Enfants comme agents de changement

Version anglaise disponible dans la Bibliothèque numérique du CRDI: Agents of change : children in developmentVersion espagnole disponible dans la Bibliothèque numérique du CRDI: Agentes de cambio : los niños en el desarroll

Development, technology and ethics

Meeting: World Conference on Ethical Choices in the Age of Pervasive Technology, 25-29 Oct. 1989, Guelph, Ont., CA"Notes for remarks prepared for I.L.Head, President, IDRC

Pharmacokinetic–pharmacodynamic modelling of the analgesic effects of lumiracoxib, a selective inhibitor of cyclooxygenase-2, in rats

Background and purpose: This study establishes a pharmacokinetic/pharmacodynamic (PK/PD) model to describe the time course and in vivo mechanisms of action of the antinociceptive effects of lumiracoxib, evaluated by the thermal hyperalgesia test in rats. Experimental approach: Female Wistar fasted rats were injected s.c. with saline or carrageenan in the right hind paw, followed by either 0, 1, 3, 10 or 30 mg·kg-1 of oral lumiracoxib at the time of carrageenan injection (experiment I), or 0, 10 or 30 mg·kg-1 oral lumiracoxib at 4 h after carrageenan injection (experiment II). Antihyperalgesic responses were measured as latency time (LT) to a thermal stimulus. PK/PD modelling of the antinociceptive response was performed using the population approach with NONMEM VI. Results: A two-compartment model described the plasma disposition. A first-order model, including lag time and decreased relative bioavailability as a function of the dose, described the absorption process. The response model was: LT = LT0/(1 + MED). LT0 is the baseline response, and MED represents the level of inflammatory mediators. The time course of MED was assumed to be equivalent to the predicted profile of COX-2 activity and was modelled according to an indirect response model with a time variant synthesis rate. Drug effects were described as a reversible inhibition of the COX-2 activity. The in vivo estimate of the dissociation equilibrium constant of the COX-2-lumiracoxib complex was 0.24 mg·mL-1. Conclusions: The model developed appropriately described the time course of pharmacological responses to lumiracoxib, in terms of its mechanism of action and pharmacokinetics

Geothermal heating in the Panama Basin. Part II: abyssal water mass transformation

Diabatic upwelling of abyssal waters is investigated in the Panama Basin employing the water mass transformation framework of Walin [1982]. We find that, in large areas of the basin, the bottom boundary layer is very weakly stratified and extends hundreds of meters above the sea floor. Within the weakly stratified bottom boundary layer (wsBBL) neutral density layers intercept the bottom of the basin. The area of these density layer incrops increases gradually as the abyssal waters become lighter. Large incrop areas are associated with strong diabatic upwelling of abyssal water, geothermal heating being the largest buoyancy source. While a significant amount of water mass transformation is due to extreme turbulence downstream of the Ecuador Trench, the only abyssal water inflow passage, water mass transformation across the upper boundary of abyssal water layer is accomplished almost entirely by geothermal heating

Geothermal heating in the Panama Basin. Part I: hydrography of the basin

The Panama Basin serves as a laboratory to investigate abyssal water upwelling. The basin has only a single abyssal water inflow pathway through the narrow Ecuador Trench. The estimated critical inflow through the Trench reaches 0.34 ± 0.07 m s−1, resulting in an abyssal water volume inflow of 0.29 ± 0.07 Sv. The same trench carries the return flow of basin waters that starts just 200 m above the bottom and is approximately 400 m deeper than the depth of the next possible deep water exchange pathway at the Carnegie Ridge Saddle. The curvature of temperature‐salinity diagrams is used to differentiate the effect of geothermal heating on the deep Panama Basin waters that was found to reach as high as 2200 m depth, which is about 500 m above the upper boundary of the abyssal water layer