This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer.
In this phase III, ...double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.
Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 95% confidence interval (CI), 10.9-not evaluable versus 5.4 (95% CI, 3.7-5.7) months hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001, and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%).
Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.
•Chinese patients with platinum-sensitive recurrent ovarian cancer received maintenance niraparib (n = 177) or placebo (n = 88).•Median PFS was longer for niraparib versus placebo: 18.3 versus 5.4 months (HR = 0.32; 95% CI, 0.23-0.45; P < 0.0001).•Niraparib had a similar PFS benefit for 249 patients receiving individualized dosing based on bodyweight and platelet count.•Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively.•In the niraparib group, Grade ≥3 platelet count decreased/thrombocytopenia occurred in 11.3% of patients.
Saccharum spontaneum L. is one of the most important germplasm resources for modern sugarcane breeding. Exploring the cold tolerance of S. spontaneum clones with different ploidy levels and screening ...for cold‐tolerant material can be helpful in parent selection for breeding cold‐tolerant sugarcane.
Morphological indices, leaf ultrastructure and physiological indices were used to evaluate the cold tolerance of 36 S. spontaneum clones with different ploidy levels (2n = 40, 48, 54, 60, 64, 78, 80, 88, 92 and 96).
The morphological indices of S. spontaneum clones with different ploidy levels were positively correlated with ploidy. Under low‐temperature stress, the chloroplast and mitochondrial structures of the clones with high ploidy were more severely damaged than were those of clones with low ploidy. A comprehensive evaluation of the physiological indices showed that the 36 S. spontaneum clones could be divided into four categories: strongly cold tolerant, cold tolerant, moderately cold tolerant and cold sensitive. Correlation analysis of the morphological indices and cold tolerance revealed a significant negative correlation between cold tolerance and ploidy. On the basis of the morphological and physiological indices, optimal stepwise regression equations that can be used for the selection of cold‐tolerant S. spontaneum resources were established.
The S. spontaneum clones with low ploidy are more cold tolerant than those with high ploidy. Clones 12‐37, 13‐10 and 12‐23 are strongly cold‐tolerant germplasm resources, which suggests these germplasm sources have high potential for use in breeding cold‐tolerant sugarcane.
The morphological and physiological indexes of 36 S. spontaneum clones with 10 different ploidy levels showed that S. spontaneum clones with low ploidy are more cold tolerant than those with high ploidy.
Dynamical quantum phase transitions are closely related to equilibrium quantum phase transitions for ground states. Here, we report an experimental observation of a dynamical quantum phase transition ...in a spinor condensate with correspondence in an excited state phase diagram, instead of the ground state one. We observe that the quench dynamics exhibits a nonanalytical change with respect to a parameter in the final Hamiltonian in the absence of a corresponding phase transition for the ground state there. We make a connection between this singular point and a phase transition point for the highest energy level in a subspace with zero spin magnetization of a Hamiltonian. We further show the existence of dynamical phase transitions for finite magnetization corresponding to the phase transition of the highest energy level in the subspace with the same magnetization. Our results open a door for using dynamical phase transitions as a tool to probe physics at higher energy eigenlevels of many-body Hamiltonians.
We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China ...Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.
A new alpha-emitting isotope U-214, produced by the fusion-evaporation reaction W-182(Ar-36,4n) U-214, was identified by employing the gas-filled recoil separator SHANS and the recoil-a correlation ...technique. More precise a-decay properties of even-even nuclei U-216,U-218 were also measured in the reactions of Ar-40, Ca-40 beams with W-180,W-182,W- 184 targets. By combining the experimental data, improved alpha-decay reduced widths delta(2) for the even-even Po-Pu nuclei in the vicinity of the magic neutron number N = 126 are deduced. Their systematic trends are discussed in terms of the N-p N-n scheme in order to study the influence of protonneutron interaction on a decay in this region of nuclei. It is strikingly found that the reduced widths of( 214,216)U are significantly enhanced by a factor of two as compared with the NpNn systematics for the 84 <= Z <= 90 and N < 126 even-even nuclei. The abnormal enhancement is interpreted by the strong monopole interaction between the valence protons and neutrons occupying the pi 1f (7/2) and nu 1f(5/2) spin-orbit partner orbits, which is supported by the large-scale shell model calculation.
