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Issues of publication bias, lack of replicability, and false discovery have long plagued the genetics community. Proper utilization of public and shared data resources presents an opportunity to ameliorate these problems. We present an approach to public database management that we term Quality Preserving Database (QPD). It enables perpetual use of the database for testing statistical hypotheses while controlling false discovery and avoiding publication bias on the one hand, and maintaining testing power on the other hand. We demonstrate it on a use case of a replication server for GWAS findings, underlining its practical utility. We argue that a shift to using QPD in managing current and future biological databases will significantly enhance the community's ability to make efficient and statistically sound use of the available data resources., (© 2014 WILEY PERIODICALS, INC.)

A recently published study by the present authors reported evidence that functional changes in the anterior cingulate cortex within a sample of 96 criminal offenders who were engaged in a Go/No-Go impulse control task significantly predicted their rearrest following release from prison. In an extended analysis, we use discrimination and calibration techniques to test the accuracy of these predictions relative to more traditional models and their ability to generalize to new observations in both full and reduced models. Modest to strong discrimination and calibration accuracy were found, providing additional support for the utility of neurobiological measures in predicting rearrest.

We report a functional magnetic resonance imaging (fMRI) study of healthy adult participants who completed a demanding Go/NoGo task. The primary purpose of this study was to delineate the neural systems underlying successful and unsuccessful response inhibition using a large sample (N=102). We identified a number of regions uniquely engaged during successful response inhibition, including a fronto-parietal network involving the anterior cingulate, supplementary motor areas, lateral and inferior prefrontal regions, and the inferior parietal lobule. Unique hemodynamic activity was also noted in the amygdala and in frontostriatal regions including the inferior frontal gyrus and portions of the basal ganglia. Also, contrasts were defined to explore three variants of hemodynamic response allowing for more specificity in identifying the underlying cognitive mechanisms of response inhibition. Addressing issues raised by prior small sample studies, we identified a stable set of regions involved in successful response inhibition. The present results help to incrementally refine the specificity of the neural correlates of response inhibition., (Copyright © 2013. Published by Elsevier B.V.)

Identification of factors that predict recurrent antisocial behavior is integral to the social sciences, criminal justice procedures, and the effective treatment of high-risk individuals. Here we show that error-related brain activity elicited during performance of an inhibitory task prospectively predicted subsequent rearrest among adult offenders within 4 y of release (N = 96). The odds that an offender with relatively low anterior cingulate activity would be rearrested were approximately double that of an offender with high activity in this region, holding constant other observed risk factors. These results suggest a potential neurocognitive biomarker for persistent antisocial behavior.

A prominent view of psychopathic moral reasoning suggests that psychopathic individuals cannot properly distinguish between moral wrongs and other types of wrongs. The present study evaluated this view by examining the extent to which 109 incarcerated offenders with varying degrees of psychopathy could distinguish between moral and conventional transgressions relative to each other and to nonincarcerated healthy controls. Using a modified version of the classic Moral/Conventional Transgressions task that uses a forced-choice format to minimize strategic responding, the present study found that total psychopathy score did not predict performance on the task. Task performance was explained by some individual subfacets of psychopathy and by other variables unrelated to psychopathy, such as IQ. The authors conclude that, contrary to earlier claims, insufficient data exist to infer that psychopathic individuals cannot know what is morally wrong.

The present study examined whether and in what ways psychopathy is associated with abnormal moral intuitions among criminal offenders. Using Haidt et al.'s Moral Foundations Questionnaire, 222 adult male offenders assessed for clinical psychopathy reported their degree of support for five moral domains: Harm Prevention, Fairness, Respect for Authority, Ingroup Loyalty, and Purity/Sanctity. As predicted, psychopathy total score explained a substantial proportion of the variance in reduced support for Harm Prevention and Fairness, but not the other domains. These results confirm that psychopathy entails a discrete set of moral abnormalities and suggest that these abnormalities could potentially help to explain the characteristic antisocial behavior of individuals with psychopathy.

