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Makito Miyake,1 Nobutaka Nishimura,1,2 Takuto Shimizu,1,3 Mikiko Ohnishi,4 Masaomi Kuwada,4 Yoshitaka Itami,5 Takeshi Inoue,5 Kenta Ohnishi,6 Yoshihiro Matsumoto,6 Takanori Yoshida,7 Yoshihiro Tatsumi,8 Masatake Shinohara,9 Shunta Hori,1 Yosuke Morizawa,1 Daisuke Gotoh,1 Yasushi Nakai,1 Satoshi Anai,1 Kazumasa Torimoto,1 Katsuya Aoki,1 Tomomi Fujii,10 Nobumichi Tanaka,1,11 Kiyohide Fujimoto1 1Department of Urology, Nara Medical University, Kashihara, Nara, 634-8522, Japan; 2Department of Urology, Okanami General Hospital, Iga, Mie, Japan; 3Department of Urology, Saiseikai Chuwa Hospital, Nara, Japan; 4Department of Urology, Matsusaka Chuo General Hospital, Matsusaka, Mie, Japan; 5Department of Urology, Nara Prefecture General Medical Center, Nara, Japan; 6Department of Urology, Hoshigaoka Medical Center, Hirakata, Osaka, Japan; 7Department of Urology, Tane General Hospital, Osaka, Japan; 8Department of Urology, JCHO Yamato Koriyama Hospital, Koriyama, Nara, Japan; 9Department of Urology, Osaka Gyoumeikan Hospital, Osaka, Japan; 10Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara, 634-8522, Japan; 11Department of Prostate Brachytherapy, Nara Medical University, Kashihara, Nara, 634-8522, JapanCorrespondence: Makito Miyake, Department of Urology, Nara Medical University, 840 Shijo-cho, Nara, 634-8522, Japan, Tel +81-744-22-3051 (ext 2338), Fax +81-744-22-9282, Email makitomiyake@yahoo.co.jpPurpose: The treatment landscape for advanced, unresectable, or metastatic urothelial carcinoma (aUC) has shifted substantially since the advent of immune checkpoint inhibitors (ICIs). We investigated the extent to which pembrolizumab therapy is superior to conventional chemotherapy as a second-line treatment.Patients and Methods: A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 94 patients (21%) who received second-line pembrolizumab and 75 (17%) who received second-line chemotherapy but never received third-line or later ICI therapy were included. We compared overall survival (OS) from the initial date of first-line chemotherapy between two groups by adjusting for prognostic factors through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The IPTW-adjusted hazard ratio and 95% confidence interval were estimated using a multivariate Cox regression analysis. To identify patients who were more likely to benefit from second-line pembrolizumab than from chemotherapy, we performed a subgroup analysis for OS with an IPTW-adjusted model.Results: The PSM-adjusted comparison showed a significant improvement in the prognosis with second-line pembrolizumab use (P = 0.01). The OS benefit with the advent of pembrolizumab was 8 months (18 months vs 26 months). Multivariable analyses using IPTW adjustment demonstrated that lymph node metastasis (P = 0.001), lung metastasis (P = 0.013), and bone metastasis (P = 0.003) were poor independent prognostic factors, and pembrolizumab use (P = 0.021) was a favorable independent prognostic factor. Subgroup analyses revealed that pembrolizumab was associated with survival benefits over chemotherapy in all subgroups, including young patients (age < 70 years), those who received radical surgery, and those without visceral metastasis.Conclusion: We demonstrated a significant improvement in prognosis after the advent of pembrolizumab for patients with aUC. ICIs should not be restricted based on patient characteristics.Keywords: urinary bladder neoplasms, immunotherapy, chemotherapy, survival, propensity score

Collisionless shocks are produced in counter-streaming plasmas with an external magnetic field. The shocks are generated due to an electrostatic field generated in counter-streaming laser-irradiated plasmas, as reported previously in a series of experiments without an external magnetic field [T. Morita et al., Phys. Plasmas, 17, 122702 (2010), Kuramitsu et al., Phys. Rev. Lett., 106, 175002 (2011)] via laser-irradiation of a double-CH-foil target. A magnetic field is applied to the region between two foils by putting an electro-magnet (∼10 T) perpendicular to the direction of plasma expansion. The generated shocks show different characteristics later in time (t > 20ns).

