Adiponectin multimers, body weight and markers of cardiovascular risk in adolescence: Northern Ireland Young Hearts Project:Northern Ireland Young Hearts Project

Background:Research examining the relationship between adiponectin (AN) isoforms, body weight and cardiovascular (CV) risk factors is limited, particularly in younger populations. Objectives:To investigate the inter-relationships between AN isoforms and CV risk factors, and their dependence on body weight status, in adolescents. Design:Blood samples from 92 obese, 92 overweight and 92 normal weight age- and sex-matched adolescents were analysed for traditional cardiovascular disease (CVD) risk biomarkers and also total, high molecular weight (HMW), medium and low molecular weight (LMW) AN. Results:A significant inverse association was observed between total and HMW AN and waist-hip ratio (P=0.015, P=0.006, respectively), triglycerides (P=0.003, P=0.003, respectively) and systolic blood pressure (P=0.012, P=0.024, respectively) and a significant positive association with high-density lipoprotein (P<0.001, P<0.001, respectively) in multi-adjusted analyses. There was no evidence of a relationship between multimeric AN and high-sensitivity C-reactive protein. There was also little evidence of a relationship between LMW AN and CVD risk factors. There was a strong, body mass index (BMI)-independent, association between AN, CVD biomarkers and the hypertriglyceridemic waist phenotype. Conclusion:Prominent, BMI-independent associations between total and HMW AN, but not LMW AN, and CVD risk factors were already evident in this young population. This research in adolescents supports the contention that AN subfractions may have different biological actions. These associations in apparently healthy adolescents suggest an important role for AN and its subfractions in the pathogenesis of metabolic syndrome traits and indicate that the potential for total or HMW AN to act as early universal biomarkers of CV risk warrants further study.

Hazardous alcohol consumption is associated with increased levels of B-type natriuretic peptide: evidence from two population-based studies

Russia has very high mortality from cardiovascular disease (CVD), with evidence that heavy drinking may play a role. To throw further light on this association we have studied the association of alcohol with predictors of CVD risk including B-type natriuretic peptide (BNP). Levels of BNP increase primarily in response to abnormal cardiac chamber wall stretch which can occur both as a result of atherosclerosis as well as due to other types of damage to the myocardium. No previous population-based studies have investigated the association with alcohol. We analysed cross-sectional data on drinking behaviour in 993 men aged 25-60 years from the Izhevsk Family Study 2 (IFS2), conducted in the Russian city of Izhevsk in 2008-2009. Relative to non-drinkers, men who drank hazardously had an odds ratio (OR) of being in the top 20 % of the BNP distribution of 4.66 (95 % CI 2.13, 10.19) adjusted for age, obesity, waist-hip ratio, and smoking. Further adjustment for class of hypertension resulted in only slight attenuation of the effect, suggesting that this effect was not secondary to the influence of alcohol on blood pressure. In contrast hazardous drinking was associated with markedly raised ApoA1 and HDL cholesterol levels, but had little impact on levels of ApoB and LDL cholesterol. Similar but less pronounced associations were found in the Belfast (UK) component of the PRIME study conducted in 1991. These findings suggest that the association of heavy drinking with increased risk of cardiovascular disease may be partly due to alcohol-induced non-atherosclerotic damage to the myocardium.

Shared common variants in prostate cancer and blood lipids

BACKGROUND: Epidemiological and clinical studies suggest comorbidity between prostate cancer (PCA) and cardiovascular disease (CVD) risk factors. However, the relationship between these two phenotypes is still not well understood. Here we sought to identify shared genetic loci between PCA and CVD risk factors.

METHODS: We applied a genetic epidemiology method based on conjunction false discovery rate (FDR) that combines summary statistics from different genome-wide association studies (GWAS), and allows identification of genetic overlap between two phenotypes. We evaluated summary statistics from large, multi-centre GWA studies of PCA (n=50 000) and CVD risk factors (n=200 000) [triglycerides (TG), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, systolic blood pressure, body mass index, waist-hip ratio and type 2 diabetes (T2D)]. Enrichment of single nucleotide polymorphisms (SNPs) associated with PCA and CVD risk factors was assessed with conditional quantile-quantile plots and the Anderson-Darling test. Moreover, we pinpointed shared loci using conjunction FDR.

