Edwin Van den Heuvel

• Professor (Full) at Eindhoven University of Technology

This study aimed to predict preterm birth in nulliparous women using machine learning and easily accessible variables from prenatal visits. Elastic net regularized logistic regression models were developed and evaluated using 5-fold cross-validation on data from 8,830 women in the Nulliparous Pregnancy Outcomes Study: New Mothers-to-Be (nuMoM2b) da...

Introducing a preregistered approach for gathering questionnaire data at scientific conferences, we examined primarily attitudes towards and practices of science communication amongst physicists employed at Dutch universities and research institutes. Tenure track physicists who participate frequently in science communication seem to be driven by st...

Background: Multimorbidity, defined as the co-occurrence of two or more chronic conditions, is highly prevalent and associated with adverse clinical outcomes. Yet, there are limited data on the most prevalent chronic conditions and overall multimorbidity in the rural Southern in US. We described the prevalence of chronic conditions, risk factors, a...

Introduction: Individuals living in rural areas have a disproportionately high rate of cardiovascular disease (CVD) mortality. Coronary artery calcium (CAC) scanning may inform CVD risk stratification. However, the prevalence of CAC in rural areas is unknown. Research Question: What is the prevalence of CAC according to age, sex, and self-reported...

Previous studies suggest that Dupuytren’s disease is associated with increased mortality, but most studies failed to account for important confounders. In this population-based cohort study, general practitioners’ (GP) data were linked to Statistics Netherlands to register all-cause and disease-specific mortality. Patients with Dupuytren’s disease...

Hazard ratios are prone to selection bias, compromising their use as causal estimands. On the other hand, if Aalen’s additive hazard model applies, the hazard difference has been shown to remain unaffected by the selection of frailty factors over time. Then, in the absence of confounding, observed hazard differences are equal in expectation to the...

Simulation studies are commonly used to evaluate the performance of newly developed meta-analysis methods. For methodology that is developed for an aggregated data meta-analysis, researchers often resort to simulation of the aggregated data directly, instead of simulating individual participant data from which the aggregated data would be calculate...

Achieving optimal cardiovascular health in rural populations can be challenging for several reasons including decreased access to care with limited availability of imaging modalities, specialist physicians, and other important health care team members. Therefore, innovative solutions are needed to optimize health care and address cardiovascular hea...

It is known that the hazard ratio lacks a useful causal interpretation. Even for data from a randomized controlled trial, the hazard ratio suffers from so-called built-in selection bias as, over time, the individuals at risk among the exposed and unexposed are no longer exchangeable. In this paper, we formalize how the expectation of the observed h...

Background Patients with Dupuytren’s disease (DD) are mostly surgically treated by percutaneous needle fasciotomy (PNF) or limited fasciectomy (LF), but data on time intervals to retreatment is lacking. We aimed to estimate the risk of retreatment within certain time periods after treatment with PNF and LF. Methods We used data of participants of...

Sustainable intensification of agriculture requires understanding of the effect of soil characteristics and nutrient supply on crop growth. As farms are increasing in size by acquiring small fields from various farmers, the soil characteristics and nutrient supply might be very different from field to field, while at the same time specific soil pro...

The growing complexity of GeoSentinel surveillance data creates opportunities for novel data science-based outbreak detection methods. Challenges may be overcome by effective multidisciplinary collaboration. The early signals generated by outbreak detection methods using GeoSentinel data may influence policymaking, shape public health responses, an...

Multimorbidity is a risk factor for patient-important outcomes including quality of life and functional decline. Multimorbidity research has focused mainly on disease counts, with less attention to patterns among chronic conditions. Network analysis has been increasingly used to examine multimorbidity clusters, but there are no guidelines for its c...

Frailty prevalence estimates vary considerably (4.0% to 59.1% in one review). Understanding these differences and what drives frailty among individuals could lead to more focused interventions. Breaking frailty into subdomains and exploring their relationships is one approach to this. A 127-item overall Frailty Index (FI) based on data collected on...

