High tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to ...investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1.
We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/kg d1, Q2W) as a monotherapy. In cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 b.i.d., d1–d14, Q3W as first-line treatment. Primary end point was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy.
In cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group 14.6 versus 4.0 months, HR = 0.48 (96% CI 0.24–0.96), P = 0.038, while PD-L1 overexpression did not correlate with significant survival benefit. A 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. A 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs.
Toripalimab has demonstrated a manageable safety profile and promising antitumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent.
ClinicalTrials.gov NCT02915432.
The generation of kinetic‐scale flux ropes (KSFRs) is closely related to magnetic reconnection. Both flux ropes and reconnection sites are detected in the magnetosheath and can impact the dynamics ...upstream of the magnetopause. In this study, using the Magnetospheric Multiscale satellite, 12,623 KSFRs with a scale <20 RCi are statistically studied in the Earth's dayside magnetosheath. It is found that they are mostly generated near the bow shock (BS), and propagate downstream in the magnetosheath. Their quantity significantly increases as the scale decreases, consistent with a flux rope coalescence model. Moreover, the solar wind parameters can control the occurrence rate of KSFRs. They are more easily generated at high Mach number, large proton density, and weak magnetic field strength of the solar wind, similar to the conditions that favor BS reconnection. Our study shows a close connection between KSFR generation and BS reconnection.
Plain Language Summary
Kinetic‐scale flux ropes (KSFRs) exist widely in near‐earth space and play an important role in mass transport, energy conversion, and dissipation during magnetic field reconnection. The KSFR in the magnetosheath can be generated by reconnection in three regions: the magnetopause, the magnetosheath, and the BS. The spatial distribution of KSFRs can indirectly reflect the reconnection situation in the magnetosheath. We use various methods to select the KSFRs and study their spatial distribution and generation in the magnetosheath. Our results show that BS reconnection plays an important role in generating the KSFR in the magnetosheath.
Key Points
Kinetic‐scale flux ropes observed in the magnetosheath are primarily generated near the bow shock (BS) and travel to downstream magnetosheath
The quantity of flux ropes significantly increases as their scale decreases, which is in accordance with the FR coalescence model
The occurrence of flux ropes is influenced by solar wind parameters, and could strongly correlate with BS reconnection
Abstract
Background
Recent studies have focused on initial clinical and epidemiological characteristics of the coronavirus disease 2019 (COVID-19), which is the mainly revealing situation in Wuhan, ...Hubei.
Aim
This study aims to reveal more data on the epidemiological and clinical characteristics of COVID-19 patients outside of Wuhan, Zhejiang, China.
Design
This study was a retrospective case series.
Methods
Eighty-eight cases of laboratory-confirmed and three cases of clinically confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020.
Results and discussion
Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2, three (3.30%) cases were clinically diagnosed. The median age of the patients was 50 (36.5–57) years, and female accounted for 59.34%. In this sample, 40 (43.96%) patients had contracted the disease from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, eight (8.79%) patients had contacted with people from Wuhan, and 11 (12.09%) patients were diagnosed after having flown together in the same flight with no passenger that could later be identified as the source of infection. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (interquartile range 3–8) days and the median time from the first visit to a doctor to the confirmed diagnosis was 1 (1–2) days. According to the chest computed tomography scans, 67.03% cases had bilateral pneumonia.
Conclusions
Social activity cluster, family cluster and flying alongside with persons already infected with COVID-19 were how people got infected with COVID-19 in Zhejiang.
We report a study of the processes of e^{+}e^{-}→K^{+}D_{s}^{-}D^{*0} and K^{+}D_{s}^{*-}D^{0} based on e^{+}e^{-} annihilation samples collected with the BESIII detector operating at BEPCII at five ...center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7 fb^{-1}. An excess of events over the known contributions of the conventional charmed mesons is observed near the D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0} mass thresholds in the K^{+} recoil-mass spectrum for events collected at sqrts=4.681 GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5_{-2.6}^{+1.8}±2.1) MeV/c^{2} and (12.8_{-4.4}^{+5.3}±3.0) MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3 σ over the contributions only from the conventional charmed mesons. This is the first candidate for a charged hidden-charm tetraquark with strangeness, decaying into D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0}. However, the properties of the excess need further exploration with more statistics.
