Assessment of Social Vulnerabilities of Care and Prognosis in Adult Ocular Melanomas in the US.

BACKGROUND: Prior works have studied the impact of social determinants on various cancers but there is limited analysis on eye-orbit cancers. Current literature tends to focus on socioeconomic status and race, with sparse analysis of interdisciplinary contributions. We examined social determinants as measured by the Centers for Disease Control and Prevention (CDC) Social Vulnerability Index (SVI), quantifying eye and orbit melanoma disparities across the United States. METHODS: A retrospective review of 15,157 patients diagnosed with eye-orbit cancers in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2017 was performed, extracting 6139 ocular melanomas. SVI scores were abstracted and matched to SEER patient data, with scores generated by weighted averages per population density of county's census tracts. Primary outcome was months survived, while secondary outcomes were advanced staging, high grading, and primary surgery receipt. RESULTS: With increased total SVI score, indicating more vulnerability, we observed significant decreases of 23.1% in months survival for melanoma histology (p < 0.001) and 19.6-39.7% by primary site. Increasing total SVI showed increased odds of higher grading (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.02-1.43) and decreased odds of surgical intervention (OR 0.94, 95% CI 0.92-0.96). Of the four themes, higher magnitude contributions were observed with socioeconomic status (26.0%) and housing transportation (14.4%), while lesser magnitude contributions were observed with minority language status (13.5%) and household composition (9.0%). CONCLUSIONS: Increasing social vulnerability, as measured by the CDC SVI and its subscores, displayed significant detrimental trends in prognostic and treatment factors for adult eye-orbit melanoma. Subscores quantified which social determinants contributed most to disparities. This lays groundwork for providers to target the highest-impact social determinant for non-clinical factors in patient care.

From microbes to microbiomes: Applications for plant health and sustainable agriculture.

Plant-microbe interaction research has had a transformative trajectory, from individual microbial isolate studies to comprehensive analyses of plant microbiomes within the broader phytobiome framework. Acknowledging the indispensable role of plant microbiomes in shaping plant health, agriculture, and ecosystem resilience, we underscore the urgent need for sustainable crop production strategies in the face of contemporary challenges. We discuss how the synergies between advancements in 'omics technologies and artificial intelligence can help advance the profound potential of plant microbiomes. Furthermore, we propose a multifaceted approach encompassing translational considerations, transdisciplinary research initiatives, public-private partnerships, regulatory policy development, and pragmatic expectations for the practical application of plant microbiome knowledge across diverse agricultural landscapes. We advocate for strategic collaboration and intentional transdisciplinary efforts to unlock the benefits offered by plant microbiomes and address pressing global issues in food security. By emphasizing a nuanced understanding of plant microbiome complexities and fostering realistic expectations, we encourage the scientific community to navigate the transformative journey from discoveries in the laboratory to field applications. As companies specializing in agricultural microbes and microbiomes undergo shifts, we highlight the necessity of understanding how to approach sustainable agriculture with site-specific management solutions. While cautioning against over-promising, we underscore the excitement of exploring the many impacts of microbiome-plant interactions. We emphasize the importance of collaborative endeavors with societal partners to accelerate our collective capacity to harness the diverse and yet-to-be-discovered beneficial activities of plant microbiomes.

Gene disruption by structural mutations drives selection in US rice breeding over the last century.

The genetic basis of general plant vigor is of major interest to food producers, yet the trait is recalcitrant to genetic mapping because of the number of loci involved, their small effects, and linkage. Observations of heterosis in many crops suggests that recessive, malfunctioning versions of genes are a major cause of poor performance, yet we have little information on the mutational spectrum underlying these disruptions. To address this question, we generated a long-read assembly of a tropical japonica rice (Oryza sativa) variety, Carolina Gold, which allowed us to identify structural mutations (>50 bp) and orient them with respect to their ancestral state using the outgroup, Oryza glaberrima. Supporting prior work, we find substantial genome expansion in the sativa branch. While transposable elements (TEs) account for the largest share of size variation, the majority of events are not directly TE-mediated. Tandem duplications are the most common source of insertions and are highly enriched among 50-200bp mutations. To explore the relative impact of various mutational classes on crop fitness, we then track these structural events over the last century of US rice improvement using 101 resequenced varieties. Within this material, a pattern of temporary hybridization between medium and long-grain varieties was followed by recent divergence. During this long-term selection, structural mutations that impact gene exons have been removed at a greater rate than intronic indels and single-nucleotide mutations. These results support the use of ab initio estimates of mutational burden, based on structural data, as an orthogonal predictor in genomic selection.

