39 research outputs found
PATRIOT: A phase I study to assess the tolerability, safety and biological effects of a specific ataxia telangiectasia and Rad3-related (ATR) inhibitor (AZD6738) as a single agent and in combination with palliative radiation therapy in patients with solid tumours.
PATRIOT is a phase I study of the ATR inhibitor, AZD6738, as monotherapy, and in combination with palliative radiotherapy. Here, we describe the protocol for this study, which opened in 2014 and is currently recruiting and comprises dose escalation of both drug and radiotherapy, and expansion cohorts
Dark Matter and Fundamental Physics with the Cherenkov Telescope Array
The Cherenkov Telescope Array (CTA) is a project for a next-generation
observatory for very high energy (GeV-TeV) ground-based gamma-ray astronomy,
currently in its design phase, and foreseen to be operative a few years from
now. Several tens of telescopes of 2-3 different sizes, distributed over a
large area, will allow for a sensitivity about a factor 10 better than current
instruments such as H.E.S.S, MAGIC and VERITAS, an energy coverage from a few
tens of GeV to several tens of TeV, and a field of view of up to 10 deg. In the
following study, we investigate the prospects for CTA to study several science
questions that influence our current knowledge of fundamental physics. Based on
conservative assumptions for the performance of the different CTA telescope
configurations, we employ a Monte Carlo based approach to evaluate the
prospects for detection. First, we discuss CTA prospects for cold dark matter
searches, following different observational strategies: in dwarf satellite
galaxies of the Milky Way, in the region close to the Galactic Centre, and in
clusters of galaxies. The possible search for spatial signatures, facilitated
by the larger field of view of CTA, is also discussed. Next we consider
searches for axion-like particles which, besides being possible candidates for
dark matter may also explain the unexpectedly low absorption by extragalactic
background light of gamma rays from very distant blazars. Simulated
light-curves of flaring sources are also used to determine the sensitivity to
violations of Lorentz Invariance by detection of the possible delay between the
arrival times of photons at different energies. Finally, we mention searches
for other exotic physics with CTA.Comment: (31 pages, Accepted for publication in Astroparticle Physics
Massive binary black holes in galactic nuclei and their path to coalescence
Massive binary black holes form at the centre of galaxies that experience a
merger episode. They are expected to coalesce into a larger black hole,
following the emission of gravitational waves. Coalescing massive binary black
holes are among the loudest sources of gravitational waves in the Universe, and
the detection of these events is at the frontier of contemporary astrophysics.
Understanding the black hole binary formation path and dynamics in galaxy
mergers is therefore mandatory. A key question poses: during a merger, will the
black holes descend over time on closer orbits, form a Keplerian binary and
coalesce shortly after? Here we review progress on the fate of black holes in
both major and minor mergers of galaxies, either gas-free or gas-rich, in
smooth and clumpy circum-nuclear discs after a galactic merger, and in
circum-binary discs present on the smallest scales inside the relic nucleus.Comment: Accepted for publication in Space Science Reviews. To appear in hard
cover in the Space Sciences Series of ISSI "The Physics of Accretion onto
Black Holes" (Springer Publisher
Preemptive analgesia. Clinical evidence of neuroplasticity contributing to postoperative pain.
