Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

This is a field-based disguised case which describes a dilemma faced by the protagonists; do they continue to do business with a land developer who has assisted them in the past when now the developer chooses to, against their recommendations, also do business with their ex-business partner? The problem for the characters in question is whether or not to work on a project that will yield them a net profit of $4 million dollars given the fact it would require them (...) to work in the same development as their former business associate. The central characters are afraid that their ex-partner will be a destabilizing factor in the development of the project and that their work sites will be in jeopardy of being vandalized. Several factors complicate this situation including: the developer’s desire for a quick land purchase, the developer’s changing the discount rate from 20% to 10% perhaps based upon difficulties that surrounded the first land deal, the protagonists’ plans to build their own homes in this new development, and the negative relationship between the protagonists and the ex-business partner. The case has a difficulty level appropriate for a sophomore or junior level course. The case is designed to be taught in one class period and is expected to require between three to five hours of outside preparation by students. (shrink)

Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to (...) genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50, which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1, showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED. (shrink)

Scientific realism has been advanced as an interpretation of the natural sciences but never the behavioral sciences. This book introduces a novel version of scientific realism, Measured Realism, that characterizes the kind of theoretical progress in the social and psychological sciences that is uneven but indisputable. It proposes a theory of measurement, Population-Guided Estimation, that connects natural, psychological, and social scientific inquiry. Presenting quantitative methods in the behavioral sciences as at once successful and regulated by the world, the book will (...) engage philosophers of science, historians of science, sociologists of science, and scientists interested in the foundations of their own disciplines. Part I introduces measured realism beginning with a novel realist theory of measurement (Population-Guided Estimation, or PGE). It examines two other versions of scientific realism — minimal (Hacking) and robust (Boyd, Putnam, and Newton-Smith) — and advances measured realism as best supported by the evidence in the behavioral sciences. It also critically evaluates the anti-realist arguments of van Fraassen, Laudan, and Fine. Part II formulates and develops a version of epistemological naturalism most appropriate to measured realism. Drawing upon the realist theory of measurement developed earlier, it favorably appraises a variety of statistical methods in the behavioral sciences against selected criticisms. It concludes that traditional, narrative methods in the behavioral and social sciences are unreliable by the measures of epistemological naturalism. (shrink)

(2002). Philosophy of Science 72 (January), 198-208.

Measurement ‐ a central epistemic activity in science ‐ relates a number and a quantity in an effort to estimate the magnitude of that quantity. A quantity is typically a property of a physical configuration, such as length or weight, and determines a function that applies to a domain or class of objects. At this high level of abstraction, the description of the purpose and relation of measurement is metaphysically neutral, leaving open the question of whether the domain is observable (...) (empirical) or unobservable (nonempirical). (shrink)

Active inference offers a unified theory of perception, learning, and decision-making at computational and neural levels of description. In this article, we address the worry that active inference may be in tension with the belief–desire–intention model within folk psychology because it does not include terms for desires at the mathematical level of description. To resolve this concern, we first provide a brief review of the historical progression from predictive coding to active inference, enabling us to distinguish between active inference formulations (...) of motor control and active inference formulations of decision processes. We then show that, despite a superficial tension when viewed at the mathematical level of description, the active inference formalism contains terms that are readily identifiable as encoding both the objects of desire and the strength of desire at the psychological level of description. We demonstrate this with simple simulations of an active inference agent motivated to leave a dark room for different reasons. Despite their consistency, we further show how active inference may increase the granularity of folk-psychological descriptions by highlighting distinctions between drives to seek information versus reward—and how it may also offer more precise, quantitative folk-psychological predictions. Finally, we consider how the implicitly conative components of active inference may have partial analogues in other systems describable by the broader free energy principle to which it conforms. (shrink)

Wondrous Truths answers two questions about the steep rise of theoretical discoveries around 1600: Why in the European West? And why so quickly? The history of science's awkward assortment of accident and luck, geography and personal idiosyncrasy, explains scientific progress alongside experimental method. J.D. Trout's blend of scientific realism and epistemic naturalism carries us through neuroscience, psychology, history, and policy, and explains how the corpuscular hunch of Boyle and Newton caught on.

