The currently available therapeutic radiopharmaceutical for high-risk neuroblastoma, ¹³¹I-MIBG, is ineffective at targeting micrometastases due to the low linear energy transfer (LET) properties of high-energy beta particles. In contrast, Auger radiation has high-LET properties with nanometer ranges in tissue, efficiently causing DNA damage when emitted in close proximity to DNA. The aim of this study was to evaluate the cytotoxicity of targeted Auger therapy in pre-clinical models of high-risk neuroblastoma. Methods: Using a radiolabeled poly(ADP-ribose) polymerase (PARP) inhibitor, ¹²⁵I-KX1, we delivered an Auger emitter iodine-125 to PARP-1: a chromatin-binding enzyme overexpressed in neuroblastoma. In vitro cytotoxicity of ¹²⁵I-KX1 was assessed in nineteen neuroblastoma cell lines, followed by in-depth pharmacological analysis in a sensitive and resistant pair of cell lines. Immunofluorescence microscopy was used to characterize ¹²⁵I-KX1-induced DNA damage. Finally, in vitro/in vivo microdosimetry was modeled from experimentally derived pharmacological variables. Results: ¹²⁵I-KX1 was highly cytotoxic in vitro across a panel of neuroblastoma cell lines, directly causing double strand DNA breaks. Based on subcellular dosimetry, ¹²⁵I-KX1 was approximately twice as effective compared to ¹³¹I-KX1, whereas cytoplasmic ¹²⁵I-MIBG demonstrated low biological effectiveness. Despite the ability to deliver focused radiation dose to the cell nuclei, ¹²⁵I-KX1 remained less effective than its alpha-emitting analog ²¹¹At-MM4, and required significantly higher activity for equivalent in vivo efficacy based on tumor microdosimetry. Conclusion: Chromatin-targeted Auger therapy is lethal to high-risk neuroblastoma cells with potential use in micrometastatic disease. This study provides the first evidence for cellular lethality from a PARP-1 targeted Auger emitter, calling for further investigation into targeted Auger therapy.

Triple negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer leading to the worst prognosis. Because current therapeutic approaches lack efficacy, there is a clinically unmet need for effective treatment alternatives. Herein, we demonstrate a promising strategy utilizing a tumor-targeting alkylphosphocholine (NM600) radiolabeled with ¹⁷⁷Lu for targeted radionuclide therapy (TRT) of TNBC. In two murine syngeneic models of TNBC, we confirmed excellent tumor targeting and rapid normal tissue clearance of the PET imaging analog ⁸⁶Y-NM600. Based on longitudinal PET/CT data acquired with ⁸⁶Y-NM600, we estimated the dosimetry of therapeutic ¹⁷⁷Lu-NM600, which showed larger absorbed doses in the tumor compared to normal tissues. Administration of ¹⁷⁷Lu-NM600 resulted in significant tumor growth inhibition and prolonged overall survival in mice bearing syngeneic 4T07 and 4T1 tumors. Complete response was attained in 60% of 4T07 bearing mice, but animals carrying aggressive 4T1 tumor grafts succumbed to metastatic progression. The injected activities used for treatment (9.25 and 18.5 MBq) were well tolerated, and only mild transient cytopenia was noted. Overall, our results suggest that ¹⁷⁷Lu-NM600 TRT has potential for treatment of TNBC and merits further exploration in a clinical setting.

Ceramides (Cers) with ultralong (~32-carbon) chains and -esterified linoleic acid, composing a subclass called omega-O-acylceramides (acylCers), are indispensable components of the skin barrier. Normal barriers typically contain acylCer concentrations of ~10 mol%; diminished concentrations, along with altered or missing long periodicity lamellar phase (LPP), and increased permeability accompany an array of skin disorders, including atopic dermatitis, psoriasis, and ichthyoses. We developed model membranes to investigate the effects of the acylCer structure and concentration on skin lipid organization and permeability. The model membrane systems contained six to nine Cer subclasses as well as fatty acids, cholesterol, and cholesterol sulfate; acylCer content—namely, acylCers containing sphingosine (Cer EOS), dihydrosphingosine (Cer EOdS), and phytosphingosine (Cer EOP) ranged from zero to 30 mol%. Systems with normal physiologic concentrations of acylCer mixture mimicked the permeability and nanostructure of human skin lipids (with regard to LPP, chain order, and lateral packing). The models also showed that the sphingoid base in acylCer significantly affects the membrane architecture and permeability and that Cer EOP, notably, is a weaker barrier component than Cer EOS and Cer EOdS. Membranes with diminished or missing acylCers displayed some of the hallmarks of diseased skin lipid barriers (i.e., lack of LPP, less ordered lipids, less orthorhombic chain packing, and increased permeability). These results could inform the rational design of new and improved strategies for the barrier-targeted treatment of skin diseases.

The estimation results might be incorrect in PROC PANEL when the RANONE and NOINT options are specified in the MODEL statement.

