Michael S. Roberts

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This paper applies simulated method of moments to a dynamic structural model to infer the magnitude of external financing costs. The model features endogenous investment, cash distributions, leverage, and default. The corporation faces taxation, costly bankruptcy, and linear-quadratic equity flotation costs. For large firms, parameter estimates imply(More)
A dispersion model of hepatic elimination, based on the residence time distribution of blood elements within the liver, is presented. The general rate equations appropriate for describing the hepatic output concentration of a tracer solute are derived. Particular consideration is given to events following a bolus input dose of a tracer. The model is shown(More)
A new model, the dispersion model of hepatic elimination, is applied to the correlation between in-vitro microsomal data and corresponding rat isolated perfused liver data for a number of drugs reported in the literature, whose extraction ratio varies over the range of 0.01 to 0.995. The dispersion model described the data better than either the(More)
OBJECTIVES To compare the plasma and subcutaneous tissue concentration-time profiles of meropenem administered by intermittent bolus dosing or continuous infusion to critically ill patients with sepsis and without renal dysfunction, and to use population pharmacokinetic modelling and Monte Carlo simulations to assess the cumulative fraction of response(More)
Earlier phylogenetic studies based on the inferred DNA sequences of the polC, rpoB and gyrA genes suggested that strains of the species Bacillus subtilis formed two clusters, indicating the presence two closely related taxa; one contained the laboratory strain 168 and the other the laboratory strain W23. Significant sexual isolation was found between strain(More)
Current physiologically based pharmacokinetic (PBPK) models are inductive. We present an additional, different approach that is based on the synthetic rather than the inductive approach to modeling and simulation. It relies on object-oriented programming. A model of the referent system in its experimental context is synthesized by assembling objects that(More)
The objectives of this study were (i) to compare the plasma concentration-time profiles for first-dose and steady-state piperacillin administered by intermittent or continuous dosing to critically ill patients with sepsis and (ii) to use population pharmacokinetics to perform Monte Carlo dosing simulations in order to assess the probability of target(More)
The residence time distribution of noneliminated solutes in the liver can be represented by a variety of stochastic models. The dispersion model (closed and mixed boundary conditions), gamma distribution, log normal distribution and normal distribution models were used to describe output concentration-time profiles after bolus injections into the liver of(More)
Enterohepatic recycling occurs by biliary excretion and intestinal reabsorption of a solute, sometimes with hepatic conjugation and intestinal deconjugation. Cycling is often associated with multiple peaks and a longer apparent half-life in a plasma concentration-time profile. Factors affecting biliary excretion include drug characteristics (chemical(More)
Nonsteroidal anti-inflammatory drugs (NSAIDs) are being administered increasingly by transdermal drug delivery for the treatment of local muscle inflammation. The human epidermal permeabilities of different NSAIDs (salicylic acid, diethylamine salicylate, indomethacin, naproxen, diclofenac and piroxicam) from aqueous solutions is dependent on the drug's(More)