An Ecological Correlation Study of Late Age-Related Macular Degeneration and the Complement Factor H Y402H Polymorphism

PURPOSE:
To investigate whether variation in the distribution of the risk allele frequency of the Y402H single-nucleotide polymorphism (SNP) across various ethnicities and geographic regions reflects differences in the prevalence of late age-related macular degeneration (AMD) in those ethnicities.

METHODS:
Published data were obtained via a systematic search. Study samples were grouped into clusters by ethnicity and geographic location and the Spearman correlation coefficient of the prevalence of late AMD and risk allele frequencies was calculated across clusters.

RESULTS:
Across all ethnicities, AMD prevalence was seen to increase with age. Populations of European descent had both higher risk allele frequencies and prevalence of late AMD than did Japanese, Chinese, and Hispanic descendants. Results for African descendants were anomalous: although allele frequency was similar to that in European populations, the age-specific prevalence of late AMD was considerably lower. The correlation coefficient for the association between allele frequency and AMD prevalence was 0.40 (95% confidence interval [CI] = -0.36 to 0.84, P = 0.28) in all populations combined and 0.71 (95% CI = 0.02-0.94, P = 0.04) when people of African descent were excluded.

CONCLUSIONS:
Evidence was found at the population level to support a positive association between the Y204H risk allele and the prevalence of AMD after exclusion of studies undertaken on persons of African ancestry. Data in African, Middle Eastern, and South American populations are needed to provide a better understanding of the association of late AMD genetic risk across ethnicities.

Taking the Next Step? Achieving another Bill of Rights

The aim of this article is to explore the recent Bill of Rights debate in the UK. This is deliberately located in the UK’s complex ‘national question’ because of the obsessive focus on achieving a proper grounding for human rights. A new form of national human rights protectionism appears to be emerging and merits careful consideration. The article suggests that it is better to acknowledge and accept the existence of a plurality of nationalisms in the UK in these discussions and understand how an essentially ‘British nationalist’ discourse sounds and works in that overall context. The concern is that the Bill of Rights debate is becoming an inadequate surrogate for the more challenging constitutional conversations that are required, and human rights discourse thus invested with expectations of national renewal that it can never meet and does not have the internal resources to resolve. If the process does go forward it may be better to prepare the ground for a deeper and wider constitutional dialogue across these islands than stumble clumsily and divisively into this territory simply via ‘another’ UK Bill of Rights.

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.