Reflections on Partial Least Squares Path Modeling

The purpose of the present article is to take stock of a recent exchange in Organizational Research Methods between critics (Rönkkö & Evermann, 2013) and proponents (Henseler et al., 2014) of partial least squares path modeling (PLS-PM). The two target articles were centered around six principal issues, namely whether PLS-PM: (1) can be truly characterized as a technique for structural equation modeling (SEM); (2) is able to correct for measurement error; (3) can be used to validate measurement models; (4) accommodates small sample sizes; (5) is able to provide null hypothesis tests for path coefficients; and (6) can be employed in an exploratory, model-building fashion. We summarize and elaborate further on the key arguments underlying the exchange, drawing from the broader methodological and statistical literature in order to offer additional thoughts concerning the utility of PLS-PM and ways in which the technique might be improved. We conclude with recommendations as to whether and how PLS-PM serves as a viable contender to SEM approaches for estimating and evaluating theoretical models.

Self-potentials in partially saturated media: the importance of explicit modeling of electrode effects

Self-potential (SP) data are of interest to vadose zone hydrology because of their direct sensitivity to water flow and ionic transport. There is unfortunately little consensus in the literature about how to best model SP data under partially saturated conditions, and different approaches (often supported by one laboratory data set alone) have been proposed. We argue that this lack of agreement can largely be traced to electrode effects that have not been properly taken into account. A series of drainage and imbibition experiments were considered in which we found that previously proposed approaches to remove electrode effects were unlikely to provide adequate corrections. Instead, we explicitly modeled the electrode effects together with classical SP contributions using a flow and transport model. The simulated data agreed overall with the observed SP signals and allowed decomposing the different signal contributions to analyze them separately. After reviewing other published experimental data, we suggest that most of them include electrode effects that have not been properly taken into account. Our results suggest that previously presented SP theory works well when considering the modeling uncertainties presently associated with electrode effects. Additional work is warranted to not only develop suitable electrodes for laboratory experiments but also to assure that associated electrode effects that appear inevitable in longer term experiments are predictable, so that they can be incorporated into the modeling framework.

In vivo 13C NMR spectroscopy and metabolic modeling in the brain: a practical perspective.

In vivo 13C NMR spectroscopy has the unique capability to measure metabolic fluxes noninvasively in the brain. Quantitative measurements of metabolic fluxes require analysis of the 13C labeling time courses obtained experimentally with a metabolic model. The present work reviews the ingredients necessary for a dynamic metabolic modeling study, with particular emphasis on practical issues.

Biological exposure indicators: quantification of biological variability using toxicokinetic modeling

Compartmental and physiologically based toxicokinetic modeling coupled with Monte Carlo simulation were used to quantify the impact of biological variability (physiological, biochemical, and anatomic parameters) on the values of a series of bio-indicators of metal and organic industrial chemical exposures. A variability extent index and the main parameters affecting biological indicators were identified. Results show a large diversity in interindividual variability for the different categories of biological indicators examined. Measurement of the unchanged substance in blood, alveolar air, or urine is much less variable than the measurement of metabolites, both in blood and urine. In most cases, the alveolar flow and cardiac output were identified as the prime parameters determining biological variability, thus suggesting the importance of workload intensity on absorbed dose for inhaled chemicals.

H2O-δD-Fe-III relations of dehydrogenation and dehydration processes in magmatic amphiboles

Stable isotope compositions of a suite of magmatic amphiboles from alkaline basalts and andesitic rocks were examined to constrain the effects of degassing processes on the hydrogen isotope compositions. The Fe3+ (as Fe3+/Fe-total) and H2O contents, as well as the H isotope compositions of the amphiboles, differ markedly (27-58%, 0.5-2.2 wt%, -107 to -15 parts per thousand, respectively) but indicate systematic variations. The observed trends can be explained either as dehydrogenation or dehydration processes, both of which are coupled to oxidation processes, the latter most probably related to O2- substitution within amphiboles. The dehydrogenation-dehydration models can be used to assess the primary compositions of the magmas. As an important example, delta D values of amphiboles of Martian meteorites are discussed in a similar context. Copyright (c) 2006 John Wiley & Sons, Ltd.

Distribution of metals exposure and associations with cardiometabolic risk factors in the "Modeling the Epidemiologic Transition Study".

