Conflicting intentions: rectifying the consistency requirements.

Many philosophers are convinced that rationality dictates that one's overall set of intentions be consistent. The starting point and inspiration for our study is Bratman's planning theory of intentions. According to this theory, one needs to appeal to the fulfilment of characteristic planning roles to justify norms that apply to our intentions. Our main objective is to demonstrate that one can be rational despite having mutually inconsistent intentions. Conversely, it is also shown that one can be irrational despite having a consistent overall set of intentions. To overcome this paradox, we argue that it is essential for a successful planning system that one's intentions are practically consistent rather than being consistent or applying an aggregation procedure. Our arguments suggest that a new type of norm is needed: whereas the consistency requirement focuses on rendering the contents of one's intentions consistent, our new practical consistency requirement demands that one's intentions be able to simultaneously and unconditionally guide one's action. We observe that for intentions that conform to the 'own-action condition', the practical consistency requirement is equivalent to the traditional consistency requirement. This implies that the consistency requirement only needs to be amended in scenarios of choice under uncertainty.

Genotype scores predict drug efficacy in subtypes of female sexual interest/arousal disorder: A double-blind, randomized, placebo-controlled cross-over trial.

Attempts to develop a drug treatment for female sexual interest/arousal disorder have so far been guided by the principle of 'one size fits all', and have failed to acknowledge the complexity of female sexuality. Guided by personalized medicine, we designed two on-demand drugs targeting two distinct hypothesized causal mechanisms for this sexual disorder. The objective of this study was to design and test a novel procedure, based on genotyping, that predicts which of the two on-demand drugs will yield a positive treatment response. In a double-blind, randomized, placebo-controlled cross-over experiment, 139 women with female sexual interest/arousal disorder received three different on-demand drug-combination treatments during three 2-week periods: testosterone 0.5 mg + sildenafil 50 mg, testosterone 0.5 mg + buspirone 10 mg, and matching placebo. The primary endpoint was change in satisfactory sexual events. Subjects' genetic profile was assessed using a microarray chip that measures 300,000 single-nucleotide polymorphisms. A preselection of single-nucleotide polymorphisms associated with genes that are shown to be involved in sexual behaviour were combined into a Phenotype Prediction Score. The Phenotype Prediction Score demarcation formula was developed and subsequently validated on separate data sets. Prediction of drug-responders with the Phenotype Prediction Score demarcation formula gave large effect sizes (d = 0.66 through 1.06) in the true drug-responders, and medium effect sizes (d = 0.51 and d = 0.47) in all patients (including identified double, and non-responders). Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the Phenotype Prediction Score demarcation formula were all between 0.78 and 0.79, and thus sufficient. The resulting Phenotype Prediction Score was validated and shown to effectively and reliably predict which women would benefit from which on-demand drug, and could therefore also be useful in clinical practice, as a companion diagnostic establishing the way to a true personalized medicine approach.