Assessment of the clinical utility of adding common single nucleotide polymorphism genetic scores to classical risk factor algorithms in coronary heart disease risk prediction in UK men

Background: Risk prediction algorithms for coronary heart disease (CHD) are recommended for clinical use. However, their predictive ability remains modest and the inclusion of genetic risk may improve their performance. Methods: QRISK2 was used to assess CHD risk using conventional risk factors (CRFs). The performance of a 19 single nucleotide polymorphism (SNP) gene score (GS) for CHD including variants identified by genome-wide association study and candidate gene studies (weighted using the results from the CARDIoGRAMplusC4D meta-analysis) was assessed using the second Northwick Park Heart Study (NPHSII) of 2775 healthy UK men (284 cases). To improve the GS, five SNPs with weak evidence of an association with CHD were removed and replaced with seven robustly associated SNPs – giving a 21-SNP GS. Results: The weighted 19 SNP GS was associated with lipid traits (p<0.05) and CHD after adjustment for CRFs, (OR=1.31 per standard deviation, p=0.03). Addition of the 19 SNP GS to QRISK2 showed improved discrimination (area under the receiver operator characteristic curve 0.68 vs. 0.70 p=0.02), a positive net reclassification index (0.07, p=0.04) compared to QRISK2 alone and maintained good calibration (p=0.17). The 21-SNP GS was also associated with CHD after adjustment for CRFs (OR=1.39 per standard deviation, 1.42×10−3), but the combined QRISK2 plus GS score was poorly calibrated (p=0.03) and showed no improvement in discrimination (p=0.55) or reclassification (p=0.10) compared to QRISK2 alone. Conclusions: The 19-SNP GS is robustly associated with CHD and showed potential clinical utility in the UK population

Effect of SORT1, APOB and APOE polymorphisms on LDL-C and coronary heart disease in Pakistani subjects and their comparison with Northwick Park Heart Study II

BACKGROUND: Many SNPs have been identified in genes regulating LDL-C metabolism, but whether their influence is similar in subjects from different ethnicities is unclear. Effect of 4 such SNPs on LDL-C and coronary heart disease (CHD) was examined in Pakistani subjects and was compared with middle aged UK men from Northwick Park Heart Study II (NPHSII). METHODS: One thousand nine hundred sixty-five (1770 non CHD, 195 CHD) UK and 623 (219 non CHD, 404 CHD) Pakistani subjects were enrolled in the study. The SNPs SORT1 rs646776, APOB rs1042031 and APOE rs429358, rs7412 were genotyped by TaqMan/KASPar technique and their gene score was calculated. LDL-C was calculated by Friedewald equation, results were analyzed using SPSS. RESULTS: Allele frequencies were significantly different (p = <0.05) between UK and Pakistani subjects. However, the SNPs were associated with LDL-C in both groups. In UK non CHD, UK CHD, Pakistani non CHD and Pakistani CHD respectively, for rs646776, per risk allele increase in LDL-C(mmol/l) was 0.18(0.04), 0.06(0.11), 0.15(0.04) and 0.27(0.06) respectively. For rs1042031, per risk allele increase in LDL-C in four groups was 0.11(0.04), 0.04(0.14), 0.15(0.06) and 0.25(0.09) respectively. For APOE genotypes, compared to Ɛ3, each Ɛ2 decreased LDL-C by 0.11(0.06), 0.07(0.15), 0.20(0.08) and 0.38(0.09), while each Ɛ4 increased LDL-C by 0.43(0.06), 0.39(0.21), 0.19(0.11) and 0.39(0.14) respectively. Overall gene score explained a considerable proportion of sample variance in four groups (3.8 %, 1.26 % 13.7 % and 12.3 %). Gene score in both non-CHD groups was significantly lower than CHD subjects. CONCLUSIONS: The SNPs show a dose response association with LDL-C levels and risk of CHD in both populations

A versatile electrolyte system for electrodeposition of p-block elements from single ohase supercritical CH2F2

For the first time, a versatile electrolyte bath is described that can be used to electrodeposit a wide range of p-block elements from supercritical difluoromethane (scCH2F2). The bath comprises the tetrabutylammonium chlorometallate complex of the element in an electrolyte of 50×10−3 mol dm−3 tetrabutylammonium chloride at 17.2 MPa and 358 K. Through the use of anionic ([GaCl4]−, [InCl4]−, [GeCl3]−, [SnCl3]−, [SbCl4]−, and [BiCl4]−) and dianionic ([SeCl6]2− and [TeCl6]2−) chlorometallate salts, the deposition of elemental Ga, In, Ge, Sn, Sb, Bi, Se, and Te is demonstrated. In all cases, with the exception of gallium, which is a liquid under the deposition conditions, the resulting deposits are characterised by SEM, energy-dispersive X-ray analysis, XRD and Raman spectroscopy. An advantage of this electrolyte system is that the reagents are all crystalline solids, reasonably easy to handle and not highly water or oxygen sensitive. The results presented herein significantly broaden the range of materials accessible by electrodeposition from supercritical fluid and open up the future possibility of utilising the full scope of these unique fluids to electrodeposit functional binary or ternary alloys and compounds of these elements

Structurally Diverse Covalent Triazine-based Framework Materials for Photocatalytic Hydrogen Evolution from Water

A structurally diverse family of 39 covalent triazine-based framework materials (CTFs) are synthesized by Suzuki–Miyaura polycondensation and tested as hydrogen evolution photocatalysts using a high-throughput workflow. The two best-performing CTFs are based on benzonitrile and dibenzo[b,d]thiophene sulfone linkers, respectively, with catalytic activities that are among the highest for this material class. The activities of the different CTFs are rationalized in terms of four variables: the predicted electron affinity, the predicted ionization potential, the optical gap, and the dispersibility of the CTFs particles in solution, as measured by optical transmittance. The electron affinity and dispersibility in solution are found to be the best predictors of photocatalytic hydrogen evolution activity

WHAT DETERMINES THE STRENGTH OF A TROPHIC CASCADE?

