The analytic strategy will use population pharmacokinetics [ 59], which uses nonlinear mixed effect modeling to identify intra- and inter-individual sources of variability [ 60].
The pharmacokinetic and pharmacodynamic variables are assumed to interact mutually independently and multiplicatively, so that the overall distribution of human interindividual variability is log normal with log variance equal to the sum of the log variances of the individual sources of human variability.
First, synaptic failures and other sources of variability at individual synapses must be minimized; a full complement of releasable vesicles and multi-vesicular release likely contribute to minimizing intrinsic synaptic variability at individual RBC synapses (see 'Discussion').
This is especially true when examining among-individual variation in mitochondrial traits, given that the in vitro conditions standardize the mitochondrial environment among individuals, which may hide the actual sources of variability in the relationship between oxygen consumption in vivo and mitochondrial ROS production [ 11].
Epidemiology, however, besides measurement, has to consider different sources of variability relating to individuals, and not captured by the covariates included in the model [ 2].
To accomplish this, large numbers of individuals need to be tested and non-cognitive sources of variability need to be controlled.
In epidemiological studies misspecification should always be considered, as different sources of variability, related to the individuals and not captured by the covariates, are always present.
As with PK models, the statistical model describes variability around the structural model, including BSV (variance of a parameter across individuals), between-occasion variability (BOV) (variance within individuals), and residual variability (unexplained variability after controlling for other sources of variability).
For example, different individuals (humans) will exhibit different sensitivity to toxic effects from the same exposure due to various sources of variability (e.g., genetics, lifestyle, health status).
Do operators systematically identify sources of variability?
The climate has many natural sources of "variability", which push temperatures up and down over months, years and decades.