Kinetic‐scale magnetic dips (KSMDs), with a significant depression in magnetic field strength, and scale length close to and less than one proton gyroradius, were reported in the turbulent plasmas ...both in recent observation and numerical simulation studies. These KSMDs likely play important roles in energy conversion and dissipation. In this study, we present observations of the KSMDs that are labeled whistler mode waves, electrostatic solitary waves, and electron cyclotron waves in the magnetosheath. The observations suggest that electron temperature anisotropy or beams within KSMD structures provide free energy to generate these waves. In addition, the occurrence rates of the waves are higher in the center of the magnetic dips than at their edges, implying that the KSMDs might be the origin of various kinds of waves. We suggest that the KSMDs could provide favorable conditions for the generation of waves and transfer energy to the waves in turbulent magnetosheath plasmas.
Plain Language Summary
The Earth's magnetosheath is a turbulent plasma environment where energy conversion, particle acceleration, and mass and momentum transport take place. Many of these key processes involve kinetic‐scale physics. However, in‐depth studies from previous missions are limited by their lower spacecraft data resolution. The recent Magnetospheric Multiscale (MMS) mission provides us with a large amount of high‐temporal cadence data for studying kinetic‐scale physics in the magnetosheath. In this study, we report whistler mode waves, electrostatic solitary waves and electron cyclotron waves within kinetic‐scale magnetic dips (KSMDs) that can be generated in the turbulent magnetosheath. These waves could be excited by electron temperature anisotropy or beams. As is well known, plasma waves are important processes in converting energy, accelerating and scattering electrons and ions, and modifying the distributions of charged particles. If plasma instabilities develop within the KSMDs, the resulting waves could absorb free energy from plasma particles and may propagate out of the KSMDs. Thus, our discoveries could significantly advance the understanding of energy conversion and dissipation for kinetic‐scale turbulence. This study provides a new reference not only for observations in space physics but also for related basic plasma theories and numerical simulations.
Key Points
MMS observations reveal KSMDs coupled with whistler mode waves, electrostatic solitary waves, and electron cyclotron waves
These waves are excited by different plasma distributions, and the ESWs could affect the electron distributions in kinetic scale
Statistical results indicate that the KSMDs in the magnetosheath are a possible origin for various kinds of waves
Abstract
The role of whistler-mode waves in the solar wind and the relationship between their electromagnetic fields and charged particles is a fundamental question in space physics. Using ...high-temporal-resolution electromagnetic field and plasma data from the Magnetospheric MultiScale spacecraft, we report observations of low-frequency whistler waves and associated electromagnetic fields and particle behavior in the Earth’s foreshock. The frequency of these whistler waves is close to half the lower-hybrid frequency (∼2 Hz), with their wavelength close to the ion gyroradius. The electron bulk flows are strongly modulated by these waves, with a modulation amplitude comparable to the solar wind velocity. At such a spatial scale, the electron flows are forcibly separated from the ion flows by the waves, resulting in strong electric currents and anisotropic ion distributions. Furthermore, we find that the low-frequency whistler wave propagates obliquely to the background magnetic field (
B
0
), and results in spatially periodic magnetic gradients in the direction parallel to
B
0
. Under such conditions, large pitch-angle electrons are trapped in wave magnetic valleys by the magnetic mirror force, and may provide free perpendicular electron energy to excite higher-frequency whistler waves. This study offers important clues and new insights into wave–particle interactions, wave generation, and microscale energy conversion processes in the solar wind.
Laboratory observations of enhancements of energetic-electron population are presented during magnetic reconnection associated with strong tearing mode in non-disruptive tokamak plasmas. The hard ...X‑ray (HXR) spectrum detected by cadmium-telluride (CdTe) scintillator detectors and the non-thermal radiation measured by the electron cyclotron emission (ECE) are used to analyze the behaviors of energetic electrons on HL-2A. A population of energetic electrons is generated by parallel electric fields
during magnetic reconnection, which is evidenced by the production of hard X-rays with energy 10 keV <
E
γ
< 200 keV. The results could assist to better understand the acceleration mechanism of electrons in the parameter-regime of tokamak plasma. It is observed that the energetic-electrons jointly accelerated by Ohmic electric fields and parallel electric fields have significant effects on the behaviors of low frequency MHD modes, namely, which excite Alfvénic and acoustic type instabilities during strong tearing modes (TMs).
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