Systematic review and meta-analysis of the association between complement component 3 and age-related macular degeneration: A HUGE review and meta-analysis

We performed a meta-analysis to estimate the magnitude of C3 gene polymorphism effects, and their possible mode of action, on age-related macular degeneration (AMD). The meta-analysis included 16 studies for rs2230199 and 7 studies for rs1047286. Data extraction and risk of bias assessments were performed in duplicate, and heterogeneity and publication bias were explored. There was moderate evidence for association between both polymorphisms and AMD in individuals of European descent. For rs2230199, patients with CG and GG genotypes were 1.44 (95% CI: 1.33 – 1.56) and 1.88 (95% CI: 1.59 – 2.23) times more likely to have AMD than patients with CC genotype. For rs1047286, those with GA and AA genotypes had 1.27 (95% CI: 1.15 – 1.41) and 1.70 (95% CI: 1.27 – 2.11) times higher risk of AMD than those with GG genotypes. These gene effects suggested an additive model. The population attributable risks for the GG/GC and AA/GA genotypes are approximately 5-10%. Stratification of studies on the basis of ethnicity indicates that these variants are very infrequent in Asian populations and the significance of the effect observed is based largely on the high frequency of these variants within individuals of European descent. This meta-analysis supports the association between C3 and AMD and provides a robust estimate of the genetic risk.

Transonic Aeroelastic Stability Analysis Using a Kriging-Based Schur Complement Formulation

A method is described to allow searches for transonic aeroelastic instability of realistically sized aircraft models in multidimensional parameter spaces when computational fluid dynamics are used to model the aerodynamics. Aeroelastic instability is predicted from a small nonlinear eigenvalue problem. The approximation of the computationally expensive interaction term modeling the fluid response is formulated to allow the automated and blind search for aeroelastic instability. The approximation uses a kriging interpolation of exact numerical samples covering the parameter space. The approach, demonstrated for the Goland wing and the multidisciplinary optimization transport wing, results in stability analyses over whole flight envelopes at an equivalent cost of several steady-state simulations.