1991 DA: An asteroid in a bizarre orbit

Asteroidal object 1991 DA has an orbit of high inclination, crossing the planets from Mars to Uranus. This is unique for an asteroid, but not unusual for a comet of the Halley-type: it therefore seems likely that 1991 DA is an extinct or dormant comet. Previous CCD imaging has shown no indication of a coma; spectroscopic observations of 1991 DA which lack any evidence of strong comet-like emissions are reported. Numerical integrations of the orbit of this object were performed which show that is has been remarkably stable for the past approximately 20,000 yr, but chaotic before that. This may allow a new estimate to be made of the physical lifetimes of comets

Rate of Diabetic Vitrectomy in a Defined Geographical Part of North East England

Purpose: To assess the yearly incidence of vitrectomy for proliferative diabetic retinopathy (PDR) over an 11-year period, in a geographically defined part of North East England. The time period covered the introduction of diabetic retinopathy screening. Methods: All patients undergoing vitrectomy for diabetic retinopathy in the Sunderland and South Tyneside area were recorded from 2000 to 2010. Incidence rates of vitrectomy specifically for the complications of PDR for the observed diabetic population, the estimated diabetic population and the population with known PDR were calculated. Results: There was a gradual and significant decline in the vitrectomy rate from 157 (95% confidence interval, CI, 135–187) to 103 (95% CI 98–109) per 100,000 of the observed diabetic population in 2000 and 2010 respectively. The rate in the estimated diabetic population showed no significant change at 68 (95% CI 48–87) in 2002 and 77 (95% CI 55–103) in 2010. The rate in the PDR population, which comprised 2.4% of the known diabetic population in 2002 and 1.8% in 2010, declined significantly from 7.7% in 2002 to 5.7% in 2010. Conclusion: This study evaluated vitrectomy rates for PDR in an area of North East England. There were apparent declining rates of vitrectomy for PDR following the introduction of diabetic retinopathy screening but these have to be interpreted in the light of several confounding factors

Self-reported quality of care for older adults from 2004 to 2011: a cohort study

Background: little is known about changes in the quality of medical care for older adults over time. Objective: to assess changes in technical quality of care over 6 years, and associations with participants' characteristics. Design: a national cohort survey covering RAND Corporation-derived quality indicators (QIs) in face-to-face structured interviews in participants' households. Participants: a total of 5,114 people aged 50 or more in four waves of the English Longitudinal Study of Ageing. Methods: the percentage achievement of 24 QIs in 10 general medical and geriatric clinical conditions was calculated for each time point, and associations with participants' characteristics were estimated using logistic regression. Results: participants were eligible for 21,220 QIs. QI achievement for geriatric conditions (cataract, falls, osteoarthritis and osteoporosis) was 41% [95% confidence interval (CI): 38–44] in 2004–05 and 38% (36–39) in 2010–11. Achievement for general medical conditions (depression, diabetes mellitus, hypertension, ischaemic heart disease, pain and cerebrovascular disease) improved from 75% (73–77) in 2004–05 to 80% (79–82) in 2010–11. Achievement ranged from 89% for cerebrovascular disease to 34% for osteoarthritis. Overall achievement was lower for participants who were men, wealthier, infrequent alcohol drinkers, not obese and living alone. Conclusion: substantial system-level shortfalls in quality of care for geriatric conditions persisted over 6 years, with relatively small and inconsistent variations in quality by participants' characteristics. The relative lack of variation by participants' characteristics suggests that quality improvement interventions may be more effective when directed at healthcare delivery systems rather than individuals

Robust 3D U-Net Segmentation of Macular Holes

Macular holes are a common eye condition which result in visual impairment. We look at the application of deep convolutional neural networks to the problem of macular hole segmentation. We use the 3D U-Net architecture as a basis and experiment with a number of design variants. Manually annotating and measuring macular holes is time consuming and error prone. Previous automated approaches to macular hole segmentation take minutes to segment a single 3D scan. Our proposed model generates significantly more accurate segmentations in less than a second. We found that an approach of architectural simplification, by greatly simplifying the network capacity and depth, exceeds both expert performance and state-of-the-art models such as residual 3D U-Nets

A consensus definition for lamellar macular hole

Background: A consensus on an optical coherence tomography (OCT) definition of lamellar macular hole (LMH) and similar conditions is needed. Methods: The panel reviewed relevant peer-reviewed literature to reach a consensus on LMH definition and to differentiate LMH from other similar conditions. Results: The panel reached a consensus on the definition of 3 clinical entities: LMH, epiretinal membrane (ERM) foveoschisis and macular pseudohole (MPH). LMH definition is based on 3 mandatory criteria and 3 optional anatomical features. The 3 mandatory criteria are the presence of irregular foveal contour, the presence of a foveal cavity with undermined edges, and the apparent loss of foveal tissue. Optional anatomical features include the presence of epiretinal proliferation, the presence of a foveal bump and the disruption of the ellipsoid line. ERM foveoschisis definition is based on 2 mandatory criteria: the presence of ERM and the presence of schisis at the level of Henle’s fiber layer. Three optional anatomical features can also be present: the presence of microcystoid spaces in the inner nuclear layer (INL), an increase of retinal thickness, and the presence of retinal wrinkling. MPH definition is based on 3 mandatory criteria and 2 optional anatomical features. Mandatory criteria include the presence of a foveal sparing ERM, the presence of a steepened foveal profile and an increased central retinal thickness. Optional anatomical features are the presence of microcystoid spaces in the INL and a normal retinal thickness. Conclusions: The use of the proposed definitions may provide uniform language for clinicians and future research

