Prevalence and causes of functional low vision in school-age children: results from standardized population surveys in Asia, Africa, and Latin America.

PURPOSE: Data on the prevalence and causes of functional low vision (FLV) in adults and children are lacking but are important for planning low-vision services. This study was conducted to determine the prevalence and causes of FLV among children recruited in eight population-based prevalence surveys of visual impairment and refractive error from six countries (India [2 locations]; China [2 locations]; Malaysia, Chile, Nepal, and South Africa). METHODS: Using the same protocol, 4082 to 6527 children aged 5 (or 7) to 15 years were examined at each site. Uncorrected and presenting visual acuities were successfully measured with retroilluminated logMAR tumbling-E charts in 3997 to 5949 children; cycloplegic autorefraction was performed and best corrected acuities assessed. All children were examined by an ophthalmologist and a cause of visual loss assigned to eyes with uncorrected acuity < or =6/12. The prevalence of FLV was determined overall and by site; associations with gender, age, parental education and urban/rural location were assessed with logistic regression. RESULTS: The prevalence of FLV ranged from 0.65 to 2.75 in 1000 children, with wide confidence intervals. The overall prevalence was 1.52 in 1000 children (95% CI 1.16-1.95). FLV was significantly associated with age (odds ratio [OR] 1.13 for each year, P = 0.01), and parental education was protective (OR 0.75 for each of five levels of education, P = 0.017). Retinal lesions and amblyopia were the commonest causes. CONCLUSIONS: More studies are needed to determine the prevalence and causes of FLV in children so that services can be planned that promote independence, improve quality of life, and increase access to education

BREXIT Election:Forecasting a Conservative Party Victory through the Pound using ARIMA and Facebook\u27s Prophet

On the 30th October, 2019, the markets watched as British Prime Minister, Boris Johnson, took a massive political gamble to call a general election to break the Withdrawal Agreement stalemate in the House of Commons to “Get BREXIT Done”. The pound had been politically sensitive owing to BREXIT uncertainty. With the polls indicating a Conservative win on 4thDecember, 2019, the margin of victory could be observed through increases in the pound. The outcome of a Conservative party victory would benefit the pound by removing the current market turbulence. We look to provide a short-term forecast of the pound. Our approach focuses on modelling the GBP/EUR and GBP/USD Fx from the inception of BREXIT referendum talks from the 1stJanuary, 2016 to the conclusion of the BREXIT election on the 12thDecember, 2019, focusing on forecasted increases in the pound from the 4thDecember, 2019. We construct two machine learning models in the form of an Auto Regressive Integrated Moving Average (ARIMA) financial time series and an additive regression financial time series using Facebook’s Prophet to investigate the hypothesis that the polls prediction of a Conservative victory could be validated by forecasted increases in the pound. The efficiency of the forecasted models was then tested based on MAPE and MSE criteria. Our results found that the ARIMA and Prophet models were effective and proficient in forecasting the polls prediction on the 4thDecember, 2019 of a Conservative win by validation of forecasted increases in the pound. The ARIMA (4,1,0) model resulted in forecasts with the lowest MAPE and MAE

Brauer-Thrall for totally reflexive modules over local rings of higher dimension

Let $R$ be a commutative Noetherian local ring. Assume that $R$ has a pair $\{x,y\}$ of exact zerodivisors such that $\dim R/(x,y)\ge2$ and all totally reflexive $R/(x)$-modules are free. We show that the first and second Brauer--Thrall type theorems hold for the category of totally reflexive $R$-modules. More precisely, we prove that, for infinitely many integers $n$, there exists an indecomposable totally reflexive $R$-module of multiplicity $n$. Moreover, if the residue field of $R$ is infinite, we prove that there exist infinitely many isomorphism classes of indecomposable totally reflexive $R$-modules of multiplicity $n$.Comment: to appear in Algebras and Representation Theor

Rare variant analyses across multiethnic cohorts identify novel genes for refractive error

