Compacted bentonite can be used as an engineered barrier to inhibit radionuclide migration in radioactive waste disposal. Thermal-hydro-mechanical-chemical coupled phenomena occur inside the ...engineered barrier and change the engineering properties of compacted bentonite, for example, swelling and permeability, for a long-term. Thus far, the properties of bentonite have been investigated in various academic fields, including clay science and mineralogy. The properties of artificially compacted bentonite have also been investigated, specifically to design engineered barriers. Therefore, previous literature and recent findings on the fundamental behavior of compacted bentonite and its influence on the performance of engineered barriers are overviewed from an engineering perspective. The compaction of powdered bentonite and microstructure of compacted bentonite are first introduced. Second, the swelling characteristics and permeability of compacted bentonite are introduced, and microscopic and macroscopic viewpoints on each research subject are distinguished. Furthermore, the effects of chemical alteration under alkaline conditions on the hydro and mechanical properties of compacted bentonite are introduced as an example of a study on thermal-hydro-mechanical-chemical coupled phenomena. An outlook for the further development of the engineering appreciations of bentonite for radioactive waste disposal is provided.
This study evaluated the shear characteristics of compacted Ca-bentonite immersed in 0.1 mol/L of NaOH, KOH, and KOH–NaOH and 0.005 mol/L of Ca(OH)2 at 40℃ over a maximum period of 1710 days. ...Triaxial compression tests were performed on the immersed specimens, and the mineral composition, mean layer charge, leachable cations, and microstructure were investigated. The dissolution of cristobalite was significant at high pH levels, whereas phillipsite was precipitated in the specimens immersed in the NaOH and NaOH–KOH solutions. The amount of leachable cations increased substantially, indicating that soluble secondary products (non-crystalline phase) were present in the specimens, as was proven by the observation of gel-like products comprised of Ca and Si on the microphotograph. An increase and decrease in the maximum deviator stress occurred as a result of the dissolution and precipitation. A structural parameter was proposed in this study by assuming the contribution of the secondary products to the cementation of the soil skeleton. This provided a series state transition of the compacted bentonite, where the maximum deviator stress increased with the cementation of the non-crystalline secondary phase. However, the progressing dissolution of the primary minerals decreased the dry density, thereby loosening the cemented structure and reducing the maximum deviator stress.
The self-sealing behaviors of compacted Na- and Ca-bentonite–sand mixtures were investigated by conducting swelling–permeability tests with specimens containing three types of technological voids. ...The technological voids, including an upper gap, a surrounding gap, and a center hole of the specimens at 0.03–17.65% of the total cell volume, were sealed by the swelling of the specimen. The vertical and lateral pressures became steady during the experiments, resulting in equal equilibrium pressure in the surrounding gap. The unequal equilibrium pressure in the vertical and lateral directions was measured when the upper gap and center hole were set. The lateral pressure tended to be higher than the vertical pressure. The residual compaction pressure likely explains the higher equilibrium lateral pressure. The coefficient of permeability depended on the average effective montmorillonite dry density in both Na- and Ca-bentonite–sand mixtures. This study proposed an effective Na-montmorillonite dry density, focusing on the high swelling potential of montmorillonite with exchangeable Na ions. The effective Na-montmorillonite dry density of the specimen, including the swollen part, exhibited a unique relation with the permeability after self-sealing, despite the different ionic types of bentonite. Under fully saturated condition, the distribution of water content throughout the specimen after self-sealing suggested that the dry density of the swollen part was lower than the initial specimen part, despite the presence of steady state pressures. It is most likely that the density distribution remained after self-sealing if external factors, including changeable boundary conditions and pore water chemistry, are not considered. Although the specimen after self-sealing exhibited the potential for heterogeneous density, its permeability was approximately evaluated by using the average effective Na-montmorillonite dry density.
•Self-sealing ability of compacted bentonite–sand mixtures.•Swelling pressure after sealing the technological voids.•Permeability after sealing the technological voids.•Distribution of water content indicated heterogeneous density at physical balance.
We evaluated the efficacy and safety of fosnetupitant (FosNTP) versus fosaprepitant (FosAPR) for preventing highly emetogenic chemotherapy-induced nausea and vomiting. This phase III study was the ...first head-to-head comparison between two different neurokinin-1 receptor antagonists in combination with palonosetron and dexamethasone.
Patients scheduled to receive cisplatin-based chemotherapy were randomly assigned 1:1 to FosNTP 235 mg or FosAPR 150 mg in combination with palonosetron 0.75 mg and dexamethasone. The primary end point was overall (0-120 hours) complete response (CR; no emetic event and no rescue medication) rate, stratified by sex and age category, to show the noninferiority of FosNTP to FosAPR (noninferiority margin, -10% for the difference in the overall CR rate).
