Developing a Continuous Severity Scale for Macular Telangiectasia Type 2 Using Deep Learning and Implications for Disease Grading.

PURPOSE: Deep learning (DL) models have achieved state-of-the-art medical diagnosis classification accuracy. Current models are limited by discrete diagnosis labels, but could yield more information with diagnosis in a continuous scale. We developed a novel continuous severity scaling system for macular telangiectasia (MacTel) type 2 by combining a DL classification model with uniform manifold approximation and projection (UMAP). DESIGN: We used a DL network to learn a feature representation of MacTel severity from discrete severity labels and applied UMAP to embed this feature representation into 2 dimensions, thereby creating a continuous MacTel severity scale. PARTICIPANTS: A total of 2003 OCT volumes were analyzed from 1089 MacTel Project participants. METHODS: We trained a multiview DL classifier using multiple B-scans from OCT volumes to learn a previously published discrete 7-step MacTel severity scale. The classifiers' last feature layer was extracted as input for UMAP, which embedded these features into a continuous 2-dimensional manifold. The DL classifier was assessed in terms of test accuracy. Rank correlation for the continuous UMAP scale against the previously published scale was calculated. Additionally, the UMAP scale was assessed in the κ agreement against 5 clinical experts on 100 pairs of patient volumes. For each pair of patient volumes, clinical experts were asked to select the volume with more severe MacTel disease and to compare them against the UMAP scale. MAIN OUTCOME MEASURES: Classification accuracy for the DL classifier and κ agreement versus clinical experts for UMAP. RESULTS: The multiview DL classifier achieved top 1 accuracy of 63.3% (186/294) on held-out test OCT volumes. The UMAP metric showed a clear continuous gradation of MacTel severity with a Spearman rank correlation of 0.84 with the previously published scale. Furthermore, the continuous UMAP metric achieved κ agreements of 0.56 to 0.63 with 5 clinical experts, which was comparable with interobserver κ values. CONCLUSIONS: Our UMAP embedding generated a continuous MacTel severity scale, without requiring continuous training labels. This technique can be applied to other diseases and may lead to more accurate diagnosis, improved understanding of disease progression, and key imaging features for pathologic characteristics. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Optic radiations representing different eccentricities age differently.

The neural pathways that carry information from the foveal, macular, and peripheral visual fields have distinct biological properties. The optic radiations (OR) carry foveal and peripheral information from the thalamus to the primary visual cortex (V1) through adjacent but separate pathways in the white matter. Here, we perform white matter tractometry using pyAFQ on a large sample of diffusion MRI (dMRI) data from subjects with healthy vision in the U.K. Biobank dataset (UKBB; N = 5382; age 45-81). We use pyAFQ to characterize white matter tissue properties in parts of the OR that transmit information about the foveal, macular, and peripheral visual fields, and to characterize the changes in these tissue properties with age. We find that (1) independent of age there is higher fractional anisotropy, lower mean diffusivity, and higher mean kurtosis in the foveal and macular OR than in peripheral OR, consistent with denser, more organized nerve fiber populations in foveal/parafoveal pathways, and (2) age is associated with increased diffusivity and decreased anisotropy and kurtosis, consistent with decreased density and tissue organization with aging. However, anisotropy in foveal OR decreases faster with age than in peripheral OR, while diffusivity increases faster in peripheral OR, suggesting foveal/peri-foveal OR and peripheral OR differ in how they age.

Race, Ethnicity, Insurance, and Population Density Associations with Pediatric Strabismus and Strabismic Amblyopia in the IRIS® Registry.

