94 research outputs found
Bayesian inference of population expansions in domestic bovines
The past population dynamics of four domestic and one wild species of bovine were estimated using Bayesian skyline plots, a coalescent Markov chain Monte Carlo method that does not require an assumed parametric model of demographic history. Four domestic species share a recent rapid population expansion not visible in the wild African buffalo (Syncerus caffer). The estimated timings of the expansions are consistent with the archaeological records of domestication
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
Fabrication of CuO nanoparticle interlinked microsphere cages by solution method
Here we report a very simple method to convert conventional CuO powders to nanoparticle interlinked microsphere cages by solution method. CuO is dissolved into aqueous ammonia, and the solution is diluted by alcohol and dip coating onto a glass substrate. Drying at 80 °C, the nanostructures with bunchy nanoparticles of Cu(OH)2can be formed. After the substrate immerges into the solution and we vaporize the solution, hollow microspheres can be formed onto the substrate. There are three phases in the as-prepared samples, monoclinic tenorite CuO, orthorhombic Cu(OH)2, and monoclinic carbonatodiamminecopper(II) (Cu(NH3)2CO3). After annealing at 150 °C, the products convert to CuO completely. At annealing temperature above 350 °C, the hollow microspheres became nanoparticle interlinked cages
Direct Measurements of the Branching Fractions for and and Determinations of the Form Factors and
The absolute branching fractions for the decays and
are determined using singly
tagged 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
meson, events for and events for decays are observed. Those yield
the absolute branching fractions to be and . The
vector form factors are determined to be
and . The ratio of the two form
factors is measured to be .Comment: 6 pages, 5 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
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
Measurement of branching fractions for the inclusive Cabibbo-favored ~K*0(892) and Cabibbo-suppressed K*0(892) decays of neutral and charged D mesons
The branching fractions for the inclusive Cabibbo-favored ~K*0 and
Cabibbo-suppressed K*0 decays of D mesons are measured based on a data sample
of 33 pb-1 collected at and around the center-of-mass energy of 3.773 GeV with
the BES-II detector at the BEPC collider. The branching fractions for the
decays D+(0) -> ~K*0(892)X and D0 -> K*0(892)X are determined to be BF(D0 ->
\~K*0X) = (8.7 +/- 4.0 +/- 1.2)%, BF(D+ -> ~K*0X) = (23.2 +/- 4.5 +/- 3.0)% and
BF(D0 -> K*0X) = (2.8 +/- 1.2 +/- 0.4)%. An upper limit on the branching
fraction at 90% C.L. for the decay D+ -> K*0(892)X is set to be BF(D+ -> K*0X)
< 6.6%
The pole in
Using a sample of 58 million events recorded in the BESII detector,
the decay is studied. There are conspicuous
and signals. At low mass, a large
broad peak due to the is observed, and its pole position is determined
to be - MeV from the mean of six analyses.
The errors are dominated by the systematic errors.Comment: 15 pages, 6 figures, submitted to PL
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