Factors associated with severe corneal endothelial damage following acute primary angle closure in Chinese subjects.

PURPOSE: To investigate the corneal endothelial damage caused by acute primary angle closure (APAC) and related risk factors for severe corneal endothelial cell damage in Chinese subjects. METHODS: In this multicentre retrospective study, 160 Chinese patients (171 eyes) diagnosed with APAC were recruited. Endothelial cell density (ECD) and morphological changes short after APAC were studied. Univariate regression and multivariate regression were used to identify risk factors associated with the extent of ECD reduction, including age, gender, education level, patients' location, systemic diseases, APAC duration (hours), highest recorded intraocular pressure (IOP), and presenting IOP. Factors associated with the probability of severe corneal damage (ECD lower than 1000/mm2) were analysed based on a linear function. RESULTS: After one APAC episode, 12.28% eyes had ECD lower than 1000/mm2, 30.41% had ECD between 1000 and 2000/mm2, and 57.31% had ECD more than 2000/mm2. Attack duration was the only factor associated with severe endothelial damage (p < 0.0001). If the attack were to be subsided within 15.0 h, possibility of ECD lower than 1000/mm2 could be controlled under 1%. CONCLUSION: Shortly after the abortion of APAC, 12.28% patients experienced severe endothelial cell damage with ECD less than 1000/mm2. The only factor associated with severe ECD decrease was attack duration. Immediate and effective treatment is pivotal for preserving corneal endothelial function in APAC patients.

Deep intronic variant in MVK as a cause for mevalonic aciduria initially presenting as non-syndromic retinitis pigmentosa.

Non-syndromic retinitis pigmentosa (NSRP) is a clinically and genetically heterogeneous group of disorders characterized by progressive degeneration of the rod and cone photoreceptors, often leading to blindness. The evolving association of syndromic genes to cause NSRP and the increasing role of intronic variants in explaining missing heritability in genetic disorders present challenges in establishing conclusive clinical and genetic diagnoses. This study sought to identify and validate the causative genetic variant(s) in a 13-year-old male initially diagnosed with NSRP. Genome sequencing identified a pathogenic missense variant in MVK [NM_000431.3:c.803T>C (p.Ile268Thr)], in trans with a novel intronic variant predicted to create a new donor splice site (c.768+71C>A). Proband cDNA analysis confirmed the inclusion of the first 68 base pairs of intron 8 that resulted in a frameshift in MVK (r.768_769ins[768+1_768+68]) and significantly reduced the expression of reference transcript (17.6%). Patient re-phenotyping revealed ataxia, cerebellar atrophy, elevated urinary mevalonate and LTE4 , in keeping with mild mevalonic aciduria and associated syndromic retinitis pigmentosa. Leakage of reference transcript likely explains the milder phenotype observed in our patient. This is the first association of a deep intronic splice variant to cause MVK-related disorder. This report highlights the importance of variant validation and patient re-phenotyping in establishing accurate diagnosis in the era of genome sequencing.

Iodous acid - a more efficient nucleation precursor than iodic acid.

Iodous acid (HIO2), a vital iodine oxyacid, potentially plays an important role in the formation of new particles in marine areas (He et al., Science, 2021, 371, 589-595). However, the nucleation mechanism of HIO2 is still poorly understood. Herein, the self-nucleation of HIO2 under different atmospheric conditions is investigated by a combination of quantum chemical calculations and the Atmospheric Cluster Dynamics Code (ACDC) simulations. The results indicate that HIO2 can form relatively stable molecular clusters through hydrogen bonds and halogen bonds, and the self-nucleation of HIO2 proceeds by sequential addition of HIO2 or HIO2-based small clusters. Besides, in order to better illustrate the role of HIO2 in new particle formation (NPF) in marine areas, we compare its nucleation properties with those of iodic acid (HIO3), a significant iodine-containing nucleation precursor in marine regions. We find that the cluster formation rate of the self-nucleation of HIO2 is higher than that of the self-nucleation of HIO3 although [HIO2] is lower than [HIO3], which indicates that the HIO2 molecule is a more efficient nucleation precursor than the HIO3 molecule. Therefore, the self-nucleation of HIO2 could become one of the most important sources for NPF in marine areas, which could provide potential theoretical evidence for explaining the intensive NPF events observed in these areas.

