Improving the economic value of photographic screening for optical coherence tomography-detectable macular oedema : a prospective, multicentre, UK study

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Temporal artery biopsies in south-east Scotland:a five year review

Temporal artery biopsy is the gold standard investigation for the diagnosis of giant cell arteritis. The aim of this retrospective study was to investigate the use of temporal artery biopsy in diagnosing giant cell arteritis in south-east Scotland over a five-year period. We aimed to quantify success rates, and predictive factors for a positive biopsy, as well as compare the different specialities performing the biopsies. The data should enable the development of better criteria for referral for investigation of giant cell arteritis. Methods Patients were identified using a database of temporal artery biopsies generated by the pathology department in NHS Lothian (south east Scotland), for all biopsies examined between January 2010 and December 2015. An electronic patient record was used to retrospectively examine the records of patients in the database. Results A total of 715 biopsies were included in the study, of which 250 (35.0%) showed features of giant cell arteritis. The main predictors for a positive biopsy were age at biopsy, specialty performing biopsy, erythrocyte sedimentation rate, jaw claudication/pain, and ophthalmic symptoms. The most important predictor of a positive biopsy was erythrocyte sedimentation rate. The length of biopsy was not found to be a predictor of positive biopsy; however, diameter of biopsy was predictive. Conclusions We have shown that many temporal artery biopsies are negative, and finding ways to reduce the number of patients unnecessarily undergoing biopsy will be essential in reducing workload and streamlining services. This study demonstrates some key predictive factors for patients with positive biopsies. The study also shows that a large proportion of biopsies taking place do not result in the recommended length of specimen, but this does not necessarily reduce the likelihood of a positive biopsy

Identification of a Novel Large Multigene Deletion and a Frameshift Indel in PDE6B as the Underlying Cause of Early-Onset Recessive Rod-Cone Degeneration

A family, with two affected identical twins with early-onset recessive inherited retinal degeneration, was analyzed to determine the underlying genetic cause of pathology. Exome sequencing revealed a rare and previously reported causative variant (c.1923_1969delinsTCTGGG; p.Asn643Glyfs*29) in th

Caste Gender and Occupational Outcomes

This chapter discusses an important concern of public policy in India which is to ensure that all persons, regardless of gender, caste, or religion, are treated fairly in the jobs market. A key aspect of this relates to inter-group differences in the likelihood of attaining different levels of occupational success. The issue here is whether these differences in likelihood are justified by differences in the distribution of employee attributes or whether they are, wholly or in part, due to employer bias. This chapter attempts to answer these questions using unit record data from the Indian Human Development Survey relating to the period 2011–12. Of particular interest to this chapter is that the Survey provides details about the occupations of approximately 62,500 persons by placing them in one or more of 99 occupations; these are aggregated in chapter 4 into six broad occupational categories. Using these data, the chapter (focusing on men and women between the ages of 21 and 60) employs the methods of multinomial logit to estimate the probabilities of persons being in these occupational categories, after controlling for their gender/caste/religion and their employment-related attributes. The main focus is the issue of differences between men and women, and differences between persons belonging to different social groups, in their likelihood of being in the different employment categories. Data on these men and women were used to decompose the observed difference between the groups, in their average proportions in the different occupations, into an “employer bias” and an “employee attributes” effect

Deaths in the Family

The purpose of this chapter is to evaluate the relative strengths of economic and social status in determining deaths in households in India. The first part of the chapter focuses on the “age at death” using National Sample Survey data for 2004 and 2014. The purpose was to ask whether after controlling for non-community factors, the fact that Indians belonged to different social groups, encapsulating different degrees of social status, exercised a significant influence on their age at death? The existence of a social group effect would suggest that there was a “social gradient” to health outcomes in India. The second part of the chapter, using data from the Indian Human Development Survey of 2011, investigated the determinants of infant and child mortality. The overriding concern now is gender bias with girls more likely to die than boys before attaining their first (infant) and fifth (child) birthdays. As this study has shown, gender bias in infant and child mortality rates is, with singular exceptions, a feature of all the social groups. In conducting this investigation, the chapter addresses for India an issue which lies at the heart of social epidemiology: estimating the relative strengths of individual and social factors in determining mortality outcomes

Real-time quantitative monitoring of hiPSC-based model of macular degeneration on Electric Cell-substrate Impedance Sensing microelectrodes

AbstractAge-related macular degeneration (AMD) is the leading cause of blindness in the developed world. Humanized disease models are required to develop new therapies for currently incurable forms of AMD.In this work, a tissue-on-a-chip approach was developed through combining human induced pluripotent stem cells, Electric Cell–substrate Impedance Sensing (ECIS) and reproducible electrical wounding assays to model and quantitatively study AMD. Retinal Pigment Epithelium (RPE) cells generated from a patient with an inherited macular degeneration and from an unaffected sibling were used to test the model platform on which a reproducible electrical wounding assay was conducted to model RPE damage. First, a robust and reproducible real-time quantitative monitoring over a 25-day period demonstrated the establishment and maturation of RPE layers on the microelectrode arrays. A spatially controlled RPE layer damage that mimicked cell loss in AMD disease was then initiated. Post recovery, significant differences (P<0.01) in migration rates were found between case (8.6±0.46μm/h) and control cell lines (10.69±0.21μm/h). Quantitative data analysis suggested this was achieved due to lower cell–substrate adhesion in the control cell line. The ECIS cell–substrate adhesion parameter (α) was found to be 7.8±0.28Ω1/2cm for the case cell line and 6.5±0.15Ω1/2cm for the control. These findings were confirmed using cell adhesion biochemical assays. The developed disease model-on-a-chip is a powerful platform for translational studies with considerable potential to investigate novel therapies by enabling real-time, quantitative and reproducible patient-specific RPE cell repair studies

Late-onset retinal degeneration pathology de to mutations in CTRP5 is mediated through HTRA1

Late-onset retinal degeneration (L-ORD) is an autosomal dominant macular degeneration characterized by the formation of sub-retinal pigment epithelium (RPE) deposits and neuroretinal atrophy. L-ORD results from mutations in the C1q-tumor necrosis factor-5 protein (CTRP5), encoded by the CTRP5/C1QTNF5 gene. To understand the mechanism underlying L-ORD pathology, we used a human cDNA library yeast two-hybrid screen to identify interacting partners of CTRP5. Additionally, we analyzed the Bruch's membrane/choroid (BM-Ch) from wild-type (Wt), heterozygous S163R Ctrp5 mutation knock-in (Ctrp5S163R/wt ), and homozygous knock-in (Ctrp5S163R/S163R ) mice using mass spectrometry. Both approaches showed an association between CTRP5 and HTRA1 via its C-terminal PDZ-binding motif, stimulation of the HTRA1 protease activity by CTRP5, and CTRP5 serving as an HTRA1 substrate. The S163R-CTRP5 protein also binds to HTRA1 but is resistant to HTRA1-mediated cleavage. Immunohistochemistry and proteomic analysis showed significant accumulation of CTRP5 and HTRA1 in BM-Ch of Ctrp5S163R/S163R and Ctrp5S163R/wt mice compared with Wt. Additional extracellular matrix (ECM) components that are HTRA1 substrates also accumulated in these mice. These results implicate HTRA1 and its interaction with CTRP5 in L-ORD pathology