Systemic lupus erythematous (SLE) is a chronic multi-organ autoimmune disease. Genetic and environmental factors contribute to disease onset and severity. Sphingolipids are signaling molecules ...involved in regulating cell functions and have been associated with multiple genetic disease processes. African-Americans are more likely to suffer from SLE morbidity than Whites. The Medical University of South Carolina has banked plasma samples from a well-characterized lupus cohort that includes African-Americans and Whites. This study examined the influence of race on plasma sphingolipid profiles in SLE patients and association of sphingolipid levels with comorbid atherosclerosis and SLE disease activity. Mass spectrometry revealed that healthy African-Americans had higher sphingomyelin levels and lower lactosylcermide levels compared to healthy Whites. SLE patients, irrespective of race, had higher levels of ceramides, and sphingoid bases (sphingosine and dihydrosphingosine) and their phosphates compared to healthy subjects. Compared to African-American controls, African-American SLE patients had higher levels of ceramides, hexosylceramides, sphingosine and dihydrosphingosine 1-phosphate. Compared to White controls, White SLE patients exhibited higher levels of sphingoid bases and their phosphates, but lower ratios of C16:0 ceramide/sphingosine 1-phosphate and C24:1 ceramide/sphingosine 1-phosphate. White SLE patients with atherosclerosis exhibited lower levels of sphingoid bases compared to White SLE patients without atherosclerosis. In contrast, African-American SLE patients with atherosclerosis had higher levels of sphingoid bases and sphingomyelins compared to African-American SLE patients without atherosclerosis. Compared to White SLE patients with atherosclerosis, African-American SLE patients with atherosclerosis had higher levels of select sphingolipids. Plasma levels of sphingosine, C16:0 ceramide/sphingosine 1-phosphate ratio and C24:1 ceramide/sphingosine 1-phosphate ratio significantly correlated with SLEDAI in the African-American but not White SLE patients. The C16:0 ceramide/sphingosine 1-phosphate ratio in SLE patients, and levels of C18:1 and C26:1 lactosylcermides, C20:0 hexosylceramide, and sphingoid bases in SLE patients with atherosclerosis could be dependent on race. Further ethnic studies in SLE cohorts are necessary to verify use of sphingolipidomics as complementary diagnostic tool.
We present the calibration of the Swift Ultraviolet and Optical Telescope (UVOT ) grisms, of which there are two, providing low-resolution field spectroscopy in the ultraviolet and optical bands, ...respectively. The UV grism covers the range λ1700–5000 Å with a spectral resolution (λ/Δλ) of 75 at λ2600 Å for source magnitudes of u=10–16 mag, while the visible grism covers the range λ2850–6600 Å with a spectral resolution of 100 at λ4000 Å for source magnitudes of b=12–17 mag. This calibration extends over all detector positions, for all modes used during operations. The wavelength accuracy (1σ) is 9 Å in the UV grism clocked mode, 17 Å in the UV grism nominal mode and 22 Å in the visible grism. The range below λ2740 Å in the UV grism and λ5200 Å in the visible grism never suffers from overlapping by higher spectral orders. The flux calibration of the grisms includes a correction we developed for coincidence loss in the detector. The error in the coincidence loss correction is less than 20 per cent. The position of the spectrum on the detector only affects the effective area (sensitivity) by a few per cent in the nominal modes, but varies substantially in the clocked modes. The error in the effective area is from 9 per cent in the UV grism clocked mode to 15 per cent in the visible grism clocked mode.
Objective
The Rheumatology Informatics System for Effectiveness (RISE) is a national electronic health record (EHR)–enabled registry. RISE passively collects data from EHRs of participating ...practices, provides advanced quality measurement and data analytic capacities, and fulfills national quality reporting requirements. Here we report the registry's architecture and initial data, and we demonstrate how RISE is being used to improve the quality of care.