BACKGROUND: Metals are known endocrine disruptors and have been linked to cardiometabolic diseases via multiple potential mechanisms, yet few human studies have both the exposure variability and biologically-relevant phenotype data available. We sought to examine the distribution of metals exposure and potential associations with cardiometabolic risk factors in the "Modeling the Epidemiologic Transition Study" (METS), a prospective cohort study designed to assess energy balance and change in body weight, diabetes and cardiovascular disease risk in five countries at different stages of social and economic development. METHODS: Young adults (25-45 years) of African descent were enrolled (N = 500 from each site) in: Ghana, South Africa, Seychelles, Jamaica and the U.S.A. We randomly selected 150 blood samples (N = 30 from each site) to determine concentrations of selected metals (arsenic, cadmium, lead, mercury) in a subset of participants at baseline and to examine associations with cardiometabolic risk factors. RESULTS: Median (interquartile range) metal concentrations (μg/L) were: arsenic 8.5 (7.7); cadmium 0.01 (0.8); lead 16.6 (16.1); and mercury 1.5 (5.0). There were significant differences in metals concentrations by: site location, paid employment status, education, marital status, smoking, alcohol use, and fish intake. After adjusting for these covariates plus age and sex, arsenic (OR 4.1, 95% C.I. 1.2, 14.6) and lead (OR 4.0, 95% C.I. 1.6, 9.6) above the median values were significantly associated with elevated fasting glucose. These associations increased when models were further adjusted for percent body fat: arsenic (OR 5.6, 95% C.I. 1.5, 21.2) and lead (OR 5.0, 95% C.I. 2.0, 12.7). Cadmium and mercury were also related with increased odds of elevated fasting glucose, but the associations were not statistically significant. Arsenic was significantly associated with increased odds of low HDL cholesterol both with (OR 8.0, 95% C.I. 1.8, 35.0) and without (OR 5.9, 95% C.I. 1.5, 23.1) adjustment for percent body fat. CONCLUSIONS: While not consistent for all cardiometabolic disease markers, these results are suggestive of potentially important associations between metals exposure and cardiometabolic risk. Future studies will examine these associations in the larger cohort over time.

Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells.

Pluripotency in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is regulated by three transcription factors-OCT3/4, SOX2, and NANOG. To fully exploit the therapeutic potential of these cells it is essential to have a good mechanistic understanding of the maintenance of self-renewal and pluripotency. In this study, we demonstrate a powerful systems biology approach in which we first expand literature-based network encompassing the core regulators of pluripotency by assessing the behavior of genes targeted by perturbation experiments. We focused our attention on highly regulated genes encoding cell surface and secreted proteins as these can be more easily manipulated by the use of inhibitors or recombinant proteins. Qualitative modeling based on combining boolean networks and in silico perturbation experiments were employed to identify novel pluripotency-regulating genes. We validated Interleukin-11 (IL-11) and demonstrate that this cytokine is a novel pluripotency-associated factor capable of supporting self-renewal in the absence of exogenously added bFGF in culture. To date, the various protocols for hESCs maintenance require supplementation with bFGF to activate the Activin/Nodal branch of the TGFβ signaling pathway. Additional evidence supporting our findings is that IL-11 belongs to the same protein family as LIF, which is known to be necessary for maintaining pluripotency in mouse but not in human ESCs. These cytokines operate through the same gp130 receptor which interacts with Janus kinases. Our finding might explain why mESCs are in a more naïve cell state compared to hESCs and how to convert primed hESCs back to the naïve state. Taken together, our integrative modeling approach has identified novel genes as putative candidates to be incorporated into the expansion of the current gene regulatory network responsible for inducing and maintaining pluripotency.

Hierarchical modeling gave plausible estimates of associations between metabolic syndrome and components of antiretroviral therapy.

OBJECTIVE: Hierarchical modeling has been proposed as a solution to the multiple exposure problem. We estimate associations between metabolic syndrome and different components of antiretroviral therapy using both conventional and hierarchical models. STUDY DESIGN AND SETTING: We use discrete time survival analysis to estimate the association between metabolic syndrome and cumulative exposure to 16 antiretrovirals from four drug classes. We fit a hierarchical model where the drug class provides a prior model of the association between metabolic syndrome and exposure to each antiretroviral. RESULTS: One thousand two hundred and eighteen patients were followed for a median of 27 months, with 242 cases of metabolic syndrome (20%) at a rate of 7.5 cases per 100 patient years. Metabolic syndrome was more likely to develop in patients exposed to stavudine, but was less likely to develop in those exposed to atazanavir. The estimate for exposure to atazanavir increased from hazard ratio of 0.06 per 6 months' use in the conventional model to 0.37 in the hierarchical model (or from 0.57 to 0.81 when using spline-based covariate adjustment). CONCLUSION: These results are consistent with trials that show the disadvantage of stavudine and advantage of atazanavir relative to other drugs in their respective classes. The hierarchical model gave more plausible results than the equivalent conventional model.

