App chaining software-as-a-service for an advanced manufacturing marketplace

Advances in the field of cloud computing and networking have led to development of Marketplaces (e.g., Awesim) that support Advanced Manufacturing enterprises consisting of Apps. These Marketplaces host Apps that perform simulation and modeling on specialized designs (e.g., pipes, automobile parts). However, the salient limitation in these App Marketplaces is the lack of a development environment that supports effective runtime capabilities for 'Agile Manufacturing' that efficiently and cost-effectively integrates several Apps when building innovative products. To address this problem, we propose a new Software-as-a-Service based App Runtime for the Marketplace environment that can be utilized for agile development of 'Apps' that involve high-performance modeling and simulation. Our solution approach features a web framework for the App runtime that chains together generic set of 'Apps' that run complex simulation jobs on Supercomputer and publish customer facing results. We demonstrate how multiple Apps can be chained using our web framework for a product case study viz., 'WheelSim' deployed in the NSF GENI Cloud platform. Our results show improved App development convenience via rich UI elements interacting with RESTful web services and through dynamic chaining of workflows. Our study also provides App developers with insights pertaining to estimation of resource cost for App pricing issues in the manufacturing Marketplace

MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis

Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in vivo in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis, by combining non-invasive neuroimaging and blood biomarkers. We performed quantitative microstructural MRI and single molecule ELISA plasma neurofilament measurement in 73 patients with newly diagnosed, immunotherapy naïve relapsing-remitting multiple sclerosis. Myelin integrity was evaluated using aggregate g-ratios, derived from magnetization transfer saturation (MTsat) and neurite orientation dispersion and density imaging (NODDI) diffusion data. We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 vs 0.57, difference 0.036, 95% CI 0.029 to 0.043, p < 0.001). Lesion volume (Spearman’s rho rs= 0.38, p < 0.001) and g-ratio (rs= 0.24 p < 0.05) correlated independently with plasma neurofilament. In patients with substantial lesion load (n = 38), those with higher g-ratio (defined as greater than median) were more likely to have abnormally elevated plasma neurofilament than those with normal g-ratio (defined as less than median) (11/23 [48%] versus 2/15 [13%] p < 0.05). These data suggest that, even at multiple sclerosis diagnosis, reduced myelin integrity is associated with axonal damage. MRI-derived g-ratio may provide useful additional information regarding lesion severity, and help to identify individuals with a high degree of axonal damage at disease onset. York, Martin et al. simultaneously measured g-ratio and plasma neurofilament in 73 relapsing-remitting multiple sclerosis patients at diagnosis using advanced MRI and single molecule ELISA. They demonstrate that g-ratio of cerebral white matter lesions varies at diagnosis, and show that high g-ratio of lesions is associated with elevated plasma neurofilament

A pilot study of oxidative pathways in MS fatigue: randomized trial of N‐acetyl cysteine

Abstract Objective To assess feasibility, tolerability, and safety of N‐acetyl cysteine (NAC) for fatigue in progressive MS. Secondary objectives evaluated changes in fatigue and oxidative pathway biomarkers on NAC versus placebo. Methods Individuals with progressive MS with Modified Fatigue Impact Scale (MFIS) > t38 were randomized 2:1 to NAC 1250mg TID or placebo for 4 weeks. The primary outcome was tolerability and safety. The secondary outcome to evaluate efficacy was MFIS change from baseline to week 4 between groups. Exploratory biomarker outcomes included change in blood GSH/GSSG ratio (reduced‐to‐oxidized glutathione (GSH)) and in vivo relative GSH using 7T MR spectroscopy (MRS) between groups. Fisher exact test was used for categorical and rank sum for continuous outcomes. Results Fifiteen were randomized (10 NAC, 5 placebo; mean age 56.1 years, 80% female, median EDSS 6.0). At least one adverse event (AE) occurred in 60% on NAC versus 80% on placebo (p = 0.75). There were two AEs attributed to NAC in one patient (abdominal pain and constipation), with 94% adherence to NAC. MFIS decreased in both groups at week 4, with the mean improvement of 11‐points on NAC versus 18‐points on placebo (p = 0.33). GSH/GSSG ratio decreased on placebo (−0.6) and NAC (−0.1) (p = 0.18). Change in GSH levels to total creatine in anterior and posterior cingulate cortex, insula, caudate, putamen, and thalamus did not differ between groups. Interpretation NAC was well‐tolerated in progressive MS, although reduction in fatigue on NAC was similar to placebo. Antioxidant blood and MRS biomarkers were not significantly altered by NAC, which could be due to dose, route of administration, time of sample collection, short half‐life, or lack of effect. Registered clinicaltrials.gov NCT02804594

A pilot study of oxidative pathways in MS fatigue: randomized trial of N-acetyl cysteine.

