Objective: To determine whether glatiramer acetate (GA) slows accumulation of disability in primary progressive multiple sclerosis. Methods: A total of 943 patients with primary progressive multiple sclerosis were randomized to GA or placebo (PBO) in this 3-year, double-blind trial. The primary end point was an intention-to-treat analysis of time to 1-(entry expanded disability status scale, 3.0 -5.0) or 0.5-point expanded disability status scale change (entry expanded disability status scale, 5.5-6.5) sustained for 3 months. The trial was stopped after an interim analysis by an independent data safety monitoring board indicated no discernible treatment effect on the primary outcome. Intention-to-treat analyses of disability and magnetic resonance imaging end points were performed. Results: There was a nonsignificant delay in time to sustained accumulated disability in GA-versus PBO-treated patients (hazard ratio, 0.87 [95% confidence interval, 0.71-1.07]; p ϭ 0.1753), with significant decreases in enhancing lesions in year 1 and smaller increases in T2 lesion volumes in years 2 and 3 versus PBO. Post hoc analysis showed that survival curves for GA-treated male patients diverged early from PBO-treated male subjects (hazard ratio, 0.71 [95% confidence interval, 0.53-0.95]; p ϭ 0.0193). Interpretation:The trial failed to demonstrate a treatment effect of GA on primary progressive multiple sclerosis. Both the unanticipated low event rate and premature discontinuation of study medication decreased the power to detect a treatment effect. Post hoc analysis suggests GA may have slowed clinical progression in male patients who showed more rapid progression when untreated.

We present optical shadowgraph flow visualization and heat transport measurements of Rayleigh–Bénard convection with rotation about a vertical axis. The fluid, water with Prandtl number 6.4, is confined in a cylindrical convection cell with radius-to-height ratio Γ = 1. For dimensionless rotation rates 150 < Ω < 8800, the onset of convection occurs at critical Rayleigh numbers Rc(Ω) much less than those predicted by linear stability analysis for a laterally infinite system and qualitatively consistent with finite-aspect-ratio, linear-stability calculations of Buell & Catton (1983). As in the calculations, the forward bifurcation at onset is to states of localized flow near the lateral walls with azimuthal periodicity of 3 < m < 8. These states precess in the rotating frame, contrary to the assumptions of Buell & Catton (1983) but in quantitative agreement with recent calculations of Goldstein et al. (1992), with a frequency that is finite at onset but goes to zero as Ω goes to zero. At Ω = 2145 we find primary and secondary stability boundaries for states with m = 4, 5, 6, and 7. Further, we show that at higher Rayleigh number, there is a transition to a vortex state where the vortices form with the symmetry of the existing azimuthal periodicity of the sidewall state. Aperiodic, time-dependent heat transport begins for Rayleigh numbers at or slightly above the first appearance of vortices. Visualization of the formation and interactions of thermal vortices is presented, and the behaviour of the Nusselt number at high Rayleigh numbers is discussed.

The mixture of peppermint oil (PO) with medium-chain triacylglycerol was emulsified in water and stabilized with a food-grade biopolymer, modified starch, to form PO nanoemulsions. The effects of emulsifying conditions including homogenization pressure, the number of processing cycles, and oil loading on the mean diameters and viscosities of nanoemulsions were characterized by dynamic light scattering, optical microscopy, and rheological measurements. The formulated PO nanoemulsions with mean diameters normally <200 nm showed high stability over at least 30 days of storage time. Their antimicrobial properties related to those of PO have also been evaluated by two assays, the minimum inhibitory concentration (MIC) and time-kill dynamic processes, against two Gram-positive bacterial strains of Listeria monocytogenes Scott A and Staphylococcus aureus ATCC 25923. Compared with bulk PO, the PO nanoemulsions showed prolonged antibacterial activities. The results suggest that the nanoemulsion technology can provide novel applications of essential oils in extending the shelf life of aqueous food products.

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