InBios International, Inc. announces the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for its diagnostic test that can be used immediately by CLIA...

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Aging Services Providers Dedicated to Fulfilling Their Critical Role in Public Health System

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Harvested produce crops feed Florida Department of Corrections’ (FDC) more than 87,000 inmates; action saves food costs while reducing COVID-19 related supply chain impacts.

(PRWeb April 20, 2020)

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Surveys provide secure, anonymous feedback from staff at all levels of healthcare organizations

(PRWeb May 06, 2020)

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Niansheng Tang, Xiaodong Yan, Xingqiu Zhao.

Source: The Annals of Statistics, Volume 48, Number 1, 607--627.

Abstract:
This article considers simultaneous variable selection and parameter estimation as well as hypothesis testing in censored survival models where a parametric likelihood is not available. For the problem, we utilize certain growing dimensional general estimating equations and propose a penalized generalized empirical likelihood, where the general estimating equations are constructed based on the semiparametric efficiency bound of estimation with given moment conditions. The proposed penalized generalized empirical likelihood estimators enjoy the oracle properties, and the estimator of any fixed dimensional vector of nonzero parameters achieves the semiparametric efficiency bound asymptotically. Furthermore, we show that the penalized generalized empirical likelihood ratio test statistic has an asymptotic central chi-square distribution. The conditions of local and restricted global optimality of weighted penalized generalized empirical likelihood estimators are also discussed. We present a two-layer iterative algorithm for efficient implementation, and investigate its convergence property. The performance of the proposed methods is demonstrated by extensive simulation studies, and a real data example is provided for illustration.

Jere Koskela, Paul A. Jenkins, Adam M. Johansen, Dario Spanò.

Source: The Annals of Statistics, Volume 48, Number 1, 560--583.

Abstract:
We study weighted particle systems in which new generations are resampled from current particles with probabilities proportional to their weights. This covers a broad class of sequential Monte Carlo (SMC) methods, widely-used in applied statistics and cognate disciplines. We consider the genealogical tree embedded into such particle systems, and identify conditions, as well as an appropriate time-scaling, under which they converge to the Kingman $n$-coalescent in the infinite system size limit in the sense of finite-dimensional distributions. Thus, the tractable $n$-coalescent can be used to predict the shape and size of SMC genealogies, as we illustrate by characterising the limiting mean and variance of the tree height. SMC genealogies are known to be connected to algorithm performance, so that our results are likely to have applications in the design of new methods as well. Our conditions for convergence are strong, but we show by simulation that they do not appear to be necessary.

Hock Peng Chan.

Source: The Annals of Statistics, Volume 48, Number 1, 346--373.

Abstract:
Lai and Robbins ( Adv. in Appl. Math. 6 (1985) 4–22) and Lai ( Ann. Statist. 15 (1987) 1091–1114) provided efficient parametric solutions to the multi-armed bandit problem, showing that arm allocation via upper confidence bounds (UCB) achieves minimum regret. These bounds are constructed from the Kullback–Leibler information of the reward distributions, estimated from specified parametric families. In recent years, there has been renewed interest in the multi-armed bandit problem due to new applications in machine learning algorithms and data analytics. Nonparametric arm allocation procedures like $epsilon $-greedy, Boltzmann exploration and BESA were studied, and modified versions of the UCB procedure were also analyzed under nonparametric settings. However, unlike UCB these nonparametric procedures are not efficient under general parametric settings. In this paper, we propose efficient nonparametric procedures.

Francesco Bravo, Juan Carlos Escanciano, Ingrid Van Keilegom.

Source: The Annals of Statistics, Volume 48, Number 1, 1--26.

