Fractional flow reserve versus angiography in guiding management to optimize outcomes in non–ST-elevation myocardial infarction (FAMOUS-NSTEMI): rationale and design of a randomized controlled clinical trial

<p>Background: In patients with acute non–ST-elevation myocardial infarction (NSTEMI), coronary arteriography is usually recommended; but visual interpretation of the angiogram is subjective. We hypothesized that functional assessment of coronary stenosis severity with a pressure-sensitive guide wire (fractional flow reserve [FFR]) would have additive diagnostic, clinical, and health economic utility as compared with angiography-guided standard care.</p> <p>Methods and design: A prospective multicenter parallel-group 1:1 randomized controlled superiority trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% severity (threshold for FFR measurement) will be conducted. Patients will be randomized immediately after coronary angiography to the FFR-guided group or angiography-guided group. All patients will then undergo FFR measurement in all vessels with a coronary stenosis ≥30% severity including culprit and nonculprit lesions. Fractional flow reserve will be disclosed to guide treatment in the FFR-guided group but not disclosed in the “angiography-guided” group. In the FFR-guided group, an FFR ≤0.80 will be an indication for revascularization by percutaneous coronary intervention or coronary artery bypass surgery, as appropriate. The primary outcome is the between-group difference in the proportion of patients allocated to medical management only compared with revascularization. Secondary outcomes include the occurrence of cardiac death or hospitalization for myocardial infarction or heart failure, quality of life, and health care costs. The minimum and average follow-up periods for the primary analysis are 6 and 18 months, respectively.</p> <p>Conclusions: Our developmental clinical trial will address the feasibility of FFR measurement in NSTEMI and the influence of FFR disclosure on treatment decisions and health and economic outcomes.</p&gt

Accretion onto the Supermassive Black Hole in M87

Chandra X-ray observations of the giant elliptical galaxy M87 resolve the thermal state of the hot interstellar medium into the accretion (Bondi) radius of its central 3 10^9 Msun black hole. We measure the X-ray gas temperature and density profiles and calculate the Bondi accretion rate, Mdot_Bondi \sim 0.1 Msun/yr. The X-ray luminosity of the active nucleus of M87 observed with Chandra is L_{x, 0.5-7 \keV} \sim 7 \times 10^{40}erg/s. This value is much less than the predicted nuclear luminosity, L_{Bondi} \sim 5 \times 10^{44} erg/s, for accretion at the Bondi rate with a canonical accretion radiative efficiency of 10%. If the black hole in M87 accretes at this rate it must do so at a much lower radiative efficiency than the canonical value. The multiwavelength spectrum of the nucleus is consistent with that predicted by an advection-dominated flow. However, as is likely, the X-ray nucleus is dominated by jet emission then the properties of flow must be modified, possibly by outflows. We show that the overall energetics of the system are just consistent with the predicted Bondi nuclear power. This suggests that either most of the accretion energy is released in the relativistic jet or that the central engine of M87 undergoes on-off activity cycles. We show that, at present, the energy dumped into the ISM by the jet may reduce the accretion rate onto the black hole by a factor \propto (v_j/c_s)^{-2}, where v_j is the jet velocity and c_s the ISM sound speed, and that this is sufficient to account for the low nuclear luminosity.Comment: emulateapj.sty, revised version, accepted by Ap

Homocysteine, grey matter and cognitive function in adults with cardiovascular disease

Background: Elevated total plasma homocysteine (tHcy) has been associated with cognitive impairment, vascular disease and brain atrophy. Methods: We investigated 150 volunteers to determine if the association between high tHcy and cerebral grey matter volume and cognitive function is independent of cardiovascular disease. Results: Participants with high tHcy (≥15 μmol/L) showed a widespread relative loss of grey matter compared with people with normal tHcy, although differences between the groups were minimal once the analyses were adjusted for age, gender, diabetes, hypertension, smoking and prevalent cardiovascular disease. Individuals with high tHcy had worse cognitive scores across a range of domains and less total grey matter volume, although these differences were not significant in the adjusted models. Conclusions: Our results suggest that the association between high tHcy and loss of cerebral grey matter volume and decline in cognitive function is largely explained by increasing age and cardiovascular diseases and indicate that the relationship is not causal

