameters between the two groups, except for blood pressure but without statistical correlation between the difference in blood pressure and the impact on enhancement measurements. There was no significant difference in clinical tolerance and image quality. Mean liver as well as aortic and portal vein enhancement measurements did not show any significant difference. Iobitridol compares favorably with Iohexol. Both products have similar safety, tolerance, and efficacy. Both contrast media have equivalent blood pool concentration and interstitial compartment diffusion. (orig.)

  13. Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel.

    Science.gov (United States)

    Hoskins, P; Vergote, I; Cervantes, A; Tu, D; Stuart, G; Zola, P; Poveda, A; Provencher, D; Katsaros, D; Ojeda, B; Ghatage, P; Grimshaw, R; Casado, A; Elit, L; Mendiola, C; Sugimoto, A; D'Hondt, V; Oza, A; Germa, J R; Roy, M; Brotto, L; Chen, D; Eisenhauer, E A

    2010-10-20

    Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy. Women aged 75 years or younger with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1-5, then four cycles of paclitaxel 175 mg/m(2) over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided. A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28-78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007) Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and

  14. Ocular comfort assessment of lifitegrast ophthalmic solution 5.0% in OPUS-3, a Phase III randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Nichols KK

    2018-01-01

    Full Text Available Kelly K Nichols,1 Edward Holland,2 Melissa M Toyos,3 James H Peace,4 Parag Majmudar,5 Aparna Raychaudhuri,6 Mohamed Hamdani,6 Monica Roy,6 Amir Shojaei6 1School of Optometry, University of Alabama at Birmingham, Birmingham, AL, 2Cincinnati Eye Institute, Edgewood, KY, 3Toyos Clinic, Nashville, TN, 4United Medical Research Institute, Inglewood, CA, 5Chicago Cornea Consultants, Ltd., Hoffman Estates, IL, 6Shire, Lexington, MA, USA Purpose: To evaluate ocular comfort of lifitegrast ophthalmic solution 5.0% among patients with dry eye disease (DED in the OPUS-3 trial. Methods: OPUS-3 was a multicenter, randomized, double-masked, placebo-controlled study. Adults with DED and recent artificial tear use were randomized 1:1 (lifitegrast:placebo to ophthalmic drops twice daily for 84 days. On days 0 (baseline, 14, 42, and 84, drop comfort score (scale, 0–10; 0 = very comfortable, 10 = very uncomfortable was measured at 0, 1, 2, and 3 minutes postinstillation. If the score was >3 at 3 minutes, assessment was repeated at 5, 10, and 15 minutes until score ≤3. Ocular treatment-emergent adverse events (TEAEs were assessed. Results: Overall, 711 participants were randomized (n=357 received lifitegrast; n=354 received placebo. Drop comfort scores for lifitegrast-treated participants improved within 3 minutes of instillation (mean scores on day 84 for both study and fellow eyes: instillation: lifitegrast, 3.4, placebo, 1.0; 3 minutes: lifitegrast, 1.5, placebo, 0.7. The majority (64%–66% of participants had scores <3 within 3 minutes postinstillation on days 14, 42, and 84. In participants with scores >3 at 3 minutes, the mean score in the lifitegrast group was similar to or better than that in the placebo group at 5, 10, or 15 minutes postinstillation. Lifitegrast appeared to be well tolerated, with ocular TEAEs rarely leading to discontinuation. Conclusion: In OPUS-3, lifitegrast appeared to be well tolerated and drop comfort scores approached placebo

  15. Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial†

    Science.gov (United States)

    Skorupski, K. A.; Uhl, J. M.; Szivek, A; Allstadt Frazier, S. D.; Rebhun, R. B.; Rodriguez, C. O.

    2016-01-01

    Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. PMID:24118677

  16. Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial.

    Science.gov (United States)

    Skorupski, K A; Uhl, J M; Szivek, A; Allstadt Frazier, S D; Rebhun, R B; Rodriguez, C O

    2016-03-01

    Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. © 2013 John Wiley & Sons Ltd.

  17. A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children

    DEFF Research Database (Denmark)

    Sirima, Sodiomon B; Mordmüller, Benjamin; Milligan, Paul

    2016-01-01

    randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. RESULTS: A cohort of 1849...... in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). CONCLUSIONS: GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially...

  18. Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial

    DEFF Research Database (Denmark)

    Bernsdorf, M.; Ingvar, C.; Jorgensen, L.

    2011-01-01

    a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups...... was pathologic complete response (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI -7....... A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment. More patients in the gefitinib group discontinued treatment because of AE....

  19. Topical Minocycline Foam for the Treatment of Impetigo in Children: Results of a Randomized, Double-Blind, Phase 2 Study.

    Science.gov (United States)

    Chamny, Shlomo; Miron, Dan; Lumelsky, Nadia; Shalev, Hana; Gazal, Elana; Keynan, Rita; Shemer, Avner; Tamarkin, Dov

    2016-10-01

    Currently available treatment options for impetigo are limited by either systemic side effects (for oral therapy) or lack of ease of use (for topical ointment). A novel foam formulation of minocycline for topical use may improve convenience and treatment utilization for pediatric patients with impetigo. To evaluate the safety and efficacy of topically applied minocycline foam (FMX-102 1% and 4%) in the treatment of impetigo and to determine the optimal therapeutic active ingredient concentration. In this randomized, parallel-group, double-blind, comparative clinical trial, 32 subjects aged ≥2 years with a clinical diagnosis of pure impetigo, impetigo contagiosa, or uncomplicated blistering impetigo were randomized to treatment with FMX-102 1% or 4%, twice daily for 7 days. Subjects were followed for up to 7 days post-treatment. Clinical cure, defined as ≥80% cured lesions (fully recovered lesions, visually determined by investigators), was achieved by 57.1% and 50.0% of FMX-102 1% and 4% subjects, respectively, at the end of treatment (visit 3). Clinical success, defined as the absence of lesions, or the drying or improvement of treated lesions (decrease in size of affected area, lesion number, or both), was demonstrated in 81.3% and 78.6% of FMX-102 1% and 4% subjects, respectively, following 3 days of treatment (visit 2), in 92.3% and 100% of the respective subjects at the end of treatment, and in 100% in both groups at follow-up (visit 4). Bacteriologic success rates at the end of treatment, defined as complete pathogen eradication, were 85% and 74% in the FMX-102 1% and 4% groups, respectively. The bacteriologic success rate for MRSA infections was 100% (11/11), with no recurrences. Both FMX-102 1% and 4% were considered well tolerated and safe. Topical minocycline foam may be a safe and effective new treatment option for impetigo in children, including those with MRSA. J Drugs Dermatol. 2016;15(10):1238-1243.

  20. A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children.

    Science.gov (United States)

    Sirima, Sodiomon B; Mordmüller, Benjamin; Milligan, Paul; Ngoa, Ulysse Ateba; Kironde, Fred; Atuguba, Frank; Tiono, Alfred B; Issifou, Saadou; Kaddumukasa, Mark; Bangre, Oscar; Flach, Clare; Christiansen, Michael; Bang, Peter; Chilengi, Roma; Jepsen, Søren; Kremsner, Peter G; Theisen, Michael

    2016-08-31

    GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Randomized phase III trial of postoperative radiochemotherapy {+-} amifostine in head and neck cancer. Is there evidence for radioprotection?

    Energy Technology Data Exchange (ETDEWEB)

    Vacha, P.; Fehlauer, F.; Mahlmann, B.; Marx, M.; Richter, E. [Dept. of Radiation Oncology and Nuclear Medicine, Univ. of Luebeck (Germany); Hinke, A. [WiSP Research Inst., Langenfeld (Germany); Sommer, K. [Dept. of Head and Neck Surgery, Univ. of Luebeck (Germany); Feyerabend, T. [Practice for Radiation Therapy Bonn-Rhein-Sieg, Bonn (Germany)

    2003-06-01

    Purpose: Experimental and clincial data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer. Patients and Methods: 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to received RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m{sup 2} carboplatin, day 1-5 week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the common toxicity criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation. Results: 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis. Conclusions: According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary. (orig.)