PURPOSE: To evaluate the associations of sociodemographic factors with pediatric strabismus diagnosis and outcomes. DESIGN: Retrospective cohort study. PARTICIPANTS: American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) patients with strabismus diagnosed before the age of 10 years. METHODS: Multivariable regression models evaluated the associations of race and ethnicity, insurance, population density, and ophthalmologist ratio with age at strabismus diagnosis, diagnosis of amblyopia, residual amblyopia, and strabismus surgery. Survival analysis evaluated the same predictors of interest with the outcome of time to strabismus surgery. MAIN OUTCOME MEASURES: Age at strabismus diagnosis, rate of amblyopia and residual amblyopia, and rate of and time to strabismus surgery. RESULTS: The median age at diagnosis was 5 years (interquartile range, 3-7) for 106 723 children with esotropia (ET) and 54 454 children with exotropia (XT). Amblyopia diagnosis was more likely with Medicaid insurance than commercial insurance (odds ratio [OR], 1.05 for ET; 1.25 for XT; P < 0.01), as was residual amblyopia (OR, 1.70 for ET; 1.53 for XT; P < 0.01). For XT, Black children were more likely to develop residual amblyopia than White children (OR, 1.34; P < 0.01). Children with Medicaid were more likely to undergo surgery and did so sooner after diagnosis (hazard ratio [HR], 1.23 for ET; 1.21 for XT; P < 0.01) than those with commercial insurance. Compared with White children, Black, Hispanic, and Asian children were less likely to undergo ET surgery and received surgery later (all HRs < 0.87; P < 0.01), and Hispanic and Asian children were less likely to undergo XT surgery and received surgery later (all HRs < 0.85; P < 0.01). Increasing population density and clinician ratio were associated with lower HR for ET surgery (P < 0.01). CONCLUSIONS: Children with strabismus covered by Medicaid insurance had increased odds of amblyopia and underwent strabismus surgery sooner after diagnosis compared with children covered by commercial insurance. After adjusting for insurance status, Black, Hispanic, and Asian children were less likely to receive strabismus surgery with a longer delay between diagnosis and surgery compared with White children. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Training Deep Learning Models to Work on Multiple Devices by Cross-Domain Learning with No Additional Annotations.

PURPOSE: To create an unsupervised cross-domain segmentation algorithm for segmenting intraretinal fluid and retinal layers on normal and pathologic macular OCT images from different manufacturers and camera devices. DESIGN: We sought to use generative adversarial networks (GANs) to generalize a segmentation model trained on one OCT device to segment B-scans obtained from a different OCT device manufacturer in a fully unsupervised approach without labeled data from the latter manufacturer. PARTICIPANTS: A total of 732 OCT B-scans from 4 different OCT devices (Heidelberg Spectralis, Topcon 1000, Maestro2, and Zeiss Plex Elite 9000). METHODS: We developed an unsupervised GAN model, GANSeg, to segment 7 retinal layers and intraretinal fluid in Topcon 1000 OCT images (domain B) that had access only to labeled data on Heidelberg Spectralis images (domain A). GANSeg was unsupervised because it had access only to 110 Heidelberg labeled OCTs and 556 raw and unlabeled Topcon 1000 OCTs. To validate GANSeg segmentations, 3 masked graders manually segmented 60 OCTs from an external Topcon 1000 test dataset independently. To test the limits of GANSeg, graders also manually segmented 3 OCTs from Zeiss Plex Elite 9000 and Topcon Maestro2. A U-Net was trained on the same labeled Heidelberg images as baseline. The GANSeg repository with labeled annotations is at https://github.com/uw-biomedical-ml/ganseg. MAIN OUTCOME MEASURES: Dice scores comparing segmentation results from GANSeg and the U-Net model with the manual segmented images. RESULTS: Although GANSeg and U-Net achieved comparable Dice scores performance as human experts on the labeled Heidelberg test dataset, only GANSeg achieved comparable Dice scores with the best performance for the ganglion cell layer plus inner plexiform layer (90%; 95% confidence interval [CI], 68%-96%) and the worst performance for intraretinal fluid (58%; 95% CI, 18%-89%), which was statistically similar to human graders (79%; 95% CI, 43%-94%). GANSeg significantly outperformed the U-Net model. Moreover, GANSeg generalized to both Zeiss and Topcon Maestro2 swept-source OCT domains, which it had never encountered before. CONCLUSIONS: GANSeg enables the transfer of supervised deep learning algorithms across OCT devices without labeled data, thereby greatly expanding the applicability of deep learning algorithms.

