Importance In improving clinical outcomes, developing a sustainable, transformative care delivery model is important for accessible, efficient, low-cost, high-quality community-based imaging and diagnosis of retinal diseases. Objective To test the feasibility and accuracy of the remote diagnosis imaging model as a clinical screening tool to facilitate the identification of referable macular degeneration. Design, Setting, and Participants A nonrandomized study of 159 patients was conducted in sites with a relatively high disease prevalence (Duke University Health System endocrinology clinic and 2 Duke University Health System assisted living centers in North Carolina). All patients underwent remote diagnosis imaging, defined as color fundus photography (CFP) and optical coherence tomography (OCT) of nondilated pupils, acquired by nonexpert imagers using a retinal imaging device located at the point of service. The criterion standard examination was defined as a traditional dilated eye examination performed by retinal specialists. Deidentified remote diagnosis images were graded for interpretability and presence of referable macular degeneration, defined as any condition requiring a retinal specialist attention. Data analysis was performed from November 20, 2015, to February 10, 2019. Main Outcomes and Measures Primary outcome was feasibility of the remote retinal imaging. Secondary outcomes were operational characteristics and diagnostic and referral accuracy. Results Of the 159 patients included in the study, the mean (SD) age of enrolled participants was 65 (17) years, with a female to male ratio of 1.3 to 1. Most patients were white (111 [69.8%]), 44 were black patients (27.7%), approximately 1% were Asian patients and Hispanic patients, and 2 patients declined to disclose their race/ethnicity. Thirty-five eyes (22.0%) were determined to require referral to the retinal specialist by criterion standard examination. Remote diagnosis image interpretability was better when OCT was used compared with CFP (241 [96.4%] vs 164 [65.6%]). Remote diagnosis had high diagnostic accuracy in identifying referable macular degeneration: OCT and CFP both had 94% sensitivity (95% CI, 84%-98%), and OCT had specificity higher than for CFP (93% [95% CI, 87%-96% ] vs 63% [95% CI, 53%-71%]). Substantial agreement was found between the criterion standard and OCT (κ = 0.83; 95% CI, 0.76-0.91; P < .001) and between the criterion standard and CFP (κ = 0.76; 95% CI, 0.64-0.87; P < .001). The nonvalidated patient satisfaction survey revealed that 122 participants (76.7%; mean score, 4.16; 95% CI, 3.98-4.35) preferred remote imaging over the standard care examination. Conclusions and Relevance Remote diagnosis imaging and a standard examination by a retinal specialist appeared equivalent in identifying referable macular degeneration in patients with high disease prevalence; these results may assist in delivering timely treatment and seem to warrant future research into additional metrics.

Background: Diabetic retinopathy (DR) is a leading cause of low vision and blindness. We evaluated the feasibility of using a handheld, noncontact digital retinal camera, Pictor, to obtain retinal images in dilated and undilated eyes for DR screening. We also evaluated the accuracy of ophthalmologists with different levels of training/experience in grading these images to identify eyes with vision-threatening DR. Methods: A prospective study of diabetic adults scheduled to have dilated eye exams at Duke Eye Center from January to May 2014 was conducted. An imager acquired retinal images pre- and postdilation with Pictor and selected 1 pre- and 1 postdilation image per eye. Five masked ophthalmologists graded images for gradability (based on image focus and centration) and the presence of no, mild, moderate, or severe nonproliferative DR (NPDR) or proliferative DR (PDR). Referable disease was defined as moderate or severe NPDR or PDR on image grading. We evaluated feasibility based on the graders’ evaluation of image gradability. We evaluated accuracy of identifying vision-threatening disease (severe NPDR or PDR documented on dilated clinical examination) based on the graders’ sensitivity and specificity of grading referable disease. Results: Images were gradable in 86-94% of predilation and 94-97% of postdilation photos. Compared to the dilated clinical exam, overall sensitivity for identifying vision-threatening DR was 64-88% and specificity was 71-90%. Conclusions: Pictor can capture retinal images of sufficient quality to screen for DR with and without dilation. Single retinal images obtained using Pictor can identify eyes with vision-threatening DR with high sensitivity and acceptable specificity compared to clinical exam.

Segmentation of anatomical and pathological structures in ophthalmic images is crucial for the diagnosis and study of ocular diseases. However, manual segmentation is often a time-consuming and subjective process. This paper presents an automatic approach for segmenting retinal layers in Spectral Domain Optical Coherence Tomography images using graph theory and dynamic programming. Results show that this method accurately segments eight retinal layer boundaries in normal adult eyes more closely to an expert grader as compared to a second expert grader.

We describe an efficient approach for the automated segmentation of pathological/morphological structures in ophthalmic Spectral Domain Optical Coherence Tomography (SDOCT) images. In this algorithm, image pixels are treated as nodes of a graph with edge weights assigned to associate pairs of pixels. The weights vary according to the distances, brightness differences, and feature variations between pixel pairs. Cuts through the graph with minimum accumulated weights correspond to morphological layer boundaries. This approach has been applied to SDOCT images with encouraging results and thus forms an adaptable framework for the segmentation of many different ophthalmic structures.

