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The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study.
IntroductionDuchenne muscular dystrophy (DMD) subjects ≥5 years with nonsense mutations were followed for 48 weeks in a multicenter, randomized, double-blind, placebo-controlled trial of ataluren. Placebo arm data (N = 57) provided insight into the natural history of the 6-minute walk test (6MWT) and other endpoints.MethodsEvaluations performed every 6 weeks included the 6-minute walk distance (6MWD), timed function tests (TFTs), and quantitative strength using hand-held myometry.ResultsBaseline age (≥7 years), 6MWD, and selected TFT performance are strong predictors of decline in ambulation (Δ6MWD) and time to 10% worsening in 6MWD. A baseline 6MWD of <350 meters was associated with greater functional decline, and loss of ambulation was only seen in those with baseline 6MWD <325 meters. Only 1 of 42 (2.3%) subjects able to stand from supine lost ambulation.ConclusionFindings confirm the clinical meaningfulness of the 6MWD as the most accepted primary clinical endpoint in ambulatory DMD trials
The missing GeV {\gamma}-ray binary: Searching for HESS J0632+057 with Fermi-LAT
The very high energy (VHE; >100 GeV) source HESS J0632+057 has been recently
confirmed as a \gamma-ray binary, a subclass of the high mass X-ray binary
(HMXB) population, through the detection of an orbital period of 321 days. We
performed a deep search for the emission of HESS J0632+057 in the GeV energy
range using data from the Fermi Large Area Telescope (LAT). The analysis was
challenging due to the source being located in close proximity to the bright
\gamma-ray pulsar PSR J0633+0632 and lying in a crowded region of the Galactic
plane where there is prominent diffuse emission. We formulated a Bayesian block
algorithm adapted to work with weighted photon counts, in order to define the
off-pulse phases of PSR J0633+0632. A detailed spectral-spatial model of a 5
deg circular region centred on the known location of HESS J0632+057 was
generated to accurately model the LAT data. No significant emission from the
location of HESS J0632+057 was detected in the 0.1-100 GeV energy range
integrating over ~3.5 years of data; with a 95% flux upper limit of F_{0.1-100
GeV} < 3 x 10-8 ph cm-2 s-1. A search for emission over different phases of the
orbit also yielded no significant detection. A search for source emission on
shorter timescales (days--months) did not yield any significant detections. We
also report the results of a search for radio pulsations using the 100-m Green
Bank Telescope (GBT). No periodic signals or individual dispersed bursts of a
likely astronomical origin were detected. We estimated the flux density limit
of < 90/40 \mu Jy at 2/9 GHz. The LAT flux upper limits combined with the
detection of HESS J0632+057 in the 136-400 TeV energy band by the MAGIC
collaboration imply that the VHE spectrum must turn over at energies <136 GeV
placing constraints on any theoretical models invoked to explain the \gamma-ray
emission.Comment: 11 pages, 4 figures, accepted for publication in Monthly Notices of
the Royal Astronomical Society (MNRAS) Main Journa
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The LSST DESC data challenge 1: Generation and analysis of synthetic images for next-generation surveys