Objectives To quantify inconsistent self-reporting of chronic conditions between the baseline (2011–2015) and first follow-up surveys (2015–2018) in the Canadian Longitudinal Study on Aging (CLSA), and to explore methods to resolve inconsistent responses and impact on multimorbidity. Methods Community-dwelling adults aged 45–85 years in the baseli...

Causal inference from observational data requires untestable identification assumptions. If these assumptions apply, machine learning methods can be used to study complex forms of causal effect heterogeneity. Recently, several machine learning methods were developed to estimate the conditional average treatment effect (ATE). If the features at hand...

Introduction We determined if the heart rate (HR) monitoring performance of a wireless and nonadhesive belt is non‐inferior compared to standard electrocardiography (ECG). Secondary objective was to explore the belt's respiratory rate (RR) monitoring performance compared to chest impedance (CI). Method In this multicenter non‐inferiority trial, pr...

The detection of arrhythmias from wearable devices is still an open challenge, while the availability of screening tools for the large population would allow reduced complications and costs. We propose a model-based approach to the detection and classification of premature contractions into atrial and ventricular. The extracted signal morphology an...

Purpose of Review Several prediction algorithms include race as a component to account for race-associated variations in disease frequencies. This practice has been questioned recently because of the risk of perpetuating race as a biological construct and diverting attention away from the social determinants of health (SDoH) for which race might be...

The optimal cut-off value of the optical density index of the galactomannan antigen assays (GM) for diagnosing invasive pulmonary aspergillosis in hematological patients is a disputed topic. This article conducts a systematic review with a meta-analysis to establish which optical density index (ODI) cut-off value should be implemented into clinical...

Lignin is a potential resource for biobased aromatics with applications in the field of fuel additives, resins, and bioplastics. Via a catalytic depolymerization process using supercritical ethanol and a mixed metal oxide catalyst (CuMgAlOx), lignin can be converted into a lignin oil, containing phenolic monomers that are intermediates to the menti...

Progression of atrial fibrillation (AF) and outcomes of ablation therapy are strongly affected by modifiable risk factors. Although previous studies show beneficial effects of modifying single risk factors, there is lack of evidence from randomized controlled trials on the effects of integrated AF lifestyle programmes. The POP trial is designed to...

Importance: Colorectal surgery is associated with substantial morbidity rates and a lowered functional capacity. Optimization of the patient's condition in the weeks prior to surgery may attenuate these unfavorable sequelae. Objective: To determine whether multimodal prehabilitation before colorectal cancer surgery can reduce postoperative compl...

Introduction: Palpitations occurring in specific body positions are often reported by patients, but the effect of body position on arrhythmia has received little research attention. We hypothesize that resting body position can exert pro-arrhythmogenic effects in various ways. For example, lateral body position is known to increase change atrial a...

Sharp upper bounds are proved for the probability that a standardized random variable takes on a value outside a possibly asymmetric interval around 0. Six classes of distributions for the random variable are considered, namely the general class of ‘distributions’, the class of ‘symmetric distributions’, of ‘concave distributions’, of ‘unimodal dis...

Objectives: Therapeutic drug monitoring (TDM) of voriconazole is recommended based on retrospective data and limited prospective studies. The aim of this study is to investigate if TDM guided treatment of voriconazole is superior to the standard treatment for invasive aspergillosis. Methods: A multicentre (n=10), prospective, cluster randomised,...

Background frailty imparts a higher risk for hospitalisation, mortality and morbidity due to COVID-19 infection, but the broader impacts of the pandemic and associated public health measures on community-living people with frailty are less known. Methods we used cross-sectional data from 23,974 Canadian Longitudinal Study on Aging participants who...

In the analysis of binary disease classification, numerous techniques exist, but they merely work well for mean differences in biomarkers between cases and controls. Biological processes are, however, much more heterogeneous, and differences could also occur in other distributional characteristics (e.g. variances, skewness). Many machine learning t...

Background Due to identifiability problems, statistical inference about treatment-by-period interactions has not been discussed for stepped wedge designs in the literature thus far. Unidirectional switch designs (USDs) generalize the stepped wedge designs and allow for estimation and testing of treatment-by-period interaction in its many flexible d...