  2. Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial.

    Science.gov (United States)

    Grosso, Federica; Steele, Nicola; Novello, Silvia; Nowak, Anna K; Popat, Sanjay; Greillier, Laurent; John, Thomas; Leighl, Natasha B; Reck, Martin; Taylor, Paul; Planchard, David; Sørensen, Jens Benn; Socinski, Mark A; von Wangenheim, Ute; Loembé, Arsène Bienvenu; Barrueco, José; Morsli, Nassim; Scagliotti, Giorgio

    2017-11-01

    Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib (200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression. The primary end point was progression-free survival (PFS). Results Eighty-seven patients were randomly assigned. The median number of pemetrexed and cisplatin cycles was six; the median treatment duration for nintedanib was 7.8 months and 5.3 months for placebo. Primary PFS favored nintedanib (hazard ratio [HR], 0.56; 95% CI, 0.34 to 0.91; P = .017), which was confirmed in updated PFS analyses (HR, 0.54; 95% CI, 0.33 to 0.87; P = .010). A trend toward improved overall survival also favored nintedanib (HR, 0.77; 95% CI, 0.46 to 1.29; P = .319). Benefit was evident in epithelioid histology, with a median overall survival gain of 5.4 months (HR, 0.70; 95% CI, 0.40 to 1.21; P = .197; median [nintedanib v placebo], 20.6 months v 15.2 months) and median PFS gain of 4.0 months (HR, 0.49; 95% CI, 0.30 to 0.82; P = .006; median [nintedanib v placebo], 9.7 v 5.7 months). Neutropenia was the most frequent grade ≥ 3 adverse event (AE; nintedanib 43.2% v placebo 12.2%); rates of febrile neutropenia were low (4.5% in nintedanib group v 0% in placebo group). AEs leading to discontinuation were reported in 6.8% of those receiving nintedanib versus 17.1% of those in the placebo group. Conclusion Addition of nintedanib to pemetrexed plus cisplatin resulted in PFS improvement. AEs were manageable. The clinical benefit was evident in patients with

  3. Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study

    Directory of Open Access Journals (Sweden)

    Moehler Markus

    2011-08-01

    Full Text Available Abstract Background Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neoadjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC has been designed to explore the efficacy of neoadjuvant chemotherapy. Methods/Design This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m2 for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m2, oxaliplatin 100 mg/m2 followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked

  4. Enhancing evidence-based diabetes and chronic disease control among local health departments: a multi-phase dissemination study with a stepped-wedge cluster randomized trial component.

    Science.gov (United States)

    Parks, Renee G; Tabak, Rachel G; Allen, Peg; Baker, Elizabeth A; Stamatakis, Katherine A; Poehler, Allison R; Yan, Yan; Chin, Marshall H; Harris, Jenine K; Dobbins, Maureen; Brownson, Ross C

    2017-10-18

    The rates of diabetes and prediabetes in the USA are growing, significantly impacting the quality and length of life of those diagnosed and financially burdening society. Premature death and disability can be prevented through implementation of evidence-based programs and policies (EBPPs). Local health departments (LHDs) are uniquely positioned to implement diabetes control EBPPs because of their knowledge of, and focus on, community-level needs, contexts, and resources. There is a significant gap, however, between known diabetes control EBPPs and actual diabetes control activities conducted by LHDs. The purpose of this study is to determine how best to support the use of evidence-based public health for diabetes (and related chronic diseases) control among local-level public health practitioners. This paper describes the methods for a two-phase study with a stepped-wedge cluster randomized trial that will evaluate dissemination strategies to increase the uptake of public health knowledge and EBPPs for diabetes control among LHDs. Phase 1 includes development of measures to assess practitioner views on and organizational supports for evidence-based public health, data collection using a national online survey of LHD chronic disease practitioners, and a needs assessment of factors influencing the uptake of diabetes control EBPPs among LHDs within one state in the USA. Phase 2 involves conducting a stepped-wedge cluster randomized trial to assess effectiveness of dissemination strategies with local-level practitioners at LHDs to enhance capacity and organizational support for evidence-based diabetes prevention and control. Twelve LHDs will be selected and randomly assigned to one of the three groups that cross over from usual practice to receive the intervention (dissemination) strategies at 8-month intervals; the intervention duration for groups ranges from 8 to 24 months. Intervention (dissemination) strategies may include multi-day in-person workshops, electronic

  5. Neuropsychiatric safety with liraglutide 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials.

    Science.gov (United States)

    O'Neil, Patrick M; Aroda, Vanita R; Astrup, Arne; Kushner, Robert; Lau, David C W; Wadden, Thomas A; Brett, Jason; Cancino, Ana-Paula; Wilding, John P H

    2017-11-01

    Liraglutide, a GLP-1 receptor agonist, regulates appetite via receptors in the brain. Because of concerns regarding the potential of centrally-acting anti-obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double-blind trials with liraglutide 3.0 mg were evaluated post hoc. Data from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 or ≥27 kg/m 2 with weight-related comorbidities were randomized to once-daily subcutaneous liraglutide 3.0 mg (n = 3384) or placebo (n = 1941), both with a 500 kcal/d deficit diet, plus exercise. Adverse events related to neuropsychiatric safety were collected in all trials. Additionally, in the phase 3a trials, validated mental-health questionnaires were prospectively and systematically administered. In the pooled analysis of 5325 randomized and exposed individuals, rates of depression (2.1 vs 2.1 events/100 person-years) and anxiety (1.9 vs 1.7 events/100 person-years) through adverse event reporting were similarly low in liraglutide and placebo groups. Nine (0.3%) individuals receiving liraglutide and 2 (0.1%) receiving placebo reported adverse events of suicidal ideation or behaviour. In phase 3a trials, mean baseline Patient Health Questionnaire-9 scores of 2.8 ± 3.0 vs 2.9 ± 3.1 for liraglutide vs placebo improved to 1.8 ± 2.7 vs 1.9 ± 2.7, respectively, at treatment end; 34/3291 individuals (1.0%) receiving liraglutide 3.0 mg vs 19/1843 (1.0%) receiving placebo reported suicidal ideation on the Columbia-Suicide Severity Rating Scale. Results of this exploratory pooled analysis provide no cause for concern regarding the neuropsychiatric safety of treatment with liraglutide 3.0 mg in patients similar to those included in the examined trials. Although there was a small numerical imbalance in suicidal ideation with liraglutide through adverse event reporting, no

  6. Temperature dependence of the surface plasmon resonance in small electron gas fragments, self consistent field approximation

    Science.gov (United States)

    Fasolato, C.; Sacchetti, F.; Tozzi, P.; Petrillo, C.

    2017-07-01

    The temperature dependence of the surface plasmon resonance in small metal spheres is calculated using an electron gas model within the Random Phase Approximation. The calculation is mainly devoted to the study of spheres with diameters up to at least 10 nm, where quantum effects can still be relevant and a simple plasmon pole approximation for the dielectric function is no more appropriate. We find a possible blue shift of the plasmon resonance position when the temperature is increased while keeping the size of the sphere fixed. The blue shift is appreciable only when the temperature is a large fraction of the Fermi energy. These results provide a guide for pump and probe experiments with a high time resolution, tailored to study the excited electron system before thermalisation with the lattice takes place.

  7. Hydrogen Beyond the Classic Approximation

    CERN Document Server

    Scivetti, I

    2003-01-01

    The classical nucleus approximation is the most frequently used approach for the resolution of problems in condensed matter physics.However, there are systems in nature where it is necessary to introduce the nuclear degrees of freedom to obtain a correct description of the properties.Examples of this, are the systems with containing hydrogen.In this work, we have studied the resolution of the quantum nuclear problem for the particular case of the water molecule.The Hartree approximation has been used, i.e. we have considered that the nuclei are distinguishable particles.In addition, we have proposed a model to solve the tunneling process, which involves the resolution of the nuclear problem for configurations of the system away from its equilibrium position

  8. Improving access to preparatory information for children undergoing general anaesthesia for tooth extraction and their families: study protocol for a Phase III randomized controlled trial.

