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High-energy-density and safe rechargeable batteries are key components to realizing a low-carbon society. All-solid-state Li-metal batteries have the potential to achieve both high safety and high energy densities. However, the large interfacial resistance between solid electrolytes and cathodes is the major challenge for developing all-solid-state Li-metal batteries. Here we deposited a Li-rich layered metal oxide Li 1.2 Mn 0.54 Ni 0.13 Co 0.13 O 2 (LMNC) thin film (6 µm thick) on an Al-doped Li 7 La 3 Zr 2 O 12 (LLZO) substrate at room temperature by aerosol deposition. The LMNC particles were coated with Li 3 BO 3 (LBO), which acted as a binder to hold LMNC and LLZO together at heating. As a result, good interfacial contact was achieved between LMNC and LLZO. Yet reactions between LMNC and LBO would occur at heat treatment temperatures above 600 °C. The highest discharge capacity of the all-solid-state Li/LLZO/LBO-LMNC cell at 0.1 C and 60 °C was 223 mAh g-1. The main reason for the cell capacity decay was the cracking of the LBO-LMNC cathode layer during cycling. Searching for a more suitable binder material with a high fracture toughness is crucial for further developing the aerosol-deposited LLZO-based all-solid-state Li metal batteries. [ABSTRACT FROM AUTHOR]

Typhoon Lionrock (2016) was unusual among tropical cyclones (TCs) in that it formed east of the monsoon gyre in the western North Pacific, and moved counterclockwise. It rapidly intensified in the monsoon gyre in an environment of weak upper-tropospheric winds and vertical wind shear. This study used a 3-km mesh nonhydrostatic model to examine the warm-core intensification of Typhoon Lionrock, which was associated with cyclone-scale vigorous convection [i.e., convective bursts (CBs)]. The simulation reproduced the multiple CBs at intervals of 1 day or shorter, which were related to the diurnal cycles and other short time-scale variations in the TC convection. Each CB tended to precede peak temperature anomalies near the TC center by 0–12 h, indicating that the warm-core intensification occurred due to diabatic heating released by the vigorous eyewall convection. Notably, updrafts due to convection during the intensification phase were stronger than those occurring during the mature and decay phases, and the maximum temperature anomaly of the upper-tropospheric warm core rapidly increased during eyewall formation. In addition, this study indicated that most of the asymmetric inner-core vigorous convection associated with CBs, which was induced by the vertical wind shear, contributed to the warm-core intensification. Furthermore, the budget analysis of potential temperature within the TC inner core showed that adiabatic heating due to subsidence from near the tropopause within the eye, often following CBs, was essential in developing the eye. The lag correlation suggested the lag time between the CBs and the subsidence within the eye was 3–9 h. [ABSTRACT FROM AUTHOR]

The temporally dense geostationary satellite observations made possible by recent technological advances enable atmospheric motion vectors (AMVs) to be derived that are suitable for capturing atmospheric flows even of mesoscale phenomena, for which in situ data are scarce. Tropical cyclone (TC) outflows around the cloud top, reflecting TC secondary circulation, were computed by using AMVs derived from successive Multifunctional Transport Satellite (MTSAT) imagery, and the relationship between TC intensification rate (defined as the change of the best-track maximum sustained wind in the previous 24 h) and the outflow was investigated for 44 TCs occurring during 2011-14. During the TC intensification phase, temporal changes in the outflow were generally synchronous with changes in the cloud-top temperature of TC inner-core convective clouds detected by MTSAT infrared band. It was noteworthy that the intensification rates of 66% of the TCs peaked 0-36 h after outflow maximization and that the intensification rate for TCs with a maximum rate of >15 m s−1 day−1 peaked after the outflow maximum. Furthermore, TCs with a large intensification rate and latent-heat release around the midlevel tended to have a large outflow during the intensification phase. A comparison of TCs with and without convective bursts (CBs) revealed that the correlation between outflow and the TC intensification rate was higher for TCs accompanied by CBs than for those without CBs, implying that a rapid deepening of inner-core convection is important for intensification of a TC's secondary circulation. The outflow tended to be most correlated with the TC intensification rate 0-6 h earlier. [ABSTRACT FROM AUTHOR]

