RESUMEN
Transdermal alcohol biosensors that do not require active participation of the subject and yield near continuous measurements have the potential to significantly enhance the data collection abilities of alcohol researchers and clinicians who currently rely exclusively on breathalyzers and drinking diaries. Making these devices accessible and practical requires that transdermal alcohol concentration (TAC) be accurately and consistently transformable into the well-accepted measures of intoxication, blood/breath alcohol concentration (BAC/BrAC). A novel approach to estimating BrAC from TAC based on covariate-dependent physics-informed hidden Markov models with two emissions is developed. The hidden Markov chain serves as a forward full-body alcohol model with BrAC and TAC, the two emissions, assumed to be described by a bivariate normal which depends on the hidden Markovian states and person-level and session-level covariates via built-in regression models. An innovative extension of hidden Markov modeling is developed wherein the hidden Markov model framework is regularized by a first-principles PDE model to yield a hybrid that combines prior knowledge of the physics of transdermal ethanol transport with data-based learning. Training, or inverse filtering, is effected via the Baum-Welch algorithm and 256 sets of BrAC and TAC signals and covariate measurements collected in the laboratory. Forward filtering of TAC to obtain estimated BrAC is achieved via a new physics-informed regularized Viterbi algorithm which determines the most likely path through the hidden Markov chain using TAC alone. The Markovian states are decoded and used to yield estimates of BrAC and to quantify the uncertainty in the estimates. Numerical studies are presented and discussed. Overall good agreement between BrAC data and estimates was observed with a median relative peak error of 22% and a median relative area under the curve error of 25% on the test set. We also demonstrate that the physics-informed Viterbi algorithm eliminates non-physical artifacts in the BrAC estimates.
RESUMEN
An output feedback LQG compensator (combined controller and state estimator) for the regulation of intravenous-infused alcohol studies and treatment using a noninvasive transdermal alcohol biosensor is developed. The design is based on a population model involving an abstract semi-linear parabolic hybrid reaction-diffusion system involving coupled partial and ordinary differential equations with random parameters known only up to their distributions. The scheme developed is based on a weak formulation of the model equations in an appropriately constructed Gelfand triple of Bochner spaces wherein the unknown random parameters are treated as additional spatial variables. Implementation relies on a Galerkin-based approximation and convergence theory and an abstract formulation involving linear semigroups of operators. The model is fit and validated using laboratory collected human subject data and the method of moments. The results of numerical simulations of controlled intravenous alcohol infusion are presented and discussed.
RESUMEN
INTRODUCTION: Wearable devices that obtain transdermal alcohol concentration (TAC) could become valuable research tools for monitoring alcohol consumption levels in naturalistic environments if the TAC they produce could be converted into quantitatively-meaningful estimates of breath alcohol concentration (eBrAC). Our team has developed mathematical models to produce eBrAC from TAC, but it is not yet clear how a variety of factors affect the accuracy of the models. Stomach content is one factor that is known to affect breath alcohol concentration (BrAC), but its effect on the BrAC-TAC relationship has not yet been studied. METHODS: We examine the BrAC-TAC relationship by having two investigators participate in four laboratory drinking sessions with varied stomach content conditions: (i) no meal, (ii) half and (iii) full meal before drinking, and (iv) full meal after drinking. BrAC and TAC were obtained every 10 min over the BrAC curve. RESULTS: Eating before drinking lowered BrAC and TAC levels, with greater variability in TAC across person-device pairings, but the BrAC-TAC relationship was not consistently altered by stomach content. The mathematical model calibration parameters, fit indices, and eBrAC curves and summary score outputs did not consistently vary based on stomach content, indicating that our models were able to produce eBrAC from TAC with similar accuracy despite variations in the shape and magnitude of the BrAC curves under different conditions. DISCUSSION AND CONCLUSIONS: This study represents the first examination of how stomach content affects our ability to model estimates of BrAC from TAC and indicates it is not a major factor.