Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci.

Funder: PfizerFunder: NovartisFunder: National Institute for Health ResearchFunder: MerckBackgroundGenetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies.MethodsWe characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci.ResultsWe identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci.ConclusionsOur findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Predicting sandy-clayey soil properties using electrical resistivity testing

Non-destructive tests are economical and easy-to-use techniques to determine different soil properties, which speed up the determination of sub-surface characteristics. They include ground-penetrating radar, seismographs, shear wave velocity and electrical resistivity testing. The latter is gaining worldwide popularity for determining sub-surface geology in geotechnical engineering as it does not require extensive testing. The aim of the study reported in this paper was to develop empirical correlations of electrical resistivity testing with different soil parameters by performing extensive conventional laboratory tests. These correlations would help in computing the required soil parameters by performing solely electrical resistivity testing, saving the time and effort required by conventional tests. The correlations developed included the relationship of resistivity values of soil with the drained angle of internal friction, effective cohesion, Atterberg's limits, maximum dry density, optimum moisture content and bearing capacity of a variety of shallow foundations. The regression coefficients obtained ensured the development of quite a good correlation, such that the result of electrical resistivity testing can be used for reasonably accurate determination of sandy-clayey soil propertie

Transient flow analysis for pumping system comprising pressure vessel using unsteady friction model

Recent myriad studies on the application of pressure vessels (PVs) to dampen the potentially hazardous transient pressure caused by pump failure are available in the literature. However, little research has been done on integrating these PVs into an instantaneous acceleration-based (IAB) model for transient flow analysis, while most of the reported investigations have been accomplished using the steady-state friction models. Also, scarce literature exists on optimizing the connection configuration of the PV. Nevertheless, unsteady friction (UF) is vital in accurately modeling a transient event, and therefore this study utilizes the IAB UF model to accurately predict the transient response of the pumping pipeline protected by a PV. Based on the proposed numerical model and computational algorithms, a novel approach is also explored to increase the working efficiency of the PV during transient events via a modified connection configuration with the main pipeline. A parametric study has been conducted to determine the impact of the PV's numerous parameters on transient pressure signals. The results reveal that the IAB UF model with two decay parameters can accurately replicate the amplitude and form of transient waves in a pumping system comprising a PV, with almost no deviations between numerical and experimental results. Furthermore, the numerical study shows that the initial air volume, polytropic exponent, installation location, PV size, and connection arrangement of PV with the pump-rising pipeline significantly affect the performance of water hammer protection. However, the flow resistance of connecting pipes containing perforated plates in a separate bypass line reduces the desired vessel volume from the standpoint of economy. The energy-based approach corroborates the use of this design for vessel-to-pipeline connections. The redesigned connection configuration reduces the required volume of PV by up to 70%, which leads to cost-effectiveness.This research was supported by the National Natural Science Foundation of China (Nos. 52079122, 51779216)

On the Recent Trends in Expansive Soil Stabilization Using Calcium-Based Stabilizer Materials (CSMs): A Comprehensive Review

Calcium-based stabilizer materials (CSMs) exhibit pozzolanic properties which improve the properties of clayey soils by hydration, cation exchange, flocculation, pozzolanic reaction, and carbonation. In this comprehensive review, comprising over past three decades from 1990 to 2019, a mechanistic literature of expansive soil stabilization by incorporating CSMs is presented by reviewing 183 published research articles. The advantages and disadvantages of CSMs as the ground stabilizing agent are succinctly presented, and the major outcomes of physicochemical effects on soil properties are discussed in detail. After blending with CSM, the main and interaction effects on soil properties with focus on chemical processes such as X-ray fluorescence, X-ray diffraction analyses, and microstructure interaction by using scanning electron microscopy and thermogravimetric analysis have been reviewed in light of findings of past researchers. This work will help geotechnical engineers to opt for suitable CSM in the field of geoenvironmental engineering in committing to sustainable construction of civil engineering structures over expansive soils

