Modeling the ratio of correlated biomarkers using copula regression.

Modeling the ratio of two dependent components as a function of covariates is a frequently pursued objective in observational research. Despite the high relevance of this topic in medical studies, where biomarker ratios are often used as surrogate endpoints for specific diseases, existing models are commonly based on oversimplified assumptions, assuming e.g.

Emotion Regulation in Obsessive-Compulsive Disorder: An Ecological Momentary Assessment Study.

Emotion dysregulation is a central process implicated in the genesis and maintenance of obsessive-compulsive disorder (OCD). However, past research on OCD has examined emotion regulation with a trait-level approach, thereby neglecting important situational and temporal dynamics. The present study is the first one to examine moment-to-moment emotion regulation in individuals with OCD.

The Deep Promotion Time Cure Model.

We propose a novel method for predicting time-to-event data in the presence of cure fractions based on flexible survival models integrated into a deep neural network (DNN) framework. Our approach allows for nonlinear relationships and high-dimensional interactions between covariates and survival and is suitable for large-scale applications. To ensure the identifiability of the overall predictor formed of an additive decomposition of interpretable linear and nonlinear effects and potential higher-dimensional interactions captured through a DNN, we employ an orthogonalization layer.

Divergent Associations of Slow-Wave Sleep versus Rapid Eye Movement Sleep with Plasma Amyloid-Beta.

Objective: Recent evidence shows that during slow-wave sleep (SWS), the brain is cleared from potentially toxic metabolites, such as the amyloid-beta protein. Poor sleep or elevated cortisol levels can worsen amyloid-beta clearance, potentially leading to the formation of amyloid plaques, a neuropathological hallmark of Alzheimer disease. Here, we explored how nocturnal neural and endocrine activity affects amyloid-beta fluctuations in the peripheral blood.

BannMI deciphers potential -to-1 information transduction in signaling pathways to unravel message of intrinsic apoptosis.

Motivation: Cell fate decisions, such as apoptosis or proliferation, are communicated via signaling pathways. The pathways are heavily intertwined and often consist of sequential interaction of proteins (kinases). Information integration takes place on the protein level via -to-1 interactions.

Accounting for time dependency in meta-analyses of concordance probability estimates.

Recent years have seen the development of many novel scoring tools for disease prognosis and prediction. To become accepted for use in clinical applications, these tools have to be validated on external data. In practice, validation is often hampered by logistical issues, resulting in multiple small-sized validation studies.

Boosting multivariate structured additive distributional regression models.

We develop a model-based boosting approach for multivariate distributional regression within the framework of generalized additive models for location, scale, and shape. Our approach enables the simultaneous modeling of all distribution parameters of an arbitrary parametric distribution of a multivariate response conditional on explanatory variables, while being applicable to potentially high-dimensional data. Moreover, the boosting algorithm incorporates data-driven variable selection, taking various different types of effects into account.

Boosting distributional copula regression.

Capturing complex dependence structures between outcome variables (e.g., study endpoints) is of high relevance in contemporary biomedical data problems and medical research.

Is age at menopause decreasing? - The consequences of not completing the generational cohort.

Background: Due to contradictory results in current research, whether age at menopause is increasing or decreasing in Western countries remains an open question, yet worth studying as later ages at menopause are likely to be related to an increased risk of breast cancer. Using data from breast cancer screening programs to study the temporal trend of age at menopause is difficult since especially younger women in the same generational cohort have often not yet reached menopause. Deleting these younger women in a breast cancer risk analyses may bias the results.

Using Background Knowledge from Preceding Studies for Building a Random Forest Prediction Model: A Plasmode Simulation Study.

There is an increasing interest in machine learning (ML) algorithms for predicting patient outcomes, as these methods are designed to automatically discover complex data patterns. For example, the random forest (RF) algorithm is designed to identify relevant predictor variables out of a large set of candidates. In addition, researchers may also use external information for variable selection to improve model interpretability and variable selection accuracy, thereby prediction quality.

Review of guidance papers on regression modeling in statistical series of medical journals.

Although regression models play a central role in the analysis of medical research projects, there still exist many misconceptions on various aspects of modeling leading to faulty analyses. Indeed, the rapidly developing statistical methodology and its recent advances in regression modeling do not seem to be adequately reflected in many medical publications. This problem of knowledge transfer from statistical research to application was identified by some medical journals, which have published series of statistical tutorials and (shorter) papers mainly addressing medical researchers.

Deselection of base-learners for statistical boosting-with an application to distributional regression.

We present a new procedure for enhanced variable selection for component-wise gradient boosting. Statistical boosting is a computational approach that emerged from machine learning, which allows to fit regression models in the presence of high-dimensional data. Furthermore, the algorithm can lead to data-driven variable selection.

Statistical model building: Background "knowledge" based on inappropriate preselection causes misspecification.

Background: Statistical model building requires selection of variables for a model depending on the model's aim. In descriptive and explanatory models, a common recommendation often met in the literature is to include all variables in the model which are assumed or known to be associated with the outcome independent of their identification with data driven selection procedures. An open question is, how reliable this assumed "background knowledge" truly is.

Systematic review of education and practical guidance on regression modeling for medical researchers who lack a strong statistical background: Study protocol.

