Under-utilization of evidence-based drug treatment in patients with heart failure is only partially explained by dissimilarity to patients enrolled in landmark trials: a report from the Euro Heart Survey on Heart Failure

Aims Surveys on heart failure management suggest under-utilization of life-saving evidence-based treatment. Evidence-based medicine and clinical guidelines are based on the results of randomized controlled trials. Therefore, we investigated how patients who fulfilled the enrolment criteria of randomized trials were treated in real life. Methods and results We selected three large placebo-controlled trials of patients with chronic heart failure, in which ACE-inhibitors (ACE-Is), β-blockers, and spironolactone proved to be safe and effective. The major enrolment criteria of trials were identified and applied to patients enrolled in the Euro Heart Survey on Heart Failure to identify the proportion of patients eligible for treatment and also treated appropriately. Of the 10 701 patients who were enrolled in the Euro Heart Survey on Heart Failure, only a small percentage (13%) would have qualified for participation in at least one of the selected trials. Patients who fulfilled enrolment criteria of the identified trials were more likely to be treated with ACE-Is (83% of SOLVD-eligible patients), β-blockers (54% of MERIT-HF-eligible patients), and aldosterone antagonists (43% of RALES-eligible patients) than trial-ineligible patients. Almost half of SOLVD-eligible patients who were treated with ACE-Is received the target dose as recommended in the guidelines, but only <10% of MERIT-HF eligible patients who were treated with β-blockers received the target dose. Conclusion ACE-Is are widely utilized but given in lower doses than proven effective in clinical trials. β-Blockers are underused and given in lower doses to patients who fulfil the enrolment criteria of relevant landmark trial

High-Energy Cosmology: gamma rays and neutrinos from beyond the galaxy

Our knowledge of the high-energy universe is undergoing a period of rapid change as new astronomical detectors of high-energy radiation start to operate at their design sensitivities. Now is a boomtime for high-energy astrophysics, with new discoveries from Swift and HESS, results from MAGIC and VERITAS starting to be reported, the upcoming launches of the gamma-ray space telescopes GLAST and AGILE, and anticipated data releases from IceCube and Auger. A formalism for calculating statistical properties of cosmological gamma-ray sources is presented. Application is made to model calculations of the statistical distributions of gamma-ray and neutrino emission from (i) beamed sources, specifically, long-duration GRBs, blazars, and extagalactic microquasars, and (ii) unbeamed sources, including normal galaxies, starburst galaxies and clusters. Expressions for the integrated intensities of faint beamed and unbeamed high-energy radiation sources are also derived. A toy model for the background intensity of radiation from dark-matter annihilation taking place in the early universe is constructed. Estimates for the gamma-ray fluxes of local group galaxies, starburst, and infrared luminous galaxies are briefly reviewed. Because the brightest extragalactic gamma-ray sources are flaring sources, and these are the best targets for sources of PeV -- EeV neutrinos and ultra-high energy cosmic rays, rapidly slewing all-sky telescopes like MAGIC and an all-sky gamma-ray observatory beyond Milagro will be crucial for optimal science return in the multi-messenger age.Comment: 10 pages, 3 figs, accepted for publication in the Barcelona Conference on Multimessenger Astronomy; corrected eq. 27, revised Fig. 3, added 2 ref

An assessment of the resolution limitation due to radiation-damage in x-ray diffraction microscopy

X-ray diffraction microscopy (XDM) is a new form of x-ray imaging that is being practiced at several third-generation synchrotron-radiation x-ray facilities. Although only five years have elapsed since the technique was first introduced, it has made rapid progress in demonstrating high-resolution threedimensional imaging and promises few-nm resolution with much larger samples than can be imaged in the transmission electron microscope. Both life- and materials-science applications of XDM are intended, and it is expected that the principal limitation to resolution will be radiation damage for life science and the coherent power of available x-ray sources for material science. In this paper we address the question of the role of radiation damage. We use a statistical analysis based on the so-called "dose fractionation theorem" of Hegerl and Hoppe to calculate the dose needed to make an image of a lifescience sample by XDM with a given resolution. We conclude that the needed dose scales with the inverse fourth power of the resolution and present experimental evidence to support this finding. To determine the maximum tolerable dose we have assembled a number of data taken from the literature plus some measurements of our own which cover ranges of resolution that are not well covered by reports in the literature. The tentative conclusion of this study is that XDM should be able to image frozen-hydrated protein samples at a resolution of about 10 nm with "Rose-criterion" image quality.Comment: 9 pages, 4 figure

The Multiwavelength Approach to Unidentified Gamma-Ray Sources

As the highest-energy photons, gamma rays have an inherent interest to astrophysicists and particle physicists studying high-energy, nonthermal processes. Gamma-ray telescopes complement those at other wavelengths, especially radio, optical, and X-ray, providing the broad, mutiwavelength coverage that has become such a powerful aspect of modern astrophysics. Multiwavelength techniques of various types have been developed to help identify and explore unidentified gamma-ray sources. This overview summarizes the ideas behind several of these methods.Comment: Proceedings of the Conference "The Multiwavelength Approach to Unidentified Sources", to appear in the journal Astrophysics and Space Scienc

Effect of a nurse-coordinated prevention programme on cardiovascular risk after an acute coronary syndrome: main results of the RESPONSE randomised trial

