Genome-Wide Association with Diabetes-Related Traits in the Framingham Heart Study

BACKGROUND: Susceptibility to type 2 diabetes may be conferred by genetic variants having modest effects on risk. Genome-wide fixed marker arrays offer a novel approach to detect these variants. METHODS: We used the Affymetrix 100K SNP array in 1,087 Framingham Offspring Study family members to examine genetic associations with three diabetes-related quantitative glucose traits (fasting plasma glucose (FPG), hemoglobin A1c, 28-yr time-averaged FPG (tFPG)), three insulin traits (fasting insulin, HOMA-insulin resistance, and 0–120 min insulin sensitivity index); and with risk for diabetes. We used additive generalized estimating equations (GEE) and family-based association test (FBAT) models to test associations of SNP genotypes with sex-age-age2-adjusted residual trait values, and Cox survival models to test incident diabetes. RESULTS: We found 415 SNPs associated (at p 1%) 100K SNPs in LD (r2 > 0.05) with ABCC8 A1369S (rs757110), KCNJ11 E23K (rs5219), or SNPs in CAPN10 or HNFa. PPARG P12A (rs1801282) was not significantly associated with diabetes or related traits. CONCLUSION: Framingham 100K SNP data is a resource for association tests of known and novel genes with diabetes and related traits posted at. Framingham 100K data replicate the TCF7L2 association with diabetes.National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1); National Center for Research Resources General Clinical Research Center (M01-RR-01066); American Diabetes Association Career Developement Award; GlaxoSmithKline; Merck; Lilly; National Institutes of Health Research Career Award (K23 DK659678-03

A review of the potential of smart homes to support independent living

Between 2015 and 2050, the proportion of the world's population over 60 years of age is expected to nearly double, from 12% to 22%. Whilst hospitals offer care to people with health problems, support at home is generally limited to carers, a costly labour intensive method that impacts on the ability of many elderly patients to live independently. This pushes the demand for housing that caters for elderly people allowing them to remain in their homes but with some level of healthcare support. In the UK, the domestic sector currently accounts for around 30% of total energy consumption and contributes in the region of 27% of total carbon dioxide and greenhouse gas emissions. With an ageing population, offering healthy environments with a cushion against rising energy prices will be essential for people spending most of their time at home and often living on limited budgets. In this context, the drive to reduce energy consumption and associated greenhouse gas emissions from housing has acted as a catalyst in the increasing installation of meters and sensors for monitoring energy use and indoor environmental conditions in buildings. These monitoring technologies can track and record a range of parameters such as temperature, air quality, occupant behaviour etc. Many of these could be optimised to help create environments that assist people such as the elderly to live at home. This paper aims to review relevant studies and technologies in the areas of smart, energy-efficient and lifetime homes, identifying some of the health needs of elderly people who could live at home if provided with adequate support, the range and type of technologies that could be employed to this objective, and suitable metrics to be used to measure the effectiveness of these technologies. The paper concludes that there is a limited evidence base on the health effects of energy-efficient homes, highlighting the need for more research and post occupancy evaluation using indoor environmental quality monitoring technology and wearable devices to analyse not only the energy performance of ‘green’ housing but also the possible effects of indoor environmental conditions on the subjective and objective wellbeing of occupants

The instrument in space : the embodiment of music in the machine age

The body exists in space and time. It moves through cultural spaces and temporal rhythms. In the combination of instantiated actions and environmental conditions a context is created, this through embodiment. In this thesis I will attempt to link definitions of embodiment with the process of creating and performing new sound theatre works that involve live interaction with media technology. I will also examine terms such as inscription or incorporation and their application to processes of learning and memory within a particular context of inter-disciplinary skills. Finally, in the light of this genre, I will approach the problematic of analytical procedures that change the very parameters of embodied knowledge. The term sound theatre could be defined as a shift of play between music, image and text, incorporating elements such as gesture, choreography, audio and visual technology into a compositional dialogue. However this approach demands a re-examination of the spatial and temporal aspects involved in such inter-activity and their consequent relation to the performer. Taking the starting-point of sound and movement within the body of the performer, my research involves investigations into medial extensions of embodiment that have developed through a discourse with machines. This project takes an essentially practical basis for its research in the form of collaborations with musicians and practitioners of media technology towards a creative product. The result is a series of written compositions, each of which examines a different aspect of sound theatre. The valuable exchange that takes place during such a situation of experimentation becomes equally as important as the final product, providing much of the material framework for issues such as terminology and analytical procedures that concern my investigation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Heritability and genome-wide association analysis of renal sinus fat accumulation in the Framingham Heart Study

