A transdiagnostic systematic review and meta-analysis of ketamine's anxiolytic effects

Background:Ketamine may be effective in treating symptoms of anxiety, but the time profile of ketamine’s anxiolytic effect is ill-defined. This systematic review and meta-analysis investigated the anxiolytic effect of ketamine at different time points across a range of clinical settings.Methods:Electronic databases were searched to capture randomised control trials measuring the anxiolytic effects of ketamine in contexts including mood disorders, anxiety disorders and chronic pain. Meta-analyses were conducted using a random-effects model. The correlations between (1) improvements in mean anxiety and depression scores, and (2) peak dissociation and improvements in mean anxiety scores were also assessed.Results:In all, 14 studies met inclusion criteria. Risk of bias was high in 11 studies. Ketamine significantly reduced anxiety scores compared to placebo at acute (<12 h; standard mean difference (SMD): −1.17, 95% confidence interval (CI) [−1.89, −0.44], p < 0.01), subacute (24 h; SMD: −0.44, 95% CI [−0.65, −0.22], p < 0.01) and sustained (7–14 days; SMD: −0.40, 95% CI [−0.63, −0.17], p < 0.01) time points. Exploratory analyses revealed improvements in anxiety and depression symptoms correlated at both subacute (R2 = 0.621, p = 0.035) and sustained time points (R2 = 0.773, p = 0.021). The relationship between peak dissociation and improvement in anxiety was not significant.Conclusions:Ketamine appears to offer rapid and sustained anxiety symptom relief across a range of clinical settings, with anxiolytic effects occurring within the first 12 h of administration and remaining effective for 1–2 weeks. Future studies could explore the effects of ketamine maintenance therapy on anxiety symptoms

Effect of Statistical Fluctuation in Monte Carlo Based Photon Beam Dose Calculation on Gamma Index Evaluation

The gamma-index test has been commonly adopted to quantify the degree of agreement between a reference dose distribution and an evaluation dose distribution. Monte Carlo (MC) simulation has been widely used for the radiotherapy dose calculation for both clinical and research purposes. The goal of this work is to investigate both theoretically and experimentally the impact of the MC statistical fluctuation on the gamma-index test when the fluctuation exists in the reference, the evaluation, or both dose distributions. To the first order approximation, we theoretically demonstrated in a simplified model that the statistical fluctuation tends to overestimate gamma-index values when existing in the reference dose distribution and underestimate gamma-index values when existing in the evaluation dose distribution given the original gamma-index is relatively large for the statistical fluctuation. Our numerical experiments using clinical photon radiation therapy cases have shown that 1) when performing a gamma-index test between an MC reference dose and a non-MC evaluation dose, the average gamma-index is overestimated and the passing rate decreases with the increase of the noise level in the reference dose; 2) when performing a gamma-index test between a non-MC reference dose and an MC evaluation dose, the average gamma-index is underestimated when they are within the clinically relevant range and the passing rate increases with the increase of the noise level in the evaluation dose; 3) when performing a gamma-index test between an MC reference dose and an MC evaluation dose, the passing rate is overestimated due to the noise in the evaluation dose and underestimated due to the noise in the reference dose. We conclude that the gamma-index test should be used with caution when comparing dose distributions computed with Monte Carlo simulation