Despite considerable progress, development of glucose-responsive insulins (GRI) still largely depends on empirical knowledge and tedious experimentation – especially on rodents. To assist the rational design and clinical translation of the therapeutic, we present a Pharmacokinetic Algorithm Mapping GRI Efficacies in Rodents and Humans (PAMERAH), built upon our previous human model. PAMERAH constitutes a framework for predicting the therapeutic efficacy of a GRI candidate from its user-specified mechanism of action, kinetics, and dosage, which we show is accurate when checked against data from experiments and literature. Results from simulated glucose clamps also agree quantitatively with recent GRI publications. We demonstrate that the model can be used to explore the vast number of permutations constituting the GRI parameter space, and thereby identify the optimal design ranges that yield desired performance. A design guide aside, PAMERAH more importantly can facilitate GRI’s clinical translation by connecting each candidate’s efficacies in rats, mice, and humans. The resultant mapping helps find GRIs which appear promising in rodents but underperform in humans (i.e. false-positives). Conversely, it also allows for the discovery of optimal human GRI dynamics not captured by experiments on a rodent population (false-negatives). We condense such information onto a translatability grid as a straightforward, visual guide for GRI development.

AS ARTISTES and musicians try to manage the situation brought on by COVID-19’s stranglehold on the world and its economy, in the interim, many have resorted to hosting live-stream events. But that only succeeds to a point. Performers retain their...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...

Fibroblast activation protein (FAP), which promotes tumor growth and progression, is overexpressed in cancer-associated fibroblasts of many human epithelial cancers. Because of its low expression in normal organs, FAP is an excellent target for theranostics. In this study, we used radionuclides with relatively long half-lives, ⁶⁴Cu (half-life, 12.7 h) and ²²⁵Ac (half-life, 10 d), to label FAP inhibitors (FAPIs) in mice with human pancreatic cancer xenografts. Methods: Male nude mice (body weight, 22.5 ± 1.2 g) were subcutaneously injected with human pancreatic cancer cells (PANC-1, n = 12; MIA PaCa-2, n = 8). Tumor xenograft mice were investigated after the intravenous injection of ⁶⁴Cu-FAPI-04 (7.21 ± 0.46 MBq) by dynamic and delayed PET scans (2.5 h after injection). Static scans 1 h after the injection of ⁶⁸Ga-FAPI-04 (3.6 ± 1.4 MBq) were also acquired for comparisons using the same cohort of mice (n = 8). Immunohistochemical staining was performed to confirm FAP expression in tumor xenografts using an FAP-α-antibody. For radioligand therapy, ²²⁵Ac-FAPI-04 (34 kBq) was injected into PANC-1 xenograft mice (n = 6). Tumor size was monitored and compared with that of control mice (n = 6). Results: Dynamic imaging of ⁶⁴Cu-FAPI-04 showed rapid clearance through the kidneys and slow washout from tumors. Delayed PET imaging of ⁶⁴Cu-FAPI-04 showed mild uptake in tumors and relatively high uptake in the liver and intestine. Accumulation levels in the tumor or normal organs were significantly higher for ⁶⁴Cu-FAPI-04 than for ⁶⁸Ga-FAPI-04, except in the heart, and excretion in the urine was higher for ⁶⁸Ga-FAPI-04 than for ⁶⁴Cu-FAPI-04. Immunohistochemical staining revealed abundant FAP expression in the stroma of xenografts. ²²⁵Ac-FAPI-04 injection showed significant tumor growth suppression in the PANC-1 xenograft mice, compared with the control mice, without a significant change in body weight. Conclusion: This proof-of-concept study showed that ⁶⁴Cu-FAPI-04 and ²²⁵Ac-FAPI-04 could be used in theranostics for the treatment of FAP-expressing pancreatic cancer. α-therapy targeting FAP in the cancer stroma is effective and will contribute to the development of a new treatment strategy.

Marking the release of an MPI brief, experts on this webinar examine the key features of English Learner (EL) instructional models and discuss state- and district-level approaches to supporting schools in implementing effective EL program models, with a particular focus on what is being done in New York and Madison Wisconsin. 

"A special challenge of hard rock exploration is to identify targets of interest within complex geological settings. Interpretation of the geology can be made from direct geological observations and knowledge of the area, and from 2D or 3D seismic surveys. These interpretations can be developed into 3D geological models that provide the basis for predictions as to likely targets for drilling and/or mining. To verify these predictions we need to simulate 3D seismic wave propagation in the proposed geological models and compare the simulation results to seismic survey data. To achieve this we convert geological surfaces created in an interpretation software package into discretised block models representing the different lithostratigraphic units, and segment these into discrete volumes to which appropriate density and seismic velocity values are assigned. This approach allows us to scale models appropriately for desired wave propagation parameters and to go from local to global geological models and vice versa. Then we use these digital models with forward modelling codes to undertake numerous 3D acoustic wave simulations. Simulations are performed with single shot and with exploding reflector (located on extracted geological surface) configurations" -- Summary.

Birmingham : printed by M. Billing, 1847.

Pac-12 Networks' Mike Yam has a conversation with UCLA's Natalie Chou during Wednesday's "Pac-12 Perspective" podcast. Chou reflects on her role models, passion for basketball and how her mom has made a big impact on her hoops career.

