Publications

Additional file 10: Table S6. Results of look-ups in two epigenome-wide association study (EWAS) catalogues, the EWAS Atlas [39] (Source: “EWAS_Atlas”) and the EWAS Catalog [40] (Source: “EWAS_Cat”). Shown are the catalogue results (significantly associated CpGs and traits) for all CpGs from our replicated metabolic measure-CpG associations (16 CpG sites total). Chromosome (CHR) and chromosomal position (Pos) taken from the Illumina HumanMethylation450 v1.2 Manifest File, available from the Illumina website.

Background— Although heat shock protein 60 (Hsp60) is implicated in the pathogenesis of atherosclerosis, its role in coronary heart disease (CHD) is uncertain. This study explored the influence of circulating Hsp60 on CHD in a large case-control study, as well as the impact of acute myocardial infarction on Hsp60 levels in a prospective study. Methods and Results— Plasma Hsp60 and anti-Hsp60 antibody levels were determined by immunoassay. In the case-control study (1003 patients with CHD, 1003 matched control subjects), Hsp60 levels were higher in patients with CHD and were related to CHD (OR comparing extreme quartiles=4.14, P <0.0001). This association remained after adjustment for traditional risk factors ( P for trend <0.0001). Individuals having high levels of Hsp60 (greater than the median of 160.24 ng/mL) and anti-Hsp60 antibody (greater than the median of 38.42 U/mL) were at a greater risk of CHD than those with low levels (OR 2.30, P <0.0001). Stronger additive effects (OR 14.04, P <0.0001) were apparent at higher Hsp60 and anti-Hsp60 antibody levels (>1000 ng/mL and greater than the median of 38.42 U/mL, respectively). The simultaneous presence of high Hsp60 and anti-Hsp60 antibody levels, current smoking, hypertension, and diabetes were cumulatively associated with CHD. Individuals who had any 4 or more of these 5 factors had an OR of 38.61 for CHD ( P <0.0001) compared with individuals who had none of these factors. For the prospective study, blood was drawn from 20 patients immediately after admission for acute myocardial infarction and 2, 3, and 7 days thereafter. Hsp60 levels were significantly higher on the day of and the day after arrival than 7 days after an acute myocardial infarction ( P =0.011 and P =0.026, respectively). Conclusions— Elevated Hsp60 levels are associated with an increased risk for CHD, and Hsp60 and anti-Hsp60 antibody levels combine to increase this risk. In addition, acute myocardial infarction induces Hsp60 release.

Introduction: The relationship between artificially sweetened beverage (ASB) intake and type 2 diabetes (T2D) risk remains inconclusive. Few studies have evaluated whether circulating metabolites that reflect ASB consumption may unveil potential mechanisms underlying the association between ASB consumption and T2D risk. Hypothesis: We hypothesized that a novel metabolomic profile reflecting habitual ASB consumption would positively associate with incident T2D among US adults. Methods: We quantified 120 plasma metabolites with liquid chromatography-mass spectroscopy in N=3,424 Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-up Study (HPFS) discovery cohort participants, and N=1,870 Framingham Heart Study (FHS) replication cohort participants. Habitual ASB consumption (servings/day; low-calorie cola or other carbonated beverages) was estimated from food frequency questionnaires at the time of blood draw. We used elastic net regression with 10-fold-cross-validation to age- and body mass index- adjusted metabolite levels to identify a metabolite profile associated with higher ASB consumption (ln-transformed). We then derived the continuous ASB metabolomic score as the weighted sum of these metabolites and replicated the analysis in an internal testing set and FHS. Finally, we evaluated the association of quartiles (Q) of the ASB-derived metabolomic score in NHS/NHSII/HPFS and FHS cohorts with incident T2D risk after blood draw (baseline for analysis) using Cox regression models to estimate hazard ratios (HR) and 95% confidence interval (CI), adjusted for demographics, lifestyle, diet, and body mass index at blood draw. Results: The ASB-derived metabolomic profile included 61 metabolites, primarily lipids and amino acids (Pearson correlation coefficients [ r ] between ASB self-reported intake and metabolomic score: r=0.08 [95% CI: 0.05, 0.11; p <0.0001] and r=0.09 [95% CI: 0.04, 0.14; p =0.001], for discovery and replication, respectively). Mean follow-up was 20 and 16 years from blood draw, including 359 and 241 confirmed incident T2D cases for NHS/NHSII/HPFS and FHS, respectively. Compared with participants in the lowest quartile of the ASB-derived metabolomic profile, higher quartiles were incrementally and significantly at higher T2D risk in NHS/NHSII/HPFS (HR [CI] for Q2, Q3, Q4 vs. Q1: 1.45 [1.04, 2.02], 1.83 [1.33, 2.52], 1.62 [1.18, 2.22], respectively; p-trend =0.003) and FHS (1.76 [1.24, 2.48], 1.82 [1.28, 2.58], 2.45 [1.77, 3.40], respectively; p-trend <0.0001). Conclusions: A robust metabolomic profile of ASB intake was not identified, yet the objective and replicable ASB-derived metabolomic profile was associated with higher incident T2D risk. The identified metabolites may reflect ASB intake, western dietary patterns, underlying metabolic health, and/or T2D-related pathophysiology.

