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Purpose: Emmetropization requires coordinated scaling of the major ocular components, corneal curvature and axial length. This coordination is achieved in part through a shared set of genetic variants that regulate eye size. Poorly coordinated scaling of corneal curvature and axial length results in refractive error. We tested the hypothesis that genetic variants regulating eye size in emmetropic eyes are distinct from those conferring susceptibility to refractive error. Methods: A genome-wide association study (GWAS) for corneal curvature in 22,180 adult emmetropic individuals was performed as a proxy for a GWAS for eye size. A polygenic score created using lead GWAS variants was tested for association with corneal curvature and axial length in an independent sample: 437 classified as emmetropic and 637 as ametropic. The genetic correlation between eye size and refractive error was calculated using linkage disequilibrium score regression for approximately 1 million genetic variants. Results: The GWAS for corneal curvature in emmetropes identified 32 independent genetic variants (P < 5.0e-08). A polygenic score created using these 32 genetic markers explained 3.5% (P < 0.001) and 2.0% (P = 0.001) of the variance in corneal curvature and axial length, respectively, in the independent sample of emmetropic individuals but was not predictive of these traits in ametropic individuals. The genetic correlation between eye size and refractive error was close to zero (rg = 0.00; SE = 0.06; P = 0.95). Conclusions: These results support the hypothesis that genetic variants regulating eye size in emmetropic eyes do not overlap with those conferring susceptibility to myopia. This suggests that distinct biological pathways regulate normal eye growth and myopia development. peerReviewed

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Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

A graph G of order $$n\ge 3$$ is pancyclic if G contains a cycle of each possible length from 3 to n, and vertex pancyclic (edge pancyclic) if every vertex (edge) is contained on a cycle of each possible length from 3 to n. A chord of a cycle is an edge between two nonadjacent vertices of the cycle, and chorded cycle is a cycle containing at least one chord. We define a graph G of order $$n\ge 4$$ to be chorded pancyclic if G contains a chorded cycle of each possible length from 4 to n. In this article, we consider extensions of the property of being chorded pancyclic to chorded vertex pancyclic and chorded edge pancyclic.

Women with metastatic breast cancer desire interventions that would allow them to self‐manage symptoms, but which do not require additional clinic appointments. We used a community based participatory research approach to develop a tablet based supportive care intervention called Nurse AMIE to address this need. The intervention modules are drawn from published evidence based clinical guidelines from ASCO and NCCN, including physical activity, soothing music, mindfulness meditation, guided imagery, cognitive behavioral therapy, and psychoeducation. Preliminary results include 61% and 55% acceptability from clinicians and patients, respectively, as well as 86% feasibility, defined as using the tablet for at least 30 of the 90‐day intervention. These preliminary results warrant additional research, particularly given the potential for this intervention to address needs of rural and medically underserved patients.

Background: Myopia prevalence has increased in the past 20 years, with many studies linking the increase to reduced time spent outdoors. A number of recent observational studies have shown an inverse association between vitamin D [25(OH)D] serum levels and myopia. However, in such studies it is difficult to separate the effects of time outdoors and vitamin D levels. In this work we use Mendelian randomization (MR) to assess if genetically determined 25(OH)D levels contribute to the degree of myopia.Methods: We performed MR using results from a meta-analysis of refractive error (RE) genome-wide association study (GWAS) that included 37 382 and 8 376 adult participants of European and Asian ancestry, respectively, published by the Consortium for Refractive Error And Myopia (CREAM). We used single nucleotide polymorphisms (SNPs) in the DHCR7 , CYP2R1, GC and CYP24A1 genes with known effects on 25(OH)D concentration as instrumental variables (IV). We estimated the effect of 25(OH)D on myopia level using a Wald-type ratio estimator based on the effect estimates from the CREAM GWAS.Results: Using the combined effect attributed to the four SNPs, the estimate for the effect of 25(OH)D on refractive error was -0.02 [95% confidence interval (CI) -0.09, 0.04] dioptres (D) per 10 nmol/l increase in 25(OH)D concentration in Caucasians and 0.01 (95% CI -0.17, 0.19) D per 10 nmol/l increase in Asians.Conclusions: The tight confidence intervals on our estimates suggest the true contribution of vitamin D levels to degree of myopia is very small and indistinguishable from zero. Previous findings from observational studies linking vitamin D levels to myopia were likely attributable to the effects of confounding by time spent outdoors.

A chord is an edge between two vertices of a cycle that is not an edge on the cycle. If a cycle has at least one chord, then the cycle is called a chorded cycle, and if a cycle has at least two chords, then the cycle is called a doubly chorded cycle. The minimum degree and the minimum degree-sum conditions are given for a graph to contain vertex-disjoint chorded (doubly chorded) cycles containing specified elements of the graph, i.e., specified vertices, specified edges as cycle-edges, specified paths, or specified edges as chords. Furthermore, the minimum degree condition is given for a graph to be partitioned into chorded cycles containing specified edges as cycle-edges.

Mental health programs to improve problem-solving skills and reduce stress through social gameplay can improve psychiatric outcomes, but little is known about whether adult patients are interested in using them. Primary care patients (n = 467) completed a cross-sectional survey to assess interest in using 2 types of group programs for mental health. A significantly greater percentage (23.7%) of patients expressed interest in a gameplay-based program than in interpersonal therapy (17.6%) (P < .001). Lonely patients and younger patients were more likely to report interest in gameplay. Results suggest that diverse patient populations are interested in using gameplay programs for mental health.

Olaparib was first FDA approved for use in women with advanced ovarian cancer and germline BRCA mutations. Based on the results of subsequent research, the use of this drug has been expanded to patients with metastatic breast cancer with germline BRCA mutation. With the use of a relatively new medication and a larger patient population eligible for therapy, monitoring for novel adverse events associated with therapy is important. This case represents a patient with metastatic breast cancer and germline BRCA2 mutation who developed erythema nodosum after initiation of therapy with olaparib capsules. Her characteristic rash appeared shortly after starting olaparib and recurred after restarting olaparib an additional two times. She was treated with short courses of prednisone therapy with or without holding olaparib with resolution of her rash. The patient was later restarted on olaparib capsules 200 mg twice daily, and she more recently has been maintained on olaparib tablets 300 mg twice daily. On both regimens, the patient experienced only attenuated episodes of erythema nodosum that have not required cessation of therapy or steroid therapy.