However, its utility has not been demonstrated in more complex situations, such as neurosurgical critically ill patients.
First, involvement of COMT in dopaminergic contributions to decision making and reward has hitherto been demonstrated in relatively complex paradigms (47 50), but our gambling task data show that even the simple trait of risky decision making is affected by COMT: high COMT activity is associated with making a higher proportion of large gambles (risky choices) compared with low COMT activity.
For example, logistic regression models use linear combinations of variables and, therefore, are not adept at modeling grossly nonlinear complex interactions as has been demonstrated in biologic and complex epidemiologic systems.
For our modeling environment we chose Biochemical Systems Theory (BST) [25] [27], because it permits mathematical analyses and simulations of biochemical pathways under a minimal set of assumptions and even if crucial quantitative information is lacking, as it has been demonstrated in other, similarly complex contexts [28] [30].
High λs, estimating recurrent risks for siblings of affected individuals have been demonstrated in many diseases with complex traits, but the genetic risk factors identified by GWAS do not account for the high λs.
Increased FA has been demonstrated in the striatum (caudate putamen complex; Rosas et al. 2006; Kloppel et al. 2008; Douaud et al. 2009) as well as in the internal capsule (Rosas et al. 2006) at preclinical and clinical stages of HD.
An example of this stepwise process that integrates experiment and computational data has been demonstrated in the elucidation of a complex regulatory network that governs the activity of the mammalian target of rapamycin complex 2 (mTORC2) signaling network [ 124].
Genome replacement has been demonstrated in hybridogenetic unisexual fishes (Poeciliopsis complex [ 35, 36], the Iberian minnow Leuciscus alburnoides [ 2, 37]), frogs (Rana esculenta complex [ 38]) and kleptogenetic unisexual Ambystoma (present study).
This has notably been demonstrated in the Chicory crop-wild complex (Hauser et al. 2012).
Poorer compliance has been demonstrated in those treated with more complex medication regimens [ 26- 30].
