The additive or synergistic sustained antitumour effect of immune checkpoint inhibitors in combination with oxaliplatin-based chemotherapy has previously been reported. We investigated the efficacy ...of nivolumab plus oxaliplatin-based chemotherapy versus placebo plus oxaliplatin-based chemotherapy as first-line therapy for patients with HER2-negative, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer.
We did a randomised, multicentre, double-blind, placebo-controlled, phase 2–3 trial (ATTRACTION-4) at 130 centres (hospitals, cancer centres, and medical centres) across Japan, South Korea, and Taiwan. We enrolled patients aged 20 years and older with previously untreated (except for neoadjuvant or adjuvant chemotherapy completed ≥180 days before recurrence), HER2-negative, unresectable, advanced or recurrent gastric or gastro-oesophageal junction cancer (regardless of PD-L1 expression), at least one measurable lesion per Response Evaluation Criteria in Solid Tumours guidelines (version 1.1), and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned (1:1) to chemotherapy every 3 weeks (intravenous oxaliplatin 130 mg/m2 on day 1 plus either oral S-1 40 mg/m2 SOX or oral capecitabine 1000 mg/m2 CAPOX, twice daily on days 1–14), in addition to either 360 mg nivolumab intravenously every 3 weeks (nivolumab plus chemotherapy group) or placebo (placebo plus chemotherapy group). Randomisation was done using an interactive web response system with block sizes of four and stratified by intensity of PD-L1 expression, ECOG performance status score, disease status, and geographical region. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoints were centrally assessed progression-free survival and overall survival in the intention-to-treat population, which included all randomly assigned patients. Safety was assessed in all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT02746796. Trial recruitment is complete and follow-up is ongoing.
Between March 23, 2017, and May 10, 2018, 724 patients were randomly assigned to treatment: 362 patients to the nivolumab plus chemotherapy group and 362 to the placebo plus chemotherapy group. At the time of data cutoff on Oct 31, 2018, with a median follow-up of 11·6 months (IQR 8·7–14·1), median progression-free survival at a prespecified interim analysis was 10·45 months (95% CI 8·44–14·75) in the nivolumab plus chemotherapy group and 8·34 months (6·97–9·40) in the placebo plus chemotherapy group (hazard ratio HR 0·68; 98·51% CI 0·51–0·90; p=0·0007). At the time of data cutoff on Jan 31, 2020, with a median follow-up of 26·6 months (IQR 24·1–29·0), median overall survival at the final analysis was 17·45 months (95% CI 15·67–20·83) in the nivolumab plus chemotherapy group and 17·15 months (15·18–19·65) in the placebo plus chemotherapy group (HR 0·90; 95% CI 0·75–1·08; p=0·26). The most common treatment-related grade 3–4 adverse events were neutrophil count decreased (71 20% of 359 patients in the nivolumab plus chemotherapy group vs 57 16% of 358 patients in the placebo plus chemotherapy group) and platelet count decreased (34 9% vs 33 9%). Treatment-related serious adverse events of any grade were observed in 88 (25%) patients in the nivolumab plus chemotherapy group and in 51 (14%) in the placebo plus chemotherapy group, of which the most common was decreased appetite (18 5% vs ten 3%). Six treatment-related deaths occurred: three in the nivolumab plus chemotherapy group (one each of febrile neutropenia, hepatic failure, and sudden death) and three in the placebo plus chemotherapy group (one each of sepsis, haemolytic anaemia, and interstitial lung disease).
Nivolumab combined with oxaliplatin-based chemotherapy significantly improved progression-free survival, but not overall survival, in Asian patients with untreated, HER2-negative, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer, and could potentially be a new first-line treatment option for these patients.
Ono Pharmaceutical and Bristol-Myers Squibb.
This study presents peer-to-peer (P2P) energy transaction mechanisms to maximize social welfare considering the uncertainty and profit fairness of the players. The P2P energy transaction problem is ...formulated as a P2P energy transaction pair matching and the determination of the P2P transaction price. To solve the problem, the optimal condition to maximize social welfare is determined using stochastic P2P energy transaction performance analysis based on the uncertainty characteristics. The analysis results show that social welfare is maximized to match the producer and consumer pairs that have similar demand characteristics; the P2P transaction price balances the profit fairness between the pair. Using these results, two centralized P2P energy transaction mechanisms are proposed by modifying the optimization problem. Moreover, a decentralized P2P energy transaction mechanism that operates in a distributed manner is suggested with the operational signal flow for the implementation of the mechanism. The simulation results show that the centralized and decentralized mechanisms have near optimal performance, with less than a 0.5% and 1% optimal gap compared to the optimal solution that requires perfect information including uncertainty, respectively. However, the decentralized mechanism is less computationally complex and uses less information than the centralized mechanisms; consequently, it can alleviate the operational burden and security and privacy problems. In addition, the results show that the performance of P2P energy transaction is related to the relative demand ratio between the producer and consumer. The optimal condition and results suggest a guide to the design of the P2P energy transaction.
