A study of the social service program with glaucoma patients at the Massachusetts Eye and Ear Infirmary

Thesis (M.S.)--Boston University, 1948. This item was digitized by the Internet Archive

Genetics of HbA1c: a case study in clinical translation.

Glycated hemoglobin (HbA1c) measures the amount of glucose in the blood in the previous 2-3 months and is used to test whether an individual has diabetes (HbA1c≥6.5%), or how well they are managing their diabetes. Genome-wide association studies have successfully identified multiple genomic loci influencing HbA1c, through both glycemic (factors that affect the amount blood glucose levels) and erythrocytic (factors that affect the red blood cell) pathways. Inaccuracies in HbA1c, due to non-glycemic variants, could lead to suboptimal care or adverse health consequences. A recently published example is the erythrocytic variant (rs1050828) in G6PD, which leads to the artificial lowering of HbA1c and missed diagnosis of diabetes using current thresholds. In this review we will discuss recent insights into the genetic etiology of HbA1c, and how these can translate to the clinic

Eleanor P. Wheeler Correspondence

Entries include a typed letter of introduction concerning the Maine Author Collection to a New York City author and summer resident of North Brooklin, Maine, a typed letter from Wheeler on plain paper describing her Maine summer home and resident kittens as represented in her books Tory House Mystery and Jemmie, a typed letter on speckled paper stationery with a research question concerning offbeat histories, secret boasts, and unknown trophies of Maine as structure for a new mystery book, and a typed letter from the Maine State Library on referring her question to the research librarian

Genetic aetiology of glycaemic traits: approaches and insights.

Glycaemic traits such as fasting and post-challenge glucose and insulin measures, as well as glycated haemoglobin (HbA1c), are used to diagnose and monitor diabetes. These traits are risk factors for cardiovascular disease even below the diabetic threshold, and their study can additionally yield insights into the pathophysiology of type 2 diabetes. To date, a diverse set of genetic approaches have led to the discovery of over 97 loci influencing glycaemic traits. In this review, we will focus on recent advances in the genetic aetiology of glycaemic traits, and the resulting biological insights. We will provide a brief overview of results ranging from common, to low- and rare-frequency variant-trait association studies, studies leveraging the diversity across populations, and studies harnessing the power of genetic and genomic approaches to gain insights into the biological underpinnings of these traits

The role of architectural ceramics in contemporary site-specific art : an analysis from the perspective of the art practitioner through four case studies of commissioned artworks

The purpose of this study was to investigate the application of architectural ceramics within contemporary site-specific art projects and architectural contexts. The research involved the adoption of appropriate research methodologies and was practice-led involving the participation of the researcher in four site-specific art projects. These formed the basis of Case Studies which followed a structure based on the actual commissioning process. The subsequent comparison and reflection on these projects highlighted key issues relating to the process of producing large-scale ceramic artwork for public places and within a collaborative context. It was found that ceramic, and particularly brick was an appropriate material for the embellishment of contemporary architecture and that its application was most effective when included as an integral feature of the building. This was best achieved through close collaboration between artist and architect at the earliest stages of the building programme. The research demonstrates the viability of ceramics for large-scale architectural features and also offers an alternative perspective to previous theory based studies of site-specific art. In addition it indicates possible ways forward for architectural ceramics through closer cooperation with industry, architects and the application of new technology

Developmental trends in voice onset time: some evidence for sex differences

This study reports on an investigation into the voice onset time (VOT) patterns of the plosives /p b t d/ in a group of 30 children aged 7 (n = 10), 9 (n = 10) and 11 (n = 10) years. Equal numbers of girls and boys participated in the study. Each child named a series of letter objects to elicit /p b t d/ in a syllable onset position with a fixed vowel context. VOT data were examined for age, sex and plosive differences with the following hypotheses: Firstly, that there would be sex differences in the VOT patterns of preadolescent children. Secondly, that the sex differences in VOT patterns would be linked to age and development, and that these would eventually become marked by the age of 11 years, by which time adult-like VOT values should have been achieved. Finally, that the extent of sex and age differences would be dependent upon the plosive being investigated. Results indicated patterns of decrease with age in the VOT values of /p b/ for the boys, with some evidence of increases in the VOT values of /t/ for the girls. In addition, 'voiced' and 'voiceless' cognates showed a more marked bimodal distribution in the girls' VOT patterns. This bimodal distribution was investigated by examining the degree of difference between the VOT values of voiced and voiceless cognate pairs /p b/ and /t d/, and examining the effects of age, sex and cognate pair. These results indicated that more marked sex differences in the 'voiced'/'voiceless' contrast emerged between the data of the 9- and 11-year-olds, a pattern, which was more marked for the alveolar plosives. These preliminary results confirmed all three hypotheses. The findings are presented and discussed both within a developmental and sociophonetic framework

Linkage analysis of GAW14 simulated data: comparison of multimarker, multipoint, and conditional approaches