Retina Vascular Structures near the Optic Disc and in the Macula in Primary Angle-Closure Suspects.

INTRODUCTION: The main aim of this article was to study the retinal peripapillary and macular vascular structures in eyes with primary angle-closure suspects (PACS) using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional study, control and PACS subjects were recruited from a community screening. Only one eye per subject was used for analysis. All participants underwent a questionnaire survey, physical and ophthalmic examinations, ocular biometry measurements, and OCTA. We compared basic demographics and vessel structure parameters between control and PACS eyes. Univariate and multivariate linear regression analyses were performed to investigate factors associated with vascular parameters in both groups. RESULTS: Data from 254 subjects including 155 PACS and 99 controls were analyzed. In the peripapillary region, PACS eyes showed similar retina nerve fiber layer (RNFL) and vessel densities (VDs) including and excluding large vessels compared to control eyes. Compared to control eyes, all macular OCTA parameters showed significant differences in PACS eyes, including decreased superficial VD (p = 0.006) and deep VD (p = 0.004), larger fovea avascular zone (FAZ) area (p = 0.006), and longer FAZ perimeter (p = 0.004). Gender (p = 0.039), age (p < 0.001), and Garway-Heath superior hemisphere RNFL (p < 0.001) were risk factors influencing optic disc VD excluding large vessels. Axial length was the major factor affecting macula superficial and deep VDs (p = 0.004 and 0.001 respectively), while PACS was an independent factor associated with larger FAZ perimeter (p = 0.046). CONCLUSION: While PACS and control eyes have comparable RNFL and vascular structure around the optic nerve head, macular vascular structures are significantly different.

Ganglion Cell Complex Parameters in Primary Angle Closure Suspects.

INTRODUCTION: This study aimed to investigate the ganglion cell complex (GCC) parameters in primary angle closure suspects (PACS) and identify the related factors. METHODS: A total of 731 subjects, including 289 subjects with PACS and 442 subjects without PACS, underwent RTVue XR OCT. GCC parameters were compared between the two groups. The linear mixed-effects model was performed to evaluate the relationships between the GCC parameters and related factors. RESULTS: Significant differences were found in gender, age, spherical refractive error, height, waist, anterior chamber depth, lens thickness, axial length, superior GCC thickness, ganglion cell complex focal loss volume, ganglion cell complex global loss volume, and ganglion cell complex root mean square between PACS and normal controls. The linear mixed-effects model showed that age (p = 0.008) and blood glucose (p = 0.001) were negatively correlated with average GCC thickness in PACS subjects, and PACS (p = 0.036) and age (p < 0.001) were the key influencing factors for average GCC thickness. CONCLUSION: GCC parameters in PACS subjects are different from those in normal controls. Careful explanation should be considered when evaluating changes of GCC parameters in patients with PACD.

Surface-enhanced Raman spectroscopy aptasensor for simultaneous determination of ochratoxin A and zearalenone using Au@Ag core-shell nanoparticles and gold nanorods.