The COS-Dwarfs Survey: The Carbon Reservoir Around sub-L* Galaxies

We report new observations of circumgalactic gas from the COS-Dwarfs survey, a systematic investigation of the gaseous halos around 43 low-mass z $\leq$ 0.1 galaxies using background QSOs observed with the Cosmic Origins Spectrograph. From the projected 1D and 2D distribution of C IV absorption, we find that C IV absorption is detected out to ~ 0.5 R$_{vir}$ of the host galaxies. The C IV absorption strength falls off radially as a power law and beyond 0.5 R$_{vir}$, no C IV absorption is detected above our sensitivity limit of ~ 50-100 m$\AA$. We find a tentative correlation between detected C IV absorption strength and star formation, paralleling the strong correlation seen in highly ionized oxygen for L~L* galaxies by the COS-Halos survey. The data imply a large carbon reservoir in the CGM of these galaxies, corresponding to a minimum carbon mass of $\gtrsim$ 1.2$\times 10^6$ $M_\odot$ out to ~ 110 kpc. This mass is comparable to the carbon mass in the ISM and more than the carbon mass currently in stars of these galaxies. The C IV absorption seen around these sub-L* galaxies can account for almost two-thirds of all $W_r$> 100 m$\AA$ C IV absorption detected at low z. Comparing the C IV covering fraction with hydrodynamical simulations, we find that an energy-driven wind model is consistent with the observations whereas a wind model of constant velocity fails to reproduce the CGM or the galaxy properties.Comment: 18 Pages, 11 Figures, ApJ 796 13

The COS-Halos Survey: Physical Conditions and Baryonic Mass in the Low-Redshift Circumgalactic Medium

We analyze the physical conditions of the cool, photoionized (T $\sim 10^4$ K) circumgalactic medium (CGM) using the COS-Halos suite of gas column density measurements for 44 gaseous halos within 160 kpc of $L \sim L^*$ galaxies at $z \sim 0.2$. These data are well described by simple photoionization models, with the gas highly ionized (n$_{\rm HII}$/n$_{\rm H} \gtrsim 99\%$) by the extragalactic ultraviolet background (EUVB). Scaling by estimates for the virial radius, R$_{\rm vir}$, we show that the ionization state (tracked by the dimensionless ionization parameter, U) increases with distance from the host galaxy. The ionization parameters imply a decreasing volume density profile n$_{\rm H}$ = (10$^{-4.2 \pm 0.25}$)(R/R$_{\rm vir})^{-0.8\pm0.3}$. Our derived gas volume densities are several orders of magnitude lower than predictions from standard two-phase models with a cool medium in pressure equilibrium with a hot, coronal medium expected in virialized halos at this mass scale. Applying the ionization corrections to the HI column densities, we estimate a lower limit to the cool gas mass M$_{\rm CGM}^{\rm cool} > 6.5 \times 10^{10}$ M$_{\odot}$ for the volume within R $<$ R$_{\rm vir}$. Allowing for an additional warm-hot, OVI-traced phase, the CGM accounts for at least half of the baryons purported to be missing from dark matter halos at the 10$^{12}$ M$_{\odot}$ scale.Comment: 19 pages, 12 Figures, and a 37-page Appendix with 36 additional figures. Accepted to ApJ June 21 201

Electronic health records to facilitate clinical research

Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research

Curvaton reheating: an application to braneworld inflation

The curvaton was introduced recently as a distinct inflationary mechanism for generating adiabatic density perturbations. Implicit in that scenario is that the curvaton offers a new mechanism for reheating after inflation, as it is a form of energy density not diluted by the inflationary expansion. We consider curvaton reheating in the context of a braneworld inflation model, {\em steep inflation}, which features a novel use of the braneworld to give a new mechanism for ending inflation. The original steep inflation model featured reheating by gravitational particle production, but the inefficiency of that process brings observational difficulties. We demonstrate here that the phenomenology of steep inflation is much improved by curvaton reheating.Comment: 8 pages RevTeX4 file with two figures incorporated. Improved referencing, matches PRD accepted versio

Discovery of a Gas-Rich Companion to the Extremely Metal-Poor Galaxy DDO 68

We present HI spectral-line imaging of the extremely metal-poor galaxy DDO 68. This system has a nebular oxygen abundance of only 3% Z$_{\odot}$, making it one of the most metal-deficient galaxies known in the local volume. Surprisingly, DDO 68 is a relatively massive and luminous galaxy for its metal content, making it a significant outlier in the mass-metallicity and luminosity-metallicity relationships. The origin of such a low oxygen abundance in DDO 68 presents a challenge for models of the chemical evolution of galaxies. One possible solution to this problem is the infall of pristine neutral gas, potentially initiated during a gravitational interaction. Using archival HI spectral-line imaging obtained with the Karl G. Jansky Very Large Array, we have discovered a previously unknown companion of DDO 68. This low-mass (M$_{\rm HI}$ $=$ 2.8$\times$10$^{7}$ M$_{\odot}$), recently star-forming (SFR$_{\rm FUV}$ $=$ 1.4$\times$10$^{-3}$ M$_{\odot}$ yr$^{-1}$, SFR$_{\rm H\alpha}$ $<$ 7$\times$10$^{-5}$ M$_{\odot}$ yr$^{-1}$) companion has the same systemic velocity as DDO 68 (V$_{\rm sys}$ $=$ 506 km s$^{-1}$; D $=$ 12.74$\pm$0.27 Mpc) and is located at a projected distance of 42 kpc. New HI maps obtained with the 100m Robert C. Byrd Green Bank Telescope provide evidence that DDO 68 and this companion are gravitationally interacting at the present time. Low surface brightness HI gas forms a bridge between these objects.Comment: Accepted for publication in the Astrophysical Journal Letter