Inflammatory Activity on Natalizumab Predicts Short-term but not Long-term Disability in Multiple Sclerosis

BACKGROUND: In people with multiple sclerosis treated with interferon-beta or glatiramer acetate, new MRI lesions and relapses during the first year of treatment predict a poor prognosis. OBJECTIVE: To study this association in those receiving natalizumab. METHODS: Data were collected on relapses, new MRI activity, and Modified Rio Score after initiation of natalizumab in an observational cohort of 161 patients with high baseline disability. These were correlated with Expanded Disability Status Scale (EDSS) progression at years 1, 2, 3, and 3-7 after treatment initiation, versus pre-treatment baseline. RESULTS: 46/161 patients had a relapse in the first year and 44/161 had EDSS progression by year 2. Relapses and Modified Rio Score in the first year of treatment predicted EDSS progression at year 1 and 2 after treatment initiation. However, this effect disappeared with longer follow-up. Paradoxically, there was a trend towards inflammatory activity on treatment (first year Modified Rio Score, relapses, and MRI activity) predicting a lower risk of EDSS progression by years 3-7, although this did not reach statistical significance. Those with and without EDSS progression did not differ in baseline age, EDSS, or pre-treatment relapse rate. Relapses in year 0-1 predicted further relapses in years 1-3. CONCLUSIONS: Breakthrough inflammatory activity after natalizumab treatment is predictive of short-term outcome measures of relapses or EDSS progression, but does not predict longer term EDSS progression, in this cohort with high baseline disability

An experimental investigation of natural convection with solidification in a differentially heated cavity

This paper introduces an experimental rig used to produce data for the validation of computational models of natural convection within water in an enclosed cavity. The rig consisted of a rectangular cavity with the two long sides maintained at constant temperature. All other surfaces were insulated and adiabatic except for the top surface which was a free surface with an air gap between the free surface and the insulation. Experimental data in the form of velocity, ice growth rate and profiles are presented at 30 min time steps with a cold wall temperature of −10 °C and hot wall temperature of 5 °C. The data produced has systematic and random errors of ±0.4% and ±0.5%, respectively

Switch-Core Design and Power Loss

Criteria for design of switch cores to be used in a magnetic-matrix switch are established. Core loss is shown to depend only on the average value of net ampere-turns excitation if certain assumptions are made about memory requirements and switch construction. Temperature effects on core output are discussed, and the problem of heat dissipation is considered. Comparison of 2 ferrite and 1 metallic core materials show the latter superior, and specifications are given for a metallic core which should be capable of driving a magnetic memory without cooling although such operation would probably be marginal under worst possible operating conditions

Analytical and experimental investigations of dual-plane PIV

In its 'classical' form particle image velocimetry (PIV) extracts two components of the flow velocity vector by measuring the displacement of tracer particles within a double-pulsed laser light sheet. The method described in this paper is based on the additional recording of a third exposure of the tracer particles in a parallel light sheet, which is slightly displaced with respect to the first one. The particle images resulting from these three exposures are stored on separate frames. The locations of the correlation peaks, as obtained by cross-correlation methods, are used to determine the projections of the velocity vectors onto the plane between both light sheets. In the manner described below, the amplitudes of these peaks are used to obtain information about the velocity component perpendicular to the light sheet planes. The mathematical background of this method is described in the paper. Numerical simulations show the influence of the main parameters (e.g. light sheet thickness, light sheet displacement and out-of-plane component) on the resolution and reliability of the new method. Two different recording procedures and their results will be shown to demonstrate the ease of operation when applying this technique to liquid flows

Sensing Winding Geometry and Information Patterns

Two properties of the sensing winding used in the Whirlwind I and MTC core memories are common to a large class of winding configurations. These are: 1) maximum partial cancellation of core "noise" 2) no inductive coupling between drive and sense wires. A new winding is suggested to replace the present zig-zag geometry. This should prove easier to implement and preliminary tests on a plane containing both old and new sense windings indicate that the two are electrically equivalent. Since core "noise" is a function of information and sense winding geometry, a different checkerboard pattern exists for this new winding. In general, checkerboard patterns for production testing should not be called "worst" patterns since no attempt is made to guarantee the disturb states of the cores, and these have a considerable effect on sense winding outputs

Inactivation of Genes for Antigenic Variation in the Relapsing Fever Spirochete \u3ci\u3eBorrelia hermsii\u3c/i\u3e Reduces Infectivity in Mice and Transmission by Ticks

Borrelia hermsii, a causative agent of relapsing fever of humans in western North America, is maintained in enzootic cycles that include small mammals and the tick vector Ornithodoros hermsi. In mammals, the spirochetes repeatedly evade the host’s acquired immune response by undergoing antigenic variation of the variable major proteins (Vmps) produced on their outer surface. This mechanism prolongs spirochete circulation in blood, which increases the potential for acquisition by fast-feeding ticks and therefore perpetuation of the spirochete in nature. Antigenic variation also underlies the relapsing disease observed when humans are infected. However, most spirochetes switch off the bloodstream Vmp and produce a different outer surface protein, the variable tick protein (Vtp), during persistent infection in the tick salivary glands. Thus the production of Vmps in mammalian blood versus Vtp in ticks is a dominant feature of the spirochete’s alternating life cycle. We constructed two mutants, one which was unable to produce a Vmp and the other was unable to produce Vtp. The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia. This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes. The mutant lacking Vtp also colonized ticks but produced neither Vtp nor a Vmp in tick salivary glands, which rendered the spirochete noninfectious by tick bite. Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector