160 research outputs found
Vedolizumab: an α4β7 integrin antagonist for ulcerative colitis and Crohn’s disease
Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic, relapsing inflammatory bowel diseases associated with significant morbidity. Conventional therapies for these diseases include corticosteroids, aminosalicylates, immunomodulators, and monoclonal antibodies. Over the years tumor necrosis factor (TNF)-α antagonists alone or in combination with other therapies have emerged as the cornerstone of treatment for induction and maintenance of remission of moderate to severe UC and CD. Unfortunately, some patients with moderate to severe UC and CD are unable to attain or maintain remission with TNF-α antagonist treatment. Vedolizumab, a humanized monoclonal antibody, is the first integrin receptor antagonist approved that selectively antagonizes α4β7 gastrointestinal integrin receptors. US Food and Drug Administration approval is for treatment of patients with moderate to severe active UC and CD who have inadequate response with, lost response to, or are intolerant to a TNF-α antagonist or an immunomodulator; or have inadequate response with, are intolerant to, or demonstrate dependence on corticosteroids. When administered according to approved dosing in patients with moderate to severe CD and UC, vedolizumab induces clinical response rates up to 31.4% and 47.1% at week 6, and clinical remission rates up to 39% and 41.8% at week 52, respectively. Serious adverse events reported with vedolizumab include serious infections, malignancies, and anaphylaxis. Since vedolizumab is gastrointestinal selective, to date, it has not shown evidence of causing progressive multifocal leukoencephalopathy; however, postmarketing studies monitoring for this adverse effect are ongoing. Further assessment of vedolizumab earlier in the course of these diseases and in combination with other therapies is warranted
The major upgrade of the MAGIC telescopes, Part II: A performance study using observations of the Crab Nebula
MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes located in
the Canary island of La Palma, Spain. During summer 2011 and 2012 it underwent
a series of upgrades, involving the exchange of the MAGIC-I camera and its
trigger system, as well as the upgrade of the readout system of both
telescopes. We use observations of the Crab Nebula taken at low and medium
zenith angles to assess the key performance parameters of the MAGIC stereo
system. For low zenith angle observations, the standard trigger threshold of
the MAGIC telescopes is ~50GeV. The integral sensitivity for point-like sources
with Crab Nebula-like spectrum above 220GeV is (0.66+/-0.03)% of Crab Nebula
flux in 50 h of observations. The angular resolution, defined as the sigma of a
2-dimensional Gaussian distribution, at those energies is < 0.07 degree, while
the energy resolution is 16%. We also re-evaluate the effect of the systematic
uncertainty on the data taken with the MAGIC telescopes after the upgrade. We
estimate that the systematic uncertainties can be divided in the following
components: < 15% in energy scale, 11-18% in flux normalization and +/-0.15 for
the energy spectrum power-law slope.Comment: 21 pages, 25 figures, accepted for publication in Astroparticle
Physic
Investigating the peculiar emission from the new VHE gamma-ray source H1722+119
The MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) telescopes observed
the BL Lac object H1722+119 (redshift unknown) for six consecutive nights
between 2013 May 17 and 22, for a total of 12.5 h. The observations were
triggered by high activity in the optical band measured by the KVA (Kungliga
Vetenskapsakademien) telescope. The source was for the first time detected in
the very high energy (VHE, GeV) -ray band with a statistical
significance of 5.9 . The integral flux above 150 GeV is estimated to