Background: The extreme flexibility of the HIV type-1 (HIV-1) genome makes it challenging to build the ideal antiretroviral treatment regimen. Interpretation of HIV-1 genotypic drug resistance is evolving from rule-based systems guided by expert opinion to data-driven engines developed through machine learning methods., Methods: The aim of the study was to investigate linear and non-linear statistical learning models for classifying short-term virological outcome of antiretroviral treatment. To optimize the model, different feature selection methods were considered. Robust extra-sample error estimation and different loss functions were used to assess model performance. The results were compared with widely used rule-based genotypic interpretation systems (Stanford HIVdb, Rega and ANRS)., Results: A set of 3,143 treatment change episodes were extracted from the EuResist database. The dataset included patient demographics, treatment history and viral genotypes. A logistic regression model using high order interaction variables performed better than rule-based genotypic interpretation systems (accuracy 75.63% versus 71.74-73.89%, area under the receiver operating characteristic curve [AUC] 0.76 versus 0.68-0.70) and was equivalent to a random forest model (accuracy 76.16%, AUC 0.77). However, when rule-based genotypic interpretation systems were coupled with additional patient attributes, and the combination was provided as input to the logistic regression model, the performance increased significantly, becoming comparable to the fully data-driven methods., Conclusions: Patient-derived supplementary features significantly improved the accuracy of the prediction of response to treatment, both with rule-based and data-driven interpretation systems. Fully data-driven models derived from large-scale data sources show promise as antiretroviral treatment decision support tools.

Motivation: Optimizing HIV therapies is crucial since the virus rapidly develops mutations to evade drug pressure. Recent studies have shown that genotypic information might not be sufficient for the design of therapies and that other clinical and demographical factors may play a role in therapy failure. This study is designed to assess the improvement in prediction achieved when such information is taken into account. We use these factors to generate a prediction engine using a variety of machine learning methods and to determine which clinical conditions are most misleading in terms of predicting the outcome of a therapy., Results: Three different machine learning techniques were used: generative-discriminative method, regression with derived evolutionary features, and regression with a mixture of effects. All three methods had similar performances with an area under the receiver operating characteristic curve (AUC) of 0.77. A set of three similar engines limited to genotypic information only achieved an AUC of 0.75. A straightforward combination of the three engines consistently improves the prediction, with significantly better prediction when the full set of features is employed. The combined engine improves on predictions obtained from an online state-of-the-art resistance interpretation system. Moreover, engines tend to disagree more on the outcome of failure therapies than regarding successful ones. Careful analysis of the differences between the engines revealed those mutations and drugs most closely associated with uncertainty of the therapy outcome., Availability: The combined prediction engine will be available from July 2008, see http://engine.euresist.org.

Can neurological evidence help courts assess criminal responsibility? To answer this question, we must first specify legal criteria for criminal responsibility and then ask how neurological findings can be used to determine whether particular defendants meet those criteria. Cognitive neuroscience may speak to at least two familiar conditions of criminal responsibility: intention and sanity. Functional neuroimaging studies in motor planning, awareness of actions, agency, social contract reasoning, and theory of mind, among others, have recently targeted a small assortment of brain networks thought to be instrumental in such determinations. Advances in each of these areas bring specificity to the problems underlying the application of neuroscience to criminal law.

When deciding a criminal's punishment, people typically exhibit both retributive and consequentialist motives in their decision making, though retribution's role may be stronger. This study aimed to discern possible functions of retribution by examining a population predicted to be deficient in retributive drive. Participants who rated either high or low in psychopathic traits read stories about a homicide. These stories were designed to evoke both retribution and the consequentialist motive of behavior control by varying, respectively, criminal intent and likelihood of recidivism. The participants then recommended a length of confinement for the offender. Individuals high in psychopathic traits were uniquely insensitive to retributive cues, and they were particularly consequentialist in their punishment of criminal offenders. These results clarify aspects of psychopathic aggression and corroborate the hypothesis that retribution may stabilize cooperative behavior., (Copyright (c) 2007 John Wiley & Sons, Ltd.)