United States Population Disparities in Ophthalmic Care: Blindness and Visual Impairment in the IRIS® Registry (Intelligent Research in Sight).

PURPOSE: To evaluate associations of patient characteristics with United States eye care use and likelihood of blindness. DESIGN: Retrospective observational study. PARTICIPANTS: Patients (19 546 016) with 2018 visual acuity (VA) records in the American Academy of Ophthalmology's IRIS® Registry (Intelligent Research in Sight). METHODS: Legal blindness (20/200 or worse) and visual impairment (VI; worse than 20/40) were identified from corrected distance acuity in the better-seeing eye and stratified by patient characteristics. Multivariable logistic regressions evaluated associations with blindness and VI. Blindness was mapped by state and compared with population characteristics. Eye care use was analyzed by comparing population demographics with United States Census estimates and proportional demographic representation among blind patients versus a nationally representative US population sample (National Health and Nutritional Examination Survey [NHANES]). MAIN OUTCOME MEASURES: Prevalence and odds ratios for VI and blindness; proportional representation in the IRIS® Registry, Census, and NHANES by patient demographics. RESULTS: Visual impairment was present in 6.98% (n = 1 364 935) and blindness in 0.98% (n = 190 817) of IRIS patients. Adjusted odds of blindness were highest among patients ≥ 85 years old (odds ratio [OR], 11.85; 95% confidence interval [CI], 10.33-13.59 vs. those 0-17 years old). Blindness also was associated positively with rural location and Medicaid, Medicare, or no insurance vs. commercial insurance. Hispanic (OR, 1.59; 95% CI, 1.46-1.74) and Black (OR, 1.73; 95% CI, 1.63-1.84) patients showed a higher odds of blindness versus White non-Hispanic patients. Proportional representation in IRIS Registry relative to the Census was higher for White than Hispanic (2- to 4-fold) or Black (11%-85%) patients (P < 0.001). Blindness overall was less prevalent in NHANES than IRIS Registry; however, prevalence in adults aged 60+ was lowest among Black participants in the NHANES (0.54%) and second highest among comparable Black adults in IRIS (1.57%). CONCLUSIONS: Legal blindness from low VA was present in 0.98% of IRIS patients and associated with rural location, public or no insurance, and older age. Compared with US Census estimates, minorities may be underrepresented among ophthalmology patients, and compared with NHANES population estimates, Black individuals may be overrepresented among blind IRIS Registry patients. These findings provide a snapshot of US ophthalmic care and highlight the need for initiatives to address disparities in use and blindness. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Imaging Amyloid and Tau in the Retina: Current Research and Future Directions.

BACKGROUND: The retina is a key focus in the search for biomarkers of Alzheimer's disease (AD) because of its accessibility and shared development with the brain. The pathological hallmarks of AD, amyloid beta (Aß), and hyperphosphorylated tau (pTau) have been identified in the retina, although histopathologic findings have been mixed. Several imaging-based approaches have been developed to detect retinal AD pathology in vivo. Here, we review the research related to imaging AD-related pathology in the retina and implications for future biomarker research. EVIDENCE ACQUISITION: Electronic searches of published literature were conducted using PubMed and Google Scholar. RESULTS: Curcumin fluorescence and hyperspectral imaging are both promising methods for detecting retinal Aß, although both require validation in larger cohorts. Challenges remain in distinguishing curcumin-labeled Aß from background fluorescence and standardization of dosing and quantification methods. Hyperspectral imaging is limited by confounding signals from other retinal features and variability in reflectance spectra between individuals. To date, evidence of tau aggregation in the retina is limited to histopathologic studies. New avenues of research are on the horizon, including near-infrared fluorescence imaging, novel Aß labeling techniques, and small molecule retinal tau tracers. Artificial intelligence (AI) approaches, including machine learning models and deep learning-based image analysis, are active areas of investigation. CONCLUSIONS: Although the histopathological evidence seems promising, methods for imaging retinal Aß require further validation, and in vivo imaging of retinal tau remains elusive. AI approaches may hold the greatest promise for the discovery of a characteristic retinal imaging profile of AD. Elucidating the role of Aß and pTau in the retina will provide key insights into the complex processes involved in aging and in neurodegenerative disease.

