Neuroimaging the consciousness of self: Review, and conceptual-methodological framework

We review neuroimaging research investigating self-referential processing (SRP), that is, how we respond to stimuli that reference ourselves, prefaced by a lexical-thematic analysis of words indicative of “self-feelings”. We consider SRP as occurring verbally (V-SRP) and non-verbally (NV-SRP), both in the controlled, “top-down” form of introspective and interoceptive tasks, respectively, as well as in the “bottom-up” spontaneous or automatic form of “mind wandering” and “body wandering” that occurs during resting state. Our review leads us to outline a conceptual and methodological framework for future SRP research that we briefly apply toward understanding certain psychological and neurological disorders symptomatically associated with abnormal SRP. Our discussion is partly guided by William James’ original writings on the consciousness of self

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Multi-wavelength characterization of the blazar S5~0716+714 during an unprecedented outburst phase

The BL Lac object S5~0716+714, a highly variable blazar, underwent an impressive outburst in January 2015 (Phase A), followed by minor activity in February (Phase B). The MAGIC observations were triggered by the optical flux observed in Phase A, corresponding to the brightest ever reported state of the source in the R-band. The comprehensive dataset collected is investigated in order to shed light on the mechanism of the broadband emission. Multi-wavelength light curves have been studied together with the broadband Spectral Energy Distributions (SEDs). The data set collected spans from radio, optical photometry and polarimetry, X-ray, high-energy (HE, 0.1 GeV 100 GeV) with MAGIC. The flaring state of Phase A was detected in all the energy bands, providing for the first time a multi-wavelength sample of simultaneous data from the radio band to the VHE. In the constructed SED the \textit{Swift}-XRT+\textit{NuSTAR} data constrain the transition between the synchrotron and inverse Compton components very accurately, while the second peak is constrained from 0.1~GeV to 600~GeV by \textit{Fermi}+MAGIC data. The broadband SED cannot be described with a one-zone synchrotron self-Compton model as it severely underestimates the optical flux in order to reproduce the X-ray to $\gamma$-ray data. Instead we use a two-zone model. The EVPA shows an unprecedented fast rotation. An estimation of the redshift of the source by combined HE and VHE data provides a value of $z = 0.31 \pm 0.02_{stats} \pm 0.05_{sys}$, confirming the literature value. The data show the VHE emission originating in the entrance and exit of a superluminal knot in and out a recollimation shock in the inner jet. A shock-shock interaction in the jet seems responsible for the observed flares and EVPA swing. This scenario is also consistent with the SED modelling

Multi-wavelength characterization of the blazar S5 0716+714 during an unprecedented outburst phase

Context. The BL Lac object S5 0716+714, a highly variable blazar, underwent an impressive outburst in January 2015 (Phase A), followed by minor activity in February (Phase B). The MAGIC observations were triggered by the optical flux observed in Phase A, corresponding to the brightest ever reported state of the source in the R-band.Aims.The comprehensive dataset collected is investigated in order to shed light on the mechanism of the broadband emission.Methods. Multi-wavelength light curves have been studied together with the broadband spectral energy distributions (SEDs). The sample includes data from Effelsberg, OVRO, Metsahovi, VLBI, CARMA, IRAM, SMA, Swift-UVOT, KVA, Tuorla, Steward, RINGO3, KANATA, AZT-8+ST7, Perkins, LX-200, Swift-XRT, NuSTAR, Fermi-LAT and MAGIC.Results. The flaring state of Phase A was detected in all the energy bands, providing for the first time a multi-wavelength sample of simultaneous data from the radio band to the very-high-energy (VHE, E> 100 GeV). In the constructed SED, the Swift-XRT +NuSTAR data constrain the transition between the synchrotron and inverse Compton components very accurately, while the second peak is constrained from 0.1 GeV to 600 GeV by Fermi+MAGIC data. The broadband SED cannot be described with a one-zone synchrotron self-Compton model as it severely underestimates the optical flux in order to reproduce the X-ray to y-ray data. Instead we use a two-zone model. The electric vector position angle (EVPA) shows an unprecedented fast rotation. An estimation of the redshift of the source by combined high-energy (HE, 0.1 GeV < E < 100 GeV) and VHE data provides a value of ,z = 0.31 +/- 0.02(stats) +/- 0.05(sys), confirming the literature value.Conclusions. The data show the VHE emission originating in the entrance and exit of a superluminal knot in and out of a recollimation shock in the inner jet. A shock-shock interaction in the jet seems responsible for the observed flares and EVPA swing. This scenario is also consistent with the SED modeling

Unraveling the Complex Behavior of Mrk 421 with Simultaneous X-Ray and VHE Observations during an Extreme Flaring Activity in 2013 April*

We report on a multiband variability and correlation study of the TeV blazar Mrk 421 during an exceptional flaring activity observed from 2013 April 11 to 19. The study uses, among others, data from GLAST-AGILE Support Program (GASP) of the Whole Earth Blazar Telescope (WEBT), Swift, Nuclear Spectroscopic Telescope Array (NuSTAR), Fermi Large Area Telescope, Very Energetic Radiation Imaging Telescope Array System (VERITAS), and Major Atmospheric Gamma Imaging Cherenkov (MAGIC). The large blazar activity and the 43 hr of simultaneous NuSTAR and MAGIC/VERITAS observations permitted variability studies on 15 minute time bins over three X-ray bands (3-7 keV, 7-30 keV, and 30-80 keV) and three very-high-energy (VHE; >0.1 TeV) gamma-ray bands (0.2-0.4 TeV, 0.4-0.8 TeV, and >0.8 TeV). We detected substantial flux variations on multi-hour and sub-hour timescales in all of the X-ray and VHE gamma-ray bands. The characteristics of the sub-hour flux variations are essentially energy independent, while the multi-hour flux variations can have a strong dependence on the energy of the X-rays and the VHE gamma-rays. The three VHE bands and the three X-ray bands are positively correlated with no time lag, but the strength and characteristics of the correlation change substantially over time and across energy bands. Our findings favor multi-zone scenarios for explaining the achromatic/chromatic variability of the fast/slow components of the light curves, as well as the changes in the flux-flux correlation on day-long timescales. We interpret these results within a magnetic reconnection scenario, where the multi-hour flux variations are dominated by the combined emission from various plasmoids of different sizes and velocities, while the sub-hour flux variations are dominated by the emission from a single small plasmoid moving across the magnetic reconnection layer

