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153 result(s) for "Kaye, Rebecca"
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Macular thickness varies with age-related macular degeneration genetic risk variants in the UK Biobank cohort
To evaluate the influence AMD risk genomic variants have on macular thickness in the normal population. UK Biobank participants with no significant ocular history were included using the UK Biobank Resource (project 2112). Spectral-domain optical coherence tomography (SD-OCT) images were taken and segmented to define retinal layers. The influence of AMD risk single-nucleotide polymorphisms (SNP) on retinal layer thickness was analysed. AMD risk associated SNPs were strongly associated with outer-retinal layer thickness. The inner-segment outer segment (ISOS)-retinal pigment epithelium (RPE) thickness measurement, representing photoreceptor outer segments was most significantly associated with the cumulative polygenic risk score, composed of 33 AMD-associated variants, resulting in a decreased thickness (p = 1.37 × 10 –67 ). Gene–gene interactions involving the NPLOC4-TSPAN10 SNP rs6565597 were associated with significant changes in outer retinal thickness. Thickness of outer retinal layers is highly associated with the presence of risk AMD SNPs. Specifically, the ISOS-RPE measurement. Changes to ISOS-RPE thickness are seen in clinically normal individuals with AMD risk SNPs suggesting structural changes occur at the macula prior to the onset of disease symptoms or overt clinical signs.
Establishing the influence of case complexity on the order of cataract lists: a cross-sectional survey
ObjectiveOrder of the theatre list and complexity of the cases are important considerations which are known to influence surgical outcomes. This survey aimed to establish their influence on cataract surgery.Methods and AnalysisCataract surgeons ordered five cataract cases according to their surgical preference, first using case notes and second using composite ORs (CORs) for posterior capsule rupture. Descriptive and non-parametric statistics were used to analyse the data.ResultsBetween 11 June and 14 July 2020, 192 cataract surgeons from 14 countries completed the online survey. Majority of the surgeons (142 vs 50) preferred to choose the order of their list (p<0.01) and to review the case notes prior to the day of surgery (89 vs 53; p=0.04). 39.86% preferred to start with the less risky case and 32.43% reserved the last position on the list for the riskiest case. There was a significant trend to order the list in an ascending level of risk, independent of whether case notes or CORs were used. Additionally, 44.79% of the respondents indicated they would be happy to have their list order planned by an automated program based on their preferred risk score.ConclusionThis survey demonstrates that cataract surgeons prefer to choose the order of their theatre list and that the order is dependent on the complexity of cases. There is support among surgeons for automated list ordering based on an objective score for risk stratification, such as a COR.
Features of intermediate and late dry age-related macular degeneration on adaptive optics ophthalmoscopy: Pinnacle Study Report 8
Background/Objectives Adaptive optics ophthalmoscopy (AOO) has the potential to provide insights into AMD pathology and to assess the risk of progression. We aim to utilise AOO to describe detailed features of intermediate AMD and to characterise microscopic changes during atrophy development. Subjects/Methods Patients with intermediate AMD were recruited into PINNACLE, a prospective observational cohort study. Participants underwent flood-illumination AOO using the commercially available rtx1 camera. AOO images were qualitatively assessed and correlated with clinical imaging including optical coherence tomography (OCT) and infrared scanning laser ophthalmoscopy. Results The visibility of cone mosaic was generally compromised in eyes with intermediate AMD. We observed an association between the visibility of cone mosaic on AOO and the detection of a well-defined normal interdigitation zone on OCT. Drusen subtypes were identified on AOO as variations in reflectance at the edge and/or the centre of the druse. The absence of a hyperreflective margin was associated with the loss of the overlying ellipsoid zone on OCT prior to the collapse of the druse. With progressive attenuation of the retinal pigment epithelium and loss of photoreceptor layers, the drusenoid lesion appeared more hyperreflective with very distinctive edges. Conclusions This cross-sectional study supports the potential value of AOO for providing information on intermediate AMD and the development of atrophic lesions that cannot be seen in conventional imaging modalities. The ongoing longitudinal PINNACLE study is assessing the significance of the described findings.
