Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence

We conducted a 1000 Genomes-imputed genome-wide association study (GWAS) meta-analysis for nicotine dependence, defined by the Fagerstrom Test for Nicotine Dependence in 17 074 ever smokers from five European-ancestry samples. We followed up novel variants in 7469 ever smokers from five independent European-ancestry samples. We identified genome-wide significant association in the alpha-4 nicotinic receptor subunit (CHRNA4) gene on chromosome 20q13: lowest P = 8.0 x 10(-9) across all the samples for rs2273500-C (frequency = 0.15; odds ratio = 1.12 and 95% confidence interval = 1.08-1.17 for severe vs mild dependence). rs2273500-C, a splice site acceptor variant resulting in an alternate CHRNA4 transcript predicted to be targeted for nonsense-mediated decay, was associated with decreased CHRNA4 expression in physiologically normal human brains (lowest P = 7.3 x 10(-4)). Importantly, rs2273500-C was associated with increased lung cancer risk (N = 28 998, odds ratio = 1.06 and 95% confidence interval = 1.00-1.12), likely through its effect on smoking, as rs2273500-C was no longer associated with lung cancer after adjustment for smoking. Using criteria for smoking behavior that encompass more than the single 'cigarettes per day' item, we identified a common CHRNA4 variant with important regulatory properties that contributes to nicotine dependence and smoking-related consequences.Peer reviewe

Manufacturing Energy and Carbon Footprints

Significant opportunities exist for improving energy efficiency in U.S. manufacturing. A first step in realizing these opportunities is to identify how industry is using energy. Where does it come from? What form is it in? Where is it used? How much is lost? Answering these questions is the focus of this paper and the analysis described herein. Manufacturing energy and carbon footprints map energy consumption and losses, as well as greenhouse gas emissions, for the fifteen most energy intensive manufacturing sectors, and for the entire U.S. manufacturing sector. Analysts and decision-makers utilize the footprints to better understand the distribution of energy use in energy-intensive industries and the accompanying energy losses. The footprints provide a benchmark from which to calculate the benefits of improving energy efficiency and for prioritizing opportunity analysis. A breakdown of energy consumption by energy type and end use allows for comparison both within and across sectors

Combining New Satellite Tools and Models to Examine Role of Mesoscale Interactions in Formation and Intensification of Tropical Cyclones