Sustainable use of soda lime glass powder (SLGP) in expansive soil stabilization

The focus of this experimental study is to ameliorate the engineering behavior of Palygorskite-rich medium Expansive soils (ES) by utilizing soda lime glass powder (SLGP). The hydrophilic ES are problematic and tend to damage the pavements, boundary walls, and slab-on-grade members Whereas, the accumulation of huge amounts of SLGP is responsible for multitude of environmental issues. Therefore, SLGP was added to the ES using various dosage levels (0 %, 6 %, 10 %, 14 %, 16 %, 18 %, and 22 % by dry weight of the ES to assess the compaction, consolidation and strength characteristics by performing geotechnical laboratory tests. Also, the effect of curing on th unconfined compressive strength of ES (UCS-ES) after 3, 7, 14, and 28 days was studied by considering the mineralogical changes. The microscopic mechanisms of the virgin ES and the SLGP-treated mixtures was evaluated by X-ray fluorescence (XRF), X-ray diffraction (XRD), and scanning electron microscopy (SEM) analyses. The results revealed that, plasticity dropped by almost 80 % (due to filler effect, cohesionless character, and higher silica amount of the SLGP), MDD increased from 18.25 to 19.16 kN/m3, and the OMC lowered down (due to the reduction in volume of clay minerals and interlayer spaces). With increasing SLGP dosage levels the coefficient of compression (Cc) decreased by 42.86 %, coefficient of volume (mv) by 60 %, coefficient of consolidation (cv) by 91.53 %, and the pre-consolidation pressures (Pc) witnessed an increase of 240 %. The UCS-ESunsoaked values exceed than the UCS-ES soaked values, particularly at early days of curing (1-7 days) such that UCS-ESsoaked = 13 x UCS-ESsoaked after one day, whereas UCS-ESsoaked = 5.25 x UCS-ESsoaked after 28 days. Similarly, a remarkable improvement (of six-fold) in strength was recorded based on California bearing ratio (CBR) values with 16 % replacement of the SLGP additive. Also, the compactability and strength characteristics were significantly improved and the plasticity plummeted due to formation of C-S-H and C-A-H compounds. Thus, the inclusion of 16 % SLGP in the medium ES was found as the optimum amount in reducing plasticity, improving consolidation characteristics and imparting strength

Incorporation of biochar and legumes into the summer gap: improving productivity of cereal-based cropping systems in Pakistan

Biochar can improve soil quality, increase crop production and sequester C in agricultural systems; however, this now needs critical evaluation in a sustainable agricultural context. In Pakistan, there is a gap in cereal-based wheat-maize-wheat cropping systems that lasts between 70-80 days. This "summer gap" can be used for growing short duration legume crops, which can provide valuable grain, fodder, or green manure and can provide a sustainable input of N into agricultural systems. We have used a field-based study to determine the effect of biochar application to an alkaline, nutrient poor, soil on the productivity of legume crops grown during the summer gap. Overall, biochar application (50 t ha-1) increased the productivity and yield of cowpea, mungbean and Sesbania over two cropping seasons compared to unamended non-biochar controls. The integration of biochar and legumes could be a useful strategy for improving the overall farm productivity of cereal-based cropping systems in Pakistan, by delivering a sustainable input of N to soil and providing increased yields from this additional summer gap crop

Correlation of electrical resistivity test with the geotechnical parameters of Sandy soil

There are different techniques to stabilize and improve the properties of soils with low shear strength, bearing capacity and other swelling parameters. This study includes the chemical analysis of expansive soils using X-ray diffraction (XRD) and scanning electron microscopy (SEM) before and after the stabilization using tire rubber powder (TRP) and cement kiln dust (CKD) in order to evaluate the geotechnical properties. Test results indicate that the inclusion of CKD-TRP mixture, not only reduces the plasticity of soil but also increases its unconfined compression strength, maximum dry density, and other strength characteristics. Finally, 5% TRP and 10% CKD addition is recommended as an optimum amount from the viewpoint of plasticity and strength characteristics

Strength, hydraulic, and microstructural characteristics of expansive soils incorporating marble dust and rice husk ash

Expansive/swell-shrink soils exhibit high plasticity and low strength, which lead to settlement and instability of lightly loaded structures. These problematic soils contain various swelling clay minerals that are unsuitable for engineering requirements. In an attempt to counter the treacherous damage of such soils in modern geotechnical engineering, efforts are underway to utilize environmentally friendly and sustainable waste materials as stabilizers. This study evaluates the strength and consolidation characteristics of expansive soils treated with marble dust (MD) and rice husk ash (RHA) through a multitude of laboratory tests, including consistency limits, compaction, uniaxial compression strength (UCS), and consolidation tests. By using X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses, the effect of curing on UCS after 3, 7, 14, 28, 56, and 112 days was studied from the standpoint of microstructural changes. Also, the long-term strength development of treated soils was analyzed in terms of the interactive response of impacting factors with the assistance of a series of ANN-based sensitivity analyses. It is found from the results that the addition of MD and RHA lowered down the water holding capacity, thereby causing a reduction in soil plasticity (by 21% for MD and 14.5% for RHA) and optimum water content (by 2% for MD and increased by 6% for RHA) along with an increase in the UCS (for 8% MD from 97 kPa to 471 kPa and for 10% RHA from 211 kPa to 665 kPa, after 3 days and 112 days of curing, respectively). Moreover, from the oedometer test results, mv initially increased up to 6% dosage and then dropped with further increase in the preconsolidation pressure. Furthermore, the compression index dropped with an increase in the preconsolidation pressure and addition of MD/RHA, while the coefficient of permeability (k) of RHA stabilized soil was higher than that of MD-treated samples for almost all dosage levels. The formation of the fibrous cementitious compounds (C-S-H; C-A-H) increased at optimum additive dosage after 7 days and at higher curing periods. Hence, the use of 10% RHA and 12% MD as replacement of the expansive soil is recommended for higher efficacy. This research would be helpful in reducing the impacts created by the disposal of both expansive soil and industrial and agricultural waste materials