Background
While the majority of studies report that a raised serum α‐fetoprotein (AFP) level before operation is associated with a high risk of recurrence and death in patients who undergo ...hepatectomy for hepatocellular carcinoma (HCC), results are conflicting. The aim of this study was to assess the prognostic value of AFP.
Methods
Serum AFP levels were measured in patients with hepatitis‐associated HCC who underwent hepatectomy between 1995 and 2012. Kaplan–Meier and multivariable analyses were performed to identify risk factors for overall and disease‐free survival. Univariable and multivariable Cox proportional hazards regression was used to evaluate the predictive value of AFP. Receiver operating characteristic (ROC) curves were generated to identify the AFP level that had the highest accuracy in discriminating between survivors and non‐survivors.
Results
Some 376 patients with hepatitis B virus (HBV)‐associated HCC were included in the study. The overall survival rate was 58·8 per cent in patients with an AFP level of 400 ng/ml or less compared with 40·4 per cent for those with a level exceeding 400 ng/ml (P = 0·001). AFP concentration above 400 ng/ml was an independent risk factor for shorter disease‐free and overall survival after surgery. ROC analysis indicated that the optimal cut‐off values for AFP varied for different subtypes of HCC. The sensitivity and specificity were lower with areas under the ROC curve of less than 0·600. An AFP level greater than 400 ng/ml was not sensitive enough to predict the prognosis in patients with an HCC diameter smaller than 3 cm.
Conclusion
A serum AFP level above 400 ng/ml predicts poor overall and recurrence‐free survival after hepatectomy in patients with HBV‐associated HCC. AFP is not a strong prognostic marker given its poor discriminatory power, with low sensitivity and specificity.
Not useful
Genetic polymorphisms of CYP2C9 significantly influence the pharmacokinetics and pharmacodynamics of some drugs, which might result in adverse drug effects and therapeutic failure. Several studies ...have been performed on CYP2C9 genetic polymorphisms in Han Chinese populations. However, these studies only focused on two commonly investigated alleles, *2 and *3, in relatively small sample sizes. To scale up the gene-scanning region and determine relatively precise data on the genetic distribution pattern in Chinese populations, unrelated healthy Han Chinese volunteers from Zhejiang Province (n=1127) and Hebei (n=1000) Province were recruited as subjects for the direct sequencing of all exons of CYP2C9. As a result, 14 previously reported alleles were detected in this work, and 8 of these alleles (*14, *16, *19, *23, *27, *29, *33 and *34) were described for the first time in Chinese populations. In addition, 37 novel mutations were also detected, of which 22 variants were non-synonymous, and 21 new alleles, *36-*56, were designated by the Human CYP Allele Nomenclature Committee. In vitro functional analysis of these 22 novel CYP2C9 variants revealed that 17 mutations had a significant influence on the protein's catalytic activity. Our study provides the most accurate data on CYP2C9 polymorphisms in Han Chinese populations and detects the largest number of novel allelic variants existing to date. These new alleles will greatly enrich the current knowledge of naturally occurring CYP2C9 variants in Chinese populations.
Control over ferroelectric polarization variants in BiFeO3 films through the use of various vicinal SrTiO3 substrates is demonstrated. The revolution of domain formation as a function of vicinality ...is characterized, and the ferroelectric polarization variants in these films and the corresponding structural variants are carefully analyzed. The piezo/ferroelectric properties of the BiFeO3 films, in turn, can be tailored through this approach.
The epidemiology of candidaemia varies between hospitals and geographic regions. Although there are many studies from Asia, a large-scale cross-sectional study across Asia has not been performed. We ...conducted a 12-month, laboratory-based surveillance of candidaemia at 25 hospitals from China, Hong Kong, India, Singapore, Taiwan and Thailand. The incidence and species distribution of candidaemia were determined. There were 1601 episodes of candidaemia among 1.2 million discharges. The overall incidence was 1.22 episodes per 1000 discharges and varied among the hospitals (range 0.16–4.53 per 1000 discharges) and countries (range 0.25–2.93 per 1000 discharges). The number of Candida blood isolates and the total number of fungal isolates were highly correlated among the six countries (R² = 0.87) and 25 hospitals (R² = 0.77). There was a moderate correlation between incidence of candidaemia and the intensive care unit (ICU)/total bed ratio (R² = 0.47), although ICUs contributed to only 23% of candidaemia cases. Of 1910 blood isolates evaluated, Candida albicans was most frequently isolated (41.3%), followed by Candida tropicalis (25.4%), Candida glabrata (13.9%) and Candida parapsilosis (12.1%). The proportion of C. tropicalis among blood isolates was higher in haemato-oncology wards than others wards (33.7% versus 24.5%, p 0.0058) and was more likely to be isolated from tropical countries than other Asian countries (46.2% versus 18.9%, p 0.04). In conclusion, the ICU settings contribute, at least in part, to the incidence variation among hospitals. The species distribution is different from Western countries. Both geographic and healthcare factors contribute to the variation of species distribution.
Quantifying signals and uncertainties in climate models is essential for the detection, attribution, prediction and projection of climate change
. Although inter-model agreement is high for ...large-scale temperature signals, dynamical changes in atmospheric circulation are very uncertain
. This leads to low confidence in regional projections, especially for precipitation, over the coming decades
. The chaotic nature of the climate system
may also mean that signal uncertainties are largely irreducible. However, climate projections are difficult to verify until further observations become available. Here we assess retrospective climate model predictions of the past six decades and show that decadal variations in North Atlantic winter climate are highly predictable, despite a lack of agreement between individual model simulations and the poor predictive ability of raw model outputs. Crucially, current models underestimate the predictable signal (the predictable fraction of the total variability) of the North Atlantic Oscillation (the leading mode of variability in North Atlantic atmospheric circulation) by an order of magnitude. Consequently, compared to perfect models, 100 times as many ensemble members are needed in current models to extract this signal, and its effects on the climate are underestimated relative to other factors. To address these limitations, we implement a two-stage post-processing technique. We first adjust the variance of the ensemble-mean North Atlantic Oscillation forecast to match the observed variance of the predictable signal. We then select and use only the ensemble members with a North Atlantic Oscillation sufficiently close to the variance-adjusted ensemble-mean forecast North Atlantic Oscillation. This approach greatly improves decadal predictions of winter climate for Europe and eastern North America. Predictions of Atlantic multidecadal variability are also improved, suggesting that the North Atlantic Oscillation is not driven solely by Atlantic multidecadal variability. Our results highlight the need to understand why the signal-to-noise ratio is too small in current climate models
, and the extent to which correcting this model error would reduce uncertainties in regional climate change projections on timescales beyond a decade.
The primary aim of this study was to evaluate the antitumor efficacy of the bromodomain inhibitor JQ1 in pancreatic ductal adenocarcinoma (PDAC) patient-derived xenograft (tumorgraft) models. A ...secondary aim of the study was to evaluate whether JQ1 decreases expression of the oncogene c-Myc in PDAC tumors, as has been reported for other tumor types. We used five PDAC tumorgraft models that retain specific characteristics of tumors of origin to evaluate the antitumor efficacy of JQ1. Tumor-bearing mice were treated with JQ1 (50 mg/kg daily for 21 or 28 days). Expression analyses were performed with tumors harvested from host mice after treatment with JQ1 or vehicle control. An nCounter PanCancer Pathways Panel (NanoString Technologies) of 230 cancer-related genes was used to identify gene products affected by JQ1. Quantitative RT-PCR, immunohistochemistry and immunoblots were carried out to confirm that changes in RNA expression reflected changes in protein expression. JQ1 inhibited the growth of all five tumorgraft models (P<0.05), each of which harbors a KRAS mutation; but induced no consistent change in expression of c-Myc protein. Expression profiling identified CDC25B, a regulator of cell cycle progression, as one of the three RNA species (TIMP3, LMO2 and CDC25B) downregulated by JQ1 (P<0.05). Inhibition of tumor progression was more closely related to decreased expression of nuclear CDC25B than to changes in c-Myc expression. JQ1 and other agents that inhibit the function of proteins with bromodomains merit further investigation for treating PDAC tumors. Work is ongoing in our laboratory to identify effective drug combinations that include JQ1.
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}.
The Energy Exascale Earth System Model Atmosphere Model version 1, the atmospheric component of the Department of Energy's Energy Exascale Earth System Model is described. The model began as a fork ...of the well‐known Community Atmosphere Model, but it has evolved in new ways, and coding, performance, resolution, physical processes (primarily cloud and aerosols formulations), testing and development procedures now differ significantly. Vertical resolution was increased (from 30 to 72 layers), and the model top extended to 60 km (~0.1 hPa). A simple ozone photochemistry predicts stratospheric ozone, and the model now supports increased and more realistic variability in the upper troposphere and stratosphere. An optional improved treatment of light‐absorbing particle deposition to snowpack and ice is available, and stronger connections with Earth system biogeochemistry can be used for some science problems. Satellite and ground‐based cloud and aerosol simulators were implemented to facilitate evaluation of clouds, aerosols, and aerosol‐cloud interactions. Higher horizontal and vertical resolution, increased complexity, and more predicted and transported variables have increased the model computational cost and changed the simulations considerably. These changes required development of alternate strategies for tuning and evaluation as it was not feasible to “brute force” tune the high‐resolution configurations, so short‐term hindcasts, perturbed parameter ensemble simulations, and regionally refined simulations provided guidance on tuning and parameterization sensitivity to higher resolution. A brief overview of the model and model climate is provided. Model fidelity has generally improved compared to its predecessors and the CMIP5 generation of climate models.
Plain Language Summary
This study provides an overview of a new computer model of the Earth's atmosphere that is used as one component of the Department of Energy's latest Earth system model. The model can be used to help understand past, present, and future changes in Earth's behavior as the system responds to changes in atmospheric composition (like pollution and greenhouse gases), land, and water use and to explore how the atmosphere interacts with other components of the Earth system (ocean, land, biology, etc.). Physical, chemical, and biogeochemical processes treated within the atmospheric model are described, and pointers to previous and recent work are listed to provide additional information. The model is compared to present‐day observations and evaluated for some important tests that provide information about what could happen to clouds and the environment as changes occur. Strengths and weaknesses of the model are listed, as well as opportunities for future work.
Key Points
A brief description and evaluation is provided for the atmospheric component of the Department of Energy's Energy Exascale Earth System Model
Model fidelity has generally improved compared to predecessors and models participating in past international model evaluations
Strengths and weaknesses of the model, as well as opportunities for future work, are described
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.
We demonstrate the room-temperature control of magnetization reversal with an electric field in an epitaxial nanostructure consisting of ferrimagnetic nanopillars embedded in a ferroelectric matrix. ...This was achieved by combining a weak, uniform magnetic field with the switching electric field to selectively switch pillars with only one magnetic configuration. On the basis of these experimental results, we propose to use an electric field to assist magnetic recording in multiferroic systems with high perpendicular magnetic anisotropy.
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