The use of null hypothesis significance testing (NHST) in psychology has been under sustained attack, despite its reliable use in the notably successful, so-called "hard" areas of psychology, such as perception and cognition. I argue that, in contrast to merely methodological analyses of hypothesis testing (in terms of "test severity," or other confirmation-theoretic notions), only a patently metaphysical position can adequately capture the uneven but undeniable successes of theories in "hard psychology." I contend that Measured Realism satisfies this description, and (...) characterizes the role of NHST in hard psychology. (shrink)

Some eliminativists have predicted that a developed neuroscience will eradicate the principles and theoretical kinds (belief, desire, etc.) implicit in our ordinary practices of mental state attribution. Prevailing defenses of common-sense psychology infer its basic integrity from its familiarity and instrumental success in everyday social commerce. Such common-sense defenses charge that eliminativist arguments are self-defeating in their folk psychological appeal to the belief that eliminativism is true. I argue that eliminativism is untouched by this simple charge of inconsistency, and introduce (...) a different dialectical strategy for arguing against the eliminativist. In keeping with the naturalistic trend in the sociology and philosophy of science, I show that neuroscientists routinely rely on folk psychological procedures of intentional state attribution in applying epistemically reliable standards of scientific evaluation. These scientific contexts place ordinary procedures of attribution under greater stress, producing evidence of folk psychological success that is less equivocal than the evidence in mundane settings. Therefore, the dependence of science on folk psychology, when combined with an independently plausible explanatory constraint on reduction and an independently motivated notion of theoretical stress, allows us to reconstitute the charge of (neurophilic) eliminativist inconsistency in a more sophisticated form. (shrink)

In “Forced to be Free”, Neil Levy surveys the raft of documented decision-making biases that humans are heir to, and advances several bold proposals designed to enhance the patient's judgment. Gratefully, Levy is moved by the psychological research on judgment and decision-making that documents people's inaccuracy when identifying courses of action will best promote their subjective well-being. But Levy is quick to favour the patient's present preferences, to ensure they get “final say” about their treatment. I urge the opposite inclination, (...) raising doubts about whether the patient's “present preferences” are the best expression of their “final say”. When there is adequate evidence that people, by their own lights, overemphasize their present preferences about the future, we should carefully depreciate those preferences, in effect biasing them to make the right decision by their own lights. (shrink)

This paper advances a novel argument that speech perception is a complex system best understood nonindividualistically and therefore that individualism fails as a general philosophical program for understanding cognition. The argument proceeds in four steps. First, I describe a "replaceability strategy", commonly deployed by individualists, in which one imagines replacing an object with an appropriate surrogate. This strategy conveys the appearance that relata can be substituted without changing the laws that hold within the domain. Second, I advance a "counterfactual test" (...) as an alternative to the replaceability strategy. Third, I show how the typical objects of cross-modal processes (in this case, auditory-visual speech perception), more clearly irreplaceable than the objects of the unimodal process examined by Burge [(1986) Individualism and psychology, The Philosophical Review, XCV, 3-45], supply a firm basis for a nonindividualist interpretation of such cases. Finally, I demonstrate that the routine violation of the individualist's Replaceability Condition occurs even in unimodal cases - so the violation of the replaceability constraint does not derive simply from the diversity of modal sources but rather from the causal complexity of psychological processes generally. The conclusion is that philosophical progress on this issue must await progress in psychology, or, at least, philosophical progress in accounting for psychological complexity--precisely the vicissitude predicted by a thoroughgoing naturalism. (shrink)

Every human being has a vast store of knowledge about health and sickness and the ability to draw conclusions on the basis of this knowledge. Yet science research continues to be based largely on `objective studies' conducted by academics and to look down on `subjective' studies. The belief that `pure' objective science is highest and subjective information is lowest, inculcated by the way science is taught in schools, deters doctors from communicating information based on personal experience lest it be decried (...) - as it certainly will be - as scientifically worthless. Alternative medicine with its open, flexible approach to the whole person, has something to teach conventional medicine. And doctors must pay more attention to what their patients can tell them. There is no rational justification for accepting the factual information that people give (in a case history) while disregarding what they have to say about their condition. Old-style science is particularly inept in helping doctors deal with psychosomatic problems. What is needed is a new `science of the subjective' which would be truly appropriate to the subject of study, the whole human being. There is a commentary on this paper by Sir Douglas Black, President of the Royal College of Physicians. (shrink)