31 research outputs found
Wittgenstein's Thought Experiments and Relativity Theory
In this paper, I discuss the similarity between Wittgensteinâs use of thought experiments and Relativity Theory. I begin with introducing Wittgensteinâs idea of âthought experimentsâ and a tentative classification of different kinds of thought experiments in Wittgensteinâs work. Then, after presenting a short recap of some remarks on the analogy between Wittgensteinâs point of view and Einsteinâs, I suggest three analogies between the status of Wittgensteinâs mental experiments and Relativity theory: the topics of time dilation, the search for invariants, and the role of measuring tools in Special Relativity. This last point will help to better define Wittgensteinâs idea of description as the core of his philosophical enterprise
Systematic Evaluation of the Descriptive and Predictive Performance of Paediatric Morphine Population Models
Purpose: A framework for the evaluation of paediatric population models is proposed and applied to two different paediatric population pharmacokinetic models for morphine. One covariate model was based on a systematic covariate analysis, the other on fixed allometric scaling principles. Methods: The six evaluation criteria in the framework were 1) number of parameters and condition number, 2) numerical diagnostics, 3) prediction-based diagnostics, 4) η-shrinkage, 5) simulation-based diagnostics, 6) diagnostics of individual and population parameter estimates versus covariates, including measurements of bias and precision of the population values compared to the observed individual values. The framework entails both an internal and external model evaluation procedure. Results: The application of the framework to the two models resulted in the detection of overparameterization and misleading diagnostics based on individual predictions caused by high shrinkage. The diagnostic of individual and population parameter estimates versus covariates proved to be highly informative in assessing obtained covariate relationships. Based on the framework, the systematic covariate model proved to be superior over the fixed allometric model in terms of predictive performance. Conclusions: The proposed framework is suitable for the evaluation of paediatric (covariate) models and should be applied to corroborate the descriptive and predictive properties of these models
The role of population PK-PD modelling in paediatric clinical research
Children differ from adults in their response to drugs. While this may be the result of changes in dose exposure (pharmacokinetics [PK]) and/or exposure response (pharmacodynamics [PD]) relationships, the magnitude of these changes may not be solely reflected by differences in body weight. As a consequence, dosing recommendations empirically derived from adults dosing regimens using linear extrapolations based on body weight, can result in therapeutic failure, occurrence of adverse effect or even fatalities. In order to define rational, patient-tailored dosing schemes, population PK-PD studies in children are needed. For the analysis of the data, population modelling using non-linear mixed effect modelling is the preferred tool since this approach allows for the analysis of sparse and unbalanced datasets. Additionally, it permits the exploration of the influence of different covariates such as body weight and age to explain the variability in drug response. Finally, using this approach, these PK-PD studies can be designed in the most efficient manner in order to obtain the maximum information on the PK-PD parameters with the highest precision. Once a population PK-PD model is developed, internal and external validations should be performed. If the model performs well in these validation procedures, model simulations can be used to define a dosing regimen, which in turn needs to be tested and challenged in a prospective clinical trial. This methodology will improve the efficacy/safety balance of dosing guidelines, which will be of benefit to the individual child
Pompas de intuiciĂłn y el uso adecuado de los experimentos mentales
Empiezo con una explicaciĂłn de lo que es un "experimento mental". Posteriormente, clarifico el papel que juegan las intuiciones en los experimentos mentales, teniendo en cuenta dos puntos importanes: (1) el carĂĄcter informativo de los experimentos mentales y (2) la legitimidad del mĂ©todo de losexperimentos mentales en la filosofĂa y en las ciencias naturales. Defiendo una explicaciĂłn naturalista de las intuiciones que provee una explicaciĂłn plausible del carĂĄcter informativo de los experimentos mentales y que, a su vez, permite reconstruirlos como argumentos. TambiĂ©n especifico criterios para la distinciĂłn de malas "pompas intuitivas" respecto de experimentos mentales legĂtimos. Esos criterios nos ayudan a evitar ser seducidos por el peligroso poder sugestivo de intuiciones engañosas