From Data to Deployment: The Collaborative Community on Ophthalmic Imaging Roadmap for Artificial Intelligence in Age-Related Macular Degeneration.

OBJECTIVE: Health care systems worldwide are challenged to provide adequate care for the 200 million individuals with age-related macular degeneration (AMD). Artificial intelligence (AI) has the potential to make a significant, positive impact on the diagnosis and management of patients with AMD; however, the development of effective AI devices for clinical care faces numerous considerations and challenges, a fact evidenced by a current absence of Food and Drug Administration (FDA)-approved AI devices for AMD. PURPOSE: To delineate the state of AI for AMD, including current data, standards, achievements, and challenges. METHODS: Members of the Collaborative Community on Ophthalmic Imaging Working Group for AI in AMD attended an inaugural meeting on September 7, 2020, to discuss the topic. Subsequently, they undertook a comprehensive review of the medical literature relevant to the topic. Members engaged in meetings and discussion through December 2021 to synthesize the information and arrive at a consensus. RESULTS: Existing infrastructure for robust AI development for AMD includes several large, labeled data sets of color fundus photography and OCT images; however, image data often do not contain the metadata necessary for the development of reliable, valid, and generalizable models. Data sharing for AMD model development is made difficult by restrictions on data privacy and security, although potential solutions are under investigation. Computing resources may be adequate for current applications, but knowledge of machine learning development may be scarce in many clinical ophthalmology settings. Despite these challenges, researchers have produced promising AI models for AMD for screening, diagnosis, prediction, and monitoring. Future goals include defining benchmarks to facilitate regulatory authorization and subsequent clinical setting generalization. CONCLUSIONS: Delivering an FDA-authorized, AI-based device for clinical care in AMD involves numerous considerations, including the identification of an appropriate clinical application; acquisition and development of a large, high-quality data set; development of the AI architecture; training and validation of the model; and functional interactions between the model output and clinical end user. The research efforts undertaken to date represent starting points for the medical devices that eventually will benefit providers, health care systems, and patients.

Endophthalmitis Rate in Immediately Sequential versus Delayed Sequential Bilateral Cataract Surgery within the Intelligent Research in Sight (IRIS®) Registry Data.

PURPOSE: To compare the rate of postoperative endophthalmitis after immediately sequential bilateral cataract surgery (ISBCS) versus delayed sequential bilateral cataract surgery (DSBCS) using the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry database. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients in the IRIS Registry who underwent cataract surgery from 2013 through 2018. METHODS: Patients who underwent cataract surgery were divided into 2 groups: (1) ISBCS and (2) DSBCS (second-eye surgery ≥1 day after the first-eye surgery) or unilateral surgery. Postoperative endophthalmitis was defined as endophthalmitis occurring within 4 weeks of surgery by International Classification of Diseases (ICD) code and ICD code with additional clinical criteria. MAIN OUTCOME MEASURES: Rate of postoperative endophthalmitis. RESULTS: Of 5 573 639 IRIS Registry patients who underwent cataract extraction, 165 609 underwent ISBCS, and 5 408 030 underwent DSBCS or unilateral surgery (3 695 440 DSBCS, 1 712 590 unilateral surgery only). A total of 3102 participants (0.056%) met study criteria of postoperative endophthalmitis with supporting clinical findings. The rates of endophthalmitis in either surgery eye between the 2 surgery groups were similar (0.059% in the ISBCS group vs. 0.056% in the DSBCS or unilateral group; P = 0.53). Although the incidence of endophthalmitis was slightly higher in the ISBCS group compared with the DSBCS or unilateral group, the odds ratio did not reach statistical significance (1.08; 95% confidence interval, 0.87-1.31; P = 0.47) after adjusting for age, sex, race, insurance status, and comorbid eye disease. Seven cases of bilateral endophthalmitis with supporting clinical data in the DSBCS group and no cases in the ISBCS group were identified. CONCLUSIONS: Risk of postoperative endophthalmitis was not statistically significantly different between patients who underwent ISBCS and DSBCS or unilateral cataract surgery.