<p>Abstract</p> <p>Background</p> <p>Ectopic fat accumulation in the renal sinus is associated with chronic kidney disease and hypertension. The genetic contributions to renal sinus fat accumulation in humans have not been well characterized.</p> <p>Methods</p> <p>The present analysis consists of participants from the Framingham Offspring and Third Generation who underwent computed tomography; renal sinus fat and visceral adipose tissue (VAT) were quantified. Renal sinus fat was natural log transformed and sex- and cohort-specific residuals were created, adjusted for (1) age, (2) age and body mass index (BMI), and (3) age and VAT. Residuals were pooled and used to calculate heritability using variance-components analysis in SOLAR. A genome-wide association study (GWAS) for renal sinus fat was performed using an additive model with approximately 2.5 million imputed single nucleotide polymorphisms (SNPs). Finally, we identified the associations of renal sinus fat in our GWAS results with validated SNPs for renal function (n = 16), BMI (n = 32), and waist-to-hip ratio (WHR, n = 14), and applied a multi-SNP genetic risk score method to determine if the SNPs for each renal and obesity trait were in aggregate associated with renal sinus fat.</p> <p>Results</p> <p>The heritability of renal sinus fat was 39% (p < 0.0001); results were not materially different after adjustment for BMI (39%) or VAT (40%). No SNPs reached genome-wide significance in our GWAS. In our candidate gene analysis, we observed nominal, direction consistent associations with renal sinus fat for one SNP associated with renal function (p = 0.01), two associated with BMI (p < 0.03), and two associated with WHR (p < 0.03); however, none remained significant after accounting for multiple testing. Finally, we observed that in aggregate, the 32 SNPs associated with BMI were nominally associated with renal sinus fat (multi-SNP genetic risk score p = 0.03).</p> <p>Conclusions</p> <p>Renal sinus fat is a heritable trait, even after accounting for generalized and abdominal adiposity. This provides support for further research into the genetic determinants of renal sinus fat. While our study was underpowered to detect genome-wide significant loci, our candidate gene BMI risk score results suggest that variability in renal sinus fat may be associated with SNPs previously known to be associated with generalized adiposity.</p

Updated Marine Mammal Distribution and Abundance Estimates in British Columbia

Information relating to the distribution and abundance of species is critical for effective conservation and management. For many species, including cetacean species of conservation concern, abundance estimates are lacking, out of date and/or highly uncertain. Systematic, line-transect marine mammal surveys were conducted in British Columbia’s (BC) coastal waters over multiple years and seasons (summer 2004, 2005, 2008, and spring/autumn 2007). In total, 10,057km of transects were surveyed in an 83,547km2 study area. Abundance estimates were calculated using two different methods: Conventional Distance Sampling (CDS) and Density Surface Modelling (DSM). CDS generates a single density estimate for each stratum, whereas DSM explicitly models spatial variation and offers potential for greater precision by incorporating environmental predictors. Although DSM yields a more relevant product for the purposes of marine spatial planning, CDS has proven to be useful in cases where there are fewer observations available for seasonal and inter-annual comparison, particularly for the scarcely observed elephant seal. The summer abundance estimates (with lower and upper 95% confidence intervals; all DSM method unless otherwise stated), assuming certain trackline detection (underestimates true population size) were: harbour porpoise (Phocoena phocoena) 8,091 (4,885–13,401); Dall’s porpoise (Phocoenoides dalli) 5,303 (4,638–6,064); Pacific white-sided dolphin (Lagenorhynchus obliquidens) 22,160 (16,522–29,721); humpback whale (Megaptera novaeangliae) 1,092 (993–1,200); fin whale (Balaenoptera physalus) 329 (274–395); killer whale (all ecotypes; Orcinus orca), 371 (222–621); common minke whale (B. acutorostrata) 522 (295–927); harbour seal (total; Phoca vitulina) 24,916 (19,666–31,569); Steller sea lion (total; Eumetopias jubatus) 4,037 (1,100–14,815); and northern elephant seal (CDS method; Mirounga angustirostris) 65 (35–121). Abundance estimates are provided on a stratum-specific basis with additional estimates provided for Steller sea lions and harbour seals that were ‘hauled out’ and ‘in water’. This analysis updates previous estimates by including additional years of effort, providing greater spatial precision with the DSM method over CDS, novel reporting for spring and autumn seasons (rather than summer alone), and providing new abundance estimates for Steller sea lion and northern elephant seal. In addition to providing a baseline of marine mammal abundance and distribution, against which future changes can be compared, this information offers the opportunity to assess the risks posed to marine mammals by existing and emerging threats, such as fisheries bycatch, ship strikes, and increased oil spill and ocean noise issues associated with increases of container ship and oil tanker traffic in British Columbia’s continental shelf waters

