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

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)

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

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

Management of Acute Coronary Syndromes During the Coronavirus Disease 2019 Pandemic: Deviations from Guidelines and Pragmatic Considerations for Patients and Healthcare Workers

Coronavirus disease 2019 (COVID-19) is forcing cardiology departments to rapidly adapt existing clinical guidelines to a new reality and this is especially the case for acute coronary syndrome pathways. In this focused review, the authors discuss how COVID-19 is affecting acute cardiology care and propose pragmatic guideline modifications for the diagnosis and management of acute coronary syndrome patients, particularly around the appropriateness of invasive strategies as well as length of hospital stay. The authors also discuss the use of personal protective equipment for healthcare workers in cardiology. Based on shared global experiences and growing peer-reviewed literature, it is possible to put in place modified acute coronary syndrome treatment pathways to offer safe pragmatic decisions to patients and staff

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity

A Replication Study of GWAS-Derived Lipid Genes in Asian Indians: The Chromosomal Region 11q23.3 Harbors Loci Contributing to Triglycerides

Recent genome-wide association scans (GWAS) and meta-analysis studies on European populations have identified many genes previously implicated in lipid regulation. Validation of these loci on different global populations is important in determining their clinical relevance, particularly for development of novel drug targets for treating and preventing diabetic dyslipidemia and coronary artery disease (CAD). In an attempt to replicate GWAS findings on a non-European sample, we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638) in our Asian Indian cohort from the Sikh Diabetes Study (SDS) comprising 3,781 individuals (2,902 from Punjab and 879 from the US). Two of the six SNPs examined showed convincing replication in these populations of Asian Indian origin. Our study confirmed a strong association of CETP rs3764261 with high-density lipoprotein cholesterol (HDL-C) (p = 2.03×10−26). Our results also showed significant associations of two GWAS SNPs (rs964184 and rs12286037) from BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG) levels in this Asian Indian cohort (rs964184: p = 1.74×10−17; rs12286037: p = 1.58×10−2). We further explored 45 SNPs in a ∼195 kb region within the chromosomal region 11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes) in 8,530 Asian Indians from the London Life Sciences Population (LOLIPOP) (UK) and SDS cohorts. Five more SNPs revealed significant associations with TG in both cohorts individually as well as in a joint meta-analysis. However, the strongest signal for TG remained with BUD13-ZNF259 (rs964184: p = 1.06×10−39). Future targeted deep sequencing and functional studies should enhance our understanding of the clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG) and, consequently, diabetes and CAD

Interventions to increase vaccination against COVID-19, influenza and pertussis during pregnancy: a systematic review and meta-analysis

Background Pregnant women and their babies face significant risks from three vaccine-preventable diseases: COVID-19, influenza, and pertussis. However, despite these vaccines' proven safety and effectiveness, vaccine uptake during pregnancy remains low. Methods We conducted a systematic review (PROSPERO CRD42023399488; January 2012 – December 2022 following PRISMA guidelines) of interventions to increase COVID-19/influenza/pertussis vaccination in pregnancy. We searched nine databases, including grey literature. Two independent investigators extracted data; discrepancies were resolved by consensus. Meta-analyses were conducted using random-effects models to estimate pooled effect sizes. Heterogeneity was assessed using the I2 statistics. Results Out of 2681 articles, we identified 39 relevant studies (n=168,262 participants) across nine countries. Fifteen studies (39%) were randomised controlled trials (RCTs); the remainder were observational cohort, quality-improvement or cross-sectional studies. The quality of 18% (7/39) was strong. Pooled results of interventions to increase influenza vaccine uptake (18 effect estimates from 12 RCTs) showed the interventions were effective but had a small effect (Risk ratio = 1.07, 95%CI 1.03, 1.13). However, pooled results of interventions to increase pertussis vaccine uptake (10 effect estimates from six RCTs) showed no clear benefit (Risk ratio = 0.98, 95%CI 0.94, 1.03). There were no relevant RCTs for COVID-19. Interventions addressed the “three Ps”: patient-, provider- and policy-level strategies. At patient level, clear recommendations from healthcare professionals backed by text reminders/written information were strongly associated with increased vaccine uptake, especially tailored face-to-face interventions, which addressed women’s concerns, dispelled myths and highlighted the benefits. Provider-level interventions included educating healthcare professionals about vaccines’ safety and effectiveness and reminders to offer vaccinations routinely. Policy-level interventions included financial incentives, mandatory vaccination data fields in electronic health records, and ensuring easy availability of vaccinations. Conclusions Interventions had a small effect on increasing influenza vaccination. Training healthcare providers to promote vaccinations during pregnancy is crucial, and could be enhanced by utilising mobile health technologies