Chengqing Wu

A comparison of association methods correcting for population stratification in case-control studies.

Population stratification is an important issue in case–control studies of disease‐marker association. Failure to properly account for population structure can lead to spurious association or reduced power. In this article, we compare the performance of six methods correcting for population stratification in case–control association studies. These methods include genomic control (GC), EIGENSTRAT, principal component‐based logistic regression (PCA‐L), LAPSTRUCT, ROADTRIPS, and EMMAX. We also include the uncorrected Armitage test for comparison. In the simulation studies, we consider a wide range of population structure models for unrelated samples, including admixture. Our simulation results suggest that PCA‐L and LAPSTRUCT perform well over all the scenarios studied, whereas GC, ROADTRIPS, and EMMAX fail to correct for population structure at single nucleotide polymorphisms (SNPs) that show strong differentiation across ancestral populations. The Armitage test does not adjust for confounding due to stratification thus has inflated type I error. Among all correction methods, EMMAX has the greatest power, based on the population structure settings considered for samples with unrelated individuals. The three methods, EIGENSTRAT, PCA‐L, and LAPSTRUCT, are comparable, and outperform both GC and ROADTRIPS in almost all situations.

Analytical and biological variation of biomarkers of oxidative stress during the menstrual cycle

Abstract Little information is available on the intra-individual variability of oxidative stress biomarkers in healthy individuals and even less in the context of the menstrual cycle. The objective of this study was to characterize the analytical and biological variability of a panel of 21 markers of oxidative damage, antioxidant defence and micronutrients in nine healthy, regularly menstruating women aged 18–44 years. Analyses included measurement of lipid peroxidation, antioxidant enzymes and antioxidant vitamins. Blood specimens were collected, processed and stored using standardized procedures on days 2, 7, 12, 13, 14, 18, 22 and 28 in one cycle for each subject. Replicate analyses of markers were performed and two-way nested random effects ANOVA was used to describe analytical, intra-individual and inter-individual variability. No statistically significant differences at α=0.05, or temporal effects across the menstrual cycle were observed. Analytical variability was the smallest component of variance for all variables. The ICC among replicates ranged from 0.80 to 0.98. Imprecision based on quality control materials ranged from 1 to 11%. The critical differences between serial results varied greatly between assays ranging from 6 to 216% of the mean level. These results provide important initial information on the variability of biomarkers of oxidative stress, antioxidant defence and micronutrients across the menstrual cycle.

Investigation of air-blast effects from spherical-and cylindrical-shaped charges

Although the distributions of peak incident overpressure and impulse generated from spherical charges and cylindrical charges of the same weight can differ greatly close to the point of detonation, spherical charges are assumed for nearly all explosive-effects computations per modern standards for blast-resistant design such as UFC-3-340-02 and the soon-to-be published ASCE Standard for the Blast Protection of Buildings. A blast-testing program was performed using a reinforced concrete slab as the target to investigate the reflected peak overpressure and impulse distributions as a function of charge shape, orientation, and scaled distance. The charge shapes were cylindrical and spherical, and the charge mass varied from 0.24 to 8.0 kg. Nine pressure transducers were installed on the surface of the slab to record the distribution of pressure histories over the face of the target. A finite element model of the explosive and the target was validated using the experimental data. The validated model was then used to undertake a parametric analysis to more broadly study the effects of detonation point, ratio of charge length to charge diameter, charge orientation and standoff distance on the distribution of reflected overpressure. Numerical results are compared with predictions of UFC-3-340-02. For cylindrical charges, the ratio of charge length (L) to diameter (D), the orientation of the longitudinal axis of the charge, and detonation point within the charge affected the distributions of reflected peak overpressure and impulse in the immediate vicinity of the explosive. The UFC-3-340-02 underpredicts substantially the reflected peak overpressure and impulse on a target aligned with the vertical axis of a cylindrical charge with an aspect ratio of 1.0.

