Methylome-wide association study of central adiposity implicates genes involved in immune and endocrine systems

Aim: We conducted a methylome-wide association study to examine associations between DNA methylation in whole blood and central adiposity and body fat distribution, measured as waist circumference, waist-to-hip ratio and waist-to-height ratio adjusted for body mass index, in 2684 African-American adults in the Atherosclerosis Risk in Communities study. Materials & methods: We validated significantly associated cytosine-phosphate-guanine methylation sites (CpGs) among adults using the Women's Health Initiative and Framingham Heart Study participants (combined n = 5743) and generalized associations in adolescents from The Raine Study (n = 820). Results & conclusion: We identified 11 CpGs that were robustly associated with one or more central adiposity trait in adults and two in adolescents, including CpG site associations near TXNIP, ADCY7, SREBF1 and RAP1GAP2 that had not previously been associated with obesity-related traits

Smoothing surfaces in voxel based finite element analysis of trabecular bones

Abstract. The (micro-)finite element analysis based on three-dimensional computed tomography (CT) data of human bone takes place on complicated domains composed of often hundreds of millions of voxel elements. The finite element analysis is used to determine stresses and strains at the trabecular level of bone. It is even used to predict fracture of osteoporotic bone. However, the computed stresses can deteriorate at the jagged surface of the voxel model. There are algorithms known to smooth surfaces of voxel models. Smoothing however can distort the element geometries. In this study we investigate the effects of smoothing on the accuracy of the finite element solution, on the condition of the resulting system matrix, and on the effectiveness of the smoothed aggregation multigrid preconditioned conjugate gradient method.

Improving quality of care: development of a risk-adjusted perioperative morbidity model for vaginal hysterectomy

OBJECTIVE: We sought to develop and evaluate a risk-adjusted perioperative morbidity model for vaginal hysterectomy. STUDY DESIGN: Medical records of women who underwent vaginal hysterectomy during 2004 and 2005 were retrospectively reviewed. Morbidity included hospital readmission, reoperation, and unplanned medical intervention or intensive care unit admission; urinary tract infections were excluded. Multivariate logistic regression identified factors associated with perioperative morbidity (adjusted for urinary tract infection). The resulting model was validated using a random 2006 sample. RESULTS: Of 712 patients, 139 (19.5%) had morbidity associated with congestive heart failure or prior myocardial infarction, perioperative hemoglobin decrease >3.1 g/dL, preoperative hemoglobin <12.0 g/dL, and prior thrombosis (c-index = 0.68). Predicted morbidity was similar to observed rates in the validation sample. CONCLUSION: History of congestive heart failure or myocardial infarction, prior thrombosis, perioperative hemoglobin decrease >3.1 g/dL, or preoperative hemoglobin <12.0 g/dL were associated with increased perioperative complications. Quality improvement efforts should modify these variables to optimize outcome

Voxel size dependency, reproducibility and sensitivity of an in vivo bone loading estimation algorithm

A bone loading estimation algorithm was previously developed that provides in vivo loading conditions required for in vivo bone remodelling simulations. The algorithm derives a bone's loading history from its microstructure as assessed by high-resolution (HR) computed tomography (CT). This reverse engineering approach showed accurate and realistic results based on micro-CT and HR-peripheral quantitative CT images. However, its voxel size dependency, reproducibility and sensitivity still need to be investigated, which is the purpose of this study. Voxel size dependency was tested on cadaveric distal radii with micro-CT images scanned at 25 mm and downscaled to 50, 61, 75, 82, 100, 125 and 150 mm. Reproducibility was calculated with repeated in vitro as well as in vivo HR-pQCT measurements at 82 mm. Sensitivity was defined using HR-pQCT images from women with fracture versus non-fracture, and low versus high bone volume fraction, expecting similar and different loading histories, respectively. Our results indicate that the algorithm is voxel size independent within an average (maximum) error of 8.2% (32.9%) at 61 mm, but that the dependency increases considerably at voxel sizes bigger than 82 mm. In vitro and in vivo reproducibility are up to 4.5% and 10.2%, respectively, which is comparable to other in vitro studies and slightly higher than in other in vivo studies. Subjects with different bone volume fraction were clearly distinguished but not subjects with and without fracture. This is in agreement with bone adapting to customary loading but not to fall loads. We conclude that the in vivo bone loading estimation algorithm provides reproducible, sensitive and fairly voxel size independent results at up to 82 mm, but that smaller voxel sizes would be advantageous