Data Challenge 1 (DC1) is the first synthetic data set produced by the Rubin Observatory Legacy Survey of Space and Time (LSST) Dark Energy Science Collaboration (DESC). DC1 is designed to develop and validate data reduction and analysis and to study the impact of systematic effects that will affect the LSST data set. DC1 is comprised of r-band observations of 40 deg2 to 10 yr LSST depth. We present each stage of the simulation and analysis process: (a) generation, by synthesizing sources from cosmological N-body simulations in individual sensor-visit images with different observing conditions; (b) reduction using a development version of the LSST Science Pipelines; and (c) matching to the input cosmological catalogue for validation and testing. We verify that testable LSST requirements pass within the fidelity of DC1. We establish a selection procedure that produces a sufficiently clean extragalactic sample for clustering analyses and we discuss residual sample contamination, including contributions from inefficiency in star-galaxy separation and imperfect deblending. We compute the galaxy power spectrum on the simulated field and conclude that: (i) survey properties have an impact of 50 per cent of the statistical uncertainty for the scales and models used in DC1; (ii) a selection to eliminate artefacts in the catalogues is necessary to avoid biases in the measured clustering; and (iii) the presence of bright objects has a significant impact (2-6) in the estimated power spectra at small scales (> 1200), highlighting the impact of blending in studies at small angular scales in LSST
Application of an evidence-based, out-patient treatment strategy for COVID-19: Multidisciplinary medical practice principles to prevent severe disease☆
The COVID-19 pandemic has devastated individuals, families, and institutions throughout the world. Despite the breakneck speed of vaccine development, the human population remains at risk of further devastation. The decision to not become vaccinated, the protracted rollout of available vaccine, vaccine failure, mutational forms of the SARS virus, which may exhibit mounting resistance to our molecular strike at only one form of the viral family, and the rapid ability of the virus(es) to hitch a ride on our global transportation systems, means that we are will likely continue to confront an invisible, yet devastating foe. The enemy targets one of our human physiology’s most important and vulnerable life-preserving body tissues, our broncho-alveolar gas exchange apparatus. Notwithstanding the fear and the fury of this microbe\u27s potential to raise existential questions across the entire spectrum of human endeavor, the application of an early treatment intervention initiative may represent a crucial tool in our defensive strategy. This strategy is driven by evidence-based medical practice principles, those not likely to become antiquated, given the molecular diversity and mutational evolution of this very clever “world traveler
Search for Early Gamma-ray Production in Supernovae Located in a Dense Circumstellar Medium with the Fermi LAT
Supernovae (SNe) exploding in a dense circumstellar medium (CSM) are
hypothesized to accelerate cosmic rays in collisionless shocks and emit GeV
gamma rays and TeV neutrinos on a time scale of several months. We perform the
first systematic search for gamma-ray emission in Fermi LAT data in the energy
range from 100 MeV to 300 GeV from the ensemble of 147 SNe Type IIn exploding
in dense CSM. We search for a gamma-ray excess at each SNe location in a one
year time window. In order to enhance a possible weak signal, we simultaneously
study the closest and optically brightest sources of our sample in a
joint-likelihood analysis in three different time windows (1 year, 6 months and
3 months). For the most promising source of the sample, SN 2010jl (PTF10aaxf),
we repeat the analysis with an extended time window lasting 4.5 years. We do
not find a significant excess in gamma rays for any individual source nor for
the combined sources and provide model-independent flux upper limits for both
cases. In addition, we derive limits on the gamma-ray luminosity and the ratio
of gamma-ray-to-optical luminosity ratio as a function of the index of the
proton injection spectrum assuming a generic gamma-ray production model.