Raman D-band spectra are reported for several different SWNTs using two different laser energies ${(E}_{\mathrm{laser}}=1.58$ and 2.41 eV). At a fixed ${E}_{\mathrm{laser}},$ individual isolated SWNTs exhibit different diameter-dependent D-band frequencies ${\ensuremath{\omega}}_{D}$ around an average value. For both semiconducting and metallic tubes, ${\ensuremath{\omega}}_{D}$ decreases with decreasing nanotube diameter, though ${\ensuremath{\omega}}_{D}$ for isolated metallic SWNTs is higher than for isolated semiconducting SWNTs. The average D-band frequency depends linearly on ${E}_{\mathrm{laser}},$ as previously observed for SWNT bundles, suggesting that the D-band in SWNTs is activated by defects or by the finite size of the SWNTs.

OBJECTIVE To prospectively investigate associations of dairy consumption with risk of type 2 diabetes and changes of cardiometabolic traits. RESEARCH DESIGN AND METHODS In 2005, 2,091 middle-aged and older Chinese men and women were recruited and followed for 6 years. Baseline dairy consumption was assessed by a 74-item food frequency questionnaire. Erythrocyte fatty acids were analyzed by gas chromatography coupled with flame ion detector. Cardiometabolic traits were measured at both baseline and follow-up visits. RESULTS Only 1,202 (57.5%) participants reported any dairy consumption, with a median intake of 0.89 (interquartile range 0.19–1.03) serving/day. Compared with nonconsumers, the relative risks (RRs) of type 2 diabetes among those having 0.5–1 serving/day and >1 serving/day were 0.70 (95% CI 0.55–0.88) and 0.65 (0.49–0.85), respectively, after multivariate adjustment (Ptrend < 0.001), which were attenuated by further adjusting for changes in glucose during follow-up (Ptrend = 0.07). Total dairy consumption was associated with favorable changes in glucose, waist circumference, BMI, diastolic blood pressure (all Ptrend < 0.05), and systolic blood pressure (Ptrend = 0.05) after multivariate adjustment, including baseline values of dependent variables. Erythrocyte trans-18:1 isomers were significantly correlated with total dairy consumption (rs = 0.37, Ptrend < 0.001), and these dairy food biomarkers were associated with a lower risk of type 2 diabetes. The RR of type 2 diabetes comparing extreme quartiles of trans-18:1 isomers was 0.82 (0.65–1.04, Ptrend = 0.02), which was attenuated after adjustment for dairy consumption (Ptrend = 0.15). CONCLUSIONS Dairy consumption was associated with a significantly lower risk of type 2 diabetes and favorable changes of cardiometabolic traits in Chinese.

A single-nucleotide polymorphism (rs10911021) was identified that was significantly associated with CHD among persons with diabetes but not in those without diabetes and was functionally related to glutamic acid metabolism, suggesting a mechanistic link.

Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms.