Exploring Nurse Educators’ Self-reflections of Simulation Facilitator Competency
The purpose of this study was to explore nurse educators’ self-reflections of simulation facilitator competency. Additionally, the study explored nurse educators’ self-reflections of a simulation experience using reflection on action. The study was designed using a phenomenological qualitative approach. Data were obtained by purposive sampling using guided semi-structured interviews online. Data were auto-coded using NVivo software and hand-coded using an adapted coding process. Seven nurse educators participated.All participants self-assessed personal simulation facilitator competency at a level of competent or higher. Three themes emerged: (a) simulation facilitator competency self-assessment is related to the simulation facilitator management of the student learner, (b) simulation facilitator competency is related to the management of self, and (c) simulation challenges communication. Simulation facilitators' challenges center around communication issues, specifically communication with self, student learners, and others. The study findings highlight the importance of communication, although study results did not indicate that initial or ongoing simulation facilitator training was something the participants verbally recommended. It is crucial to prioritize communication skills, as even trained and seasoned facilitators face obstacles in this area.
Parasites and Parasitic Diseases of Laboratory Animals in Plateau State Nigeria: The zoonotic implications
Parasitic agents in laboratory animals, are detrimental to the success of researches and can also infect personnel and researchers. This study is aimed at investigating the parasitic infections of laboratory animals maintained in animal houses of The National Veterinary Research Institute, Vom, Nigeria, as well as determining the zoonotic implications of these parasites. Two hundred and six laboratory animals (72 rabbits, 55 guinea pigs, 50 mice and 29 rats) were randomly sampled. Faecal samples and skin scrapings were collected and subjected to parasitological analyses. Pathological examinations were conducted on laboratory animals that had skin lesions. Sixteen different species comprising of 7 nematodes, 5 cestodes, 3 protozoans, and 1 mite were detected. Eimeria species (40/206; 19.42%; 95% CI = 14.44–25.25) was the most prevalent parasite, followed by Syphacia muris (26/206; 12.62%; 95% CI = 8.59–17.69). Entamoeba caviae , Tritrichomonas caviae , Rodentolepis microstoma , Rodentolepis nana , Heterakis spumosa , Capillaria hepatica and Cysticercus fasciolaris were the least prevalent with a 0.49% prevalence each. Three, four, five and six different species of parasites were detected in mice, guinea pigs, rats and rabbits respectively. The Chi-Square analysis revealed that the infection rate of parasites was significantly higher ( p  =  < 0.01) in mice compared to rats, rabbits and guinea pigs. Of the Sixteen species of parasites detected, Eimeria species, Syphacia muris , Rodentolepis diminuta , Rodentolepis microstoma , Rodentolepis nana , and Capillaria hepatica are zoonotic. This study showed that 40.29% of the studied laboratory animals were infected with one parasite species or the other. The outcome of this study stresses the zoonotic implications of the parasites detected. We thereby advise researchers and handlers to take caution and apply utmost sanitary measures in the handling of laboratory animals so as to prevent themselves from being infected with these zoonotic parasites.
Resolvin D1 treatment on goblet cell mucin and immune responses in the chronic allergic eye disease (AED) model
Severe, chronic eye allergy is an understudied, vision-threatening condition. Treatments remain limited. We used a mouse model of severe allergic eye disease (AED) to determine whether topical application of the pro-resolution mediator Resolvin D1 (RvD1) terminates the response. AED was induced by injection of ovalbumin (OVA) followed by topical challenge of OVA daily. RvD1 was applied topically prior to OVA. Clinical symptoms were scored. Eye washes were assayed for MUC5AC. After 7 days, eyes were removed and the number of goblet cells, T helper cell responses and presence of immune cells in draining lymph nodes and conjunctiva determined. Topical RvD1 treatment significantly reduced symptoms of AED. RvD1 did not alter the systemic type 2 immune response in the lymph nodes. AED increased the total amount of goblet cell mucin secretion, but not the number of goblet cells. RvD1 prevented this increase, but did not alter goblet cell number. Absolute numbers of CD4 + T cells, total CD11b + myeloid cells, eosinophils, neutrophils, and monocytes, but not macrophages increased in AED versus RvD1-treated mice. We conclude that topical application of RvD1 reduced the ocular allergic response by local actions in conjunctival immune response and a decrease in goblet cell mucin secretion.