The design and fabrication of a surface-enhanced Raman scattering (SERS) aptasensor for simultaneous detection of zearalenone (ZEN) and ochratoxin A (OTA) in wheat and corn samples is described. The capture and reporter probes were SH-cDNA-modified gold nanorods and SH-Apt-modified Au@Ag core-shell nanoparticles, respectively. After recognizing OTA and ZEN aptamers and complementary strands (SH-cDNA), the reporter probe generated a strong SERS signal. The preferred binding of OTA and ZEN aptamers to OTA and ZEN, respectively, caused reporter probes to release the capture probes, resulting in a linear decrease in SERS intensity. The detection of OTA showed good linearity with an R2 value of 0.986, which could be maintained across a wide concentration range (0.01 to 100 ng/mL), with the limit of detection of 0.018 ng/mL. For detection of ZEN, good linearity with an R2 value of 0.987 could be maintained across a wide concentration range (0.05 to 500 ng/mL), with 0.054 ng/mL as the limit of detection. Good accuracy (relative standard deviation < 4.2%) during mycotoxin determination as well as excellent quantitative recoveries (96.0-110.7%) during the analysis of spiked real samples was achieved. The proposed SERS aptasensor exhibited excellent performance in the detection of OTA and ZEN in real food samples. Hence, by simply changing the aptamer, this new model can be applied to the detection of multiple mycotoxins in the food industry.

DYNC2H1 hypomorphic or retina-predominant variants cause nonsyndromic retinal degeneration.

PURPOSE: Determining the role of DYNC2H1 variants in nonsyndromic inherited retinal disease (IRD). METHODS: Genome and exome sequencing were performed for five unrelated cases of IRD with no identified variant. In vitro assays were developed to validate the variants identified (fibroblast assay, induced pluripotent stem cell [iPSC] derived retinal organoids, and a dynein motility assay). RESULTS: Four novel DYNC2H1 variants (V1, g.103327020_103327021dup; V2, g.103055779A>T; V3, g.103112272C>G; V4, g.103070104A>C) and one previously reported variant (V5, g.103339363T>G) were identified. In proband 1 (V1/V2), V1 was predicted to introduce a premature termination codon (PTC), whereas V2 disrupted the exon 41 splice donor site causing incomplete skipping of exon 41. V1 and V2 impaired dynein-2 motility in vitro and perturbed IFT88 distribution within cilia. V3, homozygous in probands 2-4, is predicted to cause a PTC in a retina-predominant transcript. Analysis of retinal organoids showed that this new transcript expression increased with organoid differentiation. V4, a novel missense variant, was in trans with V5, previously associated with Jeune asphyxiating thoracic dystrophy (JATD). CONCLUSION: The DYNC2H1 variants discussed herein were either hypomorphic or affecting a retina-predominant transcript and caused nonsyndromic IRD. Dynein variants, specifically DYNC2H1 variants are reported as a cause of non syndromic IRD.

Metabolomic Profiling Reveals That Reprogramming of Cerebral Glucose Metabolism Is Involved in Ischemic Preconditioning-Induced Neuroprotection in a Rodent Model of Ischemic Stroke.

Ischemic tolerance renders the brain resistant to ischemia-reperfusion (I/R) injury as a result of the activation of endogenous adaptive responses triggered by various types of preconditioning. The complex underlying metabolic mechanisms responsible for the neuroprotection of cerebral ischemic preconditioning (IPC) remain elusive. Herein, gas chromatography-mass spectrometry (GC-MS) technique was applied to delineate the dynamic changes of brain metabolome in a rodent model of ischemic stroke (transient occlusion of the middle cerebral artery, tMCAO), alone or after pretreatment with nonlethal ischemic tolerance induction (transient occlusion of the bilateral common carotid arteries, tBCCAO). Metabolomic analysis showed that accumulation of glucose (concentration increased more than 4 fold) and glycolytic intermediates is the prominent feature of brain I/R-induced metabolic disturbance. IPC attenuated brain I/R damage by subduing postischemic hyperglycolysis, increasing the pentose phosphate pathway (PPP) flux and promoting the utilization of ß-hydroxybutyrate. The expression analysis of pivotal genes and proteins involved in relevant metabolic pathways revealed that the downregulation of AMP-activated protein kinase (AMPK)-mediated glucose transporter-1 (GLUT-1) and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) and reduced mRNA levels of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) subunits were associated with IPC-induced metabolic flexibility, which allows the brain to be more capable of withstanding severe I/R insults. The present study provided mechanistic insights into the metabolic signature of IPC and indicated that adaptively modulating brain glucose metabolism could be an effective approach for the therapeutic intervention of ischemic stroke.