AMS Conference on Satellite Meteorology; 15-18 Oct. 2001; Madison, WI; United StatesThe objective of this research is to start filling the mesoscale gap to improve understanding and probability forecasts of formation and intensity variations of tropical cyclones. Sampling by aircraft equipped to measure mesoscale processes is expensive, thus confined in place and time. Hence we turn to satellite products. This paper reports preliminary results of a tropical cyclone genesis and early intensification study. We explore the role of mesoscale processes using a combination of products from TRMM, QuikSCAT, AMSU, also SSM/I, geosynchronous and model output. Major emphasis is on the role of merging mesoscale vortices. These initially form in midlevel stratiform cloud. When they form in regions of lowered Rossby radius of deformation (strong background vorticity) the mesoscale vortices can last long enough to interact and merge, with the weaker vortex losing vorticity to the stronger, which can then extend down to the surface. In an earlier cyclongenesis case (Oliver 1993) off Australia, intense deep convection occurred when the stronger vortex reached the surface; this vortex became the storm center while the weaker vortex was sheared out as the major rainband. In our study of Atlantic tropical cyclones originating from African waves, we use QuikSCAT to examine surface winds in the African monsoon trough and in the vortices which move westward off the coast, which may or may not undergo genesis (defined by NHC as reaching TD, or tropical depression, with a west wind to the south of the surface low). We use AMSU mainly to examine development of warm cores. TRMM passive microwave TMI is used with SSM/I to look at the rain structure, which often indicates eye formation, and to look at the ice scattering signatures of deep convection. The TRMM precipitation radar, PR, when available, gives precipitation cross sections. So far we have detailed studies of two African-origin cyclones, one which became severe hurricane Floyd 1999, and the other reached TD2 in June 2000 and then died out. The atmosphere off West African is dry and stable. It becomes less so between June and September, as the SST and convection heat up. QuikSCAT shows the African monsoon trough and shear zone extend westward over the ocean to nearly 30 degrees West. The evidence is strong that the two cyclones had in common multiple midlevel mergers, which extended to the surface keeping the surface vortex strong. These continued until both systems were designated TD's by NHC. In the June 2000 case, the main reason for failure was the lower SST and dry, stable atmosphere. This is shown by the comparison of the equivalent potential temperature maps and profiles with those from pre-Floyd. In the vortex which became Floyd, QuikSCAT shows continuous importation of high theta e (warm, moist) air from the south. From September 2-8, this air flowed around the vortex center, building up a high theta-e pool to the north. Then late on September 9, a 100-km wide jet of high theta-e air penetrated the vortex core, a major convective burst' was observed, and an intensifying, more elevated warm core was seen on AMSU. Rapid pressure fall and wind intensification were underway by 0000 UTC on September 10. Floyd became a Hurricane at 1200 UTC on Sept 10, 1999, with successive convective bursts running the hurricane thermodynamic engine by intensifying the warm core. TD2 was a strong African vortex, sustained by moderate convection (up to about 12.5 km) offshore of Africa. It peaked on June 23, showing an apparent "eye" on passive microwave composites. However, it could not assemble the ingredients for a convective burst. Thus it failed to get the thermodynamic hurricane engine going before it moved too far west of the region of lowered Rossby radius. By June 26, cloud systems were dying out. On June 25, a surface vortex was no longer seen on QuikSCAT, although one continued above the surface on model profiles until June 27. One of our main findings so far is showing the role of the mesoscale vortex interactions in sustaining some African vortices far out in to the mid Atlantic, where under adequate thermal/moisture conditions the hurricane heat engine can sometimes be started. We are working on similar studies of Cindy and Irene 1999. Cindy illustrates a case of wind shear working against an early-stage hurricane heat engine, while Irene formed from a Caribbean wave. An enormous value of combinations of satellite tools is that tropical cyclones can be studied in all parts of the global oceans where they occur. Detailed studies like ours are labor intensive but many statistical studies can be based on physical postulates developed. There are other new tools such as MODIS on TERRA of the Earth Observing System (EOS) which can be used to study the microphysics of tropical cyclones world wide, in particular to investigate the presence of mixed phase and the impact of atmospheric aerosols on the hydrometeor structure and rainfall from tropical cyclones.Approved for public release; distribution is unlimited

Impact of personally measured pollutants on cardiac function

Epidemiological studies have shown associations between ambient air pollution and changes in heart rate variability (HRV). However, studies using personal air pollution measurements, especially with exposure averages <24 h, are still rare. Between February and March 2008 HRV data as well as personal exposure to particulate matter <2.5 mu m (PM25), and particle number concentrations (PNC) were collected in five volunteers for up to 8.3 h on a 5 min resolution. Information about the participant's whereabouts was also collected. Mixed models were used to analyze concurrent and up to 30 min delayed effects of air pollutants as well as being in traffic on 5 min-averages of heart rate (HR), high and low frequency power (HF and LF), standard deviation of all normal-to-normal intervals (SDNN), and the root mean square of successive interval differences (RMSSD). Results are presented as %-change from the mean per increase in interquartile range of air pollutant. In total, 474 5-min segments were available for analysis. We observed concurrent and delayed reductions in SDNN of about 0.8-1.0% in association with a 5.4 mu g/m3 increase in PM25. However, being in traffic by car led to an increase of about 20% 10-14 min and 15-19 min later. An increase in PM25 or PNC was associated with lagged decreases for RMSSD and HF. We detected concurrent reductions in RMSSD (-17.6% [95%-confidence interval: 29.1; -4.3]) when being in traffic by bike/foot. Being in traffic by car was associated with an immediate reduction in LF while more delayed increases in LF were observed when being in traffic by bike/foot. Air pollution and traffic effects on HR were less consistent. These rapid changes in HRV within 30 min might be mediated by the autonomic nervous system in response to direct reflexes from receptors in the lungs. (C) 2013 Elsevier GmbH. All rights reserved