Furthermore, we present detailed flux predictions based on multi-wavelength
observations and the corresponding flux upper limit at 95% confidence level
(CL) for the source SN 2010jl (PTF10aaxf).Comment: Accepted for publication in ApJ. Corresponding author: A. Franckowiak
([email protected]), updated author list and acknowledgement
Gamma-ray flaring activity from the gravitationally lensed blazar PKS 1830-211 observed by Fermi LAT
The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope
routinely detects the highly dust-absorbed, reddened, and MeV-peaked flat
spectrum radio quasar PKS 1830-211 (z=2.507). Its apparent isotropic gamma-ray
luminosity (E>100 MeV) averaged over 3 years of observations and peaking
on 2010 October 14/15 at 2.9 X 10^{50} erg s^{-1}, makes it among the brightest
high-redshift Fermi blazars. No published model with a single lens can account
for all of the observed characteristics of this complex system. Based on radio
observations, one expects time delayed variability to follow about 25 days
after a primary flare, with flux about a factor 1.5 less. Two large gamma-ray
flares of PKS 1830-211 have been detected by the LAT in the considered period
and no substantial evidence for such a delayed activity was found. This allows
us to place a lower limit of about 6 on the gamma rays flux ratio between the
two lensed images. Swift XRT observations from a dedicated Target of
Opportunity program indicate a hard spectrum and with no significant
correlation of X-ray flux with the gamma-ray variability. The spectral energy
distribution can be modeled with inverse Compton scattering of thermal photons
from the dusty torus. The implications of the LAT data in terms of variability,
the lack of evident delayed flare events, and different radio and gamma-ray
flux ratios are discussed. Microlensing effects, absorption, size and location
of the emitting regions, the complex mass distribution of the system, an
energy-dependent inner structure of the source, and flux suppression by the
lens galaxy for one image path may be considered as hypotheses for
understanding our results.Comment: 14 pages, 6 figures, 2 tables. Accepted by the The Astrophysical
Journal. Corresponding authors: S. Ciprini (ASI ASDC & INAF OAR, Rome,
Italy), S. Buson (INAF Padova & Univ. of Padova, Padova, Italy), J. Finke
(NRL, Washington, DC, USA), F. D'Ammando (INAF IRA, Bologna, Italy
Fermi observations of high-energy gamma-ray emission from GRB 090217A
The Fermi observatory is advancing our knowledge of Gamma-Ray Bursts (GRBs)
through pioneering observations at high energies, covering more than 7 decades
in energy with the two on-board detectors, the Large Area Telescope (LAT) and
the Gamma-ray Burst Monitor (GBM). Here we report on the observation of the
long GRB 090217A which triggered the GBM and has been detected by the LAT with
a significance greater than 9 sigma. We present the GBM and LAT observations
and on-ground analyses, including the time-resolved spectra and the study of
the temporal profile from 8 keV up to 1 GeV. All spectra are well reproduced by
a Band model. We compare these observations to the first two LAT-detected, long
bursts GRB 080825C and GRB 080916C. These bursts were found to have
time-dependent spectra and exhibited a delayed onset of the high-energy
emission, which are not observed in the case of GRB 090217A. We discuss some
theoretical implications for the high-energy emission of GRBs.Comment: 17 pages, 4 figures. Contact Authors: Fred, Piron; Sara, Cutini;
Andreas, von Kienli
Search for extended gamma-ray emission from the Virgo galaxy cluster with Fermi-LAT
Galaxy clusters are one of the prime sites to search for dark matter (DM)
annihilation signals. Depending on the substructure of the DM halo of a galaxy
cluster and the cross sections for DM annihilation channels, these signals
might be detectable by the latest generation of -ray telescopes. Here
we use three years of Fermi Large Area Telescope (LAT) data, which are the most
suitable for searching for very extended emission in the vicinity of nearby
Virgo galaxy cluster. Our analysis reveals statistically significant extended
emission which can be well characterized by a uniformly emitting disk profile
with a radius of 3\deg that moreover is offset from the cluster center. We
demonstrate that the significance of this extended emission strongly depends on
the adopted interstellar emission model (IEM) and is most likely an artifact of
our incomplete description of the IEM in this region. We also search for and
find new point source candidates in the region. We then derive conservative
upper limits on the velocity-averaged DM pair annihilation cross section from
Virgo. We take into account the potential -ray flux enhancement due to
DM sub-halos and its complex morphology as a merging cluster. For DM
annihilating into , assuming a conservative sub-halo model
setup, we find limits that are between 1 and 1.5 orders of magnitude above the
expectation from the thermal cross section for
. In a more optimistic scenario, we
exclude
for for the same channel. Finally, we
derive upper limits on the -ray-flux produced by hadronic cosmic-ray
interactions in the inter cluster medium. We find that the volume-averaged
cosmic-ray-to-thermal pressure ratio is less than .Comment: 15 pages, 11 figures, 4 tables, accepted for publication in ApJ;
corresponding authors: T. Jogler, S. Zimmer & A. Pinzk
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