Abstract:
In both parametric and certain nonparametric statistical models, the empirical likelihood ratio satisfies a nonparametric version of Wilks’ theorem. For many semiparametric models, however, the commonly used two-step (plug-in) empirical likelihood ratio is not asymptotically distribution-free, that is, its asymptotic distribution contains unknown quantities, and hence Wilks’ theorem breaks down. This article suggests a general approach to restore Wilks’ phenomenon in two-step semiparametric empirical likelihood inferences. The main insight consists in using as the moment function in the estimating equation the influence function of the plug-in sample moment. The proposed method is general; it leads to a chi-squared limiting distribution with known degrees of freedom; it is efficient; it does not require undersmoothing; and it is less sensitive to the first-step than alternative methods, which is particularly appealing for high-dimensional settings. Several examples and simulation studies illustrate the general applicability of the procedure and its excellent finite sample performance relative to competing methods.

Zhenhua Lin, Fang Yao.

Source: The Annals of Statistics, Volume 47, Number 6, 3533--3577.

Abstract:
In this work we develop a novel and foundational framework for analyzing general Riemannian functional data, in particular a new development of tensor Hilbert spaces along curves on a manifold. Such spaces enable us to derive Karhunen–Loève expansion for Riemannian random processes. This framework also features an approach to compare objects from different tensor Hilbert spaces, which paves the way for asymptotic analysis in Riemannian functional data analysis. Built upon intrinsic geometric concepts such as vector field, Levi-Civita connection and parallel transport on Riemannian manifolds, the developed framework applies to not only Euclidean submanifolds but also manifolds without a natural ambient space. As applications of this framework, we develop intrinsic Riemannian functional principal component analysis (iRFPCA) and intrinsic Riemannian functional linear regression (iRFLR) that are distinct from their traditional and ambient counterparts. We also provide estimation procedures for iRFPCA and iRFLR, and investigate their asymptotic properties within the intrinsic geometry. Numerical performance is illustrated by simulated and real examples.

Benjamin Eltzner, Stephan F. Huckemann.

Source: The Annals of Statistics, Volume 47, Number 6, 3360--3381.

Abstract:
The (CLT) central limit theorems for generalized Fréchet means (data descriptors assuming values in manifolds, such as intrinsic means, geodesics, etc.) on manifolds from the literature are only valid if a certain empirical process of Hessians of the Fréchet function converges suitably, as in the proof of the prototypical BP-CLT [ Ann. Statist. 33 (2005) 1225–1259]. This is not valid in many realistic scenarios and we provide for a new very general CLT. In particular, this includes scenarios where, in a suitable chart, the sample mean fluctuates asymptotically at a scale $n^{alpha }$ with exponents $alpha <1/2$ with a nonnormal distribution. As the BP-CLT yields only fluctuations that are, rescaled with $n^{1/2}$, asymptotically normal, just as the classical CLT for random vectors, these lower rates, somewhat loosely called smeariness, had to date been observed only on the circle. We make the concept of smeariness on manifolds precise, give an example for two-smeariness on spheres of arbitrary dimension, and show that smeariness, although “almost never” occurring, may have serious statistical implications on a continuum of sample scenarios nearby. In fact, this effect increases with dimension, striking in particular in high dimension low sample size scenarios.

Xi Chen, Weidong Liu, Yichen Zhang.

Source: The Annals of Statistics, Volume 47, Number 6, 3244--3273.

Abstract:
This paper studies the inference problem in quantile regression (QR) for a large sample size $n$ but under a limited memory constraint, where the memory can only store a small batch of data of size $m$. A natural method is the naive divide-and-conquer approach, which splits data into batches of size $m$, computes the local QR estimator for each batch and then aggregates the estimators via averaging. However, this method only works when $n=o(m^{2})$ and is computationally expensive. This paper proposes a computationally efficient method, which only requires an initial QR estimator on a small batch of data and then successively refines the estimator via multiple rounds of aggregations. Theoretically, as long as $n$ grows polynomially in $m$, we establish the asymptotic normality for the obtained estimator and show that our estimator with only a few rounds of aggregations achieves the same efficiency as the QR estimator computed on all the data. Moreover, our result allows the case that the dimensionality $p$ goes to infinity. The proposed method can also be applied to address the QR problem under distributed computing environment (e.g., in a large-scale sensor network) or for real-time streaming data.