Blast Testing of Aluminum Foam–Protected Reinforced Concrete Slabs

Aluminum foam is a newly developed mobile and lightweight material with excellent energy absorption capacities. Applying aluminum foam as a sacrificial protection layer on the bearing faces of protected structures can mitigate blast effects on the resistance capacities of structures against impact or blast loading. The aluminum foam undergoes great plastic deformation under transient dynamic loads before becoming fully densified, making it excellent for mitigating blast effects on these structures. In this paper, we conducted quasi-static testing on two types of aluminum foam specimens and obtained the primary parameters for the mechanical properties of aluminum foam specimens. We then used these two types of aluminum foams to protect the reinforced concrete (RC) slabs, and we conducted a series of tests to investigate the performance of the aluminum foam–protected RC slabs against blast loads. We tested a total of five foam-protected slabs and one control RC slab in the blast test program. The test resul...

Numerical Modeling of Concrete-Filled Double-Skin Steel Square Tubular Columns under Blast Loading

AbstractConcrete-filled double-skin tubes (CFDST) have been widely used in constructing high-rise buildings, arch bridges, and factories over the past years. Although a number of researches have been conducted to study the behavior of CFDST columns under a variety of loading conditions, their performance when subjected to lateral impact load is still lacking. In this paper, numerical models of CFDST columns with two different cross sections are developed: one is with a CHS (circular hollow section) outer and CHS (circular hollow section) inner, and the other one is with SHS (square hollow section) outer and SHS (square hollow section) inner. Conventional concrete is filled in double-skin steel tubes. Different blast loads are applied to the surface of these columns for dynamic analysis. In addition, different axial loads are also applied to simulate combined load conditions. The displacement-time history obtained from each simulation is recorded and then compared. The key parameters that affect the perfor...

Blast testing of RC slabs retrofitted with NSM CFRP plates

In this paper, blast testing was performed on two reinforced concrete specimens: a plain reinforced concrete (RC) specimen; and an identical RC specimen retrofitted with near surface mounted (NSM) carbon fibre reinforced polymer (CFRP) plates. Each specimen was subjected to two separate explosive loads at a standoff distance of 0.6m, with the aim of investigating the performances of both specimens within both their elastic and plastic response ranges. The first blast (Blast 1) and second blast (Blast 2) consisted of an equivalent TNT charge weight of 0.079kg and 2.09kg respectively. The elastic-range responses of both specimens after the small shot (Blast 1), such as acceleration and deflection were obtained and comparisons were made between the specimens. The plastic performances of both specimens, such as tension face scabbing, crack patterns, plastic hinges and permanent deflection, after the large shot (Blast 2) were also analysed and compared. A number of unique failures and behaviours of both specimens were observed, investigated and analyzed. The test results provide a vital direction in the development of an optimal retrofit in future research.

Fuzzy-random probabilistic analysis of rock mass responses to explosive loads

Abstract This paper addresses the effects of randomness of initial damage in a rock mass and the critical tensile strain of the rock material on its dynamic responses and damage under explosive loads. A fuzzy definition is proposed to describe the fuzzy nature of failure phenomenon in a rock mass. The initial damage of the rock mass is estimated using the longitudinal and transverse elastic wave velocities. By using statistical analysis, the initial damage of the rock mass is found having the Beta distribution. The statistical estimation of a damage state and properties of randomly damaged rock mass are evaluated by the Rosenbluths point estimate method. In numerical calculation, an isotropic continuum damage model with the initial damage and the cumulative damage dependent on an equivalent tensile strain is suggested to model the rock mass behavior under blast loads. A Beta distribution is proposed to represent the probabilistic distribution of the damage variable of the rock mass under explosive loads. Several types of membership functions are suggested to represent the fuzziness of material failure. Based on the fuzzy–random probabilistic theory, a model including both the effects of randomness and fuzziness is proposed for the failure analysis of rock mass under explosive loads. The suggested models are coded and linked with an available computer program AUTODYN2D through its users subroutine capacity. The fuzzy failure probability and dynamic responses of the rock mass are calculated. Numerical results are compared with those obtained from independent field tests.

