Prediction of circulating adipokine levels based on body fat compartments and adipose tissue gene expression

BACKGROUND: Adipokines are hormones secreted from adipose tissue (AT), and a number of them have been established as risk factors for chronic diseases. However, it is not clear whether and to what extent adiposity, gene expression, and other factors determine their circulating levels. OBJECTIVES: To assess to what extent adiposity, as measured by the amount of subcutaneous AT (SAT) and visceral AT (VAT) using magnetic resonance imaging, and gene expression levels in SAT determine plasma concentrations of the adipokines adiponectin, leptin, soluble leptin receptor, resistin, interleukin 6, and fatty acid-binding protein 4 (FABP4). METHODS: We performed a cross-sectional analysis of 156 participants from the EPIC Potsdam cohort study and analyzed multiple regression models and partial correlation coefficients. RESULTS: For leptin and FABP4 concentrations, 81 and 45% variance were explained by SAT mass, VAT mass, and gene expression in SAT in multivariable regression models. For the remaining adipokines, AT mass and gene expression explained <16% variance of plasma concentrations. Gene expression in SAT was a less important predictor compared to AT mass. SAT mass was a better predictor than VAT mass for leptin (partial correlation r = 0.81, 95% confidence interval 0.75–0.86, vs. r = 0.58, 95% confidence interval 0.46–0.67), while differences between AT compartments were small for the other adipokines. CONLUSIONS: While plasma levels of leptin and FABP4 can be explained in a large and medium part by the amount of AT and SAT gene expression, surprisingly, these predictors explained only little variance for all other investigated adipokines

Non-fasting lipids and risk of cardiovascular disease in patients with diabetes mellitus

The aim of this study was to examine the effect of postprandial time on the associations and predictive value of non-fasting lipid levels and cardiovascular disease risk in participants with diabetes. This study was conducted among 1,337 participants with diabetes from the Dutch and German (Potsdam) contributions to the European Prospective Investigation into Cancer and Nutrition. At baseline, total cholesterol, LDL- and HDL-cholesterol and triacylglycerol concentrations were measured and the ratio of total cholesterol/HDL-cholesterol was calculated. Participants were followed for incidence of cardiovascular disease. Lipid concentrations changed minimally with increasing postprandial time, except for triacylglycerol which was elevated just after a meal and declined over time (1.86 at 0.1 h to 1.33 at >6 h, p for trend <0.001). During a mean follow-up of 8 years, 116 cardiovascular events were documented. After adjustment for potential confounders, triacylglycerol (HR for third tertile compared with first tertile (HR(t)₃(to)₁), 1.73 [95% CI 1.04, 2.87]), HDL-cholesterol (HR(t)₃(to)₁, 0.41 [95% CI 0.23, 0.72]) and total cholesterol/HDL-cholesterol ratio (HR(t)₃(to)₁, 1.65 [95% CI 0.95, 2.85]) were associated with cardiovascular disease, independent of postprandial time. Cardiovascular disease risk prediction using the UK Prospective Diabetes Study risk engine was not affected by postprandial time. Postprandial time did not affect associations between lipid concentrations and cardiovascular disease risk in patients with diabetes, nor did it influence prediction of cardiovascular disease. Therefore, it may not be necessary to use fasting blood samples to determine lipid concentrations for cardiovascular disease risk prediction in patients with diabete

DEVELOPMENT OF A STRATEGIC BUSINESS DECISION-MAKING ENVIRONMENT FOR COMMERCIAL JET ENGINE SELECTION

Presented at the 41st AIAA Aerospace Sciences, Meeting and Exhibit, Reno, NV, January 6-10, 2003.In today?s business climate, aerospace companies are more than ever in need of rational methods and techniques that provide insights as to the best strategies which may be pursued for increased profitability and risk mitigation. However, the use of subjective, anecdotal decision-making remains prevalent due to the absence of analytical methods capable of capturing and forecasting future needs. Negotiations between airframe and engine manufacturers could benefit greatly from a structured environment that facilitates efficient, rational, decision-making. Creation of such an environment can be developed through a parametric physics-based, stochastic formulation that uses meta-models to expedite the process. This paper describes such an approach in order to demonstrate the types of insights that might be gained as an engine manufacturer tries to forecast the effects of uncertainties and future vehicle requirements on engine related characteristics for the design of a hypothetical regional business jet. Game theory concepts are suggested as a potential means by which one can attach business payoffs to the selection of any engine design point

Sensitivity of Boundary Layer Ingestion Effects to Tube and Wing Airframe Design Features

Conceptual design of boundary layer ingesting (BLI) aircraft requires a methodology that captures the aero-propulsive interactions in a parametric fashion. This entails modeling the impacts of BLI as a function of the airframe and propulsor design. Previous work has analyzed the sensitivity of these BLI effects to the propulsor size and throttle. This paper assesses the sensitivity of the BLI effects to the airframe design through a series of experiments, using CFD. The scope of this analysis is restricted to tube and wing type BLI concepts. Results from these studies help identify the critical airframe design space that needs to be considered when generating a parametric model of the BLI effects. Guidelines regarding the level of detail required for the airframe geometry model are discussed