ObjectiveTo assess feasibility, tolerability, and safety of N-acetyl cysteine (NAC) for fatigue in progressive MS. Secondary objectives evaluated changes in fatigue and oxidative pathway biomarkers on NAC versus placebo.MethodsIndividuals with progressive MS with Modified Fatigue Impact Scale (MFIS) > t38 were randomized 2:1 to NAC 1250mg TID or placebo for 4 weeks. The primary outcome was tolerability and safety. The secondary outcome to evaluate efficacy was MFIS change from baseline to week 4 between groups. Exploratory biomarker outcomes included change in blood GSH/GSSG ratio (reduced-to-oxidized glutathione (GSH)) and in vivo relative GSH using 7T MR spectroscopy (MRS) between groups. Fisher exact test was used for categorical and rank sum for continuous outcomes.ResultsFifiteen were randomized (10 NAC, 5 placebo; mean age 56.1 years, 80% female, median EDSS 6.0). At least one adverse event (AE) occurred in 60% on NAC versus 80% on placebo (p = 0.75). There were two AEs attributed to NAC in one patient (abdominal pain and constipation), with 94% adherence to NAC. MFIS decreased in both groups at week 4, with the mean improvement of 11-points on NAC versus 18-points on placebo (p = 0.33). GSH/GSSG ratio decreased on placebo (-0.6) and NAC (-0.1) (p = 0.18). Change in GSH levels to total creatine in anterior and posterior cingulate cortex, insula, caudate, putamen, and thalamus did not differ between groups.InterpretationNAC was well-tolerated in progressive MS, although reduction in fatigue on NAC was similar to placebo. Antioxidant blood and MRS biomarkers were not significantly altered by NAC, which could be due to dose, route of administration, time of sample collection, short half-life, or lack of effect. REGISTERED: clinicaltrials.gov NCT02804594

Temperature dependent interaction of hydrogen with PdAg nanocomposite thin films revealed by in-situ synchrotron XRD

PdAg nanocomposite alloy thin films were synthesized using a DC magnetron sputtering process to study the structural changes that occur in the alloy film during the process of hydrogenation and dehydrogenation at different temperatures. The atomic composition of the nano-composite film is 88 at % Pd and 12% at Ag, as determined by the EDAX analysis. In-situ synchrotron X-ray diffraction (XRD) has been used to monitor the subtle structural changes that occurred throughout the hydrogenation and dehydrogenation cycles at an interval of 10 s. This aspect has not been addressed so far. In-situ XRD studies reveal that the XRD peak shifts towards a lower angle due to the lattice expansion in the alloy due to hydrogenation. The change in peak shift is found to be different for different temperatures. The present study also shows no hysteresis during the hydrogen absorption and desorption processes. In addition, the results show that (i) the phase segregation has been observed at 250 , (ii) the peak shift during the hydrogenation process at higher temperatures is not significant, whereas the peak shift throughout the process is more rapid and pronounced at ambient temperature

In-situ investigation on hydrogenation-dehydrogenation of Pd–Ag alloy films

The present work reports on synthesis of PdeAg nano-composite films by magnetron cosputteringand the structural changes in the alloy film during hydrogenation and dehydrogenation.Synchrotron X-ray diffraction is employed in-situ to reveal subtle structuralchanges occurring during hydrogenation and dehydrogenation processes, an aspect notinvestigated so far. It is revealed that the nanocomposite film having 88 at% Pd shows theformation of a-phase as an intermediate phase, however, completion of the hydrogenationprocess yields only b-phase. No b-phase formation is observed in nanocomposite thin filmcontaining 54 at% of Pd, suggesting the suppression of formation of b-phase with increasein Ag concentration. On dehydrogenation, the peak returns to its original position i.e. thevalue before hydrogenation. The data also demonstrated that the addition of Ag in Pd resultsin complete removal of dissolved hydrogen thereby eliminates the problem of hysteresis.The study shows that the lower concentrations of Ag in Pd are better in terms ofextent of peak-shift on hydrogenation/dehydrogenation and faster response/recoverykinetics

Making Every Step Count: Minute-by-Minute Characterization of Step Counts Augments Remote Activity Monitoring in People With Multiple Sclerosis.