Ruofei Zhao, Yuanzhi Li, Yuekai Sun.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 632--660.

Abstract:
We study the convergence behavior of the Expectation Maximization (EM) algorithm on Gaussian mixture models with an arbitrary number of mixture components and mixing weights. We show that as long as the means of the components are separated by at least $Omega (sqrt{min {M,d}})$, where $M$ is the number of components and $d$ is the dimension, the EM algorithm converges locally to the global optimum of the log-likelihood. Further, we show that the convergence rate is linear and characterize the size of the basin of attraction to the global optimum.

Maddalena Cavicchioli.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 605--631.

Abstract:
The paper treats the modeling of stationary multivariate stochastic processes via a frequency domain model expressed in terms of cepstrum theory. The proposed model nests the vector exponential model of [20] as a special case, and extends the generalised cepstral model of [36] to the multivariate setting, answering a question raised by the last authors in their paper. Contemporarily, we extend the notion of generalised autocovariance function of [35] to vector time series. Then we derive explicit matrix formulas connecting generalised cepstral and autocovariance matrices of the process, and prove the consistency and asymptotic properties of the Whittle likelihood estimators of model parameters. Asymptotic theory for the special case of the vector exponential model is a significant addition to the paper of [20]. We also provide a mathematical machinery, based on matrix differentiation, and computational methods to derive our results, which differ significantly from those employed in the univariate case. The utility of the proposed model is illustrated through Monte Carlo simulation from a bivariate process characterized by a high dynamic range, and an empirical application on time varying minimum variance hedge ratios through the second moments of future and spot prices in the corn commodity market.

Emanuel Ben-David, Bala Rajaratnam.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 580--604.

Abstract:
The Wishart distribution defined on the open cone of positive-definite matrices plays a central role in multivariate analysis and multivariate distribution theory. Its domain of parameters is often referred to as the Gindikin set. In recent years, varieties of useful extensions of the Wishart distribution have been proposed in the literature for the purposes of studying Markov random fields and graphical models. In particular, generalizations of the Wishart distribution, referred to as Type I and Type II (graphical) Wishart distributions introduced by Letac and Massam in Annals of Statistics (2007) play important roles in both frequentist and Bayesian inference for Gaussian graphical models. These distributions have been especially useful in high-dimensional settings due to the flexibility offered by their multiple-shape parameters. Concerning Type I and Type II Wishart distributions, a conjecture of Letac and Massam concerns the domain of multiple-shape parameters of these distributions. The conjecture also has implications for the existence of Bayes estimators corresponding to these high dimensional priors. The conjecture, which was first posed in the Annals of Statistics, has now been an open problem for about 10 years. In this paper, we give a necessary condition for the Letac and Massam conjecture to hold. More precisely, we prove that if the Letac and Massam conjecture holds on a decomposable graph, then no two separators of the graph can be nested within each other. For this, we analyze Type I and Type II Wishart distributions on appropriate Markov equivalent perfect DAG models and succeed in deriving the aforementioned necessary condition. This condition in particular identifies a class of counterexamples to the conjecture.

Jean-Marc Bardet, Kare Kamila, William Kengne.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 2009--2052.

Abstract:
This paper studies the model selection problem in a large class of causal time series models, which includes both the ARMA or AR($infty $) processes, as well as the GARCH or ARCH($infty $), APARCH, ARMA-GARCH and many others processes. To tackle this issue, we consider a penalized contrast based on the quasi-likelihood of the model. We provide sufficient conditions for the penalty term to ensure the consistency of the proposed procedure as well as the consistency and the asymptotic normality of the quasi-maximum likelihood estimator of the chosen model. We also propose a tool for diagnosing the goodness-of-fit of the chosen model based on a Portmanteau test. Monte-Carlo experiments and numerical applications on illustrative examples are performed to highlight the obtained asymptotic results. Moreover, using a data-driven choice of the penalty, they show the practical efficiency of this new model selection procedure and Portemanteau test.

Matthias Löwe, Kristina Schubert.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 1796--1815.

Abstract:
We show how to exactly reconstruct the block structure at the critical line in the so-called Ising block model. This model was recently re-introduced by Berthet, Rigollet and Srivastava in [2]. There the authors show how to exactly reconstruct blocks away from the critical line and they give an upper and a lower bound on the number of observations one needs; thereby they establish a minimax optimal rate (up to constants). Our technique relies on a combination of their methods with fluctuation results obtained in [20]. The latter are extended to the full critical regime. We find that the number of necessary observations depends on whether the interaction parameter between two blocks is positive or negative: In the first case, there are about $Nlog N$ observations required to exactly recover the block structure, while in the latter case $sqrt{N}log N$ observations suffice.

Tuo Chen, Zhihua Su, Yi Yang, Shanshan Ding.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 143--173.

