Indication for the disappearance of reactor electron antineutrinos in the Double Chooz experiment

The Double Chooz Experiment presents an indication of reactor electron antineutrino disappearance consistent with neutrino oscillations. A ratio of 0.944 $\pm$ 0.016 (stat) $\pm$ 0.040 (syst) observed to predicted events was obtained in 101 days of running at the Chooz Nuclear Power Plant in France, with two 4.25 GW$_{th}$ reactors. The results were obtained from a single 10 m$^3$ fiducial volume detector located 1050 m from the two reactor cores. The reactor antineutrino flux prediction used the Bugey4 measurement as an anchor point. The deficit can be interpreted as an indication of a non-zero value of the still unmeasured neutrino mixing parameter \sang. Analyzing both the rate of the prompt positrons and their energy spectrum we find \sang = 0.086 $\pm$ 0.041 (stat) $\pm$ 0.030 (syst), or, at 90% CL, 0.015 $<$ \sang $\ <$ 0.16.Comment: 7 pages, 4 figures, (new version after PRL referee's comments

Angiopoietin-1 is required for Schlemm’s canal development in mice and humans

Made available in accordance with publisher's policyPrimary congenital glaucoma (PCG) is a leading cause of blindness in children worldwide and is caused by developmental defects in 2 aqueous humor outflow structures, Schlemm’s canal (SC) and the trabecular meshwork. We previously identified loss-of-function mutations in the angiopoietin (ANGPT) receptor TEK in families with PCG and showed that ANGPT/TEK signaling is essential for SC development. Here, we describe roles for the major ANGPT ligands in the development of the aqueous outflow pathway. We determined that ANGPT1 is essential for SC development, and that Angpt1-knockout mice form a severely hypomorphic canal with elevated intraocular pressure. By contrast, ANGPT2 was dispensable, although mice deficient in both Angpt1 and Angpt2 completely lacked SC, indicating that ANGPT2 compensates for the loss of ANGPT1. In addition, we identified 3 human subjects with rare ANGPT1 variants within an international cohort of 284 PCG patients. Loss of function in 2 of the 3 patient alleles was observed by functional analysis of ANGPT1 variants in a combined in silico, in vitro, and in vivo approach, supporting a causative role for ANGPT1 in disease. By linking ANGPT1 with PCG, these results highlight the importance of ANGPT/TEK signaling in glaucoma pathogenesis and identify a candidate target for therapeutic development

The genetics of myopia

Myopia is the most common eye condition worldwide and its prevalence is increasing. While changes in environment, such as time spent outdoors, have driven myopia rates, within populations myopia is highly heritable. Genes are estimated to explain up to 80% of the variance in refractive error. Initial attempts to identify myopia genes relied on family studies using linkage analysis or candidate gene approaches with limited progress. More genome-wide association study (GWAS) approaches have taken over, ultimately resulting in the identification of hundreds of genes for refractive error and myopia, providing new insights into its molecular machinery. These studies showed myopia is a complex trait, with many genetic variants of small effect influencing retinal signaling, eye growth and the normal process of emmetropization. The genetic architecture and its molecular mechanisms are still to be clarified and while genetic risk score prediction models are improving, this knowledge must be expanded to have impact on clinical practice

Flipped classroom approach to global outreach: cross-cultural teaching of horizontal strabismus to Chinese ophthalmology residents.

AimTo evaluate the flipped classroom model for teaching horizontal strabismus didactics in an ophthalmology residency program in China as part of a visiting professorship from the United States.MethodsResidents from an ophthalmology residency program in China were invited to participate in flipped classroom sessions taught by an experienced American ophthalmology faculty in 2018. Residents were instructed to watch a pre-class video lecture prior to the in-class-case-based activity. Content tests (5 Ophthalmic Knowledge Assessment Program style questions) and surveys were administered before and after the classroom sessions (100% response rate). These results were compared to that of an American cohort who were taught the same content.ResultsThe Chinese cohort of 12 residents preferred the flipped classroom to the traditional classroom at higher rates than the American cohort of 40 residents (92% vs 55%, P=0.04) and felt that all ophthalmology topics would be appropriate for the flipped classroom teaching style (P-values between 0.008 and &lt;0.001). In both Chinese and American cohorts, we found that the exotropia curriculum saw a small but significant improvement in performance following the flipped classroom session (P=0.025 for Chinese residents; P=0.001 for US residents), whereas scores in both groups for the esotropia course did not significantly improve.ConclusionThis is the first study to evaluate the flipped classroom model implemented by a visiting ophthalmology professor in a global outreach setting. The flipped classroom sessions are viewed favorably by the Chinese residents relative to the US cohort with a modest impact on knowledge. Decreased in-person interpreter requirement and increased student engagement make this model valuable in cross-cultural visiting professorship settings. Finally, the flipped classroom may lend itself well to a virtual format to prevent the transmission of COVID-19, although such a format requires further study

Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity

Published version made available in accordance publisher policy. Article available freely at PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922711/Primary congenital glaucoma (PCG) is a devastating eye disease and an important cause of childhood blindness worldwide. In PCG, defects in the anterior chamber aqueous humor outflow structures of the eye result in elevated intraocular pressure (IOP); however, the genes and molecular mechanisms involved in the etiology of these defects have not been fully characterized. Previously, we observed PCG-like phenotypes in transgenic mice that lack functional angiopoietin-TEK signaling. Herein, we identified rare TEK variants in 10 of 189 unrelated PCG families and demonstrated that each mutation results in haploinsufficiency due to protein loss of function. Multiple cellular mechanisms were responsible for the loss of protein function resulting from individual TEK variants, including an absence of normal protein production, protein aggregate formation, enhanced proteasomal degradation, altered subcellular localization, and reduced responsiveness to ligand stimulation. Further, in mice, hemizygosity for Tek led to the formation of severely hypomorphic Schlemm’s canal and trabecular meshwork, as well as elevated IOP, demonstrating that anterior chamber vascular development is sensitive to Tek gene dosage and the resulting decrease in angiopoietin-TEK signaling. Collectively, these results identify TEK mutations in patients with PCG that likely underlie disease and are transmitted in an autosomal dominant pattern with variable expressivity

Mutations in SCO2 are associated with autosomal-dominant high-grade myopia

10.1016/j.ajhg.2013.04.005American Journal of Human Genetics925820-826AJHG