86 research outputs found
Artistic Practices: social interactions and cultural dynamics
This is the final version of the article. Available from the publisher via the link in this record.Book Review of: Zembylas, T. (Ed.). (2014). Artistic Practices: social interactions and cultural dynamics. Routledg
High-resolution in vivo fundus angiography using a non-adaptive optics imaging system
Purpose: We provide a proof of concept for the detailed characterization of retinal capillary features and surrounding photoreceptor mosaic using a customized nonadaptive optics angiography imaging system. Methods: High-resolution fluorescein angiography (FFA) and/or indocyanine green angiography (ICGA) images were obtained using a modified Heidelberg retina angiograph (HRA2) device with a reduced scan angle enabling 3° field of view. Colocalized images of the photoreceptor mosaic also were captured in vivo using the same instrument. Visibility of vascular subbranches were compared between high-resolution images and conventional fundus angiography (FA) with a 30° field of view. Results: High-resolution angiographic and infrared images (3° à 3° field of view, a 10-fold magnification) were obtained in 10 participants. These included seven patients with various retinal diseases, including myopic degeneration, diabetic retinopathy, macular telangiectasia, and central serous chorioretinopathy, as well as three healthy controls. Images of the retinal vasculature down to the capillary level were obtained on angiography with the ability to visualize a mean 1.2 levels more subbranches compared to conventional FA. In addition, imaging of the photoreceptor cone mosaic, to a sufficient resolution to calculate cone density, was possible. Movement of blood cells within the vasculature also was discernible on infrared videography. Conclusions: This exploratory study demonstrates that fast high-resolution angiography and cone visualization is feasible using a commercially available imaging system. Translational Relevance: This offers potential to better understand the relationship between the retinal neurovascular system in health and disease and the timing of therapeutic interventions in disease states
Validation of automated artificial intelligence segmentation of optical coherence tomography images
PURPOSE
To benchmark the human and machine performance of spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) image segmentation, i.e., pixel-wise classification, for the compartments vitreous, retina, choroid, sclera.
METHODS
A convolutional neural network (CNN) was trained on OCT B-scan images annotated by a senior ground truth expert retina specialist to segment the posterior eye compartments. Independent benchmark data sets (30 SDOCT and 30 SSOCT) were manually segmented by three classes of graders with varying levels of ophthalmic proficiencies. Nine graders contributed to benchmark an additional 60 images in three consecutive runs. Inter-human and intra-human class agreement was measured and compared to the CNN results.
RESULTS
The CNN training data consisted of a total of 6210 manually segmented images derived from 2070 B-scans (1046 SDOCT and 1024 SSOCT; 630 C-Scans). The CNN segmentation revealed a high agreement with all grader groups. For all compartments and groups, the mean Intersection over Union (IOU) score of CNN compartmentalization versus group graders' compartmentalization was higher than the mean score for intra-grader group comparison.
CONCLUSION
The proposed deep learning segmentation algorithm (CNN) for automated eye compartment segmentation in OCT B-scans (SDOCT and SSOCT) is on par with manual segmentations by human graders
Causative Pathogens of Endophthalmitis after Intravitreal Anti-VEGF Injection: An International Multicenter Study
Purpose: The main objective of this study was to investigate
the microbiological spectrum of endophthalmitis after anti-
VEGF injections and to compare streptococcal with nonstreptococcus-
associated cases with regard to baseline characteristics and injection procedure. Methods: Retrospective,international multicenter study of patients with culture-positive
endophthalmitis after intravitreal anti-VEGF injection at
17 different retina referral centers. Results: Eighty-three cases
with 87 identified pathogens were included. Coagulasenegative
staphylococci (59%) and viridans streptococci
(15%) were the most frequent pathogens found. The use of
postoperative antibiotics and performance of injections in
an operating room setting significantly reduced the rate of
streptococcus-induced endophthalmitis cases (p = 0.01 for
both). Conclusion: We found a statistically significant lower
rate of postinjectional local antibiotic therapy and operating
room-based procedures among the streptococcus-induced
cases compared to cases caused by other organisms
Genome defence in hypomethylated developmental contexts
Retrotransposons constitute around 40% of the mammalian genome and their aberrant
activation can have wide ranging detrimental consequences, both throughout
development and into somatic lineages. DNA methylation is one of the major
epigenetic mechanisms in mammals, and is essential in repressing retrotransposons
throughout mammalian development. Yet during normal mouse embryonic
development some cell lineages become extensively DNA hypomethylated and it is
not clear how these cells maintain retrotransposon silencing in a globally
hypomethylated genomic context.