Abstract:
As a generalization of the classical linear regression, expectile regression (ER) explores the relationship between the conditional expectile of a response variable and a set of predictor variables. ER with respect to different expectile levels can provide a comprehensive picture of the conditional distribution of the response variable given the predictors. We adopt an efficient estimation method called the envelope model ([8]) in ER, and construct a novel envelope expectile regression (EER) model. Estimation of the EER parameters can be performed using the generalized method of moments (GMM). We establish the consistency and derive the asymptotic distribution of the EER estimators. In addition, we show that the EER estimators are asymptotically more efficient than the ER estimators. Numerical experiments and real data examples are provided to demonstrate the efficiency gains attained by EER compared to ER, and the efficiency gains can further lead to improvements in prediction.

Gwenaëlle Castellan, Anthony Cousien, Viet Chi Tran.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 50--81.

Abstract:
Global sensitivity analysis is a set of methods aiming at quantifying the contribution of an uncertain input parameter of the model (or combination of parameters) on the variability of the response. We consider here the estimation of the Sobol indices of order 1 which are commonly-used indicators based on a decomposition of the output’s variance. In a deterministic framework, when the same inputs always give the same outputs, these indices are usually estimated by replicated simulations of the model. In a stochastic framework, when the response given a set of input parameters is not unique due to randomness in the model, metamodels are often used to approximate the mean and dispersion of the response by deterministic functions. We propose a new non-parametric estimator without the need of defining a metamodel to estimate the Sobol indices of order 1. The estimator is based on warped wavelets and is adaptive in the regularity of the model. The convergence of the mean square error to zero, when the number of simulations of the model tend to infinity, is computed and an elbow effect is shown, depending on the regularity of the model. Applications in Epidemiology are carried to illustrate the use of non-parametric estimators.

Daniel R. Kowal, Antonio Canale.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 1744--1772.

Abstract:
We propose a simple yet powerful framework for modeling integer-valued data, such as counts, scores, and rounded data. The data-generating process is defined by Simultaneously Transforming and Rounding (STAR) a continuous-valued process, which produces a flexible family of integer-valued distributions capable of modeling zero-inflation, bounded or censored data, and over- or underdispersion. The transformation is modeled as unknown for greater distributional flexibility, while the rounding operation ensures a coherent integer-valued data-generating process. An efficient MCMC algorithm is developed for posterior inference and provides a mechanism for adaptation of successful Bayesian models and algorithms for continuous data to the integer-valued data setting. Using the STAR framework, we design a new Bayesian Additive Regression Tree model for integer-valued data, which demonstrates impressive predictive distribution accuracy for both synthetic data and a large healthcare utilization dataset. For interpretable regression-based inference, we develop a STAR additive model, which offers greater flexibility and scalability than existing integer-valued models. The STAR additive model is applied to study the recent decline in Amazon river dolphins.

Zhixin Zhou, Ping Li.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 1302--1347.

Abstract:
The Chernoff coefficient is known to be an upper bound of Bayes error probability in classification problem. In this paper, we will develop a rate optimal Chernoff bound on the Bayes error probability. The new bound is not only an upper bound but also a lower bound of Bayes error probability up to a constant factor. Moreover, we will apply this result to community detection in the stochastic block models. As a clustering problem, the optimal misclassification rate of community detection problem can be characterized by our rate optimal Chernoff bound. This can be formalized by deriving a minimax error rate over certain parameter space of stochastic block models, then achieving such an error rate by a feasible algorithm employing multiple steps of EM type updates.

We study the misclassification error for community detection in general heterogeneous stochastic block models (SBM) with noisy or partial label information. We establish a connection between the misclassification rate and the notion of minimum energy on the local neighborhood of the SBM. We develop an optimally weighted message passing algorithm to reconstruct labels for SBM based on the minimum energy flow and the eigenvectors of a certain Markov transition matrix. The general SBM considered in this paper allows for unequal-size communities, degree heterogeneity, and different connection probabilities among blocks. We focus on how to optimally weigh the message passing to improve misclassification.

We study the identity testing problem in the context of spin systems or undirected graphical models, where it takes the following form: given the parameter specification of the model $M$ and a sampling oracle for the distribution $mu_{M^*}$ of an unknown model $M^*$, can we efficiently determine if the two models $M$ and $M^*$ are the same? We consider identity testing for both soft-constraint and hard-constraint systems. In particular, we prove hardness results in two prototypical cases, the Ising model and proper colorings, and explore whether identity testing is any easier than structure learning. For the ferromagnetic (attractive) Ising model, Daskalakis et al. (2018) presented a polynomial-time algorithm for identity testing. We prove hardness results in the antiferromagnetic (repulsive) setting in the same regime of parameters where structure learning is known to require a super-polynomial number of samples. Specifically, for $n$-vertex graphs of maximum degree $d$, we prove that if $|eta| d = omega(log{n})$ (where $eta$ is the inverse temperature parameter), then there is no polynomial running time identity testing algorithm unless $RP=NP$. In the hard-constraint setting, we present hardness results for identity testing for proper colorings. Our results are based on the presumed hardness of #BIS, the problem of (approximately) counting independent sets in bipartite graphs.

