C.T. Miller

Asenapine (Saphris®): GC–MS Method Validation and the Postmortem Distribution of a New Atypical Antipsychotic Medication

Asenapine (Saphris®) is an atypical antipsychotic approved in the USA in 2009 for the treatment of schizophrenia and bipolar disorder. The Los Angeles County Department of Coroner Toxicology Laboratory developed an analytical method for the detection and quantitation of asenapine by gas chromatography-mass spectroscopy in multiple specimens of postmortem casework. Asenapine was isolated from specimens through a basic, liquid-liquid extraction procedure and quantitated utilizing D5-fentanyl as an internal standard. Method validation for asenapine was conducted utilizing the Scientific Working Group Toxicology (SWGTOX) method validation draft proposal and the tissue distribution of four case studies was determined. The authors believe that these are the first cases to be reported in the literature and are intended to assist other forensic toxicologists with interpreting their casework.

Estimating interfacial areas resulting from lattice Boltzmann simulation of two-fluid-phase flow in a porous medium

The relationship among capillary pressure, fluid saturations, and interfacial areas ( psa relationship) has been a subject of significant recent attention in multiphase porous medium dynamics. First, we consider a set of computational approaches for estimating interfacial areas based upon both integer and real number representations of fluid distributions. We quantify the errors associated with such computations for model systems, and we show relatively accurate estimates are possible for the sorts of data that are available for multiphase prous medium systems. Second, we performed a preliminary investigation of the psa relationship using a lattice-Boltzmann (LB) simulation approach, which we have previously shown to agree well with highly resolved laboratory experiments. Preliminary results are presented and compared to other observations of the psa relationship that have appeared in the literature.

An evaluation of lattice Boltzmann equation methods for simulating flow through porous media

We evaluated lattice Boltzmann equation (LBE) methods for modeling flow through porous media. We compared a three-dimensional, 19-velocity, multiple-relaxation-time (MRT) LBE model with a popular single-relaxation-time, Bhatnagar-Gross-Krook (BGK) LBE model. It can be shown that the latter (BGK-LBE) model is a special case of the former (MRT-LBE) model for a certain set of parameter constraints used in the collision operator. We compared the accuracy of the two models for two test cases: (1) Poiseuille flow between parallel plates, and (2) flow past a periodic simple cubic (SC) array of spheres. We also compared two solid-phase, boundary condition approximations: (1) a linearly interpolated bounce-back (LIBB) method, and (2) a standard bounce-back (SBB) method without interpolation. Our results clearly demonstrate advantages of the MRT-LBE model over its BGK counterpart, and the benefits of the LIBB method over the SBB method in terms of numerical accuracy.

On gravity currents in heterogeneous porous media

We examine the case of density-dependent flow in heterogeneous porous medium systems bounded by a free surface using homogenization methods for leading-order approximations. Specifically we consider the two-dimensional case in which variations occur in both the horizontal and vertical directions. Such problems lead to the need to solve cell problems to compute the solution, which is generally done using numerical approaches. We review the general homogenization results for general topology and aspect ratio. We derive an analytical solution for a case with two-dimensional variability in the slender limit for certain assumed scaling of the permeability, and we find excellent agreement with the numerical solution. We also consider the case of two miscible fluids with an assumed sharp interface and contrasting densities. We derive an analytical solution in a thin limit neglecting mixing and show agreement with known solutions for limiting cases.

Viscous coupling effects for two-phase flow in porous media

Recent studies have revealed that viscous coupling effects in immiscible two-phase flow, caused by momentum transfer between the two fluid phases, are important for a range of cases of porous medium flow. Generalized governing equations for coupled immiscible two-phase flow in porous media have been suggested through a formulation that includes two viscous coupling coefficients, in addition to the two conventional relative permeabilities. However, a quantitative understanding of the coupling effects and their dependence on factors including capillary number, viscosity ratio, and wettability still remains as an open issue. In this work, we use a three-dimensional parallel processing version of a two-fluid-phase lattice Boltzmann (LB) model to investigate this phenomenon. A multiple-relaxation-time (MRT) approximation of the LB equations is used in the simulator, which leads to stable results. We validate our model by verifying the velocity profile for flow through a channel with a square cross-section. We then simulate co-current flow through a sphere-pack porous medium and determine the relative permeabilities. Correlations of the relative permeabilities as a function of the fluid viscosities and wettability are investigated. The results are qualitatively consistent with experimental observations by Avraam and Payatakes [1] and the numerical simulations of Langaas and Papatzacos [12].

