Inductive queries for a drug designing robot scientist

It is increasingly clear that machine learning algorithms need to be integrated in an iterative scientific discovery loop, in which data is queried repeatedly by means of inductive queries and where the computer provides guidance to the experiments that are being performed. In this chapter, we summarise several key challenges in achieving this integration of machine learning and data mining algorithms in methods for the discovery of Quantitative Structure Activity Relationships (QSARs). We introduce the concept of a robot scientist, in which all steps of the discovery process are automated; we discuss the representation of molecular data such that knowledge discovery tools can analyse it, and we discuss the adaptation of machine learning and data mining algorithms to guide QSAR experiments

Cross-screening in observational studies that test many hypotheses

We discuss observational studies that test many causal hypotheses, either hypotheses about many outcomes or many treatments. To be credible an observational study that tests many causal hypotheses must demonstrate that its conclusions are neither artifacts of multiple testing nor of small biases from nonrandom treatment assignment. In a sense that needs to be defined carefully, hidden within a sensitivity analysis for nonrandom assignment is an enormous correction for multiple testing: in the absence of bias, it is extremely improbable that multiple testing alone would create an association insensitive to moderate biases. We propose a new strategy called "cross-screening", different from but motivated by recent work of Bogomolov and Heller on replicability. Cross-screening splits the data in half at random, uses the first half to plan a study carried out on the second half, then uses the second half to plan a study carried out on the first half, and reports the more favorable conclusions of the two studies correcting using the Bonferroni inequality for having done two studies. If the two studies happen to concur, then they achieve Bogomolov-Heller replicability; however, importantly, replicability is not required for strong control of the family-wise error rate, and either study alone suffices for firm conclusions. In randomized studies with a few hypotheses, cross-split screening is not an attractive method when compared with conventional methods of multiplicity control, but it can become attractive when hundreds or thousands of hypotheses are subjected to sensitivity analyses in an observational study. We illustrate the technique by comparing 46 biomarkers in individuals who consume large quantities of fish versus little or no fish.Comment: 33 pages, 2 figures, 5 table

Modeling Epistemological Principles for Bias Mitigation in AI Systems: An Illustration in Hiring Decisions

Artificial Intelligence (AI) has been used extensively in automatic decision making in a broad variety of scenarios, ranging from credit ratings for loans to recommendations of movies. Traditional design guidelines for AI models focus essentially on accuracy maximization, but recent work has shown that economically irrational and socially unacceptable scenarios of discrimination and unfairness are likely to arise unless these issues are explicitly addressed. This undesirable behavior has several possible sources, such as biased datasets used for training that may not be detected in black-box models. After pointing out connections between such bias of AI and the problem of induction, we focus on Popper's contributions after Hume's, which offer a logical theory of preferences. An AI model can be preferred over others on purely rational grounds after one or more attempts at refutation based on accuracy and fairness. Inspired by such epistemological principles, this paper proposes a structured approach to mitigate discrimination and unfairness caused by bias in AI systems. In the proposed computational framework, models are selected and enhanced after attempts at refutation. To illustrate our discussion, we focus on hiring decision scenarios where an AI system filters in which job applicants should go to the interview phase

On null hypotheses in survival analysis

The conventional nonparametric tests in survival analysis, such as the log-rank test, assess the null hypothesis that the hazards are equal at all times. However, hazards are hard to interpret causally, and other null hypotheses are more relevant in many scenarios with survival outcomes. To allow for a wider range of null hypotheses, we present a generic approach to define test statistics. This approach utilizes the fact that a wide range of common parameters in survival analysis can be expressed as solutions of differential equations. Thereby we can test hypotheses based on survival parameters that solve differential equations driven by cumulative hazards, and it is easy to implement the tests on a computer. We present simulations, suggesting that our tests perform well for several hypotheses in a range of scenarios. Finally, we use our tests to evaluate the effect of adjuvant chemotherapies in patients with colon cancer, using data from a randomised controlled trial

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions

Collective Implicit Attitudes: A Stakeholder Conception of Implicit Bias

Psychologists and philosophers have not yet resolved what they take implicit attitudes to be; and, some, concerned about limitations in the psychometric evidence, have even challenged the predictive and theoretical value of positing implicit attitudes in explanations for social behavior. In the midst of this debate, prominent stakeholders in science have called for scientific communities to recognize and countenance implicit bias in STEM fields. In this paper, I stake out a stakeholder conception of implicit bias that responds to these challenges in ways that are responsive to the psychometric evidence, while also being resilient to the sorts of disagreements and scientific progress that would not undermine the soundness of this call. Along the way, my account advocates for attributing collective (group-level) implicit attitudes rather than individual-level implicit attitudes. This position raises new puzzles for future research on the relationship (metaphysical, epistemic, and ethical) between collective implicit attitudes and individual-level attitudes

The influence of the Ratio Bias phenomenon on the elicitation of Standard Gamble utilities

This paper tests whether logically equivalent risk formats can lead to different health state utilities elicited by means of the standard gamble (SG) method. We compare SG utilities elicited when probabilities are framed in terms of frequencies with respect to 100 people in the population (i.e., X out of 100) with SG utilities elicited for frequencies with respect to 1,000 people in the population (i.e., Y out of 1,000). We found that utilities were significant higher when success and failure probabilities were framed as frequencies type “Y out of 1,000” rather than as frequencies type “X out of 100”. This framing effect, known as Ratio Bias, may have important consequences in resource allocation decisions.Framing effect, risk format, standard gamble, health state, dual-process theories.