Peer reviewe

APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans

Myopia is the most common vision disorder and the leading cause of visual impairment worldwide. However, gene variants identified to date explain less than 10% of the variance in refractive error, leaving the majority of heritability unexplained (“missing heritability”). Previously, we reported that expression of APLP2 was strongly associated with myopia in a primate model. Here, we found that low-frequency variants near the 5’-end of APLP2 were associated with refractive error in a prospective UK birth cohort (n = 3,819 children; top SNP rs188663068, p = 5.0 × 10&lt;sup&gt;−4&lt;/sup&gt;) and a CREAM consortium panel (n = 45,756 adults; top SNP rs7127037, p = 6.6 × 10&lt;sup&gt;−3&lt;/sup&gt;). These variants showed evidence of differential effect on childhood longitudinal refractive error trajectories depending on time spent reading (gene x time spent reading x age interaction, p = 4.0 × 10&lt;sup&gt;−3&lt;/sup&gt;). Furthermore, Aplp2 knockout mice developed high degrees of hyperopia (+11.5 ± 2.2 D, p &lt; 1.0 × 10&lt;sup&gt;−4&lt;/sup&gt;) compared to both heterozygous (-0.8 ± 2.0 D, p &lt; 1.0 × 10&lt;sup&gt;−4&lt;/sup&gt;) and wild-type (+0.3 ± 2.2 D, p &lt; 1.0 × 10&lt;sup&gt;−4&lt;/sup&gt;) littermates and exhibited a dose-dependent reduction in susceptibility to environmentally induced myopia (F(2, 33) = 191.0, p &lt; 1.0 × 10&lt;sup&gt;−4&lt;/sup&gt;). This phenotype was associated with reduced contrast sensitivity (F(12, 120) = 3.6, p = 1.5 × 10&lt;sup&gt;−4&lt;/sup&gt;) and changes in the electrophysiological properties of retinal amacrine cells, which expressed Aplp2. This work identifies APLP2 as one of the “missing” myopia genes, demonstrating the importance of a low-frequency gene variant in the development of human myopia. It also demonstrates an important role for APLP2 in refractive development in mice and humans, suggesting a high level of evolutionary conservation of the signaling pathways underlying refractive eye development.</p

Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia

Determining Possible Shared Genetic Architecture Between Myopia and Primary Open-Angle Glaucoma

PURPOSE: To determine genetic correlations between common myopia and primary open-angle glaucoma (POAG). // METHODS: We tested the association of myopia polygenic risk scores (PRSs) with POAG and POAG endophenotypes using two studies: the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) study comprising 798 POAG cases with 1992 controls, and the Rotterdam Study (RS), a population-based study with 11,097 participants, in which intraocular pressure (IOP) and optic disc parameter measurements were catalogued. PRSs were derived from genome-wide association study meta-analyses conducted by the Consortium for Refractive Error and Myopia (CREAM) and 23andMe. In total, 12 PRSs were constructed and tested. Further, we explored the genetic correlation between myopia, POAG, and POAG endophenotypes by using the linkage disequilibrium score regression (LDSC) method. // RESULTS: We did not find significant evidence for an association between PRS of myopia with POAG (P = 0.81), IOP (P = 0.07), vertical cup-disc ratio (P = 0.42), or cup area (P = 0.25). We observed a nominal association with retinal nerve fiber layer (P = 7.7 × 10-3) and a significant association between PRS for myopia and disc area (P = 1.59 × 10-9). Using the LDSC method, we found a genetic correlation only between myopia and disc area (genetic correlation [RhoG] = -0.12, P = 1.8 × 10-3), supporting the findings of the PRS approach. // CONCLUSIONS: Using two complementary approaches we found no evidence to support a genetic overlap between myopia and POAG; our results suggest that the comorbidity of these diseases is not influenced by common variants. The association between myopia and optic disc size is well known and validates this methodology

Epidemiologic analyses with error-prone exposures: review of current practice and recommendations.

PURPOSE: Variables in observational studies are commonly subject to measurement error, but the impact of such errors is frequently ignored. As part of the STRengthening Analytical Thinking for Observational Studies Initiative, a task group on measurement error and misclassification seeks to describe the current practice for acknowledging and addressing measurement error. METHODS: Task group on measurement error and misclassification conducted a literature survey of four types of research studies that are typically impacted by exposure measurement error: (1) dietary intake cohort studies, (2) dietary intake population surveys, (3) physical activity cohort studies, and (4) air pollution cohort studies. RESULTS: The survey revealed that while researchers were generally aware that measurement error affected their studies, very few adjusted their analysis for the error. Most articles provided incomplete discussion of the potential effects of measurement error on their results. Regression calibration was the most widely used method of adjustment. CONCLUSIONS: Methods to correct for measurement error are available but require additional data regarding the error structure. There is a great need to incorporate such data collection within study designs and improve the analytical approach. Increased efforts by investigators, editors, and reviewers are needed to improve presentation of research when data are subject to error