The sperm membrane protein zonadhesin (ZAN) has been characterized in mammals and has been implicated in species-specific egg-sperm binding interactions. Zonadhesin is the only protein that contains MAM, mucin and von Willebrand D domains. A zonadhesin-like transcript was obtained fi-om an Atlantic salmon gut tissue cDNA library. This transcript and the corresponding genomic locus were sequenced. A zonadhesin-like gene (ZLG) with a predicted open reading fi-ame of 4,5 18 nucleotides that encodes MAM, mucin and VWD domains was characterized. Although the predicted protein contains the same major domains as zonadhesin, the domain order is altered. ZLG is expressed in the liver and the gut but not in the testis as a typical zonadhesin. This gene is unlikely to be directly involved in reproduction, because it has a unique domain structure and expression, but is likely to have a novel function. In contrast, zonadhesin-like genes with the same domain content and order as mammalian zonadhesins can be deduced from puffer fish and zebrafish genomic sequencing projects. Zonadhesin-like genes from these three fish species are compared and evolutionary relationships are explored. Efaminers: //

The development of appropriate nuisance criteria is an evolving process due to both the difficulties of defining emission rates and the lack of definitive information of what constitutes a nuisance. However, progress has been made in this area in recent years, particularly in Europe with the work on linking surveyed odour annoyance to modelled odour impact. There is currently a lack of knowledge in Australia, which has led to arbitrary impact criteria being selected and adopted by regulators in various regions.

This paper presents a software program, the Virtual NMR Spectrometer, for computer simulation of multichannel, multidimensional NMR experiments on user-defined spin systems. The program is capable of reproducing most features of the modern NMR experiment, including homo- and heteronuclear pulse sequences, phase cycling, pulsed field gradients, and shaped pulses. Two different approaches are implemented to simulate the effect of pulsed field gradients on coherence selection, an explicit calculation of all coherence transfer pathways, and an effective approximate method using integration over multiple positions in the sample. The applications of the Virtual NMR Spectrometer are illustrated using homonuclear COSY and DQF COSY experiments with gradient selection, heteronuclear HSQC, and TROSY. The program uses an intuitive graphical user interface, which resembles the appearance and operation of a real spectrometer. A translator is used to allow the user to design pulse sequences with the same programming language used in the actual experiment on a real spectrometer. The Virtual NMR Spectrometer is designed as a useful tool for developing new NMR experiments and for tuning and adjusting the experimental setup for existing ones prior to running costly NMR experiments, in order to reduce the setup time on a real spectrometer. It will also be a useful aid for learning the general principles of magnetic resonance and contemporary innovations in NMR pulse sequence design.

Chromosomal region 15q11-q13 has been implicated to harbor a susceptibility gene or genes underlying autism. Evidence has been derived from the existence of cytogenetic anomalies in this region associated with autism, and the report of linkage in a modest collection of multiplex families. Most recently, linkage disequilibrium with the marker GABRB3-155CA2 in the candidate locus GABRB3, located in this region, has been reported. We searched for linkage using eight microsatellite markers located in this region of chromosome 15 in 147 affected sib-pairs from 139 multiplex autism families. We also tested for linkage disequilibrium in the same set of families with the same markers. We found no evidence for excess allele sharing (linkage) for the markers in this region. Also, we found no evidence of linkage disequilibrium, including for the locus GABRB3-155CA2. Thus, it appears that the role of this region of chromosome 15 is minor, at best, in the majority of individuals with autism.

We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps greater than or equal to 15) and are less compatible with models specifying less than or equal to 10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.

Several studies have suggested a role for the histocompatibility complex of loci (HLA) in the genetic susceptibility to autism. We have tested this hypothesis by linkage analysis using genetic marker loci in the HLA region on chromosome 6p in multiplex families with autism. We have examined sharing of alleles identical by descent in 97 affected sib pairs from 90 families. Results demonstrate no deviation from the null expectation of 50% sharing of alleles in this region; in fact, for most marker loci, the observed sharing was less than 50%. Thus, it is unlikely that loci in this region contribute to the genetic etiology of autism to any significant extent in our families.

We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps >/=15) and are less compatible with models specifying </=10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.

We investigated an increase in cases of multidrug-resistant tuberculosis (MDRTB) at a large urban facility where a prior nosocomial outbreak of MDRTB had occurred. Nosocomial transmission appeared to account for this outbreak as well, including a cluster of cases in a newborn nursery. Seven of 24 patients (29%) described in this investigation may have been exposed in the hospital nursery during an approximately 2-week period. We believe this to be the first documented outbreak of MDRTB in a hospital nursery. The transmission in the nursery demonstrates that the possibility of exposure to unrecognized active tuberculosis in nursery and hospital personnel is always present. Infection and active disease in the infants developed after a relatively short period of exposure. These findings underscore the need for adherence to published infection control guidelines in health care settings.