In many applications, observed data are influenced by some combination of latent causes. For example, suppose sensors are placed inside a building to record responses such as temperature, humidity, power consumption and noise levels. These random, observed responses are typically affected by many unobserved, latent factors (or features) within the building such as the number of individuals, the turning on and off of electrical devices, power surges, etc. These latent factors are usually present for a contiguous period of time before disappearing; further, multiple factors could be present at a time. This paper develops new probabilistic methodology and inference methods for random object generation influenced by latent features exhibiting temporal persistence. Every datum is associated with subsets of a potentially infinite number of hidden, persistent features that account for temporal dynamics in an observation. The ensuing class of dynamic models constructed by adapting the Indian Buffet Process — a probability measure on the space of random, unbounded binary matrices — finds use in a variety of applications arising in operations, signal processing, biomedicine, marketing, image analysis, etc. Illustrations using synthetic and real data are provided.

We consider the problem of learning causal models from observational data generated by linear non-Gaussian acyclic causal models with latent variables. Without considering the effect of latent variables, the inferred causal relationships among the observed variables are often wrong. Under faithfulness assumption, we propose a method to check whether there exists a causal path between any two observed variables. From this information, we can obtain the causal order among the observed variables. The next question is whether the causal effects can be uniquely identified as well. We show that causal effects among observed variables cannot be identified uniquely under mere assumptions of faithfulness and non-Gaussianity of exogenous noises. However, we are able to propose an efficient method that identifies the set of all possible causal effects that are compatible with the observational data. We present additional structural conditions on the causal graph under which causal effects among observed variables can be determined uniquely. Furthermore, we provide necessary and sufficient graphical conditions for unique identification of the number of variables in the system. Experiments on synthetic data and real-world data show the effectiveness of our proposed algorithm for learning causal models.

Given a response $Y$ and a vector $X = (X^1, dots, X^d)$ of $d$ predictors, we investigate the problem of inferring direct causes of $Y$ among the vector $X$. Models for $Y$ that use all of its causal covariates as predictors enjoy the property of being invariant across different environments or interventional settings. Given data from such environments, this property has been exploited for causal discovery. Here, we extend this inference principle to situations in which some (discrete-valued) direct causes of $ Y $ are unobserved. Such cases naturally give rise to switching regression models. We provide sufficient conditions for the existence, consistency and asymptotic normality of the MLE in linear switching regression models with Gaussian noise, and construct a test for the equality of such models. These results allow us to prove that the proposed causal discovery method obtains asymptotic false discovery control under mild conditions. We provide an algorithm, make available code, and test our method on simulated data. It is robust against model violations and outperforms state-of-the-art approaches. We further apply our method to a real data set, where we show that it does not only output causal predictors, but also a process-based clustering of data points, which could be of additional interest to practitioners.

Motivated by modern applications in which one constructs graphical models based on a very large number of features, this paper introduces a new class of cluster-based graphical models, in which variable clustering is applied as an initial step for reducing the dimension of the feature space. We employ model assisted clustering, in which the clusters contain features that are similar to the same unobserved latent variable. Two different cluster-based Gaussian graphical models are considered: the latent variable graph, corresponding to the graphical model associated with the unobserved latent variables, and the cluster-average graph, corresponding to the vector of features averaged over clusters. Our study reveals that likelihood based inference for the latent graph, not analyzed previously, is analytically intractable. Our main contribution is the development and analysis of alternative estimation and inference strategies, for the precision matrix of an unobservable latent vector Z. We replace the likelihood of the data by an appropriate class of empirical risk functions, that can be specialized to the latent graphical model and to the simpler, but under-analyzed, cluster-average graphical model. The estimators thus derived can be used for inference on the graph structure, for instance on edge strength or pattern recovery. Inference is based on the asymptotic limits of the entry-wise estimates of the precision matrices associated with the conditional independence graphs under consideration. While taking the uncertainty induced by the clustering step into account, we establish Berry-Esseen central limit theorems for the proposed estimators. It is noteworthy that, although the clusters are estimated adaptively from the data, the central limit theorems regarding the entries of the estimated graphs are proved under the same conditions one would use if the clusters were known in advance. As an illustration of the usage of these newly developed inferential tools, we show that they can be reliably used for recovery of the sparsity pattern of the graphs we study, under FDR control, which is verified via simulation studies and an fMRI data analysis. These experimental results confirm the theoretically established difference between the two graph structures. Furthermore, the data analysis suggests that the latent variable graph, corresponding to the unobserved cluster centers, can help provide more insight into the understanding of the brain connectivity networks relative to the simpler, average-based, graph.

Graphical models are commonly used to represent conditional dependence relationships between variables. There are multiple methods available for exploring them from high-dimensional data, but almost all of them rely on the assumption that the observations are independent and identically distributed. At the same time, observations connected by a network are becoming increasingly common, and tend to violate these assumptions. Here we develop a Gaussian graphical model for observations connected by a network with potentially different mean vectors, varying smoothly over the network. We propose an efficient estimation algorithm and demonstrate its effectiveness on both simulated and real data, obtaining meaningful and interpretable results on a statistics coauthorship network. We also prove that our method estimates both the inverse covariance matrix and the corresponding graph structure correctly under the assumption of network “cohesion”, which refers to the empirically observed phenomenon of network neighbors sharing similar traits.