Nanotechnology Approaches for Prevention and Treatment of Chemotherapy-Induced Neurotoxicity, Neuropathy, and Cardiomyopathy in Breast and Ovarian Cancer Survivors.

Nanotechnology has emerged as a promising approach for the targeted delivery of therapeutic agents while improving their efficacy and safety. As a result, nanomaterial development for the selective targeting of cancers, with the possibility of treating off-target, detrimental sequelae caused by chemotherapy, is an important area of research. Breast and ovarian cancer are among the most common cancer types in women, and chemotherapy is an essential treatment modality for these diseases. However, chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy are common side effects that can affect breast and ovarian cancer survivors quality of life. Therefore, there is an urgent need to develop effective prevention and treatment strategies for these adverse effects. Nanoparticles (NPs) have extreme potential for enhancing therapeutic efficacy but require continued research to elucidate beneficial interventions for women cancer survivors. In short, nanotechnology-based approaches have emerged as promising strategies for preventing and treating chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy. NP-based drug delivery systems and therapeutics have shown potential for reducing the side effects of chemotherapeutics while improving drug efficacy. In this article, the latest nanotechnology approaches and their potential for the prevention and treatment of chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy in breast and ovarian cancer survivors are discussed.

Improved maize reference genome with single-molecule technologies.

Complete and accurate reference genomes and annotations provide fundamental tools for characterization of genetic and functional variation. These resources facilitate the determination of biological processes and support translation of research findings into improved and sustainable agricultural technologies. Many reference genomes for crop plants have been generated over the past decade, but these genomes are often fragmented and missing complex repeat regions. Here we report the assembly and annotation of a reference genome of maize, a genetic and agricultural model species, using single-molecule real-time sequencing and high-resolution optical mapping. Relative to the previous reference genome, our assembly features a 52-fold increase in contig length and notable improvements in the assembly of intergenic spaces and centromeres. Characterization of the repetitive portion of the genome revealed more than 130,000 intact transposable elements, allowing us to identify transposable element lineage expansions that are unique to maize. Gene annotations were updated using 111,000 full-length transcripts obtained by single-molecule real-time sequencing. In addition, comparative optical mapping of two other inbred maize lines revealed a prevalence of deletions in regions of low gene density and maize lineage-specific genes.

Ensembl Genomes 2020-enabling non-vertebrate genomic research.

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of interfaces to genomic data across the tree of life, including reference genome sequence, gene models, transcriptional data, genetic variation and comparative analysis. Data may be accessed via our website, online tools platform and programmatic interfaces, with updates made four times per year (in synchrony with Ensembl). Here, we provide an overview of Ensembl Genomes, with a focus on recent developments. These include the continued growth, more robust and reproducible sets of orthologues and paralogues, and enriched views of gene expression and gene function in plants. Finally, we report on our continued deeper integration with the Ensembl project, which forms a key part of our future strategy for dealing with the increasing quantity of available genome-scale data across the tree of life.

Trends in Glaucoma Surgeries Performed by Glaucoma Subspecialists versus Nonsubspecialists on Medicare Beneficiaries from 2008 through 2016.

PURPOSE: To characterize the use of laser and incisional glaucoma surgeries among Medicare beneficiaries from 2008 through 2016 and to compare the use of these surgeries by glaucoma subspecialists versus nonsubspecialists. DESIGN: Retrospective, observational analysis. PARTICIPANTS: Medicare beneficiaries (n = 1 468 035) undergoing ≥1 laser or incisional glaucoma surgery procedure during 2008 through 2016. METHODS: Claims data from a 20% sample of enrollees in fee-for-service Medicare throughout the United States were analyzed to identify all laser and incisional glaucoma surgeries performed from 2008 through 2016. We assessed use of traditional incisional glaucoma surgery techniques (trabeculectomy and glaucoma drainage implant [GDI] procedure) and microinvasive glaucoma surgery (MIGS). Enrollee and procedure counts were multiplied by 5 to estimate use throughout all of Medicare. Linear regression was used to compare trends in use of glaucoma surgeries between ophthalmologists who could be characterized as glaucoma subspecialists versus nonsubspecialists. MAIN OUTCOME MEASURES: Numbers of laser and incisional glaucoma surgeries performed overall and stratified by glaucoma subspecialist status. RESULTS: The number of Medicare beneficiaries undergoing any glaucoma therapeutic procedure increased by 10.6%, from 218 375 in 2008 to 241 565 in 2016. The total number of traditional incisional glaucoma surgeries decreased by 11.7%, from 37 225 to 32 885 (P = 0.02). The total number of MIGS procedures increased by 426% from 13 705 in 2012 (the first year MIGS codes were available) to 58 345 in 2016 (P = 0.001). Throughout the study period, glaucoma subspecialists performed most of the trabeculectomies (76.7% in 2008, 83.1% in 2016) and GDI procedures (77.7% in 2008, 80.6% in 2016). Many MIGS procedures were performed by nonsubspecialists. The proportions of endocyclophotocoagulations, iStent (Glaukos; San Clemente, CA) insertions, goniotomies, and canaloplasties performed by glaucoma subspecialists in 2016 were 22.0%, 25.2%, 56.9%, and 62.8%, respectively. CONCLUSIONS: From 2008 through 2016, a large shift in practice from traditional incisional glaucoma surgeries to MIGS procedures was observed. Although glaucoma subspecialists continue to perform most traditional incisional glaucoma surgeries, many MIGS procedures are performed by nonsubspecialists. These results highlight the importance of training residents in performing MIGS procedures and managing these patients perioperatively. Future studies should explore the impact of this shift in care on outcomes and costs.

Reduced Mammography Screening for Breast Cancer among Women with Visual Impairment.

PURPOSE: Timely mammography to screen for breast cancer in accordance with the United States Preventive Services Task Force (USPSTF) recommendations can reduce morbidity and mortality substantially. This study assessed whether the odds of undergoing screening mammography are similar for women with and without visual impairment (VI). DESIGN: Retrospective, longitudinal cohort study. PARTICIPANTS: Women aged 65 to 72 years enrolled in fee-for-service Medicare from January 1, 2008, through December 31, 2015. METHODS: Patients with no vision loss (NVL), partial vision loss (PVL), and severe vision loss (SVL) were matched 1:1:1 based on age, race, time in Medicare, urbanicity of residence, and overall health. Women with pre-existing breast cancer were excluded. Multivariable conditional logistic regression modeling compared the odds of undergoing screening mammography within a 2-year follow-up period among the 3 groups. MAIN OUTCOMES MEASURES: Proportion of participants undergoing mammography and adjusted odds ratios (ORs) of undergoing mammography within 2 years of follow-up. RESULTS: A total of 1044 patients were matched (348 in each group). The mean ± standard deviation age at the index date was 69.0 ± 1.5 years for all 3 groups. The proportion of women undergoing 1 mammography screening or more within the 2-year follow-up was 69.0% (n = 240), 56.9% (n = 198), and 56.0% (n = 195) for the NVL, PVL, and SVL groups, respectively (P = 0.0005). The mean ± standard deviation number of mammography screenings undergone per patient during the 5-year period (3-year look-back plus 2-year follow-up) was 3.1 ± 2.0, 2.5 ± 2.0, and 2.3 ± 2.1 for the NVL, PVL, and SVL groups, respectively (P < 0.0001). Women with SVL had 42% decreased odds (OR, 0.58; 95% CI, 0.37-0.90; P = 0.01), and those with PVL had 44% decreased odds (OR, 0.56; CI, 0.36-0.87; P = 0.009) of undergoing mammography during follow-up compared with those with NVL. CONCLUSIONS: Women with VI were significantly less likely to undergo mammography screening for breast cancer than women without VI. Clinicians should look for ways to help ensure that patients with VI undergo mammography and other preventive screenings as recommended by the USPSTF.

Predicting rapid progression phases in glaucoma using a soft voting ensemble classifier exploiting Kalman filtering.

In managing patients with chronic diseases, such as open angle glaucoma (OAG), the case treated in this paper, medical tests capture the disease phase (e.g. regression, stability, progression, etc.) the patient is currently in. When medical tests have low residual variability (e.g. empirical difference between the patient's true and recorded value is small) they can effectively, without the use of sophisticated methods, identify the patient's current disease phase; however, when medical tests have moderate to high residual variability this may not be the case. This paper presents a framework for handling the latter case. The framework presented integrates the outputs of interacting multiple model Kalman filtering with supervised learning classification. The purpose of this integration is to estimate the true values of patients' disease metrics by allowing for rapid and non-rapid phases; and dynamically adapting to changes in these values over time. We apply our framework to classifying whether a patient with OAG will experience rapid progression over the next two or three years from the time of classification. The performance (AUC) of our model increased by approximately 7% (increased from 0.752 to 0.819) when the Kalman filtering results were incorporated as additional features in the supervised learning model. These results suggest the combination of filters and statistical learning methods in clinical health has significant benefits. Although this paper applies our methodology to OAG, the methodology developed is applicable to other chronic conditions.

Glaucoma in Adults-Screening, Diagnosis, and Management: A Review.

Importance: Glaucoma is the most common cause of irreversible blindness worldwide. Many patients with glaucoma are asymptomatic early in the disease course. Primary care clinicians should know which patients to refer to an eye care professional for a complete eye examination to check for signs of glaucoma and to determine what systemic conditions or medications can increase a patient's risk of glaucoma. Open-angle and narrow-angle forms of glaucoma are reviewed, including a description of the pathophysiology, risk factors, screening, disease monitoring, and treatment options. Observations: Glaucoma is a chronic progressive optic neuropathy, characterized by damage to the optic nerve and retinal nerve fiber layer, that can lead to permanent loss of peripheral or central vision. Intraocular pressure is the only known modifiable risk factor. Other important risk factors include older age, nonwhite race, and a family history of glaucoma. Several systemic medical conditions and medications including corticosteroids, anticholinergics, certain antidepressants, and topiramate may predispose patients to glaucoma. There are 2 broad categories of glaucoma, open-angle and angle-closure glaucoma. Diagnostic testing to assess for glaucoma and to monitor for disease progression includes measurement of intraocular pressure, perimetry, and optical coherence tomography. Treatment of glaucoma involves lowering intraocular pressure. This can be achieved with various classes of glaucoma medications as well as laser and incisional surgical procedures. Conclusions and Relevance: Vision loss from glaucoma can be minimized by recognizing systemic conditions and medications that increase a patient's risk of glaucoma and referring high-risk patients for a complete ophthalmologic examination. Clinicians should ensure that patients remain adherent with taking glaucoma medications and should monitor for adverse events from medical or surgical interventions used to treat glaucoma.

Receipt of Eye Care Services among Medicare Beneficiaries with and without Dementia.