    Science.gov (United States)

    Hosey, Marie Therese; Donaldson, Ana Nora; Huntington, Corinne; Liossi, Christina; Reynolds, Patricia A; Alharatani, Reham; Newton, J Timothy

    2014-06-11

    Children can find anaesthesia induction especially distressing and postoperative psychological and physical morbidity are common. Preparation programmes for general anaesthesia (GA) are highly effective in reducing this distress. A Phase II study has already verified the effectiveness of a prototype preoperative GA-coping computer game to help children cope with induction in a dental GA setting. The biggest patient users of pediatric GA services in the UK are children who need to have teeth removed (estimated to be 100,000 yearly). Tooth decay is the most common disease in children worldwide. This study is a Phase III randomized controlled trial (RCT) and will evaluate the effectiveness of the new internet version of this game. The Phase III RCT will use a double-blind three-armed design. The clinical trial will recruit up to 210 children and will compare the web-based game against standard care and another non-medical game. At least 53 patients in each group will be required for 90% statistical power. Distress will be assessed through an evaluation of the child's behaviour during the visit and later parental reports of physical and psychological morbidity. The satisfaction of parents and children will be measured; the mode of usage of the web-based game will be automatically recorded and the impact on the service (for example, recovery time and throughput) will be reported.The Phase III study primary outcome will measure: (1) patient experience: acceptance of anaesthetic induction, child cooperation and distress, reduction of peri- and postoperative morbidity, child and family satisfaction, and (2) service improvement: anaesthetic time and improvement in throughput. Measures will be administered at baseline, at the time of the GA treatment visit, and at 48 hours and one week postoperatively. This study aims to determine the effectiveness of an online GA-coping game for children and families undergoing tooth extraction under GA. ISRCTN18265148 (registered 24

  9. A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study.

    Directory of Open Access Journals (Sweden)

    Ian Mcgowan

    Full Text Available The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK, and pharmacodynamics (PD of three tenofovir (TFV gels for rectal application. The vaginal formulation (VF gel was previously used in the CAPRISA 004 and VOICE vaginal microbicide Phase 2B trials and the RMP-02/MTN-006 Phase 1 rectal safety study. The reduced glycerin VF (RGVF gel was used in the MTN-007 Phase 1 rectal microbicide trial and is currently being evaluated in the MTN-017 Phase 2 rectal microbicide trial. A third rectal specific formulation (RF gel was also evaluated in the CHARM-01 study.Participants received 4 mL of the three TFV gels in a blinded, crossover design: seven daily doses of RGVF, seven daily doses of RF, and six daily doses of placebo followed by one dose of VF, in a randomized sequence. Safety, acceptability, compartmental PK, and explant PD were monitored throughout the trial.All three gels were found to be safe and acceptable. RF and RGVF PK were not significantly different. Median mucosal mononuclear cell (MMC TFV-DP trended toward higher values for RF compared to RGVF (1136 and 320 fmol/106 cells respectively. Use of each gel in vivo was associated with significant inhibition of ex vivo colorectal tissue HIV infection. There was also a significant negative correlation between the tissue levels of TFV, tissue TFV-DP, MMC TFV-DP, rectal fluid TFV, and explant HIV-1 infection.All three formulations were found to be safe and acceptable. However, the safety profile of the VF gel was only based on exposure to one dose whereas participants received seven doses of the RGVF and RF gels. There was a trend towards higher tissue MMC levels of TFV-DP associated with use of the RF gel. Use of all gels was associated with significant inhibition of ex vivo tissue HIV infection.ClinicalTrials.gov NCT01575405.

  10. Good points for diophantine approximation

    Indian Academy of Sciences (India)

    Given a sequence ( x n ) n = 1 ∞ of real numbers in the interval [0,1) and a sequence ( n ) n = 1 ∞ of positive numbers tending to zero, we consider the size of the set of numbers in [0,1] which can be `well approximated' by terms of the first sequence, namely, those y ∈ [ 0 , 1 ] for which the inequality | y − x n | < n holds ...

  11. Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

    Directory of Open Access Journals (Sweden)

    Maneeton Narong

    2012-09-01

    Full Text Available Abstract Background Schizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect. Objectives This meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD. Only the randomized controlled trials (RCTs comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012. Data sources MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression. Study eligible criteria, participants and interventions Eligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i depression severity, ii response rate, iii overall discontinuation rate, or iv discontinuation rate due to adverse events. No language restriction was applied. Study appraisal and synthesis methods All abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs and weighted mean differences (WMDs with 95% confidence intervals (CIs were computed by using a random effect model. Results A total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR. The pooled mean change scores of the Montgomery-Asberg Depression

  12. Assessment of quality of life in advanced, metastatic prostate cancer: an overview of randomized phase III trials.

    Science.gov (United States)

    Adamowicz, Krzysztof

    2017-04-01

    The chief therapeutic goal in metastatic prostate cancer is prolongation of survival with good quality of life . Quality of life (health-related) is often used as an endpoint parameter in phase III trials in metastatic prostate cancer, but the value of using HRQOL in this context has not been assessed to date. In order to evaluate the role of HRQOL assessment in contemporary phase III trials in prostate cancer, we searched the PubMed database to identify publications presenting the results of these trials on systemic therapies for prostate cancer published between January 2000 and December 2015. The analysis was separately presented in ten leading journals. We searched for companion papers reporting on QOL separately. We identified 84 studies which included a total of 57,193 patients in ten leading journals and 27 studies (7270 patients) in other journals. HRQOL parameters were described or mentioned in the main publication in 25 publications and four companions in total. There was no obvious trend in quality of life reported over two 8-year periods . The explicit statistical comparisons were reported in 22/25 cases (88 %), with significant difference in only 10/25 (40 %) studies and in eight cases (80 %) was conducive to the examined arm. There was no significant association between improvements in HRQOL and improvements in overall survival (OS) or any other primary endpoint in the analyzed studies. Only one study was found which presented the difference in quality of life with no difference in the primary endpoint. HRQOL is an indicator of benefit during treatment of patients with metastatic prostate cancer, but it is unlikely that HRQOL results can help clinicians choose between treatments given that they are not correlated with changes in OS or at other primary endpoints.

  13. Many Faces of Boussinesq Approximations

    CERN Document Server

    Vladimirov, Vladimir A

    2016-01-01

    The \\emph{equations of Boussinesq approximation} (EBA) for an incompressible and inhomogeneous in density fluid are analyzed from a viewpoint of the asymptotic theory. A systematic scaling shows that there is an infinite number of related asymptotic models. We have divided them into three classes: `poor', `reasonable' and `good' Boussinesq approximations. Each model can be characterized by two parameters $q$ and $k$, where $q =1, 2, 3, \\dots$ and $k=0, \\pm 1, \\pm 2,\\dots$. Parameter $q$ is related to the `quality' of approximation, while $k$ gives us an infinite set of possible scales of velocity, time, viscosity, \\emph{etc.} Increasing $q$ improves the quality of a model, but narrows the limits of its applicability. Parameter $k$ allows us to vary the scales of time, velocity and viscosity and gives us the possibility to consider any initial and boundary conditions. In general, we discover and classify a rich variety of possibilities and restrictions, which are hidden behind the routine use of the Boussinesq...

