1,720,970 research outputs found
The role of Tetraspanin-10 in the retinal pigment epithelium and its influence in age-related macular degeneration
No full textAge related macular degeneration (AMD) is the leading cause of vision loss in the Western World [1], accounting for 5.6% of global blindness [1][2, 3]. Irreversible visual impairment arises due to the gradual loss of photoreceptors and their supportive cells: the retinal pigment epithelium (RPE). Currently therapeutics are only available to treat 50% of patients with AMD and in the long-term are ineffective. This is due to an incomplete understanding of the pathophysiology. Genetic risk is a key element of AMD susceptibility and multiple risk loci have been identified including a novel single nucleotide polymorphism (SNP) at Tetraspanin 10 (TSPAN10) [4-7]. The purpose of this work was to elucidate the role of TSPAN10 within the RPE and subsequently understand how it contributes to AMD. CRISPR/Cas-9 gene editing was utilised to produce two TSPAN10 knock-out (k.o) clones in human embryonic stem cells (hESCs) that were then differentiated into RPE. Three separate differentiations for both TSPAN10 k.o and WT cells were produced for robustness, and their genomic DNA, transcripts and protein characterised. TSPAN10 has a significant influence on hESC-RPE pigmentation. TSPAN10 k.o cells were less pigmented than WT hESC-RPE, evidenced both macroscopically in culture, microscopically using transmission electron microscopy (TEM), and through measurement of tyrosinase production and function. Transcriptomics suggested TSPAN10 k.o has a significant influence on oxidative stress in the RPE. Catalase (CAT) is a key enzyme protecting the cell from oxidative stress, CAT mRNA expression was significantly reduced in TSPAN10 k.o clones (padj= 1.39 x 10-20). Functional correlation revealed increased oxidative stress in k.o cells at baseline and reduced catalase production. A functional assay also assessed the effect of TSPAN10 k.o on RPE phagocytic function, revealing a similar response to oxidatively stressed WT RPE. Finally, a cohort study in human beings analysing the impact of AMD genetic risk loci on outer retinal thickness, revealed the AMD risk SNP at TSPAN10 to be significantly associated with thinning of the RPE-Bruch’s membrane and photoreceptor complexes. The work presented within this thesis demonstrates the multiple plausible roles that TSPAN10 may have in the RPE and gives insight into its role in AMD. Aligning this with further functional work is a key next ste
A case report of acute zonal occult outer retinopathy.
No full textPURPOSE:To describe the diagnostic complexities of a patient with acute zonal occult outer retinopathy. CASE REPORT:A healthy female presented with acute bilateral visual field loss and photopsia. On initial examination, her visual acuity, colour vision, fundus examination and fluorescein angiography were normal. Fundus autofluorescence, however, revealed scattered hyperautofluorescence in both eyes and electrodiagnostic tests were abnormal. A differential diagnosis including acute zonal occult outer retinopathy was postulated and serology requested. The patient's past medical history included both breast and endometrial cancer and raised the possibility of cancer-associated retinopathy. A normal full-body positron emission tomography scan, negative antibodies for cancer-associated retinopathy and abnormal electroretinogram led to a diagnosis of acute zonal occult outer retinopathy. CONCLUSION:It has been more than 20 years since Gass first described the syndrome of acute zonal occult outer retinopathy. Typically affecting young, healthy females, acute zonal occult outer retinopathy is characterised by photopsia, minimal fundoscopic changes and electroretinographic abnormalities. Visual field loss is permanent and often associated with slow-progressing degeneration of the retinal pigment epithelial cells. Retinal photoreceptor dysfunction is an uncommon and unrecognised cause of acute visual loss. Acute zonal occult outer retinopathy should be considered as a differential diagnosis in those patients with deceptively normal fundal examinations, abnormal electroretinograms and visual field loss
Future research strategies in CSCR
No full textCentral serous chorioretinopathy is an enigmatic disease. We are only now beginning to glimpse an understanding of the pathophysiological processes at play behind the condition, therefore future research strategies seem to present themselves at almost every aspect of the disease. This chapter outlines current research, with suggestions of possible avenues that could be taken to further enhance our understanding of this condition, in addition to highlighting important studies that warrant replication
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Recurrent bacterial keratitis
No full textPurpose.: To investigate the rate of recurrent bacterial keratitis, associated bacteria, and surgical intervention.Methods.: Patients with suspected bacterial keratitis were identified from microbiological requests over a 16-year period between 1995 and 2010. Recurrences and number of surgical interventions were analyzed according to bacterial type.Results.: A total of 2418 patients were included, of whom 2124 (87.84%) had only one episode of keratitis, 294 (12.15%) at least two, 88 (3.63%) at least three, 40 (1.65%) at least four, and 22 (0.91%) five or more episodes. The bacterial isolation rate was 35.74% (SD 9.41%), increasing to 56.01% in patients with two or more episodes. There was an increase in the isolation of Staphylococcus aureus with increasing number of episodes (P = 0.008), and S. aureus occurred more commonly in patients with recurrent disease due to the same bacterial group (P = 0.04). Patients whose recurrent keratitis was associated with S. aureus had a higher rate of requiring subsequent corneal transplantation (7 of 10) compared to those with Enterobacteriaceae (2 of 7), Pseudomonas aeruginosa (2 of 4), streptococci (2 of 5), or coagulase-negative staphylococci (none of 8) (P = 0.02).Conclusions.: S. aureus is particularly associated with recurrent keratitis. Identification and treatment of the possible source of the infection may be necessary to reduce the risk of recurrent disease. The potential for the autocthonous S. aureus colonizing the nasopharynx or conjunctiva or lid margin to be a reservoir for recurrent keratitis suggests that decolonization of S. aureus could be considered as a potential intervention in those patients with recurrent disease
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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