Background: In the THOR trial (NCT03390504) Cohort 1, erdafitinib demonstrated significantly prolonged overall survival (OS) (median 12.1 versus 7.8 months) and reduced risk of death by 36% (hazard ratio 0.64, P = 0.005) compared with chemotherapy in metastatic urothelial carcinoma (mUC) patients with FGFR alterations who progressed after ≥ 1 prior treatments, including anti-PD-(L)1. There have been no reports of the Japanese subgroup results yet.THOR Cohort 1 randomized patients to erdafitinib once daily or docetaxel/vinflunine once every 3 weeks. Primary endpoint was OS. Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). No specific statistical power was set for this Japanese subgroup analysis.Of 266 patients randomized, 27 (14 erdafitinib; 13 chemotherapy) were Japanese. Baseline characteristics were generally similar between treatments and to the overall population, except for more males, lower body weight, and more upper tract primary tumors among Japanese patients. Compared with chemotherapy, erdafitinib showed improved OS (median 25.4 versus 12.4 months), PFS (median 8.4 versus 2.9 months) and ORR (57.1% versus 15.4%). Any grade treatment-related adverse events (AEs) occurred in all patients from both arms but Grade 3/4 AEs and AEs leading to discontinuation were lower in the erdafitinib arm. No new safety signals were observed in the Japanese subgroup.In the Japanese subgroup, erdafitinib showed improved survival and response compared to chemotherapy, with no new safety concerns. These results support erdafitinib as a treatment option for Japanese mUC patients with FGFR alterations, and early FGFR testing after diagnosis of mUC should be considered.Methods: In the THOR trial (NCT03390504) Cohort 1, erdafitinib demonstrated significantly prolonged overall survival (OS) (median 12.1 versus 7.8 months) and reduced risk of death by 36% (hazard ratio 0.64, P = 0.005) compared with chemotherapy in metastatic urothelial carcinoma (mUC) patients with FGFR alterations who progressed after ≥ 1 prior treatments, including anti-PD-(L)1. There have been no reports of the Japanese subgroup results yet.THOR Cohort 1 randomized patients to erdafitinib once daily or docetaxel/vinflunine once every 3 weeks. Primary endpoint was OS. Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). No specific statistical power was set for this Japanese subgroup analysis.Of 266 patients randomized, 27 (14 erdafitinib; 13 chemotherapy) were Japanese. Baseline characteristics were generally similar between treatments and to the overall population, except for more males, lower body weight, and more upper tract primary tumors among Japanese patients. Compared with chemotherapy, erdafitinib showed improved OS (median 25.4 versus 12.4 months), PFS (median 8.4 versus 2.9 months) and ORR (57.1% versus 15.4%). Any grade treatment-related adverse events (AEs) occurred in all patients from both arms but Grade 3/4 AEs and AEs leading to discontinuation were lower in the erdafitinib arm. No new safety signals were observed in the Japanese subgroup.In the Japanese subgroup, erdafitinib showed improved survival and response compared to chemotherapy, with no new safety concerns. These results support erdafitinib as a treatment option for Japanese mUC patients with FGFR alterations, and early FGFR testing after diagnosis of mUC should be considered.Results: In the THOR trial (NCT03390504) Cohort 1, erdafitinib demonstrated significantly prolonged overall survival (OS) (median 12.1 versus 7.8 months) and reduced risk of death by 36% (hazard ratio 0.64, P = 0.005) compared with chemotherapy in metastatic urothelial carcinoma (mUC) patients with FGFR alterations who progressed after ≥ 1 prior treatments, including anti-PD-(L)1. There have been no reports of the Japanese subgroup results yet.THOR Cohort 1 randomized patients to erdafitinib once daily or docetaxel/vinflunine once every 3 weeks. Primary endpoint was OS. Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). No specific statistical power was set for this Japanese subgroup analysis.Of 266 patients randomized, 27 (14 erdafitinib; 13 chemotherapy) were Japanese. Baseline characteristics were generally similar between treatments and to the overall population, except for more males, lower body weight, and more upper tract primary tumors among Japanese patients. Compared with chemotherapy, erdafitinib showed improved OS (median 25.4 versus 12.4 months), PFS (median 8.4 versus 2.9 months) and ORR (57.1% versus 15.4%). Any grade treatment-related adverse events (AEs) occurred in all patients from both arms but Grade 3/4 AEs and AEs leading to discontinuation were lower in the erdafitinib arm. No new safety signals were observed in the Japanese subgroup.In the Japanese subgroup, erdafitinib showed improved survival and response compared to chemotherapy, with no new safety concerns. These results support erdafitinib as a treatment option for Japanese mUC patients with FGFR alterations, and early FGFR testing after diagnosis of mUC should be considered.Conclusion: In the THOR trial (NCT03390504) Cohort 1, erdafitinib demonstrated significantly prolonged overall survival (OS) (median 12.1 versus 7.8 months) and reduced risk of death by 36% (hazard ratio 0.64, P = 0.005) compared with chemotherapy in metastatic urothelial carcinoma (mUC) patients with FGFR alterations who progressed after ≥ 1 prior treatments, including anti-PD-(L)1. There have been no reports of the Japanese subgroup results yet.THOR Cohort 1 randomized patients to erdafitinib once daily or docetaxel/vinflunine once every 3 weeks. Primary endpoint was OS. Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). No specific statistical power was set for this Japanese subgroup analysis.Of 266 patients randomized, 27 (14 erdafitinib; 13 chemotherapy) were Japanese. Baseline characteristics were generally similar between treatments and to the overall population, except for more males, lower body weight, and more upper tract primary tumors among Japanese patients. Compared with chemotherapy, erdafitinib showed improved OS (median 25.4 versus 12.4 months), PFS (median 8.4 versus 2.9 months) and ORR (57.1% versus 15.4%). Any grade treatment-related adverse events (AEs) occurred in all patients from both arms but Grade 3/4 AEs and AEs leading to discontinuation were lower in the erdafitinib arm. No new safety signals were observed in the Japanese subgroup.In the Japanese subgroup, erdafitinib showed improved survival and response compared to chemotherapy, with no new safety concerns. These results support erdafitinib as a treatment option for Japanese mUC patients with FGFR alterations, and early FGFR testing after diagnosis of mUC should be considered. [ABSTRACT FROM AUTHOR]

