The paper proposes to analyze epidemiological data using regression models which enable subject-matter (epidemiological) interpretation of such data whether with uncorrelated or correlated predictors. To this end, response functions should include not only terms linear in predictors but also higher order ones (e.g. quadratic and cross terms). For epidemiological interpretation of a regression model, the suggestion is to construct conditional functions derived from the general regression function with the values of all predictor variables held fixed excepting one predictor. Unlike the conventional techniques based on linear-predictor models in which the coefficient at any variable is interpreted, our approach proposes to interpret this conditional function, which is multivariate for any predictor being dependent on the values of all the other predictors. It is such functions that can describe relationships between Y and a predictor that have different forms in different predictor domains. The paper discusses differences in the interpretation of the proposed conditional functions between cases involving correlated and uncorrelated predictor variables. The construction and analysis of regression models for epidemiological and environmental data are illustrated with examples.
Wastewater based epidemiology is recognized as one of the monitoring pillars, providing essential information for pandemic management. Central in the methodology are data modelling concepts for both communicating the monitoring results but also for analysis of the signal. It is due to the fast development of the field that a range of modelling concepts are used but without a coherent framework. This paper provides for such a framework, focusing on robust and simple concepts readily applicable, rather than applying latest findings from e.g., machine learning. It is demonstrated that data prepro…
This article reviews bias-correction models for measurement error of exposure variables in the field of nutritional epidemiology. Measurement error usually attenuates estimated slope towards zero. Due to the influence of measurement error, inference of parameter estimate is conservative and confidence interval of the slope parameter is too narrow. Bias-correction in estimators and confidence intervals are of primary interest. We review the following bias-correction models: regression calibration methods, likelihood based models, missing data models, simulation based methods, nonparametric mode…
Background: There is increasing interest in approaches for analyzing the effect of exposure mixtures on health. A key issue is how to simultaneously analyze often highly collinear components of the mixture, which can create problems such as confounding by co-exposure and co-exposure amplification bias (CAB). Evaluation of novel mixtures methods, typically using synthetic data, is critical to their ultimate utility. Objectives: This paper aims to answer two questions. How do causal models inform the interpretation of statistical models and the creation of synthetic data used to test them? Are n…
Excess hazard modeling is one of the main tools in population-based cancer survival research. Indeed, this setting allows for direct modeling of the survival due to cancer even in the absence of reliable information on the cause of death, which is common in population-based cancer epidemiology studies. We propose a unifying link-based additive modeling framework for the excess hazard that allows for the inclusion of many types of covariate effects, including spatial and time-dependent effects, using any type of smoother, such as thin plate, cubic splines, tensor products and Markov random fiel…
The proportional hazards model represents the most commonly assumed hazard structure when analysing time to event data using regression models. We study a general hazard structure which contains, as particular cases, proportional hazards, accelerated hazards, and accelerated failure time structures, as well as combinations of these. We propose an approach to apply these different hazard structures, based on a flexible parametric distribution (Exponentiated Weibull) for the baseline hazard. This distribution allows us to cover the basic hazard shapes of interest in practice: constant, bathtub, …
An increasing amount of geo-referenced mobile phone data enables the identification of behavioral patterns, habits and movements of people. With this data, we can extract the knowledge potentially useful for many applications including the one tackled in this study - understanding spatial variation of epidemics. We explored the datasets collected by a cell phone service provider and linked them to spatial HIV prevalence rates estimated from publicly available surveys. For that purpose, 224 features were extracted from mobility and connectivity traces and related to the level of HIV epidemic in…
The Cox proportional hazard model is one of the most popular tools in analyzing time-to-event data in public health studies. When outcomes observed in clinical data from different regions yield a varying pattern correlated with location, it is often of great interest to investigate spatially varying effects of covariates. In this paper, we propose a geographically weighted Cox regression model for sparse spatial survival data. In addition, a stochastic neighborhood weighting scheme is introduced at the county level. Theoretical properties of the proposed geographically weighted estimators are …
The Risk Ratio (RR) is the ratio of the outcome among the exposed to risk of the outcome among the unexposed. This is a simple concept, which makes one wonder why it has not gained the same popularity as the odds ratio. Using logistic regression to estimate the odds ratio is quite common in epidemiology and interpreting the odds ratio as a risk ratio, under the assumption that the outcome is rare, is also common. On one hand, estimating the odds ratio is simple but interpreting it is hard. On the other, estimating the risk ratio is challenging but its interpretation is straightforward. Issues …