  14. Response to duloxetine in chronic low back pain: exploratory post hoc analysis of a Japanese Phase III randomized study

    Directory of Open Access Journals (Sweden)

    Tsuji T

    2017-09-01

    Full Text Available Toshinaga Tsuji,1 Naohiro Itoh,1 Mitsuhiro Ishida,2 Toshimitsu Ochiai,3 Shinichi Konno4 1Medical Affairs Department, 2Clinical Research Development, 3Biostatistics Department, Shionogi & Co. Ltd, Osaka, 4Department of Orthopedic Surgery, Fukushima Medical University, Fukushima, Japan Purpose: Duloxetine is efficacious for chronic low back pain (CLBP. This post hoc analysis of a Japanese randomized, placebo-controlled trial (ClinicalTrials.gov, NCT01855919 assessed whether patients with CLBP with early pain reduction or treatment-related adverse events of special interest (TR-AESIs; nausea, somnolence, constipation have enhanced responses to duloxetine. Patients and methods: Patients (N = 456 with CLBP for ≥6 months and Brief Pain Inventory (BPI average pain severity score of ≥4 were randomized (1:1 to duloxetine 60 mg/day or placebo for 14 weeks. Primary outcome was change from baseline in BPI average pain severity score (pain reduction. Subgroup analyses included early pain reduction (≥30%, 10%–30%, or <10% at Week 4 and early TR-AESIs (with or without TR-AESIs by Week 2. Measures included changes from baseline in BPI average pain severity score and BPI Interference scores (quality of life; QOL, and response rate (≥30% or ≥50% pain reduction at Week 14. Results: Patients with ≥30% early pain reduction (n = 108 or early TR-AESIs (n = 50 had significantly greater improvements in pain and QOL than placebo-treated patients (n = 226, whereas patients with 10%–30% (n = 63 or <10% (n = 48 pain reduction did not; patients without early TR-AESIs (n = 180 had significant improvements in pain at Week 14. Response rates (≥30%/≥50% pain reduction were 94.4%/82.4%, 66.7%/49.2%, and 25.0%/18.8% for patients with ≥30%, 10%–30%, and <10% early pain reduction, respectively, 74.0%/64.0% for patients with early TR-AESIs, 67.2%/54.4% for patients without early TR-AESIs, and 52.2%/39.4% for placebo.Conclusion: Early pain reduction or TR

  15. Quality of life with cediranib in relapsed ovarian cancer: The ICON6 phase 3 randomized clinical trial.

    Science.gov (United States)

    Stark, Dan P; Cook, Adrian; Brown, Julia M; Brundage, Michael D; Embleton, Andrew C; Kaplan, Richard S; Raja, Fharat A; Swart, Ann Marie W; Velikova, Galina; Qian, Wendi; Ledermann, Jonathan A

    2017-07-15

    The ICON6 trial showed that cediranib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, improved clinical outcomes for patients with platinum-sensitive relapsed ovarian cancer when it was used with chemotherapy and was continued as maintenance therapy. This study describes health-related quality of life (QOL) during the first year of treatment. Four hundred fifty-six women were randomly allocated to receive standard chemotherapy only, chemotherapy with concurrent cediranib, or chemotherapy with cediranib administered concurrently and continued as maintenance. Patients completed QOL questionnaires until disease progression every 3 weeks during chemotherapy and then every 6 weeks to 1 year. Patients alive with disease progression completed a QOL form 1 year after randomization. The primary QOL endpoint was the global score from the Quality of Life Questionnaire Core 30 (of the European Organization for Research and Treatment of Cancer) at 1 year, with the standard chemotherapy group compared with the concurrent-maintenance cediranib group. The rate of questionnaire compliance was 90% at the baseline and 76% at 1 year and was similar across the 3 groups. The mean global QOL score at 1 year was 62.6 points for the standard chemotherapy group and 68.7 points for the concurrent-maintenance group (+4.5; 95% confidence interval, -2.0 to 11.0; P = .18). Sensitivity analyses suggested that this finding was robust to the effect of missing data, and the improvement became statistically significant after adjustments for self-reported diarrhea. The 6th study by the International Collaboration in Ovarian Neoplasm (ICON6) showed a significant improvement in progression-free survival with cediranib as concurrent and maintenance therapy. No QOL detriment with cediranib was found 1 year after treatment was commenced. The maintenance of QOL along with prolonged cancer control suggests that cediranib has a valuable role in the treatment of relapsed ovarian

  16. A randomized double-blinded controlled trial of hCG as luteal phase support in natural cycle frozen embryo transfer.

    Science.gov (United States)

    Lee, Vivian Chi Yan; Li, Raymond Hang Wun; Yeung, William Shu Biu; Pak Chung, H O; Ng, Ernest Hung Yu

    2017-05-01

    Does the use of hCG as luteal phase support in natural cycle frozen embryo transfer (FET) increase the ongoing pregnancy rate? The use of hCG in natural cycle FET did not improve the ongoing pregnancy rate. The use of luteal phase support in stimulated cycles has been associated with higher live-birth rates and the results are similar when using hCG or progesterone. This is a randomized double-blinded controlled trial of 450 women recruited between August 2013 and October 2015. Women with regular cycles undergoing natural cycle FET were recruited. Serial serum hormonal concentrations were used to time natural ovulation and at least Day 2 cleavage embryos were replaced. Patients were randomized into either: (i) the treatment group, receiving 1500 IU hCG on the day of FET and 6 days after FET, or (ii) the control group, receiving normal saline on these 2 days. The ongoing pregnancy rate [60/225 (26.7%) in the treatment group vs 70/225 (31.3%) in the control group, odds ratio 1.242 (95% CI 0.825-1.869)], implantation rate and miscarriage rate were comparable between the two groups. In the treatment group, there were significantly more cycles with top quality embryos transferred and a significantly higher serum oestradiol level, but a comparable serum progesterone level, 6 days after FET. However, no significant differences were observed in serum oestradiol and progesterone levels 6 days after FET between the pregnant and non-pregnant women. In the multivariate logistic regression, the number of embryos transferred was the only significant factor predictive of the ongoing pregnancy rate after natural cycle FET. This study only included FET with cleavage stage embryos and only hCG, not vaginal progesterone, was used as luteal phase support. The findings in this study do not support the use of hCG for luteal phase support in natural cycle FET. No external funding was used and there were no competing interests. clinicaltrial.gov identifier: NCT01931384. 23/8/2013. 30/8/2013.

  17. Photoelectron spectroscopy and the dipole approximation

    Energy Technology Data Exchange (ETDEWEB)

    Hemmers, O.; Hansen, D.L.; Wang, H. [Univ. of Nevada, Las Vegas, NV (United States)] [and others

    1997-04-01

    Photoelectron spectroscopy is a powerful technique because it directly probes, via the measurement of photoelectron kinetic energies, orbital and band structure in valence and core levels in a wide variety of samples. The technique becomes even more powerful when it is performed in an angle-resolved mode, where photoelectrons are distinguished not only by their kinetic energy, but by their direction of emission as well. Determining the probability of electron ejection as a function of angle probes the different quantum-mechanical channels available to a photoemission process, because it is sensitive to phase differences among the channels. As a result, angle-resolved photoemission has been used successfully for many years to provide stringent tests of the understanding of basic physical processes underlying gas-phase and solid-state interactions with radiation. One mainstay in the application of angle-resolved photoelectron spectroscopy is the well-known electric-dipole approximation for photon interactions. In this simplification, all higher-order terms, such as those due to electric-quadrupole and magnetic-dipole interactions, are neglected. As the photon energy increases, however, effects beyond the dipole approximation become important. To best determine the range of validity of the dipole approximation, photoemission measurements on a simple atomic system, neon, where extra-atomic effects cannot play a role, were performed at BL 8.0. The measurements show that deviations from {open_quotes}dipole{close_quotes} expectations in angle-resolved valence photoemission are observable for photon energies down to at least 0.25 keV, and are quite significant at energies around 1 keV. From these results, it is clear that non-dipole angular-distribution effects may need to be considered in any application of angle-resolved photoelectron spectroscopy that uses x-ray photons of energies as low as a few hundred eV.