Numerical Simulations of Various Rotor Designs in Hover and Forward Flight

This paper presents numerical simulations of different rotor designs using high-fidelity CFD methods. Firstly, hover results are presented for the PSP rotor blade. The impact of a transitional turbulence model on the blade performance was examined and good correlation with test data was obtained. A grid sensitivity study indicated an influence on the transition location predictions, however, the effect on the integrated loads was not significant. The surface pressure distributions and sectional loads were also examined. The PSP rotor was also simulated in forward flight and blade surface pressure was compared with wind tunnel data. The predictions were found to follow data obtained from pressure transducers

Policy-relevant spatial indicators of urban liveability and sustainability : Scaling from local to global

[English] Urban liveability is a global priority for creating healthy, sustainable cities. Measurement of policy-relevant spatial indicators of the built and natural environment supports city planning at all levels of government. Analysis of their spatial distribution within cities, and impacts on individuals and communities, is crucial to ensure planning decisions are effective and equitable. This paper outlines challenges and lessons from a 5-year collaborative research program, scaling up a software workflow for calculating a composite indicator of urban liveability for residential address points across Melbourne, to Australia’s 21 largest cities, and further extension to 25 global cities in diverse contexts. [Chinese] 城市宜居性是创建健康、可持续城市的全球优先事项。对建筑和自然环境的政策相关空间指标的测量支持各级政府的城市规划。分析它们在城市中的空间分布，以及对个人和社区的影响，对于确保规划决策的有效性和公平性至关重要。本文概述了一个为期5年的合作研究项目所面临的挑战和经验教训，该项目将计算墨尔本住宅地址点的城市宜居性综合指标的软件工作流程扩大到澳大利亚21个最大的城市，并进一步扩展到25个不同背景的全球城市

Lifestyle, dietary factors and antibody levels to oral bacteria in cancer-free participants of a European cohort study

Background—Increasing evidence suggests that oral microbiota play a pivotal role in chronic diseases, in addition to the well-established role in periodontal disease. Moreover, recent studies suggest that oral bacteria may also be involved in carcinogenesis; periodontal disease has been linked several cancers. In this study, we examined whether lifestyle factors have an impact on antibody levels to oral bacteria. Methods—Data on demographic characteristics, lifestyle factors, and medical conditions were obtained at the time of blood sample collection. For the current analysis, we measured antibody levels to 25 oral bacteria in 395 cancer-free individuals using an immunoblot array. Combined total immunglobin G (IgG) levels were obtained by summing concentrations for all oral bacteria measured. Results—IgG antibody levels were substantially lower among current and former smokers (1697 and 1677 ng/mL, respectively) than never smokers (1960 ng/mL; p-trend = 0.01), but did not vary by other factors, including BMI, diabetes, physical activity, or by dietary factors, after adjusting for age, sex, education, country and smoking status. The highest levels of total IgG were found among individuals with low education (2419 ng/mL). Conclusions—Our findings on smoking are consistent with previous studies and support the notion that smokers have a compromised humoral immune response. Moreover, other major factors known to be associated with inflammatory markers, including obesity, were not associated with antibody levels to a large number of oral bacteria

The 'At-risk mental state' for psychosis in adolescents : clinical presentation, transition and remission.

Despite increased efforts over the last decade to prospectively identify individuals at ultra-high risk of developing a psychotic illness, limited attention has been specifically directed towards adolescent populations (<18 years). In order to evaluate how those under 18 fulfilling the operationalised criteria for an At-Risk Mental State (ARMS) present and fare over time, we conducted an observational study. Participants (N = 30) generally reported a high degree of functional disability and frequent and distressing perceptual disturbance, mainly in the form of auditory hallucinations. Seventy percent (21/30) were found to fulfil the criteria for a co-morbid ICD-10 listed mental health disorder, with mood (affective; 13/30) disorders being most prevalent. Overall transition rates to psychosis were low at 24 months follow-up (2/28; 7.1 %) whilst many participants demonstrated a significant reduction in psychotic-like symptoms. The generalisation of these findings may be limited due to the small sample size and require replication in a larger sample

Identification of novel genes whose expression in adipose tissue affects body fat mass and distribution: an RNA-Seq and Mendelian Randomization study

Many studies have shown that abdominal adiposity is more strongly related to health risks than peripheral adiposity. However, the underlying pathways are still poorly understood. In this cross-sectional study using data from RNA-sequencing experiments and whole-body MRI scans of 200 participants in the EPIC-Potsdam cohort, our aim was to identify novel genes whose gene expression in subcutaneous adipose tissue has an effect on body fat mass (BFM) and body fat distribution (BFD). The analysis identified 625 genes associated with adiposity, of which 531 encode a known protein and 487 are novel candidate genes for obesity. Enrichment analyses indicated that BFM-associated genes were characterized by their higher than expected involvement in cellular, regulatory and immune system processes, and BFD-associated genes by their involvement in cellular, metabolic, and regulatory processes. Mendelian Randomization analyses suggested that the gene expression of 69 genes was causally related to BFM and BFD. Six genes were replicated in UK Biobank. In this study, we identified novel genes for BFM and BFD that are BFM- and BFD-specific, involved in different molecular processes, and whose up-/downregulated gene expression may causally contribute to obesity