The Community Atmosphere Model (CAM), version 5, is now coupled to extensive tropospheric and stratospheric chemistry, called CAM5-chem, and is available in addition to CAM4-chem in the Community ...Earth System Model (CESM) version 1.2. The main focus of this paper is to compare the performance of configurations with internally derived "free running" (FR) meteorology and "specified dynamics" (SD) against observations from surface, aircraft, and satellite, as well as understand the origin of the identified differences. We focus on the representation of aerosols and chemistry. All model configurations reproduce tropospheric ozone for most regions based on in situ and satellite observations. However, shortcomings exist in the representation of ozone precursors and aerosols. Tropospheric ozone in all model configurations agrees for the most part with ozonesondes and satellite observations in the tropics and the Northern Hemisphere within the variability of the observations. Southern hemispheric tropospheric ozone is consistently underestimated by up to 25%. Differences in convection and stratosphere to troposphere exchange processes are mostly responsible for differences in ozone in the different model configurations. Carbon monoxide (CO) and other volatile organic compounds are largely underestimated in Northern Hemisphere mid-latitudes based on satellite and aircraft observations. Nitrogen oxides (NOx) are biased low in the free tropical troposphere, whereas peroxyacetyl nitrate (PAN) is overestimated in particular in high northern latitudes. The present-day methane lifetime estimates are compared among the different model configurations. These range between 7.8 years in the SD configuration of CAM5-chem and 8.8 years in the FR configuration of CAM4-chem and are therefore underestimated compared to observational estimations. We find that differences in tropospheric aerosol surface area between CAM4 and CAM5 play an important role in controlling the burden of the tropical tropospheric hydroxyl radical (OH), which causes differences in tropical methane lifetime of about half a year between CAM4-chem and CAM5-chem. In addition, different distributions of NOx from lightning explain about half of the difference between SD and FR model versions in both CAM4-chem and CAM5-chem. Remaining differences in the tropical OH burden are due to enhanced tropical ozone burden in SD configurations compared to the FR versions, which are not only caused by differences in chemical production or loss but also by transport and mixing. For future studies, we recommend the use of CAM5-chem configurations, due to improved aerosol description and inclusion of aerosol–cloud interactions. However, smaller tropospheric surface area density in the current version of CAM5-chem compared to CAM4-chem results in larger oxidizing capacity in the troposphere and therefore a shorter methane lifetime.
The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the "pain" pathway. Heterologously expressed VR1 can be activated by vanilloid compounds, protons, ...or heat (>43°C), but whether this channel contributes to chemical or thermal sensitivity in vivo is not known. Here, we demonstrate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli. VR1-/-mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation. Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia.
The aim of this study was to compare the safety and efficacy of Resolute zotarolimus-eluting stents (ZES) (Medtronic Cardiovascular, Santa Rosa, California) with Xience V everolimus-eluting stents ...(EES) (Abbott Vascular Devices, Santa Clara, California) at 1-year follow-up.
Only 1 randomized trial previously compared these stents.
This investigator-initiated, patient-blinded, randomized noninferiority study had limited exclusion criteria (acute ST-segment elevation myocardial infarctions not eligible). Patients (n = 1,391; 81.4% of eligible population) were randomly assigned to ZES (n = 697) or EES (n = 694). Liberal use of stent post-dilation was encouraged. Cardiac biomarkers were systematically assessed. The primary endpoint was target vessel failure (TVF), a composite of cardiac death, myocardial infarction not clearly attributable to non-target vessels, and clinically indicated target-vessel revascularization. An external independent research organization performed clinical event adjudication (100% follow-up data available). Analysis was by intention-to-treat.
Acute coronary syndromes were present in 52% and "off-label" feature in 77% of patients. Of the lesions, 70% were type B2/C; the post-dilation rate was very high (82%). In ZES and EES, TVF occurred in 8.2% and 8.1%, respectively (absolute risk-difference 0.1%; 95% confidence interval: -2.8% to 3.0%, p(noninferiority) = 0.001). There was no significant between-group difference in TVF components. The definite-or-probable stent thrombosis rates were relatively low and similar for ZES and EES (0.9% and 1.2%, respectively, p = 0.59). Definite stent thrombosis rates were also low (0.58% and 0%, respectively, p = 0.12). In EES, probable stent thrombosis beyond day 8 was observed only in patients not adhering to dual antiplatelet therapy.
Resolute ZES were noninferior to Xience V EES in treating "real-world" patients with a vast majority of complex lesions and "off-label" indications for drug-eluting stents, which were implanted with liberal use of post-dilation. (The Real-World Endeavor Resolute Versus XIENCE V Drug-Eluting SteNt Study: Head-to-head Comparison of Clinical Outcome After Implantation of Second Generation Drug-eluting Stents in a Real World Scenario; NCT01066650).
A large body of published work shows that proton (hydrogen 1 (1)H) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors ...present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.