  18. Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial

    DEFF Research Database (Denmark)

    Bernsdorf, Mogens; Ingvar, Christian; Jörgensen, Leif

    2011-01-01

    between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher pCR...... (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI -7.19 to 6.33; P = 0.44). CR...... was observed in 10% of patients in both the gefitinib (7/71) and the placebo group (7/73) (0.27% difference, 95% CI -9.6 to 10.2; P = 0.96). There was no significant difference in OR (5.96%; 95% CI -9.9 to 21.9; P = 0.45) between the two groups. Post hoc subgroup analysis showed a significant difference in pCR...

  19. Intravenous Hydroxypropyl β-Cyclodextrin Formulation of Letermovir: A Phase I, Randomized, Single-Ascending, and Multiple-Dose Trial.

    Science.gov (United States)

    Erb-Zohar, K; Kropeit, D; Scheuenpflug, J; Stobernack, H-P; Hulskotte, Egj; van Schanke, A; Zimmermann, H; Rübsamen-Schaeff, H

    2017-07-04

    Letermovir is a novel antiviral in clinical development for prophylaxis against human cytomegalovirus in immunocompromised transplant recipients. This two-part, single-center, randomized, double-blind, placebo-controlled trial evaluated the safety and pharmacokinetics of a hydroxypropyl β-cyclodextrin (HPβCD)-based intravenous formulation of letermovir in healthy women. Subjects received single, escalating doses (120, 240, 480, 720, and 960 mg; 6 letermovir, 2 placebo per cohort) or multiple, once-daily doses (240 mg; 8 letermovir, 4 placebo) of HPβCD-formulated letermovir and the associated pharmacokinetic profiles and adverse events were investigated. Single-dose and multiple-dose regimens were generally well tolerated. Single-dose escalation resulted in a slightly more-than-dose-proportional increase in the area under the letermovir plasma concentration-time curve (AUC), whereas increase in the maximal observed letermovir plasma concentration (Cmax ) was dose proportional. After once-daily dosing, accumulation ratios in AUC and Cmax were 1.22 and 1.03, respectively. The terminal half-life was 28.3 h, supporting once-daily dosing (EudraCT Number: 2012-001603-20). © 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  20. Randomized phase II exploratory study of prophylactic amifostine in cancer patients who receive radical radiotherapy to the pelvis

    Directory of Open Access Journals (Sweden)

    Karavasilis Vasileios

    2010-06-01

    Full Text Available Abstract Background This study aimed to investigate the efficacy of prophylactic amifostine in reducing the risk of severe radiation colitis in cancer patients receiving radical radiotherapy to the pelvis. Methods Patients with pelvic tumours referred for radical radiotherapy who consented participation in this trial, were randomly assigned to receive daily amifostine (A (subcutaneously, 500 mg flat dose before radiotherapy or radiotherapy alone (R. Sigmoidoscopy and blinded biopsies were scheduled to conduct prior to initiation and following completion of radiotherapy and again 6 to 9 months later. Radiation colitis was assessed by clinical, endoscopic and histolopathological criteria. Results A total 44 patients were enrolled in this trial, the majority with rectal (20 patients and cervical cancer (12 patients and were assigned 23 in R arm and 21 in the A arm. In total 119 sigmoidoscopies were performed and 18 patients (18/44, 40.9% were diagnosed with radiation colitis (15 grade 1 and 2, and 3 grade 3 and 4. Of them, 6 patients belonged to the A group (6/21, 28.6% and 12 to the R group (12/23, 52.2%. Acute and grade IV radiation colitis was only developed in four patients (17.4% in the R group. Amifostine side effects were mild. Amifostine treated patients were less likely to develop histologically detectable mucosal lesions, which indicate protection from acute mucosal injury. Conclusions Amifostine given subcutaneously can lower the risk of acute severe radiation colitis in patients who receive radical radiotherapy to pelvic tumors.

  1. Randomized phase II exploratory study of prophylactic amifostine in cancer patients who receive radical radiotherapy to the pelvis.

    Science.gov (United States)

    Katsanos, Konstantinos H; Briasoulis, Evangelos; Tsekeris, Pericles; Batistatou, Anna; Bai, Maria; Tolis, Christos; Capizzello, Antonio; Panelos, Ioannis; Karavasilis, Vasileios; Christodoulou, Dimitrios; Tsianos, Epameinondas V

    2010-06-10

    This study aimed to investigate the efficacy of prophylactic amifostine in reducing the risk of severe radiation colitis in cancer patients receiving radical radiotherapy to the pelvis. Patients with pelvic tumours referred for radical radiotherapy who consented participation in this trial, were randomly assigned to receive daily amifostine (A) (subcutaneously, 500 mg flat dose) before radiotherapy or radiotherapy alone (R). Sigmoidoscopy and blinded biopsies were scheduled to conduct prior to initiation and following completion of radiotherapy and again 6 to 9 months later. Radiation colitis was assessed by clinical, endoscopic and histolopathological criteria. A total 44 patients were enrolled in this trial, the majority with rectal (20 patients) and cervical cancer (12 patients) and were assigned 23 in R arm and 21 in the A arm. In total 119 sigmoidoscopies were performed and 18 patients (18/44, 40.9%) were diagnosed with radiation colitis (15 grade 1 and 2, and 3 grade 3 and 4). Of them, 6 patients belonged to the A group (6/21, 28.6%) and 12 to the R group (12/23, 52.2%). Acute and grade IV radiation colitis was only developed in four patients (17.4%) in the R group. Amifostine side effects were mild. Amifostine treated patients were less likely to develop histologically detectable mucosal lesions, which indicate protection from acute mucosal injury. Amifostine given subcutaneously can lower the risk of acute severe radiation colitis in patients who receive radical radiotherapy to pelvic tumors.

  2. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters

    Directory of Open Access Journals (Sweden)

    Carolina L. Haass-Koffler

    2017-12-01

    Full Text Available The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled “Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers” (Haass-Koffler et al., 2017 [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73. Keywords: Glutamate receptor subtype 5 (mGlu5, Allosteric modulator, GET 73, Safety, Tolerability

  3. HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: results of a randomized phase II exploratory clinical trial.

    Science.gov (United States)

    Ensoli, Fabrizio; Cafaro, Aurelio; Casabianca, Anna; Tripiciano, Antonella; Bellino, Stefania; Longo, Olimpia; Francavilla, Vittorio; Picconi, Orietta; Sgadari, Cecilia; Moretti, Sonia; Cossut, Maria R Pavone; Arancio, Angela; Orlandi, Chiara; Sernicola, Leonardo; Maggiorella, Maria T; Paniccia, Giovanni; Mussini, Cristina; Lazzarin, Adriano; Sighinolfi, Laura; Palamara, Guido; Gori, Andrea; Angarano, Gioacchino; Di Pietro, Massimo; Galli, Massimo; Mercurio, Vito S; Castelli, Francesco; Di Perri, Giovanni; Monini, Paolo; Magnani, Mauro; Garaci, Enrico; Ensoli, Barbara

    2015-04-29

    The phase II multicenter, randomized, open label, therapeutic trial (ISS T-002, Clinicaltrials.gov NCT00751595) was aimed at evaluating the immunogenicity and the safety of the biologically active HIV-1 Tat protein administered at 7.5 or 30 μg, given 3 or 5 times monthly, and at exploring immunological and virological disease biomarkers. The study duration was 48 weeks, however, vaccinees were followed until the last enrolled subject reached the 48 weeks. Reported are final data up to 144 weeks of follow-up. The ISS T-002 trial was conducted in 11 clinical centers in Italy on 168 HIV positive subjects under Highly Active Antiretroviral Therapy (HAART), anti-Tat Antibody (Ab) negative at baseline, with plasma viremia immune homeostasis and effective anti-viral responses capable of attacking the virus reservoir. Thus, Tat immunization represents a promising pathogenesis-driven intervention to intensify HAART efficacy.

