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Background and objectivesAn unmet need exists for validated quantitative tools to measure multiple sclerosis (MS) disease activity and progression. We developed a custom immunoassay-based MS disease activity (MSDA) Test incorporating 18 protein concentrations into an algorithm to calculate four Disease Pathway scores (Immunomodulation, Neuroinflammation, Myelin Biology, and Neuroaxonal Integrity) and an overall Disease Activity score. The objective was to clinically validate the MSDA Test based on associations between scores and clinical/radiographic assessments.MethodsSerum samples (N=614) from patients with MS at multiple sites were split into Train (n=426; algorithm development) and Test (n=188; evaluation) subsets. Subsets were stratified by demographics, sample counts per site, and gadolinium-positive (Gd+) lesion counts; age and sex were used to demographically adjust protein concentrations. MSDA Test results were evaluated for potential association with Gd+ lesion presence/absence, new and enlarging (N/E) T2 lesion presence, and active versus stable disease status (composite endpoint combining radiographic and clinical evidence of disease activity).ResultsA multi-protein model was developed (trained and cross-validated) using the Train subset. When applied to the Test subset, the model classified the Gd+ lesion presence/absence, N/E T2 lesion presence, and active versus stable disease status assessments with an area under the receiver operating characteristic (AUROC) of 0.781, 0.750, and 0.768, respectively. In each case, the multi-protein model had significantly (bootstrapped, one-sidedpDiscussionThe MSDA Test was clinically validated; the multi-protein model had greater performance compared with the top-performing single-protein model. The MSDA Test may serve as a quantitative and objective tool to enhance care for MS.

The small-angle approximation to the radiative transport equation is applied to particle suspensions that emulate ocean water. A particle size distribution is constructed from polystyrene and glass spheres with the best available data for particle size distributions in the ocean. A volume scattering function is calculated from the Mie theory for the particles in water and in oil. The refractive-index ratios of particles in water and particles in oil are 1.19 and 1.01, respectively. The ratio 1.19 is comparable to minerals and nonliving diatoms in ocean water, and the ratio 1.01 is comparable to the lower limit for microbes in water. The point-spread functions are measured as a function of optical thickness for both water and oil mixtures and compared with the point-spread functions generated from the small-angle approximation. Our results show that, under conditions that emulate ocean water, the small-angle approximation is valid only for small optical thicknesses. Specifically, the approximation is valid only for optical thicknesses less than 3.

The Majorana Project will endeavor to provide direct limits on the effective Majorana mass of the electron neutrino through the measurement of 0νββ decay in 76Ge. Our goal is an experiment with a scalable sensitivity starting at 100 meV (corresponding to the quasi‐degenerate mass scale) and ultimately extending well below that level. The current Majorana design consists of several modules, each a close‐packed array of 57 Ge detectors, enriched to 86% in 76Ge, in a single cryostat. The ultimate background goal for Majorana is of order one count per tonne of Ge per year in the four keV region of interest around Qββ. This background will allow us to reach an effective Majorana‐neutrino mass sensitivity approximately five times better than current results and should cover the quasi‐degenerate mass scale.

The small-angle approximation to the radiative transport equation is used extensively in imaging models in which the transport medium is optically thick. The small-angle approximation is generally considered valid when the particles are very large compared with the wavelength, when the refractive-index ratio of the particle to the medium is close to 1, and when the optical thickness is not too large. We report results showing the limits of the validity of the small-angle approximation as a function of particle size and concentration for a particle-to-medium fixed refractive-index ratio of 1.196. This refractive-index ratio is comparable with that of minerals or diatoms suspended in water.