Background: Apalutamide, a nonsteroidal potent androgen receptor antagonist, was safe and effective in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic-CRPC (mCRPC) in global studies. In this phase 1 study, safety, pharmacokinetics (PK), and efficacy of apalutamide were evaluated in Japanese patients with mCRPC. Methods: In this open-label, multi-center study, patients received apalutamide 240 mg (once-daily, orally) for first 1 week (PK week) during which PK parameters were assessed. 1 week later (Cycle 1 Day1), after reassessing safety, continuous daily dosing (4 weeks/cycle; once-daily orally) was initiated. Endpoints evaluated were: safety, tolerability, PK and antitumour efficacy of apalutamide. Dose-limiting toxicities (DLTs) were evaluated during PK week and Cycle 1. Results: All six patients received apalutamide. The most common treatment-emergent adverse events (TEAEs) were abdominal discomfort, nasopharyngitis, dysgeusia, rash, and hot flush [2/6 patients (33.3%) each]. No death or DLTs were reported. Grade 3 TEAEs were spinal-cord compression and renal disorder (1/6 patient each). In continuous daily dosing period, PK steady-state of apalutamide was reached approximately by week 4. A significant accumulation of apalutamide was observed (mean accumulation index 3.55), based on AUC0–24. Median (range) serum prostate-specific antigen level decreased from 54.42 (8.92–310.11) ng/mL at baseline to 11.70 (0.37–47.74) ng/mL at week 12 with ≥ 50% reduction in 4/6 (66.7%) patients and 90% reduction in 2/6 (33.3%) patients. Conclusion: Apalutamide had manageable safety profile, without any DLT or any new safety signals, and favourable efficacy in Japanese mCRPC patients. Thus, it was ascertained to be an adequate dosage regimen in Japanese mCRPC patients. Trial registration: ClinicalTrials.gov identifier: NCT02162836. [ABSTRACT FROM AUTHOR]