Background
Components of the metabolic syndrome (MetS), such as elevated fasting glucose levels and abdominal obesity, have been suggested as potential risk factors for pancreatic cancer. However, ...data are still insufficient to assure the influence of MetS on incident pancreatic cancer. The objective of the current study was to investigate the association between MetS, metabolic components, and the risk of pancreatic cancer.
Methods
In the Korea National Health Information Database, 223,138 individuals who were without pancreatic cancer in 2009 were enrolled and followed until 2013. They were categorized into 4 groups according to the number of baseline metabolic components (0, 1, 2, 3, and 4‐5). A multivariate Cox proportional hazard model was used to calculate the adjusted hazard ratios (HRs) and 95% CIs for incident pancreatic cancer according to the presence of MetS and the number of metabolic components. In addition, the risk of pancreatic cancer was evaluated in individuals who had a single metabolic component.
Results
The presence of MetS was significantly associated with incident pancreatic cancer (adjusted HR, 1.47; 95% CI, 1.19‐1.81). The group with 4 or 5 baseline metabolic components had a higher risk of pancreatic cancer than the other groups (0 components: reference category; 1 component: adjusted HR, 0.94 95% CI, 0.61‐1.45; 2 components: adjusted HR, 1.03 95% CI, 0.68‐1.56; 3 components: adjusted HR, 1.35 95% CI, 0.89‐2.04; 4‐5 components: adjusted HR, 1.64 95% CI, 1.06‐2.51). Regarding associations between the individual metabolic components and pancreatic cancer, no metabolic component alone had a statistically significant association with pancreatic cancer.
Conclusions
MetS is a potential risk factor for pancreatic cancer. The presence of ≥4 metabolic components leads to a higher risk of pancreatic cancer even within categories of the MetS.
The metabolic syndrome (MetS) is a potential risk factor for incident pancreatic cancer. The presence of abnormalities in more components of the MetS leads to a higher risk of pancreatic cancer even within categories of the MetS.
Forecasting uncertainties limit the widespread adoption of wind power generation. Energy storage systems (ESSs) are essential for managing uncertainty, and ESS sizing determines the availability of ...uncertainty management. However, most ESS sizing studies utilize heuristic approaches. Therefore, research on the determination of ESS sizing related to uncertainty management performance is needed. This paper proposes a theoretical ESS sizing method that considers the stochastic properties of the uncertainty. In the proposed method, the power subsystem (PS) and energy subsystem (ES) capacities, which are related to the instantaneous and accumulated uncertainty characteristics of the ESS, respectively, are determined in terms of the confidence interval of the uncertainty statistic. They are presented as simple formulas by applying the extreme value theory. Furthermore, to demonstrate the uncertainty management performance of ESS sizing, the mean absolute error (MAE) is analyzed, as the variance and absolute errors of the uncertainty determine the MAE of the PS and ES, respectively. A numerical study using real wind power generation and its forecasting data verifies that the proposed method suitably reflects the characteristics of the uncertainty, with an analysis gap between the analyzed MAE and the actual measured value of less than 1%. This study can act as a reference for the expected performance when using ESS and can be extended to the theoretical economic evaluation of ESS usage.
•Generalized theoretical ESS sizing is proposed with statistical uncertainty analysis.•An extreme value theorem is used to organize ESS sizing as simple closed formulas.•Uncertainty management performance is analyzed using MAE.•The analysis gap is less than 1% of the wind power generation capacity.•The theoretical results provide the appropriate ESS size to manage mismatch errors.
This paper proposes a novel integrated low-voltage dc-dc converter (LDC) and onboard battery charger (OBC) for electric vehicles (xEVs) that share heatsinks, terminals, sensing circuits, and circuit ...components between both parts. The proposed OBC-LDC integrated power unit (OLPU) can be simplified by modifying the internal connections of the vehicle, thus eliminating the cost of high-power cables. In addition, the OLPU decreases the number of circuit components and increases the total power density by combining or sharing heatsinks, terminals, sensing circuits, and circuit components. Further, the proposed circuit satisfies the performance characteristics of conventional OBCs and LDCs and can be operated as such. Moreover, a simultaneous charging method for both a high-voltage battery and a low-voltage battery is suggested through an additional operational mode that results from the integration. This paper also specifically describes the operating characteristics and the design method in each mode. Design considerations, including possible problems with the integrated circuit structure, are presented, and an additional compensation circuit is suggested to solve these problems. The prototype is built, and experiments are carried out to verify the performance and validity of the proposed power unit.
Fish are an essential resource in human society, and while ecological research on them is challenging, it is absolutely necessary. Recent technologies enabled researchers to monitor underwater fish ...behavior. Acoustic signals, satellite-mediated location estimation, and light-based geolocation are powerful tools for tracking fish movements from freshwater to deep-sea habitats. These tools allow us to track various fish species and elucidate their ecology. Furthermore, based on these technologies, we can develop fisheries management plans and enhance aquaculture productivity. In this review, we also discuss challenges in improving current technologies and provide future recommendations for fish bio-logging studies.