  4. A Phase II, Randomized, Safety and Immunogenicity Trial of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Children and Adults Living in Puerto Rico.

    Science.gov (United States)

    Bauer, Kristen; Esquilin, Ines O; Cornier, Alberto Santiago; Thomas, Stephen J; Quintero Del Rio, Ana I; Bertran-Pasarell, Jorge; Morales Ramirez, Javier O; Diaz, Clemente; Carlo, Simon; Eckels, Kenneth H; Tournay, Elodie; Toussaint, Jean-Francois; De La Barrera, Rafael; Fernandez, Stefan; Lyons, Arthur; Sun, Wellington; Innis, Bruce L

    2015-09-01

    This was a double-blind, randomized, controlled, phase II clinical trial, two dose study of re-derived, live-attenuated, tetravalent dengue virus (TDEN) vaccine (two formulations) or placebo in subjects 1-50 years of age. Among the 636 subjects enrolled, 331 (52%) were primed, that is, baseline seropositive to at least one dengue virus (DENV) type. Baseline seropositivity prevalence increased with age (10% [vaccines were similar to placebo regardless of priming status. No vaccine-related serious adverse events (SAEs) were reported. Among unprimed subjects, immunogenicity (geometric mean antibody titers [GMT] and seropositivity rates) for each DENV increased substantially in both TDEN vaccine groups with at least 74.6% seropositive for four DENV types. The TDEN vaccine candidate showed an acceptable safety and immunogenicity profile in children and adults ranging from 1 to 50 years of age, regardless of priming status. ClinicalTrials.gov: NCT00468858. © The American Society of Tropical Medicine and Hygiene.

  5. Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients

    DEFF Research Database (Denmark)

    Russell, James A; Vincent, Jean-Louis; Kjølbye, Anne Louise

    2017-01-01

    BACKGROUND: Vasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V1A agonists are superior. The initial pharmacodynamic effects, pharmacokinetics, and safety of selepressin, a novel V1A-selective vasopressin analogue......, was examined in a phase IIa trial in septic shock patients. METHODS: This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support) who received selepressin 1.25 ng/kg/minute (n = 10), 2.5 ng...... for selepressin 2.5 ng/kg/minute and placebo. Two patients were infused at 3.75 ng/kg/minute, one of whom had the study drug infusion discontinued for possible safety reasons, with subsequent discontinuation of this dose group. CONCLUSIONS: In septic shock patients, selepressin 2.5 ng/kg/minute was able...

  6. Cognitive Behavioral Therapy as an Adjunct Treatment to Light Therapy for Delayed Sleep Phase Disorder in Young Adults: A Randomized Controlled Feasibility Study.

    Science.gov (United States)

    Danielsson, Katarina; Jansson-Fröjmark, Markus; Broman, Jan-Erik; Markström, Agneta

    2016-01-01

    Delayed sleep phase disorder (DSPD) is common among young people, but there is still no evidence-based treatment available. In the present study, the feasibility of cognitive behavioral therapy (CBT) was evaluated as an additive treatment to light therapy (LT) in DSPD. A randomized controlled trial with participants aged 16 to 26 years received LT for two weeks followed by either four weeks of CBT or no treatment (NT). LT advanced sleep-wake rhythm in both groups. Comparing LT+CBT with LT+NT, no significant group differences were observed in the primary endpoints. Although anxiety and depression scores were low at pretreatment, they decreased significantly more in LT+CBT compared to LT+NT. The results are discussed and some suggestions are given for further studies.

  7. Tolerability during double-blind randomized phase I trials with the house dust mite allergy immunotherapy tablet in adults and children.

    Science.gov (United States)

    Corzo, J L; Carrillo, T; Pedemonte, C; Plaza Martin, A M; Martín Hurtado, S; Dige, E; Calderon, M A

    2014-01-01

    The orodispersible house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (ALK, Denmark) is being developed for the treatment of HDM respiratory allergic disease. The objective of the 2 phase I trials was to investigate tolerability and the acceptable dose range of HDM SLIT-tablet treatment in adults and children with HDM respiratory allergic disease. The trials were randomized, multiple-dose, dose-escalation, double-blind, placebo-controlled phase I trials including patients with HDM-induced asthma, with or without rhinoconjunctivitis. Both trials were registered in EudraCT (Trial 1: 2005-002151-41; Trial 2: 2007-000402-67). Trial 1 included 71 adults (18-63 years) and trial 2 included 72 children (5-14 years). Both trials included 6 dose groups that were randomized 3:1 to active treatment or placebo once daily for 28 days. Adverse events (AEs) were coded in MedDRA (version 8.1 or later). Immunological variables included specific IgE and IgE-blocking factor. No serious AEs were reported. In trial 1 (maximum dose, 32 development units [DU]), 1 patient in the 16 DU group discontinued due to AEs. The entire 32 DU group was discontinued as 1 patient had a severe adverse reaction. In trial 2 (maximum dose, 12 DU), no patients discontinued prematurely. The most frequently reported AEs were mild application-site related events. The total number of events was dose-related within each trial. HDM SLIT-tablet treatment induced changes in immunological parameters in a dose-dependent manner. These trials demonstrate that doses up to 12 DU of HDM SLIT-tablet were tolerated in the selected populations, and thus are suitable for further clinical investigations in adults and children with HDM respiratory allergic disease.

  8. Efficacy and safety of adjunctive brexpiprazole 2 mg in major depressive disorder: a phase 3, randomized, placebo-controlled study in patients with inadequate response to antidepressants.

    Science.gov (United States)

    Thase, Michael E; Youakim, James M; Skuban, Aleksandar; Hobart, Mary; Augustine, Carole; Zhang, Peter; McQuade, Robert D; Carson, William H; Nyilas, Margaretta; Sanchez, Raymond; Eriksson, Hans

    2015-09-01

    To assess the efficacy, tolerability, and safety of brexpiprazole as adjunctive therapy to antidepressant treatments (ADTs) in adults with major depressive disorder (as defined by DSM-IV-TR criteria) and inadequate response to ADTs. Patients with historical inadequate response to 1-3 ADTs were enrolled. All patients entered a prospective 8-week phase on physician-determined, open-label ADT. Those with inadequate response were randomized to ADT + brexpiprazole 2 mg/d or ADT + placebo for 6 weeks. The study was conducted between July 2011 and May 2013. The primary efficacy end point was change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The key secondary end point was change from baseline to week 6 in Sheehan Disability Scale (SDS) mean score. The efficacy population comprised all patients who had ≥ 1 dose of study drug in the double-blind phase and both baseline and ≥ 1 postrandomization MADRS scores. The efficacy population per final protocol included patients from the efficacy population who met amended randomization criteria of inadequate response throughout prospective treatment. Brexpiprazole (n = 175) reduced mean MADRS total score versus placebo (n = 178) at week 6 in the efficacy population per final protocol (-8.36 vs -5.15, P = .0002). Brexpiprazole improved SDS mean score versus placebo (-1.35 vs -0.89, P = .0349). The most common treatment-related adverse events were weight gain (brexpiprazole, 8.0%; placebo, 3.1%) and akathisia (7.4% vs 1.0%). Adjunctive brexpiprazole therapy demonstrated efficacy and was well tolerated in patients with major depressive disorder and inadequate response to ADTs. ClinicalTrials.gov identifier: NCT01360645. © Copyright 2015 Physicians Postgraduate Press, Inc.

