Stochastic analysis of exit fluid temperature records from the active TAG hydrothermal mound (Mid-Atlantic Ridge, 26°N) : 1. Modes of variability and implications for subsurface flow

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 112 (2007): B07101, doi:10.1029/2006JB004435.Yearlong time series records of exit fluid temperature from the active TAG hydrothermal mound (Mid-Atlantic Ridge, 26°N) reveal a complex space-time pattern of flow variability within the mineral deposit. Exit fluid temperatures were measured every 8–10 min from 17 sites distributed across the upper terrace of the mound from June 2003 to June 2004. High-temperature records were obtained using Deep Sea Power and Light SeaLogger® probes deployed in fractures discharging ∼360°C black smoker fluids, and low-temperature records were obtained using VEMCO Ltd. Minilog probes deployed in cracks discharging ∼20°C diffuse flow fluids. The temperature records are considerably more variable than those acquired from vent fields on the fast spreading East Pacific Rise and exhibit a complex mix of both episodic and periodic variability. The diffuse flow records alternate between periods of discharge and periods of what I infer to be recharge when fluid temperatures are equal to background water column levels (∼2.7°C) as ambient seawater is drawn into the seafloor. The space-time patterns of these episodic variations suggest that they represent reorganizations of the secondary circulation system driving diffuse discharge on the upper terrace of the mound on timescales from a few hours to a few days, most likely in response to permeability perturbations. Harmonic temperature oscillations were observed over a range of periods, with the principal lunar semidiurnal tidal period (M2) being most dominant. During certain times, exit fluid temperatures at diffuse sites pulse at diurnal and semidiurnal tidal periods when they are hovering near background water column levels, which I interpret as flow reversals associated with the vertical displacement of a fluid boundary layer at the seafloor interface when the local net flux is near zero. The pulsing behavior is predicted by poroelastic models of tidal loading but is not consistent with effects from tidal currents, which demonstrates that poroelastic effects from tidal loading modulate shallow subsurface flow at the active TAG mound.This work was supported by the National Science Foundation (OCE-0137329)

Genomic correlates of glatiramer acetate adverse cardiovascular effects lead to a novel locus mediating coronary risk

Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products reported by drug-gene interaction database to interact with glatiramer acetate we explored a large meta-analysis on CAD genome-wide association studies aiming firstly, to investigate whether variants in these genes also affect cardiovascular risk and secondly, to identify new CAD risk genes. We traced association signals in a 200-kb region around genomic positions of genes interacting with glatiramer in up to 60 801 CAD cases and 123 504 controls. We validated the identified association in additional 21 934 CAD cases and 76 087 controls. We identified three new CAD risk alleles within the TGFB1 region on chromosome 19 that independently affect CAD risk. The lead SNP rs12459996 was genome-wide significantly associated with CAD in the extended meta-analysis (odds ratio 1.09, p = 1.58×10-12). The other two SNPs at the locus were not in linkage disequilibrium with the lead SNP and by a conditional analysis showed p-values of 4.05 × 10-10 and 2.21 × 10-6. Thus, studying genes reported to interact with glatiramer acetate we identified genetic variants that concordantly with the drug increase the risk of CAD. Of these, TGFB1 displayed signal for association. Indeed, the gene has been associated with CAD previously in both in vivo and in vitro studies. Here we establish genome-wide significant association with CAD in large human samples.This work was supported by grants from the Fondation Leducq (CADgenomics: Understanding CAD Genes, 12CVD02), the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (e:AtheroSysMed, grant 01ZX1313A-2014 and SysInflame, grant 01ZX1306A), and the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no HEALTH-F2-2013-601456 (CVgenes-at-target). Further grants were received from the DFG as part of the Sonderforschungsbereich CRC 1123 (B2). T.K. was supported by a DZHK Rotation Grant. I.B. was supported by the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ‘Inflammation at Interfaces’. F.W.A. is supported by a Dekker scholarship-Junior Staff Member 2014T001 - Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Attitude, subjective norm and perceived behavioural control as predictors of women's intentions to take hormone replacement therapy

Objectives. To examine women's attitudes towards the use of hormone replacement therapy (HRT) and to predict intention to take it in a sample of 1200 women using the theory of planned behaviour (Ajzen, 1988) and a measure of similar prior behaviour. Design. The design was cross-sectional. A postal survey was carried out. Methods. Questionnaires were sent to a random sample of 1200 women aged between 38 and 58 generated from the Kent Family Health Services Authority records. Questions based on the theory of planned behaviour were used to predict women's intentions to take HRT. Information was also collected about the women's sources of information on the menopause, their experience of the menopause and the time leading up to it, their general health, and their sociodemographic circumstances. Results. Analysis was carried out on the responses of the 641 women who were not yet taking and had never taken HRT. Hierarchical multiple regression analysis showed that similar prior behaviour made a small independent contribution to the prediction of behavioural intention when entered after the components of the model. Structural equation modelling was carried out to show the paths between the variables. When age was included, similar prior behaviour was shown to influence behaviour through perceived behavioural control and attitude. Conclusions. In predicting women's intention to take HRT, the beliefs of significant others, the women's personal beliefs, their degree of confidence in their ability to carry out the behaviour and the experience of similar prior behaviour are important considerations

Appreciative inquiry in occupational therapy education

Appreciative inquiry (AI) is a business tool that has proved to be an effective approach to changing organisational culture. More recently attention has turned to its application in health care. The authors suggest that as AI encourages creative thinking and is based on considering what can be done as opposed to what cannot, it might have an application in occupational therapy education. To date, only one school of occupational therapy in the UK is known to have incorporated AI into its problem-based learning programme; students are encouraged to think positively and creatively about clients and themselves. This study evaluated this pedagogic approach, with particular focus on its usefulness in practice placements. Twenty five students were included in focus groups and six teaching staff took part in semi-structured interviews. Qualitative thematic content analysis suggested that students found AI an enjoyable and interesting learning method, and staff enjoyed teaching this way. AI encouraged students to think more positively about clients on practice placement, especially in mental health settings. The authors conclude that AI provides students with an approach to practice that enables them to think more creatively in therapeutic interventions, and provides therapists with another tool that they could use when working with clients