Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87–0.94), with an additional relative risk for CVD of 0.92 (0.87–0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75–0.93), 0.76 (0.67–0.85), 0.69 (0.59–0.79), or 0.63 (0.52–0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Catchment scale tracer testing from karstic features in a porous limestone

Tracer testing was undertaken from sinking streams feeding the Chalk, a porous limestone aquifer characterised by frequent small-scale surface karst features. The objective was to investigate the nature and extent of sub-surface karstic development in the aquifer. Previous tracer testing has demonstrated rapid flow combined with low attenuation of tracer. In this study, at two sites rapid groundwater flow was combined with very high attenuation and at two other sites no tracer was detected at springs within the likely catchment area of the stream sinks tested, suggesting that tracer was totally attenuated along the flowpath. It is proposed that the networks beneath stream sinks in the Chalk and other mildly karstic aquifers distribute recharge into multiple enlarged fractures that divide and become smaller at each division whereas the networks around springs have a predominantly tributary topology that concentrates flow into a few relatively large cavities, a morphology with similarities to that of the early stages of karstification. Tracer attenuation is controlled by the degree to which the two networks are directly connected. In the first state, there is no direct linkage and flow between the two networks is via primary fractures in which tracer attenuation is extreme. The second state is at a percolation threshold in which a single direct link joins the two networks. A very small proportion of tracer reaches the spring rapidly but overall attenuation is very high. In the third state, the recharge and discharge networks are integrated therefore a large fraction of tracer reaches the spring and peak concentrations are relatively high. Despite the large number of stream sinks that recharge the Chalk aquifer, these results suggest that sub-surface conduit development may not always be continuous, with flow down smaller fissures and fractures causing high attenuation of solutes and particulates providing a degree of protection to groundwater outlets that is not seen in more highly karstic aquifers. Bacteriophage tracers that can be detected at very large dilutions (1015) are recommended for investigating groundwater pathways where attenuation may be high

Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 mu m/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 mu m/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.Thrombosis and Hemostasi

Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials. © 2020 American Heart Association, Inc

Limits on an Energy Dependence of the Speed of Light from a Flare of the Active Galaxy PKS 2155-304

Accepted for publication by Phys. Rev. LettersIn the past few decades, several models have predicted an energy-dependence of the speed of light in the context of quantum gravity. For cosmological sources such as active galaxies, this minuscule effect can add up to measurable photon-energy dependent time lags. In this paper a search for such time lags during the H.E.S.S. observations of the exceptional very high energy flare of the active galaxy PKS 2155-304 on 28 July in 2006 is presented. Since no significant time lag is found, lower limits on the energy scale of speed of light modifications are derived

Discovery of Gamma-Ray Emission From the Shell-Type Supernova Remnant RCW 86 With Hess

6 pages, 5 figuresThe shell-type supernova remnant (SNR) RCW 86, possibly associated with the historical supernova SN 185, with its relatively large size (about 40' in diameter) and the presence of non-thermal X-rays is a promising target for gamma-ray observations. The high sensitivity, good angular resolution of a few arc minutes and the large field of view of the High Energy Stereoscopic System (H.E.S.S.) make it ideally suited for the study of the gamma-ray morphology of such extended sources. H.E.S.S. observations have indeed led to the discovery of the SNR RCW 86 in very high energy (VHE; E > 100 GeV) gamma-rays. With 31 hours of observation time, the source is detected with a statistical significance of 8.5 sigma and is significantly more extended than the H.E.S.S. point spread function. Morphological studies have been performed and show that the gamma-ray flux does not correlate perfectly with the X-ray emission. The flux from the remnant is ~10% of the flux from the Crab nebula, with a similar photon index of about 2.5. Possible origins of the very high energy gamma-ray emission, via either Inverse Compton scattering by electrons or the decay of neutral pions produced by proton interactions, are discussed on the basis of spectral features obtained both in the X-ray and gamma-ray regimes

Energy Spectrum of Cosmic-Ray Electrons at TeV Energies

5 pages, 3 figures. Accepted for publication by Phys. Rev. Letters; modified to include latest ATIC data pointsThe very large collection area of ground-based gamma-ray telescopes gives them a substantial advantage over balloon/satellite based instruments in the detection of very-high-energy (>600 GeV) cosmic-ray electrons. Here we present the electron spectrum derived from data taken with the H.E.S.S. system of imaging atmospheric Cherenkov telescopes. In this measurement, the first of this type, we are able to extend the measurement of the electron spectrum beyond the range accessible to direct measurements. We find evidence for a substantial steepening in the energy spectrum above 600 GeV compared to lower energies