244 research outputs found

    Interacting Multiple Try Algorithms with Different Proposal Distributions

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    We propose a new class of interacting Markov chain Monte Carlo (MCMC) algorithms designed for increasing the efficiency of a modified multiple-try Metropolis (MTM) algorithm. The extension with respect to the existing MCMC literature is twofold. The sampler proposed extends the basic MTM algorithm by allowing different proposal distributions in the multiple-try generation step. We exploit the structure of the MTM algorithm with different proposal distributions to naturally introduce an interacting MTM mechanism (IMTM) that expands the class of population Monte Carlo methods. We show the validity of the algorithm and discuss the choice of the selection weights and of the different proposals. We provide numerical studies which show that the new algorithm can perform better than the basic MTM algorithm and that the interaction mechanism allows the IMTM to efficiently explore the state space

    On the flexibility of the design of Multiple Try Metropolis schemes

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    The Multiple Try Metropolis (MTM) method is a generalization of the classical Metropolis-Hastings algorithm in which the next state of the chain is chosen among a set of samples, according to normalized weights. In the literature, several extensions have been proposed. In this work, we show and remark upon the flexibility of the design of MTM-type methods, fulfilling the detailed balance condition. We discuss several possibilities and show different numerical results

    Sampling constrained probability distributions using Spherical Augmentation

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    Statistical models with constrained probability distributions are abundant in machine learning. Some examples include regression models with norm constraints (e.g., Lasso), probit, many copula models, and latent Dirichlet allocation (LDA). Bayesian inference involving probability distributions confined to constrained domains could be quite challenging for commonly used sampling algorithms. In this paper, we propose a novel augmentation technique that handles a wide range of constraints by mapping the constrained domain to a sphere in the augmented space. By moving freely on the surface of this sphere, sampling algorithms handle constraints implicitly and generate proposals that remain within boundaries when mapped back to the original space. Our proposed method, called {Spherical Augmentation}, provides a mathematically natural and computationally efficient framework for sampling from constrained probability distributions. We show the advantages of our method over state-of-the-art sampling algorithms, such as exact Hamiltonian Monte Carlo, using several examples including truncated Gaussian distributions, Bayesian Lasso, Bayesian bridge regression, reconstruction of quantized stationary Gaussian process, and LDA for topic modeling.Comment: 41 pages, 13 figure

    An Adaptive Interacting Wang-Landau Algorithm for Automatic Density Exploration

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    While statisticians are well-accustomed to performing exploratory analysis in the modeling stage of an analysis, the notion of conducting preliminary general-purpose exploratory analysis in the Monte Carlo stage (or more generally, the model-fitting stage) of an analysis is an area which we feel deserves much further attention. Towards this aim, this paper proposes a general-purpose algorithm for automatic density exploration. The proposed exploration algorithm combines and expands upon components from various adaptive Markov chain Monte Carlo methods, with the Wang-Landau algorithm at its heart. Additionally, the algorithm is run on interacting parallel chains -- a feature which both decreases computational cost as well as stabilizes the algorithm, improving its ability to explore the density. Performance is studied in several applications. Through a Bayesian variable selection example, the authors demonstrate the convergence gains obtained with interacting chains. The ability of the algorithm's adaptive proposal to induce mode-jumping is illustrated through a trimodal density and a Bayesian mixture modeling application. Lastly, through a 2D Ising model, the authors demonstrate the ability of the algorithm to overcome the high correlations encountered in spatial models.Comment: 33 pages, 20 figures (the supplementary materials are included as appendices

    Testing blood and CSF in people with epilepsy: a practical guide.

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    Laboratory investigations, whilst not essential to the diagnosis of seizures or of epilepsy, can be fundamental to determining the cause and guiding management. Over 50% of first seizures have an acute symptomatic cause, including a range of metabolic, toxic or infectious cause. The same triggers can precipitate status epilepticus, either de novo or as part of a deterioration in control in individuals with established epilepsy. Some, such as hypoglycaemia or severe hyponatraemia, can be fatal without prompt identification and treatment. Failure to identify seizures associated with recreational drug or alcohol misuse can lead to inappropriate AED treatment, as well as a missed opportunity for more appropriate intervention. In individuals with established epilepsy on treatment, some laboratory monitoring is desirable at least occasionally, in particular, in relation to bone health, as well as in situations where changes in AED clearance or metabolism are likely (extremes of age, pregnancy, comorbid disorders of renal or hepatic function). For any clinician managing people with epilepsy, awareness of the commoner derangements associated with individual AEDs is essential to guide practice. In this article, we review indications for tests on blood, urine and/or cerebrospinal fluid in patients presenting with new-onset seizures and status epilepticus and in people with established epilepsy presenting acutely or as part of planned monitoring. Important, but rare, neurometabolic and genetic disorders associated with epilepsy are also mentioned

    The proteasome cap RPT5/Rpt5p subunit prevents aggregation of unfolded ricin A chain

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    The plant cytotoxin ricin enters mammalian cells by receptor-mediated endocytosis, undergoing retrograde transport to the endoplasmic reticulum (ER) where its catalytic A chain (RTA) is reductively separated from the holotoxin to enter the cytosol and inactivate ribosomes. The currently accepted model is that the bulk of ER-dislocated RTA is degraded by proteasomes. We show here that the proteasome has a more complex role in ricin intoxication than previously recognised, that the previously reported increase in sensitivity of mammalian cells to ricin in the presence of proteasome inhibitors simply reflects toxicity of the inhibitors themselves, and that RTA is a very poor substrate for proteasomal degradation. Denatured RTA and casein compete for a binding site on the regulatory particle of the 26S proteasome, but their fates differ. Casein is degraded, but the mammalian 26S proteasome AAA-ATPase subunit RPT5 acts as a chaperone that prevents aggregation of denatured RTA and stimulates recovery of catalytic RTA activity in vitro. Furthermore, in vivo, the ATPase activity of Rpt5p is required for maximal toxicity of RTA dislocated from the Saccharomyces cerevisiae ER. Our results implicate RPT5/Rpt5p in the triage of substrates in which either activation (folding) or inactivation (degradation) pathways may be initiated

    Insulin Sensitivity Measured With Euglycemic Clamp Is Independently Associated With Glomerular Filtration Rate in a Community-Based Cohort

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    OBJECTIVE—To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR

    Causal hierarchy within the thalamo-cortical network in spike and wave discharges

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    Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al
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