Overall, 795 patients were randomly assigned, of whom 785 received the study drug (FosNTP N = 392
FosAPR N = 393) and were evaluated for efficacy and safety. The overall CR rate was 75.2% versus 71.0%, respectively (Mantel-Haenszel common risk difference, 4.1%; 95% CI, -2.1% to 10.3%), demonstrating noninferiority of FosNTP to FosAPR. The CR rates in the acute (0-24 hours), delayed (24-120 hours), and beyond delayed (120-168 hours) phases, and at 0-168 hours were 93.9% versus 92.6%, 76.8% versus 72.8%, 86.5% versus 81.4%, and 73.2% versus 66.9%, respectively. The incidence rates of treatment-related adverse events with FosNTP versus FosAPR were 22.2% versus 25.4%, whereas adverse events or treatment-related adverse events relevant to injection site reactions were 11.0% versus 20.6% (
< .001) and 0.3% versus 3.6% (
< .001), respectively.
FosNTP demonstrated noninferiority to FosAPR, with a favorable safety profile and lower risk for injection site reactions. Thus, FosNTP is valuable in the prophylaxis of acute, delayed, and beyond delayed chemotherapy-induced nausea and vomiting.
We herein report a 42-year-old man with advanced lung adenocarcinoma and nivolumab-associated dermatomyositis. Nivolumab, an anticancer drug that is classified as an immune checkpoint inhibitor, ...often induces immune-related adverse events (irAEs). However, there have so far been no reports regarding nivolumab-associated dermatomyositis. This patient was diagnosed with dermatomyositis due to the presence of proximal muscle weakness with abnormal electromyography and magnetic resonance imaging findings; skin lesions, such as heliotrope rash, shawl sign, and periungual erythema; and an elevated serum aldolase level after nivolumab administration. It is important to consider drug-associated dermatomyositis in the differential diagnosis of patients presenting with skin lesions and muscle weakness after nivolumab treatment.
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Ways to reduce the duration of column percolation tests specified in ISO/TS 21268-3 were proposed.Four equilibrium periods and two flow rates on four different soils were ...tested.The time to perform column percolation tests can be shortened from 20 to 30days to 7⿿9 days.The recommended initial equilibrium period is 12⿿16h, shorten from 48h.The recommended flow rate is 36mL/h which is three times that specified in ISO/TS 21268-3.
Column percolation tests may be suitable for prediction of chemical leaching from soil and soil materials. However, compared with batch leaching tests, they are time-consuming. It is therefore important to investigate ways to shorten the tests without affecting the quality of results. In this study, we evaluate the feasibility of decreasing testing time by increasing flow rate and decreasing equilibration time compared to the conditions specified in ISO/TS 21268-3, with equilibration periods of 48h and flow rate of 12mL/h. We tested three equilibration periods (0, 12⿿16, and 48h) and two flow rates (12 and 36mL/h) on four different soils and compared the inorganic constituent releases. For soils A and D, we observed similar values for all conditions except for the 0h⿿36mL/h case. For soil B, we observed no appreciable differences between the tested conditions, while for soil C there were no consistent trends probably due to the difference in ongoing oxidation reactions between soil samples. These results suggest that column percolation tests can be shortened from 20 to 30days to 7⿿9days by decreasing the equilibration time to 12⿿16h and increasing the flow rate to 36mL/h for inorganic substances.
The global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum‐based chemotherapy in patients with resected stage IB–IIIA non‐small cell lung ...cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)–IIIA NSCLC. Upon completing 1–4 cycles of adjuvant cisplatin‐based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator‐assessed disease‐free survival, tested hierarchically first in patients with stage II–IIIA NSCLC whose tumors expressed programmed death‐ligand 1 (PD‐L1) on ≥1% of tumor cells, then in all randomized patients with stage II–IIIA NSCLC, and finally in the intention‐to‐treat (ITT) population (stage IB–IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all‐randomized stage II–IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD‐L1 tumor cells ≥1% stage II–IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease‐free survival improvement with atezolizumab vs BSC was observed in the PD‐L1 tumor cells ≥1% stage II–IIIA (unstratified hazard ratio HR, 0.52; 95% confidence interval CI, 0.25–1.08), all‐randomized stage II–IIIA (unstratified HR, 0.62; 95% CI, 0.35–1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34–1.10) populations. Atezolizumab‐related grade 3/4 adverse events occurred in 16% of patients; no treatment‐related grade 5 events occurred. Adjuvant atezolizumab showed disease‐free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.
