The Effect of Cone Opsin Mutations on Retinal Structure and the Integrity of the Photoreceptor Mosaic

Purpose. To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations. Methods. Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness were measured using cross-sectional spectral-domain optical coherence tomography (SD-OCT) images. Molecular genetic analyses were performed to characterize the OPN1LW/OPN1MW gene array. Results. While disruptions in retinal lamination and cone mosaic structure were observed in all subjects, genotype-specific differences were also observed. For example, subjects with “L/M interchange” mutations resulting from intermixing of ancestral OPN1LW and OPN1MW genes had significant residual cone structure in the parafovea (∼25% of normal), despite widespread retinal disruption that included a large foveal lesion and thinning of the parafoveal inner retina. These subjects also reported a later-onset, progressive loss of visual function. In contrast, subjects with the C203R missense mutation presented with congenital blue cone monochromacy, with retinal lamination defects being restricted to the ONL+HFL and the degree of residual cone structure (8% of normal) being consistent with that expected for the S-cone submosaic. Conclusions. The photoreceptor phenotype associated with OPN1LW and OPN1MW mutations is highly variable. These findings have implications for the potential restoration of visual function in subjects with opsin mutations. Our study highlights the importance of high-resolution phenotyping to characterize cellular structure in inherited retinal disease; such information will be critical for selecting patients most likely to respond to therapeutic intervention and for establishing a baseline for evaluating treatment efficacy

Computational modelling of full interaction between crystal plasticity and oxygen diffusion at a crack tip

Oxidation-promoted crack growth, one of the major concerns for nickel-based superalloys, is closely linked to the diffusion of oxygen into the crack tip. The phenomenon is still not well understood yet, especially the full interaction between oxygen diffusion and severe near-tip mechanical deformation. This work aimed at the development of a robust numerical strategy to model the full coupling of crystal plasticity and oxygen diffusion in a single crystal nickel-based superalloy. In order to accomplish this, finite element package ABAQUS is used as a platform to develop a series of user-defined subroutines to model the fully coupled process of deformation and diffusion. The formulation allowed easy incorporation of nonlinear material behaviour, various loading conditions and arbitrary model geometries. Using this method, finite element analyses of oxygen diffusion, coupled with crystal plastic deformation, were carried out to simulate oxygen penetration at a crack tip and associated change of near-tip stress field, which has significance in understanding crack growth acceleration in oxidation environment. Based on fully coupled diffusion-deformation analyses, a case study was carried out to predict crack growth rate in oxidation environment and under dwell-fatigue loading conditions, for which a two-parameter failure criterion, in terms of accumulated inelastic strain and oxygen concentration at the crack tip, has been utilized

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Length scale effects on the geometric softening of precipitated single crystals

The understanding of the conditions under which inelastic deformation evolves in precipitated γ/γ' single crystal materials requires analytical and numerical frameworks which incorporate both time and spatial-dependent behaviour. In this work, an existing rate-dependent crystallographic formulation is employed to investigate the effect of the normalised length scale associated with the soft γ channel width on the geometric softening caused by the activation of additional slip systems due to large lattice rotations