A collisionless Weibel-instability mediated shock in a self-generated magnetic field is studied using two-dimensional particle-in-cell simulation [Kato and Takabe, Astophys. J. Lett. 681, L93 (2008)]. It is predicted that the generation of the Weibel shock requires to use NIF-class high-power laser system. Collisionless electrostatic shocks are produced in counter-streaming plasmas using Gekko XII laser system [Kuramitsu et al., Phys. Rev. Lett. 106, 175002 (2011)]. A NIF facility time proposal is approved to study the formation of the collisionless Weibel shock. OMEGA and OMEGA EP experiments have been started to study the plasma conditions of counter-streaming plasmas required for the NIF experiment using Thomson scattering and to develop proton radiography diagnostics.

The experiments to simulate astrophysical jet generation are performed using Gekko XII (GXII) HIPER laser system at the Institute of Laser Engineering. In the experiments a fast plasma flow generated by shooting a CH plane (10 μm thickness) is observed at the rear side of the plane. By separating the focal spot of the main beams, a non-uniform plasma is generated. The non-uniform plasma flow in an external magnetic field (0.2∼0.3 T) perpendicular to the plasma is more collimated than that without the external magnetic field. The plasma β, the ratio between the plasma and magnetic pressure, is ≫ 1, and the magnetic Reynolds number is ∼150 in the collimated plasma. It is considered that the magnetic field is distorted by the plasma flow and enhances the jet collimation.

Process of counterstreaming plasma generation for laser irradiation of the innner-surface of the first plane of a double-plane target is investigated. The image taken by streaked self-emission optical pyrometer and radiation hydrodynamic simulation show the plasma from the second plane is ablated by radiation almost at the laser timing. After ∼5ns, increase in brightness and the generation of a plasma on the second plane are observed. According to the contemporary measurement of streaked interferometry, this is caused by the ablation of the second plane by the first plane plasma.

We consider a fractional 2mfactorial design derived from a simple array (SA) such that the (ℓ + 1)-factor and higher-order interactions are negligible, where 2ℓ ⩽m. The purpose of this article is to give a necessary and sufficient condition for an SA to be a balanced fractional 2mfactorial design of resolution 2ℓ + 1. Such a design is concretely characterized by the suffixes of the indices of an SA. [ABSTRACT FROM PUBLISHER]

We report the first direct measurement of temporally and spatially resolved plasma temperatures at a shock as well as its spatial structure and propagation in laser-produced counter-streaming plasmas. Two shocks are formed in counter-streaming collisionless plasmas early in time, and they propagate opposite directions. This indicates the existence of counter-streaming collisionless flows to keep exciting the shocks, even though the collisional effects increase later in time. The shock images are observed with optical diagnostics, and the upstream and downstream plasma parameters of one of the shocks are measured using Thomson scattering technique. [ABSTRACT FROM AUTHOR]

Adult testicular cytochrome P-450 was purified by a two-step procedureutilizing preparative isoelectrofocusing. Purification was achieved 1132 timeswith a yield of 4.82%. 17α-hydroxylase activity was shown to be 14.5nmol of product/min/nmol of P-450. The cytochrome P-450 was determined tohave an isoelectric point of 6.45 on analytical isoelectric focusing. Thepurified cytochrome P-450 was found to be homogeneous and its molecular weightwas estimated to be 52000 on polyacrylamide gel electrophoresis in the presenceof sodium dodecyl sulfate. The carbon monoxide difference spectrum with apeak at 448 nm exhibited the absorption spectrum of a typical cytochrome P-450. [ABSTRACT FROM AUTHOR]