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PD-1 and PD-L1 inhibitors are active in metastatic urothelial carcinoma, but positive randomised data supporting their use as a first-line treatment are lacking. In this study we assessed outcomes with first-line pembrolizumab alone or combined with chemotherapy versus chemotherapy for patients with previously untreated advanced urothelial carcinoma. KEYNOTE-361 is a randomised, open-label, phase 3 trial of patients aged at least 18 years, with untreated, locally advanced, unresectable, or metastatic urothelial carcinoma, with an Eastern Cooperative Oncology Group performance status of up to 2. Eligible patients were enrolled from 201 medical centres in 21 countries and randomly allocated (1:1:1) via an interactive voice-web response system to intravenous pembrolizumab 200 mg every 3 weeks for a maximum of 35 cycles plus intravenous chemotherapy (gemcitabine [1000 mg/m] on days 1 and 8 and investigator's choice of cisplatin [70 mg/m] or carboplatin [area under the curve 5] on day 1 of every 3-week cycle) for a maximum of six cycles, pembrolizumab alone, or chemotherapy alone, stratified by choice of platinum therapy and PD-L1 combined positive score (CPS). Neither patients nor investigators were masked to the treatment assignment or CPS. At protocol-specified final analysis, sequential hypothesis testing began with superiority of pembrolizumab plus chemotherapy versus chemotherapy alone in the total population (all patients randomly allocated to a treatment) for the dual primary endpoints of progression-free survival (p value boundary 0·0019), assessed by masked, independent central review, and overall survival (p value boundary 0·0142), followed by non-inferiority and superiority of overall survival for pembrolizumab versus chemotherapy in the patient population with CPS of at least 10 and in the total population (also a primary endpoint). Safety was assessed in the as-treated population (all patients who received at least one dose of study treatment). This study i

The detailed understanding of tsunami hazard risk using numerical simulations requires a numerical model that can accurately predict tsunami inundation phenomena on land. In such models, the structural effects are indirectly considered using the variation of bottom roughness as a proxy for the differences in building densities. Only a few studies have conducted intermodel tests to investigate tsunami inundation in complex coastal urban cities. During the tsunami analysis hackathon held in September 2020, eight research groups met to have a detailed discussion on the current urban inundation problems. In this study, we conducted an intermodel comparison of the numerical tsunami models, using the data from physical experiments that were performed on a detailed urban model. Our objective was to investigate the necessary conditions of an accurate numerical model based that can ensure high reproducibility and practicality. It was confirmed that the accuracy of topographic data is an important parameter for tsunami inundation simulations in complex urban areas. Based on the computational cost and accuracy, we suggest that a resolution of 1 cm of topographic data is a sufficient condition for tsunami inundation simulations on 1/250 scale model.

Researchers have developed tsunami inundation models based on nonlinear shallow water equations to estimate tsunami propagation and inundation. However, their empirical results are not in perfect agreement with those of other research institutes, even though the same governing equations are used. Therefore, we quantitatively evaluated the variability of tsunami simulations in this study. Several research institutes have conducted tsunami simulations under the same input conditions using tsunami inundation models adopted for tsunami hazard assessment, resulting in a certain degree of variability among them. By examining the spatial and temporal differences in various physical quantities, we identified the characteristic topography where the variability between tsunami simulations increases. A novel method for calculating statistics from the area integrals of physical quantities was proposed to demonstrate the variability in the overall simulation results. In addition, the effects of different setting parameters and computational environments on the simulation results of a single model were evaluated. The findings of this study are expected to not only serve as a basis to verify the reliability of source codes employed by users of the tsunami inundation model, but also contribute useful technical information to advance probabilistic tsunami hazard assessment in the future.

Tsunamis caused by submarine landslides are not accompanied by seismic waves and thus may appear at the coast without warning. In this study, detailed bathymetric surveys with a multi-narrow beam echo sounder were used to map submarine landslides on the continental shelf near Cape Muroto, in the Nankai trough off southwestern Japan. One of the surveyed submarine landslides was selected to supply dimensions for the simulation of a submarine mass movement by a two-layer flow model in which the upper and lower layers correspond to seawater and turbidity currents, respectively. The time series of seafloor deformation during this simulated landslide was used as the boundary condition to drive a tsunami simulation. The results showed strong directivity effects during tsunami generation in which pushing-dominant (positive) tsunami waves propagated seaward, in the direction of the submarine landslide, and pulling-dominant (negative) tsunami waves propagated landward. Both types of waves were strongly modified by frequency dispersion. For pulling-dominant waves, a tsunami simulation that included dispersion (Boussinesq) terms predicted greater maximum tsunami heights than a non-dispersive tsunami simulation. To avoid underestimation of tsunami heights, we recommend including dispersion terms when modeling tsunamis caused by submarine landslides for disaster planning purposes.

* Revised：A Panel Study of ‘Zombie’ SMEs in Japan: Identification, Borrowing and Investment Behavior [13-16, 2013], We estimated the extent to which ‘zombie’ SMEs existed in Japan by using panel data set of firms and investigated borrowing and investment functions of ‘zombie’ SMEs. We found that 5%~13% of SMEs are ‘zombie’ firms. As for borrowing behavior, ‘zombie’ firms did not succeed in reducing their loans. A fall in land value of SMEs induced an increase in borrowing of ‘zombie’firms or ever-greening. We also find that the profitability of investment, measured by marginal q and the increment of output, did not increase investment for the ‘zombie’firm, but rather ever-greening of loans increased investment in less productive and profitable projects.