RESULTS: We found the strongest enrichment of P-values in PCA was conditional on LDL and conditional on TG. In contrast, we found only weak enrichment conditional on HDL or conditional on the other traits investigated. Conjunction FDR identified altogether 17 loci; 10 loci were associated with PCA and LDL, 3 loci were associated with PCA and TG and additionally 4 loci were associated with PCA, LDL and TG jointly (conjunction FDR <0.01). For T2D, we detected one locus adjacent to HNF1B.

CONCLUSIONS: We found polygenic overlap between PCA predisposition and blood lipids, in particular LDL and TG, and identified 17 pleiotropic gene loci between PCA and LDL, and PCA and TG, respectively. These findings provide novel pathobiological insights and may have implications for trials using targeting lipid-lowering agents in a prevention or cancer setting.

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.

Opportunity cost based analysis of corporate eco-efficiency: A methodology and its application to the CO2-efficiency of German companies

In this paper, we propose the return-to-cost-ratio (RCR) as an alternative approach to the analysis of operational eco-efficiency of companies based on the notion of opportunity costs. RCR helps to overcome two fundamental deficits of existing approaches to eco-efficiency. (1) It translates eco-efficiency into managerial terms by applying the well-established notion of opportunity costs to eco-efficiency analysis. (2) RCR allows to identify and quantify the drivers behind changes in corporate eco-efficiency. RCR is applied to the analysis of the CO2-efficiency of German companies in order to illustrate its usefulness for a detailed analysis of changes in corporate eco-efficiency as well as for the development of effective environmental strategies. (C) 2010 Elsevier Ltd. All rights reserved.

Novel linkage to chromosome 20p using latent classes of psychotic illness in 270 Irish high-density families

Background: Several lines of evidence suggest that the clinical heterogeneity of schizophrenia is due to genetic heterogeneity. Genetic heterogeneity may decrease the signal-to-noise ratio in linkage and association studies. Therefore, linkage studies of clinically homogeneous classes of psychotic illness may result in greater power to detect at least some loci.

A high C/O ratio and weak thermal inversion in the atmosphere of exoplanet WASP-12b

The carbon-to-oxygen ratio (C/O) in a planet provides critical information about its primordial origins and subsequent evolution. A primordial C/O greater than 0.8 causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth; the atmosphere can also differ from those in the Solar System. The solar C/O is 0.54 (ref. 3). Here we report an analysis of dayside multi-wavelength photometry of the transiting hot-Jupiter WASP-12b (ref. 6) that reveals C/O>=1 in its atmosphere. The atmosphere is abundant in CO. It is depleted in water vapour and enhanced in methane, each by more than two orders of magnitude compared to a solar-abundance chemical-equilibrium model at the expected temperatures. We also find that the extremely irradiated atmosphere (T>2,500K) of WASP-12b lacks a prominent thermal inversion (or stratosphere) and has very efficient day-night energy circulation. The absence of a strong thermal inversion is in stark contrast to theoretical predictions for the most highly irradiated hot-Jupiter atmospheres.

