Existing guidance on the installation of screw piles suggest that they should be installed in a pitch-matched manner to avoid disturbance to the soil that may have a detrimental effect on the in... Show moreExisting guidance on the installation of screw piles suggest that they should be installed in a pitch-matched manner to avoid disturbance to the soil that may have a detrimental effect on the in-service performance of the pile. Recent insights from centrifuge modelling have shown that installing screw piles in this way requires large vertical compressive (or crowd) forces, which is inconsistent with the common assumption that screw piles pull themselves into the ground requiring minimal vertical compressive force. In this paper, through the use of the discrete element method (DEM), the effects of advancement ratio, i.e., the ratio between the vertical displacement per rotation to the geometric pitch of the helix of the screw pile helix, on the installation resistance and in-service capacity of a screw pile is investigated. The findings are further used to assess the applicability of empirical torque capacity correlation factors for large diameter screw piles. The results of the investigation show that it is possible to reduce the required vertical compressive installation force by 96% by reducing the advancement ratio and that although over-flighting a screw pile can decrease the subsequent compressive capacity, it appears to increase the tensile capacity significantly. Show less
Evangelou, E.; Warren, H.R.; Mosen-Ansorena, D.; Mifsu, B.; Pazoki, R.; Gao, H.; ... ; Million Vet Program 2018
Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between... Show moreObesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation. Show less
Background-In contrast to clear associations between variants in genes participating in low-density lipoprotein metabolism and cardiovascular disease risk, such associations for high-density... Show moreBackground-In contrast to clear associations between variants in genes participating in low-density lipoprotein metabolism and cardiovascular disease risk, such associations for high-density lipoprotein (HDL)-related genes are not well supported by recent large studies. We aimed to determine whether genetic variants at the locus encoding phospholipid transfer protein (PLTP), a protein involved in HDL remodeling, underlie altered PLTP activity, HDL particle concentration and size, and cardiovascular disease risk. Methods and Results-We assessed associations between 6 PLTP tagging single nucleotide polymorphisms and PLTP activity in 2 studies (combined n = 384) and identified 2 variants that show reproducible associations with altered plasma PLTP activity. A gene score based on these variants is associated with lower hepatic PLTP transcription (P = 3.2 x 10(-18)) in a third study (n = 957) and with an increased number of HDL particles of smaller size (P = 3.4 x 10(-17)) in a fourth study (n = 3375). In a combination of 5 cardiovascular disease case-control studies (n = 4658 cases and 11 459 controls), a higher gene score was associated with a lower cardiovascular disease risk (per-allele odds ratio, 0.94; 95% confidence interval, 0.90 to 0.98; P = 1.2 x 10(-3); odds ratio for highest versus lowest gene score, 0.69; 95% confidence interval, 0.55 to 0.86; P = 1.0 x 10(-3)). Conclusions-A gene score based on 2 PLTP single nucleotide polymorphisms is associated with lower PLTP transcription and activity, an increased number of HDL particles, smaller HDL size, and decreased risk of cardiovascular disease. These findings indicate that PLTP is a proatherogenic entity and suggest that modulation of specific elements of HDL metabolism may offer cardiovascular benefit. (Circulation. 2010; 122: 470-477.) Show less
Chambers, J.C.; Zhang, W.H.; Lord, G.M.; Harst, P. van der; Lawlor, D.A.; Sehmi, J.S.; ... ; Kooner, J.S. 2010
Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these,... Show moreUsing genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease. Show less