Recent evidence suggests that surgical incision and other noxious perioperative events may induce prolonged changes in central neural function that later contribute to postoperative pain. The present study tested the hypothesis that patients receiving epidural fentanyl before incision would have less pain and need fewer analgesics post-operatively than patients receiving the same dose of epidural fentanyl after incision. Thirty patients (ASA physical status 2) scheduled for elective thoracic surgery through a posterolateral thoracotomy incision were randomized to one of two groups of equal size and prospectively studied in a double-blind manner. Epidural catheters were placed via the L2-L3 or L3-L4 interspaces preoperatively, and the position was confirmed with lidocaine. Group 1 received epidural fentanyl (4 micrograms/kg, in 20 ml normal saline) before surgical incision, followed by epidural normal saline (20 ml) infused 15 min after incision. Group 2 received epidural normal saline (20 ml) before surgical incision, followed by epidural fentanyl (4 micrograms/kg, in 20 ml normal saline) infused 15 min after incision. No additional analgesics were used before or during the operation. Anesthesia was induced with thiopental (3-5 mg/kg) and maintained with N2O/O2 and isoflurane. Paralysis was achieved with pancuronium (0.1 mg/kg). Postoperative analgesia consisted of patient-controlled intravenous morphine. Visual analogue scale pain scores were significantly less in group 1 (2.6 +/- 0.44) than in group 2 (4.7 +/- 0.58) 6 h after surgery (P less than 0.05), by which time plasma fentanyl concentrations had decreased to subtherapeutic levels (less than 0.15 ng/ml) in both groups
Introduced parasite Anguillicola crassus infection significantly impedes swim bladder function in the European eel Anguilla anguilla (L.)
No abstract available
Multimodal analgesia before thoracic surgery does not reduce postoperative pain
Several reports have suggested that preoperative nociceptive block may reduce postoperative pain, analgesic requirements, or both, beyond the anticipated duration of action of the analgesic agents. We have investigated, in a double-blind, placebo-controlled study, pre-emptive analgesia and the respiratory effects of preoperative administration of a multimodal antinociceptive regimen. Thirty patients undergoing thoracotomy were allocated randomly to two groups. Before surgery, the treatment group (n = 15) received morphine 0.15 mg kgâ1 i.m. with perphenazine 0.03mg kgâ1 i.m. and a rectal suppository of indomethacin 100 mg, while the placebo group (n = 15) received midazolam 0.05mg kgâ1 i.m. and a placebo rectal suppository. After induction of anaesthesia, the treatment group received intercostal nerve block with 0.5% bupivacaine and adrenaline 1:200000 (3 ml) in the interspace of the incision and in the two spaces above and two spaces below. The placebo group received identical injections but with normal saline only. The treatment group consumed significantly less morphine by patient-controlled analgesia in the first 6 h after operation, but the total dose of morphine consumed on days 2 and 3 after surgery was significantly greater in the treatment group. There were no differences between the groups in postoperative VAS scores (at rest or after movement), Paco2 values or postoperative spirometry. However, pain thresholds to pressure applied at the side of the chest contralateral to the site of incision decreased significantly from preoperative values on days 1 and 2 after surgery in both groups. The results of this study do not support the preoperative use of this combined regimen for post-thoracotomy pain
The density and pseudo-phase-space density profiles of cold dark matter haloes
Cosmological N-body simulations indicate that the spherically-averaged
density profiles of cold dark matter halos are accurately described by Einasto
profiles, where the logarithmic slope is a power-law of adjustable exponent,
\gamma =dln\rho /dlnr ~ r^\alpha $. The pseudo-phase-space density (PPSD)
profiles of CDM halos also show remarkable regularity, and are well
approximated by simple power laws, Q(r)=\rho /\sigma ^3 ~ r^-\chi . We show
that this is expected from dynamical equilibrium considerations, since Jeans'
equations predict that the pseudo-phase-space density profiles of Einasto halos
should resemble power laws over a wide range of radii. For the values of \alpha
typical of CDM halos, the inner Q profiles of equilibrium halos deviate
significantly from a power law only very close to the center, and simulations
of extremely high-resolution would be needed to detect such deviations
unambiguously. We use an ensemble of halos drawn from the Millennium-II
simulation to study which of these two alternatives describe best the mass
profile of CDM halos. Our analysis indicates that at the resolution of the best
available simulations, both Einasto and power-law PPSD profiles (with
adjustable exponents \alpha and \chi, respectively) provide equally acceptable
fits to the simulations. A full account of the structure of CDM halos requires
understanding how the shape parameters that characterize departures from
self-similarity, like \alpha or \chi, are determined by evolutionary history,
environment or initial conditions.Comment: 9 pages, 7 figures, submitted to MNRA