In this thesis I determine that hypomethylation in multiple contexts results in the
consistent activation of only one gene in the mouse genome - Tex19.1. Thus if a generic
compensatory mechanism for loss of DNA methylation exists in mice, it must function
through this gene. Tex19.1-/- mice de-repress retrotransposons in the hypomethylated
component of the placenta and in the mouse germline, and have developmental defects
in these tissues. In this thesis I examine the mechanism of TEX19.1 mediated genome
defence and the developmental consequences upon its removal. I show that TEX19.1
functions in repressing retrotransposons, at least in part, through physically interacting
with the transcriptional co-repressor, KAP1. Tex19.1-/- ES cells have reduced levels of
KAP1 bound retrotransposon chromatin and reduced levels of the repressive
H3K9me3 modification at these loci. Furthermore, these subsets of retrotransposon
loci are de-repressed in Tex19.1-/- placentas. Thus, my data indicates that mouse cells
respond to hypomethylation by activating expression of Tex19.1, which in turn
augments compensatory, repressive histone modifications at retrotransposon
sequences, thereby helping developmentally hypomethylated cells to maintain genome
stability.
I next aimed to further elucidate the role of Tex19.1 in the developing hypomethylated
placenta. I determine that Tex19.1-/- placental defects precede intrauterine growth
restriction of the embryo and that alterations in mRNA abundance in E12.5 Tex19.1-/-
placentas is likely in part due to genic transcriptional changes. De-repression of LINE-
1 is evident in these placentas and elements of the de-repressed subfamily are
associated with significantly downregulated genes. If retrotransposon de-repression is
contributing to developmental defects by interfering with gene expression remains to
be determined, however I identify a further possible mechanism leading to placental
developmental defects. I determine that Tex19.1-/- placentas have an increased innate
immune response and I propose that this is contributing to the developmental defects
observed.
Developmental defects and retrotransposon de-repression are also observed in
spermatogenesis in Tex19.1-/- testes, the molecular basis for which is unclear. I
therefore investigate the possibility that the TEX19.1 interacting partners, the E3
ubiquitin ligase proteins, may be contributing to the phenotypes observed in Tex19.1-
/- testes. I show that repression of MMERVK10C in the testes is dependent on UBR2,
alongside TEX19.1. Furthermore, I have identified a novel role for the TEX19.1
interacting partner, UBR5, in spermatogenesis, whose roles are distinct from those of
TEX19.1.
The work carried out during the course of this thesis provides mechanistic insights into
TEX19.1 mediated genome defence and highlights the importance of protecting the
genome from aberrant retrotransposon expression
On the role of 4-hydroxynonenal in health and disease
AbstractPolyunsaturated fatty acids are susceptible to peroxidation and they yield various degradation products, including the main α,ÎČ-unsaturated hydroxyalkenal, 4-hydroxy-2,3-trans-nonenal (HNE) in oxidative stress. Due to its high reactivity, HNE interacts with various macromolecules of the cell, and this general toxicity clearly contributes to a wide variety of pathological conditions. In addition, growing evidence suggests a more specific function of HNE in electrophilic signaling as a second messenger of oxidative/electrophilic stress. It can induce antioxidant defense mechanisms to restrain its own production and to enhance the cellular protection against oxidative stress. Moreover, HNE-mediated signaling can largely influence the fate of the cell through modulating major cellular processes, such as autophagy, proliferation and apoptosis. This review focuses on the molecular mechanisms underlying the signaling and regulatory functions of HNE. The role of HNE in the pathophysiology of cancer, cardiovascular and neurodegenerative diseases is also discussed
Non-adherence or non-persistence to intravitreal injection therapy for neovascular age-related macular degeneration: a mixed-methods systematic review
TOPIC: Systematic review of risk factors for non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection therapy for neovascular age-related macular degeneration (nAMD). CLINICAL RELEVANCE: Lack of adherence (non-adherence) or under-treatment (non-persistence) with respect to evidence from clinical trials remains a significant barrier to optimizing real-world outcomes for patients with nAMD. Contributing factors and strategies to address this are poorly understood. METHODS: Studies that reported factors for non-adherence and/or non-persistence to anti-VEGF therapy as well as studies examining strategies to improve this were included. Trial eligibility and data extraction were conducted according to Cochrane review methods. Risk of bias was assessed using the Mixed Method Assessment Tool and certainty of evidence evaluated according to the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative Research) tool. Data were collated descriptively. RESULTS: Of the 1284 abstract results screened, 124 articles were assessed in full and 37 studies met the inclusion criteria. Definitions of non-adherence and non-persistence varied or were not reported. Non-persistence occurred early with up to 50% of patients stopping treatment by 24 months. High rates of non-adherence were similarly reported, occurring in 32 - 95% of patients. Certainty of this finding was downgraded to moderate level due to heterogeneity in definitions used across studies. Multiple factors determine non-adherence and non-persistence, including at condition, therapy, patient, social/economic and health systems/health-care team level. Moderate quality evidence points to lower baseline vision and poorer response to treatment as condition-related variables. The effects of other factors were of lower certainty, predominantly due to small numbers and potential biases in retrospective assessment. Although many factors are non-modifiable (e.g., patient co-morbidity), other factors are potentially correctable (e.g., lack of transport or mismatched patient expectations). Evidence on strategies to improve adherence and persistence is limited, but where available, these have proven effective. CONCLUSIONS: Awareness of factors related to poor patient adherence and persistence in nAMD could help identify at-risk populations and improve real world outcomes. Further work is required to develop uniform definitions as well as establishing high quality evidence on interventions that can be easily implemented
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