The impact of the assimilation of high spatial and temporal resolution atmospheric motion vectors (AMVs) on tropical cyclone (TC) forecasts has been investigated. The high-resolution AMVs are derived from the full disk scan of the new generation geostationary satellite Himawari-8. Forecast experiments for three TCs in 2016 in a western North Pacific basin are performed using the National Centers for Environmental Prediction (NCEP) operational Hurricane Weather Research and Forecasting Model (HWRF). Two different ensemble–variational hybrid data assimilation configurations (using background error covariance created by global ensemble forecast and HWRF ensemble forecast), based on the Gridpoint Statistical Interpolation (GSI), are used for the sensitivity experiments. The results show that the inclusion of high-resolution Himawari-8 AMVs (H8AMV) can benefit the track forecast skill, especially for long-range lead times. The diagnosis of optimal steering flow indicates that the improved track forecast seems to be attributed to the improvement of initial steering flow surrounding the TC. However, the assimilation of H8AMV increases the negative intensity bias and error, especially for short-range forecast lead times. The investigation of the structural change from the assimilation of H8AMV revealed that the following two factors are likely related to this degradation: 1) an increase of inertial stability outside the radius of maximum wind (RMW), which weakens the boundary layer inflow; and 2) a drying around and outside the RMW. Assimilating H8AMV using background error covariance created from HWRF ensemble forecast contributes to a significant reduction in negative intensity bias and error, and there is a significant benefit to TC size forecast. [ABSTRACT FROM AUTHOR]

The article reports on a study that explored the origin and evolutionary process of the sequential relationship between Langerhans cell histiocytosis (LCH) and acute lymphoblastic leukemia (ALL). Topics discussed include the comprehensive genomic analysis of the dynamics of clonal architecture for one case and the genomic analysis performed for another 2 ALL cases that subsequently developed LCH. The derivation of LCH from a founding clone with genomic alterations common to ALL is mentioned.

T-LGL leukemia has been rarely reported in children. We report a child with T-LGL leukemia who presented with anemia and went on to develop Crohn's disease. Although prednisolone treatment proved effective in the treatment of anemia, large granular lymphocyte counts increased as the doses were tapered. T-cell rearrangement studies revealed a clonal rearrangement of the TCR Vβ/jβ2 gene. Concurrently, the patient developed severe diarrhea. Inflammatory changes across the upper and lower intestines led to the diagnosis of Crohn's disease. This case highlights that T-LGL leukemia could be occurred in children. Flow cytometry and/or T-cell gene rearrangement studies are recommend in patients of anemia and various kind of autoimmune diseases including Crohn's disease, even in children. [ABSTRACT FROM AUTHOR]

This study investigates the assimilation impact of rapid-scan (RS) atmospheric motion vectors (AMVs) derived from the geostationary satellite Himawari-8 on tropical cyclone (TC) forecasts. Forecast experiments for three TCs in 2016 in the western North Pacific basin are performed using the National Centers for Environmental Prediction (NCEP) operational Hurricane Weather Research and Forecasting Model (HWRF). An ensemble-variational hybrid data assimilation system is used as an initialization. The results show that the assimilation of RS-AMVs can improve the track forecast skill, while the weak bias or slow intensification bias increases at the shorter forecast lead time. A vortex initialization in HWRF has a substantial impact on TC structure, but it has neutral impacts on the track and intensity forecasts. A thinning of AMVs mitigates the weak bias caused by RS-AMV assimilation, resulting in the reduction of intensity error. However, it degrades the track forecast skill for a longer lead time. A decomposition of the TC steering flows demonstrated that the change in TC-induced flow was a primary factor for reducing the track forecast error, and the change in environmental flow has less impact on the track forecast. The investigation of the structural change from the assimilation of RS-AMV revealed that the following two factors are likely related to the intensity forecast degradation: (1) an increase of inertial stability outside the radius of maximum wind (RMW), which weakens the boundary layer inflow; and (2) a drying around and outside the RMW. [ABSTRACT FROM AUTHOR]