Biallelic Mutations in GNB3 Cause a Unique Form of Autosomal-Recessive Congenital Stationary Night Blindness.

Congenital stationary night blindness (CSNB) is a heterogeneous group of non-progressive inherited retinal disorders with characteristic electroretinogram (ERG) abnormalities. Riggs and Schubert-Bornschein are subtypes of CSNB and demonstrate distinct ERG features. Riggs CSNB demonstrates selective rod photoreceptor dysfunction and occurs due to mutations in genes encoding proteins involved in rod phototransduction cascade; night blindness is the only symptom and eye examination is otherwise normal. Schubert-Bornschein CSNB is a consequence of impaired signal transmission between the photoreceptors and bipolar cells. Schubert-Bornschein CSNB is subdivided into complete CSNB with an ON bipolar signaling defect and incomplete CSNB with both ON and OFF pathway involvement. Both subtypes are associated with variable degrees of night blindness or photophobia, reduced visual acuity, high myopia, and nystagmus. Whole-exome sequencing of a family screened negative for mutations in genes associated with CSNB identified biallelic mutations in the guanine nucleotide-binding protein subunit beta-3 gene (GNB3). Two siblings were compound heterozygous for a deletion (c.170_172delAGA [p.Lys57del]) and a nonsense mutation (c.1017G>A [p.Trp339(∗)]). The maternal aunt was homozygous for the nonsense mutation (c.1017G>A [p.Trp339(∗)]). Mutational analysis of GNB3 in a cohort of 58 subjects with CSNB identified a sporadic case individual with a homozygous GNB3 mutation (c.200C>T [p.Ser67Phe]). GNB3 encodes the ß subunit of G protein heterotrimer (Gαßγ) and is known to modulate ON bipolar cell signaling and cone transducin function in mice. Affected human subjects showed an unusual CSNB phenotype with variable degrees of ON bipolar dysfunction and reduced cone sensitivity. This unique retinal disorder with dual anomaly in visual processing expands our knowledge about retinal signaling.

Comparison of movement rate with different initial moment-to-force ratios.

INTRODUCTION: The objective of this clinical prospective study was to evaluate the effect of the 2 treatment strategies, translation or controlled tipping, followed by root correction on canine retraction efficiency, specifically canine movement rate. METHODS: Twenty-one patients who needed bilateral maxillary canine retraction to close extraction space as part of their treatment plan were selected for this study. Segmental T-loops designed for controlled tipping or for translation were applied randomly to each side. Two digital maxillary dental casts (taken before and after treatment) were used to measure the tooth displacements of each patient. The coordinate system located at the center of canine crown on the pretreatment model with the 3 axes defined in the mesial-distal (M-D), buccal-lingual, and occlusal-gingival directions was used to express the 6 tooth displacement components. The movement rates on the occlusal plane and in the M-D direction were computed. Movement rates were calculated by dividing the M-D displacements or the resultant displacement on the occlusal plane with the corresponding treatment time. RESULTS: T-Loops for controlled tipping moved canines faster (33.3% on occlusal plane and 38.5% in the M-D direction) than T-loops for translation. The differences were statistically significant (P = 0.041 on the occlusal plane and 0.020 in the M-D direction). CONCLUSIONS: Moment-to-force ratio (M/F) affects the canine movement rate in a maxillary canine retraction treatment with the use of a segmented T-loop mechanism. Within the neighborhood of the ratio for translation, lower M/F moves the canine faster than higher M/F both on the occlusal plane and in the M-D direction.

Aeromonas veronii and aerolysin are important for the pathogenesis of motile aeromonad septicemia in cyprinid fish.