Wei-Kuo Chen.

Source: The Annals of Statistics, Volume 47, Number 5, 2734--2756.

Abstract:
We consider the problem of detecting a deformation from a symmetric Gaussian random $p$-tensor $(pgeq3)$ with a rank-one spike sampled from the Rademacher prior. Recently, in Lesieur et al. (Barbier, Krzakala, Macris, Miolane and Zdeborová (2017)), it was proved that there exists a critical threshold $eta_{p}$ so that when the signal-to-noise ratio exceeds $eta_{p}$, one can distinguish the spiked and unspiked tensors and weakly recover the prior via the minimal mean-square-error method. On the other side, Perry, Wein and Bandeira (Perry, Wein and Bandeira (2017)) proved that there exists a $eta_{p}'<eta_{p}$ such that any statistical hypothesis test cannot distinguish these two tensors, in the sense that their total variation distance asymptotically vanishes, when the signa-to-noise ratio is less than $eta_{p}'$. In this work, we show that $eta_{p}$ is indeed the critical threshold that strictly separates the distinguishability and indistinguishability between the two tensors under the total variation distance. Our approach is based on a subtle analysis of the high temperature behavior of the pure $p$-spin model with Ising spin, arising initially from the field of spin glasses. In particular, we identify the signal-to-noise criticality $eta_{p}$ as the critical temperature, distinguishing the high and low temperature behavior, of the Ising pure $p$-spin mean-field spin glass model.

Bo Zhou, Ramon van den Akker, Bas J. M. Werker.

Source: The Annals of Statistics, Volume 47, Number 5, 2601--2638.

Abstract:
We propose a new class of unit root tests that exploits invariance properties in the Locally Asymptotically Brownian Functional limit experiment associated to the unit root model. The invariance structures naturally suggest tests that are based on the ranks of the increments of the observations, their average and an assumed reference density for the innovations. The tests are semiparametric in the sense that they are valid, that is, have the correct (asymptotic) size, irrespective of the true innovation density. For a correctly specified reference density, our test is point-optimal and nearly efficient. For arbitrary reference densities, we establish a Chernoff–Savage-type result, that is, our test performs as well as commonly used tests under Gaussian innovations but has improved power under other, for example, fat-tailed or skewed, innovation distributions. To avoid nonparametric estimation, we propose a simplified version of our test that exhibits the same asymptotic properties, except for the Chernoff–Savage result that we are only able to demonstrate by means of simulations.

Anru Zhang, Lawrence D. Brown, T. Tony Cai.

Source: The Annals of Statistics, Volume 47, Number 5, 2538--2566.

Abstract:
We propose a general semi-supervised inference framework focused on the estimation of the population mean. As usual in semi-supervised settings, there exists an unlabeled sample of covariate vectors and a labeled sample consisting of covariate vectors along with real-valued responses (“labels”). Otherwise, the formulation is “assumption-lean” in that no major conditions are imposed on the statistical or functional form of the data. We consider both the ideal semi-supervised setting where infinitely many unlabeled samples are available, as well as the ordinary semi-supervised setting in which only a finite number of unlabeled samples is available. Estimators are proposed along with corresponding confidence intervals for the population mean. Theoretical analysis on both the asymptotic distribution and $ell_{2}$-risk for the proposed procedures are given. Surprisingly, the proposed estimators, based on a simple form of the least squares method, outperform the ordinary sample mean. The simple, transparent form of the estimator lends confidence to the perception that its asymptotic improvement over the ordinary sample mean also nearly holds even for moderate size samples. The method is further extended to a nonparametric setting, in which the oracle rate can be achieved asymptotically. The proposed estimators are further illustrated by simulation studies and a real data example involving estimation of the homeless population.

Benedikt Bauer, Michael Kohler.

Source: The Annals of Statistics, Volume 47, Number 4, 2261--2285.

