Evaluation of three accelerometer devices for physical activity measurement amongst south Asians and Europeans

We recruited 62 South Asians and 40 Europeans aged 25 to 75 years, to assess the potential validity of three physical activity accelerometers for use amongst South Asians. Participants completed an exercise treadmill test (following Bruce protocol) while wearing the 3 accelerometers: Actigraph GT3X+ [GT3X+] and Geneactiv [GA] on ankle, waist and wrist; and Actiheart [AH] on chest. We compared relationships between energy expenditure (EE) measured by accelerometers (Measured) and actual EE on the treadmill (Actual) in the two ethnicities and tested for potential confounding effects. All accelerometers under-reported EE. Difference between Measured and Actual EE was smallest for GT3X+ankle (Measured – Actual at peak exercise [Mets]: GT3X+ankle –6.52 (1.77); GT3X+waist –8.46 (1.29); GT3X+wrist –11.17 (1.03); GAankle –8.17 (1.19); GAwaist –10.24 (0.64); GAwrist –11.21 (1.10); AHchest –9.09 (1.43), P 0.05). Relationship between Measured and Actual EE was not influenced by age, gender, height, waist, weight or waist-hip ratio (all P > 0.05). Amongst the devices and positions tested, GT3X+ankle is the most accurate device for measuring EE during an exercise treadmill test. Accelerometer performance is similar in South Asians and Europeans and is not influenced by anthropometric differences between the two populations

Risk factors for progression to blindness in high tension primary open angle glaucoma: Comparison of blind and nonblind subjects

Karanjit S Kooner1, Mohannad AlBdoor1, Byung J Cho3, Beverley Adams-Huet21Department of Ophthalmology, 2Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA; 3Konkuk University Hospital, Seoul, KoreaAims: To determine which risk factors for blindness were most critical in patients diagnosed with high tension primary open angle glaucoma (POAG) in a large ethnically diverse population managed with a uniform treatment strategy.Methods: A longitudinal observational study was designed to follow 487 patients (974 eyes) with POAG for an average of 5.5 ± 3.6 years. Detailed ocular and systemic information was collected on each patient and updated every six months. For this study, blindness was defined as visual acuity of 20/200 or worse and/or visual field less than 20° in either eye. Known risk factors were compared between patients with blindness in at least one eye versus nonblind patients.Results: The patients with blindness had on average: higher intraocular pressure (IOP, mmHg): (24.2 ± 11.2 vs. 22.1 ± 7.7, p = 0.03), wide variation of IOP in the follow-up period (5.9 vs. 4.1 mmHg, p = 0.031), late detection (p = 0.006), poor control of IOP (p < 0.0001), and noncompliance (p < 0.0003). Other known risk factors such as race, age, myopia, family history of glaucoma, history of ocular trauma, hypertension, diabetes, vascular disease, smoking, alcohol abuse, dysthyoidism, and steroid use were not significant.Conclusions: The most critical factors associated with the development of blindness among our patients were: elevated initial IOP, wide variations and poor control of IOP, late detection of glaucoma, and noncompliance with therapy.Keywords: primary open angle glaucoma, blindness, intraocular pressure, risk factors, and noncomplianc

South Asians have elevated postexercise blood pressure and myocardial oxygen consumption compared to Europeans despite equivalent resting pressure

