Anderson localization of polaron states

Using the vanishing of the typical polaron tunneling rate as an indicator of the breakdown of itinerancy, we study the localization of polaron states in a generic model for a disordered polaronic material. We find that extremely small disorder causes an Anderson localization of small polaron states. However, the ratio between the critical disorder strength needed to localize all states in the polaron band and the renormalized bandwidth is not necessarily smaller than for a bare electron.Comment: 4 pages, 3 figure

Macrospin approximation and quantum effects in models for magnetization reversal

The thermal activation of magnetization reversal in magnetic nanoparticles is controlled by the anisotropy-energy barrier. Using perturbation theory, exact diagonalization and stability analysis of the ferromagnetic spin-s Heisenberg model with coupling or single-site anisotropy, we study the effects of quantum fluctuations on the height of the energy barrier. Opposed to the classical case, there is no critical anisotropy strength discriminating between reversal via coherent rotation and via nucleation/domain-wall propagation. Quantum fluctuations are seen to lower the barrier depending on the anisotropy strength, dimensionality and system size and shape. In the weak-anisotropy limit, a macrospin model is shown to emerge as the effective low-energy theory where the microscopic spins are tightly aligned due to the ferromagnetic exchange. The calculation provides explicit expressions for the anisotropy parameter of the effective macrospin. We find a reduction of the anisotropy-energy barrier as compared to the classical high spin-s limit.Comment: 10 pages, 11 figure

The Dynamical Cluster Approximation: Non-Local Dynamics of Correlated Electron Systems

We recently introduced the dynamical cluster approximation(DCA), a new technique that includes short-ranged dynamical correlations in addition to the local dynamics of the dynamical mean field approximation while preserving causality. The technique is based on an iterative self-consistency scheme on a finite size periodic cluster. The dynamical mean field approximation (exact result) is obtained by taking the cluster to a single site (the thermodynamic limit). Here, we provide details of our method, explicitly show that it is causal, systematic, $\Phi$-derivable, and that it becomes conserving as the cluster size increases. We demonstrate the DCA by applying it to a Quantum Monte Carlo and Exact Enumeration study of the two-dimensional Falicov-Kimball model. The resulting spectral functions preserve causality, and the spectra and the CDW transition temperature converge quickly and systematically to the thermodynamic limit as the cluster size increases.Comment: 19 pages, 13 postscript figures, revte

Electron correlation vs. stabilization: A two-electron model atom in an intense laser pulse

We study numerically stabilization against ionization of a fully correlated two-electron model atom in an intense laser pulse. We concentrate on two frequency regimes: very high frequency, where the photon energy exceeds both, the ionization potential of the outer {\em and} the inner electron, and an intermediate frequency where, from a ``single active electron''-point of view the outer electron is expected to stabilize but the inner one is not. Our results reveal that correlation reduces stabilization when compared to results from single active electron-calculations. However, despite this destabilizing effect of electron correlation we still observe a decreasing ionization probability within a certain intensity domain in the high-frequency case. We compare our results from the fully correlated simulations with those from simpler, approximate models. This is useful for future work on ``real'' more-than-one electron atoms, not yet accessible to numerical {\em ab initio} methods.Comment: 8 pages, 8 figures in an extra ps-file, submitted to Phys. Rev. A, updated references and shortened introductio

Split First Dose Administration of Intravenous Daratumumab for the Treatment of Multiple Myeloma (MM) : Clinical and Population Pharmacokinetic Analyses