Aeromonas species are ubiquitous inhabitants of freshwater environments, and are responsible for fish motile aeromonad septicemia (MAS). A. hydrophila is implicated as the primary etiologic agent of MAS. Here, we analysed MAS epidemiological data for cyprinid fish in southern China, and found that A. veronii infections dominated. Consistent with this observation, A. veronii isolates were generally more virulent than A. hydrophila isolates when infecting germ-free zebrafish larvae via continuous immersion challenge. Through in vivo screening of the transposon library of the A. veronii strain Hm091, aerolysin was identified as the key virulence factor. Further results indicated that A. veronii Hm091 aerolysin disrupts the intestinal barrier of zebrafish, enabling systematic invasion by not only A. veronii Hm091 in a mono-infection, but also A. hydrophila NJ-1 in a mixed infection. Moreover, the differences in aerolysin expression and activity were the major contributor to the observed differences between the A. veronii and A. hydrophila strains regarding invasion efficacy via intestine. Together, our results provide new insights into the aetiology and pathogenesis of Aeromonas infections, and highlight the importance of A. veronii-targeted treatments in future efforts against MAS.

Type B Response Regulators Act As Central Integrators in Transcriptional Control of the Auxin Biosynthesis Enzyme TAA1.

During embryogenesis and organ formation, establishing proper gradient is critical for auxin function, which is achieved through coordinated regulation of both auxin metabolism and transport. Expression of auxin biosynthetic genes is often tissue specific and is regulated by environmental signals. However, the underlying regulatory mechanisms remain elusive. Here, we investigated the transcriptional regulation of a key auxin biosynthetic gene, l-Tryptophan aminotransferase of Arabidopsis1 (TAA1). A canonical and a novel Arabidopsis (Arabidopsis thaliana) response regulator (ARR) binding site were identified in the promoter and the second intron of TAA1, which were required for its tissue-specific expression. C-termini of a subset of the type B ARRs selectively bind to one or both cis elements and activate the expression of TAA1 We further demonstrated that the ARRs not only mediate the transcriptional regulation of TAA1 by cytokinins, but also mediate its regulation by ethylene, light, and developmental signals. Through direct protein-protein interactions, the transcriptional activity of ARR1 is enhanced by ARR12, DELLAs, and ethylene-insenstive3 (EIN3). Our study thus revealed the ARR proteins act as key node that mediate the regulation of auxin biosynthesis by various hormonal, environmental, and developmental signals through transcriptional regulation of the key auxin biosynthesis gene TAA1.

Experimental study on improvement effect of guide wall to water flow in bend of spillway chute.

In order to improve water flow in a bend of a spillway chute using a guide wall, modeling experiments with or without a guide wall under conditions of three different bend axial radii, three chute bottom slopes and three flow rates were carried out in this study. Two indexes were calculated, which are the improved water surface uniformity and the reduced rate of water surface difference in concave and convex banks of the cross-section. The results show that: (1) setting a guide wall in a bend can improve water flow in the bend because it increased the water surface uniformity of the cross-section and reduced the water surface difference in the concave and convex banks; (2) the smaller the bend axial radius, the better the water surface improvement effect will be using a guide wall; (3) the steeper the bottom slope, the more cross-sections with less water surface difference; and (4) flow rates have a great influence on water surface improvement in the bend, and the guide wall can improve water flow obviously when the water depth in the starting section of the bend is lower than the height of the guide wall. This study has important implications in engineering design of guide walls.

Hounsfield unit change in root and alveolar bone during canine retraction.

INTRODUCTION: The objective of this study was to determine the Hounsfield unit (HU) changes in the alveolar bone and root surfaces during controlled canine retractions. METHODS: Eighteen maxillary canine retraction patients were selected for this split-mouth design clinical trial. The canines in each patient were randomly assigned to receive either translation or controlled tipping treatment. Pretreatment and posttreatment cone-beam computed tomography scans of each patient were used to determine tooth movement direction and HU changes. The alveolar bone and root surface were divided into 108 divisions, respectively. The HUs in each division were measured. Mixed-model analysis of variance was applied to test the HU change distribution at the P <0.05 significance level. RESULTS: The HU changes varied with the directions relative to the canine movement. The HU reductions occurred at the root surfaces. Larger reductions occurred in the divisions that were perpendicular to the moving direction. However, HUs decreased in the alveolar bone in the moving direction. The highest HU reduction was at the coronal level. CONCLUSIONS: HU reduction occurs on the root surface in the direction perpendicular to tooth movement and in the alveolar bone in the direction of tooth movement when a canine is retracted.

Specialist versus generalist life histories and nucleotide diversity in Caenorhabditis nematodes.

Species with broad ecological amplitudes with respect to a key focal resource, niche generalists, should maintain larger and more connected populations than niche specialists, leading to the prediction that nucleotide diversity will be lower and more subdivided in specialists relative to their generalist relatives. This logic describes the specialist-generalist variation hypothesis (SGVH). Some outbreeding species of Caenorhabditis nematodes use a variety of invertebrate dispersal vectors and have high molecular diversity. By contrast, Caenorhabditis japonica lives in a strict association and synchronized life cycle with its dispersal host, the shield bug Parastrachia japonensis, itself a diet specialist. Here, we characterize sequence variation for 20 nuclear loci to investigate how C. japonica's life history shapes nucleotide diversity. We find that C. japonica has more than threefold lower polymorphism than other outbreeding Caenorhabditis species, but that local populations are not genetically disconnected. Coupled with its restricted range, we propose that its specialist host association contributes to a smaller effective population size and lower genetic variation than host generalist Caenorhabditis species with outbreeding reproductive modes. A literature survey of diverse organisms provides broader support for the SGVH. These findings encourage further testing of ecological and evolutionary hypotheses with comparative population genetics in Caenorhabditis and other taxa.

Dentists' Information Needs and Opinions on Accessing Patient Information via Health Information Exchange: Survey Study.

BACKGROUND: The integration of medical and dental records is gaining significance over the past 2 decades. However, few studies have evaluated the opinions of practicing dentists on patient medical histories. Questions remain on dentists' information needs; their perception of the reliability of patient-reported medical history; satisfaction with the available information and the methods to gather this information; and their attitudes to other options, such as a health information exchange (HIE) network, to collect patient medical history. OBJECTIVE: This study aims to determine Indiana dentists' information needs regarding patients' medical information and their opinions about accessing it via an HIE. METHODS: We administered a web-based survey to Indiana Dental Association members to assess their current medical information-retrieval approaches, the information critical for dental care, and their willingness to access or share information via an HIE. We used descriptive statistics to summarize survey results and multivariable regression to examine the associations between survey respondents' characteristics and responses. RESULTS: Of the 161 respondents (161/2148, 7.5% response rate), 99.5% (n=160) respondents considered patients' medical histories essential to confirm no contraindications, including allergies or the need for antibiotic prophylaxis during dental care and other adverse drug events. The critical information required were medical conditions or diagnosis, current medications, and allergies, which were gathered from patient reports. Furthermore, 88.2% (n=142) of respondents considered patient-reported histories reliable; however, they experienced challenges obtaining information from patients and physicians. Additionally, 70.2% (n=113) of respondents, especially those who currently access an HIE or electronic health record, were willing to use an HIE to access or share their patient's information, and 91.3% (n=147) shared varying interests in such a service. However, usability, data accuracy, data safety, and cost are the driving factors in adopting an HIE. CONCLUSIONS: Patients' medical histories are essential for dentists to optimize dental care, especially for those with chronic conditions. In addition, most dentists are interested in using an HIE to access patient medical histories. The findings from this study can provide an alternative option for improving communications between dental and medical professionals and help the health information technology system or tool developers identify critical requirements for more user-friendly designs.