Locomotion of soft robots typically relies on control of multiple inflatable actuators by electronic computers and hard valves. Soft pneumatic oscillators can reduce the demand on controllers by generating complex movements required for locomotion from a single, constant input pressure, but either have been constrained to low rates of flow of air or have required complex fabrication processes. Here, we describe a pneumatic oscillator fabricated from flexible, but inextensible, sheets that provides high rates of airflow for practical locomotion by combining three instabilities: out-of-plane buckling of the sheets, kinking of tubing attached to the sheets, and a system-level instability resulting from connection of an odd number of pneumatic inverters made from these sheets in a loop. This device, which we call a “buckling-sheet ring oscillator” (BRO), directly generates movement from its own interaction with its surroundings and consists only of readily available materials assembled in a simple process—specifically, stacking acetate sheets, nylon film, and double-sided tape, and attaching an elastomeric tube. A device incorporating a BRO is capable of both translational and rotational motion over varied terrain (even without a tether) and can climb upward against gravity and downward against the buoyant force encountered under water.

Recent evidence suggests that the fat mass and obesity-associated gene (FTO) genotype may interact with dietary intakes in relation to adiposity. We tested the effect of FTO variant on weight loss in response to 2-year diet interventions. FTO rs1558902 was genotyped in 742 obese adults who were randomly assigned to one of four diets differing in the proportions of fat, protein, and carbohydrate. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography. We found significant modification effects for intervention varying in dietary protein on 2-year changes in fat-free mass, whole body total percentage of fat mass, total adipose tissue mass, visceral adipose tissue mass, and superficial adipose tissue mass (for all interactions, P < 0.05). Carriers of the risk allele had a greater reduction in weight, body composition, and fat distribution in response to a high-protein diet, whereas an opposite genetic effect was observed on changes in fat distribution in response to a low-protein diet. Likewise, significant interaction patterns also were observed at 6 months. Our data suggest that a high-protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals with the risk allele of the FTO variant rs1558902.

Introduction: Adiponectin is an anti-inflammatory peptide hormone secreted by adipocytes and has been related with decreased risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), but longitudinal data are limited and inconsistent. Hypothesis: Higher circulating adiponectin levels are associated with lower risk of T2D, CVD, and all-cause mortality in healthy women. Methods: Baseline adiponectin levels, measured by an immunoassay, were available on 15,131 women from the Nurses’ Health study I and II, who were part of 11 separate nested case-control studies and free of T2D, CVD, and cancer at study baseline. Associations of adiponectin levels with incident T2D, CVD (including coronary heart disease [CHD], stroke, and CVD death), and all-cause mortality were estimated using Cox regressions adjusted for study design characters, established risk factors and confounders including menopausal status, hormone therapy, and continuous body mass index. We also analyzed associations of 26 adiponectin expression-associated variants (in adipose tissue) with T2D, CVD, and all-cause mortality in the UK Biobank study. Results: During up to 22 years (289,408 person-years) of follow-up, 2,578 T2D cases, 1,827 CVD cases (including 745 CHD, 1,108 stroke and 428 CVD deaths), and 2,741 deaths occurred. In multivariable models, hazard ratios (95% confidence intervals) comparing the highest quartile of plasma adiponectin to the lowest were 0.17 (0.14-0.21; P trend <0.001) for T2D, 0.82 (0.69-0.96; P trend =0.005) for CVD, 0.66 (0.51-0.86; P trend <0.001) for CHD, 0.91 (0.73-1.12; P trend =0.34) for stroke, 0.69 (0.48-0.98; P trend =0.10) for CVD death, and 0.77 (0.66-0.90; P trend =0.005) for all-cause mortality. Genetic alleles associated with increased adiponectin expression in adipose tissue were associated with decreased risk of CVD, but no associations were observed for T2D and all-cause mortality. Conclusions: Higher adiponectin levels are associated with decreased risk of cardiometabolic diseases and all-cause mortality.

Stainless steel square honeycomb core sandwich and solid monolithic beams have been subjected to high-pressure, short-duration impulses using a shock simulation technique involving high-speed impact of Al foam projectiles. The experiments have been designed to achieve two objectives: (i) to demonstrate the benefits of sandwich construction, and (ii) to assess the fidelity of dynamic finite element calculations in simulating the structural response. The results affirm that, when subjected to impulse levels representative of those associated with nearby explosions, the sandwich beams exhibit smaller displacements than the solid beams at equivalent weight. The benefit is especially large at lower impulses where the effective dynamic strength of the honeycomb core prevents crushing. The measurements and finite element simulations having greatest relevance to the shock resistance are found to correspond closely, particularly the displacements and the core crushing strains. One implication is that the dynamic finite element model has the requisite fidelity at impulse levels of interest.