PURPOSE: To examine the relationship between dementia status and receipt of eye care among US Medicare beneficiaries. DESIGN: Retrospective, claims-based analysis. PARTICIPANTS: A 20% representative sample of Medicare beneficiaries who received care between January 1, 2006, and December 31, 2015. METHODS: Dementia was identified from diagnosis codes documented in a beneficiary's first 3 years of observed Medicare enrollment. Eye care visits were identified from provider specialty codes on each encounter claim. We used multivariable Cox proportional hazards regression models with time-varying covariates to compare the likelihood of receiving eye care between beneficiaries with and without dementia. All models were adjusted for potential confounders, including demographics, urban/rural residence, systemic health (Charlson Index), and ocular comorbidities. MAIN OUTCOME MEASURES: Hazard ratio (HR) and 95% confidence interval (CI) for (1) being seen by any eye care provider (ophthalmologist or optometrist); (2) being seen by an ophthalmologist specifically; and (3) receiving cataract surgery (among beneficiaries with ophthalmologist encounters). RESULTS: A total of 4 451 200 beneficiaries met inclusion criteria; 3 805 718 (85.5%) received eye care during the study period, and 391 556 (8.8%) had diagnosed dementia. Some 73.4% of beneficiaries diagnosed with dementia saw an eye care provider during the study period and 55.4% saw an ophthalmologist versus 86.7% and 74.0% of beneficiaries, respectively, without dementia diagnoses. Compared with those without dementia diagnoses, beneficiaries with diagnosed dementia had lower likelihood of seeing any eye care provider (adjusted HR, 0.69; 95% CI, 0.69-0.70) and were less likely to see an ophthalmologist (adjusted HR, 0.55; 95% CI, 0.55-0.55). Among the subset of beneficiaries who did see ophthalmologists, those with diagnosed dementia were also less likely to receive cataract surgery than beneficiaries without diagnosed dementia (HR, 0.62; 95% CI, 0.62-0.63) and less likely to receive a cataract diagnosis (18% vs. 82%). CONCLUSIONS: US Medicare beneficiaries diagnosed with dementia are less likely to receive eye care than those without diagnosed dementia. Depending on visual acuity and functional status, this may have implications for injury prevention, physical and cognitive function, and quality of life. Further work is needed to identify barriers to receiving eye care, determine eye care services and settings that provide greatest value to patients with dementia, and implement measures to improve access to appropriate eye care.

Gramene 2018: unifying comparative genomics and pathway resources for plant research.

Gramene (http://www.gramene.org) is a knowledgebase for comparative functional analysis in major crops and model plant species. The current release, #54, includes over 1.7 million genes from 44 reference genomes, most of which were organized into 62,367 gene families through orthologous and paralogous gene classification, whole-genome alignments, and synteny. Additional gene annotations include ontology-based protein structure and function; genetic, epigenetic, and phenotypic diversity; and pathway associations. Gramene's Plant Reactome provides a knowledgebase of cellular-level plant pathway networks. Specifically, it uses curated rice reference pathways to derive pathway projections for an additional 66 species based on gene orthology, and facilitates display of gene expression, gene-gene interactions, and user-defined omics data in the context of these pathways. As a community portal, Gramene integrates best-of-class software and infrastructure components including the Ensembl genome browser, Reactome pathway browser, and Expression Atlas widgets, and undergoes periodic data and software upgrades. Via powerful, intuitive search interfaces, users can easily query across various portals and interactively analyze search results by clicking on diverse features such as genomic context, highly augmented gene trees, gene expression anatomograms, associated pathways, and external informatics resources. All data in Gramene are accessible through both visual and programmatic interfaces.

Ensembl Genomes 2018: an integrated omics infrastructure for non-vertebrate species.

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including genome sequence, gene models, transcript sequence, genetic variation, and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments and expansions. These include the incorporation of almost 20 000 additional genome sequences and over 35 000 tracks of RNA-Seq data, which have been aligned to genomic sequence and made available for visualization. Other advances since 2015 include the release of the database in Resource Description Framework (RDF) format, a large increase in community-derived curation, a new high-performance protein sequence search, additional cross-references, improved annotation of non-protein-coding genes, and the launch of pre-release and archival sites. Collectively, these changes are part of a continuing response to the increasing quantity of publicly-available genome-scale data, and the consequent need to archive, integrate, annotate and disseminate these using automated, scalable methods.

Association between cycline antibiotic and development of pseudotumor cerebri syndrome.