Introduction Palpitations occurring in specific body positions are often reported by patients, but the effect of body position on arrhythmia has received little research attention. We hypothesize that resting body position can exert pro-arrhythmogenic effects in various ways. For example, lateral body position is known to increase change atrial and...

Copas’ method corrects a pooled estimate from an aggregated data meta-analysis for publication bias. Its performance has been studied for one particular mechanism of publication bias. We show through simulations that Copas’ method is not robust against other realistic mechanisms. This questions the usefulness of Copas’ method, since publication bia...

Hazard ratios are prone to selection bias, compromising their use as causal estimands. On the other hand, the hazard difference has been shown to remain unaffected by the selection of frailty factors over time. Therefore, observed hazard differences can be used as an unbiased estimator for the causal hazard differences in the absence of confounding...

It is known that the hazard ratio lacks a useful causal interpretation. Even for data from a randomized controlled trial, the hazard ratio suffers from built-in selection bias as, over time, the individuals at risk in the exposed and unexposed are no longer exchangeable. In this work, we formalize how the observed hazard ratio evolves and deviates...

Causal inference from observational data requires untestable assumptions. If these assumptions apply, machine learning (ML) methods can be used to study complex forms of causal-effect heterogeneity. Several ML methods were developed recently to estimate the conditional average treatment effect (CATE). If the features at hand cannot explain all hete...

In recent years the field of causal inference from observational data has emerged rapidly. This literature has focused on (conditional) average causal effect estimation. When (remaining) variability of individual causal effects (ICEs) is considerable, average effects may be less informative, and possibly misleading for an individual. The fundamenta...

Objectives To determine if the electrical heart axis in different types of congenital heart defects (CHD) differs from that of a healthy cohort at mid-gestation. Methods Non-invasive fetal electrocardiography (NI-fECG) was performed in singleton pregnancies with suspected CHD between 16 and 30 weeks of gestation. The mean electrical heart axis (ME...

Background Premature onset of cardiovascular disease (CVD) imposes a significant societal burden and challenges prevention efforts. Methods and Results Trends in the incidence of premature CVD (before age 55, 60, or 65 years, separate analysis for each threshold) were evaluated in 14 464 Framingham Heart Study participants over 7 decades of observ...

Anomaly detection when observing a large number of data streams is essential in a variety of applications, ranging from epidemiological studies to monitoring of complex systems. High-dimensional scenarios are usually tackled with scan-statistics and related methods, requiring stringent modeling assumptions for proper calibration. In this work we ta...

The United States Pharmacopoeia (USP) presents two approaches for showing non-inferiority of an alternate qualitative microbiological method versus a compendial method. One approach compares the positive rates for the alternate and compendial methods at one spike level, while the other one compares multiple most probable number (MPN) estimates from...

Introduction: Complex surveys use stratified or cluster sampling to recruit participants. Researchers analyzing these surveys often wish to make inferences about the source populations from which the participants are drawn. In such cases, methodologists recommend employing sample weights in regression analyses; however, the utilization of weights i...

Gau\ss (1823) proved a sharp upper bound on the probability that a random variable falls outside a symmetric interval around zero when its distribution is unimodal with mode at zero. For the class of all distributions with mean at zero, Bienaym\'e (1853) and Chebyshev (1867) independently provided another, simpler sharp upper bound on this probabil...

In this paper, we extend the work of Pimentel et al. (2015) and propose an adjusted estimator of Kendall's $\tau$ for bivariate zero-inflated count data. We provide achievable lower and upper bounds of our proposed estimator and show its relationship with current literature. In addition, we also suggest an estimator of the achievable bounds, thereb...

Sum scores from questionnaire data are frequently analyzed under the normality assumption which is not always tenable due to for instance the skewness of the distribution, or the discreteness of the sum scores for small number of items. Alternatively, an ordinal regression analysis can be applied, but this approach seems appropriate only for very s...