be per cent of the Crab Nebula flux. We used contemporaneous
high energy (HE, 100 MeV GeV) -ray observations from
Fermi-LAT (Large Area Telescope) to estimate the redshift of the source. Within
the framework of the current extragalactic background light models, we estimate
the redshift to be . Additionally, we used contemporaneous
X-ray to radio data collected by the instruments on board the Swift satellite,
the KVA, and the OVRO (Owens Valley Radio Observatory) telescope to study
multifrequency characteristics of the source. We found no significant temporal
variability of the flux in the HE and VHE bands. The flux in the optical and
radio wavebands, on the other hand, did vary with different patterns. The
spectral energy distribution (SED) of H1722+119 shows surprising behaviour in
the Hz frequency range. It can be modelled
using an inhomogeneous helical jet synchrotron self-Compton model.Comment: 12 pages, 5 figures, 2 table
MAGIC detection of short-term variability of the high-peaked BL Lac object 1ES 0806+524
The high-frequency-peaked BL Lac (HBL) 1ES 0806+524 (z = 0.138) was
discovered in VHE rays in 2008. Until now, the broad-band spectrum of
1ES 0806+524 has been only poorly characterized, in particular at high
energies. We analysed multiwavelength observations from rays to radio
performed from 2011 January to March, which were triggered by the high activity
detected at optical frequencies. These observations constitute the most precise
determination of the broad-band emission of 1ES 0806+524 to date. The
stereoscopic MAGIC observations yielded a -ray signal above 250 GeV of
per cent of the Crab Nebula flux with a statistical
significance of 9.9 . The multiwavelength observations showed
significant variability in essentially all energy bands, including a VHE
-ray flare that lasted less than one night, which provided
unprecedented evidence for short-term variability in 1ES 0806+524. The spectrum
of this flare is well described by a power law with a photon index of between 150 GeV and 1 TeV and an integral flux of
per cent of the Crab Nebula flux above 250 GeV. The spectrum during the
non-flaring VHE activity is compatible with the only available VHE observation
performed in 2008 with VERITAS when the source was in a low optical state. The
broad-band spectral energy distribution can be described with a one-zone
Synchrotron Self Compton model with parameters typical for HBLs, indicating
that 1ES 0806+524 is not substantially different from the HBLs previously
detected.Comment: 12 pages, 8 figures, 3 tables, accepted 2015 April 20 for publication
in Monthly Notices of the Royal Astronomical Society Main Journa
Detection of very high energy gamma-ray emission from the gravitationally-lensed blazar QSO B0218+357 with the MAGIC telescopes
Context. QSO B0218+357 is a gravitationally lensed blazar located at a
redshift of 0.944. The gravitational lensing splits the emitted radiation into
two components, spatially indistinguishable by gamma-ray instruments, but
separated by a 10-12 day delay. In July 2014, QSO B0218+357 experienced a
violent flare observed by the Fermi-LAT and followed by the MAGIC telescopes.
Aims. The spectral energy distribution of QSO B0218+357 can give information on
the energetics of z ~ 1 very high energy gamma- ray sources. Moreover the
gamma-ray emission can also be used as a probe of the extragalactic background
light at z ~ 1. Methods. MAGIC performed observations of QSO B0218+357 during
the expected arrival time of the delayed component of the emission. The MAGIC
and Fermi-LAT observations were accompanied by quasi-simultaneous optical data
from the KVA telescope and X-ray observations by Swift-XRT. We construct a
multiwavelength spectral energy distribution of QSO B0218+357 and use it to
model the source. The GeV and sub-TeV data, obtained by Fermi-LAT and MAGIC,
are used to set constraints on the extragalactic background light. Results.
