Degree irregularity and rank probability bias in network meta-analysis

Network meta-analysis (NMA) is a statistical technique for the comparison of treatment options. The nodes of the network are the competing treatments and edges represent comparisons of treatments in trials. Outcomes of Bayesian NMA include estimates of treatment effects, and the probabilities that each treatment is ranked best, second best and so on. How exactly network geometry affects the accuracy and precision of these outcomes is not fully understood. Here we carry out a simulation study and find that disparity in the number of trials involving different treatments leads to a systematic bias in estimated rank probabilities. This bias is associated with an increased variation in the precision of treatment effect estimates. Using ideas from the theory of complex networks, we define a measure of ‘degree irregularity’ to quantify asymmetry in the number of studies involving each treatment. Our simulations indicate that more regular networks have more precise treatment effect estimates and smaller bias of rank probabilities. We also find that degree regularity is a better indicator of NMA quality than both the total number of studies in a network and the disparity in the number of trials per comparison. These results have implications for planning future trials. We demonstrate that choosing trials which reduce the network’s irregularity can improve the precision and accuracy of NMA outcomes.

Social Cost Bias, Probability Bias, and Self-Efficacy as Correlates of Behavioral Action in Social Anxiety

The present study investigated the role of social cost bias, probability bias, and self-efficacy as correlates of behavioral action in a nonclinical sample of 197 individuals, using a series of vignettes and self-report measures. The findings indicated that, as hypothesized, social cost bias, probability bias, and self-efficacy were associated with social anxiety. While social anxiety was associated with behavioral action, the three cognitive factors were associated with behavioral action above and beyond the contribution of social anxiety. However, contrary to the hypothesis, self-efficacy was the only cognitive factor directly associated with behavioral action when all variables were in the model. This information has implications for potential methods and target mechanisms for increasing client engagement with exposures and behavioral experiments in treatments for social anxiety.

A template-based approach to the modification of binding properties of globular proteins II: Rationale and proposed approach.

We present a rationale and proposed approach to the modification and development of bind sites using their respective cognate ligands as template. This is in support of a plausible “instructive” role for the ligand and therefore its involvement in determination of the structure and properties of bind sites. We emphasize the relationship between substrate and active site as an example of the relationship between ligand and bind sites, respectively. This is based on the assumption that there are shared features between all ligand:bind site complexes. Therefore, principles that apply to a specific complex can be applied, in general, to other protein-based complexes. We define ligand-associated probability bias as the difference between the probability of finding activity-determining conformations (ADCs) in the presence- and absence of ligands. For cognate ligands, the given bias is in favor of these ADCs. Thus, bind sites are more likely to assume ADCs when their cognate ligands are present. We relate such probability bias to structural reorganization, disorganization, and preorganization events. We then propose a means of deriving an [apparent] preorganized bind site structure by way of reorganization events that occur with cognate ligand. Finally, we propose a means of deriving an [actual] preorganized bind site structure by way of reorganization events that occur with cognate ligand, albeit during the folding process. The assumption is that the role of the ligand in derivation of such [actual] preorganized bind site structures is an instructive role, and is in support of the Haurowitz-Pauling hypothesis.

A template-based approach to the modification of binding properties of globular proteins II: Rationale and proposed approach.

We present a rationale and proposed approach to the modification and development of bind sites using their respective cognate ligands as template. This is in support of a plausible “instructive” role for the ligand and therefore its involvement in determination of the structure and properties of bind sites. We emphasize the relationship between substrate and active site as an example of the relationship between ligand and bind sites, respectively. This is based on the assumption that there are shared features between all ligand:bind site complexes. Therefore, principles that apply to a specific complex can be applied, in general, to other protein-based complexes. We define ligand-associated probability bias as the difference between the probability of finding activity-determining conformations (ADCs) in the presence- and absence of ligands. For cognate ligands, the given bias is in favor of these ADCs. Thus, bind sites are more likely to assume ADCs when their cognate ligands are present. We relate such probability bias to structural reorganization, disorganization, and preorganization events. We then propose a means of deriving an [apparent] preorganized bind site structure by way of reorganization events that occur with cognate ligand. Finally, we propose a means of deriving an [actual] preorganized bind site structure by way of reorganization events that occur with cognate ligand, albeit during the folding process. The assumption is that the role of the ligand in derivation of such [actual] preorganized bind site structures is an instructive role, and is in support of the Haurowitz-Pauling hypothesis.

A template-based approach to the modification of binding properties of globular proteins II: Rationale and proposed approach.

We present a rationale and proposed approach to the modification and development of bind sites using their respective cognate ligands as template. This is in support of a plausible “instructive” role for the ligand and therefore its involvement in determination of the structure and properties of bind sites. We emphasize the relationship between substrate and active site as an example of the relationship between ligand and bind sites, respectively. This is based on the assumption that there are shared features between all ligand:bind site complexes. Therefore, principles that apply to a specific complex can be applied, in general, to other protein-based complexes. We define ligand-associated probability bias as the difference between the probability of finding activity-determining conformations (ADCs) in the presence- and absence of ligands. For cognate ligands, the given bias is in favor of these ADCs. Thus, bind sites are more likely to assume ADCs when their cognate ligands are present. We relate such probability bias to structural reorganization, disorganization, and preorganization events. We then propose a means of deriving an [apparent] preorganized bind site structure by way of reorganization events that occur with cognate ligand. Finally, we propose a means of deriving an [actual] preorganized bind site structure by way of reorganization events that occur with cognate ligand, albeit during the folding process. The assumption is that the role of the ligand in derivation of such [actual] preorganized bind site structures is an instructive role, and is in support of the Haurowitz-Pauling hypothesis.