The case-cohort study design bypasses resource constraints by collecting certain expensive covariates for only a small subset of the full cohort. Weighted Cox regression is the most widely used approach for analysing case-cohort data within the Cox model, but is inefficient. Alternative approaches based on multiple imputation and nonparametric maximum likelihood suffer from incompatibility and computational issues respectively. We introduce a novel Bayesian framework for case-cohort Cox regression that avoids the aforementioned problems. Users can include auxiliary variables to help predict th…
Statistical learning (SL) includes methods that extract knowledge from complex data. SL methods beyond generalized linear models are being increasingly implemented in public health research and epidemiology because they can perform better in instances with complex or high-dimensional data---settings when traditional statistical methods fail. These novel methods, however, often include random sampling which may induce variability in results. Best practices in data science can help to ensure robustness. As a case study, we included four SL models that have been applied previously to analyze the …
Comparing statistical learning models in wastewater-based epidemiology: An application to norovirus
School of Public Health, Imperial College London（帝国理工学院公共卫生学院）；MRC Centre for Environment and Health, Imperial College London（帝国理工学院环境与健康医学研究委员会中心）；MRC Centre for Global Infectious Disease Analysis, Imperial College London（帝国理工学院全球传染病分析医学研究委员会中心）
Count data, for example the number of observed cases of a disease in a city, often arise in the fields of healthcare analytics and epidemiology. In this paper, we consider performing regression on multivariate data in which our outcome is a count. Specifically, we derive log-likelihood functions for finite mixtures of regression models involving counts that come from a Poisson distribution, as well as a negative binomial distribution when the counts are significantly overdispersed. Within our proposed modeling framework, we carry out optimal component selection using the information criteria s…
Background: We propose a method for estimating the timing of in-bed intervals using objective data in a large representative U.S. sample, and quantify the association between these intervals and age, sex, and day of the week. Methods: The study included 11,951 participants six years and older from the National Health and Nutrition Examination Survey (NHANES) 2003-2006, who wore accelerometers to measure physical activity for seven consecutive days. Participants were instructed to remove the device just before the nighttime sleep period and put it back on immediately after. This nighttime perio…
We consider the situation of estimating Cox regression in which some covariates are subject to missing, and there exists additional information (including observed event time, censoring indicator and fully observed covariates) which may be predictive of the missing covariates. We propose to use two working regression models: one for predicting the missing covariates and the other for predicting the missing probabilities. For each missing covariate observation, these two working models are used to define a nearest neighbor imputing set. This set is then used to nonparametrically impute covariat…
We study explained variation under the additive hazards regression model for right-censored data. We consider different approaches for developing such a measure, and focus on one that estimates the proportion of variation in the failure time explained by the covariates. We study the properties of the measure both analytically, and through extensive simulations. We apply the measure to a well-known survival data set as well as the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database for prediction of mortality in early-stage prostate cancer patients using high dimensional …
Residuals in regression models are often spatially correlated. Prominent examples include studies in environmental epidemiology to understand the chronic health effects of pollutants. I consider the effects of residual spatial structure on the bias and precision of regression coefficients, developing a simple framework in which to understand the key issues and derive informative analytic results. When unmeasured confounding introduces spatial structure into the residuals, regression models with spatial random effects and closely-related models such as kriging and penalized splines are biased, …
Classical epidemiology has focused on the control of confounding but it is only recently that epidemiologists have started to focus on the bias produced by colliders. A collider for a certain pair of variables (e.g., an outcome Y and an exposure A) is a third variable (C) that is caused by both. In a directed acyclic graph (DAG), a collider is the variable in the middle of an inverted fork (i.e., the variable C in A -> C <- Y). Controlling for, or conditioning an analysis on a collider (i.e., through stratification or regression) can introduce a spurious association between its causes. This po…
Discovering equations from data: symbolic regression in dynamical systems
Institute of Sciences Mathematics and Computation, Universidade de São Paulo-Campus de São Carlos（数学与计算科学研究院，圣保罗大学-萨o卡洛斯校区）；Statistic Department, State University of Maringá（统计系，马林加州立大学）；Department of Mathematics Applied and Statistics, Institute of Sciences Mathematics and Computation, Universidade de São Paulo-Campus de São Carlos（应用数学与统计系，数学与计算科学研究院，圣保罗大学-萨o卡洛斯校区）