Distance limits to intermediate- and high-velocity clouds

We present optical spectra of 403 stars and quasi-stellar objects in order to obtain distance limits towards intermediate- and high-velocity clouds (IHVCs), including new Fibre-fed Extended Range Optical Spectrograph (FEROS) observations plus archival ELODIE, FEROS, High Resolution Echelle Spectrometer (HIRES) and Ultraviolet and Visual Echelle Spectrograph (UVES) data. The non-detection of Ca II K interstellar (IS) absorption at a velocity of −130 to −60 km s−1 towards HDE 248894 (d ∼ 3 kpc) and HDE 256725 (d ∼ 8 kpc) in data at signal-to-noise ratio (S/N) > 450 provides a new firm lower distance limit of 8 kpc for the anti-centre shell HVC. Similarly, the non-detection of Ca II K IS absorption towards HD 86248 at S/N ∼ 500 places a lower distance limit of 7.6 kpc for Complex EP, unsurprising since this feature is probably related to the Magellanic System. The lack of detection of Na I D at S/N = 35 towards Mrk 595 puts an improved upper limit for the Na I column density of log (NNaD <) 10.95 cm−2 towards this part of the Cohen Stream where Ca II was detected by Wakker et al. Absorption at ∼ −40 km s−1 is detected in Na I D towards the Galactic star PG 0039+049 at S/N = 75, placing a firm upper distance limit of 1 kpc for the intermediate-velocity cloud south (IVS), where a tentative detection had previously been obtained by Centurion et al. Ca ´ II K and Na I D absorption is detected at −53 km s−1 towards HD 93521, which confirms the upper distance limit of 2.4 kpc for part of the IV arch complex obtained using the International Ultraviolet Explorer (IUE) data by Danly. Towards HD 216411 in Complex H a non-detection in Na D towards gas with log(NH I) = 20.69 cm−2 puts a lower distance limit of 6.6 kpc towards this HVC complex. Additionally, Na I D absorption is detected at −43.7 km s−1 in the star HD 218915 at a distance of 5.0 kpc in gas in the same region of the sky as Complex H. Finally, the Na I/Ca II and Ca II/H I ratios of the current sample are found to lie in the range observed for previous studies of IHVCs.

Resonant Rayleigh light scattering response of individual Au nanoparticles to antigen--antibody interaction

A proof-of-concept study was reported on analysis of antigen–antibody recognition based on resonant Rayleigh scattering response of single Au nanoparticles in an imaging chamber. As benefited by a traditional dark-field microscope and a spectrograph, individual Au nanoparticles (30 nm) were observed with high signal-to-noise ratio and they were effectively utilized to monitor changes in refractive index induced by specific binding of the adsorbates. Using PSA antigen as a model, a LSPR ?max shift of about 2.85 nm was recorded for a molecular binding corresponding to 0.1 pg ml-1 of the protein biomarker. This result successfully demonstrates a non-labeling detection system for proteins as well as thousands of different chemical or biological species, and it possesses a great potential as a sensitive, on-chip and multiplexing detection.

Design methodology for low power and arametric robustness through output-quality modulation:Application to color-interpolation filtering

Power dissipation and robustness to process variation have conflicting design requirements. Scaling of voltage is associated with larger variations, while Vdd upscaling or transistor upsizing for parametric-delay variation tolerance can be detrimental for power dissipation. However, for a class of signal-processing systems, effective tradeoff can be achieved between Vdd scaling, variation tolerance, and output quality. In this paper, we develop a novel low-power variation-tolerant algorithm/architecture for color interpolation that allows a graceful degradation in the peak-signal-to-noise ratio (PSNR) under aggressive voltage scaling as well as extreme process variations. This feature is achieved by exploiting the fact that all computations used in interpolating the pixel values do not equally contribute to PSNR improvement. In the presence of Vdd scaling and process variations, the architecture ensures that only the less important computations are affected by delay failures. We also propose a different sliding-window size than the conventional one to improve interpolation performance by a factor of two with negligible overhead. Simulation results show that, even at a scaled voltage of 77% of nominal value, our design provides reasonable image PSNR with 40% power savings. © 2006 IEEE.

Design methodology to trade off power, output quality and error resiliency: Application to color interpolation filtering

Power dissipation and tolerance to process variations pose conflicting design requirements. Scaling of voltage is associated with larger variations, while Vdd upscaling or transistor up-sizing for process tolerance can be detrimental for power dissipation. However, for certain signal processing systems such as those used in color image processing, we noted that effective trade-offs can be achieved between Vdd scaling, process tolerance and "output quality". In this paper we demonstrate how these tradeoffs can be effectively utilized in the development of novel low-power variation tolerant architectures for color interpolation. The proposed architecture supports a graceful degradation in the PSNR (Peak Signal to Noise Ratio) under aggressive voltage scaling as well as extreme process variations in. sub-70nm technologies. This is achieved by exploiting the fact that some computations are more important and contribute more to the PSNR improvement compared to the others. The computations are mapped to the hardware in such a way that only the less important computations are affected by Vdd-scaling and process variations. Simulation results show that even at a scaled voltage of 60% of nominal Vdd value, our design provides reasonable image PSNR with 69% power savings.