Digital technologies, especially information and communication technologies, paved the way for social welfare by providing efficient and effective means for services. In the energy sector, advanced ...metering infrastructures (AMIs) are essential for providing various services through information measurement. In this article, we focus on the deployment of an AMI in multi-dwelling units where automated meter reading (AMR) infrastructures are installed. In particular, we explore whether the AMR should substitute the AMI with few alterations, while ensuring desirable accuracy. To determine the adequacy of technology, information measurement performance, service performance, and implementation cost are used as the indicators. Through a case study using real data recorded in Korea, we quantitatively estimate that AMR-based information measurement can exhibit adequate performance and performance degradation of less than 1% in a service environment utilizing AMI with a low-cost investment. We also discuss several technologies and implementation issues in the upcycling of AMR for more reliable service. This study provides a guide for when configuring an information measurement system for a new energy service.
We present the results of high-resolution (R ≥ 30,000) optical and near-infrared (NIR) spectroscopic monitoring observations of an FU Orionis-type object (FUor), V960 Mon, which underwent an outburst ...in 2014 November. We have monitored this object with the Bohyunsan Optical Echelle Spectrograph and the Immersion GRating INfrared Spectrograph since 2014 December. Various features produced by a wind, disk, and outflow/jet were detected. The wind features varied over time and continually weakened after the outburst. We detected double-peaked line profiles in the optical and NIR, and the line widths tend to decrease with increasing wavelength, indicative of Keplerian disk rotation. The disk features in the optical and NIR spectra fit well with G-type and K-type stellar spectra convolved with a kernel to account for the maximum projected disk rotation velocities of about 40.3 3.8 km s−1 and 36.3 3.9 km s−1, respectively. We also report the detection of S ii and H2 emission lines, which are jet/outflow tracers and rarely found in FUors.
► This study dealt with mapping groundwater potential zones using a GIS. ► The importance of SPC-related factors was determined by a sensitivity analysis. ► The relationship between SPC and its ...related factors was calculated from a FR model. ► The groundwater potential map using the FR showed a prediction accuracy of 77.78%.
This study analyzed the relationships between groundwater specific capacity (SPC) and its related hydrological factors to assess the sensitivity of each factor and map the regional groundwater potential for the area of Pohang City, Korea, using a geographic information system (GIS) and a probability model. All related factors including topography, geology, lineament, and soil data were collected and entered into a spatial database. SPC data were collected from well locations, and SPC values of ≥6.25
m
3/d/m, corresponding to a yield of 500
m
3/d, were input to a spatial database. SPC data were then randomly selected in a 66/34 ratio to train and validate the model. A frequency-ratio model and sensitivity analysis were used to determine the relationships between SPC and its related factors and the importance of SPC-related factors. Sensitivity analysis allows for comparison of the combined effects of all factors except for one. The validation of the groundwater potential map overlain by all factors showed 77.78% accuracy. In the sensitivity analysis, the best accuracy was obtained by omitting ground elevation data (78.64%), and the worst accuracy resulted when soil texture was not included (76.64%). The results show that soil texture had the greatest effect on the groundwater potential and ground elevation had the least effect. Such information and the maps generated from it can be applied to groundwater management and groundwater resource exploration.
Whey protein concentrate (WPC), which contains α-lactalbumin and β-lactoglobulin, is utilized widely in the food industry. The Maillard reaction is a complex reaction that produces Maillard reaction ...products (MRPs), which are associated with the formation of antioxidant compounds. In this study, the hepatoprotection activity of MRPs of WPC against oxidative stress through the nuclear factor-E2-related factor 2 (Nrf2)-dependent antioxidant pathway in HepG2 cells was examined. Glucose–whey protein concentrate conjugate (Glc-WPC) was obtained from Maillard reaction between WPC and glucose. The fluorescence intensity of Glc-WPC increased after 7 d compared to native WPC, and resulted in loss of 48% of the free amino groups of WPC. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns of Glc-WPC showed the presence of a high-molecular-weight portion. Treatment of HepG2 cells with Glc-WPC increased cell viability in the presence of oxidative stress, inhibited the generation of intracellular reactive oxygen species by tert-butyl hydroperoxide (t-BHP), and increased the glutathione level. Nrf2 translocation and Nrf2, reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H)-quinone oxidoreductase 1 (NOQ1), heme oxygenase-1 (HO-1), glutamate-L-cysteine ligase (GCL)M and GCLC mRNA levels were increased by Glc-WPC. Also, Glc-WPC increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK). The results of this study demonstrate that Glc-WPC activates the Nrf2-dependent pathway through the phosphorylation of ERK1/2 and JNK in HepG2 cells, and induces production of antioxidant enzymes and phase II enzymes.
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