Abstract:
Assuming that a smoothness condition and a suitable restriction on the structure of the regression function hold, it is shown that least squares estimates based on multilayer feedforward neural networks are able to circumvent the curse of dimensionality in nonparametric regression. The proof is based on new approximation results concerning multilayer feedforward neural networks with bounded weights and a bounded number of hidden neurons. The estimates are compared with various other approaches by using simulated data.

James G. Scott, James O. Berger

Source: Ann. Statist., Volume 38, Number 5, 2587--2619.

Abstract:
This paper studies the multiplicity-correction effect of standard Bayesian variable-selection priors in linear regression. Our first goal is to clarify when, and how, multiplicity correction happens automatically in Bayesian analysis, and to distinguish this correction from the Bayesian Ockham’s-razor effect. Our second goal is to contrast empirical-Bayes and fully Bayesian approaches to variable selection through examples, theoretical results and simulations. Considerable differences between the two approaches are found. In particular, we prove a theorem that characterizes a surprising aymptotic discrepancy between fully Bayes and empirical Bayes. This discrepancy arises from a different source than the failure to account for hyperparameter uncertainty in the empirical-Bayes estimate. Indeed, even at the extreme, when the empirical-Bayes estimate converges asymptotically to the true variable-inclusion probability, the potential for a serious difference remains.

Intended meaning. In computing, semantics is the assumed or explicit set of understandings used in a system to give meaning to data. One of the biggest challenges when integrating separate computer systems and applications is to correctly match up the intended meanings within each system. Simple metadata classifications such as 'price' or 'location' may have wildly different meanings in each system, while apparently different terms, such as 'client' and 'patient' may turn out to be effectively equivalent.

Joseph Antonelli, Maitreyi Mazumdar, David Bellinger, David Christiani, Robert Wright, Brent Coull.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 257--275.

Abstract:
Humans are routinely exposed to mixtures of chemical and other environmental factors, making the quantification of health effects associated with environmental mixtures a critical goal for establishing environmental policy sufficiently protective of human health. The quantification of the effects of exposure to an environmental mixture poses several statistical challenges. It is often the case that exposure to multiple pollutants interact with each other to affect an outcome. Further, the exposure-response relationship between an outcome and some exposures, such as some metals, can exhibit complex, nonlinear forms, since some exposures can be beneficial and detrimental at different ranges of exposure. To estimate the health effects of complex mixtures, we propose a flexible Bayesian approach that allows exposures to interact with each other and have nonlinear relationships with the outcome. We induce sparsity using multivariate spike and slab priors to determine which exposures are associated with the outcome and which exposures interact with each other. The proposed approach is interpretable, as we can use the posterior probabilities of inclusion into the model to identify pollutants that interact with each other. We utilize our approach to study the impact of exposure to metals on child neurodevelopment in Bangladesh and find a nonlinear, interactive relationship between arsenic and manganese.

Zhenguo Gao, Pang Du, Ran Jin, John L. Robertson.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 143--159.

Abstract:
Liver procurement experiments with surface-temperature monitoring motivated Gao et al. ( J. Amer. Statist. Assoc. 114 (2019) 773–781) to develop a variance change-point detection method under a smoothly-changing mean trend. However, the spotwise change points yielded from their method do not offer immediate information to surgeons since an organ is often transplanted as a whole or in part. We develop a new practical method that can analyze a defined portion of the organ surface at a time. It also provides a novel addition to the developing field of functional data monitoring. Furthermore, numerical challenge emerges for simultaneously modeling the variance functions of 2D locations and the mean function of location and time. The respective sample sizes in the scales of 10,000 and 1,000,000 for modeling these functions make standard spline estimation too costly to be useful. We introduce a multistage subsampling strategy with steps educated by quickly-computable preliminary statistical measures. Extensive simulations show that the new method can efficiently reduce the computational cost and provide reasonable parameter estimates. Application of the new method to our liver surface temperature monitoring data shows its effectiveness in providing accurate status change information for a selected portion of the organ in the experiment.

Paul J. Birrell, Lorenz Wernisch, Brian D. M. Tom, Leonhard Held, Gareth O. Roberts, Richard G. Pebody, Daniela De Angelis.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 74--93.

Abstract:
A prompt public health response to a new epidemic relies on the ability to monitor and predict its evolution in real time as data accumulate. The 2009 A/H1N1 outbreak in the UK revealed pandemic data as noisy, contaminated, potentially biased and originating from multiple sources. This seriously challenges the capacity for real-time monitoring. Here, we assess the feasibility of real-time inference based on such data by constructing an analytic tool combining an age-stratified SEIR transmission model with various observation models describing the data generation mechanisms. As batches of data become available, a sequential Monte Carlo (SMC) algorithm is developed to synthesise multiple imperfect data streams, iterate epidemic inferences and assess model adequacy amidst a rapidly evolving epidemic environment, substantially reducing computation time in comparison to standard MCMC, to ensure timely delivery of real-time epidemic assessments. In application to simulated data designed to mimic the 2009 A/H1N1 epidemic, SMC is shown to have additional benefits in terms of assessing predictive performance and coping with parameter nonidentifiability.

Francisco J. R. Ruiz, Susan Athey, David M. Blei.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 1--27.

Abstract:
We develop SHOPPER, a sequential probabilistic model of shopping data. SHOPPER uses interpretable components to model the forces that drive how a customer chooses products; in particular, we designed SHOPPER to capture how items interact with other items. We develop an efficient posterior inference algorithm to estimate these forces from large-scale data, and we analyze a large dataset from a major chain grocery store. We are interested in answering counterfactual queries about changes in prices. We found that SHOPPER provides accurate predictions even under price interventions, and that it helps identify complementary and substitutable pairs of products.

Seth Flaxman, Michael Chirico, Pau Pereira, Charles Loeffler.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2564--2585.

Abstract:
We propose a generic spatiotemporal event forecasting method which we developed for the National Institute of Justice’s (NIJ) Real-Time Crime Forecasting Challenge (National Institute of Justice (2017)). Our method is a spatiotemporal forecasting model combining scalable randomized Reproducing Kernel Hilbert Space (RKHS) methods for approximating Gaussian processes with autoregressive smoothing kernels in a regularized supervised learning framework. While the smoothing kernels capture the two main approaches in current use in the field of crime forecasting, kernel density estimation (KDE) and self-exciting point process (SEPP) models, the RKHS component of the model can be understood as an approximation to the popular log-Gaussian Cox Process model. For inference, we discretize the spatiotemporal point pattern and learn a log-intensity function using the Poisson likelihood and highly efficient gradient-based optimization methods. Model hyperparameters including quality of RKHS approximation, spatial and temporal kernel lengthscales, number of autoregressive lags and bandwidths for smoothing kernels as well as cell shape, size and rotation, were learned using cross validation. Resulting predictions significantly exceeded baseline KDE estimates and SEPP models for sparse events.

Kun Liang.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2452--2482.

Abstract:
Finding differentially expressed genes is a common task in high-throughput transcriptome studies. While traditional statistical methods rank the genes by their test statistics alone, we analyze an RNA sequencing dataset using the auxiliary information of gene length and the test statistics from a related microarray study. Given the auxiliary information, we propose a novel nonparametric empirical Bayes procedure to estimate the posterior probability of differential expression for each gene. We demonstrate the advantage of our procedure in extensive simulation studies and a psoriasis RNA sequencing study. The companion R package calm is available at Bioconductor.

Carolyn M. Rutter, Jonathan Ozik, Maria DeYoreo, Nicholson Collier.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2189--2212.

