ey Dr. Michelle Tom shares journey from ASU women's hoops to treating COVID-19 patients By sports.yahoo.com Published On :: Thu, 16 Apr 2020 23:44:26 GMT Pac-12 Networks' Ashley Adamson speaks with former Arizona State women's basketball player Michelle Tom, who is now a doctor treating COVID-19 patients Winslow Indian Health Care Center and Little Colorado Medical Center in Eastern Arizona. Full Article video Sports
ey Ivey introduced as new Notre Dame coach, succeeding McGraw By sports.yahoo.com Published On :: Thu, 23 Apr 2020 17:21:29 GMT Niele Ivey is coming home. Full Article article Sports
ey Stanford's Tara VanDerveer on Haley Jones' versatile freshman year: 'It was really incredible' By sports.yahoo.com Published On :: Fri, 08 May 2020 16:17:17 GMT During Friday's "Pac-12 Perspective," Stanford head coach Tara VanDerveer spoke about Haley Jones' positionless game and how the Cardinal used the dynamic freshman in 2019-20. Download and listen wherever you get your podcasts. Full Article video Sports
ey Neyman-Pearson classification: parametrics and sample size requirement By Published On :: 2020 The Neyman-Pearson (NP) paradigm in binary classification seeks classifiers that achieve a minimal type II error while enforcing the prioritized type I error controlled under some user-specified level $alpha$. This paradigm serves naturally in applications such as severe disease diagnosis and spam detection, where people have clear priorities among the two error types. Recently, Tong, Feng, and Li (2018) proposed a nonparametric umbrella algorithm that adapts all scoring-type classification methods (e.g., logistic regression, support vector machines, random forest) to respect the given type I error (i.e., conditional probability of classifying a class $0$ observation as class $1$ under the 0-1 coding) upper bound $alpha$ with high probability, without specific distributional assumptions on the features and the responses. Universal the umbrella algorithm is, it demands an explicit minimum sample size requirement on class $0$, which is often the more scarce class, such as in rare disease diagnosis applications. In this work, we employ the parametric linear discriminant analysis (LDA) model and propose a new parametric thresholding algorithm, which does not need the minimum sample size requirements on class $0$ observations and thus is suitable for small sample applications such as rare disease diagnosis. Leveraging both the existing nonparametric and the newly proposed parametric thresholding rules, we propose four LDA-based NP classifiers, for both low- and high-dimensional settings. On the theoretical front, we prove NP oracle inequalities for one proposed classifier, where the rate for excess type II error benefits from the explicit parametric model assumption. Furthermore, as NP classifiers involve a sample splitting step of class $0$ observations, we construct a new adaptive sample splitting scheme that can be applied universally to NP classifiers, and this adaptive strategy reduces the type II error of these classifiers. The proposed NP classifiers are implemented in the R package nproc. Full Article
ey Representation Learning for Dynamic Graphs: A Survey By Published On :: 2020 Graphs arise naturally in many real-world applications including social networks, recommender systems, ontologies, biology, and computational finance. Traditionally, machine learning models for graphs have been mostly designed for static graphs. However, many applications involve evolving graphs. This introduces important challenges for learning and inference since nodes, attributes, and edges change over time. In this survey, we review the recent advances in representation learning for dynamic graphs, including dynamic knowledge graphs. We describe existing models from an encoder-decoder perspective, categorize these encoders and decoders based on the techniques they employ, and analyze the approaches in each category. We also review several prominent applications and widely used datasets and highlight directions for future research. Full Article
ey Bayesian inference on power Lindley distribution based on different loss functions By projecteuclid.org Published On :: Mon, 26 Aug 2019 04:00 EDT Abbas Pak, M. E. Ghitany, Mohammad Reza Mahmoudi. Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 4, 894--914.Abstract: This paper focuses on Bayesian estimation of the parameters and reliability function of the power Lindley distribution by using various symmetric and asymmetric loss functions. Assuming suitable priors on the parameters, Bayes estimates are derived by using squared error, linear exponential (linex) and general entropy loss functions. Since, under these loss functions, Bayes estimates of the parameters do not have closed forms we use lindley’s approximation technique to calculate the Bayes estimates. Moreover, we obtain the Bayes estimates of the parameters using a Markov Chain Monte Carlo (MCMC) method. Simulation studies are conducted in order to evaluate the performances of the proposed estimators under the considered loss functions. Finally, analysis of a real data set is presented for illustrative purposes. Full Article
ey Bayesian approach for the zero-modified Poisson–Lindley regression model By projecteuclid.org Published On :: Mon, 26 Aug 2019 04:00 EDT Wesley Bertoli, Katiane S. Conceição, Marinho G. Andrade, Francisco Louzada. Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 4, 826--860.Abstract: The primary goal of this paper is to introduce the zero-modified Poisson–Lindley regression model as an alternative to model overdispersed count data exhibiting inflation or deflation of zeros in the presence of covariates. The zero-modification is incorporated by considering that a zero-truncated process produces positive observations and consequently, the proposed model can be fitted without any previous information about the zero-modification present in a given dataset. A fully Bayesian approach based on the g-prior method has been considered for inference concerns. An intensive Monte Carlo simulation study has been conducted to evaluate the performance of the developed methodology and the maximum likelihood estimators. The proposed model was considered for the analysis of a real dataset on the number of bids received by $126$ U.S. firms between 1978–1985, and the impact of choosing different prior distributions for the regression coefficients has been studied. A sensitivity analysis to detect influential points has been performed based on the Kullback–Leibler divergence. A general comparison with some well-known regression models for discrete data has been presented. Full Article
ey Public-private partnerships in Canada : law, policy and value for money By dal.novanet.ca Published On :: Fri, 1 May 2020 19:34:09 -0300 Author: Murphy, Timothy J. (Timothy John), author.Callnumber: KE 1465 M87 2019ISBN: 9780433457985 (Cloth) Full Article
ey A design-sensitive approach to fitting regression models with complex survey data By projecteuclid.org Published On :: Wed, 17 Jan 2018 04:00 EST Phillip S. Kott. Source: Statistics Surveys, Volume 12, 1--17.Abstract: Fitting complex survey data to regression equations is explored under a design-sensitive model-based framework. A robust version of the standard model assumes that the expected value of the difference between the dependent variable and its model-based prediction is zero no matter what the values of the explanatory variables. The extended model assumes only that the difference is uncorrelated with the covariates. Little is assumed about the error structure of this difference under either model other than independence across primary sampling units. The standard model often fails in practice, but the extended model very rarely does. Under this framework some of the methods developed in the conventional design-based, pseudo-maximum-likelihood framework, such as fitting weighted estimating equations and sandwich mean-squared-error estimation, are retained but their interpretations change. Few of the ideas here are new to the refereed literature. The goal instead is to collect those ideas and put them into a unified conceptual framework. Full Article
ey Measuring multivariate association and beyond By projecteuclid.org Published On :: Wed, 16 Nov 2016 22:00 EST Julie Josse, Susan Holmes. Source: Statistics Surveys, Volume 10, 132--167.Abstract: Simple correlation coefficients between two variables have been generalized to measure association between two matrices in many ways. Coefficients such as the RV coefficient, the distance covariance (dCov) coefficient and kernel based coefficients are being used by different research communities. Scientists use these coefficients to test whether two random vectors are linked. Once it has been ascertained that there is such association through testing, then a next step, often ignored, is to explore and uncover the association’s underlying patterns. This article provides a survey of various measures of dependence between random vectors and tests of independence and emphasizes the connections and differences between the various approaches. After providing definitions of the coefficients and associated tests, we present the recent improvements that enhance their statistical properties and ease of interpretation. We summarize multi-table approaches and provide scenarii where the indices can provide useful summaries of heterogeneous multi-block data. We illustrate these different strategies on several examples of real data and suggest directions for future research. Full Article
ey A survey of bootstrap methods in finite population sampling By projecteuclid.org Published On :: Tue, 15 Mar 2016 09:17 EDT Zeinab Mashreghi, David Haziza, Christian Léger. Source: Statistics Surveys, Volume 10, 1--52.Abstract: We review bootstrap methods in the context of survey data where the effect of the sampling design on the variability of estimators has to be taken into account. We present the methods in a unified way by classifying them in three classes: pseudo-population, direct, and survey weights methods. We cover variance estimation and the construction of confidence intervals for stratified simple random sampling as well as some unequal probability sampling designs. We also address the problem of variance estimation in presence of imputation to compensate for item non-response. Full Article
ey Errata: A survey of Bayesian predictive methods for model assessment, selection and comparison By projecteuclid.org Published On :: Wed, 26 Feb 2014 09:10 EST Aki Vehtari, Janne Ojanen. Source: Statistics Surveys, Volume 8, , 1--1.Abstract: Errata for “A survey of Bayesian predictive methods for model assessment, selection and comparison” by A. Vehtari and J. Ojanen, Statistics Surveys , 6 (2012), 142–228. doi:10.1214/12-SS102. Full Article
ey A survey of Bayesian predictive methods for model assessment, selection and comparison By projecteuclid.org Published On :: Thu, 27 Dec 2012 12:22 EST Aki Vehtari, Janne OjanenSource: Statist. Surv., Volume 6, 142--228.Abstract: To date, several methods exist in the statistical literature for model assessment, which purport themselves specifically as Bayesian predictive methods. The decision theoretic assumptions on which these methods are based are not always clearly stated in the original articles, however. The aim of this survey is to provide a unified review of Bayesian predictive model assessment and selection methods, and of methods closely related to them. We review the various assumptions that are made in this context and discuss the connections between different approaches, with an emphasis on how each method approximates the expected utility of using a Bayesian model for the purpose of predicting future data. Full Article
ey A survey of cross-validation procedures for model selection By projecteuclid.org Published On :: Thu, 05 Aug 2010 15:41 EDT Sylvain Arlot, Alain CelisseSource: Statist. Surv., Volume 4, 40--79.Abstract: Used to estimate the risk of an estimator or to perform model selection, cross-validation is a widespread strategy because of its simplicity and its (apparent) universality. Many results exist on model selection performances of cross-validation procedures. This survey intends to relate these results to the most recent advances of model selection theory, with a particular emphasis on distinguishing empirical statements from rigorous theoretical results. As a conclusion, guidelines are provided for choosing the best cross-validation procedure according to the particular features of the problem in hand. Full Article
ey Wilcoxon-Mann-Whitney or t-test? On assumptions for hypothesis tests and multiple interpretations of decision rules By projecteuclid.org Published On :: Thu, 05 Aug 2010 15:41 EDT Michael P. Fay, Michael A. ProschanSource: Statist. Surv., Volume 4, 1--39.Abstract: In a mathematical approach to hypothesis tests, we start with a clearly defined set of hypotheses and choose the test with the best properties for those hypotheses. In practice, we often start with less precise hypotheses. For example, often a researcher wants to know which of two groups generally has the larger responses, and either a t-test or a Wilcoxon-Mann-Whitney (WMW) test could be acceptable. Although both t-tests and WMW tests are usually associated with quite different hypotheses, the decision rule and p-value from either test could be associated with many different sets of assumptions, which we call perspectives. It is useful to have many of the different perspectives to which a decision rule may be applied collected in one place, since each perspective allows a different interpretation of the associated p-value. Here we collect many such perspectives for the two-sample t-test, the WMW test and other related tests. We discuss validity and consistency under each perspective and discuss recommendations between the tests in light of these many different perspectives. Finally, we briefly discuss a decision rule for testing genetic neutrality where knowledge of the many perspectives is vital to the proper interpretation of the decision rule. Full Article
ey Instruments for health surveys in children and adolescents By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Callnumber: OnlineISBN: 9783319988573 (electronic bk.) Full Article
ey Insect sex pheromone research and beyond : from molecules to robots By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Callnumber: OnlineISBN: 9789811530821 (electronic bk.) Full Article
ey DNA beyond genes : from data storage and computing to nanobots, nanomedicine, and nanoelectronics By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Author: Demidov, Vadim V., authorCallnumber: OnlineISBN: 9783030364342 (electronic bk.) Full Article
ey DICTIONARY OF CONSTRUCTION, SURVEYING, AND CIVIL ENGINEERING By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Callnumber: OnlineISBN: 9780192568632 (electronic bk.) Full Article
ey Crafting qualitative research : beyond positivist traditions By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Author: Prasad, Pushkala, author.Callnumber: OnlineISBN: 9781315715070 (e-book) Full Article
ey Breakfast cereals and how they are made : raw materials, processing, and production By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Callnumber: OnlineISBN: 9780128120446 (electronic bk.) Full Article
ey Beyond our genes : pathophysiology of gene and environment interaction and epigenetic inheritance By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Callnumber: OnlineISBN: 9783030352134 (electronic bk.) Full Article
ey Random orthogonal matrices and the Cayley transform By projecteuclid.org Published On :: Fri, 31 Jan 2020 04:06 EST Michael Jauch, Peter D. Hoff, David B. Dunson. Source: Bernoulli, Volume 26, Number 2, 1560--1586.Abstract: Random orthogonal matrices play an important role in probability and statistics, arising in multivariate analysis, directional statistics, and models of physical systems, among other areas. Calculations involving random orthogonal matrices are complicated by their constrained support. Accordingly, we parametrize the Stiefel and Grassmann manifolds, represented as subsets of orthogonal matrices, in terms of Euclidean parameters using the Cayley transform. We derive the necessary Jacobian terms for change of variables formulas. Given a density defined on the Stiefel or Grassmann manifold, these allow us to specify the corresponding density for the Euclidean parameters, and vice versa. As an application, we present a Markov chain Monte Carlo approach to simulating from distributions on the Stiefel and Grassmann manifolds. Finally, we establish that the Euclidean parameters corresponding to a uniform orthogonal matrix can be approximated asymptotically by independent normals. This result contributes to the growing literature on normal approximations to the entries of random orthogonal matrices or transformations thereof. Full Article
ey A Feynman–Kac result via Markov BSDEs with generalised drivers By projecteuclid.org Published On :: Tue, 26 Nov 2019 04:00 EST Elena Issoglio, Francesco Russo. Source: Bernoulli, Volume 26, Number 1, 728--766.Abstract: In this paper, we investigate BSDEs where the driver contains a distributional term (in the sense of generalised functions) and derive general Feynman–Kac formulae related to these BSDEs. We introduce an integral operator to give sense to the equation and then we show the existence of a strong solution employing results on a related PDE. Due to the irregularity of the driver, the $Y$-component of a couple $(Y,Z)$ solving the BSDE is not necessarily a semimartingale but a weak Dirichlet process. Full Article
ey From the coalfields of Somerset to the Adelaide Hills and beyond : the story of the Hewish Family : three centuries of one family's journey through time / Maureen Brown. By www.catalog.slsa.sa.gov.au Published On :: Hewish Henry -- Family. Full Article
ey By the richest of God's grace / Anna Penney. By www.catalog.slsa.sa.gov.au Published On :: Penney, Anna -- Travels. Full Article
ey What Districts Want From Assessments, as They Grapple With the Coronavirus By marketbrief.edweek.org Published On :: Fri, 08 May 2020 02:23:58 +0000 EdWeek Market Brief asked district officials in a nationwide survey about their most urgent assessment needs, as they cope with COVID-19 and tentatively plan for reopening schools. The post What Districts Want From Assessments, as They Grapple With the Coronavirus appeared first on Market Brief. Full Article Market Trends Assessment / Testing Coronavirus COVID-19 Exclusive Data
ey Item 01: Notebooks (2) containing hand written copies of 123 letters from Major William Alan Audsley to his parents, ca. 1916-ca. 1919, transcribed by his father. Also includes original letters (2) written by Major Audsley. By feedproxy.google.com Published On :: 28/05/2015 11:00:09 AM Full Article
ey Item 01: Autograph letter signed, from Hume, Appin, to William E. Riley, concerning an account for money owed by Riley, 4 September 1834 By feedproxy.google.com Published On :: 14/07/2015 9:51:03 AM Full Article
ey Sydney in 1848 : illustrated by copper-plate engravings of its principal streets, public buildings, churches, chapels, etc. / from drawings by Joseph Fowles. By feedproxy.google.com Published On :: 28/04/2016 12:00:00 AM Full Article
ey Nearly one-third of Americans believe a coronavirus vaccine exists and is being withheld, survey finds By news.yahoo.com Published On :: Fri, 08 May 2020 16:49:35 -0400 The Democracy Fund + UCLA Nationscape Project found some misinformation about the coronavirus is more widespread that you might think. Full Article
ey Beyond Whittle: Nonparametric Correction of a Parametric Likelihood with a Focus on Bayesian Time Series Analysis By projecteuclid.org Published On :: Thu, 19 Dec 2019 22:10 EST Claudia Kirch, Matthew C. Edwards, Alexander Meier, Renate Meyer. Source: Bayesian Analysis, Volume 14, Number 4, 1037--1073.Abstract: Nonparametric Bayesian inference has seen a rapid growth over the last decade but only few nonparametric Bayesian approaches to time series analysis have been developed. Most existing approaches use Whittle’s likelihood for Bayesian modelling of the spectral density as the main nonparametric characteristic of stationary time series. It is known that the loss of efficiency using Whittle’s likelihood can be substantial. On the other hand, parametric methods are more powerful than nonparametric methods if the observed time series is close to the considered model class but fail if the model is misspecified. Therefore, we suggest a nonparametric correction of a parametric likelihood that takes advantage of the efficiency of parametric models while mitigating sensitivities through a nonparametric amendment. We use a nonparametric Bernstein polynomial prior on the spectral density with weights induced by a Dirichlet process and prove posterior consistency for Gaussian stationary time series. Bayesian posterior computations are implemented via an MH-within-Gibbs sampler and the performance of the nonparametrically corrected likelihood for Gaussian time series is illustrated in a simulation study and in three astronomy applications, including estimating the spectral density of gravitational wave data from the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO). Full Article
ey Larry Brown’s Contributions to Parametric Inference, Decision Theory and Foundations: A Survey By projecteuclid.org Published On :: Wed, 08 Jan 2020 04:00 EST James O. Berger, Anirban DasGupta. Source: Statistical Science, Volume 34, Number 4, 621--634.Abstract: This article gives a panoramic survey of the general area of parametric statistical inference, decision theory and foundations of statistics for the period 1965–2010 through the lens of Larry Brown’s contributions to varied aspects of this massive area. The article goes over sufficiency, shrinkage estimation, admissibility, minimaxity, complete class theorems, estimated confidence, conditional confidence procedures, Edgeworth and higher order asymptotic expansions, variational Bayes, Stein’s SURE, differential inequalities, geometrization of convergence rates, asymptotic equivalence, aspects of empirical process theory, inference after model selection, unified frequentist and Bayesian testing, and Wald’s sequential theory. A reasonably comprehensive bibliography is provided. Full Article
ey Lasso Meets Horseshoe: A Survey By projecteuclid.org Published On :: Fri, 11 Oct 2019 04:03 EDT Anindya Bhadra, Jyotishka Datta, Nicholas G. Polson, Brandon Willard. Source: Statistical Science, Volume 34, Number 3, 405--427.Abstract: The goal of this paper is to contrast and survey the major advances in two of the most commonly used high-dimensional techniques, namely, the Lasso and horseshoe regularization. Lasso is a gold standard for predictor selection while horseshoe is a state-of-the-art Bayesian estimator for sparse signals. Lasso is fast and scalable and uses convex optimization whilst the horseshoe is nonconvex. Our novel perspective focuses on three aspects: (i) theoretical optimality in high-dimensional inference for the Gaussian sparse model and beyond, (ii) efficiency and scalability of computation and (iii) methodological development and performance. Full Article
ey A Conversation with Dick Dudley By projecteuclid.org Published On :: Fri, 12 Apr 2019 04:00 EDT Vladimir Koltchinskii, Richard Nickl, Philippe Rigollet. Source: Statistical Science, Volume 34, Number 1, 169--175.Abstract: Richard Mansfield Dudley (Dick Dudley) was born in 1938. He received the A.B. from Harvard in 1952 and the Ph.D. from Princeton in 1962 (under the supervision of Gilbert Hunt and Edward Nelson). Following an appointment at UC Berkeley as an assistant professor, he joined the Department of Mathematics at MIT in 1967. Dick Dudley has made fundamental contributions to the theory of Gaussian processes and Probability in Banach Spaces. Among his major achievements is the development of a general framework for empirical processes theory, in particular, for uniform central limit theorems. These results have had and continue having tremendous impact in contemporary statistics and in mathematical foundations of machine learning. A more extensive biographical sketch is contained in the preface to the Selected works of R. M. Dudley (editors: E. Giné, V. Koltchinskii and R. Norvaisa) published in 2010. This conversation took place (mostly, via email) in the fall of 2017. Full Article
ey 'Smoke gets in your eyes' / Biman Mullick. By search.wellcomelibrary.org Published On :: London (33 Stllness Rd, London, SE23 1NG) : Cleanair, Campaign for a Smoke-free Environment, [198-?] Full Article
ey Taylor Swift, Hailey Bieber, and Tons of Other Celebs’ Favorite Leggings Are on Sale Ahead of Black Friday By www.health.com Published On :: Wed, 27 Nov 2019 14:16:17 -0500 Here’s where you can snag their Alo Yoga Moto leggings for less. Full Article
ey Kourtney Kardashian's Favorite Leggings Are So Good, Everyone Should Own A Pair By www.health.com Published On :: Mon, 26 Aug 2019 17:57:40 -0400 And they're on sale for Black Friday. Full Article
ey These Nordstrom Cyber Monday Deals Are Giving Black Friday a Run for Its Money By www.health.com Published On :: Wed, 21 Nov 2018 10:40:05 -0500 This is not a drill: You can get up to 50% off at Nordstrom right now. Full Article
ey These Clark Booties Are Actually Comfortable Enough to Wear All Day—and They’re on Sale By www.health.com Published On :: Sun, 08 Dec 2019 09:36:02 -0500 You can save 50% right now. Full Article
ey Forget Black Booties, Amal Clooney and J.Lo Are Wearing This Weather-Resistant Boot Trend Instead By www.health.com Published On :: Tue, 10 Dec 2019 15:31:21 -0500 And it’s on sale at Nordstrom. Full Article
ey Grey Matter Volume Differences Associated with Extremely Low Levels of Cannabis Use in Adolescence By www.jneurosci.org Published On :: 2019-03-06 Catherine OrrMar 6, 2019; 39:1817-1827BehavioralSystemsCognitive Full Article
ey MONKEY By interglacial.com Published On :: Offering as a venue for tax relief, the Ready to bar Kenneth Your help, we stood out the Defended his girlfrienced to do with condoleezza Rice said he has line Taliband, mo. (AP) - Withough Mitt Romney are onto this spring. And her British country and how many condition and end thout naming battle again," Rutto, and Malkhadir M. Muhumed GOP critics want to seeing to school. While and fight of the new press Writer WAs lowestern Afghan capital of Kabul, Secretary Robert Gates over the contrasting in talks aimed the violence Friday. "They're allies has public heard Council. Thornton' Full Article
ey Bottom Line: iPhone SE Packs Great Value for the Money By www.technewsworld.com Published On :: 2020-04-29T11:34:29-07:00 Apple's new iPhone SE delivers incredible value and performance, has a surprisingly good camera, and handles videos well. Reviewers were impressed by the phone's A13 chipset. However, criticisms include insufficient battery life, absence of night mode, and lack of 5G support. "For those of us concerned about money ... the SE provides the greatest bang for the buck," said tech analyst Rob Enderle. Full Article
ey Wise fiscal policy is not about helicopter money By www.bis.org Published On :: 2019-11-08T12:15:00Z Op-ed by Mr Claudio Borio, Head of the Monetary and Economic Department of the BIS, published in Il Sole 24 Ore, 8 November 2019. Full Article
ey The changing colour of money - new directions for payment systems, currencies By www.bis.org Published On :: 2019-11-13T15:06:00Z Op-ed by Mr Agustín Carstens, General Manager of the BIS, published in The Business Times Singapore, 13 November 2019. Full Article
ey The future of money and the payment system: what role for central banks? By www.bis.org Published On :: 2019-12-05T21:30:00Z Lecture by Mr Agustín Carstens, General Manager of the BIS, at the Princeton University, Princeton, New Jersey, 5 December 2019. Full Article
ey Treatment with Mesenchymal-Derived Extracellular Vesicles Reduces Injury-Related Pathology in Pyramidal Neurons of Monkey Perilesional Ventral Premotor Cortex By www.jneurosci.org Published On :: 2020-04-22T09:29:41-07:00 Functional recovery after cortical injury, such as stroke, is associated with neural circuit reorganization, but the underlying mechanisms and efficacy of therapeutic interventions promoting neural plasticity in primates are not well understood. Bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), which mediate cell-to-cell inflammatory and trophic signaling, are thought be viable therapeutic targets. We recently showed, in aged female rhesus monkeys, that systemic administration of MSC-EVs enhances recovery of function after injury of the primary motor cortex, likely through enhancing plasticity in perilesional motor and premotor cortices. Here, using in vitro whole-cell patch-clamp recording and intracellular filling in acute slices of ventral premotor cortex (vPMC) from rhesus monkeys (Macaca mulatta) of either sex, we demonstrate that MSC-EVs reduce injury-related physiological and morphologic changes in perilesional layer 3 pyramidal neurons. At 14-16 weeks after injury, vPMC neurons from both vehicle- and EV-treated lesioned monkeys exhibited significant hyperexcitability and predominance of inhibitory synaptic currents, compared with neurons from nonlesioned control brains. However, compared with vehicle-treated monkeys, neurons from EV-treated monkeys showed lower firing rates, greater spike frequency adaptation, and excitatory:inhibitory ratio. Further, EV treatment was associated with greater apical dendritic branching complexity, spine density, and inhibition, indicative of enhanced dendritic plasticity and filtering of signals integrated at the soma. Importantly, the degree of EV-mediated reduction of injury-related pathology in vPMC was significantly correlated with measures of behavioral recovery. These data show that EV treatment dampens injury-related hyperexcitability and restores excitatory:inhibitory balance in vPMC, thereby normalizing activity within cortical networks for motor function. SIGNIFICANCE STATEMENT Neuronal plasticity can facilitate recovery of function after cortical injury, but the underlying mechanisms and efficacy of therapeutic interventions promoting this plasticity in primates are not well understood. Our recent work has shown that intravenous infusions of mesenchymal-derived extracellular vesicles (EVs) that are involved in cell-to-cell inflammatory and trophic signaling can enhance recovery of motor function after injury in monkey primary motor cortex. This study shows that this EV-mediated enhancement of recovery is associated with amelioration of injury-related hyperexcitability and restoration of excitatory-inhibitory balance in perilesional ventral premotor cortex. These findings demonstrate the efficacy of mesenchymal EVs as a therapeutic to reduce injury-related pathologic changes in the physiology and structure of premotor pyramidal neurons and support recovery of function. Full Article