Search

Background Antibodies to myelin oligodendrocyte glycoprotein (MOG) are associated with a CNS inflammatory disorder distinct from multiple sclerosis (MS) and aquaporin-4 antibody-positive neuromyelitis optica (NMO). Knowledge of the clinical spectrum of MOG antibody disease (MOGAD) remains incomplete, particularly in comparison to two related inflammatory demyelinating diseases, MS and NMO. Objective Compare demographics, clinical characteristics, estimated disability, laboratory results, and treatment responses of a U.S. MOGAD cohort with age- and sex-matched MS and NMO patients. Design, setting, and participants This observational, case-control, single-center study identified each group via ICD-10 diagnosis code searches through the electronic medical records of adult patients seen at the John L. Trotter MS Center between January 1, 2019 and January 1, 2020. MOGAD and NMO patients were confirmed to have at least one positive antibody test; those in the MS group had a confirmed diagnosis by a physician with MS subspecialty training. Data were collected after IRB approval. Results Twenty-six patients were included in each group. MOGAD patients were predominantly Caucasian (88.5%) with mean onset age of 43.9 years. MOGAD patients had no comorbid other autoimmune diseases and comparatively lower rates of family members with autoimmune disease (20.0%) than either MS (40.0%) or NMO (34.6%) matched cohorts. 91% of MOGAD attacks were monofocal, and over 70% presented with optic neuritis. Severity of MOGAD attacks was similar to that of seropositive NMO, but the robust degree of recovery was more similar to MS. Four MOGAD patients converted to negative antibody status, with no attacks occurring after conversion. Serum ANA and ENA were less frequently elevated in MOGAD (21.7%, 5.0%) than in seropositive NMO patients (66.7%, 42.9%). Elevated IgG synthesis rate and positive CSF-restricted oligoclonal bands were not seen in our MOGAD cohort, and only one MOGAD patient had an elevated IgG index. Despite anti-CD20 therapy, 28.6% of MOGAD patients continued to suffer relapses. Conclusions MOGAD was characterized by a predominantly monofocal presentation (typically optic neuritis) and severe attacks with better recovery than seen with seropositive NMO attacks. Lack of CSF-restricted oligoclonal bands distinguished MOGAD from MS.

Background The Expanded Disability Status Scale (EDSS), a common outcome measure in Multiple Sclerosis (MS), is obtained prospectively through a direct standardized evaluation. The objective of this study is to develop and validate an algorithm to derive EDSS scores from previous neurological clinical documentation. Methods The algorithm utilizes data from the history, review of systems, and physical exam. EDSS scores formally obtained from research patients were compared to captured EDSS (c‐EDSS) scores. To test inter‐rater reliability, a second investigator captured scores from a subset of patients. Agreement between formal and c-EDSS scores was assessed using a weighted kappa. Clinical concordance was defined as a difference of one-step in EDSS (0.5) and functional system (1.0) scores. Results Clinical documentation from 92 patients (EDSS range 0.0–8.5) was assessed. Substantial agreement between the c‐EDSS and formal EDSS (kappa 0.80; 95% CI 0.74–0.86) was observed. The mean difference between scores was 0.16. The clinical concordance was 78%. Near-perfect agreement was found between the two raters (kappa 0.89; 95% CI 0.84–0.95). The mean inter-rater difference in c-EDSS was 0.23. Conclusions This algorithm reliably captures EDSS scores retrospectively with substantial correlation with formal EDSS and high inter‐rater agreement. This algorithm may have practical implications in clinic, MS research and clinical trials.

Multiple sclerosis (MS) is an immune-mediated disorder that affects the central nervous system (CNS), often first affecting people in early adulthood. Although most MS patients have a relapsing-remitting course (RRMS) at disease onset, a substantial proportion later develop chronic progression, termed secondary progressive MS (SPMS). Approximately 10% of MS patients experience chronic progression from disease onset, termed primary progressive multiple sclerosis (PPMS). Although several disease-modifying treatment (DMT) options exist for relapsing forms of this disease, DMT options are few for progressive MS (PPMS and SPMS). Herein, we strive to define progressive MS, review major clinical trials aimed at progressive MS, and delineate potential strategies in the management of progressive MS. In 2017, the first DMT for PPMS, the B lymphocyte-depleting monoclonal antibody, ocrelizumab, came to market. Ocrelizumab reduced 12-week confirmed disability progression (CDP) by 24% versus placebo. Siponimod, a selective sphingosine-1-phosphate receptor modulator, reduced 3-month CDP by 21% versus placebo in SPMS. Ibudilast slowed brain atrophy in PPMS and SPMS patients in a multicenter phase 2b study. Smaller early phase studies of alpha-lipoic acid and simvastatin each found slowing of rate of whole brain atrophy in SPMS patients. Reasons now exist for optimism in the search for DMTs for progressive MS. It remains a challenge to identify outcome measures that accurately reflect the underlying pathology in progressive MS, which is less inflammatory and more degenerative than RRMS.

Many scientific applications running on today's supercomputers deal with increasingly large data sets and are correspondingly bottlenecked by the time it takes to read or write the data from/to the file system. We therefore undertook a study to characterize the parallel I/O performance of two of today's leading parallel supercomputers: the Columbia system at NASA Ames Research Center and the NEC SX-8 supercluster at the University of Stuttgart, Germany. On both systems, we ran a total of seven parallel I/O benchmarks, comprising five low-level benchmarks: (i) IO_Bench, (ii) MPI Tile IO, (iii) IOR (POSIX and MPI-IO), (iv) b_eff_io (five different patterns), and (v) SPIOBENCH, and two scalable synthetic compact application (SSCA) benchmarks: (a) HPCS (high productivity computing systems) SSCA #3 and (b) FLASH IO (parallel HDF5). We present the results of these experiments characterizing the parallel I/O performance of these two systems.

Many large-scale parallel scientific and engineering applications, especially climate modeling, often run for lengthy periods and require data checkpointing periodically to save the state of the computation for a program restart. In addition, such applications need to write data to disks for post-processing, e.g., visualization. Both these scenarios involve a write-only pattern using Hierarchal Data Format (HDF) files. In this paper, we study the scalability of CXFS by HDF based Structured Adaptive Mesh Refinement (AMR) appli- cation for three different block sizes. The code used is a block-structured AMR hydrodynamics code that solves compressible, reactive hydrodynamic equations and characterizes physics and mathematical algorithms used in studying nuclear flashes on neutron stars and white dwarfs. The computational domain is divided into blocks distributed across the processors. Typically, a block contains 8 zones in each coordinate direction (x, y, and z) and a perimeter of guard cells (in this case, 4 zones deep) to hold information from the neighbors. We used three different block sizes of 8 × 8 × 8, 16 × 16 × 16, and 32 × 32 × 32. Results of parallel I/O bandwidths (checkpoint file and two plot files) are presented for all three-block sizes on a wide range of processor counts, ranging from 1 to 508 processors of the Co- lumbia system.