Abstract:
Microsimulation models (MSMs) are used to inform policy by predicting population-level outcomes under different scenarios. MSMs simulate individual-level event histories that mark the disease process (such as the development of cancer) and the effect of policy actions (such as screening) on these events. MSMs often have many unknown parameters; calibration is the process of searching the parameter space to select parameters that result in accurate MSM prediction of a wide range of targets. We develop Incremental Mixture Approximate Bayesian Computation (IMABC) for MSM calibration which results in a simulated sample from the posterior distribution of model parameters given calibration targets. IMABC begins with a rejection-based ABC step, drawing a sample of points from the prior distribution of model parameters and accepting points that result in simulated targets that are near observed targets. Next, the sample is iteratively updated by drawing additional points from a mixture of multivariate normal distributions and accepting points that result in accurate predictions. Posterior estimates are obtained by weighting the final set of accepted points to account for the adaptive sampling scheme. We demonstrate IMABC by calibrating CRC-SPIN 2.0, an updated version of a MSM for colorectal cancer (CRC) that has been used to inform national CRC screening guidelines.

Jason Xu, Samson Koelle, Peter Guttorp, Chuanfeng Wu, Cynthia Dunbar, Janis L. Abkowitz, Vladimir N. Minin.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2091--2119.

Abstract:
Single-cell lineage tracking strategies enabled by recent experimental technologies have produced significant insights into cell fate decisions, but lack the quantitative framework necessary for rigorous statistical analysis of mechanistic models describing cell division and differentiation. In this paper, we develop such a framework with corresponding moment-based parameter estimation techniques for continuous-time, multi-type branching processes. Such processes provide a probabilistic model of how cells divide and differentiate, and we apply our method to study hematopoiesis , the mechanism of blood cell production. We derive closed-form expressions for higher moments in a general class of such models. These analytical results allow us to efficiently estimate parameters of much richer statistical models of hematopoiesis than those used in previous statistical studies. To our knowledge, the method provides the first rate inference procedure for fitting such models to time series data generated from cellular barcoding experiments. After validating the methodology in simulation studies, we apply our estimator to hematopoietic lineage tracking data from rhesus macaques. Our analysis provides a more complete understanding of cell fate decisions during hematopoiesis in nonhuman primates, which may be more relevant to human biology and clinical strategies than previous findings from murine studies. For example, in addition to previously estimated hematopoietic stem cell self-renewal rate, we are able to estimate fate decision probabilities and to compare structurally distinct models of hematopoiesis using cross validation. These estimates of fate decision probabilities and our model selection results should help biologists compare competing hypotheses about how progenitor cells differentiate. The methodology is transferrable to a large class of stochastic compartmental and multi-type branching models, commonly used in studies of cancer progression, epidemiology and many other fields.

Bret Zeldow, Vincent Lo Re III, Jason Roy.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1989--2010.

Abstract:
Bayesian Additive Regression Trees (BART) is a flexible machine learning algorithm capable of capturing nonlinearities between an outcome and covariates and interactions among covariates. We extend BART to a semiparametric regression framework in which the conditional expectation of an outcome is a function of treatment, its effect modifiers, and confounders. The confounders are allowed to have unspecified functional form, while treatment and effect modifiers that are directly related to the research question are given a linear form. The result is a Bayesian semiparametric linear regression model where the posterior distribution of the parameters of the linear part can be interpreted as in parametric Bayesian regression. This is useful in situations where a subset of the variables are of substantive interest and the others are nuisance variables that we would like to control for. An example of this occurs in causal modeling with the structural mean model (SMM). Under certain causal assumptions, our method can be used as a Bayesian SMM. Our methods are demonstrated with simulation studies and an application to dataset involving adults with HIV/Hepatitis C coinfection who newly initiate antiretroviral therapy. The methods are available in an R package called semibart.

Chanmin Kim, Michael J. Daniels, Joseph W. Hogan, Christine Choirat, Corwin M. Zigler.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1927--1956.

