78 research outputs found

    Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study

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    Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. Methods: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. Results: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). Conclusions: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression

    Nonlinear Dynamics in HfO<sub>2</sub>/SiO<sub>2</sub>-Based Interface Dipole Modulation Field-Effect Transistors for Synaptic Applications

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    In the pursuit of energy-efficient spiking neural network (SNN) hardware, synaptic devices leveraging emerging memory technologies hold significant promise. This study investigates the application of the recently proposed HfO2/SiO2-based interface dipole modulation (IDM) memory for synaptic spike timing-dependent plasticity (STDP) learning. Firstly, through pulse measurements of IDM metal–oxide–semiconductor (MOS) capacitors, we demonstrate that IDM exhibits an inherently nonlinear and near-symmetric response. Secondly, we discuss the drain current response of a field-effect transistor (FET) incorporating a multi-stack IDM structure, revealing its nonlinear and asymmetric pulse response, and suggest that the degree of the asymmetry depends on the modulation current ratio. Thirdly, to emulate synaptic STDP behavior, we implement double-pulse-controlled drain current modulation of IDMFET using a simple bipolar rectangular pulse. Additionally, we propose a double-pulse-controlled synaptic depression that is valuable for optimizing STDP-based unsupervised learning. Integrating the pulse response characteristics of IDMFETs into a two-layer SNN system for synaptic weight updates, we assess training and classification performance on handwritten digits. Our results demonstrate that IDMFET-based synaptic devices can achieve classification accuracy comparable to previously reported simulation-based results

    Low temperature preparation of HfO 2

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    Study of Direct-Contact HfO2/Si Interfaces

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    Controlling monolayer Si oxide at the HfO2/Si interface is a challenging issue in scaling the equivalent oxide thickness of HfO2/Si gate stack structures. A concept that the author proposes to control the Si oxide interface by using ultra-high vacuum electron-beam HfO2 deposition is described in this review paper, which enables the so-called direct-contact HfO2/Si structures to be prepared. The electrical characteristics of the HfO2/Si metal-oxide-semiconductor capacitors are reviewed, which suggest a sufficiently low interface state density for the operation of metal-oxide-semiconductor field-effect-transistors (MOSFETs) but reveal the formation of an unexpected strong interface dipole. Kelvin probe measurements of the HfO2/Si structures provide obvious evidence for the formation of dipoles at the HfO2/Si interfaces. The author proposes that one-monolayer Si-O bonds at the HfO2/Si interface naturally lead to a large potential difference, mainly due to the large dielectric constant of the HfO2. Dipole scattering is demonstrated to not be a major concern in the channel mobility of MOSFETs
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