Shape analysis of subcortical nuclei in Huntington's disease, global versus local atrophy--results from the TRACK-HD study.

Huntington's disease (HD) is characterized by brain atrophy. Localized atrophy of a specific structure could potentially be a more sensitive biomarker reflecting neuropathologic changes rather than global volume variation. We examined 90 TRACK-HD participants of which 30 were premanifest HD, 30 were manifest HD and 30 were controls. Using FMRIB's Integrated Registration and Segmentation Tool, segmentations were obtained for the pallidum, caudate nucleus, putamen, thalamus, accumbens nucleus, amygdala, and hippocampus and overall volumes were calculated. A point distribution model of each structure was obtained using Growing and Adaptive Meshes. Permutation testing between groups was performed to detect local displacement in shape between groups. In premanifest HD overall volume loss occurred in the putamen, accumbens and caudate nucleus. Overall volume reductions in manifest HD were found in all subcortical structures, except the amygdala, as compared to controls. In premanifest HD shape analysis showed small areas of displacement in the putamen, pallidum, accumbens and caudate nucleus. When the premanifest group was split into two groups according to predicted disease onset, the premanifest HD group close to expected disease onset showed more pronounced displacements in caudate nucleus and putamen compared to premanifest HD far from disease onset or the total premanifest group. Analysis of shape in manifest HD showed widespread shape differences, most prominently in the caudal part of the accumbens nucleus, body of the caudate nucleus, putamen and dorsal part of the pallidum. We conclude that shape analysis provides new insights in localized intrastructural atrophy patterns in HD, but can also potentially serve as specific target areas for disease tracking.

Preparation and characterization of nanoparticles bearing heparin or dextran covalently-linked to poly(methyl methacrylate).

Nanoparticles have been obtained directly in aqueous media, from amphiphilic copolymers synthesized by radical polymerization of methyl methacrylate (MMA) initiated by Ce(IV) ions in the presence of heparin or dextran. The reaction conditions under which the copolymers spontaneously formed nanoparticles depended on the type of polysaccharide and on the concentrations of the reagents. Fluorescent nanoparticles containing N-vinyl carbazole (NVC), covalently linked to PMMA, were also prepared by random copolymerization of MMA and NVC in similar polymerization systems. The non-fluorescent nanoparticle suspensions were stable for several months without using surfactant. The fluorescent particles were larger and less stable then the unlabelled ones. Since all the particles are monodisperse, and in the submicron range, they can be used as models of drug carriers; the covalently-linked fluorescent species allowing them to be followed in vivo. The average molecular weights of the PMMA blocks of the copolymers and of oxidized heparin and dextran were determined by viscometry and/or gel permeation chromatography. The antithrombic activity of oxidized heparin was measured. The results show that the polysaccharide chains were cleaved by Ce(IV) in aqueous nitric acid, resulting in formation of block copolymers made of one or two blocks of PMMA linked to the ends of one polysaccharide block. Taken together, the results suggest that the particles were organized with the polysaccharidic moieties on the surface of the particles and the more hydrophobic PMMA or P(MMA-co-NVC) in the core, in a brush-like structure. This should confer 'stealth' properties to such particles.

Modeling shared resources with generalized synchronization within a Petri net bottom-up approach.

This paper proposes a simple and effective way to represent shared resources in manufacturing systems within a Petri net model previously developed. Such a model relies on the bottom-up and modular approach to synthesis and analysis. The designer may define elementary tasks and then connect them with one another with three kinds of connections: self-loops, inhibitor arcs and simple synchronizations. A theoretical framework has been established for the analysis of liveness and reversibility of such models. The generalized synchronization, here formalized, represents an extension of the simple synchronization, allowing the merging of suitable subnets among elementary tasks. It is proved that under suitable, but not restrictive, hypotheses the generalized synchronization may be substituted for a simple one, thus being compatible with all the developed theoretical body.