BACKGROUND: Cycline antibiotics (CAs) are commonly used to treat acne, blepharitis, and dry eye syndrome. Prescribers or patients may hesitate to use Cas because they may increase the risk of pseudotumor cerebri syndrome (PTCS). OBJECTIVE: We sought to assess whether CA use is associated with an increased risk of PTCS or papilledema and whether the risk depends upon dosage or duration of CA intake. METHODS: We studied patients 12 to 65 years of age who were diagnosed with acne, blepharitis, or dry eye syndrome, who were enrolled in a nationwide managed care network between January 1, 2001 and December 31, 2015, and who had no preexisting diagnosis of papilledema or PTCS. Multivariable Cox regression modeling was used to assess the risk of developing papilledema or PTCS from exposure to CAs. RESULTS: Among the 728,811 eligible enrollees (mean age, 34.7 years; 72% female), 42.0% filled ≥1 CA prescription. Of the 305,823 CA users, 170 (0.06%) were diagnosed with papilledema or PTCS. By comparison, of the 57.0% with no record of CA use, 121 (0.03%) were diagnosed with papilledema or PTCS (P < .0001). In the unadjusted model, every additional year of CA use was associated with a 70% (doxycycline: hazard ratio, 1.70 [95% confidence interval 0.98-2.97]; P = .06) or 91% (minocycline: hazard ratio, 1.91 [95% confidence interval 1.11-3.29]; P = .02) increased hazard of papilledema/PTCS relative to nonusers of CAs. After adjustment for confounders, the increased hazard of PTCS/papilledema with CA use was no longer statistically significant (P = .06, doxycycline; P = .08, minocycline). LIMITATIONS: This study relies on claims data, which lack clinical data. CONCLUSION: This study offers some evidence that CAs may increase the risk of PTCS/papilledema. However, after accounting for confounding factors in our multivariable models, we found no statistically significant association between CA use and the development of PTCS. Moreover, there was no dose-response effect whereby greater CA use was associated with a higher PTCS risk.

Vision-Related Quality of Life Associated with Unilateral and Bilateral Ocular Conditions.

PURPOSE: To present ophthalmic patient time-tradeoff vision utilities for quantifying vision-related quality-of-life when the fellow eye still has good vision. These utilities are important for performing reliable cost-utility analyses. DESIGN: Consecutive time-tradeoff vision utilities were obtained from ophthalmic patients with good vision (20/20-20/25) in one eye and vision ranging from 20/20 to no light perception in the fellow eye over a 15-year period from 2000 through 2014. PARTICIPANTS: Five hundred eighty-six ophthalmic participant interviews from Wills Eye Hospital, New York Eye and Ear Hospital, and ophthalmology office practices in Pennsylvania and New Jersey. METHODS: Participants underwent a full ophthalmic examination, after which time-tradeoff vision utilities were obtained by personal interview by the authors using a standardized, validated instrument. MAIN OUTCOME MEASURES: Time-tradeoff vision utilities. RESULTS: Mean time-tradeoff vision utilities were as follows in participants with good vision (20/20-20/25) in at least one eye and the following visions in the fellow eyes: no light perception, 0.79; counting fingers to light perception, 0.87; 20/200 to 20/400, 0.88; 20/60 to 20/100, 0.88; 20/30 to 20/50, 0.87; and 20/20 to 20/25, 0.94. CONCLUSIONS: In people with good vision (20/20-20/25) in one eye, the associated mean time-tradeoff vision utility is a remarkably consistent 0.87 to 0.88 when vision in the fellow eye ranges from 20/30 to light perception. Vision of 20/20 to 20/25 in the fellow eye results in a significantly higher associated utility of 0.94 (P < 0.01), whereas vision of no light perception in the fellow eye results in a significantly lower utility of 0.079 (P < 0.01). These utilities are important for calculating reliable patient value (quality-adjusted life-year) gains in ophthalmic cost-utility analysis populations in which there is unilateral and bilateral disease involvement.

Personalized Prediction of Glaucoma Progression Under Different Target Intraocular Pressure Levels Using Filtered Forecasting Methods.