Methods
RISE is a certified Centers for Medicare and Medicaid Services Qualified Clinical Data Registry, allowing collection of data without individual patient informed consent. We analyzed data between October 1, 2014 and September 30, 2015 to characterize initial practices and patients captured in RISE. We also analyzed medication use among rheumatoid arthritis (RA) patients and performance on several quality measures.
Results
Across 55 sites, 312 clinicians contributed data to RISE; 72% were in group practice, 21% in solo practice, and 7% were part of a larger health system. Sites contributed data on 239,302 individuals. Among the subset with RA, 34.4% of patients were taking a biologic or targeted synthetic disease‐modifying antirheumatic drug (DMARD) at their last encounter, and 66.7% were receiving a nonbiologic DMARD. Examples of quality measures include that 55.2% had a disease activity score recorded, 53.6% a functional status score, and 91.0% were taking a DMARD in the last year.
Conclusion
RISE provides critical infrastructure for improving the quality of care in rheumatology and is a unique data source to generate new knowledge. Data validation and mapping are ongoing and RISE is available to the research and clinical communities to advance rheumatology.
The etiology and reasons underlying the ethnic disparities in systemic sclerosis (SSc) remain unknown. African Americans are disproportionally affected by SSc and yet are underrepresented in ...research. The aim of this study was to comprehensively investigate the association of DNA methylation levels with SSc in dermal fibroblasts from patients of African ancestry. Reduced representation bisulfite sequencing (RRBS) was performed on primary dermal fibroblasts from 15 SSc patients and 15 controls of African ancestry, and over 3.8 million CpG sites were tested for differential methylation patterns between cases and controls. The dermal fibroblasts from African American patients exhibited widespread reduced DNA methylation. Differentially methylated CpG sites were most enriched in introns and intergenic regions while depleted in 5' UTR, promoters, and CpG islands. Seventeen genes and eleven promoters showed significant differential methylation, mostly in non-coding RNA genes and pseudogenes. Gene set enrichment analysis (GSEA) and gene ontology (GO) analyses revealed an enrichment of pathways related to interferon signaling and mesenchymal differentiation. The hypomethylation of
and
was accompanied by these genes' overexpression in patients but underexpression for lncRNA
. These data show that differential methylation occurs in dermal fibroblasts from African American patients with SSc and identifies novel coding and non-coding genes.
The development of nephritis increases the risk of morbidity and mortality in systemic lupus erythematosus (SLE) patients. While standard induction therapies, such as mycophenolate mofetil (MMF) ...induce clinical remission (i.e., complete response) in approximately 50% of SLE patients with nephritis, many patients fail to respond. Therapeutic response is often not assessed until 6-12 months after beginning treatment. Those patients that fail to respond to treatment continue to accumulate organ damage, thus, there is a critical need to predict which patients will fail therapy before beginning treatment, allowing physicians to optimize therapy. Our previous studies demonstrated elevated urine, but not serum, glycosphingolipids (GSLs) in SLE patients with nephritis compared to SLE patients without nephritis, suggesting the urine GSLs were derived from the kidney. In this study, we measured the GSLs hexosylceramide and lactosylceramide in extracellular vesicles isolated from longitudinal urine samples of LN patients that were treated with MMF for 12 months. GSL levels were significantly elevated in the baseline samples (prior to treatment) of non-responders compared to complete responders. While a few other proteins measured in the whole urine were higher in non-responders at baseline, only GSLs demonstrated a significant ability to discriminate treatment response in lupus nephritis patients.
Identifying patients with certain clinical criteria based on manual chart review of doctors' notes is a daunting task given the massive amounts of text notes in the electronic health records (EHR). ...This task can be automated using text classifiers based on Natural Language Processing (NLP) techniques along with pattern recognition machine learning (ML) algorithms. The aim of this research is to evaluate the performance of traditional classifiers for identifying patients with Systemic Lupus Erythematosus (SLE) in comparison with a newer Bayesian word vector method.
