Some effects of different constitutive laws on simulating mitral valve dynamics with FSI

In this paper, three different constitutive laws for mitral leaflets and two laws for chordae tendineae are selected to study their effects on mitral valve dynamics with fluid-structure interaction. We first fit these three mitral leaflet constitutive laws and two chordae tendineae laws with experimental data. The fluid-structure interaction is implemented in an immersed boundary framework with finite element extension for solid, that is the hybrid immersed boundary/finite element(IB/FE) method. We specifically compare the fluid-structure results of different constitutive laws since fluid-structure interaction is the physiological loading environment. This allows us to look at the peak jet velocity, the closure regurgitation volume, and the orifice area. Our numerical results show that different constitutive laws can affect mitral valve dynamics, such as the transvalvular flow rate, closure regurgitation and the orifice area, while the differences in fiber strain and stress are insignificant because all leaflet constitutive laws are fitted to the same set of experimental data. In addition, when an exponential constitutive law of chordae tendineae is used, a lower closure regurgitation flow is observed compared to that of a linear material model. In conclusion, combining numerical dynamic simulations and static experimental tests, we are able to identify suitable constitutive laws for dynamic behaviour of mitral leaflets and chordae under physiological conditions

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

Immersed boundary-finite element model of fluid-structure interaction in the aortic root

It has long been recognized that aortic root elasticity helps to ensure efficient aortic valve closure, but our understanding of the functional importance of the elasticity and geometry of the aortic root continues to evolve as increasingly detailed in vivo imaging data become available. Herein, we describe fluid-structure interaction models of the aortic root, including the aortic valve leaflets, the sinuses of Valsalva, the aortic annulus, and the sinotubular junction, that employ a version of Peskin's immersed boundary (IB) method with a finite element (FE) description of the structural elasticity. We develop both an idealized model of the root with three-fold symmetry of the aortic sinuses and valve leaflets, and a more realistic model that accounts for the differences in the sizes of the left, right, and noncoronary sinuses and corresponding valve cusps. As in earlier work, we use fiber-based models of the valve leaflets, but this study extends earlier IB models of the aortic root by employing incompressible hyperelastic models of the mechanics of the sinuses and ascending aorta using a constitutive law fit to experimental data from human aortic root tissue. In vivo pressure loading is accounted for by a backwards displacement method that determines the unloaded configurations of the root models. Our models yield realistic cardiac output at physiological pressures, with low transvalvular pressure differences during forward flow, minimal regurgitation during valve closure, and realistic pressure loads when the valve is closed during diastole. Further, results from high-resolution computations demonstrate that IB models of the aortic valve are able to produce essentially grid-converged dynamics at practical grid spacings for the high-Reynolds number flows of the aortic root

Direct Measurements of the Branching Fractions for D0→K−e+νeD^0 \to K^-e^+\nu_e and D0→π−e+νeD^0 \to \pi^-e^+\nu_e and Determinations of the Form Factors f+K(0)f_{+}^{K}(0) and f+π(0)f^{\pi}_{+}(0)

The absolute branching fractions for the decays $D^0 \to K^-e ^+\nu_e$ and $D^0 \to \pi^-e^+\nu_e$ are determined using $7584\pm 198 \pm 341$ singly tagged $\bar D^0$ sample from the data collected around 3.773 GeV with the BES-II detector at the BEPC. In the system recoiling against the singly tagged $\bar D^0$ meson, $104.0\pm 10.9$ events for $D^0 \to K^-e ^+\nu_e$ and $9.0 \pm 3.6$ events for $D^0 \to \pi^-e^+\nu_e$ decays are observed. Those yield the absolute branching fractions to be $BF(D^0 \to K^-e^+\nu_e)=(3.82 \pm 0.40\pm 0.27)$ and $BF(D^0 \to \pi^-e^+\nu_e)=(0.33 \pm 0.13\pm 0.03)$. The vector form factors are determined to be $|f^K_+(0)| = 0.78 \pm 0.04 \pm 0.03$ and $|f^{\pi}_+(0)| = 0.73 \pm 0.14 \pm 0.06$. The ratio of the two form factors is measured to be $|f^{\pi}_+(0)/f^K_+(0)|= 0.93 \pm 0.19 \pm 0.07$.Comment: 6 pages, 5 figure

The σ\sigma pole in J/ψ→ωπ+π−J/\psi \to \omega \pi^+ \pi^-

Using a sample of 58 million $J/\psi$ events recorded in the BESII detector, the decay $J/\psi \to \omega \pi^+ \pi^-$ is studied. There are conspicuous $\omega f_2(1270)$ and $b_1(1235)\pi$ signals. At low $\pi \pi$ mass, a large broad peak due to the $\sigma$ is observed, and its pole position is determined to be $(541 \pm 39)$ - $i$ $(252 \pm 42)$ MeV from the mean of six analyses. The errors are dominated by the systematic errors.Comment: 15 pages, 6 figures, submitted to PL

Search for the Lepton Flavor Violation Processes J/ψ→J/\psi \to μτ\mu\tau and eτe\tau

The lepton flavor violation processes $J/\psi \to \mu\tau$ and $e\tau$ are searched for using a sample of 5.8$\times 10^7$ $J/\psi$ events collected with the BESII detector. Zero and one candidate events, consistent with the estimated background, are observed in $J/\psi \to \mu\tau, \tau\to e\bar\nu_e\nu_{\tau}$ and $J/\psi\to e\tau, \tau\to\mu\bar\nu_{\mu}\nu_{\tau}$ decays, respectively. Upper limits on the branching ratios are determined to be $Br(J/\psi\to\mu\tau)<2.0 \times 10^{-6}$ and $Br(J/\psi \to e\tau) < 8.3 \times10^{-6}$ at the 90% confidence level (C.L.).Comment: 9 pages, 2 figure

Measurements of J/psi Decays into 2(pi+pi-)eta and 3(pi+pi-)eta

Based on a sample of 5.8X 10^7 J/psi events taken with the BESII detector, the branching fractions of J/psi--> 2(pi+pi-)eta and J/psi-->3(pi+pi-)eta are measured for the first time to be (2.26+-0.08+-0.27)X10^{-3} and (7.24+-0.96+-1.11)X10^{-4}, respectively.Comment: 11 pages, 6 figure

Observation of the decay \psip\rar\kstark

Using 14 million $\psi(2S)$ events collected with the BESII detector, branching fractions of \psip\rar\kstarkpm and \kstarknn are determined to be: \calB(\psip\rar\kstarkpm)=(2.9^{+1.3}_{-1.7}\pm0.4)\times 10^{-5} and \calB(\psip\rar\kstarknn)=(13.3^{+2.4}_{-2.7}\pm1.9)\times 10^{-5}. The results confirm the violation of the "12%" rule for these two decay channels with higher precision. A large isospin violation between the charged and neutral modes is observed.Comment: 5 pages, 3 figure

BESII Detector Simulation

A Monte Carlo program based on Geant3 has been developed for BESII detector simulation. The organization of the program is outlined, and the digitization procedure for simulating the response of various sub-detectors is described. Comparisons with data show that the performance of the program is generally satisfactory.Comment: 17 pages, 14 figures, uses elsart.cls, to be submitted to NIM