Investigation of the correlation patterns and the Compton dominance variability of Mrk 421 in 2017

Aims. We present a detailed characterisation and theoretical interpretation of the broadband emission of the paradigmatic TeV blazar Mrk 421, with a special focus on the multi-band flux correlations.Methods. The dataset has been collected through an extensive multi-wavelength campaign organised between 2016 December and 2017 June. The instruments involved are MAGIC, FACT, Fermi-LAT, Swift, GASP-WEBT, OVRO, Medicina, and Metsahovi. Additionally, four deep exposures (several hours long) with simultaneous MAGIC and NuSTAR observations allowed a precise measurement of the falling segments of the two spectral components.Results. The very-high-energy (VHE; E > 100 GeV) gamma rays and X-rays are positively correlated at zero time lag, but the strength and characteristics of the correlation change substantially across the various energy bands probed. The VHE versus X-ray fluxes follow different patterns, partly due to substantial changes in the Compton dominance for a few days without a simultaneous increase in the X-ray flux (i.e., orphan gamma-ray activity). Studying the broadband spectral energy distribution (SED) during the days including NuSTAR observations, we show that these changes can be explained within a one-zone leptonic model with a blob that increases its size over time. The peak frequency of the synchrotron bump varies by two orders of magnitude throughout the campaign. Our multi-band correlation study also hints at an anti-correlation between UV-optical and X-ray at a significance higher than 3 sigma. A VHE flare observed on MJD 57788 (2017 February 4) shows gamma-ray variability on multi-hour timescales, with a factor ten increase in the TeV flux but only a moderate increase in the keV flux. The related broadband SED is better described by a two-zone leptonic scenario rather than by a one-zone scenario. We find that the flare can be produced by the appearance of a compact second blob populated by high energetic electrons spanning a narrow range of Lorentz factors, from gamma(min)' = 2 x 10(4) to gamma(max)' = 6 x 10(5).</p

Multiband variability studies and novel broadband SED modeling of Mrk 501 in 2009

Aims. We present an extensive study of the BL Lac object Mrk 501 based on a data set collected during the multi-instrument campaign spanning from 2009 March 15 to 2009 August 1, which includes, among other instruments, MAGIC, VERITAS, Whipple 10 m, and Fermi-LAT to cover the gamma-ray range from 0.1 GeV to 20 TeV; RXTE and Swift to cover wavelengths from UV to hard X-rays; and GASP-WEBT, which provides coverage of radio and optical wavelengths. Optical polarization measurements were provided for a fraction of the campaign by the Steward and St. Petersburg observatories. We evaluate the variability of the source and interband correlations, the gamma-ray flaring activity occurring in May 2009, and interpret the results within two synchrotron self-Compton (SSC) scenarios.Methods. The multiband variability observed during the full campaign is addressed in terms of the fractional variability, and the possible correlations are studied by calculating the discrete correlation function for each pair of energy bands where the significance was evaluated with dedicated Monte Carlo simulations. The space of SSC model parameters is probed following a dedicated grid-scan strategy, allowing for a wide range of models to be tested and offering a study of the degeneracy of model-to-data agreement in the individual model parameters, hence providing a less biased interpretation than the "single-curve SSC model adjustment" typically reported in the literature.Results. We find an increase in the fractional variability with energy, while no significant interband correlations of flux changes are found on the basis of the acquired data set. The SSC model grid-scan shows that the flaring activity around May 22 cannot be modeled adequately with a one-zone SSC scenario (using an electron energy distribution with two breaks), while it can be suitably described within a two (independent) zone SSC scenario. Here, one zone is responsible for the quiescent emission from the averaged 4.5-month observing period, while the other one, which is spatially separated from the first, dominates the flaring emission occurring at X-rays and very-high-energy (> 100 GeV, VHE) gamma-rays. The flaring activity from May 1, which coincides with a rotation of the electric vector polarization angle (EVPA), cannot be satisfactorily reproduced by either a one-zone or a two-independent-zone SSC model, yet this is partially affected by the lack of strictly simultaneous observations and the presence of large flux changes on sub-hour timescales (detected at VHE gamma rays).Conclusions. The higher variability in the VHE emission and lack of correlation with the X-ray emission indicate that, at least during the 4.5-month observing campaign in 2009, the highest energy (and most variable) electrons that are responsible for the VHE gamma rays do not make a dominant contribution to the similar to 1 keV emission. Alternatively, there could be a very variable component contributing to the VHE gamma-ray emission in addition to that coming from the SSC scenario. The studies with our dedicated SSC grid-scan show that there is some degeneracy in both the one-zone and the two-zone SSC scenarios probed, with several combinations of model parameters yielding a similar model-to-data agreement, and some parameters better constrained than others. The observed gamma-ray flaring activity, with the EVPA rotation coincident with the first gamma-ray flare, resembles those reported previously for low frequency peaked blazars, hence suggesting that there are many similarities in the flaring mechanisms of blazars with different jet properties