Generating ion-photon entanglement is a crucial step for scalable trapped-ion quantum networks. To avoid the crosstalk on memory qubits carrying quantum information, it is common to use a different ...ion species for ion-photon entanglement generation such that the scattered photons are far off-resonant for the memory qubits. However, such a dual-species scheme can be subject to inefficient sympathetic cooling due to the mass mismatch of the ions. Here we demonstrate a trapped-ion quantum network node in the dual-type qubit scheme where two types of qubits are encoded in the S and F hyperfine structure levels of
Yb
ions. We generate ion photon entanglement for the S-qubit in a typical timescale of hundreds of milliseconds, and verify its small crosstalk on a nearby F-qubit with coherence time above seconds. Our work demonstrates an enabling function of the dual-type qubit scheme for scalable quantum networks.
Summary
Activated calcium‐/calmodulin‐dependent protein kinaseII (CaMKII) is important to promote chondrocytes from proliferative to pre‐hypertrophic state, which probably plays a role in ...osteoarthritis (OA), a widespread degeneration disease with enhanced aberrant chondrocyte differentiation. Our aim was to detect the role of CaMKII, and its relationship with the feedback loop of Indian hedgehog (Ihh) and Parathyroid‐related peptide (PTHrP) in the temporomandibular joints (TMJs) OA. KN93, the competitive inhibitor of CaMKII, was added to the culture medium in vitro and was locally injected to rats TMJs (n = 54, female) every other day for 4 weeks from the beginning of the 5th and 9th week after installing of unilateral anterior crossbite (UAC), termed as 4 wk+4 wk and 8 wk+4 wk, accordingly. The RNA expression of CaMKII α (1.49 ± 0.09), CaMKII β (3.36 ± 0.20), Ihh (1.88 ± 0.06) and PTHrP (1.87 ± 0.12) was all enhanced, especially at 24 dyn/cm2 in vitro (all P < .05), accompanied with downregulated expression of cartilage matrix, but upregulated markers of chondrocytes differentiation (all P < 0.05). Similarity was observed in the 4 wk+4 wk group in vivo. In the 8 wk+4 wk group, UAC upregulated the RNA expression of CaMKII α (1.81 ± 0.24), CaMKII β (1.36 ± 0.07) and Ihh (1.70 ± 0.21), however, down‐regulated PTHrP (0.53 ± 0.04) (all P < .05), in consonance with the protein expression. All these changes were attenuated by KN93 (all P < .05). In conclusion, CaMKII took a role, via Ihh and PTHrP pathways, in promoting biomechanically induced TMJ chondrocytes differentiation, the initiation issue of UAC stimulated osteoarthritic changes in rodent TMJs. Inhibiting CaMKII is helpful to rescue the biomechanically stimulated cartilage degradation and prospective to be a target treatment of OA.
A Nationwide Nitrogen Deposition Monitoring Network (NNDMN) containing 43 monitoring sites was established in China to measure gaseous NH3, NO2, and HNO3 and particulate NH4+ and NO3− in air and/or ...precipitation from 2010 to 2014. Wet/bulk deposition fluxes of Nr species were collected by precipitation gauge method and measured by continuous-flow analyzer; dry deposition fluxes were estimated using airborne concentration measurements and inferential models. Our observations reveal large spatial variations of atmospheric Nr concentrations and dry and wet/bulk Nr deposition. On a national basis, the annual average concentrations (1.3–47.0 μg N m−3) and dry plus wet/bulk deposition fluxes (2.9–83.3 kg N ha−1 yr−1) of inorganic Nr species are ranked by land use as urban > rural > background sites and by regions as north China > southeast China > southwest China > northeast China > northwest China > Tibetan Plateau, reflecting the impact of anthropogenic Nr emission. Average dry and wet/bulk N deposition fluxes were 20.6 ± 11.2 (mean ± standard deviation) and 19.3 ± 9.2 kg N ha−1 yr−1 across China, with reduced N deposition dominating both dry and wet/bulk deposition. Our results suggest atmospheric dry N deposition is equally important to wet/bulk N deposition at the national scale. Therefore, both deposition forms should be included when considering the impacts of N deposition on environment and ecosystem health.
We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (mχ) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on ...time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in mχ are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σχNSI at 90% confidence level are derived as 2×10−32∼7×10−35 cm2 for TI analysis at mχ∼50–180 MeV/c2, and 3×10−32∼9×10−38 cm2 for AM analysis at mχ∼75 MeV/c2–3.0 GeV/c2.