PURPOSE: To generate personalized forecasts of how patients with open-angle glaucoma (OAG) experience disease progression at different intraocular pressure (IOP) levels to aid clinicians with setting personalized target IOPs. DESIGN: Secondary analyses using longitudinal data from 2 randomized controlled trials. PARTICIPANTS: Participants with moderate or advanced OAG from the Collaborative Initial Glaucoma Treatment Study (CIGTS) or the Advanced Glaucoma Intervention Study (AGIS). METHODS: By using perimetric and tonometric data from trial participants, we developed and validated Kalman Filter (KF) models for fast-, slow-, and nonprogressing patients with OAG. The KF can generate personalized and dynamically updated forecasts of OAG progression under different target IOP levels. For each participant, we determined how mean deviation (MD) would change if the patient maintains his/her IOP at 1 of 7 levels (6, 9, 12, 15, 18, 21, or 24 mmHg) over the next 5 years. We also model and predict changes to MD over the same time horizon if IOP is increased or decreased by 3, 6, and 9 mmHg from the level attained in the trials. MAIN OUTCOME MEASURES: Personalized estimates of the change in MD under different target IOP levels. RESULTS: A total of 571 participants (mean age, 64.2 years; standard deviation, 10.9) were followed for a mean of 6.5 years (standard deviation, 2.8). Our models predicted that, on average, fast progressors would lose 2.1, 6.7, and 11.2 decibels (dB) MD under target IOPs of 6, 15, and 24 mmHg, respectively, over 5 years. In contrast, on average, slow progressors would lose 0.8, 2.1, and 4.1 dB MD under the same target IOPs and time frame. When using our tool to quantify the OAG progression dynamics for all 571 patients, we found no statistically significant differences over 5 years between progression for black versus white, male versus female, and CIGTS versus AGIS participants under different target IOPs (P > 0.05 for all). CONCLUSIONS: To our knowledge, this is the first clinical decision-making tool that generates personalized forecasts of the trajectory of OAG progression at different target IOP levels. This approach can help clinicians determine appropriate, personalized target IOPs for patients with OAG.

Development of a rapid point-of-care patient reported outcome measure for cataract surgery in India.

BACKGROUND: For patient undergoing cataract surgery in India, existing patient-reported outcome (PRO) measures are either not culturally relevant, have not been adequately validated, or are too long to be used in a busy clinical setting. We sought to develop and validate a brief and culturally relevant point-of-care PRO measure to address this need. METHODS: Twelve items from the Indian Visual Functioning Questionnaire (IND-VFQ) were selected based on preliminary data. Patients 18 years and older were prospectively recruited at Aravind Eye Care System in Madurai, India. Clinical and sociodemographic data were collected and the 12-item short-form IND-VFQ (SF-IND-VFQ) was administered pre- and post-operatively to 225 patients; Factor analysis and Rasch modeling was performed to assess its psychometric properties. RESULTS: One item that did not fit a unidimensional scale and had poor fit with the Rasch model was eliminated from the questionnaire. The remaining 11 items represented a single construct (no residual correlations> 0.1) and were largely unaffected by differential item functioning. Five items had disordered thresholds resolved by collapsing the response scale from four to three categories. The survey had adequate reliability (0.80) and good construct (infit range, 0.77-1.29; outfit range, 0.56-1.30) and content (item separation index, 5.87 logits) validity. Measurement precision was fair (person separation index, 1.97). There was evidence that items were not optimally targeted to patients' visual ability (preoperatively, - 1.92 logits; overall, - 3.41 logits), though the survey measured a very large effect (Cohen's d 1.80). In a subset of patients, the average time to complete the questionnaire was 2 min 6.3 s. CONCLUSIONS: The SF-IND-VFQ is a valid, reliable, sensitive, and rapidly administered point-of-care PRO measure to assess changes in visual functioning in patients undergoing cataract surgery in India.

Gramene 2016: comparative plant genomics and pathway resources.