Protocol-driven adjustment of ocular hypotensive medication in patients at low risk of conversion to glaucoma

AIM: To investigate the safety and potential savings of decreasing medication use in low-risk patients with ocular hypertension (OH).
METHODS: Patients with OH receiving pressure-lowering medication identified by medical record review at a university hospital underwent examination by a glaucoma specialist with assessment of visual field (VF), vertical cup-to-disc ratio (vCDR), central corneal thickness and intraocular pressure (IOP). Subjects with estimated 5-year risk of glaucoma conversion <15% were asked to discontinue ≥1 medication, IOP was remeasured 1 month later and risk was re-evaluated at 1 year.
RESULTS: Among 212 eyes of 126 patients, 44 (20.8%) had 5-year risk >15% and 14 (6.6%) had unreliable baseline VF. At 1 month, 15 patients (29 eyes, 13.7%) defaulted follow-up or refused to discontinue medication and 11 eyes (5.2%) had risk >15%. The remaining 69 patients (107 eyes, 50.7%) successfully discontinued 141 medications and completed 1-year follow-up. Mean IOP (20.5±2.65 mm Hg vs 20.3±3.40, p=0.397) did not change, though mean VF pattern SD (1.58±0.41 dB vs 1.75±0.56 dB, p=0.001) and glaucoma conversion risk (7.31±3.74% vs 8.76±6.28%, p=0.001) increased at 1 year. Mean defect decreased (-1.42±1.60 vs -1.07±1.52, p=0.022). One eye (0.47%) developed a repeatable VF defect and 13 eyes (6.1%) had 5-year risk >15% at 1 year. The total 1-year cost of medications saved was US$4596.
CONCLUSIONS: Nearly half (43.9%) of low-risk OH eyes in this setting could safely reduce medications over 1 year, realising substantial savings.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Resistance of alkali activated slag concretes to chloride environments based on chloride penetration measurements

ABSTRACT

One of the binder systems with low environmental footprint is alkali activated slag concretes (AASC), made by adding alkalis such as sodium hydroxide and sodium silicate to industrial by-products such as ground granulated blast furnace slag (GGBS). Whilst they have the similar behaviour as that of traditional cement systems in terms of strength and structural behaviour, AASC do exhibit superior performance in terms of abrasion and acid resistance and fire protection.
In this article, the authors focus their attention on chloride ingress into different grades of AASC. The mix variables in AASC included water-to-binder, binder to aggregate ratio, percentage of alkali and the SiO2/Na2O ratio (silica modulus, Ms). The first challenge is to get mixes for different range of workability (with slump values from 40mm to 240mm) and reasonable early age and long term compressive strength according to each one. Then the chloride diffusion and migration in those mixes were measured and compared with same normal concretes in the existed literature based on chloride penetration depth. Comparing the chloride ingress between tradition concretes and AASCs is worthwhile to prove the possibility of increasing concrete lifetime in proximity to sea and deciding while such concretes are practical for use. Findings show that compared to the PC concretes, the AAS concretes have lower rate of chloride ingress.

Resistance of alkali activated slag concretes to chloride environments

ABSTRACT: Researchers are focusing their attention on alternative binder systems using 100% supplementary cementitious materials as it allows better control over the microstructure formation and low to moderate environmental footprint. One such system being considered is alkali activated slag concretes (AASC), made by adding alkalis such as sodium hydroxide and sodium silicate to ground granulated blast furnace slag (GGBS). Whilst they have a similar behaviour as that of traditional cement systems in terms of strength and structural behaviour, AASC are reported to exhibit superior performance in terms of abrasion,acid resistance and fire protection.
In this article, the authors investigate chloride ingress into different grades of AASC. The mix variables in AASC included water to binder, and binder to aggregate ratio, percentage of alkali and the SiO2/Na2O ratio (silica modulus, Ms). The first challenge was to develop mixes for different range of workability (with slump values from 40mm to 240mm) and reasonable early age and long term compressive strength. Further chloride ingress into those mixes were assessed and compared with the data from normal concretes based on literature. Findings show that compared to the PC concretes, the AAS concretes have lower rate of chloride ingress.