Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

CONTRIBUTION TO THE KNOWLEDGE OF THE GROUND BEETLE FAUNA FROM SERBIA (COLEOPTERA: CARABIDAE)

During a two-year period of research on the ground beetle fauna in agroecosystems in northern Serbia 19,003 carabid specimens were collected. A total of 67 species from 29 genera were identified. Harpalus distinguendus (Duftschmid, 1812), Amara aenea (De Geer, 1774), Poecilus cupreus (Linnaeus, 1758), and Amara similata (Goeze, 1777) were the dominant species in the winter oilseed rape and winter wheat. The ground beetle genera richest in species were Harpalus, Amara, Calathus, Poecilus and Brachinus. Seven species were new for the ground beetle fauna of Serbia: Calathus cinctus Motschulsky, 1850, Laemostenus complanatus (Dejean, 1828), Brachinus nigricornis Gebler, 1829, Cychrus attenuatus (Fabricius, 1792), Patrobus septentrionis Dejean, 1828, Anchomenus cyaneus Dejean, 1828 and Pterostichus leonisi Apfelbeck, 1904. Three species were recorded for the first time for Vojvodina Province in Serbia: Harpalus signaticornis (Duftschmid, 1812), Harpalus taciturnus Dejean, 1829 and Patrobus atrorufus (Ström, 1768). Newly recorded species were collected in epigeic pitfall traps. Six of them were found in oilseed rape while one was found in winter wheat

A high-precision rf trap with minimized micromotion for an In+ multiple-ion clock

We present an experiment to characterize our new linear ion trap designed for the operation of a many-ion optical clock using 115-In^+ as clock ions. For the characterization of the trap as well as the sympathetic cooling of the clock ions we use 172-Yb^+. The trap design has been derived from finite element method (FEM) calculations and a first prototype based on glass-reinforced thermoset laminates was built. This paper details on the trap manufacturing process and micromotion measurement. Excess micromotion is measured using photon-correlation spectroscopy with a resolution of 1.1nm in motional amplitude, and residual axial rf fields in this trap are compared to FEM calculations. With this method, we demonstrate a sensitivity to systematic clock shifts due to excess micromotion of |({\Delta}{\nu}/{\nu})| = 8.5x10^-20. Based on the measurement of axial rf fields of our trap, we estimate a number of twelve ions that can be stored per trapping segment and used as an optical frequency standard with a fractional inaccuracy of \leq 1x10^-18 due to micromotion.Comment: 19 pages with 14 picture

International Physical Activity and Built Environment Study of Adolescents : IPEN Adolescent design, protocol and measures

Introduction: Only international studies can provide the full variability of built environments and accurately estimate effect sizes of relations between contrasting environments and health-related outcomes. The aims of the International Physical Activity and Environment Study of Adolescents (IPEN Adolescent) are to estimate the strength, shape and generalisability of associations of the community environment (geographic information systems (GIS)-based and self-reported) with physical activity and sedentary behaviour (accelerometer-measured and self-reported) and weight status (normal/overweight/obese). Methods and analysis: The IPEN Adolescent observational, cross-sectional, multicountry study involves recruiting adolescent participants (ages 11-19 years) and one parent/guardian from neighbourhoods selected to ensure wide variations in walkability and socioeconomic status using common protocols and measures. Fifteen geographically, economically and culturally diverse countries, from six continents, participated: Australia, Bangladesh, Belgium, Brazil, Czech Republic, Denmark, Hong Kong SAR, India, Israel, Malaysia, New Zealand, Nigeria, Portugal, Spain and USA. Countries provided survey and accelerometer data (15 countries), GIS data (11), global positioning system data (10), and pedestrian environment audit data (8). A sample of n=6950 (52.6% female; mean age=14.5, SD=1.7) adolescents provided survey data, n=4852 had 4 or more 8+ hours valid days of accelerometer data, and n=5473 had GIS measures. Physical activity and sedentary behaviour were measured by waist-worn ActiGraph accelerometers and self-reports, and body mass index was used to categorise weight status. Ethics and dissemination: Ethical approval was received from each study site's Institutional Review Board for their in-country studies. Informed assent by adolescents and consent by parents was obtained for all participants. No personally identifiable information was transferred to the IPEN coordinating centre for pooled datasets. Results will be communicated through standard scientific channels and findings used to advance the science of environmental correlates of physical activity, sedentary behaviour and weight status, with the ultimate goal to stimulate and guide actions to create more activity-supportive environments internationally

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations