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Biomedical subjects

D J Svendsgaard

Publications and source records attributed to D J Svendsgaard.

5 recordsLinked to original sources

Quantitative methods for cross-species mapping (CSM).

Cross-species extrapolation will be defined as prediction from one species to another without empirical vetification. Cross-species mapping (CSM) is the same except empirical vetification is performed. CSM may be viewed as validation of methods for extrapolation. Algorithms for CSM may originate from theory, from empirical observations or a combination of the two. Regardless of their origins, CSM algorithms must be explicated and confidence intervals given around their predictions. This paper offers a quantitative method for constructing CSM equations which is useful in evaluation of the CSM and as an aid in the design of new experiments in CSM and extrapolation. The method requires fitting mathematical models for the physiological or behavioral phenomena to be mapped across species. A CSM equation can then be derived from the models in each species and approximate confidence limits may be obtained for predictions from the equation. The method is useful even when the models in the two species differ in form, implying differences in physiology or behavioral principles between species. The method proposed has a number of remaining uncertainties and possible problems.

Animals

U-shaped dose-response curves: their occurrence and implications for risk assessment.

A class of curvilinear dose-response relationships in toxicological and epidemiological studies may be roughly described by "U-shaped" curves. Such curves reflect an apparent reversal or inversion in the effect of an otherwise toxic agent at a low or intermediate region of the dose continuum. Several examples of U-shaped dose-response functions are presented to illustrate the variety of agents and end points that can follow this form. Such findings are not thought to represent a unitary phenomenon, but may be explained through numerous possible principles or mechanisms, some of which are illustrated and discussed in general terms. U-shaped dose-response curves raise important issues for toxicological and environmental health risk assessments, particularly in the identification of no-observed-effect levels and in the evaluation of multiple outcomes and the tradeoffs between potential risks and benefits of a given agent. It is especially important to avoid focusing exclusively on an apparent improvement in one end point and failing to consider other, possibly deleterious effects of the same agent.

Animals

Lead and child development.

A group of independent epidemiological studies shows that fetal exposure to levels of lead previously considered safe is linked to impairment of infant mental development.

Abnormalities, Drug-Induced