Genetic Epidemiology and Lipids: A Pattern So Grand and Complex

Intensive research over the course of the last several decades led to dramatic improvements in understanding, treating, and preventing cardiovascular disease. Despite this progress, cardiovascular disease remains the leading cause of mortality in both high- and low-income countries, and the leading source of morbidity in high-income countries. Lipids are well known determinants of cardiovascular disease risk; epidemiological evidence was published long ago. Total cholesterol and low-density lipoprotein cholesterol (LDL), which tend to be strongly correlated, are associated with increased disease risk. LDL can be readily oxidized, which causes inflammation and atherosclerosis to occur, and small, dense LDL particles are considered the most atherogenic lipid particles. High-density lipoprotein cholesterol (HDL), by contrast, is associated with beneficial effects, in terms of cardiovascular disease risk. Several mechanisms are likely to account for the protective consequences of increased HDL concentrations. HDL exhibits anti-inflammatory properties. Additionally, it is thought to be an anti-oxidant, helping to offset the deleterious effects of oxidized LDL. HDL is also involved in reverse cholesterol transp

DETERMINING OPTIMAL CHARACTERISTICS OF FILAMENT FOR FUSED FILAMENT FABRICATION (FFF) 3D PRINTING TECHNOLOGY

poster abstractFilament Fused Fabrication (FFF) is a 3D printing method that uses a heated nozzle to deposit partially melted material (i.e. thermoplastic filament) under software control that form layers to create a 3D part. This study analyzes optimal characteristics of filament for FFF 3D printing. Commercial filament suppliers, 3D printer manufacturers, and end-users regard filament diameter tolerance as an important indicator of 3D print quality. Despite the important role of the diameter consistency in the FFF process, few studies have addressed acceptable tolerance levels to achieve the highest 3D printing quality. The objective of this study is to investigate the impact of filament diameter tolerance on 3D printing quality. Drive gears bite into filament and force it into the heated nozzle and produces a pressure responsible for filament flow rate. Physic’s demonstrates that varying a cross sectional area (i.e. filament diameter) under a force will affect pressure. Previous studies have shown flow rate can impact surface quality, printer performance, and the mechanical properties of 3D parts. This study hypothesizes a consequence of robust nozzle designs capable of handling diameter variance do so at the expense of 3D printing quality. A pelletbased extruder is utilized to fabricate acrylonitrile butadiene styrene (ABS) filament samples using a nozzle of 1.75 mm in diameter. Temperature and extrusion rate are controlled parameters. An optical comparator and an array of digital calipers are used to measure and select fabricated samples based on filament diameter. A Self-Replicating Rapid Prototype (RepRap) 3D Printer is used and under software control print test samples into pre-defined line widths sensitive to flow rate fluctuation. The anticipated outcome of test sample line width error against its respective filament diameter tolerance will determine the acceptable filament tolerance on 3D printing quality. This study was sponsored by the Indiana University-Purdue University Indianapolis Multidisciplinary Undergraduate Research Institute (MURI

Failing beta-cell adaptation in South Asian families with a high risk of type 2 diabetes

We performed an extended oral glucose tolerance test (OGTT) to investigate the relationship between early and late beta-cell response and type 2 diabetes (T2D) in families of South Asian origin and indigenous Dutch, burdened by T2D. Based on the OGTT, 22 individuals were normoglycemic, 12 glucose intolerant and 23 had T2D in the South Asian families; these numbers were 34, 12 and 18 in the Caucasian families, respectively. The OGTT had 11 blood samplings in 3.5 h for glucose, insulin and C-peptide measurements. Through early and late insulin secretion rate (ISR), the above basal glucose area-under-the-curve after glucose load (glucose disposal) and insulin sensitivity index (ISI), we obtained early and late disposition indices (DI). South Asians on average had lower ISI than Caucasians (3.8 ± 2.9 vs. 6.5 ± 4.7, respectively, P < 0.001), with rapid decline of their early and late DI between normal glucose tolerance versus impaired fasting glucose/impaired glucose tolerance (late DI; P < 0.0001). Adjusted for ISI, age, gender and waist-to-hip ratio, early ISR was significantly associated with glucose disposal in South Asians (β = 0.55[0.186; 0.920]), but not in Caucasians (β = 0.09[-0.257; 0.441]). Similarly, early ISR was strongly associated with late ISR (β = 0.71[0.291; 1.123]; R2 = 45.5 %) in South Asians, but not in Caucasians (β = 0.27[-0.035; 0.576]; R2 = 17.4 %), with significant interaction between ethnicity and early ISR (β = 0.341[0.018; 0.664]). Ordinal regression analyses confirmed that all South Asian OGTT subgroups were homogenously resistant to insulin and solely predicted by early ISR (β = -0.782[-1.922; 0.359], β = -0.020[-0.037; -0.002], respectively), while in Caucasian families both ISI and early ISR were related to glucose tolerance state (β = -0.603[-1.105; -0.101], β = -0.066[-0.105; -0.027], respectively). In South Asian individuals, rapid beta-cell deterioration might occur under insulin resistant conditions. As their early insulin response correlates strongly with both glucose disposal and late insulin response, alterations in beta-cell dynamics may give an explanation to their extreme early onset of T2D, although larger prospective studies are required

Heritabilities, proportions of heritabilities explained by GWAS findings, and implications of cross-phenotype effects on PR interval

Electrocardiogram (ECG) measurements are a powerful tool for evaluating cardiac function and are widely used for the diagnosis and prediction of a variety of conditions, including myocardial infarction, cardiac arrhythmias, and sudden cardiac death. Recently, genome-wide association studies (GWASs) identified a large number of genes related to ECG parameter variability, specifically for the QT, QRS, and PR intervals. The aims of this study were to establish the heritability of ECG traits, including indices of left ventricular hypertrophy, and to directly assess the proportion of those heritabilities explained by GWAS variants. These analyses were conducted in a large, Dutch family-based cohort study, the Erasmus Rucphen Family study using variance component methods implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) software package. Heritability estimates ranged from 34 % for QRS and Cornell voltage product to 49 % for 12-lead sum. Trait-specific GWAS findings for each trait explained a fraction of their heritability (17 % for QRS, 4 % for QT, 2 % for PR, 3 % for Sokolow–Lyon index, and 4 % for 12-lead sum). The inclusion of all ECG-associated single nucleotide polymorphisms explained an additional 6 % of the heritability of PR. In conclusion, this study shows that, although GWAS explain a portion of ECG trait variability, a large amount of heritability remains to be explained. In addition, larger GWAS for PR are likely to detect loci already identified, particularly those observed for QRS and 12-lead sum