Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day, 1.37 ± 2.745 hours for safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia.

electrostrictive actuators are large capacitors with the added complexity of having to perform mechanically as well as electrically. High operating fields and severe operating conditions make it necessary to predict and liimit stress levels generated in the device. A constitutive three-dimensional model for electrostrictors has been develoiped and implemented as a design tool for actuators. The effects of electrode geometry and transition-layer thickness on stress levels have been modeled and failure in high-stress regioins has been correlated with the presence of flaws (pores andl delaminations) in the devices. [

A three-dimensional, electromechanical constitutive law has been formulated for electrostrictive ceramic materials. This fully coupled, phenomenological model relates the key state variables of stress, strain, electric field, polarization and temperature in a set of compact nonlinear equations. The direct and converse electrostrictive effects are modeled by assuming that the electrically induced strain depends on second-order polarization terms. In addition, a simple empirical relationship for the dielectric behavior is used to model the saturation of the induced polarization with increasing electric field.Unlike previous electrostrictive constitutive laws based on polynomial expansions, this constitutive law depends on a manageable number of material constants. As an example, material constants for the model were determined from induced strain and dielectic data for a relaxor-ferroelectric based on lead magnesium niobate, Pb(Mg 1/3 Nb 2/3 )O 3 -PbTiO 3 -BaTiO 3 (PMN-PT-BT). Finally, predictions of the material's mechanical behavior under constant electric field and its electrical behavior under constant applied stress are made.

BACKGROUND AND AIMS:To encourage student participation in the learning process, the authors introduced a modified team based learning (TBL)

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