Gramene (http://www.gramene.org) is an online resource for comparative functional genomics in crops and model plant species. Its two main frameworks are genomes (collaboration with Ensembl Plants) and pathways (The Plant Reactome and archival BioCyc databases). Since our last NAR update, the database website adopted a new Drupal management platform. The genomes section features 39 fully assembled reference genomes that are integrated using ontology-based annotation and comparative analyses, and accessed through both visual and programmatic interfaces. Additional community data, such as genetic variation, expression and methylation, are also mapped for a subset of genomes. The Plant Reactome pathway portal (http://plantreactome.gramene.org) provides a reference resource for analyzing plant metabolic and regulatory pathways. In addition to ∼ 200 curated rice reference pathways, the portal hosts gene homology-based pathway projections for 33 plant species. Both the genome and pathway browsers interface with the EMBL-EBI's Expression Atlas to enable the projection of baseline and differential expression data from curated expression studies in plants. Gramene's archive website (http://archive.gramene.org) continues to provide previously reported resources on comparative maps, markers and QTL. To further aid our users, we have also introduced a live monthly educational webinar series and a Gramene YouTube channel carrying video tutorials.

Ensembl Genomes 2016: more genomes, more complexity.

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including reference sequence, gene models, transcriptional data, genetic variation and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments. These include the development of new analyses and views to represent polyploid genomes (of which bread wheat is the primary exemplar); and the continued up-scaling of the resource, which now includes over 23 000 bacterial genomes, 400 fungal genomes and 100 protist genomes, in addition to 55 genomes from invertebrate metazoa and 39 genomes from plants. This dramatic increase in the number of included genomes is one part of a broader effort to automate the integration of archival data (genome sequence, but also associated RNA sequence data and variant calls) within the context of reference genomes and make it available through the Ensembl user interfaces.

Large Disparities in Receipt of Glaucoma Care between Enrollees in Medicaid and Those with Commercial Health Insurance.

PURPOSE: To determine whether the type of health insurance a patient possesses and a patient's race/ethnicity affect receipt of common tests to monitor open-angle glaucoma (OAG). DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: A total of 21 766 persons aged ≥40 years with newly diagnosed OAG between 2007 and 2011 enrolled in Medicaid or a large United States managed care network. METHODS: We determined the proportion of patients with newly diagnosed OAG who underwent visual field (VF) testing, fundus photography (FP), other ocular imaging (OOI), or none of these tests within the first 15 months after initial OAG diagnosis. Multivariable logistic regression was used to assess the extent by which health insurance type and race/ethnicity affected the odds of undergoing glaucoma testing. MAIN OUTCOME MEASURES: Odds ratios (OR) of undergoing VF testing, FP, OOI, or none of these tests in the 15 months after initial OAG diagnosis with 95% confidence intervals (CI). RESULTS: A total of 18 372 persons with commercial health insurance and 3394 Medicaid recipients met the study inclusion criteria. The proportions of persons with commercial health insurance with newly diagnosed OAG who underwent VF, FP, and OOI were 63%, 22%, and 54%, respectively, whereas the proportions were 35%, 19%, and 30%, respectively, for Medicaid recipients. Compared with those with commercial health insurance, Medicaid recipients were 234% more likely to not receive any glaucoma testing in the 15 months after initial diagnosis (OR = 3.34; 95% CI, 3.07-3.63). After adjustment for confounders, whites with OAG enrolled in Medicaid had 198% higher odds of receiving no glaucoma testing compared with whites possessing commercial health insurance (OR = 2.98; 95% CI, 2.66-3.33). Blacks with Medicaid insurance demonstrated 291% higher odds (OR = 3.91; 95% CI, 3.40-4.49) of not receiving any glaucoma testing compared with blacks with commercial health insurance. CONCLUSIONS: Irrespective of race/ethnicity, Medicaid recipients with OAG are receiving substantially less glaucoma testing compared with persons with commercial health insurance. Disparities in testing are observed across all races/ethnicities but were most notable for blacks. These findings are particularly disconcerting because blacks are more likely than whites to go blind from OAG and there are disproportionately more blacks in Medicaid. Efforts are needed to improve the quality of glaucoma care for Medicaid recipients, especially racial minorities.