The cerebral and systemic kinetics of thiopentone and propofol in halothane anaesthetized sheep

Publisher's copy made available with the permission of the publisher © Australian Society of AnaesthetistsThe cerebral and systemic kinetics of intravenous thiopentone (250 mg over 2 minutes, n=5) and propofol (100 mg over 2 minutes, n=6) were determined in sheep anaesthetized with halothane (2.0%) and mechanically ventilated to an end-expired carbon dioxide tension of 40 mmHg. The sheep were previously instrumented with arterial and sagittal sinus (effluent from the brain) blood sampling catheters. Systemic kinetics were inferred from the time-course of the arterial blood concentrations, and cerebral kinetics from the time-course of the arterio-sagittal sinus concentration difference across the brain. Under halothane anaesthesia, the peak arterial concentrations of each drug occurred at the end of the two-minute infusion, and was 42.3 mg/l and 12.3 mg/l for thiopentone and propofol, respectively. Propofol had a significantly larger systemic clearance (3.19 l/min) than thiopentone (0.99 l/min). The brain concentrations of propofol equilibrated more slowly with the arterial concentrations than those of thiopentone. The extraction ratio across the brain near the end of the infusions (1.5 min) were 0.85 and 0.46 respectively. These data were also compared to analogous previously published data for initially conscious sheep. The systemic kinetics of thiopentone were little affected by halothane anaesthesia. For propofol, halothane anaesthesia was associated with a statistically significant reduction in clearance (50% of awake), a slower initial half-life (247% of awake), and the emergence of a second slower half-life in some sheep. The cerebral kinetics of both drugs were subtly altered by halothane anaesthesia.R. N. Upton, G. L. Ludbrook, C. Granthttp://www.aaic.net.au/Article.asp?D=200024

Systematic review of economic evaluations and cost analyses of guideline implementation strategies

Objectives To appraise the quality of economic studies undertaken as part of evaluations of guideline implementation strategies; determine their resources use; and recommend methods to improve future studies. Methods Systematic review of economic studies undertaken alongside robust study designs of clinical guideline implementation strategies published (1966-1998). Studies assessed against the BMJ economic evaluations guidelines for each stage of the guideline process (guideline development, implementation and treatment). Results 235 studies were identified, 63 reported some information on cost. Only 3 studies provided evidence that their guideline was effective and efficient. 38 reported the treatment costs only, 12 implementation and treatment costs, 11 implementation costs alone, and two guideline development, implementation and treatment costs. No study gave reasonably complete information on costs. Conclusions Very few satisfactory economic evaluations of guideline implementation strategies have been performed. Current evaluations have numerous methodological defects and rarely consider all relevant costs and benefits. Future evaluations should focus on evaluating the implementation of evidence based guidelines. Keywords: Cost-effectiveness analysis, physician (or health care professional) behaviour, practice guidelines, quality improvement, systematic review.Peer reviewedAuthor versio

Review of AdS/CFT Integrability, Chapter V.2: Dual Superconformal Symmetry

Scattering amplitudes in planar N=4 super Yang-Mills theory reveal a remarkable symmetry structure. In addition to the superconformal symmetry of the Lagrangian of the theory, the planar amplitudes exhibit a dual superconformal symmetry. The presence of this additional symmetry imposes strong restrictions on the amplitudes and is connected to a duality relating scattering amplitudes to Wilson loops defined on polygonal light-like contours. The combination of the superconformal and dual superconformal symmetries gives rise to a Yangian, an algebraic structure which is known to be related to the appearance of integrability in other regimes of the theory. We discuss two dual formulations of the symmetry and address the classification of its invariants.Comment: 22 pages, see also overview article arXiv:1012.3982, v2: references to other chapters updated, v3 added references, typos fixe

Statistical Survey of Type III Radio Bursts at Long Wavelengths Observed by the Solar TErrestrial RElations Observatory (STEREO)/Waves Instruments: Radio Flux Density Variations with Frequency

We have performed a statistical study of $152$ Type III radio bursts observed by Solar TErrestrial RElations Observatory (STEREO)/Waves between May 2007 and February 2013. We have investigated the flux density between $125$kHz and $16$MHz. Both high- and low-frequency cutoffs have been observed in $60\,$ of events suggesting an important role of propagation. As already reported by previous authors, we observed that the maximum flux density occurs at $1$MHz on both spacecraft. We have developed a simplified analytical model of the flux density as a function of radial distance and compared it to the STEREO/Waves data.Comment: published in Solar Physic

Chaos in a double driven dissipative nonlinear oscillator

We propose an anharmonic oscillator driven by two periodic forces of different frequencies as a new time-dependent model for investigating quantum dissipative chaos. Our analysis is done in the frame of statistical ensemble of quantum trajectories in quantum state diffusion approach. Quantum dynamical manifestation of chaotic behavior, including the emergence of chaos, properties of strange attractors, and quantum entanglement are studied by numerical simulation of ensemble averaged Wigner function and von Neumann entropy.Comment: 9 pages, 18 figure

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Molecular and translational advances in meningiomas.

Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas

Effects of sleep deprivation on neural functioning: an integrative review

Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research