Blur limits for defocus, astigmatism and trefoil

We investigated the limits at which blur due to defocus, crossed-cylinder astigmatism, and trefoil became noticeable, troublesome or objectionable. Black letter targets (0.1, 0.35 and 0.6 logMAR) were presented on white backgrounds. Subjects were cyclopleged and had effectively 5 mm pupils. Blur was induced with a deformable, adaptive-optics mirror operating under open-loop conditions. Mean defocus blur limits of six subjects with uncorrected intrinsic higher-order ocular aberrations ranged from 0.18 ± 0.08 D (noticeable blur criterion, 0.1 logMAR) to 1.01 ± 0.27 D (objectionable blur criterion, 0.6 logMAR. Crossed-cylinder astigmatic blur limits were approximately 90% of those for defocus, but with considerable meridional influences. In two of the subjects, the intrinsic aberrations of the eye were subsequently corrected before the defocus and astigmatic blur were added. This resulted in only minor reductions in their blur limits. When assessed with trefoil blur and corrected intrinsic ocular aberrations, the ratio of objectionable to noticeable blur limits in these two subjects was much higher for trefoil (3.5) than for defocus (2.5) and astigmatism (2.2).

Limits of spherical blur determined with an adaptive optics mirror

We extended an earlier study (Vision Research, 45, 1967–1974, 2005) in which we investigated limits at which induced blur of letter targets becomes noticeable, troublesome and objectionable. Here we used a deformable adaptive optics mirror to vary spherical defocus for conditions of a white background with correction of astigmatism; a white background with reduction of all aberrations other than defocus; and a monochromatic background with reduction of all aberrations other than defocus. We used seven cyclopleged subjects, lines of three high-contrast letters as targets, 3–6 mm artificial pupils, and 0.1–0.6 logMAR letter sizes. Subjects used a method of adjustment to control the defocus component of the mirror to set the 'just noticeable', 'just troublesome' and 'just objectionable' defocus levels. For the white-no adaptive optics condition combined with 0.1 logMAR letter size, mean 'noticeable' blur limits were ±0.30, ±0.24 and ±0.23 D at 3, 4 and 6 mm pupils, respectively. White-adaptive optics and monochromatic-adaptive optics conditions reduced blur limits by 8% and 20%, respectively. Increasing pupil size from 3–6 mm decreased blur limits by 29%, and increasing letter size increased blur limits by 79%. Ratios of troublesome to noticeable, and of objectionable to noticeable, blur limits were 1.9 and 2.7 times, respectively. The study shows that the deformable mirror can be used to vary defocus in vision experiments. Overall, the results of noticeable, troublesome and objectionable blur agreed well with those of the previous study. Attempting to reduce higher-order aberrations or chromatic aberrations, reduced blur limits to only a small extent.

Interactions of phenyldithioesters with gold nanoparticles (AuNPs): Implications for AuNP functionalization and molecular barcoding of AuNP assemblies

The interactions of phenyldithioesters with gold nanoparticles (AuNPs) have been studied by monitoring changes in the surface plasmon resonance (SPR), depolarised light scattering, and surface enhanced Raman spectroscopy (SERS). Changes in the SPR indicated that an AuNP-phenyldithioester charge transfer complex forms in equilibrium with free AuNPs and phenyldithioester. Analysis of the Langmuir binding isotherms indicated that the equilibrium adsorption constant, Kads, was 2.3 ± 0.1 × 106 M−1, which corresponded to a free energy of adsorption of 36 ± 1 kJ mol−1. These values are comparable to those reported for interactions of aryl thiols with gold and are of a similar order of magnitude to moderate hydrogen bonding interactions. This has significant implications in the application of phenyldithioesters for the functionalization of AuNPs. The SERS results indicated that the phenyldithioesters interact with AuNPs through the C═S bond, and the molecules do not disassociate upon adsorption to the AuNPs. The SERS spectra are dominated by the portions of the molecule that dominate the charge transfer complex with the AuNPs. The significance of this in relation to the use of phenyldithioesters for molecular barcoding of nanoparticle assemblies is discussed.

Numerical methods for fractional partial differential equations with Riesz space fractional derivatives

In this paper, we consider the numerical solution of a fractional partial differential equation with Riesz space fractional derivatives (FPDE-RSFD) on a finite domain. Two types of FPDE-RSFD are considered: the Riesz fractional diffusion equation (RFDE) and the Riesz fractional advection–dispersion equation (RFADE). The RFDE is obtained from the standard diffusion equation by replacing the second-order space derivative with the Riesz fractional derivative of order αset membership, variant(1,2]. The RFADE is obtained from the standard advection–dispersion equation by replacing the first-order and second-order space derivatives with the Riesz fractional derivatives of order βset membership, variant(0,1) and of order αset membership, variant(1,2], respectively. Firstly, analytic solutions of both the RFDE and RFADE are derived. Secondly, three numerical methods are provided to deal with the Riesz space fractional derivatives, namely, the L1/L2-approximation method, the standard/shifted Grünwald method, and the matrix transform method (MTM). Thirdly, the RFDE and RFADE are transformed into a system of ordinary differential equations, which is then solved by the method of lines. Finally, numerical results are given, which demonstrate the effectiveness and convergence of the three numerical methods.