This paper considers a new identifiability condition for additive noise models (ANMs) in which each variable is determined by an arbitrary Borel measurable function of its parents plus an independent error. It has been shown that ANMs are fully recoverable under some identifiability conditions, such as when all error variances are equal. However, this identifiable condition could be restrictive, and hence, this paper focuses on a relaxed identifiability condition that involves not only error variances, but also the influence of parents. This new class of identifiable ANMs does not put any constraints on the form of dependencies, or distributions of errors, and allows different error variances. It further provides a statistically consistent and computationally feasible structure learning algorithm for the identifiable ANMs based on the new identifiability condition. The proposed algorithm assumes that all relevant variables are observed, while it does not assume faithfulness or a sparse graph. Demonstrated through extensive simulated and real multivariate data is that the proposed algorithm successfully recovers directed acyclic graphs.

Danilo Covaes Nogarotto, Caio Lucidius Naberezny Azevedo, Jorge Luis Bazán.

Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 2, 304--322.

Abstract:
The interest on the analysis of the zero–one augmented beta regression (ZOABR) model has been increasing over the last few years. In this work, we developed a Bayesian inference for the ZOABR model, providing some contributions, namely: we explored the use of Jeffreys-rule and independence Jeffreys prior for some of the parameters, performing a sensitivity study of prior choice, comparing the Bayesian estimates with the maximum likelihood ones and measuring the accuracy of the estimates under several scenarios of interest. The results indicate, in a general way, that: the Bayesian approach, under the Jeffreys-rule prior, was as accurate as the ML one. Also, different from other approaches, we use the predictive distribution of the response to implement Bayesian residuals. To further illustrate the advantages of our approach, we conduct an analysis of a real psychometric data set including a Bayesian residual analysis, where it is shown that misleading inference can be obtained when the data is transformed. That is, when the zeros and ones are transformed to suitable values and the usual beta regression model is considered, instead of the ZOABR model. Finally, future developments are discussed.

Saralees Nadarajah, Yuancheng Si.

Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 1, 183--187.

Abstract:
Da Paz, Balakrishnan and Bazan [Braz. J. Probab. Stat. 33 (2019), 455–479] introduced the L-logistic distribution, studied its properties including estimation issues and illustrated a data application. This note derives a closed form expression for moment properties of the distribution. Some computational issues are discussed.

Nandini Kannan, Debasis Kundu.

Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 1, 2--17.

Abstract:
In this article, we consider models for time-to-event data obtained from experiments in which stress levels are altered at intermediate stages during the observation period. These experiments, known as step-stress tests, belong to the larger class of accelerated tests used extensively in the reliability literature. The analysis of data from step-stress tests largely relies on the popular cumulative exposure model. However, despite its simple form, the utility of the model is limited, as it is assumed that the hazard function of the underlying distribution is discontinuous at the points at which the stress levels are changed, which may not be very reasonable. Due to this deficiency, Kannan et al. ( Journal of Applied Statistics 37 (2010b) 1625–1636) introduced the cumulative risk model, where the hazard function is continuous. In this paper, we propose a class of parametric models based on the cumulative risk model assuming the underlying population contains long-term survivors or ‘cured’ fraction. An EM algorithm to compute the maximum likelihood estimators of the unknown parameters is proposed. This research is motivated by a study on altitude decompression sickness. The performance of different parametric models will be evaluated using data from this study.

Flávio B. Gonçalves, Bárbara C. C. Dias.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 4, 782--800.

Abstract:
Educational assessment usually considers a contextual questionnaire to extract relevant information from the applicants. This may include items related to socio-economical profile as well as items to extract other characteristics potentially related to applicant’s performance in the test. A careful analysis of the questionnaires jointly with the test’s results may evidence important relations between profiles and test performance. The most coherent way to perform this task in a statistical context is to use the information from the questionnaire to help explain the variability of the abilities in a joint model-based approach. Nevertheless, the responses to the questionnaire typically present missing values which, in some cases, may be missing not at random. This paper proposes a statistical methodology to model the abilities in dichotomous IRT models using the information of the contextual questionnaires via linear regression. The proposed methodology models the missing data jointly with the all the observed data, which allows for the estimation of the former. The missing data modelling is flexible enough to allow the specification of missing not at random structures. Furthermore, even if those structures are not assumed a priori, they can be estimated from the posterior results when assuming missing (completely) at random structures a priori. Statistical inference is performed under the Bayesian paradigm via an efficient MCMC algorithm. Simulated and real examples are presented to investigate the efficiency and applicability of the proposed methodology.

Sylvia Frühwirth-Schnatter.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 4, 706--733.

