Theory of mind and relational complexity

Cognitive complexity and control theory and relational complexity theory attribute developmental changes in theory of mind (TOM) to complexity. In 3 studies, 3-, 4-, and 5-year-olds performed TOM tasks (false belief, appearance-reality), less complex connections (Level 1 perspective-taking) tasks, and transformations tasks (understanding the effects of location changes and colored filters) with content similar to TOM. There were also predictor tasks at binary-relational and ternary-relational complexity levels, with different content. Consistent with complexity theories: (a) connections and transformations were easier and mastered earlier than TOM; (b) predictor tasks accounted for more than 80% of age-related variance in TOM; and (c) ternary-relational items accounted for TOM variance, before and after controlling for age and binary-relational items. Prediction did not require hierarchically structured predictor tasks.

Risk taking from the participant's perspective: The case of driving and accident risk

Although perceived health risk plays a prominent role in theories of health behavior. its empirical role in risk taking is less clear. In Study 1 (N = 129), 2 measures of drivers' risk-taking behavior were found to be unrelated to self-estimates of accident concern but to be related to self-ratings of driving skill and the perceived thrill of driving. In Study 2 (N = 405), out of a wide range of potential influences, accident concern had the weakest relationship with risk taking. The authors concluded that although health risk is a key feature in many theories of health behavior and a central focus for researchers and policy makers, it may not be such a prominent factor for those actually taking the risk.

Acyl glucuronide reactivity in perspective: biological consequences

The metabolic conjugation of exogenous and endogenous carboxylic acid substrates with endogenous glucuronic acid, mediated by the uridine diphosphoglucuronosyl transferase (UGT) superfamily of enzymes, leads to the formation of acyl glucuronide metabolites. Since the late 1970s, acyl glucuronides have been increasingly identified as reactive electrophilic metabolites, capable of undergoing three reactions: intramolecular rearrangement, hydrolysis, and intermolecular reactions with proteins leading to covalent drug-protein adducts. This essential dogma has been accepted for over a decade. The key question proposed by researchers, and now the pharmaceutical industry, is: does or can the covalent modification of endogenous proteins, mediated by reactive acyl glucuronide metabolites, lead to adverse drug reactions, perhaps idiosyncratic in nature? This review evaluates the evidence for acyl glucuronide-derived perturbation of homeostasis, particularly that which might result from the covalent modification of endogenous proteins and other macromolecules. Because of the availability of acyl glucuronides for test tube/in vitro experiments, there is now a substantial literature documenting their rearrangement, hydrolysis and covalent modification of proteins in vitro. It is certain from in vitro experiments that serum albumin, dipeptidyl peptidase IV, tubulin and UGTs are covalently modified by acyl glucuronides. However, these in vitro experiments have been specifically designed to amplify any interference with a biological process in order to find biological effects. The in vivo situation is not at all clear. Certainly it must be concluded that all humans taking carboxylate drugs that form reactive acyl glucuronides will form covalent drug-protein adducts, and it must also be concluded that this in itself is normally benign. However, there is enough in vivo evidence implicating acyl glucuronides, which, when backed up by in vivo circumstantial and documented in vitro evidence, supports the view that reactive acyl glucuronides may initiate toxicity/immune responses. In summary, though acyl glucuronide-derived covalent modification of endogenous macromolecules is well-defined, the work ahead needs to provide detailed links between such modification and its possible biological consequences. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.