A GPU-based finite-size pencil beam algorithm with 3D-density correction for radiotherapy dose calculation

Targeting at the development of an accurate and efficient dose calculation engine for online adaptive radiotherapy, we have implemented a finite size pencil beam (FSPB) algorithm with a 3D-density correction method on GPU. This new GPU-based dose engine is built on our previously published ultrafast FSPB computational framework [Gu et al. Phys. Med. Biol. 54 6287-97, 2009]. Dosimetric evaluations against Monte Carlo dose calculations are conducted on 10 IMRT treatment plans (5 head-and-neck cases and 5 lung cases). For all cases, there is improvement with the 3D-density correction over the conventional FSPB algorithm and for most cases the improvement is significant. Regarding the efficiency, because of the appropriate arrangement of memory access and the usage of GPU intrinsic functions, the dose calculation for an IMRT plan can be accomplished well within 1 second (except for one case) with this new GPU-based FSPB algorithm. Compared to the previous GPU-based FSPB algorithm without 3D-density correction, this new algorithm, though slightly sacrificing the computational efficiency (~5-15% lower), has significantly improved the dose calculation accuracy, making it more suitable for online IMRT replanning

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

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

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

The opioid system in depression

Opioid receptors are widely distributed throughout the brain and play an essential role in modulating aspects of human mood, reward, and well-being. Accumulating evidence indicates the endogenous opioid system is dysregulated in depression and that pharmacological modulators of mu, delta, and kappa opioid receptors hold potential for the treatment of depression. Here we review animal and clinical data, highlighting evidence to support: dysregulation of the opioid system in depression, evidence for opioidergic modulation of behavioural processes and brain regions associated with depression, and evidence for opioidergic modulation in antidepressant responses. We evaluate clinical trials that have examined the safety and efficacy of opioidergic agents in depression and consider how the opioid system may be involved in the effects of other treatments, including ketamine, that are currently understood to exert antidepressant effects through non-opioidergic actions. Finally, we explore key neurochemical and molecular mechanisms underlying the potential therapeutic effects of opioid system engagement, that together provides a rationale for further investigation into this relevant target in the treatment of depression

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

Variants in the zinc transporter-3 encoding gene (SLC30A3) in schizophrenia and bipolar disorder: effects on brain glutamate–A pilot study

Zinc transporter 3 (ZnT3) has been implicated in the aetiopathology of schizophrenia. In this pilot study, we tested the hypothesis that the presence of a minor allele of two variants in the gene encoding ZnT3 (SLC30A3) affects brain glutamate and cognitive activity in patients with schizophrenia and bipolar affective disorder. Fifteen patients with schizophrenia (SCZ), 15 with bipolar affective disorder type 2 (BD), and 14 healthy volunteers (HV) were genotyped for two SLC30A3 single nucleotide polymorphisms (rs11126936 and rs11126929). They also underwent structural and functional MRI (n-back) imaging as well as static (PRESS) and functional magnetic resonance spectroscopy (n-back) on a 3 Tesla MRI system. SCZ with at least one copy of the minor allele showed reductions in dorsal anterior cingulate cortex glutamate during the n-back task, whereas SCZ without the minor allele showed an increase in glutamate. BD with the minor allele had reduced glutamate in the anterior cingulate cortex (p < 0.05). There was no effect of SLC30A3 genotype on BOLD activation during n-back or on cortical brain volume. This study supports the further investigation of SLC30A3 and its role in glutamatergic neurotransmission and in the neuropathology of mental illness