Abstract:
Emission control technologies installed on power plants are a key feature of many air pollution regulations in the US. While such regulations are predicated on the presumed relationships between emissions, ambient air pollution and human health, many of these relationships have never been empirically verified. The goal of this paper is to develop new statistical methods to quantify these relationships. We frame this problem as one of mediation analysis to evaluate the extent to which the effect of a particular control technology on ambient pollution is mediated through causal effects on power plant emissions. Since power plants emit various compounds that contribute to ambient pollution, we develop new methods for multiple intermediate variables that are measured contemporaneously, may interact with one another, and may exhibit joint mediating effects. Specifically, we propose new methods leveraging two related frameworks for causal inference in the presence of mediating variables: principal stratification and causal mediation analysis. We define principal effects based on multiple mediators, and also introduce a new decomposition of the total effect of an intervention on ambient pollution into the natural direct effect and natural indirect effects for all combinations of mediators. Both approaches are anchored to the same observed-data models, which we specify with Bayesian nonparametric techniques. We provide assumptions for estimating principal causal effects, then augment these with an additional assumption required for causal mediation analysis. The two analyses, interpreted in tandem, provide the first empirical investigation of the presumed causal pathways that motivate important air quality regulatory policies.

Gaoxiang Jia, Xinlei Wang, Qiwei Li, Wei Lu, Ximing Tang, Ignacio Wistuba, Yang Xie.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1617--1647.

Abstract:
Formalin-fixed paraffin-embedded (FFPE) samples have great potential for biomarker discovery, retrospective studies and diagnosis or prognosis of diseases. Their application, however, is hindered by the unsatisfactory performance of traditional gene expression profiling techniques on damaged RNAs. NanoString nCounter platform is well suited for profiling of FFPE samples and measures gene expression with high sensitivity which may greatly facilitate realization of scientific and clinical values of FFPE samples. However, methodological development for normalization, a critical step when analyzing this type of data, is far behind. Existing methods designed for the platform use information from different types of internal controls separately and rely on an overly-simplified assumption that expression of housekeeping genes is constant across samples for global scaling. Thus, these methods are not optimized for the nCounter system, not mentioning that they were not developed for FFPE samples. We construct an integrated system of random-coefficient hierarchical regression models to capture main patterns and characteristics observed from NanoString data of FFPE samples and develop a Bayesian approach to estimate parameters and normalize gene expression across samples. Our method, labeled RCRnorm, incorporates information from all aspects of the experimental design and simultaneously removes biases from various sources. It eliminates the unrealistic assumption on housekeeping genes and offers great interpretability. Furthermore, it is applicable to freshly frozen or like samples that can be generally viewed as a reduced case of FFPE samples. Simulation and applications showed the superior performance of RCRnorm.

Ahmed Aziz Ezzat, Mikyoung Jun, Yu Ding.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1484--1510.

Abstract:
Accurate short-term forecasts are indispensable for the integration of wind energy in power grids. On a wind farm, local wind conditions exhibit sizeable variations at a fine temporal resolution. Existing statistical models may capture the in-sample variations in wind behavior, but are often shortsighted to those occurring in the near future, that is, in the forecast horizon. The calibrated regime-switching method proposed in this paper introduces an action of regime dependent calibration on the predictand (here the wind speed variable), which helps correct the bias resulting from out-of-sample variations in wind behavior. This is achieved by modeling the calibration as a function of two elements: the wind regime at the time of the forecast (and the calibration is therefore regime dependent), and the runlength, which is the time elapsed since the last observed regime change. In addition to regime-switching dynamics, the proposed model also accounts for other features of wind fields: spatio-temporal dependencies, transport effect of wind and nonstationarity. Using one year of turbine-specific wind data, we show that the calibrated regime-switching method can offer a wide margin of improvement over existing forecasting methods in terms of both wind speed and power.

Anton Thalmaier, James Thompson.

Source: Bernoulli, Volume 26, Number 3, 2202--2225.

Abstract:
In this article, we derive moment estimates, exponential integrability, concentration inequalities and exit times estimates for canonical diffusions firstly on sub-Riemannian limits of Riemannian foliations and secondly in the nonsmooth setting of $operatorname{RCD}^{*}(K,N)$ spaces. In each case, the necessary ingredients are Itô’s formula and a comparison theorem for the Laplacian, for which we refer to the recent literature. As an application, we derive pointwise Carmona-type estimates on eigenfunctions of Schrödinger operators.