We present evidence of a potentially serious source of error intrinsic to all spotted cDNA microarrays that use IMAGE clones of expressed sequence tags (ESTs). We found that a high proportion of these EST sequences contain 5V-end poly(dT) sequences that are remnants from the oligo(dT)-primed reverse transcription of polyadenylated mRNA templates used to generate EST cDNA for sequence clone libraries. Analysis of expression data from two single-dye cDNA microarray experiments showed that ESTs whose sequences contain repeats of consecutive 5V- end (...) dT residues appeared to be strongly coexpressed, while expression data of all other sequences exhibited no such pattern. Our analysis suggests that expression data from sequences containing 5V poly(dT) tracts are more likely to be due to systematic cross-hybridization of these poly(dT) tracts than to true mRNA coexpression. This indicates that existing data generated by cDNA microarrays containing IMAGE clone ESTs should be filtered to remove expression data containing significant 5V poly(dT) tracts. D 2003 Elsevier Inc. All rights reserved. (shrink)

Conditioning can make imprecise probabilities uniformly more imprecise. We call this effect "dilation". In a previous paper (1993), Seidenfeld and Wasserman established some basic results about dilation. In this paper we further investigate dilation on several models. In particular, we consider conditions under which dilation persists under marginalization and we quantify the degree of dilation. We also show that dilation manifests itself asymptotically in certain robust Bayesian models and we characterize the rate at which dilation occurs.

We report two issues concerning diverging sets of Bayesian (conditional) probabilities-divergence of "posteriors"-that can result with increasing evidence. Consider a set P of probabilities typically, but not always, based on a set of Bayesian "priors." Fix E, an event of interest, and X, a random variable to be observed. With respect to P, when the set of conditional probabilities for E, given X, strictly contains the set of unconditional probabilities for E, for each possible outcome X = x, call this (...) phenomenon dilation of the set of probabilities (Seidenfeld and Wasserman 1993). Thus, dilation contrasts with the asymptotic merging of posterior probabilities reported by Savage (1954) and by Blackwell and Dubins (1962). (1) In a wide variety of models for Robust Bayesian inference the extent to which X dilates E is related to a model specific index of how far key elements of P are from a distribution that makes X and E independent. (2) At a fixed confidence level, (1-α), Classical interval estimates A n for, e.g., a Normal mean θ have length O(n -1/2 ) (for sample size n). Of course, the confidence level correctly reports the (prior) probability that θ ∈ A n ,P(A n )=1-α , independent of the prior for θ . However, as shown by Pericchi and Walley (1991), if an ε -contamination class is used for the prior on the parameter θ , there is asymptotic (posterior) dilation for the A n , given the data. If, however, the intervals A ′ n are chosen with length $O(\sqrt{\log (\text{n})/\text{n})}$ , then there is no asymptotic dilation. We discuss the asymptotic rates of dilation for ClassClassical and Bayesian interval estimates and relate these to Bayesian hypothesis testing. (shrink)

DNA microarrays are perfectly suited for comparing gene expression in different populations of cells. An important application of microarray techniques is identifying genes which are activated by a particular drug of interest. This process will allow biologists to identify therapies targeted to particular diseases, and, eventually, to gain more knowledge about the biological processes in organisms. Such an application is described in this paper. It is focused on diabetes and obesity, which is a genetically heterogeneous disease, meaning that multiple defective (...) genes are responsible for the diseases. The paper is divided in three parts, each dealing with a different problem addressed to our study. First we validate the data from our microarray experiment. We identified significant systematic sources of variability which are potentially issues for other microarray datasets. Second, we applied multiple hypothesis testing to identify differentially expressed genes. We found a set of genes which appear to change in expression level over time in response to a drug treatment. Third, we tried to address the problem of identification of co-expressed genes using cluster analysis. This last problem is still under discussion. (shrink)

We discuss two general issues concerning diverging sets of Bayesian (conditional) probabilities—divergence of “posteriors”—that can result with increasing evidence. Consider a setof probabilities typically, but not always, based on a set of Bayesian “priors.” Incorporating sets of probabilities, rather than relying on a single probability, is a useful way to provide a rigorous mathematical framework for studying sensitivity and robustness in Classical and Bayesian inference. See: Berger (1984, 1985, 1990); Lavine (1991); Huber and Strassen (1973); Walley (1991); and Wasserman (...) and Kadane (1990). Also, sets of probabilities arise in group decision problems. See: Levi (1982); and Seidenfeld, Kadane, and Schervish (1989). Third, sets of probabilities are one consequence of weakening traditional axioms for uncertainty. See: Good (1952); Smith (1961); Kyburg (1961); Levi (1974); Fishburn (1986); Seidenfeld, Schervish, and Kadane (1990); and Walley (1991). (shrink)

James M. Robins, Richard Scheines, Peter Spirtes, and Larry Wasserman. The Limits of Causal Knowledge.

