Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

The first airborne comparison of N 2 O 5 measurements over the UK using a CIMS and BBCEAS during the RONOCO campaign

Dinitrogen pentoxide (N 2 O 5 ) plays a central role in nighttime tropospheric chemistry as its formation and subsequent loss in sink processes limits the potential for tropospheric photochemistry to generate ozone the next day. Since accurate observational data for N 2 O 5 are critical to examine our understanding of this chemistry, it is vital also to evaluate the capabilities of N 2 O 5 measurement techniques through the co-deployment of the available instrumentation. This work compares measurements of N 2 O 5 from two aircraft instruments on board the Facility for Airborne Atmospheric Measurements (FAAM) BAe-146 aircraft during the Role of Nighttime Chemistry in Controlling the Oxidising Capacity of the Atmosphere (RONOCO) measurement campaigns over the United Kingdom in 2010 and 2011. A chemical ionisation mass spectrometer (CIMS), deployed for the first time for ambient N 2 O 5 detection during RONOCO, measured N 2 O 5 directly using I - ionisation chemistry and an aircraft-based broadband cavity enhanced absorption spectrometer (BBCEAS), developed specifically for RONOCO, measured N 2 O 5 by thermally dissociating N 2 O 5 and quantifying the resultant NO 3 spectroscopically within a high finesse optical cavity. N 2 O 5 mixing ratios were simultaneously measured at 1 second time resolution (1 Hz) by the two instruments for 8 flights during RONOCO. The sensitivity for the CIMS instrument was 52 ion counts per pptv with a limit of detection of 7.4 pptv for 1 Hz measurements. BBCEAS, a proven technique for N 2 O 5 measurement, had a limit of detection of 2 pptv. Comparison of the observed N 2 O 5 mixing ratios show excellent agreement between the CIMS and BBCEAS methods for the whole dataset, as indicated by the square of the linear correlation coefficient, R 2 = 0.89. Even stronger correlations (R 2 values up to 0.98) were found for individual flights. Altitudinal profiles of N 2 O 5 obtained by CIMS and BBCEAS also showed close agreement (R 2 = 0.93). Similarly, N 2 O 5 mixing ratios from both instruments were greatest within pollution plumes and were strongly positively correlated with the NO 2 concentrations. The transition from day to nighttime chemistry was observed during a dusk-to-dawn flight during the summer 2011 RONOCO campaign: the CIMS and BBCEAS instruments simultaneously detected the increasing N 2 O 5 concentrations after sunset. The performance of the CIMS and BBCEAS techniques demonstrated in the RONOCO dataset illustrate the benefits that accurate, high-frequency, aircraft-based measurements have for improving understanding the nighttime chemistry of N 2 O 5

Energy and ozone fluxes over sea ice

We present surface layer measurements made over Hudson Bay seaice during February/March 2008 from the COBRA (Impact of combined iodine and bromine release on the Arctic atmosphere) experiment which formed part of the International OASIS (Ocean-Atmosphere-SeaIce-Snowpack) IPY programme. All components of the local surface energy balance were measured and it was defined by net radiative cooling throughout most of the day, mainly balanced by the conductive heat flux from the warmer sea water to the cooler seaice at the surface, and a small net radiative warming for a few hours after midday. Unique ground-level ozonefluxes were measured by eddy covariance and deposition velocities ranged from +0.5 mm s−1 (deposition) to −1.5 mm s−1 (emission). Ozone profile measurements suggested ozoneflux divergence within the surface layer. The observed bi-directional fluxes and flux divergence with height reveal the complexity of surface ozonefluxes in the Arctic spring time surface layer, and show that ozone exchange with the seaice surface is best probed using the eddy covariance method alongside frequent or continuous profile measurements. In this study, the local in-situ ozone-halogen photochemistry was identified as weakly controlling the measured ozoneflux, whereas horizontal advection and vertical mixing were considered more important in influencing fluxes. Under these conditions, several measurement sites would be desirable in order to quantify the contribution of advection to the local surface exchange

Airborne measurements of HC(O)OH in the European Arctic: A winter – summer comparison

This study represents the first airborne, in-situ measurements of HC(O)OH in the European Arctic, across the winter and summer seasons. HC(O)OH concentrations are under predicted at present, particularly in the mid to high northern latitudes. Data presented here probe unconfirmed sources of HC(O)OH in the Arctic, and would suggest an ocean source of HC(O)OH is more significant than proposed land sources in both winter and summer environments. A maximum concentration of 420 ppt was recorded over the ocean during the July 2012 campaign. This was more than 1.7 times greater than the maximum land concentration reported. Calculated estimates on HC(O)OH production would suggest diiodomethane photolysis could represent a significant source of HC(O)OH in marine environments in the European Arctic. Enhanced HC(O)OH concentrations observed at altitudes greater than 2 km particularly during the March campaign highlight the significance of long range transport on the European Arctic budget. In addition, two HC(O)OH vertical profiles between the altitudes 0.3–6.6 km are presented to provide a more representative vertical profile for this latitude which may be used to improve forthcoming regional and global modelling of the HC(O)OH budget