Abstract:
Finite mixture models and their extensions to Markov mixture and mixture of experts models are very popular in analysing data of various kind. A challenge for these models is choosing the number of components based on marginal likelihoods. The present paper suggests two innovative, generic bridge sampling estimators of the marginal likelihood that are based on constructing balanced importance densities from the conditional densities arising during Gibbs sampling. The full permutation bridge sampling estimator is derived from considering all possible permutations of the mixture labels for a subset of these densities. For the double random permutation bridge sampling estimator, two levels of random permutations are applied, first to permute the labels of the MCMC draws and second to randomly permute the labels of the conditional densities arising during Gibbs sampling. Various applications show very good performance of these estimators in comparison to importance and to reciprocal importance sampling estimators derived from the same importance densities.

Achillefs Tzioufas.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 3, 674--684.

Abstract:
The epidemic process on a graph is considered for which infectious contacts occur at rate which depends on whether a susceptible is infected for the first time or not. We show that the Vasershtein coupling extends if and only if secondary infections occur at rate which is greater than that of initial ones. Nonetheless we show that, with respect to the probability of occurrence of an infinite epidemic, the said proviso may be dropped regarding the totally asymmetric process in one dimension, thus settling in the affirmative this special case of the conjecture for arbitrary graphs due to [ Ann. Appl. Probab. 13 (2003) 669–690].

Salem M. Al-Gezeri, Robert G. Aykroyd.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 3, 498--519.

Abstract:
The use of Markov random field (MRF) models has proven to be a fruitful approach in a wide range of image processing applications. It allows local texture information to be incorporated in a systematic and unified way and allows statistical inference theory to be applied giving rise to novel output summaries and enhanced image interpretation. A great advantage of such low-level approaches is that they lead to flexible models, which can be applied to a wide range of imaging problems without the need for significant modification. This paper proposes and explores the use of conditional MRF models for situations where multiple images are to be processed simultaneously, or where only a single image is to be reconstructed and a sequential approach is taken. Although the coupling of image intensity values is a special case of our approach, the main extension over previous proposals is to allow the direct coupling of other properties, such as smoothness or texture. This is achieved using a local modulating function which adjusts the influence of global smoothing without the need for a fully inhomogeneous prior model. Several modulating functions are considered and a detailed simulation study, motivated by remote sensing applications in archaeological geophysics, of conditional reconstruction is presented. The results demonstrate that a substantial improvement in the quality of the image reconstruction, in terms of errors and residuals, can be achieved using this approach, especially at locations with rapid changes in the underlying intensity.

Rosineide F. da Paz, Narayanaswamy Balakrishnan, Jorge Luis Bazán.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 3, 455--479.

Abstract:
Tadikamalla and Johnson [ Biometrika 69 (1982) 461–465] developed the $L_{B}$ distribution to variables with bounded support by considering a transformation of the standard Logistic distribution. In this manuscript, a convenient parametrization of this distribution is proposed in order to develop regression models. This distribution, referred to here as L-Logistic distribution, provides great flexibility and includes the uniform distribution as a particular case. Several properties of this distribution are studied, and a Bayesian approach is adopted for the parameter estimation. Simulation studies, considering prior sensitivity analysis, recovery of parameters and comparison of algorithms, and robustness to outliers are all discussed showing that the results are insensitive to the choice of priors, efficiency of the algorithm MCMC adopted, and robustness of the model when compared with the beta distribution. Applications to estimate the vulnerability to poverty and to explain the anxiety are performed. The results to applications show that the L-Logistic regression models provide a better fit than the corresponding beta regression models.

Bomin Kim, Kevin H. Lee, Lingzhou Xue, Xiaoyue Niu.

Source: Statistics Surveys, Volume 12, 105--135.

Abstract:
We present a selective review of statistical modeling of dynamic networks. We focus on models with latent variables, specifically, the latent space models and the latent class models (or stochastic blockmodels), which investigate both the observed features and the unobserved structure of networks. We begin with an overview of the static models, and then we introduce the dynamic extensions. For each dynamic model, we also discuss its applications that have been studied in the literature, with the data source listed in Appendix. Based on the review, we summarize a list of open problems and challenges in dynamic network modeling with latent variables.

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.

Miklós Z. Rácz, Sébastien Bubeck.

Source: Statistics Surveys, Volume 11, 1--47.

Abstract:
Extracting information from large graphs has become an important statistical problem since network data is now common in various fields. In this minicourse we will investigate the most natural statistical questions for three canonical probabilistic models of networks: (i) community detection in the stochastic block model, (ii) finding the embedding of a random geometric graph, and (iii) finding the original vertex in a preferential attachment tree. Along the way we will cover many interesting topics in probability theory such as Pólya urns, large deviation theory, concentration of measure in high dimension, entropic central limit theorems, and more.

José A. Ferreira.

Source: Statistics Surveys, Volume 9, 106--208.

Abstract:
This article provides a concise and essentially self-contained exposition of some of the most important models and non-parametric methods for the analysis of observational data, and a substantial number of illustrations of their application. Although for the most part our presentation follows P. Rosenbaum’s book, “Observational Studies”, and naturally draws on related literature, it contains original elements and simplifies and generalizes some basic results. The illustrations, based on simulated data, show the methods at work in some detail, highlighting pitfalls and emphasizing certain subjective aspects of the statistical analyses.