Introduction Cardiorespiratory monitoring is used in the neonatal intensive care unit (NICU) to assess the clinical status of newborn infants and detect critical deteriorations in cardiorespiratory function. Currently, heart rate (HR) is monitored by electrocardiography (ECG) and respiration by chest impedance (CI). Disadvantages of current monitor...

The DerSimonian–Laird (DL) weighted average method for aggregated data meta‐analysis has been widely used for the estimation of overall effect sizes. It is criticized for its underestimation of the standard error of the overall effect size in the presence of heterogeneous effect sizes. Due to this negative property, many alternative estimation appr...

Background: Predicting progression of Dupuytren disease becomes relevant in an upcoming era with progression-preventing treatment. This study aimed to determine the course of Dupuytren disease and identify factors associated with progression. Methods: Two hundred fifty-eight patients with Dupuytren disease participated in this prospective cohort...

Introduction: The RURAL cohort study addresses critical knowledge gaps regarding heart and lung disorders in rural Southeastern USA. Using CDC mortality data, RURAL selected ten counties from four states (Alabama, Mississippi, Louisiana, and Kentucky) that are ecologically paired for their five-year low and high CVD mortality rates. RURAL will recr...

In the previous chapter we computed descriptive statistics for the dataset on faces. The results showed that the average rating was 58.37 and that men rated the faces higher than women on average. If we are only interested in the participants in the study and we are willing to believe that the results are fully deterministic, we could claim that th...

In this book we have introduced both the practice of analyzing data using R, and covered probability theory, including estimation and testing. For most of the text we have, however, considered what some would call Frequentist statistics (the name deriving from the notion of probability as a long-run frequency): in this school of thought regarding p...

The field of inferential statistics tries to use the information from a sample to make statements or decisions about the population of interest. It takes into account the uncertainty that the information is coming from sampling and does not perfectly represent the population, since another sample would give different outcomes. An important aspect o...

In the first chapter we discussed the calculation of some statistics that could be useful to summarize the observed data. In Chap. 2 we explained sampling approaches for the proper collection of data from populations. We demonstrated, using the appropriate statistics, how we may extend our conclusions beyond our sample to our population. Probabilit...

Up to now we have mainly focussed on the analysis of a single variable. We have discussed probability density functions (PDFs), probability mass functions (PMFs), and distribution functions (CDFs) as descriptions of the population values for such a single variable and connected these functions to a single random variable. These probability function...

Up till now we have covered ways of summarizing data, and we have paid a lot of attention to understanding how summaries computed on sample data (sample statistics) vary as a function of the sampling plan and the population characteristics. In Chap. 5 we also covered the idea that we can use our sample to estimate population parameters; in this cas...

For data scientists, the most important use of statistics will be in making sense of data. Therefore, in this first chapter we immediately start by examining, describing, and visualizing data. We will use a dataset called face-data.csv throughout this chapter; this dataset, as well as all the other datasets we use throughout this book, is described...

Statistics is a science that is concerned with principles, methods, and techniques for collecting, processing, analyzing, presenting, and interpreting (numerical) data. Statistics can be divided roughly into descriptive statistics (Chap. 1) and inferential statistics (Chap. 2), as we have already suggested. Descriptive statistics summarizes and vis...

This work discusses the problem of informative censoring in survival studies. A joint model for the time to event and the time to censoring is presented. Their hazard functions include a latent factor in order to identify this joint model without sacrificing the flexibility of the parametric specification. Furthermore, a fully Bayesian formulation...

Background Sex-specific and race-specific pooled cohort equations (PCEs) are recommended for estimating the 10-year risk of cardiovascular disease, with an absolute risk of more than 7·5% indicating a clinical decision threshold. We compared differences between Black and White individuals in PCE-estimated absolute cardiovascular disease risk across...

In the original version of the book, the following belated corrections have been made

Introduction A fetal anomaly scan in mid-pregnancy is performed, to check for the presence of congenital anomalies, including congenital heart disease (CHD). Unfortunately, 40% of CHD is still missed. The combined use of ultrasound and electrocardiography might boost detection rates. The electrical heart axis is one of the characteristics which can...