Ozone changes and associated climate impacts in the Coupled Model Intercomparison Project Phase 5 (CMIP5) simulations are analyzed over the historical (1960–2005) and future (2006–2100) period under ...four Representative Concentration Pathways (RCP). In contrast to CMIP3, where half of the models prescribed constant stratospheric ozone, CMIP5 models all consider past ozone depletion and future ozone recovery. Multimodel mean climatologies and long‐term changes in total and tropospheric column ozone calculated from CMIP5 models with either interactive or prescribed ozone are in reasonable agreement with observations. However, some large deviations from observations exist for individual models with interactive chemistry, and these models are excluded in the projections. Stratospheric ozone projections forced with a single halogen, but four greenhouse gas (GHG) scenarios show largest differences in the northern midlatitudes and in the Arctic in spring (~20 and 40 Dobson units (DU) by 2100, respectively). By 2050, these differences are much smaller and negligible over Antarctica in austral spring. Differences in future tropospheric column ozone are mainly caused by differences in methane concentrations and stratospheric input, leading to ~10 DU increases compared to 2000 in RCP 8.5. Large variations in stratospheric ozone particularly in CMIP5 models with interactive chemistry drive correspondingly large variations in lower stratospheric temperature trends. The results also illustrate that future Southern Hemisphere summertime circulation changes are controlled by both the ozone recovery rate and the rate of GHG increases, emphasizing the importance of simulating and taking into account ozone forcings when examining future climate projections.
Key Points
CMIP5 models all consider past ozone depletion and future ozone recovery
Multimodel ozone agrees well with observations but individual models deviate
Future climate is sensitive to rates of both ozone recovery and GHG increases
In the months since the publication of the first results, the noise performance of LISA Pathfinder has improved because of reduced Brownian noise due to the continued decrease in pressure around the ...test masses, from a better correction of noninertial effects, and from a better calibration of the electrostatic force actuation. In addition, the availability of numerous long noise measurement runs, during which no perturbation is purposely applied to the test masses, has allowed the measurement of noise with good statistics down to 20 μHz. The Letter presents the measured differential acceleration noise figure, which is at (1.74±0.05) fm s^{-2}/sqrtHz above 2 mHz and (6±1)×10 fm s^{-2}/sqrtHz at 20 μHz, and discusses the physical sources for the measured noise. This performance provides an experimental benchmark demonstrating the ability to realize the low-frequency science potential of the LISA mission, recently selected by the European Space Agency.
We examined mortality in relation to coronary artery disease (CAD) as assessed by ≥64-detector row coronary computed tomography angiography (CCTA).
Although CCTA has demonstrated high diagnostic ...performance for detection and exclusion of obstructive CAD, the prognostic findings of CAD by CCTA have not, to date, been examined for age- and sex-specific outcomes.
We evaluated a consecutive cohort of 24,775 patients undergoing ≥64-detector row CCTA between 2005 and 2009 without known CAD who met inclusion criteria. In these patients, CAD by CCTA was defined as none (0% stenosis), mild (1% to 49% stenosis), moderate (50% to 69% stenosis), or severe (≥70% stenosis). CAD severity was judged on a per-patient, per-vessel, and per-segment basis. Time to mortality was estimated using multivariable Cox proportional hazards models.
At a 2.3 ± 1.1-year follow-up, 404 deaths had occurred. In risk-adjusted analysis, both per-patient obstructive (hazard ratio HR: 2.60; 95% confidence interval CI: 1.94 to 3.49; p < 0.0001) and nonobstructive (HR: 1.60; 95% CI: 1.18 to 2.16; p = 0.002) CAD conferred increased risk of mortality compared with patients without evident CAD. Incident mortality was associated with a dose-response relationship to the number of coronary vessels exhibiting obstructive CAD, with increasing risk observed for nonobstructive (HR: 1.62; 95% CI: 1.20 to 2.19; p = 0.002), obstructive 1-vessel (HR: 2.00; 95% CI: 1.43 to 2.82; p < 0.0001), 2-vessel (HR: 2.92; 95% CI: 2.00 to 4.25; p < 0.0001), or 3-vessel or left main (HR: 3.70; 95% CI: 2.58 to 5.29; p < 0.0001) CAD. Importantly, the absence of CAD by CCTA was associated with a low rate of incident death (annualized death rate: 0.28%). When stratified by age <65 years versus ≥65 years, younger patients experienced higher hazards for death for 2-vessel (HR: 4.00; 95% CI: 2.16 to 7.40; p < 0.0001 vs. HR: 2.46; 95% CI: 1.51 to 4.02; p = 0.0003) and 3-vessel (HR: 6.19; 95% CI: 3.43 to 11.2; p < 0.0001 vs. HR: 3.10; 95% CI: 1.95 to 4.92; p < 0.0001) CAD. The relative hazard for 3-vessel CAD (HR: 4.21; 95% CI: 2.47 to 7.18; p < 0.0001 vs. HR: 3.27; 95% CI: 1.96 to 5.45; p < 0.0001) was higher for women as compared with men.
Among individuals without known CAD, nonobstructive and obstructive CAD by CCTA are associated with higher rates of mortality, with risk profiles differing for age and sex. Importantly, absence of CAD is associated with a very favorable prognosis.
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