We obtained clinical notes for patients with SLE diagnosis along with controls from the Rheumatology Clinic (662 total patients). Sparse bag-of-words (BOWs) and Unified Medical Language System (UMLS) Concept Unique Identifiers (CUIs) matrices were produced using NLP pipelines. These matrices were subjected to several different NLP classifiers: neural networks, random forests, naïve Bayes, support vector machines, and Word2Vec inversion, a Bayesian inversion method. Performance was measured by calculating accuracy and area under the Receiver Operating Characteristic (ROC) curve (AUC) of a cross-validated (CV) set and a separate testing set.
We calculated the accuracy of the ICD-9 billing codes as a baseline to be 90.00% with an AUC of 0.900, the shallow neural network with CUIs to be 92.10% with an AUC of 0.970, the random forest with BOWs to be 95.25% with an AUC of 0.994, the random forest with CUIs to be 95.00% with an AUC of 0.979, and the Word2Vec inversion to be 90.03% with an AUC of 0.905.
Our results suggest that a shallow neural network with CUIs and random forests with both CUIs and BOWs are the best classifiers for this lupus phenotyping task. The Word2Vec inversion method failed to significantly beat the ICD-9 code classification, but yielded promising results. This method does not require explicit features and is more adaptable to non-binary classification tasks. The Word2Vec inversion is hypothesized to become more powerful with access to more data. Therefore, currently, the shallow neural networks and random forests are the desirable classifiers.
Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder that can cause significant morbidity and mortality. A large body of evidence has shown that African-Americans experience the ...disease more severely than other racial-ethnic groups. Relevant literature for the years 2000 to August 2015 were obtained from systematic searches of PubMed, Scopus, and the EBSCOHost platform that includes MEDLINE, CINAHL, etc. to evaluate research focused on SLE in African-Americans. Thirty-six of the 1502 articles were classified according to their level of evidence. The systematic review of the literature reported a wide range of adverse outcomes in African-American SLE patients and risk factors observed in other mono and multi-ethnic investigations. Studies limited to African-Americans with SLE identified novel methods for more precise ascertainment of risk and observed novel findings that hadn't been previously reported in African-Americans with SLE. Both environmental and genetic studies included in this review have highlighted unique African-American populations in an attempt to isolate risk attributable to African ancestry and observed increased genetic influence on overall disease in this cohort. The review also revealed emerging research in areas of quality of life, race-tailored interventions, and self-management. This review reemphasizes the importance of additional studies to better elucidate the natural history of SLE in African-Americans and optimize therapeutic strategies for those who are identified as being at high risk.
Highlights • Slow clinical trial patient accrual is key to high costs for new drugs/devices. • Clinicians’ unawareness of open trials, and effort to refer, are key to slow accrual. • Non-interruptive ...notice of relevant trials and one-click referral can boost accrual. • Some trials infeasible by standard accrual mechanisms became feasible via our system. • User satisfaction with our system was high. Very few clinicians opted out.
We present the earliest ultraviolet (UV) spectrum of a gamma-ray burst (GRB) as observed with the Swift Ultra-Violet/Optical Telescope (UVOT). The GRB 081203A spectrum was observed for 50 s with the ...UV-grism starting 251 s after the Swift-Burst-Alert-Telescope (BAT) trigger. During this time, the GRB was ≈13.4 mag (u filter) and was still rising to its peak optical brightness. In the UV-grism spectrum, we find a damped Lyα line, Lyβ and the Lyman continuum break at a redshift z= 2.05 ± 0.01. A model fit to the Lyman absorption implies a gas column density of log NH i= 22.0 ± 0.1 cm−2, which is typical of GRB host galaxies with damped Lyα absorbers. This observation of GRB 081203A demonstrates that for brighter GRBs (v≈ 14 mag) with moderate redshift (0.5 < z < 3.5) the UVOT is able to provide redshifts, and probe for damped Lyα absorbers within 4–6 min from the time of the Swift-BAT trigger.
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