Exploring undergraduate nursing students' experiences towards home-based learning as pedagogy during the COVID-19 pandemic: a descriptive qualitative exploration.

BACKGROUND: The global COVID-19 pandemic has led to the need for educators to explore online platforms in delivering lessons to students. Home-based learning is one of the most commonly-used teaching methods that allow learning to take place despite a physical separation between the students and the educators. METHODS: A descriptive qualitative approach was used to explore the experiences of nursing undergraduates when using home-based learning as a pedagogy during the COVID-19 pandemic. Data were collected from twenty-three nursing students (n = 14 in year one; n = 9 in year two) of their full-time pre-registration nursing program in a public-funded university in Singapore. Semi-structured interviews using an interview guide was conducted through Zoom-based video-conferencing from November 2020 to January 2021. The interview lasted between 45 and 65 min (median = 45 min). Data collection took place concurrently with thematic analysis through Braun and Clarke's six-step approach. This study was reported according to the Consolidated Criteria for Reporting Qualitative Research. RESULTS: Three main themes identified during the data analysis were: (1) challenges of home-based learning, where students detailed their experiences and difficulties encountered during the process; (2) the effectiveness of home-based learning, which explored the pedagogy's impact on the students' learning experience; and (3) students' motivation to learn, where the effects on student morale and motivation in partaking in learning tasks were discussed. CONCLUSIONS: Results from this study suggested that universities should incorporate more home-based learning opportunities as home-based learning to continue playing a crucial role in the foreseeable future. Universities should continue to incorporate more home-based learning opportunities into the existing nursing curriculaa in order to test their capacities and address technical challenges in online learning. Future studies should also consider incorporating other pedagogical strategies when conducting lessons online.

RESPONSE OF INFLAMMATORY CYSTOID MACULAR EDEMA TO TREATMENT USING ORAL ACETAZOLAMIDE.

PURPOSE: To determine the treatment effect of oral acetazolamide on refractory inflammatory macular edema. METHODS: A retrospective review of identified patients with uveitic or pseudophakic macular edema treated using acetazolamide between 2007 and 2014. Visual acuity and central macular subfield thickness was determined at baseline and at first follow-up. Baseline optical coherence tomography features were analyzed as predictors of acetazolamide response. RESULTS: Sixteen patients (19 eyes) of 61 screened met all criteria. Mean age was 57.9 years (19.7-81.1). The most common diagnosis was idiopathic uveitis (n = 6, 31.6%). Mean uveitis duration was 4.4 years (0.2-27.5). Average central macular subfield thickness decreased significantly (from 471.8 ± 110.6 µm to 358.3 ± 50.4 µm) (P < 0.0001). Average visual acuity (logarithm of the minimum angle of resolution) improved significantly from 20/54 (0.43 ± 0.25) to 20/37 (0.27 ± 0.16) (P = 0.003). Pretreatment optical coherence tomographies demonstrated intraretinal fluid (n = 19, 100%), subretinal fluid (n = 8, 42.1%), epiretinal membrane (n = 13, 68.3%), and vitreomacular traction (n = 1, 5.2%). No optical coherence tomography characteristic was predictive of a response to therapy. CONCLUSION: There is a significant benefit to vision and central macular subfield thickness after acetazolamide treatment in patients with inflammatory macular edema. In patients with refractory inflammatory macular edema, treatment using acetazolamide can provide anatomical and visual benefit without corticosteroid-related adverse effects.