The purposes of this study were 1) to examine the performance of a new multimarker regression approach for model-free linkage analysis in comparison to a conventional multipoint approach, and 2) to determine the whether a conditioning strategy would improve the performance of the conventional multipoint method when applied to data from two interacting loci. Linkage analysis of the Kofendrerd Personality Disorder phenotype to chromosomes 1 and 3 was performed in three populations for all 100 replicates of the Genetic Analysis Workshop 14 simulated data. Three approaches were used: a conventional multipoint analysis using the Zlr statistic as calculated in the program ALLEGRO; a conditioning approach in which the per-family contribution on one chromosome was weighted according to evidence for linkage on the other chromosome; and a novel multimarker regression approach. The multipoint and multimarker approaches were generally successful in localizing known susceptibility loci on chromosomes 1 and 3, and were found to give broadly similar results. No advantage was found with the per-family conditioning approach. The effect on power and type I error of different choices of weighting scheme (to account for different numbers of affected siblings) in the multimarker approach was examined

Synergistic insights into human health from aptamer- and antibody-based proteomic profiling.

Funder: Wellcome TrustAffinity-based proteomics has enabled scalable quantification of thousands of protein targets in blood enhancing biomarker discovery, understanding of disease mechanisms, and genetic evaluation of drug targets in humans through protein quantitative trait loci (pQTLs). Here, we integrate two partly complementary techniques-the aptamer-based SomaScan® v4 assay and the antibody-based Olink assays-to systematically assess phenotypic consequences of hundreds of pQTLs discovered for 871 protein targets across both platforms. We create a genetically anchored cross-platform proteome-phenome network comprising 547 protein-phenotype connections, 36.3% of which were only seen with one of the two platforms suggesting that both techniques capture distinct aspects of protein biology. We further highlight discordance of genetically predicted effect directions between assays, such as for PILRA and Alzheimer's disease. Our results showcase the synergistic nature of these technologies to better understand and identify disease mechanisms and provide a benchmark for future cross-platform discoveries.The Fenland Study (10.22025/2017.10.101.00001) is funded by the Medical Research Council (MC_UU_12015/1). We are grateful to all the volunteers and to the General Practitioners and practice staff for assistance with recruitment. We thank the Fenland Study Investigators, Fenland Study Co-ordination team and the Epidemiology Field, Data and Laboratory teams. We further acknowledge support for genomics from the Medical Research Council (MC_PC_13046). Proteomic measurements were supported and governed by a collaboration agreement between the University of Cambridge and Somalogic. JCZ is supported by a 4-year Wellcome Trust PhD Studentship and the Cambridge Trust, CL, EW, and NJW are funded by the Medical Research Council (MC_UU_12015/1). NJW is a NIHR Senior Investigator. ADH is an NIHR Senior Investigator and supported by the UCL Hospitals NIHR Biomedical Research Centre and the UCL BHF Research Accelerator (AA/18/6/34223). We thank Philippa Pettingill, Ida Grundberg, Klev Diamanti, and Andrea Ballagi for advice and comments on an earlier draft of this manuscript. We thank Vladimir Saudek for generating a 3D-model of variant GDF-15 protein

Love is the triumph of the imagination: daydreams about significant others are associated with increased happiness, love and connection

Social relationships and interactions contribute to daily emotional well-being. The emotional benefits that come from engaging with others are known to arise from real events, but do they also come from the imagination during daydreaming activity? Using experience sampling methodology with 101 participants, we obtained 371 reports of naturally occurring daydreams with social and non-social content and self-reported feelings before and after daydreaming. Social, but not non-social, daydreams were associated with increased happiness, love and connection and this effect was not solely attributable to the emotional content of the daydreams. These effects were only present when participants were lacking in these feelings before daydreaming and when the daydream involved imagining others with whom the daydreamer had a high quality relationship. Findings are consistent with the idea that social daydreams may function to regulate emotion: imagining close others may serve the current emotional needs of daydreamers by increasing positive feelings towards themselves and others

Proteomic signatures for identification of impaired glucose tolerance

The implementation of recommendations for type 2 diabetes (T2D) screening and diagnosis focuses on the measurement of glycated hemoglobin (HbA1c) and fasting glucose. This approach leaves a large number of individuals with isolated impaired glucose tolerance (iIGT), who are only detectable through oral glucose tolerance tests (OGTTs), at risk of diabetes and its severe complications. We applied machine learning to the proteomic profiles of a single fasted sample from 11,546 participants of the Fenland study to test discrimination of iIGT defined using the gold-standard OGTTs. We observed significantly improved discriminative performance by adding only three proteins (RTN4R, CBPM and GHR) to the best clinical model (AUROC = 0.80 (95% confidence interval: 0.79–0.86), P = 0.004), which we validated in an external cohort. Increased plasma levels of these candidate proteins were associated with an increased risk for future T2D in an independent cohort and were also increased in individuals genetically susceptible to impaired glucose homeostasis and T2D. Assessment of a limited number of proteins can identify individuals likely to be missed by current diagnostic strategies and at high risk of T2D and its complications