Advancements in Design, Analysis, and Retrofitting of Structures Exposed to Blast

The objective of this special issue is to provide an overview on the current trends and recent advancements in terms of design, analysis, experimental testing, and retrofitting of structural systems and assemblies exposed to exceptional loads such as explosions

Vented Methane-air Explosion Overpressure Calculation—A simplified approach based on CFD

This paper presents new correlations developed through numerical simulations to estimate peak overpressures for vented methane-air explosions in cylindrical enclosures. A series of experimental tests are carried out first and the results are used to validate the numerical models developed with the commercial CFD software FLACS. More than 350 simulations consisting of 16 enclosure scales, 12 vent area to enclosure roof area ratios, 8 gas equivalence ratios and 9 vent activation pressures are then carried out to develop the Vented Methane-air Explosion Overpressure Calculation (VMEOC) correlations. Parameters associated with burning velocity and turbulence generation, oscillatory combustion and flame instabilities in vented gas explosion are taken into account in the development of new correlations. Comparing to CFD simulations, the VMEOC correlations provide a faster way to estimate the peak overpressure of a vented explosion. Additionally, it is proved in this study that the VMEOC correlations are easier to use and more accurate than the equations given in the up-to-date industrial standard- NFPA-68 2013 edition

Genetic Susceptible Locus in NOTCH2 Interacts with Arsenic in Drinking Water on Risk of Type 2 Diabetes

Abstract: Background: Chronic exposure to arsenic in drinking water is associated with increased risk of type 2 diabetes mellitus (T2DM) but the underlying molecular mechanism remains unclear. Objectives: This study evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes associated with diabetes and arsenic exposure in drinking water on the risk of developing T2DM. Methods: In 2009-2011, we conducted a follow up study of 957 Bangladeshi adults who participated in a case-control study of arsenic-induced skin lesions in 2001-2003. Logistic regression models were used to evaluate the association between 38 SNPs in 18 genes and risk of T2DM measured at follow up. T2DM was defined as having a blood hemoglobin A1C level greater than or equal to 6.5% at follow-up. Arsenic exposure was characterized by drinking water samples collected from participants' tubewells. False discovery rates were applied in the analysis to control for multiple comparisons. Results: Median arsenic levels in 2001-2003 were higher among diabetic participants compared with non-diabetic ones (71.6 mu g/L vs. 12.5 mu g/L, p-value <0.001). Three SNPs in ADAMTS9 were nominally associated with increased risk of T2DM (rs17070905, Odds Ratio (OR) = 2.30, 95% confidence interval (CI) 1.17-4.50; rs17070967, OR = 2.02, 95% CI 1.00-4.06; rs6766801, OR = 2.33, 95% CI 1.18-4.60), but these associations did not reach the statistical significance after adjusting for multiple comparisons. A significant interaction between arsenic and NOTCH2 (rs699780) was observed which significantly increased the risk of T2DM (p for interaction = 0.003; q-value = 0.021). Further restricted analysis among participants exposed to water arsenic of less than 148 mu g/L showed consistent results for interaction between the NOTCH2 variant and arsenic exposure on T2DM (p for interaction = 0.048; q-value = 0.004)

Arsenic Reduction in Drinking Water and Improvement in Skin Lesions: A Follow-Up Study in Bangladesh

BACKGROUND: Chronic exposure to arsenic is associated with skin lesions. However, it is not known whether reducing arsenic exposure will improve skin lesions. OBJECTIVE: We evaluated the association between reduced arsenic exposures and skin lesion recovery over time. METHODS: A follow-up study of 550 individuals was conducted in 2009-2011 on a baseline population of skin lesion cases (n = 900) previously enrolled in Bangladesh in 2001-2003. Arsenic in drinking water and toenails, and skin lesion status and severity were ascertained at baseline and follow-up. We used logistic regression and generalized estimating equation (GEE) models to evaluate the association between log(10)-transformed arsenic exposure and skin lesion persistence and severity. RESULTS: During the study period, water arsenic concentrations decreased in this population by 41% overall, and 65 individuals who had skin lesions at baseline had no identifiable lesions at follow-up. In the adjusted models, every log(10) decrease in water arsenic and toenail arsenic was associated with 22% [odds ratio (OR) = 1.22; 95% CI: 0.85, 1.78] and 4.5 times (OR = 4.49; 95% CI: 1.94, 11.1) relative increase in skin lesion recovery, respectively. In addition, lower baseline arsenic levels were significantly associated with increased odds of recovery. A log(10) decrease in toenail arsenic from baseline to follow-up was also significantly associated with reduced skin lesion severity in cases over time (mean score change of -5.22 units; 95% CI: -8.61, -1.82). CONCLUSIONS: Reducing arsenic exposure increased the odds that an individual with skin lesions would recover or show less severe lesions within 10 years. Reducing arsenic exposure must remain a public health priority in Bangladesh and in other regions affected by arsenic-contaminated water.This is the publisher’s final pdf. The published article is copyrighted by National Institute of Environmental Health Sciences and can be found at: http://ehp.niehs.nih.gov/. Reproduced with permission from Environmental Health Perspectives.Keywords: Arsenic, Change, Skin lesion, Bangladesh, RecoveryKeywords: Arsenic, Change, Skin lesion, Bangladesh, Recover

Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity.

The endoplasmic reticulum (ER) is the main site of protein and lipid synthesis, membrane biogenesis, xenobiotic detoxification and cellular calcium storage, and perturbation of ER homeostasis leads to stress and the activation of the unfolded protein response. Chronic activation of ER stress has been shown to have an important role in the development of insulin resistance and diabetes in obesity. However, the mechanisms that lead to chronic ER stress in a metabolic context in general, and in obesity in particular, are not understood. Here we comparatively examined the proteomic and lipidomic landscape of hepatic ER purified from lean and obese mice to explore the mechanisms of chronic ER stress in obesity. We found suppression of protein but stimulation of lipid synthesis in the obese ER without significant alterations in chaperone content. Alterations in ER fatty acid and lipid composition result in the inhibition of sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and ER stress. Correcting the obesity-induced alteration of ER phospholipid composition or hepatic Serca overexpression in vivo both reduced chronic ER stress and improved glucose homeostasis. Hence, we established that abnormal lipid and calcium metabolism are important contributors to hepatic ER stress in obesity

Fetal Window of Vulnerability to Airborne Polycyclic Aromatic Hydrocarbons on Proportional Intrauterine Growth Restriction

Background: Although the entire duration of fetal development is generally considered a highly susceptible period, it is of public health interest to determine a narrower window of heightened vulnerability to polycyclic aromatic hydrocarbons (PAHs) in humans. We posited that exposure to PAHs during the first trimester impairs fetal growth more severely than a similar level of exposure during the subsequent trimesters. Methods: In a group of healthy, non-smoking pregnant women with no known risks of adverse birth outcomes, personal exposure to eight airborne PAHs was monitored once during the second trimester for the entire cohort (n = 344), and once each trimester within a subset (n = 77). Both air monitoring and self-reported PAH exposure data were used in order to statistically estimate PAH exposure during the entire gestational period for each individual newborn. Results: One natural-log unit increase in prenatal exposure to the eight summed PAHs during the first trimester was associated with the largest decrement in the Fetal Growth Ratio (FGR) (23%, 95 % Confidence Interval (CI), 25 to20%), birthweight (2105 g, 95 % CI, 2188 to 222 g), and birth length (20.78 cm, 95 % CI, 21.30 to 20.26 cm), compared to the unit effects of PAHs during the subsequent trimesters, after accounting for confounders. Furthermore, a unit exposure during the first trimester was associated with the largest elevation in Cephalization Index (head to weight ratio) (3 mm/g, 95 % CI, 1 to 5 mm/g). PAH exposure was not associated with evidence of asymmetric growth restriction in this cohort

Do Market-Level Hospital and Physician Resources Affect Small Area Variation in Hospital Use?

This study evaluates the effect of market-level physician and hospital resources on hospital use. It is anticipated that higher hospital discharges are associated with (1) greater hospital and physician resources, (2) more differentiated hospital and physician resources, and (3) higher levels of teaching intensity in the community. Data on 14 modified diagnostically related groups (DRGs) and 58 hospital market communities in Michigan are analyzed during a 7-year period. Findings indicate that physician resources, hospital resources, differentiation of hospital and physician resources, and teaching intensity contribute only modestly to discharges, holding constant the socioeconomic attributes of the community and adjusting for the variation in hospital use over time. With the inclusion of hospital and physician resource variables, socioeconomic factors remain important determinants of the variation across market communities. Findings are discussed in terms of their implications for health care organizations, managed care programs, and cost control efforts in general.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68450/2/6.pd

Exposure to Low Levels of Lead in Utero and Umbilical Cord Blood DNA Methylation in Project Viva: An Epigenome-Wide Association Study