Oxidation of tertiary amine-derivatized surfaces to control protein adhesion

Selective oxidation of omega-tertiary amine self-assembled thiol monolayers to tertiary amine N-oxides is shown to transform the adhesion of model proteins lysozyme and fibrinogen upon them. Efficient preparation of both secondary and tertiary linker amides as judged by X-ray photoelectron spectroscopy (XPS) and water droplet contact angle was achieved with an improved amide bond formation on gold quartz crystal microbalance (QCM) sensors using 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl hexafluorophosphate methanaminium uronium (HATU). Oxidation with hydrogen peroxide was similarly assessed, and adhesion of lysozyme and fibrinogen from phosphate buffered saline was then assayed by QCM and imaged by AFM. Tertiary amine-functionalized sensors adsorbed multilayers of aggregated lysozyme, whereas tertiary amine N-oxides and triethylene glycol-terminated monolayers are consistent with small protein aggregates. The surface containing a dimethylamine N-oxide headgroup and ethyl secondary amide linker showed the largest difference in adsorption of both proteins. Oxidation of tertiary amine decorated surfaces therefore holds the potential for selective deposition of proteins and cells through masking and other patterning techniques

Development and reproducibility of a computed tomography-based measurement of renal sinus fat

BACKGROUND: Renal sinus fat may mediate obesity-related vascular disease, although this fat depot has not been assessed in a community-based sample. We sought to develop a protocol to quantify renal sinus fat accumulation using multi-detector computed tomography (MDCT). METHODS: Protocol development was performed in participants in the Framingham Offspring cohort who underwent MDCT. Volumetric renal sinus fat was measured separately within the right and left kidneys, and renal sinus fat area within a single MDCT scan slice was measured in the right kidney. Due to the high correlation of volumetric and single-slice renal sinus fat in the right kidney (Pearson correlation [r] = 0.85, p < 0.0001), we optimized a single-slice protocol to capture renal sinus fat in the right kidney alone. Pearson correlation coefficients were used to compare to assess the correlation of volumetric and single-slice renal sinus fat in the right kidney with other measures of adiposity. Inter- and intra-reader reproducibility was assessed using intra-class correlation coefficients. RESULTS: Single-slice measurements were obtained in 92 participants (mean age 60 years, 49% women, median renal sinus fat 0.43 cm(2)). Intra- and inter-reader intra-class correlation coefficients were 0.93 and 0.86, respectively. Single-slice renal sinus fat was correlated with body mass index (r = 0.35, p = 0.0006), waist circumference (r = 0.31, p = 0.003), and abdominal visceral fat (r = 0.48, p < 0.0001). Similar correlations were observed for volumetric renal sinus fat in the right kidney. CONCLUSIONS: Measuring renal sinus fat is feasible and reproducible using MDCT scans in a community-based sample

Risks of use and non-use of antibiotics in primary care: qualitative study of prescribers' views.