Associations between recent and established ophthalmic conditions and risk of Alzheimer's disease.

INTRODUCTION: Identifying ophthalmic diseases associated with increased risk of Alzheimer's disease (AD) may enable better screening and understanding of those at risk of AD. METHODS: Diagnoses of glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR) were based on International Classification of Diseases, 9th revision, codes for 3877 participants from the Adult Changes in Thought study. The adjusted hazard ratio for developing probable or possible AD for recent (within 5 years) and established (>5 years) diagnoses were assessed. RESULTS: Over 31,142 person-years of follow-up, 792 AD cases occurred. The recent and established hazard ratio were 1.46 (P = .01) and 0.87 (P = .19) for glaucoma, 1.20 (P = .12) and 1.50 (P < .001) for AMD, and 1.50 (P = .045) and 1.50 (P = .03) for DR. DISCUSSION: Increased AD risk was found for recent glaucoma diagnoses, established AMD diagnoses, and both recent and established DR. People with certain ophthalmic conditions may have increased AD risk.

Determinants of Outcomes of Adenoviral Keratoconjunctivitis.

PURPOSE: To determine host and pathogen factors predictive of outcomes in a large clinical cohort with keratoconjunctivitis. DESIGN: Retrospective analyses of the clinical and molecular data from a randomized, controlled, masked trial for auricloscene for keratoconjunctivitis (NVC-422 phase IIB, NovaBay; clinicaltrials.gov identifier, NCT01877694). PARTICIPANTS: Five hundred participants from United States, India, Brazil, and Sri Lanka with clinical diagnosis of keratoconjunctivitis and positive rapid test results for adenovirus. METHODS: Clinical signs and symptoms and bilateral conjunctival swabs were obtained on days 1, 3, 6, 11, and 18. Polymerase chain reaction (PCR) analysis was performed to detect and quantify adenovirus in all samples. Regression models were used to evaluate the association of various variables with keratoconjunctivitis outcomes. Time to resolution of each symptom or sign was assessed by adenoviral species with Cox regression. MAIN OUTCOME MEASURES: The difference in composite scores of clinical signs between days 1 and 18, mean visual acuity change between days 1 and 18, and time to resolution of each symptom or sign. RESULTS: Of 500 participants, 390 (78%) showed evidence of adenovirus by PCR. Among adenovirus-positive participants, adenovirus D species was most common (63% of total cases), but a total of 4 species and 21 different types of adenovirus were detected. Adenovirus D was associated with more severe signs and symptoms, a higher rate of subepithelial infiltrate development, and a slower decline in viral load compared with all other adenovirus species. The clinical courses of all patients with non-adenovirus D species infection and adenovirus-negative keratoconjunctivitis were similar. Mean change in visual acuity between days 1 and 18 was a gain of 1.9 letters; worse visual outcome was associated with older age. CONCLUSIONS: A substantial proportion of keratoconjunctivitis is not associated with a detectable adenovirus. The clinical course of those with adenovirus D keratoconjunctivitis is significantly more severe than those with non-adenovirus D species infections or adenovirus-negative keratoconjunctivitis; high viral load at presentation and non-United States origin of participants is associated with poorer clinical outcome.

VISUAL ACUITY IMPROVEMENT WHEN SWITCHING FROM RANIBIZUMAB TO AFLIBERCEPT IS NOT SUSTAINED.