Characteristics of beta parapapillary atrophy in primary angle-closure suspect.

OBJECTIVE: To investigate the characteristics of beta parapapillary atrophy (ß-PPA) in patients with primary angle-closure suspect (PACS). METHODS AND ANALYSIS: In total, 215 and 259 eyes with PACS and non-PACS (NPACS), respectively, were enrolled in this observational, cross-sectional study. Stereoscopic fundus and optical coherence tomography images were used to characterise ß-PPA; the former was also used to measure the major ß-PPA parameters. Univariate and multiple logistic regression analyses were used to identify the factors correlated with the presence of ß-PPA and with ß-PPA parameters. RESULTS: The ß-PPA occurrence rates were 48.80% and 44.40% in the PACS and NPACS groups, respectively, with no significant difference between groups. Compared with that in the NPACS group, the ß-PPA area was significantly larger (p=0.005) in the PACS group, but the angular extent and maximum radial length did not differ between groups (p=0.110 and 0.657, respectively) after adjusting for age and axial length. The presence of ß-PPA was associated with older age (OR 1.057, 95% CI 1.028 to 1.088, p<0.001) and larger disc area (OR 1.716, 95% CI 1.170 to 2.517, p=0.006). A larger ß-PPA area was associated with older age (p=0.014), greater vertical cup-to-disc ratio (p=0.028), larger disc area (p<0.001) and PACS diagnosis (p=0.035). CONCLUSION: 48.80% of participants with PACS had ß-PPA, which is slightly larger than NPACS. The area of ß-PPA was larger in PACS, while the angular extent and maximum radial length did not differ between groups.

Deep Learning Classification of Angle Closure based on Anterior Segment OCT.

PURPOSE: To assess the performance and generalizability of a convolutional neural network (CNN) model for objective and high-throughput identification of primary angle-closure disease (PACD) as well as PACD stage differentiation on anterior segment swept-source OCT (AS-OCT). DESIGN: Cross-sectional. PARTICIPANTS: Patients from 3 different eye centers across China and Singapore were recruited for this study. Eight hundred forty-one eyes from the 2 Chinese centers were divided into 170 control eyes, 488 PACS, and 183 PAC + PACG eyes. An additional 300 eyes were recruited from Singapore National Eye Center as a testing data set, divided into 100 control eyes, 100 PACS, and 100 PAC + PACG eyes. METHODS: Each participant underwent standardized ophthalmic examination and was classified by the presiding physician as either control, primary angle-closure suspect (PACS), primary angle closure (PAC), or primary angle-closure glaucoma (PACG). Deep Learning model was used to train 3 different CNN classifiers: classifier 1 aimed to separate control versus PACS versus PAC + PACG; classifier 2 aimed to separate control versus PACD; and classifier 3 aimed to separate PACS versus PAC + PACG. All classifiers were evaluated on independent validation sets from the same region, China and further tested using data from a different country, Singapore. MAIN OUTCOME MEASURES: Area under receiver operator characteristic curve (AUC), precision, and recall. RESULTS: Classifier 1 achieved an AUC of 0.96 on validation set from the same region, but dropped to an AUC of 0.84 on test set from a different country. Classifier 2 achieved the most generalizable performance with an AUC of 0.96 on validation set and AUC of 0.95 on test set. Classifier 3 showed the poorest performance, with an AUC of 0.83 and 0.64 on test and validation data sets, respectively. CONCLUSIONS: Convolutional neural network classifiers can effectively distinguish PACD from controls on AS-OCT with good generalizability across different patient cohorts. However, their performance is moderate when trying to distinguish PACS versus PAC + PACG. FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.

Efficacy of Morning Versus Evening Latanoprost/Timolol Fixed Combination for Open-Angle Glaucoma and Ocular Hypertension: A Randomized Clinical Trial.