  9. EFFECT OF SUPERVISED MODERATE INTENSITY EXERCISE PROGRAM IN PHASE ONE CARDIAC REHABILITATION OF POST OPERATIVE CABG PATIENTS - A RANDOMIZED CONTROLLED TRAIL

    Directory of Open Access Journals (Sweden)

    Rajan Modi

    2014-10-01

    Full Text Available Background: With the increasing number of cases for CABG, the cardiac rehabilitation has gained importance. The trends in rehabilitation of a coronary artery disease patient are changing by incorporating a variety of aerobic exercises and resisted training in to their rehabilitation program. The outcome of any exercise chiefly depends on the training parameters like intensity, frequency and duration. Hence the present study focused to know the effects of supervised moderate intensity exercises on patients during hospital discharge following CABG. The objective of is to study the effectiveness of supervised moderate intensity exercise on distance walked and Quality of Life at hospital discharge following CABG. Methods: Study recruited randomly 46 patients between age group 40-65 years who were posted for non-emergency CABG for the first time. Pre-operative assessment was done thoroughly and was divided in to two groups, Group A conventional treatment and Group B Moderate intensity exercise group. The patients were treated using different protocols in terms of intensity for 8-10 days immediate post CABG. Then the outcome parameters of 6MWT and sf-36 were compared for analysis. Results: Both groups individually showed extremely significant results for two outcome measures. 6 MWD difference between two treatment groups showed significant results with unpaired t test (t = 8.5720,p<0.001. Quality of life score difference within group showed very significant results but there is no difference found between both groups. Conclusion: Moderate intensity exercises can also be included in the immediate post-operative phase of CABG, as they reduce the length of hospital stay and quicken the cardiac rehabilitation process. But there need to be a lot of randomized control trails to confirm the benefits of moderate intensity exercises in phase one rehabilitation program after CABG.

  10. Efficacy profile of a bivalent Staphylococcus aureus glycoconjugated vaccine in adults on hemodialysis: Phase III randomized study.

    Science.gov (United States)

    Fattom, Ali; Matalon, Albert; Buerkert, John; Taylor, Kimberly; Damaso, Silvia; Boutriau, Dominique

    2015-01-01

    In a previous study in end-stage renal disease (ESRD) hemodialysis patients, a single dose of Staphylococcus aureus type 5 and 8 capsular polysaccharides (T5/T8) conjugated to nontoxic recombinant Pseudomonas aeruginosa exotoxin A investigational vaccine showed no efficacy against S. aureus bacteremia 1 year post-vaccination, but a trend for efficacy was observed over the first 40 weeks post-vaccination. Vaccine efficacy (VE) of 2 vaccine doses was therefore evaluated. In a double-blind trial 3359 ESRD patients were randomized (1:1) to receive vaccine or placebo at week 0 and 35. VE in preventing S. aureus bacteremia was assessed between 3-35 weeks and 3-60 weeks post-dose-1. Anti-T5 and anti-T8 antibodies were measured. Serious adverse events (SAEs) were recorded for 42 days post-vaccination and deaths until study end. No significant difference in the incidence of S. aureus bacteremia was observed between vaccine and placebo groups between weeks 3-35 weeks post-dose 1 (VE -23%, 95%CI: -98;23, p = 0.39) or at 3-60 weeks post-dose-1 (VE -8%, 95%CI: -57;26, p = 0.70). Day 42 geometric mean antibody concentrations were 272.4 μg/ml and 242.0 μg/ml (T5 and T8, respectively) in vaccinees. SAEs were reported by 24%/25.3% of vaccinees/placebo recipients. These data do not show a protective effect of either 1 or 2 vaccine doses against S. aureus bacteremia in ESRD patients. The vaccine induced a robust immune response and had an acceptable safety profile. Further investigation suggested possible suboptimal vaccine quality (manufacturing) and a need to expand the antigen composition of the vaccine. This study is registered at www.clinicaltrials.gov NCT00071214.

  11. RECAST (Remote Ischemic Conditioning After Stroke Trial): A Pilot Randomized Placebo Controlled Phase II Trial in Acute Ischemic Stroke.

    Science.gov (United States)

    England, Timothy J; Hedstrom, Amanda; O'Sullivan, Saoirse; Donnelly, Richard; Barrett, David A; Sarmad, Sarir; Sprigg, Nikola; Bath, Philip M

    2017-05-01

    Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke. We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures. Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75-9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group: 2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group ( P =0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5-5) versus 3 (interquartile range, 2-9.5; P =0.04); RIC augmented plasma HSP27 (heat shock protein 27; P stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted. URL: http://www.isrctn.com. Unique identifier: ISRCTN86672015. © 2017 American Heart Association, Inc.

  12. A Randomized, Phase I Pharmacokinetic Study Comparing SB2 and Infliximab Reference Product (Remicade(®)) in Healthy Subjects.

    Science.gov (United States)

    Shin, Donghoon; Kim, Youngdoe; Kim, Yoo Seok; Körnicke, Thomas; Fuhr, Rainard

    2015-12-01

    SB2, a biosimilar to infliximab reference product (INF), has an identical amino acid sequence and similar physicochemical functional properties to its reference product. The primary objective of this study is to demonstrate pharmacokinetic (PK) bioequivalence between SB2 and EU-sourced INF (EU-INF), between SB2 and US-sourced INF (US-INF), and between EU-INF and US-INF. This study was a randomized, single-blind, three-arm, parallel group study in 159 healthy subjects. All subjects received a single 5 mg/kg intravenous infusion of study drug and then were observed for 10 weeks to study PK, safety and immunogenicity. The primary PK parameters were area under the concentration-time curve (AUC) from time zero to infinity (AUCinf), AUC from time zero to the last quantifiable concentration (AUClast) and maximum concentration (C max). Bioequivalence for the primary PK parameters was to be concluded using an analysis of variance (ANOVA) if the 90 % confidence intervals (CIs) for the ratio of geometric least squares means (LSMeans) of the treatments compared were completely contained within the pre-defined equivalence margin, 0.8-1.25. All of the 90 % CIs for the geometric LSMean ratios of primary PK parameters for each comparison were within the pre-defined equivalence margin. The proportion of subjects who experienced treatment-emergent adverse events was comparable between treatments. The incidences of anti-drug antibodies between the three treatments were comparable. This study demonstrated biosimilarity of SB2 to its marketed reference products of infliximab in terms of PK equivalence in healthy subjects. SB2 was generally well tolerated and showed comparable safety and immunogenicity profiles to the reference products (ClinicalTrials.gov Identifier: NCT01922336).

  13. A prospective phase III randomized trial of hypofractionation versus conventional fractionation in patients with high-risk prostate cancer.

    Science.gov (United States)

    Arcangeli, Giorgio; Saracino, Biancamaria; Gomellini, Sara; Petrongari, Maria Grazia; Arcangeli, Stefano; Sentinelli, Steno; Marzi, Simona; Landoni, Valeria; Fowler, Jack; Strigari, Lidia

    2010-09-01

    To compare the toxicity and efficacy of hypofractionated (62 Gy/20 fractions/5 weeks, 4 fractions per week) vs. conventional fractionation radiotherapy (80 Gy/40 fractions/8 weeks) in patients with high-risk prostate cancer. From January 2003 to December 2007, 168 patients were randomized to receive either hypofractionated or conventional fractionated schedules of three-dimensional conformal radiotherapy to the prostate and seminal vesicles. All patients received a 9-month course of total androgen deprivation (TAD), and radiotherapy started 2 months thereafter. The median (range) follow-up was 32 (8-66) and 35 (7-64) months in the hypofractionation and conventional fractionation arms, respectively. No difference was found for late toxicity between the two treatment groups, with 3-year Grade 2 rates of 17% and 16% for gastrointestinal and 14% and 11% for genitourinary in the hypofractionation and conventional fractionation groups, respectively. The 3-year freedom from biochemical failure (FFBF) rates were 87% and 79% in the hypofractionation and conventional fractionation groups, respectively (p = 0.035). The 3-year FFBF rates in patients at a very high risk (i.e., pretreatment prostate-specific antigen (iPSA) >20 ng/mL, Gleason score >or=8, or T >or=2c), were 88% and 76% (p = 0.014) in the former and latter arm, respectively. The multivariate Cox analysis confirmed fractionation, iPSA, and Gleason score as significant prognostic factors. Our findings suggest that late toxicity is equivalent between the two treatment groups and that the hypofractionated schedule used in this trial is superior to the conventional fractionation in terms of FFBF. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  14. Energy spectrum and phase diagrams of two-sublattice hard-core boson model

    Directory of Open Access Journals (Sweden)

    I.V. Stasyuk

    2013-06-01

    Full Text Available The energy spectrum, spectral density and phase diagrams have been obtained for two-sublattice hard-core boson model in frames of random phase approximation approach. Reconstruction of boson spectrum at the change of temperature, chemical potential and energy difference between local positions in sublattices is studied. The phase diagrams illustrating the regions of existence of a normal phase which can be close to Mott-insulator (MI or charge-density (CDW phase diagrams as well as the phase with the Bose-Einstein condensate (SF phase are built.

