614 research outputs found
Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists
PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(â1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(â1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(â1)) emesis by 68% (45â91%) during the acute phase (day 1) and by 67% (48â86%) and 53% (38â68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret
Rapid diagnosis of experimental meningitis by bacterial heat production in cerebrospinal fluid
BACKGROUND: Calorimetry is a nonspecific technique which allows direct measurement of heat generated by biological processes in the living cell. We evaluated the potential of calorimetry for rapid detection of bacterial growth in cerebrospinal fluid (CSF) in a rat model of bacterial meningitis. METHODS: Infant rats were infected on postnatal day 11 by direct intracisternal injection with either Streptococcus pneumoniae, Neisseria meningitidis or Listeria monocytogenes. Control animals were injected with sterile saline or heat-inactivated S. pneumoniae. CSF was obtained at 18 hours after infection for quantitative cultures and heat flow measurement. For calorimetry, 10 microl and 1 microl CSF were inoculated in calorimetry ampoules containing 3 ml trypticase soy broth (TSB). RESULTS: The mean bacterial titer (+/- SD) in CSF was 1.5 +/- 0.6 x 108 for S. pneumoniae, 1.3 +/- 0.3 x 106 for N. meningitidis and 3.5 +/- 2.2 x 104 for L. monocytogenes. Calorimetric detection time was defined as the time until heat flow signal exceeded 10 microW. Heat signal was detected in 10-microl CSF samples from all infected animals with a mean (+/- SD) detection time of 1.5 +/- 0.2 hours for S. pneumoniae, 3.9 +/- 0.7 hours for N. meningitidis and 9.1 +/- 0.5 hours for L. monocytogenes. CSF samples from non-infected animals generated no increasing heat flow (<10 microW). The total heat was the highest in S. pneumoniae ranging from 6.7 to 7.5 Joules, followed by L. monocytogenes (5.6 to 6.1 Joules) and N. meningitidis (3.5 to 4.4 Joules). The lowest detectable bacterial titer by calorimetry was 2 cfu for S. pneumoniae, 4 cfu for N. meningitidis and 7 cfu for L. monocytogenes. CONCLUSION: By means of calorimetry, detection times of <4 hours for S. pneumoniae and N. meningitidis and <10 hours for Listeria monocytogenes using as little as 10 microl CSF were achieved. Calorimetry is a new diagnostic method allowing rapid and accurate diagnosis of bacterial meningitis from a small volume of CSF
Comparative Study of Clinical and Radiological Outcomes of Unconstrained Bicondylar Total Knee Endoprostheses with Anti-allergic Coating
Self-Medication as Adaptive Plasticity: Increased Ingestion of Plant Toxins by Parasitized Caterpillars
Self-medication is a specific therapeutic behavioral change in response to disease or parasitism. The empirical literature on self-medication has so far focused entirely on identifying cases of self-medication in which particular behaviors are linked to therapeutic outcomes. In this study, we frame self-medication in the broader realm of adaptive plasticity, which provides several testable predictions for verifying self-medication and advancing its conceptual significance. First, self-medication behavior should improve the fitness of animals infected by parasites or pathogens. Second, self-medication behavior in the absence of infection should decrease fitness. Third, infection should induce self-medication behavior. The few rigorous studies of self-medication in non-human animals have not used this theoretical framework and thus have not tested fitness costs of self-medication in the absence of disease or parasitism. Here we use manipulative experiments to test these predictions with the foraging behavior of woolly bear caterpillars (Grammia incorrupta; Lepidoptera: Arctiidae) in response to their lethal endoparasites (tachinid flies). Our experiments show that the ingestion of plant toxins called pyrrolizidine alkaloids improves the survival of parasitized caterpillars by conferring resistance against tachinid flies. Consistent with theoretical prediction, excessive ingestion of these toxins reduces the survival of unparasitized caterpillars. Parasitized caterpillars are more likely than unparasitized caterpillars to specifically ingest large amounts of pyrrolizidine alkaloids. This case challenges the conventional view that self-medication behavior is restricted to animals with advanced cognitive abilities, such as primates, and empowers the science of self-medication by placing it in the domain of adaptive plasticity theory
Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay
We reconstruct the rare decays , , and in a data sample
corresponding to collected in collisions at
by the CDF II detector at the Fermilab Tevatron
Collider. Using and decays we report the branching ratios. In addition, we report
the measurement of the differential branching ratio and the muon
forward-backward asymmetry in the and decay modes, and the
longitudinal polarization in the decay mode with respect to the squared
dimuon mass. These are consistent with the theoretical prediction from the
standard model, and most recent determinations from other experiments and of
comparable accuracy. We also report the first observation of the {\mathcal{B}}(B^0_s \to
\phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}27 \pm 6B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let
Planetary Rings
Planetary rings are the only nearby astrophysical disks, and the only disks
that have been investigated by spacecraft. Although there are significant
differences between rings and other disks, chiefly the large planet/ring mass
ratio that greatly enhances the flatness of rings (aspect ratios as small as
1e-7), understanding of disks in general can be enhanced by understanding the
dynamical processes observed at close-range and in real-time in planetary
rings. We review the known ring systems of the four giant planets, as well as
the prospects for ring systems yet to be discovered. We then review planetary
rings by type. The main rings of Saturn comprise our system's only dense broad
disk and host many phenomena of general application to disks including spiral
waves, gap formation, self-gravity wakes, viscous overstability and normal
modes, impact clouds, and orbital evolution of embedded moons. Dense narrow
rings are the primary natural laboratory for understanding shepherding and
self-stability. Narrow dusty rings, likely generated by embedded source bodies,
are surprisingly found to sport azimuthally-confined arcs. Finally, every known
ring system includes a substantial component of diffuse dusty rings. Planetary
rings have shown themselves to be useful as detectors of planetary processes
around them, including the planetary magnetic field and interplanetary
impactors as well as the gravity of nearby perturbing moons. Experimental rings
science has made great progress in recent decades, especially numerical
simulations of self-gravity wakes and other processes but also laboratory
investigations of coefficient of restitution and spectroscopic ground truth.
