Subcutaneous administration of tocilizumab is effective in myointimal hyperplasia remodelling in refractory Takayasu arteritis

Takayasu arteritis (TA) is a chronic inflammatory disease of unknown origin that involves large and mediumsized arteries, primarily the aorta and its major branches. TA is a therapeutic challenge because corticosteroids and conventional immunosuppressive agents are not always effective or safe. Interleukin 6 (IL-6) has emerged as a key cytokine in the pathogenesis of TA and its serum levels have been shown to well correlate with disease activity. We report a 19 years old female patient with TA refractory to conventional immunosuppressive agents, successfully treated with subcutaneous tocilizumab, a humanized monoclonal antibody against IL-6 receptor, in which ultrasonography (US) was used as imaging tool to follow up the patient. Currently, clinical indices of disease activity, inflammatory markers, carotid intima media thickness (cIMT) as well as carotid pulse wave velocity (cPWV) normalised, while the prednisone dosage has been tapered. Tocilizumab appears to be a good option in refractory TA, with a remarkable steroid-sparing effect. In addition, it seems to have a favourable effect on endothelial function, as it improved cIMT and PWV

Paving the way toward autonomous shipping development for European Waters – The AUTOSHIP project

New developments in maritime industry include the design and operation of autonomous ships. The AUTOSHIP project is one initiative promoting the use of autonomous ships in European waters focusing on two specific use cases, a Short Sea Shipping (SSS) cargo vessel and an Inland Waterways (IWW) barge. The AUTOSHIP objectives include thorough regulatory, societal, financial, safety and security analyses for the two investigated use cases as well as the development of a novel framework and methods for the design of autonomous vessels. This objective is achieved with the support of a number of activities, including supply chain, regulatory, risk and gaps analyses. Some results and findings from these activities are presented in this paper. The results demonstrate that the supply chain analysis is important to understand the complex relationships between different partners and phases for the effective design of maritime autonomous systems. Furthermore, a number of regulatory gaps needs to be addressed for the wider adoption of the AUTOSHIP use cases. There is a number of essential hazards associated with each of the two use cases; measures to mitigate these hazards are presented

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan–Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8–91.5%) at month 12, 78.8% (95% CI: 78.8–85.2%) at month 24, 63.8% (95% CI: 55.1–73.8%) at month 36, and 59.9% (95% CI: 55.1–73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results

Assessment of Aerodynamics Models for Wind Turbines Aeroelasticity

A comprehensive computational tool for the aeroelastic analysis of horizontal axis wind turbines (HAWT) is presented. The proposed aeroelastic tool couples a nonlinear beam model for blades structural dynamics with an unsteady state-space sectional aerodynamic model taking into account dynamic stall. Three-dimensional wake inflow effects are described by a Boundary Element Method for the solution of incompressible, potential, attached flows. To this aim, different coupling approaches are compared. The resulting aeroelastic differential system is integrated through the Galerkin method, with the introduction of a novel technique for the spatial integration of the additional aerodynamic states related to wake vorticity and dynamic stall. Periodic blade responses are determined by a harmonic balance approach. The effectiveness of the proposed unsteady aerodynamic modelling is discussed, with numerical and experimental comparisons

Subcutaneous administration of tocilizumab is effective in myointimal hyperplasia remodelling in refractory Takayasu arteritis

Takayasu arteritis (TA) is a chronic inflammatory disease of unknown origin that involves large and mediumsized arteries, primarily the aorta and its major branches. TA is a therapeutic challenge because corticosteroids and conventional immunosuppressive agents are not always effective or safe. Interleukin 6 (IL-6) has emerged as a key cytokine in the pathogenesis of TA and its serum levels have been shown to well correlate with disease activity. We report a 19 years old female patient with TA refractory to conventional immunosuppressive agents, successfully treated with subcutaneous tocilizumab, a humanized monoclonal antibody against IL-6 receptor, in which ultrasonography (US) was used as imaging tool to follow up the patient. Currently, clinical indices of disease activity, inflammatory markers, carotid intima media thickness (cIMT) as well as carotid pulse wave velocity (cPWV) normalised, while the prednisone dosage has been tapered. Tocilizumab appears to be a good option in refractory TA, with a remarkable steroid-sparing effect. In addition, it seems to have a favourable effect on endothelial function, as it improved cIMT and PWV

A Comprehensive Numerical Model for Horizontal Axis Wind Turbines Aeroelasticity

"This paper deals with a computational aeroelastic tool aimed at the analysis of performance,. response and stability of horizontal axis wind turbines. It couples a nonlinear beam model. for blades structural dynamics with an unsteady state-space sectional aerodynamic load. model taking into account dynamic stall and inflow effects induced by rotor wake. An. extension of 2D static coefficients for high angles of attack is provided to characterize. operations in deep stall regime. The Galerkin method is applied to the aeroelastic differential. system, with the introduction of a novel approach for the spatial integration of the additional. aerodynamic states related to wake vorticity and dynamic stall. Periodic blade responses are. determined by a harmonic balance approach and a standard eigenproblem is solved for the. stability analysis. Validation of the applied unsteady, sectional aerodynamics model is. performed through comparisons with experimental data concerning NACA0012 and S809. airfoil undergoing oscillatory pitch motion. Further, results obtained by the aeroelastic code. including dynamic stall modeling applied to the NREL\/NASA Ames Phase VI two-bladed. rotor in axial flow are presented, with comparisons to available experimental and numerical data..

Rotorcraft Aeroelastic Stability Using Robust Analysis

This paper discusses the impact of different models of aerodynamic loads on rotorcraft-pilot couplings stability using a robust stability analysis approach. The aeroelasticity of the main rotor of a helicopter is formulated using aerodynamic models based on the blade ele- ment/momentum theory and boundary element method coupled to a finite element model of the blade. The resulting linearized models are used to determine stability limits according to the generalized Nyquist criterion, associated with the accelerations of the pilot’s seat caused by the involuntary action of the pilot on the control in- ceptors. The resulting stability curves are discussed considering examples of involuntary pilot transfer functions from the literature

Evaluation of Rotorcraft Aeroelastic Stability Using Robust Analysis

This paper discusses the impact of different aerodynamics models on rotorcraft-pilot couplings stability using a robust stability analysis approach. Models based on blade element/momentum theory and boundary element method, coupled to a finite element model of the blade, are used to formulate the aeroelasticity of the main rotor of a helicopter. The main rotor is coupled to a dynamic model of the airframe that also includes the dynamics of the control system. The resulting linearized models are used to determine stability limits according to the generalized Nyquist criterion, associated with the accelerations of the pilot's seat caused by the involuntary motion of the control inceptors. The resulting stability curves are discussed considering examples of involuntary pilot transfer functions from the literature