Investigating Biomarkers for USH2A Retinopathy Using Multimodal Retinal Imaging

Pathogenic mutations in USH2A are a leading cause of visual loss secondary to non-syndromic or Usher syndrome-associated retinitis pigmentosa (RP). With an increasing number of RP-targeted clinical trials in progress, we sought to evaluate the photoreceptor topography under-lying patterns of loss observed on clinical retinal imaging to guide surrogate endpoint selection in USH2A retinopathy. In this prospective cross-sectional study, twenty-five patients with molecularly confirmed USH2A-RP underwent fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO) retinal imaging. Analysis comprised measurement of FAF horizontal inner (IR) and outer (OR) hyperautofluorescent ring diameter; SD-OCT ellipsoid zone (EZ) and external limiting membrane (ELM) width, normalised EZ reflectance; AOSLO foveal cone density and intact macular photoreceptor mosaic (IMPM) diam-eter. Thirty-two eyes from 16 patients (mean age ± SD, 36.0 ± 14.2 years) with USH2A-associated Usher syndrome type 2 (n = 14) or non-syndromic RP (n = 2) met the inclusion criteria. Spatial align-ment was observed between IR-EZ and OR-ELM diameters/widths (p <0.001). The IMPM border occurred just lateral to EZ loss (p < 0.001), although sparser intact photoreceptor inner segments were detected until ELM disruption. EZ width and IR diameter displayed a biphasic relationship with cone density whereby slow cone loss occurred until retinal degeneration reached ~1350 µm from the fovea, beyond which greater reduction in cone density followed. Normalised EZ reflectance and cone density were significantly associated (p <0.001). As the strongest correlate of cone density (p < 0.001) and best-corrected visual acuity (p <0.001), EZ width is the most sensitive biomarker of structural and functional decline in USH2A retinopathy, rendering it a promising trial endpoint

Federated Critical Infrastructure Simulators: Towards Ontologies for Support of Collaboration

Our society relies greatly on a variety of critical infrastructures (CI), such as power system networks, water distribution, oil and natural gas systems, telecommunication networks and others. Interdependency between those systems is high and may result in cascading failures spanning different infrastructures. Behavior of each CI can be observed and analyzed through the use of domain simulators, but this does not account for their interdependency. To explore CI interdependencies, domain simulators need to be integrated in a federation where they can collaborate. This paper explores three different simulators: the EPANET water distribution simulator, the PSCAD power system simulator and the I2Sim infrastructure interdependency simulator. Each simulator’s modeling approach is explored and their similarities and differences between modeling approaches are determined. Core ontology for each simulation engine is created as well as initial mapping between them. Ontologies and their mapping will support collaboration of simulators by enabling exchange of information in a semantic manner

Fortaleza: The emergence of a network hub

Digitalisation, accelerated by the pandemic, has brought the opportunity for companies to expand their businesses beyond their geographic location and has considerably affected networks around the world. Cloud services have a better acceptance nowadays, and it is foreseen that this industry will grow exponentially in the following years. With more distributed networks that need to support customers in different locations, the model of one-single server in big financial centres has become outdated and companies tend to look for alternatives that will meet their needs, and this seems to be the case with Fortaleza, in Brazil. With several submarine cables connections available, the city has stood out as a possible hub to different regions, and this is what this paper explores. Making use of real traffic data through looking glasses, we established a latency classification that ranges from exceptionally low to high and analysed 800 latencies from Roubaix, Fortaleza and Sao Paulo to Miami, Mexico City, Frankfurt, Paris, Milan, Prague, Sao Paulo, Santiago, Buenos Aires and Luanda. We found that non-developed countries have a big dependence on the United States to route Internet traffic. Despite this, Fortaleza proves to be an alternative for serving different regions with relatively low latencies

Cellular imaging of inherited retinal diseases using adaptive optics

Adaptive optics (AO) is an insightful tool that has been increasingly applied to existing imaging systems for viewing the retina at a cellular level. By correcting for individual optical aberrations, AO offers an improvement in transverse resolution from 10-15 μm to ~2 μm, enabling assessment of individual retinal cell types. One of the settings in which its utility has been recognised is that of the inherited retinal diseases (IRDs), the genetic and clinical heterogeneity of which warrants better cellular characterisation. In this review, we provide a summary of the basic principles of AO, its integration into multiple retinal imaging modalities and its clinical applications, focusing primarily on IRDs. Furthermore, we present a comprehensive summary of AO-based cellular findings in IRDs according to their associated disease-causing genes

Psychological type and attitude towards Celtic Christianity among committed Churchgoers in the United Kingdom: an empirical study

This article takes the burgeoning interest in Celtic Christianity as a key example of the way in which churches may be responding to the changing spiritual and religious landscape in the United Kingdom today and examines the power of psychological type theory to account for variation in the attitude of committed churchgoers to this innovation. Data provided by a sample of 248 Anglican clergy and lay church officers (who completed the Francis Psychological Type Scales together with the Attitude toward Celtic Christianity Scale) demonstrated that intuitive types, feeling types, and perceiving types reported a more positive attitude towards Celtic Christianity than sensing types, thinking types, and judging types. These findings are interpreted to analyse the appeal of Celtic Christianity and to suggest why some committed churchgoers may find this innovation less attractive

How does it feel to be a problem? Patients' experiences of self-management support in New Zealand and Canada

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Practicing Sustainability: Illuminating ‘Use’ in Wearing Clothes

Aspects of the ordinary in everyday dressing remain elusive to fashion studies, meaning the life of what Judy Attfield calls ‘design in the lower case’ escapes notice. In this article, the authors assemble a practice-oriented perspective to illuminate ‘wearing’ as an outcome of sets of commonplace and routine practices related to dressing, that wear a garment in and out over time, and enhance the visibility of clothing use. The central example is a research project that tests the theory of loosening the meaning of clean by trialling alternative laundering techniques to understand the transition to sustain-ability, or less resource-intensive competencies in the spectrum of clothing use. The promise of an interdisciplinary conceptual framework that draws from ‘theories of practice’ at the intersection of cultural studies, sociology and design is also tested as appropriate for the analysis of the quotidian realm of wearing and laundering; the analysis is particularly assisted with sustainable design research about the transition toward sustainable ways of living such as the development of ‘slow fashion’

Use of Bayesian inference for parameter recovery in DC and AC voltammetry

We describe the use of Bayesian inference for quantitative comparison of voltammetric methods for investigating electrode kinetics. We illustrate the utility of the approach by comparing the information content in both DC and AC voltammetry at a planar electrode for the case of a quasi-reversible one electron reaction mechanism. Using synthetic data (i. e. simulated data based on Butler-Volmer electrode kinetics for which the true parameter values are known and to which realistic levels of simulated experimental noise have been added), we are able to show that AC voltammetry is less affected by experimental noise (so that in effect it has a greater information content then the corresponding DC measurement) and hence yields more accurate estimates of the experimental parameters for a given level of noise. Significantly, the AC approach is shown to be able to distinguish higher values of the rate constant. The results of using synthetic data are then confirmed for an illustrative case of experimental data for the [Fe(CN)6]3−/4−process