Purpose: To compare the efficacy of morning and evening latanoprost/timolol fixed-combination (LTFC) dosing in patients with primary open-angle glaucoma (POAG) and ocular hypertension. Methods: In this double-blind, randomized clinical trial, 63 untreated Chinese patients with POAG and ocular hypertension were enrolled. All patients received LTFC and were randomized (1:1) to group 1, morning (8 AM) dosing, or group 2, evening (8 PM) dosing. Vehicle drops were used in the morning or evening, accordingly, to preserve masking. Patients were treated for 4 weeks. Outcomes included mean reduction of the 24-hour intraocular pressure (IOP) and IOP fluctuation from baseline after a 4-week treatment. Results: Fifty-six patients were included in the final analysis. In both groups, the posttreatment IOP values were significantly lower than those at baseline at each 24-hour measuring time point. A significant difference between the groups in IOP reduction from baseline was observed at the 9:30 AM time point (4.01 ± 2.62 vs. 2.42 ± 3.23 mm Hg, evening dosing versus morning dosing group; P = 0.048). Both groups showed decreased IOP fluctuation after treatment. However, the morning dosing group had a significantly greater decrease in diurnal IOP fluctuation than that of the evening dosing group (2.04 ± 2.32 mm Hg vs. 0.50 ± 1.70 mm Hg, respectively; P = 0.012). Conclusions: Both morning and evening LTFC dosing can effectively reduce 24-hour IOP and IOP fluctuation. Morning dosing is more likely to effectively control diurnal IOP fluctuations. Translational Relevance: This multicenter, double-blind, randomized clinical trial generates robust evidence on the optimal LTFC dosing regimen to help clinical decision-making in the treatment of raised IOP.

Measurement of δ18O, δ17O, and 17O-excess in water by off-axis integrated cavity output spectroscopy and isotope ratio mass spectrometry.

Stable isotopes of water have long been used to improve understanding of the hydrological cycle, catchment hydrology, and polar climate. Recently, there has been increasing interest in measurement and use of the less-abundant (17)O isotope in addition to (2)H and (18)O. Off-axis integrated cavity output spectroscopy (OA-ICOS) is demonstrated for accurate and precise measurements δ(18)O, δ(17)O, and (17)O-excess in liquid water. OA-ICOS involves no sample conversion and has a small footprint, allowing measurements to be made by researchers collecting the samples. Repeated (514) high-throughput measurements of the international isotopic reference water standard Greenland Ice Sheet Precipitation (GISP) demonstrate the precision and accuracy of OA-ICOS: δ(18)OVSMOW-SLAP = -24.74 ± 0.07‰ (1σ) and δ(17)OVSMOW-SLAP = -13.12 ± 0.05‰ (1σ). For comparison, the International Atomic Energy Agency (IAEA) value for δ(18)OVSMOW-SLAP is -24.76 ± 0.09‰ (1σ) and an average of previously reported values for δ(17)OVSMOW-SLAP is -13.12 ± 0.06‰ (1σ). Multiple (26) high-precision measurements of GISP provide a (17)O-excessVSMOW-SLAP of 23 ± 10 per meg (1σ); an average of previously reported values for (17)O-excessVSMOW-SLAP is 22 ± 11 per meg (1σ). For all these OA-ICOS measurements, precision can be further enhanced by additional averaging. OA-ICOS measurements were compared with two independent isotope ratio mass spectrometry (IRMS) laboratories and shown to have comparable accuracy and precision as the current fluorination-IRMS techniques in δ(18)O, δ(17)O, and (17)O-excess. The ability to measure accurately δ(18)O, δ(17)O, and (17)O-excess in liquid water inexpensively and without sample conversion is expected to increase vastly the application of δ(17)O and (17)O-excess measurements for scientific understanding of the water cycle, atmospheric convection, and climate modeling among others.