The age of self-sustained ring systems is a matter of debate; formation
scenarios are most plausible in the context of the early solar system, while
signs of youthfulness indicate at least that rings have never been static
phenomena.Comment: 82 pages, 34 figures. Final revision of general review to be
published in "Planets, Stars and Stellar Systems", P. Kalas and L. French
(eds.), Springer (http://refworks.springer.com/sss
GavisconÂŽ vs. omeprazole in symptomatic treatment of moderate gastroesophageal reflux. a direct comparative randomised trial
<p>Abstract</p> <p>Background</p> <p>Medical management of GERD mainly uses proton pump inhibitors. Alginates also have proven efficacy. The aim of this trial was to compare short-term efficacy of an alginate (Gaviscon<sup>ÂŽ</sup>, 4 Ă 10 mL/day) and omeprazole (20 mg/day) on GERD symptoms in general practice.</p> <p>Methods</p> <p>A 14-day multicentre randomised double-blind double-dummy non-inferiority trial compared Gaviscon<sup>ÂŽ </sup>(4 Ă 10 mL/day) and omeprazole (20 mg/day) in patients with 2-6 day heartburn episodes weekly without alarm signals. The primary outcome was the mean time to onset of the first 24-h heartburn-free period after initial dosing. Secondary outcomes were the proportion of patients without heartburn by D7, pain relief by D7, and reduction in pain intensity by D7 and D14.</p> <p>Results</p> <p>278 patients were recruited; 120 were included in the Gaviscon<sup>ÂŽ </sup>group and 121 in the omeprazole group for the per protocol non-inferiority analysis. The mean time to onset of the first 24-h heartburn-free period after initial dosing was 2.0 (Âą 2.2) days for Gaviscon<sup>ÂŽ </sup>and 2.0 (Âą 2.3) days for omeprazole (<it>p </it>= 0.93); mean intergroup difference was 0.01 Âą 1.55 days (95% CI = -0.41 to 0.43): i.e., less than the lower limit of the 95% CI of -0.5 days predetermined to demonstrate non-inferiority. The mean number of heartburn-free days by D7 was significantly greater in the omeprazole group: 3.7 Âą 2.3 days vs. 3.1 Âą 2.1 (<it>p </it>= 0.02). On D7, overall quality of pain relief was slightly in favour of omeprazole (<it>p </it>= 0.049). There was no significant difference in the reduction in pain intensity between groups by D7 (<it>p = </it>0.11) or D14 (<it>p = </it>0.08). Tolerance and safety were good and comparable in both groups.</p> <p>Conclusion</p> <p>Gaviscon<sup>ÂŽ </sup>was non-inferior to omeprazole in achieving a 24-h heartburn-free period in moderate episodic heartburn, and is a relevant effective alternative treatment in moderate GERD in primary care.</p> <p>Trial registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN62203233">ISRCTN62203233</a>.</p
Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons
We report measurements of the resonance properties of Lambda_c(2595)+ and
Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as
Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+
pi+/- final states. These measurements are performed using data corresponding
to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV,
collected with the CDF II detector at the Fermilab Tevatron. Exploiting the
largest available charmed baryon sample, we measure masses and decay widths
with uncertainties comparable to the world averages for Sigma_c states, and
significantly smaller uncertainties than the world averages for excited
Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17
pages, 15 figure
Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV
We present a search for a new heavy charged vector boson decaying
to an electron-neutrino pair in collisions at a center-of-mass
energy of 1.96\unit{TeV}. The data were collected with the CDF II detector
and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No
significant excess above the standard model expectation is observed and we set
upper limits on . Assuming standard
model couplings to fermions and the neutrino from the boson decay to
be light, we exclude a boson with mass less than
1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
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