Dynamic linear models with Gaussian observations and Gaussian states lead to closed-form formulas for posterior simulation. However, these closed-form formulas break down when the response or state evolution ceases to be Gaussian. Dynamic, generalized linear models exemplify a class of models for which this is the case, and include, amongst other models, dynamic binomial logistic regression and dynamic negative binomial regression. Finding and appraising posterior simulation techniques for these models is important since modeling temporally correlated categories or counts is useful in a variet…
Highly non-linear, chaotic or near chaotic, dynamic models are important in fields such as ecology and epidemiology: for example, pest species and diseases often display highly non-linear dynamics. However, such models are problematic from the point of view of statistical inference. The defining feature of chaotic and near chaotic systems is extreme sensitivity to small changes in system states and parameters, and this can interfere with inference. There are two main classes of methods for circumventing these difficulties: information reduction approaches, such as Approximate Bayesian Computat…
Biomedical studies have a common interest in assessing relationships between multiple related health outcomes and high-dimensional predictors. For example, in reproductive epidemiology, one may collect pregnancy outcomes such as length of gestation and birth weight and predictors such as single nucleotide polymorphisms in multiple candidate genes and environmental exposures. In such settings, there is a need for simple yet flexible methods for selecting true predictors of adverse health responses from a high-dimensional set of candidate predictors. To address this problem, one may either consi…
Broad Institute of MIT and Harvard（麻省理工学院与哈佛大学博德研究所）
We detail distributed algorithms for scalable, secure multiparty linear regression and feature selection at essentially the same speed as plaintext regression. While the core geometric ideas are simple, the recognition of their broad utility when combined is novel. Our scheme opens the door to efficient and secure genome-wide association studies across multiple biobanks.
In environmental epidemiology studies, health response data (e.g. hospitalization or mortality) are often noisy because of hospital organization and other social factors. The noise in the data can hide the true signal related to the exposure. The signal can be unveiled by performing a temporal aggregation on health data and then using it as the response in regression analysis. From aggregated series, a general methodology is introduced to account for the particularities of an aggregated response in a regression setting. This methodology can be used with usually applied regression models in wea…
The use of prior information in the linear regression is well known to provide more efficient estimators of regression coefficients. The methods of non-stochastic restricted regression estimation proposed by Theil and Goldberger (1961) are preferred when prior information is available. In this study, we will consider parameter estimation and the variable selection in non-stochastic restricted linear regression model, using least absolute shrinkage and selection operator (LASSO) method introduced by Tibshirani (1996). A small simulation study and real data example are provided to illustrate the…
It is well established that migratory birds in general have advanced their arrival times in spring, and in this paper we investigate potential ways of enhancing the level of detail in future phenological analyses. We perform single as well as multiple species analyses, using linear models on empirical quantiles, non-parametric quantile regression and likelihood-based parametric quantile regression with asymmetric Laplace distributed error terms. We conclude that non-parametric quantile regression appears most suited for single as well as multiple species analyses.
This paper deals with improvement of linear quantile regression, when there are a few distinct values of the covariates but many replicates. On can improve asymptotic efficiency of the estimated regression coefficients by using suitable weights in quantile regression, or simply by using weighted least squares regression on the conditional sample quantiles. The asymptotic variances of the unweighted and weighted estimators coincide only in some restrictive special cases, e.g., when the density of the conditional response has identical values at the quantile of interest over the support of the c…
In contrast to conventional, univariate analysis, various types of multivariate analysis have been applied to functional magnetic resonance imaging (fMRI) data. In this paper, we compare two contemporary approaches for multivariate regression on task-based fMRI data: linear regression with ridge regularization and non-linear symbolic regression using genetic programming. The data for this project is representative of a contemporary fMRI experimental design for visual stimuli. Linear and non-linear models were generated for 10 subjects, with another 4 withheld for validation. Model quality is e…
Mitscherlich's function is a well-known three-parameter non-linear regression function that quantifies the relation between a stimulus or a time variable and a response. Optimal designs for this function have been constructed only for normally distributed responses with homoscedastic variances. In this paper, we construct D-optimal designs for discrete and continuous responses having their distribution function in the exponential family. We also demonstrate the connection with D-optimality for weighted linear regression.