Didier Chauveau, David R. Hunter, Michael Levine.

Source: Statistics Surveys, Volume 9, 1--31.

Abstract:
The conditional independence assumption for nonparametric multivariate finite mixture models, a weaker form of the well-known conditional independence assumption for random effects models for longitudinal data, is the subject of an increasing number of theoretical and algorithmic developments in the statistical literature. After presenting a survey of this literature, including an in-depth discussion of the all-important identifiability results, this article describes and extends an algorithm for estimation of the parameters in these models. The algorithm works for any number of components in three or more dimensions. It possesses a descent property and can be easily adapted to situations where the data are grouped in blocks of conditionally independent variables. We discuss how to adapt this algorithm to various location-scale models that link component densities, and we even adapt it to a particular class of univariate mixture problems in which the components are assumed symmetric. We give a bandwidth selection procedure for our algorithm. Finally, we demonstrate the effectiveness of our algorithm using a simulation study and two psychometric datasets.

Volodymyr Melnykov, Ranjan Maitra

Source: Statist. Surv., Volume 4, 80--116.

Abstract:
Finite mixture models have a long history in statistics, having been used to model population heterogeneity, generalize distributional assumptions, and lately, for providing a convenient yet formal framework for clustering and classification. This paper provides a detailed review into mixture models and model-based clustering. Recent trends as well as open problems in the area are also discussed.

Application and use of deep learning algorithms for different healthcare applications is gaining interest at a steady pace. However, use of such algorithms can prove to be challenging as they require large amounts of training data that capture different possible variations. This makes it difficult to use them in a clinical setting since in most health applications researchers often have to work with limited data. Less data can cause the deep learning model to over-fit. In this paper, we ask how can we use data from a different environment, different use-case, with widely differing data distributions. We exemplify this use case by using single-sensor accelerometer data from healthy subjects performing activities of daily living - ADLs (source dataset), to extract features relevant to multi-sensor accelerometer gait data (target dataset) for Parkinson's disease classification. We train the pre-trained model using the source dataset and use it as a feature extractor. We show that the features extracted for the target dataset can be used to train an effective classification model. Our pre-trained source model consists of a convolutional autoencoder, and the target classification model is a simple multi-layer perceptron model. We explore two different pre-trained source models, trained using different activity groups, and analyze the influence the choice of pre-trained model has over the task of Parkinson's disease classification.

We study the information content of nuclear masses from the perspective of global models of nuclear binding energies. To this end, we employ a number of statistical methods and diagnostic tools, including Bayesian calibration, Bayesian model averaging, chi-square correlation analysis, principal component analysis, and empirical coverage probability. Using a Bayesian framework, we investigate the structure of the 4-parameter Liquid Drop Model by considering discrepant mass domains for calibration. We then use the chi-square correlation framework to analyze the 14-parameter Skyrme energy density functional calibrated using homogeneous and heterogeneous datasets. We show that a quite dramatic parameter reduction can be achieved in both cases. The advantage of Bayesian model averaging for improving uncertainty quantification is demonstrated. The statistical approaches used are pedagogically described; in this context this work can serve as a guide for future applications.

Beginning from a basic neural-network architecture, we test the potential benefits offered by a range of advanced techniques for machine learning, in particular deep learning, in the context of a typical classification problem encountered in the domain of high-energy physics, using a well-studied dataset: the 2014 Higgs ML Kaggle dataset. The advantages are evaluated in terms of both performance metrics and the time required to train and apply the resulting models. Techniques examined include domain-specific data-augmentation, learning rate and momentum scheduling, (advanced) ensembling in both model-space and weight-space, and alternative architectures and connection methods.

Following the investigation, we arrive at a model which achieves equal performance to the winning solution of the original Kaggle challenge, whilst being significantly quicker to train and apply, and being suitable for use with both GPU and CPU hardware setups. These reductions in timing and hardware requirements potentially allow the use of more powerful algorithms in HEP analyses, where models must be retrained frequently, sometimes at short notice, by small groups of researchers with limited hardware resources. Additionally, a new wrapper library for PyTorch called LUMINis presented, which incorporates all of the techniques studied.

Factor analysis is a flexible technique for assessment of multivariate dependence and codependence. Besides being an exploratory tool used to reduce the dimensionality of multivariate data, it allows estimation of common factors that often have an interesting theoretical interpretation in real problems. However, standard factor analysis is only applicable when the variables are scaled, which is often inappropriate, for example, in data obtained from questionnaires in the field of psychology,where the variables are often categorical. In this framework, we propose a factor model for the analysis of multivariate ordered and non-ordered polychotomous data. The inference procedure is done under the Bayesian approach via Markov chain Monte Carlo methods. Two Monte-Carlo simulation studies are presented to investigate the performance of this approach in terms of estimation bias, precision and assessment of the number of factors. We also illustrate the proposed method to analyze participants' responses to the Motivational State Questionnaire dataset, developed to study emotions in laboratory and field settings.