5,010 research outputs found
Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses
Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011.
<p/>Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs).
<p/>Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion.
<p/>Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage
Damagnetization cooling of a gas
We demonstrate demagnetization cooling of a gas of ultracold Cr atoms.
Demagnetization is driven by inelastic dipolar collisions which couple the
motional degrees of freedom to the spin degree. By that kinetic energy is
converted into magnetic work with a consequent temperature reduction of the
gas. Optical pumping is used to magnetize the system and drive continuous
demagnetization cooling. Applying this technique, we can increase the phase
space density of our sample by one order of magnitude, with nearly no atom
loss. This method can be in principle extended to every dipolar system and
could be used to achieve quantum degeneracy via optical means.Comment: 10 pages, 5 figure
Observations of the Askaryan Effect in Ice
We report on the first observations of the Askaryan effect in ice: coherent impulsive radio Cherenkov radiation from the charge asymmetry in an electromagnetic (EM) shower. Such radiation has been observed in silica sand and rock salt, but this is the first direct observation from an EM shower in ice. These measurements are important since the majority of experiments to date that rely on the effect for ultra-high energy neutrino detection are being performed using ice as the target medium. As part of the complete validation process for the Antarctic Impulsive Transient Antenna (ANITA) experiment, we performed an experiment at the Stanford Linear Accelerator Center (SLAC) in June 2006 using a 7.5 metric ton ice target, yielding results fully consistent with theoretical expectations
International Veterinary Epilepsy Task Force Consensus Proposal: Diagnostic approach to epilepsy in dogs
This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset 6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose
Drivers of lichen species richness at multiple spatial scales in temperate forests
Only few studies analysing lichen diversity have simultaneously considered
interactions among drivers that operate at different spatial and temporal scales.
Aims: The aims of this study were to evaluate the relative importance of host tree, and local,
landscape and historical factors in explaining lichen diversity in managed temperate forests, and
to test the potential interactions among factors acting at different spatial scales.
Methods: Thirty-five stands were selected in the ĆrsĂ©g region, western Hungary. Linear models
and multi-model inference within an information-theory framework were used to evaluate the
role of different variables on lichen species richness.
Results: Drivers at multiple spatial scales contributed to shaping lichen species richness both at
the tree and plot levels. Tree level species richness was related to both tree and plot level
factors. With increasing relative diffuse light lichen species richness increased; this effect was
stronger on higher than on lower part of the trunks. At the plot-scale, species richness was
affected by local drivers. Landscape and historical factors had no or only marginal effect.
Conclusions: Lichen conservation in temperate managed forests could be improved if the
complex interactions among host tree quality and availability, micro-climatic conditions, and
management were taken into consideration
New Limits on the Ultra-high Energy Cosmic Neutrino Flux from the ANITA Experiment
We report initial results of the first flight of the Antarctic Impulsive
Transient Antenna (ANITA-1) 2006-2007 Long Duration Balloon flight, which
searched for evidence of a diffuse flux of cosmic neutrinos above energies of 3
EeV. ANITA-1 flew for 35 days looking for radio impulses due to the Askaryan
effect in neutrino-induced electromagnetic showers within the Antarctic ice
sheets. We report here on our initial analysis, which was performed as a blind
search of the data. No neutrino candidates are seen, with no detected physics
background. We set model-independent limits based on this result. Upper limits
derived from our analysis rule out the highest cosmogenic neutrino models. In a
background horizontal-polarization channel, we also detect six events
consistent with radio impulses from ultra-high energy extensive air showers.Comment: 4 pages, 2 table
Locomotor adaptability in persons with unilateral transtibial amputation
Background
Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Objective
Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). Methods
The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Results
Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Conclusions
Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb
Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers
We present a review of the interplay between the evolution of circumstellar
disks and the formation of planets, both from the perspective of theoretical
models and dedicated observations. Based on this, we identify and discuss
fundamental questions concerning the formation and evolution of circumstellar
disks and planets which can be addressed in the near future with optical and
infrared long-baseline interferometers. Furthermore, the importance of
complementary observations with long-baseline (sub)millimeter interferometers
and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics
Review"; The final publication is available at http://www.springerlink.co
Measuring the Quality of Data Collection in a Large Observational Cohort of HIV and AIDS
The aim of this study was to examine the quality of data collection by studying the validity of collected data. Data were extracted from the clinic charts of two anonymous outpatients by 38 data collectors. A standard for the data to be collected was determined (168 items). The validity was measured by comparing the collected items with the standard; in this way, the percentages of the collected items that were âcorrectâ could be calculated. The percentage âcorrectâ was higher for clinic chart 1 (mean: 83% correct, SD 7%) than for clinic chart 2 (mean: 78% correct, SD 8%). All categories contained incorrectly collected data. These data were divided into missing data, incorrect start-stop dates, and surplus collected data. Almost all start-stop dates would change into âcorrectâ if âmonthyearâ was considered correct (instead of the standard âdaymonthyearâ). Not all data collectors used specific protocols, and sources other than the written comments were not always checked. This study shows that a high proportion of data was correctly collected. However, the collection of start-stop dates was not optimal, and the collected data included surplus and missing data. Data collectors should be more knowledgeable about HIV disease and trained in the use of difficult protocols, so that they can better recognize what data to collect and how it should be collected. Among physicians, there should be more agreement about what information to record in the charts, to facilitate data extraction for data collectors
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