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Stroke mortality rate is higher in South Asians than in Europeans, despite equivalent or lower resting blood pressure (BP). Elevated recovery BP after exercise predicts stroke, independently of resting values. We hypothesized that South Asians would have adverse postexercise hemodynamics and sought explanations for this. METHODS AND RESULTS: A population-based sample of 147 European and 145 South Asian middle-aged men and women performed the Dundee 3-minute step test. Cardiovascular risk factors were measured. BP, heart rate, and rate-pressure product, a measure of myocardial oxygen consumption, were compared. With 90% power and 5% significance, we could detect a difference of 0.38 of a standard deviation in any outcome measure. Resting systolic BP was similar in South Asians (144 mm Hg) and Europeans (142 mm Hg) (P=0.2), as was exercise BP (P=0.4). However, recovery systolic BP at 3 minutes after exercise was higher in South Asians by 4.3 mm Hg (95% confidence interval [CI], 0.2 to 8.3 mm Hg; P=0.04). This effect persisted when adjusted for exercise BP and work effort (5.4 mm Hg [95% CI, 2.2 to 8.7 mm Hg; P=0.001]). Adjustment for baroreflex insensitivity and greater aortic stiffness in South Asians contributes greatly to attenuating this ethnic difference (1.9 mm Hg [95% CI, -0.9 to 4.6 mm Hg; P=0.4]). Similarly, rate-pressure product recovery after exercise was impaired in South Asians by 735 mm Hg/min (95% CI, 137 to 1334 mm Hg/min; P=0.02); again, adjustment for baroreflex insensitivity and aortic stiffness attenuated this difference (261 mm Hg/min [95% CI, -39 to 561 mm Hg/min; P=0.3]). CONCLUSION: Postexercise recovery of BP and rate-pressure product is impaired in South Asians compared to Europeans even though resting and exercise BP are similar. This is associated with the autonomic dysfunction and aortic stiffness in South Asians.The British Heart Foundation funded this project. Drs Chaturvedi, Kooner, John Chambers, and Hughes received support from the NIHR (UK National Institute for Health Research) Biomedical Research Centre. Dr Shore received support from the Peninsula NIHR Clinical Research Facility

The South Asian genome

Genetics of disease Microarrays Variant genotypes Population genetics Sequence alignment AllelesThe genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers)

Coronary heart disease in Indian Asians.

The Indian Asian population accounts for a fifth of all global deaths from coronary heart disease (CHD). CHD deaths on the Indian subcontinent have doubled since 1990, and are predicted to rise a further 50% by 2030. Reasons underlying the increased CHD mortality among Indian Asians remain unknown. Although conventional cardiovascular risk factors contribute to CHD in Indian Asians as in other populations, these do not account for their increased risk. Type-2 diabetes, insulin resistance and related metabolic disturbances are more prevalent amongst Indian Asians than Europeans, and have been proposed as major determinants of higher CHD risk among Indian Asians. However, this view is not supported by prospective data. Genome-wide association studies have not identified differences in allele frequencies or effect sizes in known loci to explain the increased CHD risk in Indian Asians. Limited knowledge of mechanisms underlying higher CHD risk amongst Indian Asians presents a major obstacle to reducing the burden of CHD in this population. Systems biology approaches such as genomics, epigenomics, metabolomics and transcriptomics, provide a non-biased approach for discovery of novel biomarkers and disease pathways underlying CHD. Incorporation of these omic approaches in prospective Indian Asian cohorts such as the London Life Sciences Population Study (LOLIPOP) provide an exciting opportunity for the identification of new risk factors underlying CHD in this high risk population

Compactifications of the Klebanov-Witten CFT and new AdS 3 backgrounds

In this paper we find various new backgrounds in Type IIB, IIA and M-theory with an $AdS_3$-factor. The solutions are smooth and preserve small amounts of SUSY. These new backgrounds are found by application of non-Abelian T-duality (sometimes combined with T-duality) on the supergravity solution dual to the Klebanov-Witten CFT compactified to two dimensions. The field theory aspects encoded by these backgrounds are studied. We give a detailed account of conserved charges, central charges, entanglement entropy and Wilson loops. Further, we present a possible field theory interpretation for our backgrounds.Comment: 38 pages plus appendices, 6 figure