Background: Early-life exposure to lead is associated with deficits in neurodevelopment and with hematopoietic system toxicity. DNA methylation may be one of the underlying mechanisms for the adverse effects of prenatal lead on the offspring, but epigenome-wide methylation data for low levels of prenatal lead exposure are lacking. Objectives: We investigated the association between prenatal maternal lead exposure and epigenome-wide DNA methylation in umbilical cord blood nucleated cells in Project Viva, a prospective U.S.-based prebirth cohort with relatively low levels of lead exposure. Methods: Among 268 mother–infant pairs, we measured lead concentrations in red blood cells (RBC) from prenatal maternal blood samples, and using HumanMethylation450 Bead Chips, we measured genome-wide methylation levels at 482,397 CpG loci in umbilical cord blood and retained 394,460 loci after quality control. After adjustment for batch effects, cell types, and covariates, we used robust linear regression models to examine associations of prenatal lead exposure with DNA methylation in cord blood at epigenome-wide significance level [false discovery rate (FDR)<0.05]. Results: The mean [standard deviation (SD)] maternal RBC lead level was 1.22 (0.63) μg/dL. CpG cg10773601 showed an epigenome-wide significant negative association with prenatal lead exposure (−1.4% per doubling increase in lead exposure; p=2.3×10−7) and was annotated to C-Type Lectin Domain Family 11, Member A (CLEC11A), which functions as a growth factor for primitive hematopoietic progenitor cells. In sex-specific analyses, we identified more CpGs with FDR<0.05 among female infants (n=38) than among male infants (n=2). One CpG (cg24637308), which showed a strong negative association with prenatal lead exposure among female infants (−4.3% per doubling increase in lead exposure; p=1.1×10−06), was annotated to Dynein Heavy Chain Domain 1 gene (DNHD1) which is highly expressed in human brain. Interestingly, there were strong correlations between blood and brain methylation for CpG (cg24637308) based on another independent set of samples with a high proportion of female participants. Conclusion: Prenatal low-level lead exposure was associated with newborn DNA methylation, particularly in female infants. https://doi.org/10.1289/EHP124

Population Differences in Transcript-Regulator Expression Quantitative Trait Loci

Gene expression quantitative trait loci (eQTL) are useful for identifying single nucleotide polymorphisms (SNPs) associated with diseases. At times, a genetic variant may be associated with a master regulator involved in the manifestation of a disease. The downstream target genes of the master regulator are typically co-expressed and share biological function. Therefore, it is practical to screen for eQTLs by identifying SNPs associated with the targets of a transcript-regulator (TR). We used a multivariate regression with the gene expression of known targets of TRs and SNPs to identify TReQTLs in European (CEU) and African (YRI) HapMap populations. A nominal p-value of <1×10−6 revealed 234 SNPs in CEU and 154 in YRI as TReQTLs. These represent 36 independent (tag) SNPs in CEU and 39 in YRI affecting the downstream targets of 25 and 36 TRs respectively. At a false discovery rate (FDR) = 45%, one cis-acting tag SNP (within 1 kb of a gene) in each population was identified as a TReQTL. In CEU, the SNP (rs16858621) in Pcnxl2 was found to be associated with the genes regulated by CREM whereas in YRI, the SNP (rs16909324) was linked to the targets of miRNA hsa-miR-125a. To infer the pathways that regulate expression, we ranked TReQTLs by connectivity within the structure of biological process subtrees. One TReQTL SNP (rs3790904) in CEU maps to Lphn2 and is associated (nominal p-value = 8.1×10−7) with the targets of the X-linked breast cancer suppressor Foxp3. The structure of the biological process subtree and a gene interaction network of the TReQTL revealed that tumor necrosis factor, NF-kappaB and variants in G-protein coupled receptors signaling may play a central role as communicators in Foxp3 functional regulation. The potential pleiotropic effect of the Foxp3 TReQTLs was gleaned from integrating mRNA-Seq data and SNP-set enrichment into the analysis

Type 2 Diabetes Modifies the association of Cad Genomic Risk Variants With Subclinical atherosclerosis

BACKGROUND: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D. METHODS: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 T2D cases leveraging whole-genome sequencing data from the Trans-Omics for Precision Medicine program. We included first-order T2D interaction terms in each model to determine whether CAD loci were modified by T2D. The genetic main and interaction effects were assessed using a joint test to determine whether a CAD variant, or gene-based rare variant set, was associated with the respective subclinical atherosclerosis measures and then further determined whether these loci had a significant interaction test. RESULTS: Using a Bonferroni-corrected significance threshold of CONCLUSIONS: These results highlight T2D as an important modifier of rare variant associations in CAD loci with CAC