A study on spline quasi-interpolation based quadrature rules for the isogeometric Galerkin BEM

Two recently introduced quadrature schemes for weakly singular integrals [Calabr\`o et al. J. Comput. Appl. Math. 2018] are investigated in the context of boundary integral equations arising in the isogeometric formulation of Galerkin Boundary Element Method (BEM). In the first scheme, the regular part of the integrand is approximated by a suitable quasi--interpolation spline. In the second scheme the regular part is approximated by a product of two spline functions. The two schemes are tested and compared against other standard and novel methods available in literature to evaluate different types of integrals arising in the Galerkin formulation. Numerical tests reveal that under reasonable assumptions the second scheme convergences with the optimal order in the Galerkin method, when performing $h$-refinement, even with a small amount of quadrature nodes. The quadrature schemes are validated also in numerical examples to solve 2D Laplace problems with Dirichlet boundary conditions

GSVD Comparison of Patient-Matched Normal and Tumor aCGH Profiles Reveals Global Copy-Number Alterations Predicting Glioblastoma Multiforme Survival

Despite recent large-scale profiling efforts, the best prognostic predictor of glioblastoma multiforme (GBM) remains the patient's age at diagnosis. We describe a global pattern of tumor-exclusive co-occurring copy-number alterations (CNAs) that is correlated, possibly coordinated with GBM patients' survival and response to chemotherapy. The pattern is revealed by GSVD comparison of patient-matched but probe-independent GBM and normal aCGH datasets from The Cancer Genome Atlas (TCGA). We find that, first, the GSVD, formulated as a framework for comparatively modeling two composite datasets, removes from the pattern copy-number variations (CNVs) that occur in the normal human genome (e.g., female-specific X chromosome amplification) and experimental variations (e.g., in tissue batch, genomic center, hybridization date and scanner), without a-priori knowledge of these variations. Second, the pattern includes most known GBM-associated changes in chromosome numbers and focal CNAs, as well as several previously unreported CNAs in 3% of the patients. These include the biochemically putative drug target, cell cycle-regulated serine/threonine kinase-encoding TLK2, the cyclin E1-encoding CCNE1, and the Rb-binding histone demethylase-encoding KDM5A. Third, the pattern provides a better prognostic predictor than the chromosome numbers or any one focal CNA that it identifies, suggesting that the GBM survival phenotype is an outcome of its global genotype. The pattern is independent of age, and combined with age, makes a better predictor than age alone. GSVD comparison of matched profiles of a larger set of TCGA patients, inclusive of the initial set, confirms the global pattern. GSVD classification of the GBM profiles of an independent set of patients validates the prognostic contribution of the pattern

Association of Glomerular Filtration Rate with High-Sensitivity Cardiac Troponin T in a Community-Based Population Study in Beijing

BACKGROUND: Reduced renal function is an independent risk factor for cardiovascular disease mortality, and persistently elevated cardiac troponin T (cTnT) is frequently observed in patients with end-stage renal disease. In the general population the relationship between renal function and cTnT levels may not be clear because of the low sensitivity of the assay. In this study, we investigated the level of cTnT using a highly sensitive assay (hs-cTnT) and evaluated the association of estimated glomerular filtration rate (eGFR) with detectable hs-cTnT levels in a community-based population. METHODS: The serum hs-cTnT levels were measured in 1365 community dwelling population aged ≥45 years in Beijing, China. eGFR was determined by the Chinese modifying modification of diet in renal disease (C-MDRD) equation. RESULTS: With the highly sensitive assay, cTnT levels were detectable (≥3pg/mL) in 744 subjects (54.5%). The result showed that eGFR was associated with Log hs-cTnT (r = -0.14, P<0.001). After adjustment for the high predicted Framingham Coronary Heart Disease (CHD) risk (10-year risk >20%) and other prognostic indicators, moderate to severe reduced eGFR was independently associated with detectable hs-cTnT, whereas normal to mildly reduced eGFR was not independently associated with detectable hs-cTnT. In addition, after adjustment for other risk factors, the high predicted Framingham CHD risk was associated with detectable hs-cTnT in the subjects with different quartile levels of eGFR. CONCLUSION: The levels of hs-cTnT are detectable in a community-based Chinese population and low eGFR is associated with detectable hs-cTnT. Moreover, eGFR and high predicted Framingham CHD risk are associated with detectable hs-cTnT in subjects with moderate-to-severe reduced renal function

Red Blood Cell Fatty Acid Patterns and Acute Coronary Syndrome

BACKGROUND:Assessment of coronary heart disease (CHD) risk is typically based on a weighted combination of standard risk factors. We sought to determine the extent to which a lipidomic approach based on red blood cell fatty acid (RBC-FA) profiles could discriminate acute coronary syndrome (ACS) cases from controls, and to compare RBC-FA discrimination with that based on standard risk factors. METHODOLOGY/PRINCIPAL FINDINGS:RBC-FA profiles were measured in 668 ACS cases and 680 age-, race- and gender-matched controls. Multivariable logistic regression models based on FA profiles (FA) and standard risk factors (SRF) were developed on a random 2/3(rds) derivation set and validated on the remaining 1/3(rd). The area under receiver operating characteristic (ROC) curves (c-statistics), misclassification rates, and model calibrations were used to evaluate the individual and combined models. The FA discriminated cases from controls better than the SRF (c = 0.85 vs. 0.77, p = 0.003) and the FA profile added significantly to the standard model (c = 0.88 vs. 0.77, p<0.0001). Hosmer-Lemeshow calibration was poor for the FA model alone (p = 0.01), but acceptable for both the SRF (p = 0.30) and combined models (p = 0.22). Misclassification rates were 23%, 29% and 20% for FA, the SRF, and the combined models, respectively. CONCLUSIONS/SIGNIFICANCE:RBC-FA profiles contribute significantly to the discrimination of ACS cases, especially when combined with standard risk factors. The utility of FA patterns in risk prediction warrants further investigation

R497K polymorphism in epidermal growth factor receptor gene is associated with the risk of acute coronary syndrome

<p>Abstract</p> <p>Background</p> <p>Previous studies suggested that genetic polymorphisms in the epidermal growth factor receptor (EGFR) gene had been implicated in the susceptibility to some tumors and inflammatory diseases. EGFR has been recently implicated in vascular pathophysiological processes associated with excessive remodeling and atherosclerosis. Acute coronary syndrome (ACS) is a clinical manifestation of preceding atherosclerosis. Our purpose was to investigate the association of the EGFR polymorphism with the risk of ACS. In this context, we analyzed the HER-1 R497K and EGFR intron 1 (CA)_nrepeat polymorphisms in 191 patients with ACS and 210 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy and direct sequencing.</p> <p>Results</p> <p>There were significant differences in the genotype and allele distribution of R497K polymorphism of the EGFR gene between cases and controls. The <it>Lys </it>allele had a significantly increased risk of ACS compared with the <it>Arg </it>allele (adjusted OR = 1.49, 95% CI: 1.12–1.98, adjusted <it>P </it>= 0.006). However, no significant relationship between the number of (CA)_nrepeats of EGFR intron 1 (both alleles < 20 or any allele ≥ 20) and the risk of ACS was observed (adjusted OR = 0.97, 95% CI: 0.58–1.64, adjusted <it>P </it>= 0.911). Considering these two polymorphisms together, there was no statistically significant difference between the two groups.</p> <p>Conclusion</p> <p>R497K polymorphism of the EGFR gene is significantly associated with the risk of ACS. Our data suggests that R497K polymorphism may be used as a genetic susceptibility marker of the ACS.</p