Objective To quantify the impact of a practical, hospital-based nurse-coordinated prevention programme on cardiovascular risk, integrated into the routine clinical care of patients discharged after an acute coronary syndrome, as compared with usual care only. Design RESPONSE (Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists) was a randomised clinical trial. Setting Multicentre trial in secondary and tertiary healthcare settings. Participants 754 patients admitted for acute coronary syndrome. Intervention A nurse-coordinated prevention programme, consisting of four outpatient nurse clinic visits, focusing on healthy lifestyles, biometric risk factors and medication adherence, in addition to usual care. Main outcome measures The main outcome was 10-year cardiovascular mortality risk as estimated by Systematic Coronary Risk Evaluation at 12 months follow-up. Secondary outcomes included Framingham Coronary Risk Score at 12 months, in addition to changes in individual risk factors. Risk factor control was classified as ‘poor’ if 0 to 3 factors were on target, ‘fair’ if 4 to 6 factors were on target, and ‘good’ if 7 to 9 were on target. Results The mean Systematic Coronary Risk Evaluation at 12 months was 4.4 per cent (SD 4.5) in the intervention group and 5.4 per cent (SD 6.2) in the control group (p=0.021), representing a 17.4% relative risk reduction. At 12 months, risk factor control classified as ‘good’ was achieved in 35% of patients in the intervention group compared with 25% in the control group (p=0.003). Attendance to the nurse-coordinated prevention programme was 92%. In the intervention group, 86 rehospitalisations were observed against 132 in the control group (relative risk reduction 34.8%, p=0.023). Conclusions The nurse-coordinated hospital-based prevention programme in addition to usual care is a practical, yet effective method for reduction of cardiovascular risk in patients with coronary disease. Our data suggest that the counselling component of the programme may lead to a reduction in hospital readmissions

Gamma rays from colliding winds of massive stars

Colliding winds of massive binaries have long been considered as potential sites of non-thermal high-energy photon production. This is motivated by the detection of non-thermal spectra in the radio band, as well as by correlation studies of yet unidentified EGRET gamma-ray sources with source populations appearing in star formation regions. This work re-considers the basic radiative processes and its properties that lead to high energy photon production in long-period massive star systems. We show that Klein-Nishina effects as well as the anisotropic nature of the inverse Compton scattering, the dominating leptonic emission process, likely yield spectral and variability signatures in the gamma-ray domain at or above the sensitivity of current or upcoming gamma ray instruments like GLAST-LAT. In addition to all relevant radiative losses, we include propagation (such as convection in the stellar wind) as well as photon absorption effects, which a priori can not be neglected. The calculations are applied to WR140 and WR147, and predictions for their detectability in the gamma-ray regime are provided. Physically similar specimen of their kind like WR146, WR137, WR138, WR112 and WR125 may be regarded as candidate sources at GeV energies for near-future gamma-ray experiments. Finally, we discuss several aspects relevant for eventually identifying this source class as a gamma-ray emitting population. Thereby we utilize our findings on the expected radiative behavior of typical colliding wind binaries in the gamma-ray regime as well as its expected spatial distribution on the gamma-ray sky

Neuroimaging and Responsibility Assessments

Could neuroimaging evidence help us to assess the degree of a person’s responsibility for a crime which we know that they committed? This essay defends an affirmative answer to this question. A range of standard objections to this high-tech approach to assessing people’s responsibility is considered and then set aside, but I also bring to light and then reject a novel objection—an objection which is only encountered when functional (rather than structural) neuroimaging is used to assess people’s responsibility

Experimental investigation of transverse spin asymmetries in muon-p SIDIS processes: Collins asymmetries

The COMPASS Collaboration at CERN has measured the transverse spin azimuthal asymmetry of charged hadrons produced in semi-inclusive deep inelastic scattering using a 160 GeV positive muon beam and a transversely polarised NH_3 target. The Collins asymmetry of the proton was extracted in the Bjorken x range 0.003<x<0.7. These new measurements confirm with higher accuracy previous measurements from the COMPASS and HERMES collaborations, which exhibit a definite effect in the valence quark region. The asymmetries for negative and positive hadrons are similar in magnitude and opposite in sign. They are compatible with model calculations in which the u-quark transversity is opposite in sign and somewhat larger than the d-quark transversity distribution function. The asymmetry is extracted as a function of Bjorken $x$, the relative hadron energy $z$ and the hadron transverse momentum p_T^h. The high statistics and quality of the data also allow for more detailed investigations of the dependence on the kinematic variables. These studies confirm the leading-twist nature of the Collins asymmetry.Comment: 11 pages, 5 figure

Low Q^2 Jet Production at HERA and Virtual Photon Structure

The transition between photoproduction and deep-inelastic scattering is investigated in jet production at the HERA ep collider, using data collected by the H1 experiment. Measurements of the differential inclusive jet cross-sections dsigep/dEt* and dsigmep/deta*, where Et* and eta* are the transverse energy and the pseudorapidity of the jets in the virtual photon-proton centre of mass frame, are presented for 0 < Q2 < 49 GeV2 and 0.3 < y < 0.6. The interpretation of the results in terms of the structure of the virtual photon is discussed. The data are best described by QCD calculations which include a partonic structure of the virtual photon that evolves with Q2.Comment: 20 pages, 5 Figure

Hadron Production in Diffractive Deep-Inelastic Scattering

Characteristics of hadron production in diffractive deep-inelastic positron-proton scattering are studied using data collected in 1994 by the H1 experiment at HERA. The following distributions are measured in the centre-of-mass frame of the photon dissociation system: the hadronic energy flow, the Feynman-x (x_F) variable for charged particles, the squared transverse momentum of charged particles (p_T^{*2}), and the mean p_T^{*2} as a function of x_F. These distributions are compared with results in the gamma^* p centre-of-mass frame from inclusive deep-inelastic scattering in the fixed-target experiment EMC, and also with the predictions of several Monte Carlo calculations. The data are consistent with a picture in which the partonic structure of the diffractive exchange is dominated at low Q^2 by hard gluons.Comment: 16 pages, 6 figures, submitted to Phys. Lett.