In the last decades, statistical methodology has developed rapidly, in particular in the field of regression modeling. Multivariable regression models are applied in almost all medical research projects. Therefore, the potential impact of statistical misconceptions within this field can be enormous Indeed, the current theoretical statistical knowledge is not always adequately transferred to the current practice in medical statistics.

Bayesian variable selection for non-Gaussian responses: a marginally calibrated copula approach.

We propose a new highly flexible and tractable Bayesian approach to undertake variable selection in non-Gaussian regression models. It uses a copula decomposition for the joint distribution of observations on the dependent variable. This allows the marginal distribution of the dependent variable to be calibrated accurately using a nonparametric or other estimator.

Cold War spy satellite images reveal long-term declines of a philopatric keystone species in response to cropland expansion.

Agricultural expansion drives biodiversity loss globally, but impact assessments are biased towards recent time periods. This can lead to a gross underestimation of species declines in response to habitat loss, especially when species declines are gradual and occur over long time periods. Using Cold War spy satellite images (Corona), we show that a grassland keystone species, the bobak marmot (), continues to respond to agricultural expansion that happened more than 50 years ago.

Candidate-gene association analysis for a continuous phenotype with a spike at zero using parent-offspring trios.

In this paper, we propose the class of generalized additive models for location, scale and shape in a test for the association of genetic markers with non-normally distributed phenotypes comprising a spike at zero. The resulting statistical test is a generalization of the quantitative transmission disequilibrium test with mating type indicator, which was originally designed for normally distributed quantitative traits and parent-offspring data. As a motivational example, we consider coronary artery calcification (CAC), which can accurately be identified by electron beam tomography.

Mixed binary-continuous copula regression models with application to adverse birth outcomes.

Bivariate copula regression allows for the flexible combination of two arbitrary, continuous marginal distributions with regression effects being placed on potentially all parameters of the resulting bivariate joint response distribution. Motivated by the risk factors for adverse birth outcomes, many of which are dichotomous, we consider mixed binary-continuous responses that extend the bivariate continuous framework to the situation where one response variable is discrete (more precisely, binary) whereas the other response remains continuous. Utilizing the latent continuous representation of binary regression models, we implement a penalized likelihood-based approach for the resulting class of copula regression models and employ it in the context of modeling gestational age and the presence/absence of low birth weight.

Quality and resource efficiency in hospital service provision: A geoadditive stochastic frontier analysis of stroke quality of care in Germany.

We specify a Bayesian, geoadditive Stochastic Frontier Analysis (SFA) model to assess hospital performance along the dimensions of resources and quality of stroke care in German hospitals. With 1,100 annual observations and data from 2006 to 2013 and risk-adjusted patient volume as output, we introduce a production function that captures quality, resource inputs, hospital inefficiency determinants and spatial patterns of inefficiencies. With high relevance for hospital management and health system regulators, we identify performance improvement mechanisms by considering marginal effects for the average hospital.

More green space is related to less antidepressant prescription rates in the Netherlands: A Bayesian geoadditive quantile regression approach.

Background: Exposure to green space seems to be beneficial for self-reported mental health. In this study we used an objective health indicator, namely antidepressant prescription rates. Current studies rely exclusively upon mean regression models assuming linear associations.

Studying the relationship between a woman's reproductive lifespan and age at menarche using a Bayesian multivariate structured additive distributional regression model.

Studies addressing breast cancer risk factors have been looking at trends relative to age at menarche and menopause. These studies point to a downward trend of age at menarche and an upward trend for age at menopause, meaning an increase of a woman's reproductive lifespan cycle. In addition to studying the effect of the year of birth on the expectation of age at menarche and a woman's reproductive lifespan, it is important to understand how a woman's cohort affects the correlation between these two variables.

Boosting joint models for longitudinal and time-to-event data.

Joint models for longitudinal and time-to-event data have gained a lot of attention in the last few years as they are a helpful technique clinical studies where longitudinal outcomes are recorded alongside event times. Those two processes are often linked and the two outcomes should thus be modeled jointly in order to prevent the potential bias introduced by independent modeling. Commonly, joint models are estimated in likelihood-based expectation maximization or Bayesian approaches using frameworks where variable selection is problematic and that do not immediately work for high-dimensional data.

Structured additive distributional regression for analysing landings per unit effort in fisheries research.

We analysed the landings per unit effort (LPUE) from the Barcelona trawl fleet targeting the red shrimp (Aristeus antennatus) using novel Bayesian structured additive distributional regression to gain a better understanding of the dynamics and determinants of variation in LPUE. The data set, covering a time span of 17 years, includes fleet-dependent variables (e.g.

Corridors restore animal-mediated pollination in fragmented tropical forest landscapes.

Tropical biodiversity and associated ecosystem functions have become heavily eroded through habitat loss. Animal-mediated pollination is required in more than 94% of higher tropical plant species and 75% of the world's leading food crops, but it remains unclear if corridors avert deforestation-driven pollination breakdown in fragmented tropical landscapes. Here, we used manipulative resource experiments and field observations to show that corridors functionally connect neotropical forest fragments for forest-associated hummingbirds and increase pollen transfer.