Crustal structure and reflectivity of the Swiss Alps from 3-Dimensional seismic modeling. 2. Penninic Nappes

Surface geological mapping, laboratory measurements of rock properties, and seismic reflection data are integrated through three-dimensional seismic modeling to determine the likely cause of upper crustal reflections and to elucidate the deep structure of the Penninic Alps in eastern Switzerland. Results indicate that the principal upper crustal reflections recorded on the south end of Swiss seismic line NFP20-EAST can be explained by the subsurface geometry of stacked basement nappes. In addition, modeling results provide improvements to structural maps based solely on surface trends and suggest the presence of previously unrecognized rock units in the subsurface. Construction of the initial model is based upon extrapolation of plunging surface. structures; velocities and densities are established by laboratory measurements of corresponding rock units. Iterative modification produces a best fit model that refines the definition of the subsurface geometry of major structures. We conclude that most reflections from the upper 20 km can be ascribed to the presence of sedimentary cover rocks (especially carbonates) and ophiolites juxtaposed against crystalline basement nappes. Thus, in this area, reflections appear to be principally due to first-order lithologic contrasts. This study also demonstrates not only the importance of three-dimensional effects (sideswipe) in interpreting seismic data, but also that these effects can be considered quantitatively through three-dimensional modeling.

Strategy selection: An introduction to the modeling challenge

Modeling the mechanisms that determine how humans and other agents choose among different behavioral and cognitive processes-be they strategies, routines, actions, or operators-represents a paramount theoretical stumbling block across disciplines, ranging from the cognitive and decision sciences to economics, biology, and machine learning. By using the cognitive and decision sciences as a case study, we provide an introduction to what is also known as the strategy selection problem. First, we explain why many researchers assume humans and other animals to come equipped with a repertoire of behavioral and cognitive processes. Second, we expose three descriptive, predictive, and prescriptive challenges that are common to all disciplines which aim to model the choice among these processes. Third, we give an overview of different approaches to strategy selection. These include cost‐benefit, ecological, learning, memory, unified, connectionist, sequential sampling, and maximization approaches. We conclude by pointing to opportunities for future research and by stressing that the selection problem is far from being resolved.