The European and United States Pharmacopoeia demand a non-inferiority study on the detection of microorganisms when an alternate qualitative microbiological method is intended to replace the compendial microbiological method. However, without imposing any modeling assumptions or constraints, non-inferiority studies require large numbers of test sam...

Background Sleep apnea patients on CPAP therapy exhibit differences in how they adhere to the therapy. Previous studies have demonstrated the benefit of describing adherence in terms of discernible longitudinal patterns. However, these analyses have been done on a limited number of patients, and did not properly represent the temporal characteristi...

Pearson’s correlation coefficient is considered a measure of linear association between bivariate random variables X and Y. It is recommended not to use it for other forms of associations. Indeed, for non-linear monotonic associations alternative measures like Spearman’s rank and Kendall’s tau correlation coefficients are considered more appropriat...

During the past two decades, methods for identifying groups with different trends in longitudinal data have become of increasing interest across many areas of research. To support researchers, we summarize the guidance from the literature regarding longitudinal clustering. Moreover, we present a selection of methods for longitudinal clustering, inc...

Age-specific reference values are important in medical science to evaluate the normal ranges of subjects and to help physicians signal potential disorders as early as possible. They are applied to many types of measurements, including discrete measures obtained from questionnaires and clinical tests. These discrete measures are typically skewed to...

The discovery of the ipRGCs was thought to fully explain the mechanism behind the relationship between light and effects beyond vision such as alertness. However, this relationship turned out to be more complicated. The current paper describes, by using personal lighting conditions in a field study, further exploration of the relationship between l...

Causal effect sizes may vary among individuals and they can even be of opposite directions. When there exists serious effect heterogeneity, the population average causal effect (ACE) is not very informative. It is well-known that individual causal effects (ICEs) cannot be determined in cross-sectional studies, but we will show that ICEs can be retr...

Objectives: Two-dimensional speckle tracking echocardiography (2D-STE) is a relatively new, promising technique to assess cardiac function in the fetus. Fetal cardiac function can be used in the evaluation of non-cardiac disease states in pregnancy. However, reliable reference values for deformation parameters measured with speckle tracking in the...

Objective To evaluate the pattern of frailty across several of social stratifiers associated with health inequalities. Design, setting and participants Cross-sectional baseline data on 51 338 community-living women and men aged 45–85 years from the population-based Canadian Longitudinal Study on Aging (collected from September 2011 to May 2015) we...

Regression based methods for the detection of publication bias in meta-analysis have been extensively evaluated in literature. When dealing with continuous outcomes, specific hidden factors (e.g., heteroscedasticity) may interfere with the test statistics. In this paper we investigate the influence of residual heteroscedasticity on the performance...

Background. Sex- and race-specific pooled cohort equations (PCE) are recommended for estimating the 10-year risk of cardiovascular disease (CVD), with an absolute risk >7.5% indicating a clinical decision threshold. Methods. We generated in silico 30,565 risk profiles in men and 29,515 in women by combining numerical (age, total and high-density li...

One-class modelling is a useful approach in metabolomics for the untargeted detection of abnormal metabolite profiles, when information from a set of reference observations is available to model “normal” or baseline metabolite profiles. Such outlying profiles are typically identified by comparing the distance between an observation and the referenc...

The DerSimonian-Laird (DL) weighted average method has been widely used for estimation of a pooled effect size from an aggregated data meta-analysis study. It is mainly criticized for its underestimation of the standard error of the pooled effect size in the presence of heterogeneous study effect sizes. The uncertainty in the estimation of the betw...

Models characterized by autoregressive structure and random coefficients are powerful tools for the analysis of high-frequency, high-dimensional and volatile time series. The available literature on such models is broad, but also sector-specific, overlapping, and confusing. Most models focus on one property of the data, while much can be gained by...

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 disc...

In the analysis of binary disease classification, single biomarkers might not have significant discriminating power and multiple biomarkers from a large set of biomarkers should be selected. Numerous approaches exist, but they merely work well for mean differences in biomarkers between cases and controls. Biological processes are however much more...

