Sedentary Behavior and Diabetes Risk Among Women Over the Age of 65 Years: The OPACH Study

OBJECTIVE: To evaluate whether sedentary time (ST) and/or sedentary behavior patterns are related to incident diabetes in the U.S.'s oldest age-groups. RESEARCH DESIGN AND METHODS: Women without physician-diagnosed diabetes (n = 4,839, mean ± SD age = 79 ± 7 years) wore accelerometers for ≥4 days and were followed up to 6 years for self-reported newly diagnosed diabetes requiring treatment with medications. Hazard ratios (HRs) for incident diabetes were estimated across quartiles of accelerometer-measured ST and mean bout duration with use of Cox proportional hazards models. We conducted isotemporal substitution analyses using Cox regression and tested associations with risk for diabetes after statistically replacing ST with light physical activity (PA) or moderate-to-vigorous PA (MVPA) and after replacing light PA with MVPA. RESULTS: During 20,949 person-years, 342 diabetes cases were identified. Women in ST quartile (Q)2, Q3, and Q4 (vs. Q1) had incident diabetes HR 1.20 (95% CI 0.87-1.65), 1.33 (0.97-1.82), and 1.21 (0.86-1.70); Ptrend = 0.04. Respective HRs following additional adjustment for BMI and MVPA were 1.04 (95% CI 0.74-1.47), 1.04 (0.72-1.50), and 0.85 (0.56-1.29); Ptrend = 0.90. Fully adjusted isotemporal substitution results indicated that each 30 min of ST replaced with MVPA (but not light PA) was associated with 15% lower risk for diabetes (HR 0.85 [95% CI 0.75-0.96]; P = 0.01); the HR for replacing 30 min of light PA with MVPA was 0.85 (95% CI 0.73-0.98); P = 0.03. Mean bout duration was not associated with incident diabetes. CONCLUSIONS: Statistically replacing ST or light PA with MVPA was associated with lower diabetes risk in older women. While reducing ST is important for several health outcomes, results indicate that to reduce diabetes risk among older adults, the primary public health focus should be on increasing MVPA

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Practically convenient and industrially-aligned methods for iridium-catalysed hydrogen isotope exchange processes

The use of alternative solvents in the iridium-catalysed hydrogen isotope exchange reaction with developing phosphine/NHC Ir(I) complexes has identified reaction media which are more widely applicable and industrially acceptable than the commonly employed chlorinated solvent, dichloromethane. Deuterium incorporation into a variety of substrates has proceeded to deliver high levels of labelling (and regioselectivity) in the presence of low catalyst loadings and over short reaction times. The preparative outputs have been complemented by DFT studies to explore ligand orientation, as well as solvent and substrate binding energies within the catalyst system

Highly active iridium (I) complexes for catalytic hydrogen isotope exchange

This poster, presented at the 16th annual symposium of the International Isotope Society's United Kingdom Group took place at the Wellcome Genome Campus, Hinxton, Cambridge, UK on 1st November 2007, reveals a series of novel iridium (I) complexes of type 2, and highlights their considerable efficiency and general applicability in the field of hydrogen isotope exchange, with levels as low as only 0.5 mol% catalyst loading over short reaction times being required to deliver extremely high levels of labelling

Probability distributions for dichotomous choice contingent valuation

SIGLEAvailable from British Library Document Supply Centre-DSC:3490.1797(CSERGE-WP-GEC--96-08) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Bound and path effects in multiple-bound dichotomous choice contingent valuation

SIGLEAvailable from British Library Document Supply Centre-DSC:3490.1797(99-12) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

New Zealand freshwater management and agricultural impacts

In New Zealand, it is increasingly recognised, including by government, that water resource allocation and water quality are issues of national importance. Agriculture is frequently portrayed by public media as a major user of water and a major contributor to worsening water quality. We outline the water management systems in New Zealand, and the use of water by agriculture. Official reports on agriculture's impact on New Zealand water availability and quality are summarised. We report how the New Zealand public perceive water, its management, and the roles of agriculture in water issues. Data from a nationwide mail survey were analysed to determine how New Zealanders assess the state of New Zealand lakes, rivers and streams, and aquifers, the performance of three agencies responsible for management of freshwater resources, and willingness to fund stream enhancement. We provide brief explanations for the failures of water resource management in New Zealand and report on options, including community-based responses that might address some of the mounting public, scientific, and government concerns about trends in water quantity and quality. A willingness to pay proposition, concerning riparian areas, included in the nationwide survey provides some evidence that the public are willing to pay for improved waterway management. Relevant non-market valuation studies also indicate that the public places considerable value on preservation values of water in New Zealand. Copyright Australian Agricultural and Resource Economics Society Inc. and Blackwell Publishing Ltd 2006.