  15. Safety and acceptability of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 in Bangladeshi infants: a phase I randomized clinical trial.

    Science.gov (United States)

    Hoy-Schulz, Yana Emmy; Jannat, Kaniz; Roberts, Thomas; Zaidi, Saira Husain; Unicomb, Leanne; Luby, Stephen; Parsonnet, Julie

    2016-02-02

    Probiotics have rarely been studied in young healthy infants from low-income countries. This phase I study investigated the safety and acceptability of two probiotics in Bangladesh. Healthy infants aged four to twelve weeks from urban slums in Bangladesh were randomized to one of three different intervention dosing arms (daily, weekly, biweekly - once every two weeks) of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 over one month or to a fourth arm that received no probiotics. All subjects were followed for two additional months. Reported gastrointestinal and respiratory symptoms as well as breastfeeding rates, hospitalizations, differential withdrawals, and caretakers' perception of probiotic use were compared among arms. In total, 160 infants were randomized (40 to each arm) with 137 (Daily n = 35, Weekly n = 35, Biweekly n = 35, Control n = 32) followed up for a median of twelve weeks; 113 completed the study. Illness and breastfeeding rates were similar across all arms. Ten hospitalizations unrelated to probiotic use occurred. Forty eight percent of the caretakers of infants in intervention arms believed that probiotics improved their baby's health. These two commonly used probiotics appeared safe and well-accepted by Bangladeshi families. ClinicalTrials.gov NCT01899378 . Registered July 10, 2013.

  16. A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results.

    Science.gov (United States)

    Coronel, Jaime; Cetina, Lucely; Pacheco, Irlanda; Trejo-Becerril, Catalina; González-Fierro, Aurora; de la Cruz-Hernandez, Erick; Perez-Cardenas, Enrique; Taja-Chayeb, Lucia; Arias-Bofill, Daymi; Candelaria, Myrna; Vidal, Silvia; Dueñas-González, Alfonso

    2011-12-01

    The reversing of epigenetic aberrations using the inhibitors of DNA methylation and histone deacetylases may have therapeutic value in cervical cancer. This is a randomized phase III, placebo-controlled study of hydralazine and valproate (HV) added to cisplatin topotecan in advanced cervical cancer. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow acetylators, and valproate at 30 mg/kg, beginning a week before chemotherapy and continued until disease progression. Response, toxicity, and PFS were evaluated, and 36 patients (17 CT + HV and 19 CT + PLA) were included. The median number of cycles was 6. There were four PRs to CT + HV and one in CT + PLA. Stable disease in five (29%) and six (32%) patients, respectively, whereas eight (47%) and 12 (63%) showed progression (P = 0.27). At a median follow-up time of 7 months (1-22), the median PFS is 6 months for CT + PLA and 10 months for CT + HV (P = 0.0384, two tailed). Although preliminary, this study represents the first randomized clinical trial to demonstrate a significant advantage in progression-free survival for epigenetic therapy over one of the current standard combination chemotherapy in cervical cancer. Molecular correlates with response and survival from this trial are pending to analyze.

  17. A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

    Science.gov (United States)

    Hegg, Roberto; Mattar, André; de Matos, João Nunes; Pedrini, José Luiz; Aleixo, Sabina Bandeira; Rocha, Roberto Odebrecht; Cramer, Renato Peixoto; van-Eyll-Rocha, Sylvie

    2016-01-01

    OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa's approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima®). PMID:27759847

  18. Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial.

    Science.gov (United States)

    Elewski, Boni E; Okun, Martin M; Papp, Kim; Baker, Christopher S; Crowley, Jeffrey J; Guillet, Gérard; Sundaram, Murali; Poulin, Yves; Gu, Yihua; Geng, Ziqian; Williams, David A; Rich, Phoebe A

    2018-01-01

    Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point. This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis. Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis). Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab [P psoriasis versus with placebo and no new safety risks were identified. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  19. Efficacy of tofacitinib for the treatment of nail psoriasis: Two 52-week, randomized, controlled phase 3 studies in patients with moderate-to-severe plaque psoriasis.

    Science.gov (United States)

    Merola, Joseph F; Elewski, Boni; Tatulych, Svitlana; Lan, Shuping; Tallman, Anna; Kaur, Mandeep

    2017-07-01

    Tofacitinib is an oral Janus kinase inhibitor. Efficacy and safety of tofacitinib in patients with moderate-to-severe plaque psoriasis have been demonstrated. We sought to assess the efficacy of tofacitinib for the treatment of nail psoriasis over a period of 52 weeks. In 2 identical phase 3 studies (OPT Pivotal 1 and 2), patients were randomized 2:2:1 to receive tofacitinib 5 mg, tofacitinib 10 mg, or placebo, twice daily. At week 16, placebo-treated patients were re-randomized to tofacitinib. This post hoc analysis of patients with existing nail psoriasis assessed the Nail Psoriasis Severity Index (NAPSI) score and proportions of patients achieving ≥50% reduction in NAPSI from baseline (NAPSI50), NAPSI75, or NAPSI100. Baseline mean NAPSI scores for patients treated with tofacitinib 5 mg (N = 487), tofacitinib 10 mg (N = 476), and placebo (N = 233) twice daily were 27.0, 27.3, and 26.9, respectively. At week 16, significantly (all P psoriasis versus placebo at week 16; improvements were maintained over 52 weeks [NCT01276639; NCT01309737]. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  20. Effect of Eischens Yoga During Radiation Therapy on Prostate Cancer Patient Symptoms and Quality of Life: A Randomized Phase II Trial.

    Science.gov (United States)

    Ben-Josef, Avital Mazar; Chen, Jerry; Wileyto, Paul; Doucette, Abigail; Bekelman, Justin; Christodouleas, John; Deville, Curtiland; Vapiwala, Neha

    2017-08-01

    A randomized phase II study was performed to measure the potential therapeutic effects of yoga on fatigue, erectile dysfunction, urinary incontinence, and overall quality of life (QOL) in prostate cancer (PCa) patients undergoing external beam radiation therapy (RT). The participants were randomized to yoga and no-yoga cohorts (1:1). Twice-weekly yoga interventions were offered throughout the 6- to 9-week courses of RT. Comparisons of standardized assessments were performed between the 2 cohorts for the primary endpoint of fatigue and the secondary endpoints of erectile dysfunction, urinary incontinence, and QOL before, during, and after RT. From October 2014 to January 2016, 68 eligible PCa patients underwent informed consent and agreed to participate in the study. Of the 68 patients, 18 withdrew early, mostly because of treatment schedule-related time constraints, resulting in 22 and 28 patients in the yoga and no-yoga groups, respectively. Throughout treatment, those in the yoga arm reported less fatigue than those in the control arm, with global fatigue, effect of fatigue, and severity of fatigue subscales showing statistically significant interactions (Pyoga having a significant time by treatment effect on the emotional, physical, and social scores but not on functional scores. A structured yoga intervention of twice-weekly classes during a course of RT was associated with a significant reduction in pre-existing and RT-related fatigue and urinary and sexual dysfunction in PCa patients. Copyright © 2017 Elsevier Inc. All rights reserved.