Trophic cascades have been documented in a diversity of ecological systems and can be important in determining biomass distribution within a community. To date, the literature on trophic cascades has focused on whether and in which systems cascades occur. Many biological (e.g., productivity:biomass ratios) and methodological (e.g., experiment size or duration) factors vary with the ecosystem in which data were collected, but ecosystem type, per se, does not provide mechanistic insights into factors controlling cascade strength. Here, we tested various hypotheses about why trophic cascades occur and what determines their magnitude using data from 114 studies that measured the indirect trophic effects of predators on plant community biomass in seven aquatic and terrestrial ecosystems. Using meta-analysis, we examined the relationship between the indirect effect of predator manipulation on plants and 18 biological and methodological factors quantified from these studies. We found, in contrast to predictions, that high system productivity and low species diversity do not consistently generate larger trophic cascades. A combination of herbivore and predator metabolic factors and predator taxonomy (vertebrate vs. invertebrate) explained 31% of the variation in cascade strength among all 114 studies. Within systems, 18% of the variation in cascade strength was explained with similar predator and herbivore characteristics. Within and across all systems, the strongest cascades occurred in association with invertebrate herbivores and endothermic vertebrate predators. These associations may result from a combination of true biological differences among species with different physiological requirements and bias among organisms studied in different systems. Thus, although cascade strength can be described by biological characteristics of predators and herbivores, future research on indirect trophic effects must further examine biological and methodological differences among studies and systems. © 2005 by the Ecological Society of America

Competitive aminal formation during the synthesis of a highly soluble, isopropyl-decorated imine porous organic cage.

The synthesis of a new porous organic cage decorated with isopropyl moieties (CC21) was achieved from the reaction of triformylbenzene and an isopropyl functionalised diamine. Unlike structurally analogous porous organic cages, its synthesis proved challenging due to competitive aminal formation, rationalised using control experiments and computational modelling. The use of an additional amine was found to increase conversion to the desired cage

Assessment of the clinical utility of adding common single nucleotide polymorphism genetic scores to classical risk factor algorithms in coronary heart disease risk prediction in UK men

UK Medical Research Council; British Heart Foundation

Nano-Scale Characterization of a Piezoelectric Polymer (Polyvinylidene Difluoride, PVDF)

The polymer polyvinylidene difluoride (PVDF) has unique piezoelectric properties favorable for Micro-Electro-Mechanical Systems (MEMS) and Nano-Electro-Mechanical Systems (NEMS) applications. In the present research, we conducted nanometer-length scale characterization of this material using several high-resolution techniques. Specifically, we used an atomic force microscope (AFM) to study the nanoand microstructures of the PVDF under stress and to measure their nanoscale conductivity and piezoelectricity. We found that the surface morphology, electronic structure, and microstructure are profoundly affected under electrical potential. Such a behavior is important for the properties and performance of MEMS and NEMS

Influence of Genetic Risk Factors on Coronary Heart Disease Occurrence in Afro-Caribbeans

Background Despite excessive rates of cardiovascular risk factors such as hypertension, diabetes, and obesity, Afro-Caribbeans have lower mortality rates from coronary heart disease (CHD) than do whites. This study evaluated the association of genetic risk markers previously identified in whites and CHD in Afro-Caribbeans. Methods We studied 537 Afro-Caribbean individuals (178 CHD cases and 359 controls) who were genotyped for 19 CHD-related single-nucleotide polymorphisms (SNPs). A genetic risk score (GRS) incorporating the 19 SNPs was calculated. These participants were compared with 1360 white individuals from the Second Northwick Park Heart Study. Results In Afro-Caribbeans, patients with CHD had higher rates of hypertension (78.7% vs 30.1%), hypercholesterolemia (52.8% vs 15.0%), and diabetes (53.9% vs 14.8%) and were more often men (64.0% vs 43.7%) and smokers (27.5% vs 13.4%) compared with non-CHD controls (all P < 0.001). The GRS was higher in Afro-Caribbeans with CHD than in those without CHD (13.90 vs 13.17; P < 0.001) and was significantly associated with CHD after adjustment for cardiovascular risk factors, with an odds ratio of 1.40 (95% confidence interval, 1.09-1.80) per standard deviation change. There were significant differences in allelic distributions between the 2 ethnic groups for 14 of the 19 SNPs. The GRS was substantially lower in Afro-Caribbean controls compared with white controls (13.17 vs 16.59; P < 0.001). Conclusions This study demonstrates that a multilocus GRS composed of 19 SNPs associated with CHD in whites is a strong predictor of the disease in Afro-Caribbeans. The differences in CHD occurrence between Afro-Caribbeans and whites might be a result of significant discrepancies in common gene variant distribution