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Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10(-11)) and 8q12 (minimum p value 1.82×10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.

BackgroundIn the absence of an effective vaccine against HIV-1, the scientific community is presented with the challenge of developing alternative methods to curb its spread. Due to the complexity of the disease, however, our ability to predict the impact of various prevention and treatment strategies is limited. While ART has been widely accepted as the gold standard of modern care, its timing is debated.ObjectivesTo evaluate the impact of medical interventions at the level of individuals on the spread of infection across the whole population. Specifically, we investigate the impact of ART initiation timing on HIV-1 spread in an MSM (Men who have Sex with Men) population.Design and methodsA stochastic multi-scale model of HIV-1 transmission that integrates within a single framework the in-host cellular dynamics and their outcomes, patient health states, and sexual contact networks. The model captures disease state and progression within individuals, and allows for simulation of therapeutic strategies.ResultsEarly ART initiation may substantially affect disease spread through a population.ConclusionsOur model provides a multi-scale, systems-based approach to evaluate the broader implications of therapeutic strategies.

Purpose: To report piloting and initial validation of the VQoL_CYP, a novel age-appropriate vision-related quality of life (VQoL) instrument for self-reporting by children with visual impairment (VI)., Methods: Participants were a random patient sample of children with VI aged 10-15 years. 69 patients, drawn from patient databases at Great Ormond Street Hospital and Moorfields Eye Hospital, United Kingdom, participated in piloting of the draft 47-item VQoL instrument, which enabled preliminary item reduction. Subsequent administration of the instrument, alongside functional vision (FV) and generic health-related quality of life (HRQoL) self-report measures, to 101 children with VI comprising a nationally representative sample enabled further item reduction and evaluation of psychometric properties using Rasch analysis. Construct validity was assessed through Pearson correlation coefficients., Results: Item reduction through piloting (8 items removed for skewness and individual item response pattern) and validation (1 item removed for skewness and 3 for misfit in Rasch) produced a 35-item scale, with fit values within acceptable limits, no notable differential item functioning, good measurement precision, ordered response categories and acceptable targeting in Rasch. The VQoL_CYP showed good construct validity, correlating strongly with HRQoL scores, moderately with FV scores but not with acuity., Conclusions: Robust child-appropriate self-report VQoL measures for children with VI are necessary for understanding the broader impacts of living with a visual disability, distinguishing these from limited functioning per se. Future planned use in larger patient samples will allow further psychometric development of the VQoL_CYP as an adjunct to objective outcomes assessment.