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Yoshiya Tanaka,1 Mark C Genovese,2,3 Hironori Matsushima4 1The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Japan; 2Division of Immunology and Rheumatology, Stanford University, Stanford, CA, USA; 3Gilead Sciences, Inc, Foster City, CA, USA; 4Gilead Sciences, Inc, Tokyo, JapanCorrespondence: Yoshiya Tanaka, The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Japan, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu, 807-8555, Japan, Tel +81-93-603-1611, Fax +81-93-691-7580, Email tanaka@med.uoeh-u.ac.jpAbstract: Filgotinib is an orally administered, preferential Janus kinase (JAK) inhibitor indicated for the treatment of moderate-to-severe rheumatoid arthritis (RA). The short-term safety, efficacy, and patient-reported outcomes (PROs) with filgotinib from Phase 2b/3 clinical trials (DARWIN 1 and 2; FINCH 1, 2, and 3) are described in patients who inadequately responded to methotrexate (MTX) and biologic disease-modifying antirheumatic drugs or who were naïve to MTX. This article reviews the safety and efficacy from the long-term extension (LTE) trials, DARWIN 3 (N=739) and FINCH 4 (N=2731), and PROs across the filgotinib development program in RA. Overall, in the DARWIN clinical trials (conducted from 2013– 2023), patients received their LTE treatment for ≤ 8 years, while in the FINCH trials (ongoing from 2016– 2025), patients received filgotinib treatment for ≤ 6 years in the LTE. The longer-term safety profile and consistent, sustained efficacy (American College of Rheumatology 20/50/70, Clinical Disease Activity Index, and Disease Activity Scale in 28 joints with C-reactive protein response rates) of filgotinib were largely similar to those observed in the shorter-term parent trials ≤ 52 weeks. PRO results from the parent trials showed improvements in patients’ quality of life with filgotinib treatment, which compared to or exceeded improvements seen with placebo and active comparators (adalimumab, MTX). Filgotinib has a higher specificity for JAK1 compared with other therapeutic treatments, leading to reduced inhibition of JAK2/3–dependent pathways, potentially providing a distinct safety profile. Filgotinib is approved in Europe and Japan for treatment of people with moderate-to-severe RA, though it has not been approved by the US Food and Drug Administration, due to concerns around the benefit/risk profile of the filgotinib 200-mg dosage and the potential impact on semen parameters.Keywords: Janus kinase inhibitors, selectivity, JAKi, disease-modifying antirheumatic drug, DMARD, RA

Ippei Watanabe,1 Mayumi Nagata,2 Hiroyuki Matsushima2 1Medical Science Liaison Unit, Seikagaku Corporation, Tokyo, Japan; 2Department of Ophthalmology, Dokkyo Medical University, Tochigi, JapanCorrespondence: Ippei WatanabeMedical Science Liaison Unit, Seikagaku Corp., 6-1, Marunouchi 1-chome, Chiyoda-ku, Tokyo 100-0005, JapanTel +81 3 352208595Fax +81 3 352208975Email ippei.watanabe@seikagaku.co.jpPurpose: To evaluate the effects of D-sorbitol addition on changes in the extrusion force of ophthalmic viscosurgical devices (OVDs).Methods: OVD formulations; the mixtures of 3% hyaluronic acid (HA) and 4% chondroitin sulfate (CS) containing 0%, 0.5%, or 1.0% D-sorbitol were prepared. Each prefilled syringe of OVD was stored at room temperature for 0, 15, 30, 60, or 120 mins after a small amount of viscoelastic agent was discharged from the needle. The extrusion force values (kgf) of these OVDs when reused after storage were measured with a texture analyzer. Moreover, 10 healthy adults (5 men and 5 women) used a pinch sensor to measure the extrusion force values for the HA/CS combination without D-sorbitol which was stored in the above manner, and used a 4-step scale to score the usability of OVD.Results: For the HA/CS combination without D-sorbitol, the extrusion force value was increased from its initial value (storage duration, 0 min) as storage duration increased. However, for the HA/CS combination containing 0.5% or 1.0% D-sorbitol, this value remained almost unchanged over time. Likewise, the pinch sensor-determined extrusion force values of HA/CS combination without D-sorbitol increased, depending on storage duration.Conclusion: The addition of D-sorbitol to viscoelastic agent may suppress the needle clogging that occurs with OVD storage, and may improve the usability of OVDs during surgery.Keywords: ophthalmic viscosurgical device, extrusion force, cataract surgery, vitreous surgery

A decrease in breakdown voltage (VBD) in the termination area of 4H-SiC PN diodes after 64 h reverse-bias stressing was analyzed. To analyze the VBD decrease, a novel analysis method based on the results of measuring depletion-layer capacitance of the PN diodes was proposed. The measurement results indicate that the positive-charge density (QTM) at the SiO2/SiC interface of the termination area increased after the reverse-bias stressing. Besides, in the case of QTM of 1012cm-2 at the SiO2/SiC interface, the decrease in the measured capacitance showed the same tendency as the decrease in the simulated capacitance. By comparing the measured full depletion voltage and simulated full depletion voltage, the amount of QTM was estimated. It is thus concluded that the proposed method for measuring the depletion-layer capacitance is effective for analyzing the QTM change in the termination area. [ABSTRACT FROM AUTHOR]

Steady state three-dimensional incompressible flow analysis based on the two-equation model of turbulence is performed. The finite element method employing the penalty function formulation by Hughes et al. (1979) is used. To reduce the computational time and computer storage, the conjugate gradient method is applied to solve algebraic equations. In applying the conjugate gradient method, the equations are preconditioned so as to arrive at converged solutions effectively. The problem cited in this study is the impingement air cooling of the large scale integrated circuit package with large plate fins. The calculated velocity vectors show good agreement with the result of flow visualization. The calculated temperature distributions also agree well with the experimental temperatures. This suggests the usefulness of this kind of numerical simulation in the research and development of new cooling technologies.