Mathematical modelling of the HIF-1 mediated hypoxic response in tumours

Solid tumours frequently display areas of low oxygen concentration (hypoxia) due to their uncontrolled proliferation and the fact that the new blood vessels they develop are irregular and have poor blood flow. The capacity for a tumour to grow therefore crucially depends on its ability to adjust to hypoxic conditions. It is frequently observed that the hypoxia response pathways, such as angiogenesis (formation of new blood vessels) and glycolysis (use of glucose, rather than oxygen, metabolism) are adapted in tumour cells to allow for aggressive growth in hypoxic conditions. The response pathways are also often upregulated in normoxic conditions. The transcription factor Hypoxia-Inducible Factor 1 (HIF-1) has been found to control the expression of a battery of genes that are crucially involved in the hypoxic response, including key angiogenic growth factors and glycolytic enzymes. Intratumoural hypoxia and HIF-1 overexpression are both associated with poor patient prognosis. In this paper, we extend an ordinary differential equation (ODE) model by Kohn et al, Mol. Biol. of the Cell, 15:3042(2004)that measures HIF-1 mediated transcription activation as a function of oxygen concetration [1]. The model considers a core sub-system of elements from the HIF-1 regulatory network,and in so doing highlights the stabilisation pathway of the oxygen-regulated HIF-1alpha subunit. In normoxic conditions HIF-1alpha undergoes a post-translational modification known as hydroxylation which allows HIF-1alpha to be targeted for degradation. In hypoxic conditions, the hydroxylation reaction does not occur, leading to stabilisation of the HIF-1alpha protein, formation of the HIF-1 complex and activation of gene transcription. We extend the Kohn model by including mechanisms that may account for the rapid attenuation of the hypoxic response upon reoxygenation of cells, after a period of hypoxia. Our results show good qualitative agreement with experimentally obtained hypoxia dose-response curves by capturing all the important characteristics of the curve

Ex-smokers with and without COPD: Investigating CT Pulmonary Vascular, Airway, Pulmonary Artery and Aorta Measurements

RATIONALE: Pulmonary hypertension is characterized by increased pressure in the pulmonary artery, and is a key contributor to worsening symptoms in individuals with chronic obstructive pulmonary disease (COPD). The pulmonary artery to aorta diameter ratio (PA:Ao), measured using computed tomography (CT), is a biomarker of pulmonary hypertension; however, longitudinal changes in this measurement and its relationship to pulmonary vascular and airway structural changes is not well understood. Our objective was to investigate longitudinal changes in PA:Ao and its relationship with CT pulmonary vascular and airway abnormalities, airflow limitation and exercise-capacity

Polymorphisms in the WNK1 gene are asociated with blood pressure variation and urinary potassium excretion

WNK1 - a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control - is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23–4.9), DBP 1.9 mmHg (95%CI:0.7–3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0–1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7×10−3, combined with BRIGHT data-set p = 2×10−4, n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p10 mmHg reduction) and risk for hypertension (OR<0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH

Application of statistical and functional methodologies for the investigation of genetic determinants of coronary heart disease biomarkers: lipoprotein lipase genotype and plasma triglycerides as an exemplar

Genome-wide association studies have proved very successful in identifying novel single-nucleotide polymorphisms (SNPs) associated with disease or traits, but the related, functional SNP is usually unknown. In this paper, we describe a methodology to locate and validate candidate functional SNPs using lipoprotein lipase (LPL), a gene previously associated with triglyceride levels, as an exemplar. Two thousand seven hundred and eighty-six healthy middle-aged men from the NPHSII UK prospective study (with up to six measures of plasma lipid levels) were genotyped for 20 LPL tagging (t)SNPs using Illumina Bead technology. Using model-selection procedures and haplotypes, we identified eight SNPs that consistently maximized the fit of the model to the phenotype. Fifteen SNPs in high linkage disequilibrium with these were identified, and functional assays were carried out on all 23 SNPs. Electrophoretic mobility shift assay (EMSA) was used to identify SNPs that had the potential to alter DNA–protein interactions, reducing the number to eight possible candidate SNPs. These were examined for ability to alter expression using a luciferase reporter assay, and two regulatory SNPs, showing genotype differences, rs327 and rs3289, were identified. Finally, multiplexed-competitor-EMSA (MC-EMSA) and supershift EMSA identified FOXA2 to rs327T, and CREB-binding protein (CBP) and CCAAT displacement protein (CDP) to rs3289C as the factors responsible for transcription binding. We have identified two novel candidate functional SNPs in LPL and presented a procedure aimed to efficiently detect SNPs potentially causal to genetic association. We believe that this methodology could be successfully applied to future re-sequencing data