This manuscript reports a subgroup analysis of Japanese patients in the global phase 3 IMpower010 study evaluating adjuvant atezolizumab vs best supportive care (BSC) following platinum‐based chemotherapy in resected stage IB‐IIIA non‐small cell lung cancer. Disease‐free survival (DFS) improvement with atezolizumab versus BSC was observed in the Japanese stage II‐IIIA population with PD‐L1 expression on ≥1% of tumor cells; in the Japanese all‐randomized stage II‐IIIA and ITT (stage IB‐IIIA) populations, unstratified DFS hazard ratios favored atezolizumab vs BSC. Adjuvant atezolizumab had a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.
This paper elucidates the influence of alkaline solutions on shear characteristics of bentonite and bentonite–sand mixtures. The compacted Ca–bentonite and bentonite–sand mixtures were immersed in ...0.1 mol/L–KOH and KOH–NaOH solutions at 40 ℃. Triaxial compression tests were executed using the immersed specimens. The mineral composition, montmorillonite content, expansivity of montmorillonite, mean layer charge, and leachable cations of the samples were investigated. The shear characteristics of the compacted bentonite changed after the immersion in alkaline solutions. The reduction of dry density, likely induced by the dissolution of minerals, and the K-exchange of montmorillonite are related to the decrease in shear strength. K-exchanged montmorillonite behaved as a pseudo-non-swelling layer. It is suggested that the precipitation of secondary products, composed of mainly calcium, contributed to the increase in shear strength. The change in the shear characteristics of the compacted bentonite was interpreted as primarily resulting from a combination of dissolution and precipitation.
To understand the self-healing property of an engineered barrier for radioactive waste disposal, the hydraulic conductivity of compacted bentonite–sand mixtures saturated with artificial seawater ...(SW) before and after gas migration was examined. Na- and Ca-bentonites were mixed with fine sand at a ratio of 70% bentonite in dry weight. Two aspects were considered during the experiment: the hydraulic conductivity of the specimen that was resaturated after gas migration and the distribution of water content immediately after gas migration to study gas migration pathways. The gas migrated through the entire cross-section of the specimen, and gas breakthrough occurred in the equilibrium swelling pressure range approximately. Subsequently, the gas flow rate reached a sufficient large value when the gas pressure was approximately twice the equilibrium axial pressure (the sum of swelling and confining pressures), which excluded the back pressure. Although the gas migration pathway was not visible when the specimen was observed immediately after gas migration, the water content distribution showed that several parts of the specimen with lower water content were connected in the direction of gas migration. After resaturation, the change in permeability was within a limited range—two to three times larger than that before gas migration for each type of bentonite in SW. This slight change suggests that gas migration creates a pore structure that cannot be sealed via crystalline swelling of montmorillonite in SW, even if highly compacted bentonite is used under a constant-volume condition.
•Gas migration of compacted bentonite–sand mixtures in seawater.•Saturated hydraulic conductivity after gas migration in seawater.•Breakthrough pressure increased along equilibrium axial pressure.•Low permeability of compacted bentonite did not change substantially.
Introduction
MET
exon 14 skipping mutation, observed in 3–4% of non-small cell lung cancer (NSCLC), is emerging as a targetable alteration
.
In recent years, immune checkpoint inhibitors (ICI) have ...been effective in treating several NSCLCs. Our research aimed to investigate the characteristics of patients with NSCLCs harboring
MET
exon 14 mutations and their response to ICI in Japan.
Methods
Among the 1954 consecutive NSCLCs diagnosed at Saitama Cancer Center between 2010 and 2019,
MET
exon 14 skipping mutations were detected in 68 (3.5%) NSCLCs. We evaluated their characteristics such as programmed cell death ligand 1 (PD-L1) expression.
Results
Median age of patients with NSCLCs harboring
MET
exon 14 skipping mutations was 73 years. PD-L1 was highly expressed in 17 (70.8%) of the 24 patients examined. Seven patients received ICI monotherapy, and three out of seven had a remarkable treatment response, resulted in objective response rate (ORR) of 42.9% and progression-free survival of 24.7 months. Three patients with donor splice-site mutations showed a long-term treatment response, despite the fact that two with acceptor splice-site mutations demonstrated no response and experienced early disease progression with ICI monotherapy.
Conclusion
Our results indicated that patients with NSCLCs harboring
MET
exon 14 mutations presented with a high rate of positive PD-L1 expression. ICI treatment showed a high ORR and long-term efficacy for NSCLCs harboring
MET
exon 14 mutations. Variants of
MET
exon 14 splice-site mutations may be associated with ICI response.
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