PURPOSE: The emergence of antimicrobial resistance has led to increasing efforts to reduce unnecessary use of antibiotics in primary care, but potential hazards from bacterial infection continue to cause concern. This study investigated how primary care prescribers perceive risk and safety concerns associated with reduced antibiotic prescribing. METHODS: Qualitative study using semistructured interviews conducted with primary care prescribers from 10 general practices in an urban area and a shire town in England. A thematic analysis was conducted. RESULTS: Thirty participants were recruited, including twenty-three general practitioners, five nurses and two pharmacists. Three main themes were identified: risk assessment, balancing treatment risks and negotiating decisions and risks. Respondents indicated that their decisions were grounded in clinical risk assessment, but this was informed by different approaches to antibiotic use, with most leaning towards reduced prescribing. Prescribers' perceptions of risk included the consequences of both inappropriate prescribing and inappropriate withholding of antibiotics. Sepsis was viewed as the most concerning potential outcome of non-prescribing, leading to possible patient harm and potential litigation. Risks of antibiotic prescribing included antibiotic resistant and Clostridium difficile infections, as well as side effects, such as rashes, that might lead to possible mislabelling as antibiotic allergy. Prescribers elicited patient preferences for use or avoidance of antibiotics to inform management strategies, which included educational advice, advice on self-management including warning signs, use of delayed prescriptions and safety netting. CONCLUSIONS: Attitudes towards antibiotic prescribing are evolving, with reduced antibiotic prescribing now being approached more systematically. The safety trade-offs associated with either use or non-use of antibiotics present difficulties especially when prescribing decisions are inconsistent with patients' expectations

Dietary Patterns, Abdominal Visceral Adipose Tissue and Cardiometabolic Risk Factors in African Americans: the Jackson Heart Study

Dietary behavior is an important lifestyle factor to impact an individual’s risk of developing cardiovascular disease (CVD). However, the influence of specific dietary factors on CVD risk for African Americans remains unclear. We conducted a cross-sectional study of 1775 participants from Jackson Heart Study (JHS) Exam 2 (between 2006 and 2009) who were free of hypertension, diabetes and CVD at the baseline (between 2001 and 2004). Dietary intakes were documented using a validated food-frequency questionnaire (FFQ) and dietary patterns were generated by factor analysis. Three major dietary patterns were identified: a “southern”, a “fast food” and a “prudent” pattern. After adjustment for age, sex, smoking and alcohol status, education level and physical activity, high “southern” pattern score was associated with an increased odds ratio (OR) for high abdominal visceral adipose tissue (VAT) (OR:1.80, 95%CI:1.1–3.0, p=0.02), hypertension (OR:1.42, 95%CI:1.1–1.9, p=0.02), diabetes (OR:2.03, 95%CI:1.1–3.9, p=0.03) and metabolic syndrome (OR:2.16, 95%CI:1.3–3.6, p=0.004). Similar associations were also observed in the “fast food” pattern (p ranges 0.03–0.0001). The “prudent” pattern was significantly associated, in a protective direction, with hypertension (OR 0.69, 95%CI 0.5–0.9, p=0.02). In conclusion, dietary patterns, especially the “southern” pattern, identified from a regional specific FFQ in this Deep South African Americans, are correlated with abdominal VAT and cardiometabolic risk factors

Everyday cosmopolitanism in representations of Europe among young Romanians in Britain

The paper presents an analysis of everyday cosmopolitanism in constructions of Europe among young Romanian nationals living in Britain. Adopting a social representations approach, cosmopolitanism is understood as a cultural symbolic resource that is part of everyday knowledge. Through a discursively-oriented analysis of focus group data, we explore the ways in which notions of cosmopolitanism intersect with images of Europeanness in the accounts of participants. We show that, for our participants, representations of Europe are anchored in an Orientalist schema of West-vs.-East, whereby the West is seen as epitomising European values of modernity and progress, while the East is seen as backward and traditional. Our findings further show that representations of cosmopolitanism reinforce this East/West dichotomy, within a discourse of ‘Occidental cosmopolitanism’. The paper concludes with a critical discussion of the diverse and complex ideological foundations of these constructions of European cosmopolitanism and their implications