Epigenetic markers in the postnatal developing rat brain
Epigenetic mechanisms provide a critical and plausible mechanism by which genes and the environment can interact and have been implicated in a number of diseases and disorders. In order to better understand how epigenetic mechanisms go awry in a diseased brain we must first understand how epigenetic mechanisms unfold during normal development. The present body of work begins to examine the role of DNA methylation in normal development and how it may contribute to a rodent model of emotion dysfunction. Using a variety of techniques, we evaluated the transcript, protein and functional output levels of DNA methyltransferase1, -3a, and -3b during several developmental timepoints in the hippocampus, amygdala and several other brain areas of normal rats as well as bred high novelty responding rats and bred low novelty responding rats. Our results lay an important foundation, paving the way for a series of new experiments that can investigate what happens when epigenetic processes go awry during critical neurodevelopmental periods. Keywords: DNA methyltransferase, DNA methylation, in situ hybridization, neurodevelopment, hippocampus, amygdala
Deep-learning-based clustering of OCT images for biomarker discovery in age-related macular degeneration (Pinnacle study report 4)
Diseases are currently managed by grading systems, where patients are stratified by grading systems into stages that indicate patient risk and guide clinical management. However, these broad categories typically lack prognostic value, and proposals for new biomarkers are currently limited to anecdotal observations. In this work, we introduce a deep-learning-based biomarker proposal system for the purpose of accelerating biomarker discovery in age-related macular degeneration (AMD). It works by first training a neural network using self-supervised contrastive learning to discover, without any clinical annotations, features relating to both known and unknown AMD biomarkers present in 46,496 retinal optical coherence tomography (OCT) images. To interpret the discovered biomarkers, we partition the images into 30 subsets, termed clusters, that contain similar features. We then conduct two parallel 1.5-hour semi-structured interviews with two independent teams of retinal specialists that describe each cluster in clinical language. Overall, both teams independently identified clearly distinct characteristics in 27 of 30 clusters, of which 23 were related to AMD. Seven were recognised as known biomarkers already used in established grading systems and 16 depicted biomarker combinations or subtypes that are either not yet used in grading systems, were only recently proposed, or were unknown. Clusters separated incomplete from complete retinal atrophy, intraretinal from subretinal fluid and thick from thin choroids, and in simulation outperformed clinically-used grading systems in prognostic value. Overall, contrastive learning enabled the automatic proposal of AMD biomarkers that go beyond the set used by clinically established grading systems. Ultimately, we envision that equipping clinicians with discovery-oriented deep-learning tools can accelerate discovery of novel prognostic biomarkers.
Clustering disease trajectories in contrastive feature space for biomarker discovery in age-related macular degeneration
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Current grading systems based on imaging biomarkers only coarsely group disease stages into broad categories and are unable to predict future disease progression. It is widely believed that this is due to their focus on a single point in time, disregarding the dynamic nature of the disease. In this work, we present the first method to automatically discover biomarkers that capture temporal dynamics of disease progression. Our method represents patient time series as trajectories in a latent feature space built with contrastive learning. Then, individual trajectories are partitioned into atomic sub-sequences that encode transitions between disease states. These are clustered using a newly introduced distance metric. In quantitative experiments we found our method yields temporal biomarkers that are predictive of conversion to late AMD. Furthermore, these clusters were highly interpretable to ophthalmologists who confirmed that many of the clusters represent dynamics that have previously been linked to the progression of AMD, even though they are currently not included in any clinical grading system.