Very high energy gamma-ray emission was detected from the direction of QSO
B0218+357 by the MAGIC telescopes during the expected time of arrival of the
trailing component of the flare, making it the farthest very high energy
gamma-ray sources detected to date. The observed emission spans the energy
range from 65 to 175 GeV. The combined MAGIC and Fermi-LAT spectral energy
distribution of QSO B0218+357 is consistent with current extragalactic
background light models. The broad band emission can be modeled in the
framework of a two zone external Compton scenario, where the GeV emission comes
from an emission region in the jet, located outside the broad line region.Comment: 11 pages, 6 figures, accepted for publication in A&
Probing the very-high-energy gamma-ray spectral curvature in the blazar PG 1553+113 with the MAGIC telescopes
PG 1553+113 is a very-high-energy (VHE, ) -ray
emitter classified as a BL Lac object. Its redshift is constrained by
intergalactic absorption lines in the range . The MAGIC telescopes
have monitored the source's activity since 2005. In early 2012, PG 1553+113 was
found in a high-state, and later, in April of the same year, the source reached
its highest VHE flux state detected so far. Simultaneous observations carried
out in X-rays during 2012 April show similar flaring behaviour. In contrast,
the -ray flux at observed by Fermi-LAT is
compatible with steady emission. In this paper, a detailed study of the flaring
state is presented. The VHE spectrum shows clear curvature, being well fitted
either by a power law with an exponential cut-off or by a log-parabola. A
simple power-law fit hypothesis for the observed shape of the PG 1553+113 VHE
-ray spectrum is rejected with a high significance (fit probability
P=2.6 ). The observed curvature is compatible with the
extragalactic background light (EBL) imprint predicted by current generation
EBL models assuming a redshift . New constraints on the redshift are
derived from the VHE spectrum. These constraints are compatible with previous
limits and suggest that the source is most likely located around the optical
lower limit, , based on the detection of Ly absorption. Finally,
we find that the synchrotron self-Compton (SSC) model gives a satisfactory
description of the observed multi-wavelength spectral energy distribution
during the flare.Comment: 13 pages, 7 figures, accepted for publication in MNRA
First broadband characterization and redshift determination of the VHE blazar MAGIC J2001+439
We aim to characterize the broadband emission from 2FGL J2001.1+4352, which
has been associated with the unknown-redshift blazar MG4 J200112+4352. Based on
its gamma-ray spectral properties, it was identified as a potential very high
energy (VHE; E > 100 GeV) gamma-ray emitter. The source was observed with MAGIC
first in 2009 and later in 2010 within a multi-instrument observation campaign.
The MAGIC observations yielded 14.8 hours of good quality stereoscopic data.
The object was monitored at radio, optical and gamma-ray energies during the
years 2010 and 2011. The source, named MAGIC J2001+439, is detected for the
first time at VHE with MAGIC at a statistical significance of 6.3 {\sigma} (E >
70 GeV) during a 1.3-hour long observation on 2010 July 16. The
multi-instrument observations show variability in all energy bands with the
highest amplitude of variability in the X-ray and VHE bands. We also organized
deep imaging optical observations with the Nordic Optical Telescope in 2013 to
determine the source redshift. We determine for the first time the redshift of
this BL Lac object through the measurement of its host galaxy during low blazar
activity. Using the observational evidence that the luminosities of BL Lac host
galaxies are confined to a relatively narrow range, we obtain z = 0.18 +/-
0.04. Additionally, we use the Fermi-LAT and MAGIC gamma-ray spectra to provide
an independent redshift estimation, z = 0.17 +/- 0.10. Using the former (more
accurate) redshift value, we adequately describe the broadband emission with a
one-zone SSC model for different activity states and interpret the few-day
timescale variability as produced by changes in the high-energy component of
the electron energy distribution.Comment: 17 pages, 15 figures, Accepted for publication in A&
Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies
We present the first joint analysis of gamma-ray data from the MAGIC
Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for
gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We
combine 158 hours of Segue 1 observations with MAGIC with 6-year observations
of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the
annihilation cross-section for dark matter particle masses between 10 GeV and
100 TeV - the widest mass range ever explored by a single gamma-ray analysis.
These limits improve on previously published Fermi-LAT and MAGIC results by up
to a factor of two at certain masses. Our new inclusive analysis approach is
completely generic and can be used to perform a global, sensitivity-optimized
dark matter search by combining data from present and future gamma-ray and
neutrino detectors.Comment: 19 pages, 3 figures. V2: Few typos corrected and references added.
Matches published version JCAP 02 (2016) 03
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