ABSTRACT
Translational multidisciplinary research is important for the Center for Devices and Radiological Health's efforts for utilizing real-world data (RWD) to enhance predictive evaluation of medical device performance in patient subpopulations. As part of our efforts for developing new RWD-based evidentiary approaches, including in silico discovery of device-related risk predictors and biomarkers, this study aims to characterize the sex/race-related trends in hip replacement outcomes and identify corresponding candidate single nucleotide polymorphisms (SNPs). Adverse outcomes were assessed by deriving RWD from a retrospective analysis of hip replacement hospital discharge data from the National Inpatient Sample (NIS). Candidate SNPs were explored using pre-existing data from the Personalized Medicine Research Project (PMRP). High-Performance Integrated Virtual Environment was used for analyzing and visualizing putative associations between SNPs and adverse outcomes. Ingenuity Pathway Analysis (IPA) was used for exploring plausibility of the sex-related candidate SNPs and characterizing gene networks associated with the variants of interest. The NIS-based epidemiologic evidence showed that periprosthetic osteolysis (PO) was most prevalent among white men. The PMRP-based genetic evidence associated the PO-related male predominance with rs7121 (odds ratio = 4.89; 95% confidence interval = 1.41-17.05) and other candidate SNPs. SNP-based IPA analysis of the expected gene expression alterations and corresponding signaling pathways suggested possible role of sex-related metabolic factors in development of PO, which was substantiated by ad hoc epidemiologic analysis identifying the sex-related differences in metabolic comorbidities in men vs. women with hip replacement-related PO. Thus, our in silico study illustrates RWD-based evidentiary approaches that may facilitate cost/time-efficient discovery of biomarkers for informing use of medical products.
Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Hip Prosthesis/adverse effects , Osteolysis/epidemiology , Prosthesis Failure , Arthroplasty, Replacement, Hip/instrumentation , Biomarkers , Comorbidity , Computer Simulation , Cost-Benefit Analysis , Feasibility Studies , Female , Genetic Predisposition to Disease , Humans , Male , Osteolysis/etiology , Osteolysis/genetics , Polymorphism, Single Nucleotide , Prevalence , Risk Assessment/economics , Risk Assessment/methods , Risk Factors , Sex FactorsABSTRACT
The relationship of lightning and elementary particle fluxes in the thunderclouds is not fully understood to date. Using the particle beams (the so-called Thunderstorm Ground Enhancements - TGEs) as a probe we investigate the characteristics of the interrelated atmospheric processes. The well-known effect of the TGE dynamics is the abrupt termination of the particle flux by the lightning flash. With new precise electronics, we can see that particle flux decline occurred simultaneously with the rearranging of the charge centers in the cloud. The analysis of the TGE energy spectra before and after the lightning demonstrates that the high-energy part of the TGE energy spectra disappeared just after lightning. The decline of particle flux coincides on millisecond time scale with first atmospheric discharges and we can conclude that Relativistic Runaway Electron Avalanches (RREA) in the thundercloud assist initiation of the negative cloud to ground lightning. Thus, RREA can provide enough ionization to play a significant role in the unleashing of the lightning flash.
