Genome-wide association study for sight-threatening diabetic retinopathy reveals association with genetic variation near the GRB2 gene

AIMS/HYPOTHESIS: Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study.

METHODS: Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot.

RESULTS: The top ranked variant was rs3805931 with p = 2.66 × 10(-7), but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10(-5)) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10(-8)). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina.

CONCLUSIONS/INTERPRETATION: Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.

Cloud benchmarking for performance

How can applications be deployed on the cloud to achieve maximum performance? This question has become significant and challenging with the availability of a wide variety of Virtual Machines (VMs) with different performance capabilities in the cloud. The above question is addressed by proposing a six step benchmarking methodology in which a user provides a set of four weights that indicate how important each of the following groups: memory, processor, computation and storage are to the application that needs to be executed on the cloud. The weights along with cloud benchmarking data are used to generate a ranking of VMs that can maximise performance of the application. The rankings are validated through an empirical analysis using two case study applications, the first is a financial risk application and the second is a molecular dynamics simulation, which are both representative of workloads that can benefit from execution on the cloud. Both case studies validate the feasibility of the methodology and highlight that maximum performance can be achieved on the cloud by selecting the top ranked VMs produced by the methodology.

Spectacle design preferences among Chinese primary and secondary students and their parents: A qualitative and quantitative study

Purpose: To identify the specific characteristics making glasses designs, particularly those compatible with adjustable glasses, more or less appealing to Chinese children and their parents. Patients and Methods: Primary and secondary school children from urban and rural China with < = -1.00 diopters of bilateral myopia and their parents ranked four conventional-style frames identified by local optical shops as popular versus four child-specific frames compatible with adjustable spectacles. Scores based on the proportion of maximum possible ranking were computed for each style. Selected children and their parents also participated in Focus Groups (FGs) discussing spectacle design preference. Recordings were transcribed and coded by two independents reviewers using NVivo software. Results: Among 136 urban primary school children (age range 9-11 years), 290 rural secondary school children (11-17 years) and 16 parents, all adjustable-style frames (scores on 0-100 scale 25.7-62.4) were ranked behind all conventional frames (63.0-87.5). For eight FGs including 12 primary children, 26 secondary children and 16 parents, average kappa values for NVivo coding were 0.81 (students) and 0.70 (parents). All groups agreed that the key changes to make adjustable designs more attractive were altering the round lenses to rectangular or oval shapes and adding curved earpieces for more stable wear. The thick frames of the adjustable designs were considered stylish, and children indicated they would wear them if the lens shape were modified. Conclusions: Current adjustable lens designs are unattractive to Chinese children and their parents, though this study identified specific modifications which would make them more appealing.

Factors influencing the success of rural cataract surgery programs in China:The study of hospital administration and relative productivity (SHARP)

PURPOSE. To explore factors potentially influencing the success or failure of rural Chinese hospitals in increasing cataract surgical output and quality. METHODS. Focus groups (FGs, n = 10) were conducted with hospital administrators, doctors, and nurses at 28 county hospitals in Guangdong Province. Discussions explored respondents' views on increasing surgical volume and quality and improving patient satisfaction. Respondents numerically ranked possible strategies to increase surgical volume and quality and patient satisfaction. FG transcripts were independently coded by two reviewers utilizing the constant comparative method following the grounded theory approach, and numerical responses were scored and ranked. RESULTS. Ten FGs and 77 ranking questionnaires were completed by 33 administrators, 23 doctors, and 21 nurses. Kappa values for the two coders were greater than 0.7 for all three groups. All groups identified a critical need for enhanced management training for hospital directors. Doctors and nurses suggested reducing surgical fees to enhance uptake, although administrators were resistant to this. Although doctors saw the need to improve equipment, administrators felt current material conditions were adequate. Respondents agreed that patient satisfaction was generally high, and did not view increasing patient satisfaction as a priority. CONCLUSIONS. Our findings highlight agreements and disagreements among the three stakeholder groups about improving surgical output and quality, which can inform strategies to improve cataract programs in rural China. Respondents' beliefs about high patient satisfaction are not in accord with other studies in the area, highlighting a potential area for intervention. © 2013 The Association for Research in Vision and Ophthalmology, Inc.