Introduction: Daratumumab, a human immunoglobulin Gκ monoclonal antibody targeting CD38, is approved as monotherapy and in combination with standard-of-care regimens for multiple myeloma. In clinical studies, the median durations of the first, second, and subsequent intravenous infusions of daratumumab were 7.0, 4.3, and 3.4 h, respectively. Splitting the first intravenous infusion of daratumumab over 2 days is an approved alternative dosing regimen to reduce the duration of the first infusion and provide flexibility for patients and healthcare providers. Methods: The feasibility of splitting the first 16-mg/kg infusion into two separate infusions of 8 mg/kg on Days 1 and 2 of the first treatment cycle was investigated in two cohorts [daratumumab, carfilzomib, and dexamethasone (D-Kd) and daratumumab, carfilzomib, lenalidomide, and dexamethasone (D-KRd)] of the phase 1b MMY1001 study. Additionally, a population pharmacokinetic (PK) analysis and simulations were used to compare the PK profiles of the split first dose regimen with the recommended single first dose regimens of daratumumab in previously approved indications. Results: In MMY1001, following administration of the second half of a split first dose on Cycle 1 Day 2, postinfusion median (range) daratumumab concentrations were similar between split first dose [D-Kd, 254.9 (125.8-435.5) µg/ml; D-KRd, 277.2 (164.0-341.8) µg/ml; combined, 256.8 (125.8-435.5) µg/ml] and single first dose [D-Kd, 319.2 (237.5-394.7) µg/ml]. At the end of weekly dosing, median (range) Cycle 3 Day 1 preinfusion daratumumab concentrations were similar between split first dose [D-Kd, 663.9 (57.7-1110.7) µg/ml; D-KRd, 575.1 (237.9-825.5) µg/ml; combined, 639.2 (57.7-1110.7) µg/ml] and single first dose [D-Kd, 463.2 (355.9-792.9) µg/ml]. The population PK simulations demonstrated virtually identical PK profiles after the first day of treatment for all approved indications and recommended dosing schedules of daratumumab. Conclusion: These data support the use of an alternative split first dose regimen of intravenous daratumumab for the treatment of MM. Trial Registration: ClinicalTrials.gov number, NCT01998971

Split First Dose Administration of Intravenous Daratumumab for the Treatment of Multiple Myeloma (MM) : Clinical and Population Pharmacokinetic Analyses

Introduction: Daratumumab, a human immunoglobulin Gκ monoclonal antibody targeting CD38, is approved as monotherapy and in combination with standard-of-care regimens for multiple myeloma. In clinical studies, the median durations of the first, second, and subsequent intravenous infusions of daratumumab were 7.0, 4.3, and 3.4 h, respectively. Splitting the first intravenous infusion of daratumumab over 2 days is an approved alternative dosing regimen to reduce the duration of the first infusion and provide flexibility for patients and healthcare providers. Methods: The feasibility of splitting the first 16-mg/kg infusion into two separate infusions of 8 mg/kg on Days 1 and 2 of the first treatment cycle was investigated in two cohorts [daratumumab, carfilzomib, and dexamethasone (D-Kd) and daratumumab, carfilzomib, lenalidomide, and dexamethasone (D-KRd)] of the phase 1b MMY1001 study. Additionally, a population pharmacokinetic (PK) analysis and simulations were used to compare the PK profiles of the split first dose regimen with the recommended single first dose regimens of daratumumab in previously approved indications. Results: In MMY1001, following administration of the second half of a split first dose on Cycle 1 Day 2, postinfusion median (range) daratumumab concentrations were similar between split first dose [D-Kd, 254.9 (125.8-435.5) µg/ml; D-KRd, 277.2 (164.0-341.8) µg/ml; combined, 256.8 (125.8-435.5) µg/ml] and single first dose [D-Kd, 319.2 (237.5-394.7) µg/ml]. At the end of weekly dosing, median (range) Cycle 3 Day 1 preinfusion daratumumab concentrations were similar between split first dose [D-Kd, 663.9 (57.7-1110.7) µg/ml; D-KRd, 575.1 (237.9-825.5) µg/ml; combined, 639.2 (57.7-1110.7) µg/ml] and single first dose [D-Kd, 463.2 (355.9-792.9) µg/ml]. The population PK simulations demonstrated virtually identical PK profiles after the first day of treatment for all approved indications and recommended dosing schedules of daratumumab. Conclusion: These data support the use of an alternative split first dose regimen of intravenous daratumumab for the treatment of MM. Trial Registration: ClinicalTrials.gov number, NCT01998971

The Effect of Tiaprofenic Acid on Blood Pressure Control in Treated Hypertensive Patients

Eleven patients with osteoarthritis and mild hypertension completed an 8-week, double-blind crossover study in which 200 mg tiaprofenic acid 3-times daily or placebo were substituted for their normal non-steroidal anti-inflammatory therapy. Systolic blood pressure was significantly higher on tiaprofenic acid therapy than on placebo and plasma renin activity was significantly lower on active treatment. No significant changes were seen in biochemical parameters, though the weight of the patient was also higher on tiaprofenic acid than on placebo. Duration of morning stiffness was also lower on tiaprofenic acid than on placebo. Blood pressure on tiaprofenic acid was not different from baseline readings on other non-steroidal anti-inflammatory drug therapy. This study suggests that tiaprofenic acid, like other non-steroidal anti-inflammatory agents, may interfere with blood pressure control in treated hypertensive patients