BackgroundAmbulatory disability is common in people with multiple sclerosis (MS). Remote monitoring using average daily step count (STEPS) can assess physical activity (activity) and disability in MS. STEPS correlates with conventional metrics such as the expanded disability status scale (Expanded Disability Status Scale; EDSS), Timed-25 Foot walk (T25FW) and timed up and go (TUG). However, while STEPS as a summative measure characterizes the number of steps taken over a day, it does not reflect variability and intensity of activity.ObjectivesNovel analytical methods were developed to describe how individuals spends time in various activity levels (e.g., continuous low versus short bouts of high) and the proportion of time spent at each activity level.Methods94 people with MS spanning the range of ambulatory impairment (unaffected to requiring bilateral assistance) were recruited into FITriMS study and asked to wear a Fitbit continuously for 1-year. Parametric distributions were fit to minute-by-minute step data. Adjusted R2 values for regressions between distributional fit parameters and STEPS with EDSS, TUG, T25FW and the patient-reported 12-item MS Walking scale (MSWS-12) were calculated over the first 4-weeks, adjusting for sex, age and disease duration.ResultsDistributional fits determined that the best statistically-valid model across all subjects was a 3-compartment Gaussian Mixture Model (GMM) that characterizes the step behavior within 3 levels of activity: high, moderate and low. The correlation of GMM parameters for baseline step count measures with clinical assessments was improved when compared with STEPS (adjusted R2 values GMM vs. STEPS: TUG: 0.536 vs. 0.419, T25FW: 0.489 vs. 0.402, MSWS-12: 0.383 vs. 0.378, EDSS: 0.557 vs. 0.465). The GMM correlated more strongly (Kruskal-Wallis: p = 0.0001) than STEPS and gave further information not included in STEPS.ConclusionsIndividuals' step distributions follow a 3-compartment GMM that better correlates with clinic-based performance measures compared with STEPS. These data support the existence of high-moderate-low levels of activity. GMM provides an interpretable framework to better understand the association between different levels of activity and clinical metrics and allows further analysis of walking behavior that takes step distribution and proportion of time at three levels of intensity into account

MWF of the corpus callosum is a robust measure of remyelination: Results from the ReBUILD trial

Myelin repair is an unrealized therapeutic goal in the treatment of multiple sclerosis (MS). Uncertainty remains about the optimal techniques for assessing therapeutic efficacy and imaging biomarkers are required to measure and corroborate myelin restoration. We analyzed myelin water fraction imaging from ReBUILD, a double-blind, randomized placebo-controlled (delayed treatment) remyelination trial, that showed a significant reduction in VEP latency in patients with MS. We focused on brain regions rich in myelin. Fifty MS subjects in two arms underwent 3T MRI at baseline and months 3 and 5. Half of the cohort was randomly assigned to receive treatment from baseline through 3 mo, whereas the other half received treatment from 3 mo to 5 mo post-baseline. We computed myelin water fraction changes occurring in normal-appearing white matter of corpus callosum, optic radiations, and corticospinal tracts. An increase in myelin water fraction was documented in the normal-appearing white matter of the corpus callosum, in correspondence with the administration of the remyelinating treatment clemastine. This study provides direct, biologically validated imaging-based evidence of medically induced myelin repair. Moreover, our work strongly suggests that significant myelin repair occurs outside of lesions. We therefore propose myelin water fraction within the normal-appearing white matter of the corpus callosum as a biomarker for clinical trials looking at remyelination

Susceptibility-based imaging aids accurate distinction of pediatric-onset MS from myelin oligodendrocyte glycoprotein antibody-associated disease.

BackgroundMyelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and pediatric-onset multiple sclerosis (POMS) share clinical and magnetic resonance imaging (MRI) features but differ in prognosis and management. Early POMS diagnosis is essential to avoid disability accumulation. Central vein sign (CVS), paramagnetic rim lesions (PRLs), and central core lesions (CCLs) are susceptibility-based imaging (SbI)-related signs understudied in pediatric populations that may help discerning POMS from MOGAD.MethodsT2-FLAIR and SbI (three-dimensional echoplanar imaging (3D-EPI)/susceptibility-weighted imaging (SWI) or similar) were acquired on 1.5T/3T scanners. Two readers assessed CVS-positive rate (%CVS+), and their average score was used to build a receiver operator curve (ROC) assessing the ability to discriminate disease type. PRLs and CCLs were identified using a consensual approach.ResultsThe %CVS+ distinguished 26 POMS cases (mean age 13.7 years, 63% females, median EDSS 1.5) from 14 MOGAD cases (10.8 years, 35% females, EDSS 1.0) with ROC = 1, p < 0.0001, (cutoff 41%). PRLs were only detectable in POMS participants (mean 2.1±2.3, range 1-10), discriminating the two conditions with a sensitivity of 69% and a specificity of 100%. CCLs were more sensitive (81%) but less specific (71.43%).ConclusionThe %CVS+ and PRLs are highly specific markers of POMS. After proper validation on larger multicenter cohorts, consideration should be given to including such imaging markers for diagnosing POMS at disease onset