Ketamine: a tale of two enantiomers

The discovery of the rapid antidepressant effects of the dissociative anaesthetic ketamine, an uncompetitive N-Methyl-D-Aspartate receptor antagonist, is arguably the most important breakthrough in depression research in the last 50 years. Ketamine remains an off-label treatment for treatment-resistant depression with factors that limit widespread use including its dissociative effects and abuse potential. Ketamine is a racemic mixture, composed of equal amounts of (S)-ketamine and (R)-ketamine. An (S)-ketamine nasal spray has been developed and approved for use in treatment-resistant depression in the United States and Europe; however, some concerns regarding efficacy and side effects remain. Although (R)-ketamine is a less potent N-Methyl-D-Aspartate receptor antagonist than (S)-ketamine, increasing preclinical evidence suggests (R)-ketamine may have more potent and longer lasting antidepressant effects than (S)-ketamine, alongside fewer side effects. Furthermore, a recent pilot trial of (R)-ketamine has demonstrated rapid-acting and sustained antidepressant effects in individuals with treatment-resistant depression. Research is ongoing to determine the specific cellular and molecular mechanisms underlying the antidepressant actions of ketamine and its component enantiomers in an effort to develop future rapid-acting antidepressants that lack undesirable effects. Here, we briefly review findings regarding the antidepressant effects of ketamine and its enantiomers before considering underlying mechanisms including N-Methyl-D-Aspartate receptor antagonism, γ-aminobutyric acid-ergic interneuron inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor activation, brain-derived neurotrophic factor and tropomyosin kinase B signalling, mammalian target of rapamycin complex 1 and extracellular signal-regulated kinase signalling, inhibition of glycogen synthase kinase-3 and inhibition of lateral habenula bursting, alongside potential roles of the monoaminergic and opioid receptor systems

Religion, Partisanship, and Attitudes Toward Science Policy

We examine issues involving science which have been contested in recent public debate. These “contested science” issues include human evolution, stem-cell research, and climate change. We find that few respondents evince consistently skeptical attitudes toward science issues, and that religious variables are generally strong predictors of attitudes toward individual issues. Furthermore, and contrary to analyses of elite discourse, partisan identification is not generally predictive of attitudes toward contested scientific issues

GPU-based ultra fast dose calculation using a finite pencil beam model

Online adaptive radiation therapy (ART) is an attractive concept that promises the ability to deliver an optimal treatment in response to the inter-fraction variability in patient anatomy. However, it has yet to be realized due to technical limitations. Fast dose deposit coefficient calculation is a critical component of the online planning process that is required for plan optimization of intensity modulated radiation therapy (IMRT). Computer graphics processing units (GPUs) are well-suited to provide the requisite fast performance for the data-parallel nature of dose calculation. In this work, we develop a dose calculation engine based on a finite-size pencil beam (FSPB) algorithm and a GPU parallel computing framework. The developed framework can accommodate any FSPB model. We test our implementation on a case of a water phantom and a case of a prostate cancer patient with varying beamlet and voxel sizes. All testing scenarios achieved speedup ranging from 200~400 times when using a NVIDIA Tesla C1060 card in comparison with a 2.27GHz Intel Xeon CPU. The computational time for calculating dose deposition coefficients for a 9-field prostate IMRT plan with this new framework is less than 1 second. This indicates that the GPU-based FSPB algorithm is well-suited for online re-planning for adaptive radiotherapy.Comment: submitted Physics in Medicine and Biolog

Measurement of inclusive D*+- and associated dijet cross sections in photoproduction at HERA

Inclusive photoproduction of D*+- mesons has been measured for photon-proton centre-of-mass energies in the range 130 < W < 280 GeV and a photon virtuality Q^2 < 1 GeV^2. The data sample used corresponds to an integrated luminosity of 37 pb^-1. Total and differential cross sections as functions of the D* transverse momentum and pseudorapidity are presented in restricted kinematical regions and the data are compared with next-to-leading order (NLO) perturbative QCD calculations using the "massive charm" and "massless charm" schemes. The measured cross sections are generally above the NLO calculations, in particular in the forward (proton) direction. The large data sample also allows the study of dijet production associated with charm. A significant resolved as well as a direct photon component contribute to the cross section. Leading order QCD Monte Carlo calculations indicate that the resolved contribution arises from a significant charm component in the photon. A massive charm NLO parton level calculation yields lower cross sections compared to the measured results in a kinematic region where the resolved photon contribution is significant.Comment: 32 pages including 6 figure

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011