PURPOSE: To assess whether visual benefits exist in switching to aflibercept in patients who have been chronically treated with ranibizumab for neovascular age-related macular degeneration. METHODS: A multicenter, national, electronic medical record database study was performed. Patients undergoing six continuous monthly ranibizumab injections and then switched to continuous aflibercept were matched to those on continuous ranibizumab therapy. Matching was performed in a 2:1 ratio and based on visual acuity 6 months before and at the time of the switch, and the number of previous ranibizumab injections. RESULTS: Patients who were switched to aflibercept demonstrated transiently significant improvement in visual acuity that peaked at an increase of 0.9 Early Treatment Diabetic Retinopathy Study letters 3 months after the switch, whereas control patients continued on ranibizumab treatment showed a steady decline in visual acuity. Visual acuity differences between the groups were significant (P < 0.05) at 2, 3, and 5 months after the switch. Beginning at 4 months after the switch, the switch group showed a visual acuity decline similar to the control group. CONCLUSION: Transient, nonsustained improvement in visual acuity occurs when switching between anti-vascular endothelial growth factor agents, which may have implications in treating patients on chronic maintenance therapy on one anti-vascular endothelial growth factor medication.

Scalable metagenomics alignment research tool (SMART): a scalable, rapid, and complete search heuristic for the classification of metagenomic sequences from complex sequence populations.

BACKGROUND: Next generation sequencing technology has enabled characterization of metagenomics through massively parallel genomic DNA sequencing. The complexity and diversity of environmental samples such as the human gut microflora, combined with the sustained exponential growth in sequencing capacity, has led to the challenge of identifying microbial organisms by DNA sequence. We sought to validate a Scalable Metagenomics Alignment Research Tool (SMART), a novel searching heuristic for shotgun metagenomics sequencing results. RESULTS: After retrieving all genomic DNA sequences from the NCBI GenBank, over 1 × 10(11) base pairs of 3.3 × 10(6) sequences from 9.25 × 10(5) species were indexed using 4 base pair hashtable shards. A MapReduce searching strategy was used to distribute the search workload in a computing cluster environment. In addition, a one base pair permutation algorithm was used to account for single nucleotide polymorphisms and sequencing errors. Simulated datasets used to evaluate Kraken, a similar metagenomics classification tool, were used to measure and compare precision and accuracy. Finally using a same set of training sequences we compared Kraken, CLARK, and SMART within the same computing environment. Utilizing 12 computational nodes, we completed the classification of all datasets in under 10 min each using exact matching with an average throughput of over 1.95 × 10(6) reads classified per minute. With permutation matching, we achieved sensitivity greater than 83 % and precision greater than 94 % with simulated datasets at the species classification level. We demonstrated the application of this technique applied to conjunctival and gut microbiome metagenomics sequencing results. In our head to head comparison, SMART and CLARK had similar accuracy gains over Kraken at the species classification level, but SMART required approximately half the amount of RAM of CLARK. CONCLUSIONS: SMART is the first scalable, efficient, and rapid metagenomics classification algorithm capable of matching against all the species and sequences present in the NCBI GenBank and allows for a single step classification of microorganisms as well as large plant, mammalian, or invertebrate genomes from which the metagenomic sample may have been derived.

Evaluating Access to Eye Care in the Contiguous United States by Calculated Driving Time in the United States Medicare Population.

