280 research outputs found
Efficacy of Continuous Interleukin 1 Blockade in Mevalonate Kinase Deficiency: A Multicenter Retrospective Study in 13 Adult Patients and Literature Review
OBJECTIVE: To report efficacy and tolerance of interleukin 1 blockade in adult patients with mevalonate kinase deficiency (MKD).
METHODS: We retrospectively collected data on 13 patients with MKD who had received anakinra (n = 10) and canakinumab (n = 7).
RESULTS: Anakinra resulted in complete or partial remission in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to canakinumab led to partial remission. Canakinumab resulted in complete or partial remission in 3/7 and 4/7 patients, respectively.
CONCLUSION: These data support frequent partial responses, showing a better response with canakinumab. The genotype and therapeutic outcomes correlation should help in the personalization of treatment
First detection of a VHE gamma-ray spectral maximum from a Cosmic source: H.E.S.S. discovery of the Vela X nebula
The Vela supernova remnant (SNR) is a complex region containing a number of
sources of non-thermal radiation. The inner section of this SNR, within 2
degrees of the pulsar PSR B0833-45, has been observed by the H.E.S.S. gamma-ray
atmospheric Cherenkov detector in 2004 and 2005. A strong signal is seen from
an extended region to the south of the pulsar, within an integration region of
radius 0.8 deg. around the position (RA = 08h 35m 00s, dec = -45 deg. 36'
J2000.0). The excess coincides with a region of hard X-ray emission seen by the
ROSAT and ASCA satellites. The observed energy spectrum of the source between
550 GeV and 65 TeV is well fit by a power law function with photon index = 1.45
+/- 0.09(stat) +/- 0.2(sys) and an exponential cutoff at an energy of 13.8 +/-
2.3(stat) +/- 4.1(sys) TeV. The integral flux above 1 TeV is (1.28 +/- 0.17
(stat) +/- 0.38(sys)) x 10^{-11} cm^{-2} s^{-1}. This result is the first clear
measurement of a peak in the spectral energy distribution from a VHE gamma-ray
source, likely related to inverse Compton emission. A fit of an Inverse Compton
model to the H.E.S.S. spectral energy distribution gives a total energy in
non-thermal electrons of ~2 x 10^{45} erg between 5 TeV and 100 TeV, assuming a
distance of 290 parsec to the pulsar. The best fit electron power law index is
2.0, with a spectral break at 67 TeV.Comment: 5 pages, 4 figures, accepted for publication in Astronomy and
Astrophysics letter
Discovery of the Binary Pulsar PSR B1259-63 in Very-High-Energy Gamma Rays around Periastron with H.E.S.S
We report the discovery of very-high-energy (VHE) gamma-ray emission of the
binary system PSR B1259-63/SS 2883 of a radio pulsar orbiting a massive,
luminous Be star in a highly eccentric orbit. The observations around the 2004
periastron passage of the pulsar were performed with the four 13 m Cherenkov
telescopes of the H.E.S.S. experiment, recently installed in Namibia and in
full operation since December 2003. Between February and June 2004, a gamma-ray
signal from the binary system was detected with a total significance above 13
sigma. The flux was found to vary significantly on timescales of days which
makes PSR B1259-63 the first variable galactic source of VHE gamma-rays
observed so far. Strong emission signals were observed in pre- and
post-periastron phases with a flux minimum around periastron, followed by a
gradual flux decrease in the months after. The measured time-averaged energy
spectrum above a mean threshold energy of 380 GeV can be fitted by a simple
power law F_0(E/1 TeV)^-Gamma with a photon index Gamma =
2.7+-0.2_stat+-0.2_sys and flux normalisation F_0 = (1.3+-0.1_stat+-0.3_sys)
10^-12 TeV^-1 cm^-2 s^-1. This detection of VHE gamma-rays provides unambiguous
evidence for particle acceleration to multi-TeV energies in the binary system.
In combination with coeval observations of the X-ray synchrotron emission by
the RXTE and INTEGRAL instruments, and assuming the VHE gamma-ray emission to
be produced by the inverse Compton mechanism, the magnetic field strength can
be directly estimated to be of the order of 1 G.Comment: 10 pages, 8 figures, accepted in Astronomy and Astrophysics on 2 June
2005, replace: document unchanged, replaced author field in astro-ph entry -
authors are all members of the H.E.S.S. collaboration and three additional
authors (99+3, see document
Observations of Mkn 421 in 2004 with H.E.S.S. at large zenith angles
Mkn 421 was observed during a high flux state for nine nights in April and
May 2004 with the fully operational High Energy Stereoscopic System (H.E.S.S.)