Objective Electrohysterography is a non-invasive technique to monitor uterine activity and has a significantly higher sensitivity compared to conventional external tocodynamometry. Whether this technique could lead to improved obstetrical outcomes is still unknown. In this propensity score matched study, clinical results of the first pilot implemen...

Background To reduce the transmission of the severe acute respiratory syndrome coronavirus 2 in its first wave, European governments have implemented successive measures to encourage social distancing. However, it remained unclear how effectively measures reduced the spread of the virus. We examined how the effective-contact rate (ECR), the mean nu...

The initial footprint of an earthquake can be extended considerably by triggering of clustered aftershocks. Such earthquake–earthquake interactions have been studied extensively for data-rich, stationary natural seismicity. Induced seismicity, however, is intrinsically inhomogeneous in time and space and may have a limited catalog of events; this m...

The growth and yield of crops within a farm largely vary among fields. Farms are increasing in size by acquiring smaller land parcels from different farmers who have different management strategies. As a result, between-field variability increases and understanding such variability is a necessity for precision farming. New data analysis techniques...

Longitudinal clustering provides a detailed yet comprehensible description of time profiles among subjects. With several approaches that are commonly used for this purpose, it remains unclear under which conditions a method is preferred over another method. We investigated the performance of five methods using Monte Carlo simulations on synthetic d...

The main reason lighting control is being applied is to reduce energy consumption. However, there are many more reasons for lighting control to be optimised in buildings. Lighting systems can be controlled to enhance or optimise effects beyond vision. Automatic control of electric lighting systems or daylight systems is one way of adjusting someone...

Objective: To investigate the effect of maternal hyperoxygenation on fetal heart rate (FHR) when applied for suspected fetal distress during the second stage of term labor. Approach: A single-center randomized controlled trial was conducted in a tertiary care hospital in The Netherlands. Participants were included during the second stage of labo...

Models characterized by autoregressive structure and random coefficients are powerful tools for the analysis of high-frequency, high-dimensional and volatile time series. The available literature on such models is broad, but also sectorial, overlapping, and confusing. Most models focus on one property of the data, while much can be gained by combin...

Simulation studies are commonly used to evaluate the performance of newly developed meta-analysis methods. For methodology that is developed for an aggregated data meta-analysis, researchers often resort to simulation of the aggregated data directly, instead of simulating individual participant data from which the aggregated data would be calculate...

Anomaly detection when observing a large number of data streams is essential in a variety of applications, ranging from epidemiological studies to monitoring of complex systems. High-dimensional scenarios are usually tackled with scan-statistics and related methods, requiring stringent modeling assumptions for proper calibration. In this work we ta...

To determine the utility of admission laboratory markers in the assessment and prognostication of COVID‐19, a systematic review and meta‐analysis was conducted on the association between admission laboratory values in hospitalized COVID‐19 patients and subsequent disease severity and mortality. Searches were conducted in MEDLINE, Pubmed, Embase, an...

Copas' method corrects a pooled estimate from an aggregated data meta-analysis for publication bias. Its performance has been studied for one particular mechanism of publication bias. We show through simulations that Copas' method is not robust against other realistic mechanisms. This questions the usefulness of Copas' method, since publication bia...

Coronavirus disease 2019 (COVID-19) is an unprecedented and fast evolving pandemic, which has caused a large number of critically ill patients and deaths globally. It is an acute public health crisis leading to overloaded critical care capacity. Timely prediction of the clinical outcome (death/survival) of hospital-admitted COVID-19 patients can pr...

An increasing number of applications in the chemical industry involve measuring nonconforming items, particularly in high‐purity processes or high‐yield processes. Dedicated monitoring tools such as the time‐between‐events (TBE) control charts have been developed for both discrete time (CCC‐charts) and continuous time (t r ‐charts) for detecting an...

Lower circulating homoarginine concentrations have been associated with morbidity and mortality in patients with established cardiovascular disease (CVD). We assayed plasma homoarginine concentrations in 3331 Framingham Offspring Study participants attending examination cycle six (mean age 58.6 years, 53% women). We evaluated correlates of plasma h...