MicroRNA Expression Profile in the Vitreous of Proliferative Diabetic Retinopathy Patients and Differences from Patients Treated with Anti-VEGF

Purpose: microRNAs (miRNAs) mediate the pathological mechanisms of diabetic retinopathy. In this study, we compared miRNA expression profiles in the vitreous between patients with proliferative diabetic retinopathy (PDR) and patients with a macular hole as non-diabetic controls, and between PDR patients treated with antivascular endothelial growth factor (VEGF) therapy and untreated PDR patients. Methods: Vitreous samples of non-diabetic and PDR patients were screened for miRNAs with quantitative polymerase chain reaction (qPCR) panels. miRNA candidates were validated in vitreous samples of a second, independent cohort. In addition, the effect of anti-VEGF therapy was investigated in the vitreous of a third study population consisting of PDR patients who had not received anti-VEGF therapy and PDR patients who had received preoperative anti-VEGF therapy. Results: During screening, seven miRNAs were found to be significantly higher in the vitreous of PDR patients, whereas two miRNAs were found to be significantly lower compared with non-diabetic controls. Validating the expression of these miRNAs in a second cohort resulted in the identification of six miRNAs that were expressed at significantly higher rates in the vitreous of PDR patients: hsa-miR-20a-5p, hsa-miR-23b3p, hsa-miR-142-3p, hsa-miR-185-5p, hsa-miR-326, and hsa-miR-362-5p. Among these six miRNAs, hsa-miR-23b-3p levels were lower in the anti-VEGF-treated group of PDR patients compared with untreated PDR patients. Conclusions: In this study, we identified six miRNAs that are expressed more highly in PDR patients and one miRNA that is expressed at a lower levels in anti-VEGF-treated PDR patients. Translational Relevance: miRNAs identified in the vitreous of PDR patients may improve our understanding of the mechanisms leading to PDR

Human iPSC disease modelling reveals functional and structural defects in retinal pigment epithelial cells harbouring the m.3243A > G mitochondrial DNA mutation.

The m.3243A > G mitochondrial DNA mutation was originally described in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. The phenotypic spectrum of the m.3243A > G mutation has since expanded to include a spectrum of neuromuscular and ocular manifestations, including reduced vision with retinal degeneration, the underlying mechanism of which remains unclear. We used dermal fibroblasts, from patients with retinal pathology secondary to the m.3243A > G mutation to generate heteroplasmic induced pluripotent stem cell (hiPSC) clones. RPE cells differentiated from these hiPSCs contained morphologically abnormal mitochondria and melanosomes, and exhibited marked functional defects in phagocytosis of photoreceptor outer segments. These findings have striking similarities to the pathological abnormalities reported in RPE cells studied from post-mortem tissues of affected m.3243A > G mutation carriers. Overall, our results indicate that RPE cells carrying the m.3243A > G mutation have a reduced ability to perform the critical physiological function of phagocytosis. Aberrant melanosomal morphology may potentially have consequences on the ability of the cells to perform another important protective function, namely absorption of stray light. Our in vitro cell model could prove a powerful tool to further dissect the complex pathophysiological mechanisms that underlie the tissue specificity of the m.3243A > G mutation, and importantly, allow the future testing of novel therapeutic agents

ARL3 mutations cause Joubert syndrome by disrupting ciliary protein composition

Joubert syndrome (JBTS) is a genetically heterogeneous autosomal recessive neurodevelopmental ciliopathy. We investigated further the underlying genetic etiology of Joubert syndrome by studying two unrelated families in whom JBTS was not associated with pathogenic variants in known JBTSrelated genes. Combined autozygosity mapping of both families highlighted a candidate locus on chromosome 10 (chr10: 101569997-109106128 (hg 19)), and exome sequencing revealed two missense variants in ARL3 within the candidate locus. The encoded protein, ADP Ribosylation Factor-Like GTPase 3, ARL3, is a small GTP-binding protein that is involved in directing lipid-modified proteins into the cilium in a GTP-dependent manner. Both missense variants replace the highly conserved Arg149 residue, which we show to be necessary for the interaction with its guanine nucleotide exchange factor ARL13B, such that the mutant protein is associated with reduced INPP5E and NPHP3 localisation in cilia. We propose that ARL3 provides a potential hub in the network of encoded ciliopathy genes, whereby perturbation of ARL3 results in the mislocalisation of multiple ciliary proteins due to abnormal displacement of lipidated protein cargo