Cost-effectiveness of an intervention to reduce emergency re-admissions to hospital among older patients

Background. The objective is to estimate the cost-effectiveness of an intervention that reduces hospital readmission among older people at high risk. A cost-effectiveness model to estimate the costs and health benefits of the intervention was implemented. Methodology/Principal Findings. The model used data from a randomised controlled trial conducted in an Australian tertiary metropolitan hospital. Participants were acute medical admissions aged >65 years with at least one risk factor for readmission: multiple comorbidities, impaired functionality, aged >75 years, 30 recent multiple admissions, poor social support, history of depression. The intervention was a comprehensive nursing and physiotherapy assessment and an individually tailored program of exercise strategies and nurse home visits with telephone follow-up; commencing in hospital and continuing following discharge for 24 weeks. The change to cost outcomes, including the costs of implementing the intervention and all subsequent use of health care services, and, the change to health benefits, represented by quality adjusted life years, were estimated for the intervention as compared to existing practice. The mean change to total costs and quality 38 adjusted life years for an average individual over 24 weeks participating in the intervention were: cost savings of $333 (95% Bayesian credible interval $-1,932:1,282) and 0.118 extra quality adjusted life years (95% Bayesian credible interval 0.1:0.136). The mean net41 monetary-benefit per individual for the intervention group compared to the usual care condition was $7,907 (95% Bayesian credible interval $5,959:$9,995) for the 24 week period. Conclusions/Significance. The estimation model that describes this intervention predicts cost savings and improved health outcomes. A decision to remain with existing practices causes unnecessary costs and reduced health. Decision makers should consider adopting this 46 program for elderly hospitalised patients.

Discovery and characterization of IGFBP-mediated endocytosis in the human retinal pigment epithelial cell line ARPE-19

Insulin-like growth factor binding proteins (IGFBPs) are prime regulators of IGF-action in numerous cell types including the retinal pigment epithelium (RPE). The RPE performs several functions essential for vision, including growth factor secretion and waste removal via a phagocytic process mediated in part by vitronectin (Vn). In the course of studying the effects of IGFBPs on IGF-mediated VEGF secretion and Vn-mediated phagocytosis in the RPE cell line ARPE-19, we have discovered that these cells avidly ingest synthetic microspheres (2.0 μm diameter) coated with IGFBPs. Given the novelty of this finding and the established role for endocytosis in mediating IGFBP actions in other cell types, we have explored the potential role of candidate cell surface receptors. Moreover, we have examined the role of key IGFBP structural motifs, by comparing responses to three members of the IGFBP family (IGFBP-3, IGFBP-4 and IGFBP-5) which display overlapping variations in primary structure and glycosylation status. Coating of microspheres (FluoSpheres®, sulfate modified polystyrene filled with a fluorophore) was conducted at 37 °C for 1 h using 20 μg/mL of test protein, followed by extensive washing. Binding of proteins was confirmed using a microBCA assay. The negative control consisted of microspheres treated with 0.1% bovine serum albumin (BSA), and all test samples were post-treated with BSA in an effort to coat any remaining free protein binding sites, which might otherwise encourage non-specific interactions with the cell surface. Serum-starved cultures of ARPE-19 cells were incubated with microspheres for 24 h, using a ratio of approximately 100 microspheres per cell. Uptake of microspheres was quantified using a fluorometer and was confirmed visually by confocal fluorescence microscopy. The ARPE-19 cells displayed little affinity for BSA-treated microspheres, but avidly ingested large quantities of those pre-treated with Vn (ANOVA; p < 0.001). Strong responses were also observed towards recombinant formulations of non-glycosylated IGFBP-3, glycosylated IGFBP-3 and glycosylated IGFBP-5 (all p < 0.001), while glycosylated IGFBP-4 induced a relatively minor response (p < 0.05). The response to IGFBP-3 was unaffected in the presence of excess soluble IGFBP-3, IGF-I or Vn. Likewise, soluble IGFBP-3 did not induce uptake of BSA-treated microspheres. Antibodies to either the transferrin receptor or type 1 IGF-receptor displayed slight inhibitory effects on responses to IGFBPs and Vn. Heparin abolished responses to Vn, IGFBP-5 and non-glycosylated IGFBP-3, but only partially inhibited the response to glycosylated IGFBP-3. Our results demonstrate for the first time IGFBP-mediated endocytosis in ARPE-19 cells and suggest roles for the IGFBP-heparin-binding domain and glycosylation status. These findings have important implications for understanding the mechanisms of IGFBP actions on the RPE, and in particular suggest a role for IGFBP-endocytosis.