An efficient formulation of Krylov's prediction model for train induced vibrations based on the dynamic reciprocity theorem.

In Krylov's analytical prediction model, the free field vibration response during the passage of a train is written as the superposition of the effect of all sleeper forces, using Lamb's approximate solution for the Green's function of a halfspace. When this formulation is extended with the Green's functions of a layered soil, considerable computational effort is required if these Green's functions are needed in a wide range of source-receiver distances and frequencies. It is demonstrated in this paper how the free field response can alternatively be computed, using the dynamic reciprocity theorem, applied to moving loads. The formulation is based on the response of the soil due to the moving load distribution for a single axle load. The equations are written in the wave-number-frequency domain, accounting for the invariance of the geometry in the direction of the track. The approach allows for a very efficient calculation of the free field vibration response, distinguishing the quasistatic contribution from the effect of the sleeper passage frequency and its higher harmonics. The methodology is validated by means of in situ vibration measurements during the passage of a Thalys high-speed train on the track between Brussels and Paris. It is shown that the model has good predictive capabilities in the near field at low and high frequencies, but underestimates the response in the midfrequency band.

Transmucosal, oral controlled-release, and transdermal drug administration in human subjects: a crossover study with melatonin.

The effect of oral controlled-release (CR), oral transmucosal (buccal; TMD) and transdermal (TDD) drug delivery systems on plasma concentrations of melatonin (MT) and its principal metabolite in human subjects using a crossover, single dose design was evaluated. Twelve adult male volunteers participated in the study and received all three dosage forms on three separate occasions. All patch dosage forms were removed after 10 h of wear. Plasma concentrations of the parent drug and its metabolite, 6-sulfatoxymelatonin (MT6s) were measured by radioimmunoassay. Between-subject plasma concentrations of MT were very variable following both oral CR and TDD. Use of the oral CR system gave plasma MT profiles in some subjects that were initially similar to physiological levels, but then differed substantially from physiological in the rate of MT offset; in a few subjects, plasma MT levels remained consistently much below normal nocturnal physiological levels. Also, the ratio of metabolite to parent drug by the oral CR route was many times greater than physiological. TDD resulted in a significant delay in systemic drug levels and a gradual decline in drug delivery after patch removal, possibly due to deposition of melatonin in the skin. TDD failed to simulate the physiological plasma profile of MT (rapid achievement of steady-state blood levels and rapid decline after removal of the patch; i.e., so-called "square-wave" profile). TMD provided prompt systemic drug levels with less variability than oral CR or TDD delivery. Also, plasma MT levels fell promptly and rapidly after removal of the patch. No indication of mucosal deposition was observed. TMD was able to mimic the physiological plasma profiles of both MT and its principal metabolite.