PURPOSE: To quantify the proximity to eye care in the contiguous United States by calculating driving routes and driving time using a census-based approach. DESIGN: Cross-sectional study based on United States (US) census data, Medicare payment data, and OpenStreetMap. PARTICIPANTS: 2010 US census survey respondents older than 65 years. METHODS: For each state in the United States, the addresses of all practicing ophthalmologists and optometrists were obtained from the 2012 Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services (CMS). The US census data from 2010 then were used to calculate the geolocation of the US population at the block group level and the number of people older than 65 years in each location. Geometries and driving speed limits of every road, street, and highway in the United States from the OpenStreetMap project were used to calculate the exact driving distance and driving time to the nearest eye care provider. MAIN OUTCOME MEASURES: Driving time and driving distance to the nearest optometrist and ophthalmologist per state. RESULTS: Driving times for 3.79×107 persons were calculated using a total of 3.88×107 available roads for the 25 508 optometrists and 17 071 ophthalmologists registered with the CMS. Nationally, the median driving times to the nearest optometrist and ophthalmologist were 2.91 and 4.52 minutes, respectively. Ninety percent of the population lives within a 13.66- and 25.21-minute drive, respectively, to the nearest optometrist and ophthalmologist. CONCLUSIONS: While there are regional variations, overall more than 90% of the US Medicare beneficiary population lives within a 30-minute drive of an ophthalmologist and within 15 minutes of an optometrist.

Computer-aided auscultation of murmurs in children: evaluation of commercially available software.

BACKGROUND: Heart murmurs are common in children and may represent congenital or acquired cardiac pathology. Auscultation is challenging and many primary-care physicians lack the skill to differentiate innocent from pathologic murmurs. We sought to determine whether computer-aided auscultation (CardioscanTM) identifies which children require referral to a cardiologist. METHODS: We consecutively enrolled children aged between 0 and 17 years with a murmur, innocent or pathologic, being evaluated in a tertiary-care cardiology clinic. Children being evaluated for the first time and patients with known cardiac pathology were eligible. We excluded children who had undergone cardiac surgery previously or were unable to sit still for auscultation. CardioscanTM auscultation was performed in a quiet room with the subject in the supine position. The sensitivity and specificity of a potentially pathologic murmur designation by CardioscanTM - that is, requiring referral - was determined using echocardiography as the reference standard. RESULTS: We enrolled 126 subjects (44% female) with a median age of 1.7 years, with 93 (74%) having cardiac pathology. The sensitivity and specificity of a potentially pathologic murmur determination by CardioscanTM for identification of cardiac pathology were 83.9 and 30.3%, respectively, versus 75.0 and 71.4%, respectively, when limited to subjects with a heart rate of 50-120 beats per minute. The combination of a CardioscanTM potentially pathologic murmur designation or an abnormal electrocardiogram improved sensitivity to 93.5%, with no haemodynamically significant lesions missed. CONCLUSIONS: Sensitivity of CardioscanTM when interpreted in conjunction with an abnormal electrocardiogram was high, although specificity was poor. Re-evaluation of computer-aided auscultation will remain necessary as advances in this technology become available.

Deep-brain stimulation associates with improved microvascular integrity in the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an accepted treatment for motor symptoms in a subset of Parkinson's disease (PD) patients. The mechanisms why DBS is effective are incompletely understood, but previous studies show that DBS targeted in brain structures other than the STN may modify the microvasculature. However, this has not been studied in PD subjects who have received STN-DBS. Here we investigated the extent and nature of microvascular changes in post-mortem STN samples from STN-DBS PD patients, compared to aged controls and PD patients who had not been treated with STN-DBS. We used immunohistochemical and immunofluorescent methods to assess serial STN-containing brain sections from PD and STN-DBS PD cases, compared to similar age controls using specific antibodies to detect capillaries, an adherens junction and tight junction-associated proteins as well as activated microglia. Cellular features in stained sections were quantified by confocal fluorescence microscopy and stereological methods in conjunction with in vitro imaging tools. We found significant upregulation of microvessel endothelial cell thickness, length and density but lowered activated microglia density and striking upregulation of all analysed adherens junction and tight junction-associated proteins in STN-DBS PD patients compared to non-DBS PD patients and controls. Moreover, in STN-DBS PD samples, expression of an angiogenic factor, vascular endothelial growth factor (VEGF), was significantly upregulated compared to the other groups. Our findings suggest that overexpressed VEGF and downregulation of inflammatory processes may be critical mechanisms underlying the DBS-induced microvascular changes.