Deficient clearance of apoptotic cells reportedly contributes to the etiopathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). Based on this knowledge, we developed a highly ...specific and sensitive test for the detection of SLE autoantibodies (AAb) utilizing secondary NEcrotic cell (SNEC)-derived material as a substrate. The goal of the present study was to validate the use of SNEC as an appropriate antigen for the diagnosis of SLE in large cohort of patients. We confirmed the presence of apoptotically modified autoantigens on SNEC (dsDNA, high mobility group box 1 protein, apoptosis-associated chromatin modifications, e.g., histones H3-K27-me3; H2A/H4 AcK8,12,16; and H2B-AcK12). Anti-SNEC AAb were measured in the serum of 155 patients with SLE, 89 normal healthy donors (NHD), and 169 patients with other autoimmune connective tissue diseases employing SNEC-based indirect enzyme-linked immunosorbent assay (SNEC ELISA). We compared the test performance of SNEC ELISA with the routine diagnostic tests dsDNA Farr radioimmunoassay (RIA) and nucleosome-based ELISA (
). SNEC ELISA distinguished patients with SLE with a specificity of 98.9% and a sensitivity of 70.6% from NHD clearly surpassing RIA and
. In contrast to the other tests, SNEC ELISA significantly discriminated patients with SLE from patients with rheumatoid arthritis, primary anti-phospholipid syndrome, spondyloarthropathy, psoriatic arthritis, and systemic sclerosis. A positive test result in SNEC ELISA significantly correlated with serological variables and reflected the uptake of opsonized SNEC by neutrophils. This stresses the relevance of SNECs in the pathogenesis of SLE. We conclude that SNEC ELISA allows for the sensitive detection of pathologically relevant AAb, enabling its diagnostic usage. A positive SNEC test reflects the opsonization of cell remnants by AAb, the neutrophil recruitment to tissues, and the enhancement of local and systemic inflammatory responses.
Ecosystems transition quickly in the Anthropocene, whereas biodiversity adapts more slowly. Here we simulated a shifting woodland ecosystem on the Colorado Plateau of western North America by using ...as its proxy over space and time the fundamental niche of the Arizona black rattlesnake (Crotalus cerberus). We found an expansive (= end-of-Pleistocene) range that contracted sharply (= present), but is blocked topographically by Grand Canyon/Colorado River as it shifts predictably northwestward under moderate climate change (= 2080). Vulnerability to contemporary wildfire was quantified from available records, with forested area reduced more than 27% over 13 years. Both ‘ecosystem metrics' underscore how climate and wildfire are rapidly converting the Plateau ecosystem into novel habitat. To gauge potential effects on C. cerberus, we derived a series of relevant ‘conservation metrics' (i.e. genetic variability, dispersal capacity, effective population size) by sequencing 118 individuals across 846 bp of mitochondrial (mt)DNA-ATPase8/6. We identified five significantly different clades (net sequence divergence = 2.2%) isolated by drainage/topography, with low dispersal (FST = 0.82) and small sizes (2Nef = 5.2). Our compiled metrics (i.e. small-populations, topographic-isolation, low-dispersal versus conserved-niche, vulnerable-ecosystem, dispersal barriers) underscore the susceptibility of this woodland specialist to a climate and wildfire tandem. We offer adaptive management scenarios that may counterbalance these metrics and avoid the extirpation of this and other highly specialized, relictual woodland clades.
Measurements of the D(d,p)T (dd) and T(t,2n)(4)He (tt) reaction yields have been compared with those of the D(t,n)(4)He (dt) reaction yield, using deuterium-tritium gas-filled inertial confinement ...fusion capsule implosions. In these experiments, carried out on the OMEGA laser, absolute spectral measurements of dd protons and tt neutrons were obtained. From these measurements, it was concluded that the dd yield is anomalously low and the tt yield is anomalously high relative to the dt yield, an observation that we conjecture to be caused by a stratification of the fuel in the implosion core. This effect may be present in ignition experiments planned on the National Ignition Facility.
Abstract
Background
In 2015, the German Federal Ministry of Education and Research initiated a large data integration and data sharing research initiative to improve the reuse of data from patient ...care and translational research. The Observational Medical Outcomes Partnership (OMOP) common data model and the Observational Health Data Sciences and Informatics (OHDSI) tools could be used as a core element in this initiative for harmonizing the terminologies used as well as facilitating the federation of research analyses across institutions.
Objective
To realize an OMOP/OHDSI-based pilot implementation within a consortium of eight German university hospitals, evaluate the applicability to support data harmonization and sharing among them, and identify potential enhancement requirements.
Methods
The vocabularies and terminological mapping required for importing the fact data were prepared, and the process for importing the data from the source files was designed. For eight German university hospitals, a virtual machine preconfigured with the OMOP database and the OHDSI tools as well as the jobs to import the data and conduct the analysis was provided. Last, a federated/distributed query to test the approach was executed.
Results
While the mapping of ICD-10 German Modification succeeded with a rate of 98.8% of all terms for diagnoses, the procedures could not be mapped and hence an extension to the OMOP standard terminologies had to be made.
Overall, the data of 3 million inpatients with approximately 26 million conditions, 21 million procedures, and 23 million observations have been imported.
A federated query to identify a cohort of colorectal cancer patients was successfully executed and yielded 16,701 patient cases visualized in a Sunburst plot.
Conclusion
OMOP/OHDSI is a viable open source solution for data integration in a German research consortium. Once the terminology problems can be solved, researchers can build on an active community for further development.
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