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Objective: The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM.Methods: Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data.Results: Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference.Conclusion: Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis.

Modulus of elasticity of loosely cross-linked poly(isobutylene) gels are measured under large compressive deformations. Gels of perfect spherical shape are prepared by the suspension cross-linking technique of dilute toluene solutions of butyl rubber using sulfur monochloride as a cross-linking agent. Compressive deformation is applied by a calibrated stainless steel cantilever to spherical poly(isobutylene) beads of sizes ca. 1.0-4.0 mm in diameter swollen in toluene. The relationship between force and deformation is obtained by using the constitutive relations from molecular theory of elasticity Moduli are measured immediately after applying compression, and after full relaxation which obtains after solvent exudes the gels under compression. The instantaneous moduli are an order of magnitude larger than equilibrium moduli. Results of mechanical measurements, which are presently of a preliminary type, are compared with those from independent thermodynamic estimates of shear moduli. (C) 2001 Elsevier Science Ltd. All rights reserved.

By treating an enzyme as a coarse-grained uniform block of material, utilizing only the alpha -Carbon positions, the normal modes of motion can be obtained. For reverse transcriptase the slower of these motions are suggestive of being involved in the processing step, where the RNA or DNA strand is copied onto a new DNA strand at a polymerase site, and the RNA strand is subsequently cut up at the distant Ribonuclease H site. The slowest mode of motion involves hinge bending about a site midway between the polymerase and Ribonuclease H sites, suggesting that it can push or pull the RNA strand between these two sites. Pulling the nucleic acid strand would require tight binding to the RNase H site. The next slowest mode involves a hinge that opens and closes the protein like a clamp, which could facilitate the release of the nucleic acids for their step-wise progression. The third mode could rotate the substrate. An overall description of the step-wise processing step would involve close coordination among these steps. Results suggest that the smaller p51 subunit serves only as ballast to support the various modes of motion involving the different parts of the p66 subunit.

Cooperative motions of cis-1,4-polybutadiene (cis-PB) and cis-1,4-polyisoprene (cis-PI) in the bulk state are analyzed and compared using the cooperative kinematics (CK) theory. The mechanisms of relaxation on a local scale are closely similar for the two polymers in dense media, resulting from the same geometry of the backbone, which is the major determinant of the types of accessible cooperative conformational rearrangements. The correlation times for the reorientation of C-H bonds of cis-PI are found to be about 1 order of magnitude longer than those for cis-PB at the same effective friction coefficient. The results are in accordance with previous NMR experiments which indicated a ratio of about 10. The molecular characteristics responsible for this difference in the local mobilities of the two polymers are examined. Three sources are identified: (i) the excess volume swept by the moving units in cis-PI due to the CH3 units appended to the backbone, (ii) the higher short-range conformational potential energies in cis-PI compared to those in cis-PB, and (iii) the restriction in the number of accessible isomeric transitions in cis-PI compared to those of cis-PB, which is due to the excluded-volume effect.

The swelling of polybutadiene (PB) networks of different cross-link densities filled with finely divided sodium chloride (NaCl) particles are studied in water, water/acetone and water/THF mixtures. Swelling over periods of 2 months are recorded. The degree of swelling was observed to increase continuously in water during this period, whereas in water/acetone mixtures it reached a peak followed by deswelling and it converged to a maximal value in water/THF mixtures. The highly cross-linked samples exhibited unusually high degrees of swelling, and calculations indicated full stretching of the network chains. The enthalpic contribution to the chemical potential of the networks in equilibrium with solvent was determined using the phantom network model of rubber elasticity theory. The swollen network-salt system was approximated by the lattice model of polymer solutions. The positive contributions of water and acetone to the chemical activity of the swollen network were offset by the negative contribution of dissociation of salt in water, resulting in a small negative enthalpy of mixing. The highest rate of diffusion of solvent was observed for the PB/water/THF ternary system. Diffusion rates of pure water and water/acetone mixture were much smaller and of comparable magnitude. Mechanical measurements of stress and strain at break, and dynamic mechanical measurements of storage and loss moduli of filled and unfilled samples showed that filling with NaCl did not change the mechanical properties of the networks significantly, in spite of the dramatic change in the swelling behaviour. (C) 1998 Elsevier Science Ltd. All rights reserved.