Pore-scale modeling of two-phase flow instabilities in porous media

Les problèmes d'écoulements multiphasiques en média poreux sont d'un grand intérêt pour de nombreuses applications scientifiques et techniques ; comme la séquestration de C02, l'extraction de pétrole et la dépollution des aquifères. La complexité intrinsèque des systèmes multiphasiques et l'hétérogénéité des formations géologiques sur des échelles multiples représentent un challenge majeur pour comprendre et modéliser les déplacements immiscibles dans les milieux poreux. Les descriptions à l'échelle supérieure basées sur la généralisation de l'équation de Darcy sont largement utilisées, mais ces méthodes sont sujettes à limitations pour les écoulements présentant de l'hystérèse. Les avancées récentes en terme de performances computationnelles et le développement de méthodes précises pour caractériser l'espace interstitiel ainsi que la distribution des phases ont favorisé l'utilisation de modèles qui permettent une résolution fine à l'échelle du pore. Ces modèles offrent un aperçu des caractéristiques de l'écoulement qui ne peuvent pas être facilement observées en laboratoire et peuvent être utilisé pour expliquer la différence entre les processus physiques et les modèles à l'échelle macroscopique existants. L'objet premier de la thèse se porte sur la simulation numérique directe : les équations de Navier-Stokes sont résolues dans l'espace interstitiel et la méthode du volume de fluide (VOF) est employée pour suivre l'évolution de l'interface. Dans VOF, la distribution des phases est décrite par une fonction fluide pour l'ensemble du domaine et des conditions aux bords particulières permettent la prise en compte des propriétés de mouillage du milieu poreux. Dans la première partie de la thèse, nous simulons le drainage dans une cellule Hele-Shaw 2D avec des obstacles cylindriques. Nous montrons que l'approche proposée est applicable même pour des ratios de densité et de viscosité très importants et permet de modéliser la transition entre déplacement stable et digitation visqueuse. Nous intéressons ensuite à l'interprétation de la pression capillaire à l'échelle macroscopique. Nous montrons que les techniques basées sur la moyenne spatiale de la pression présentent plusieurs limitations et sont imprécises en présence d'effets visqueux et de piégeage. Au contraire, une définition basée sur l'énergie permet de séparer les contributions capillaires des effets visqueux. La seconde partie de la thèse est consacrée à l'investigation des effets d'inertie associés aux reconfigurations irréversibles du ménisque causé par l'interface des instabilités. Comme prototype pour ces phénomènes, nous étudions d'abord la dynamique d'un ménisque dans un pore angulaire. Nous montrons que, dans un réseau de pores cubiques, les sauts et reconfigurations sont si fréquents que les effets d'inertie mènent à différentes configurations des fluides. A cause de la non-linéarité du problème, la distribution des fluides influence le travail des forces de pression, qui, à son tour, provoque une chute de pression dans la loi de Darcy. Cela suggère que ces phénomènes devraient être pris en compte lorsque que l'on décrit l'écoulement multiphasique en média poreux à l'échelle macroscopique. La dernière partie de la thèse s'attache à démontrer la validité de notre approche par une comparaison avec des expériences en laboratoire : un drainage instable dans un milieu poreux quasi 2D (une cellule Hele-Shaw avec des obstacles cylindriques). Plusieurs simulations sont tournées sous différentes conditions aux bords et en utilisant différents modèles (modèle intégré 2D et modèle 3D) afin de comparer certaines quantités macroscopiques avec les observations au laboratoire correspondantes. Malgré le challenge de modéliser des déplacements instables, où, par définition, de petites perturbations peuvent grandir sans fin, notre approche numérique apporte de résultats satisfaisants pour tous les cas étudiés. - Problems involving multiphase flow in porous media are of great interest in many scientific and engineering applications including Carbon Capture and Storage, oil recovery and groundwater remediation. The intrinsic complexity of multiphase systems and the multi scale heterogeneity of geological formations represent the major challenges to understand and model immiscible displacement in porous media. Upscaled descriptions based on generalization of Darcy's law are widely used, but they are subject to several limitations for flow that exhibit hysteric and history- dependent behaviors. Recent advances in high performance computing and the development of accurate methods to characterize pore space and phase distribution have fostered the use of models that allow sub-pore resolution. These models provide an insight on flow characteristics that cannot be easily achieved by laboratory experiments and can be used to explain the gap between physical processes and existing macro-scale models. We focus on direct numerical simulations: we solve the Navier-Stokes equations for mass and momentum conservation in the pore space and employ the Volume Of Fluid (VOF) method to track the evolution of the interface. In the VOF the distribution of the phases is described by a fluid function (whole-domain formulation) and special boundary conditions account for the wetting properties of the porous medium. In the first part of this thesis we simulate drainage in a 2-D Hele-Shaw cell filled with cylindrical obstacles. We show that the proposed approach can handle very large density and viscosity ratios and it is able to model the transition from stable displacement to viscous fingering. We then focus on the interpretation of the macroscopic capillary pressure showing that pressure average techniques are subject to several limitations and they are not accurate in presence of viscous effects and trapping. On the contrary an energy-based definition allows separating viscous and capillary contributions. In the second part of the thesis we investigate inertia effects associated with abrupt and irreversible reconfigurations of the menisci caused by interface instabilities. As a prototype of these phenomena we first consider the dynamics of a meniscus in an angular pore. We show that in a network of cubic pores, jumps and reconfigurations are so frequent that inertia effects lead to different fluid configurations. Due to the non-linearity of the problem, the distribution of the fluids influences the work done by pressure forces, which is in turn related to the pressure drop in Darcy's law. This suggests that these phenomena should be taken into account when upscaling multiphase flow in porous media. The last part of the thesis is devoted to proving the accuracy of the numerical approach by validation with experiments of unstable primary drainage in a quasi-2D porous medium (i.e., Hele-Shaw cell filled with cylindrical obstacles). We perform simulations under different boundary conditions and using different models (2-D integrated and full 3-D) and we compare several macroscopic quantities with the corresponding experiment. Despite the intrinsic challenges of modeling unstable displacement, where by definition small perturbations can grow without bounds, the numerical method gives satisfactory results for all the cases studied.