in Namibia. The observations were carried out at zenith angles of
60--65, which result in an average energy threshold of 1.5 TeV
and a collection area reaching 2~km at 10~TeV. Roughly 7000 photons from
Mkn~421 were accumulated with an average gamma-ray rate of 8 photons/min. The
overall significance of the detection exceeds 100 standard deviations. The
light-curve of integrated fluxes above 2~TeV shows changes of the diurnal flux
up to a factor of 4.3. For nights of high flux, intra-night variability is
detected with a decay time of less than 1 hour. The time averaged energy
spectrum is curved and is well described by a power-law with a photon index
\egamm and an exponential cutoff at \ecut~TeV and an average integral flux
above 2~TeV of 3 Crab flux units. Significant variations of the spectral shape
are detected with a spectral hardening as the flux increases. Contemporaneous
multi-wavelength observations at lower energies (X-rays and gamma-rays above
~GeV) indicate smaller relative variability amplitudes than seen
above 2~TeV during high flux state observed in April 2004.Comment: 5 pages, 4 figures, published in A&
A possible association of the new VHE gamma-ray source HESS J1825--137 with the pulsar wind nebula G18.0--0.7
We report on a possible association of the recently discovered very
high-energy -ray source HESS J1825--137 with the pulsar wind nebula
(commonly referred to as G 18.0--0.7) of the year old
Vela-like pulsar PSR B1823--13. HESS J1825--137 was detected with a
significance of 8.1 in the Galactic Plane survey conducted with the
H.E.S.S. instrument in 2004. The centroid position of HESS J1825--137 is offset
by 11\arcmin south of the pulsar position. \emph{XMM-Newton} observations have
revealed X-ray synchrotron emission of an asymmetric pulsar wind nebula
extending to the south of the pulsar. We argue that the observed morphology and
TeV spectral index suggest that HESS J1825--137 and G 18.0--0.7 may be
associated: the lifetime of TeV emitting electrons is expected to be longer
compared to the {\it XMM-Newton} X-ray emitting electrons, resulting in
electrons from earlier epochs (when the spin-down power was larger)
contributing to the present TeV flux. These electrons are expected to be
synchrotron cooled, which explains the observed photon index of , and
the longer lifetime of TeV emitting electrons naturally explains why the TeV
nebula is larger than the X-ray size. Finally, supernova remnant expansion into
an inhomogeneous medium is expected to create reverse shocks interacting at
different times with the pulsar wind nebula, resulting in the offset X-ray and
TeV -ray morphology.Comment: 5 pages, 3 figures, to appear in Astronomy and Astrophysics Letter
Very high energy gamma rays from the direction of Sagittarius A*.
We report the detection of a point-like source of very high energy (VHE) -rays coincident within 1' of Sgr A *, obtained with the HESS array of Cherenkov telescopes. The -rays exhibit a power-law energy spectrum with a spectral index of and a flux above the 165 GeV threshold of m -2 s -1. The measured flux and spectrum differ substantially from recent results reported in particular by the CANGAROO collaboration
3.9 day orbital modulation in the TeV gamma-ray flux and spectrum from the X-ray binary LS 5039
New observations of LS 5039, a High Mass X-ray Binary comprising a massive
star and compact object, were carried out with the High Energy Stereoscopic
System of Cherenkov Telescopes (H.E.S.S.) in 2005 at very high energy (VHE)
gamma-ray energies. These observations reveal that its flux and energy spectrum
are modulated with the 3.9 day orbital period of the binary system. This is the
first time in gamma-ray astronomy that orbital modulation has been observed,
and periodicity clearly established using ground-based gamma-ray detectors. The
VHE gamma-ray emission is largely confined to half of the orbit, peaking around
the inferior conjunction epoch of the compact object. For this epoch, there is
also a hardening of the energy spectrum in the energy range between 0.2 TeV and
a few TeV. The flux vs. orbital phase profile provides the first clear
indication of gamma-ray absorption via pair production within an astrophysical
source, a process which is expected to occur if the gamma-ray production site
is situated within ~1 AU of the compact object. Moreover the production region
size must be not significantly greater than the binary separation (~0.15 AU).
Notably, these constraints are also considerably smaller than the collimated
outflows or jets (extending out to ~1000 AU) observed in LS 5039. The spectral
hardening could arise from variations with phase in the maximum electron
energies, and/or the dominant VHE gamma-ray production mechanism.Comment: 8 pages, 8 figures, accepted for publication in Astronomy &
Astrophysic
Prevalence of von Hippel-Lindau gene mutations in sporadic renal cell carcinoma: results from the Netherlands cohort study
BACKGROUND: Biallelic von Hippel-Lindau (VHL) gene defects, a rate-limiting event in the carcinogenesis, occur in approximately 75% of sporadic clear-cell Renal Cell Carcinoma (RCC). We studied the VHL mutation status in a large population-based case group. METHODS: Cases were identified within the Netherlands cohort study on diet and cancer, which includes 120,852 men and women. After 11.3 years of follow-up, 337 incident cases with histologically confirmed epithelial cancers were identified. DNA was isolated from paraffin material collected from 51 pathology laboratories and revised by one pathologist, leaving material from 235 cases. VHL mutational status was assessed by SSCP followed by direct sequencing, after testing SSCP as a screening tool in a subsample. RESULTS: The number of mutations was significantly higher for clear-cell RCC compared to other histological types. We observed 131 mutations in 114 out of 187 patients (61%) with clear-cell RCC. The majority of mutations were truncating mutations (47%). The mean tumor size was 72.7 mm for mutated tumors compared to 65.3 mm for wildtype tumors (p = 0.06). No statistically significant differences were observed for nuclear grade, TNM distribution or stage. In other histological types, we observed 8 mutations in 7 out of 48 patients (15%), 1 mutation in 1 of 6 oncocytoma, 3 mutations in 2 of 7 chromophobe RCC, 2 mutations in 2 of 30 papillary RCC, no mutations in 1 collecting duct carcinoma and 2 mutations in 2 of 4 unclassified RCC. CONCLUSION: VHL mutations were detected in 61% of sporadic clear-cell RCC. VHL mutated and wildtype clear-cell RCC did not differ with respect to most parameters
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