Characteristics of Confined Blast Loading in Unvented Structures

Confined blast loading occurs in many scenarios and the effects of confined blast loading may result in more serious damage to buildings due to multiple shock reflections (Shi et al. 2009). However, spherical charges are assumed for all confined explosive-effects computations in modern standards for blast-resistant design such as UFC-3-340-02 (2008) and the soon-to-be published ASCE Standard for the Blast Protection of Buildings (ASCE forthcoming) without consideration of effects of charge shape on the distribution of reflected overpressure and impulse. As confinement is an aggravation factor of explosion effects, analysis and design of infrastructure under critical scenarios of confined blast loading should take the aggravation factor into consideration. This paper is to develop a numerical model for prediction of blast loads inside unvented structures as a result of variation of the charge shape, charge orientation, geometries and volumes of confined chambers. A finite element program, AUTODYN (Century Dynamics, 2003), is utilized extensively to generate a model which is capable of being calibrated with the experimental results conducted by Wu et al. (2010) in external conditions and by Zyskowski et al. (2004) in a confined small box. The calibrated AUTODYN model is then used to conduct parametric studies to analyze the effects of the variation of charge shape, charge orientation, chamber geometry and chamber volume on the peak reflected overpressure and impulse on the walls of the chamber. The quasi-static overpressure for fully confined blast loading is characterized and the simulated results are used to derive the relationships between the quasi-static overpressure and scaled distance for the fully confined blast loading. Discussion is made on characteristics of fully confined blast loading inside chambers.

Derivation of Normalized Pressure Impulse Curves for Flexural Ultra High Performance Concrete Slabs

In previous studies, a finite-difference procedure was developed to analyze the dynamic response of simply supported normal reinforced concrete (NRC) slabs under blast loads. Ultra high performance concrete (UHPC) is a relatively new material with high strength and high deformation capacity in comparison with conventional normal strength concrete. Therefore, the finite-difference procedure for analysis of conventional reinforced concrete members against blast loads needs to be significantly adapted and extended to accommodate UHPC. In this paper, an advanced moment-rotation analysis model, employed to simulate the behavior of the plastic hinge of an UHPC member, is incorporated into the finite-difference procedure for the dynamic response analysis of reinforced UHPC slabs under blast loads. The accuracy of the finite-difference analysis model that utilized the moment-rotation analysis technique was validated using results from blast tests conducted on UHPC slabs. The validated finite-difference model was then used to generate pressure impulse (PI) curves. Parametric studies were then conducted to investigate the effects of various sectional and member properties on PI curves. Based on the simulated results, two equations were derived that can be used to normalize a PI curve. Further numerical testing of the normalization equations for UHPC members was then undertaken. The generated normalized PI curve, accompanied by the derived normalization equations, can be used for the purposes of general UHPC blast design.

A pilot genome-wide association study shows genomic variants enriched in the non-tumor cells of patients with well-differentiated neuroendocrine tumors of the ileum.

Genetic studies of midgut carcinoid cancer have exclusively focused on genomic changes of the tumor cells. We investigated the role of constitutional genetic polymorphisms in predisposing individuals to ileal carcinoids. In all, 239 cases and 110 controls were collected from three institutions: the Uppsala University Hospital; the Dana-Farber Cancer Institute; and the MD Anderson Cancer Center, and were genotyped using microarrays assaying >300 000 single nucleotide polymorphisms. Association with rs2208059 in KIF16B approached statistical significance (Mantel-Haenszel odds ratio=2.42, P=4.16×10(-7)) at a Bonferroni-corrected level (<1.62×10(-7)). Using two computational algorithms, four copy-number variants (CNVs) were identified in multiple cases that were absent in study controls and markedly less frequent in ∼1500 population-based controls. Of these four constitutional CNVs identified in blood-derived DNA, a 40 kb heterozygous deletion in Chr18q22.1 corresponded with a region frequently showing loss of heterozygosity (LOH) in ileal carcinoid tumor cells based on our meta-analysis of previously published cytogenetic studies (69.7% LOH, 95% confidence interval=60.0-77.9%). We analyzed the constitutional 40 kb deletion on chr18 in our study samples with a real-time quantitative PCR assay; 14/226 cases (6.19%) and 2/97 controls (2.06%) carried the CNV, although the exact boundaries of each deletion have not been determined. Given the small sample size, our findings warrant an independent cohort for a replication study. Owing to the rarity of this disease, we believe these results will provide a valuable resource for future work on this serious condition by allowing others to make efficient use of their samples in targeted studies.