Validation of the i-STAT®1 Analyzer for Postmortem Vitreous Humor Electrolytes and Glucose Analysis

The analytical value of vitreous humor as a specimen in postmortem forensic toxicology has been known for some time. Numerous medical examiner laboratories outsource the analysis of this important specimen for electrolyte and glucose measurements. This can be both time-consuming and costly. The utility of the i-STAT®1 medical device to measure electrolytes and glucose in whole blood samples has been demonstrated for over two decades in a clinical setting through single-use disposable cartridges that introduce samples to the i-STAT®1. Different cartridge types allow for the analysis of various analytes including sodium, potassium, chloride, creatinine, urea nitrogen and glucose. With only 100 μL of sample, results are obtained in under 4 min. In this study, we utilized the i-STAT®1 using an alternative specimen matrix, postmortem vitreous humor and quantitatively determined the validity and reliability of the instrument for this purpose. Acceptable criterion was used for each test as suggested by the Scientific Working Group for Forensic Toxicology. All analytes of interest, except creatinine, demonstrated a percent error < ±10% for both accuracy and precision studies. Drug interference and stability studies were performed with many of the analytes demonstrating a percent error < ±20%. Throughout drug interference and stability studies, all analytes of interest were detectable except for potassium, which gave inconclusive results. Significant interference with commonly found drugs were shown for creatinine and chloride but must be evaluated carefully. Volume additions to ethanol spiked samples caused significant interference for all analytes and is considered a limitation for this method of analysis that requires additional studies. As vitreous humor continues to be used in forensic medicine to aid in diagnostic interpretation, the i-STAT®1 has the potential to give accurate results in a timely and cost-effective manner.

Pore-scale modeling of residual nonaqueous phase liquid dissolution

For nonaqueous phase liquids (NAPLs) that are commonly found at contaminted sites, the aqueous/ nonaqueous phase mass transfer is a process of crucial importance for both predicting groundwater contamination and determining the best cleanup methodology. The mass transfer process deserves further study as the constitutive relations derived from the experimental porous medium systems are generally not applicable to other media. In this work, we applied a multi-step pore-scale modeling approach to simulate the dissolution of a residual NAPL in a three-dimensional random sphere-pack medium. The residual NAPL distribution was generated using a morphological approach. With a detailed flow field simulated with a lattice-Boltzmann (LB) approach, we solved the advection-diffusion equation in the pore space using a high-resolution, adaptive-stencil numerical scheme and operator splitting. The mass transfer rate predicted in the approach was compared to experimental observations by Miller et al. [16].

A Three-Dimensional Finite Element - Finite Difference Model for Simulating Confined and Unconfined Groundwater Flow

Publisher Summary This chapter discusses finite difference model for simulating confined and unconfined ground-water flow. Numerical models for the simulation of ground-water flow and contaminant transport are well-established. It is clear that accurate simulation of many contaminant transport problems requires a three-dimensional ground-water flow solution. Some three-dimensional ground-water flow models have been developed and tested. Application of these models often has been constrained by core storage and central processing unit (CPU) time requirements, especially, for unconfined flow problems. Elements that become completely drained by pumping—or conversely, previously drained elements that become refilled by recharge-can cause numerical difficulties. A procedure was introduced that not only effectively removes the influence of the drained element and the associated nodes, but also allows for refilling. The procedure consists of imposing Dirichlet conditions on the associated drained nodes, equal to the head from the layer immediately below. If a source or a sink term exists at a drained node, the location of the source or sink is temporarily removed from the drained node and the quantity of the source or sink is allocated to the remaining layers below.