A similarity-based QSAR model for predicting acute toxicity towards the fathead minnow (Pimephales promelas).

REACH regulation demands information about acute toxicity of chemicals towards fish and supports the use of QSAR models, provided compliance with OECD principles. Existing models present some drawbacks that may limit their regulatory application. In this study, a dataset of 908 chemicals was used to develop a QSAR model to predict the LC50 96 hours for the fathead minnow. Genetic algorithms combined with k nearest neighbour method were applied on the training set (726 chemicals) and resulted in a model based on six molecular descriptors. An automated assessment of the applicability domain (AD) was carried out by comparing the average distance of each molecule from the nearest neighbours with a fixed threshold. The model had good and balanced performance in internal and external validation (182 test molecules), at the expense of a percentage of molecules outside the AD. Principal Component Analysis showed apparent correlations between model descriptors and toxicity.

Validation and extension of a similarity-based approach for prediction of acute aquatic toxicity towards Daphnia magna.

Quantitative structure-activity relationship (QSAR) models for predicting acute toxicity to Daphnia magna are often associated with poor performances, urging the need for improvement to meet REACH requirements. The aim of this study was to evaluate the accuracy, stability and reliability of a previously published QSAR model by means of further external validation and to optimize its performance by means of extension to new data as well as a consensus approach. The previously published model was validated with a large set of new molecules and then compared with ChemProp model, from which most of the validation data were taken. Results showed better performance of the proposed model in terms of accuracy and percentage of molecules outside the applicability domain. The model was re-calibrated on all the available data to confirm the efficacy of the similarity-based approach. The extended dataset was also used to develop a novel model based on the same similarity approach but using binary fingerprints to describe the chemical structures. The fingerprint-based model gave lower regression statistics, but also less unpredicted compounds. Eventually, consensus modelling was successfully used to enhance the accuracy of the predictions and to halve the percentage of molecules outside the applicability domain.

Inhibitory control efficiency in a Piaget-like class-inclusion task in school-age children and adults: a developmental negative priming study.

Most children under 7 years of age presented with 10 daisies and 2 roses fail to indicate that there are more flowers than daisies. Instead of the appropriate comparison of the relative numerosities of the superordinate class (flowers) to its subordinate class (daisies), they perform a direct perceptual comparison of the extensions of the 2 subordinate classes (daisies vs. roses). In our experiment, we investigated whether increasing efficiency in solving the Piagetian class-inclusion task is related to increasing efficiency in the ability to resist (inhibit) this direct comparison of the subordinate classes' extensions. Ten-year-old and young adult participants performed a computerized priming version of a Piaget-like class-inclusion task. The experimental design was such that the misleading perceptual strategy to inhibit on the prime (in which a superordinate class had to be compared with a subordinate class) became a congruent strategy to activate on the probe (in which the two subordinate classes' extensions were directly compared). We found a negative priming effect of 291 ms in children and 129 ms in adults. These results provide evidence for the first time (a) that adults still need to inhibit the comparison of the subordinate classes' extensions in class-inclusion tasks and (b) that the ability to inhibit this heuristic increases with age (resulting in a lower executive cost). Taken together, these findings provide additional support for the neo-Piagetian approach of cognitive development that suggests that the acquisition of increasingly complex knowledge is based on the ability to resist (inhibit) heuristics and previously acquired knowledge.

Counterfactually mediated emotions: a developmental study of regret and relief in a probabilistic gambling task.

Regret and relief are related to counterfactual thinking and rely on comparison processes between what has been and what might have been. In this article, we study the development of regret and relief from late childhood to adulthood (11.2-20.2 years), and we examine how these two emotions affect individuals' willingness to retrospectively reconsider their choice in a computerized monetary gambling task. We asked participants to choose between two "wheels of fortune" that differed in the amount of gain and loss expected and the probability of winning. We manipulated the outcome of the wheel of fortune that was not selected by participants to induce regret or relief. For each trial, participants rated how they felt about the outcome and their willingness to modify their choice. Participants' ratings suggest that regret and relief are stronger in adults than in children and adolescents. Regret affects participants' willingness to modify their initial choice, but this desire is stronger for adults than for children. In children, the experience of regret seems to be dissociated from the willingness to reconsider a choice. This study provides the first evidence that the ability to experience counterfactually mediated emotions, such as regret and relief, and the ability to take them into consideration continue to develop during late childhood and adolescence.