This essay contains a partial exploration of some key concepts associated with the epistemology of realist philosophies of science. It shows that neither reference nor approximate truth will do the explanatory jobs that realists expect of them. Equally, several widely-held realist theses about the nature of inter-theoretic relations and scientific progress are scrutinized and found wanting. Finally, it is argued that the history of science, far from confirming scientific realism, decisively confutes several extant versions of avowedly 'naturalistic' forms of scientific (...) realism. (shrink)

The patient preference predictor is a proposed computer-based algorithm that would predict the treatment preferences of decisionally incapacitated patients. Incorporation of a PPP into the decision-making process has the potential to improve implementation of the substituted judgement standard by providing more accurate predictions of patients’ treatment preferences than reliance on surrogates alone. Yet, critics argue that methods for making treatment decisions for incapacitated patients should be judged on a number of factors beyond simply providing them with the treatments they would (...) have chosen for themselves. These factors include the extent to which the decision-making process recognises patients’ freedom to choose and relies on evidence the patient themselves would take into account when making treatment decisions. These critics conclude that use of a PPP should be rejected on the grounds that it is inconsistent with these factors, especially as they relate to proper respect for patient autonomy. In this paper, we review and evaluate these criticisms. We argue that they do not provide reason to reject use of a PPP, thus supporting efforts to develop a full-scale PPP and to evaluate it in practice. There are no data in this work. (shrink)

Temkin presents a new way of thinking about equality and inequality that challenges the assumptions of philosophers, welfare economists, and others, and has significant implications on both a practical and theoretical level.

In choosing between moral alternatives -- choosing between various forms of ethical action -- we typically make calculations of the following kind: A is better than B; B is better than C; therefore A is better than C. These inferences use the principle of transitivity and are fundamental to many forms of practical and theoretical theorizing, not just in moral and ethical theory but in economics. Indeed they are so common as to be almost invisible. What Larry Temkin's book (...) shows is that, shockingly, if we want to continue making plausible judgments, we cannot continue to make these assumptions. Temkin shows that we are committed to various moral ideals that are, surprisingly, fundamentally incompatible with the idea that "better than" can be transitive. His book develops many examples where value judgments that we accept and find attractive, are incompatible with transitivity. While this might seem to leave two options -- reject transitivity, or reject some of our normative commitments in order to keep it -- Temkin is neutral on which path to follow, only making the case that a choice is necessary, and that the cost either way will be high. Temkin's book is a very original and deeply unsettling work of skeptical philosophy that mounts an important new challenge to contemporary ethics. (shrink)

In "Futurc Generations: Further Problems,"‘ and Part Four of Reasons and Persons} Derek Pariit raises many perplexing questions. Although some think his ingenious arguments little more than delightful puzzles, I believe they challenge some of our deepest beliefs. In this article, I examine some of Pariit’s arguments, focusing mainly on "The Mere Addition Paradox." If my analysis is correct, Parfit’s arguments have extremely interesting and important implications that not even Pariit rcalized. In Part I, I present ParHt’s argument for the (...) Merc Addition Paradox, and show that given Pa.rHt’s assumptions, a radical conclusion seems t0 follow; the notion of "bctter th2m"—indced, even the notion of "aH things.. (shrink)

Normative naturalism is a view about the status of epistemology and philosophy of science; it is a meta-epistemology. It maintains that epistemology can both discharge its traditional normative role and nonetheless claim a sensitivity to empirical evidence. The first sections of this essay set out the central tenets of normative naturalism, both in its epistemic and its axiological dimensions; later sections respond to criticisms of that species of naturalism from Gerald Doppelt, Jarrett Leplin and Alex Rosenberg.

In "Equality, Priority, and Compassion," Roger Crisp rejects both egalitarianism and prioritarianism. Crisp contends that our concern for those who are badly off is best accounted for by appealing to "a sufficiency principle" based -- indirectly, via the notion of an impartial spectator -- on compassion for those who are badly off" (p. 745). A key example of Crisp's is the Beverly Hills case (discussed below). This example is directed against prioritarianism, but it also threatens egalitarianism. In this article, I (...) respond to the Beverly Hills case. I also challenge the wide person-affecting principle and Crisp's welfarist restriction, which some believe underlie the Levelling Down Objection against egalitarianism. My aim in this article is to defend egalitarianism by illuminating both its nature and appeal. (shrink)

This paper aims to illuminate some issues in the equality, priority, or what debate. I characterize egalitarianism and prioritarianism, respond to the view that we should care about sufficiency or compassion rather than equality or priority, discuss the levelling down objection, and illustrate the significance of the distinction between prioritarianism and egalitarianism, establishing that the former is no substitute for the latter. In addition, I respond to Bertil Tungodden's views regarding the Slogan, the levelling down objection, the Pareto Principle, leximin, (...) the principle of personal good, strict moderate egalitarianism, the Hammond Equity Condition, the intersection approach, and non-aggregative reasoning. (shrink)

Jaegwon Kim’s causal exclusion argument has rarely been evaluated from an empirical perspective. This is puzzling because its conclusion seems to be making a testable claim about the world: supervenient properties are causally inefficacious. An empirical perspective, however, reveals Kim’s argument to rest on a mistaken conception about how to test whether a property is causally efficacious. Moreover, the empirical perspective makes visible a metaphysical bias that Kim brings to his argument that involves a principle of non-inclusion.

Embodied Cognition is an approach to cognition that departs from traditional cognitive science in its reluctance to conceive of cognition as computational and in its emphasis on the significance of an organism's body in how and what the organism thinks. Three lines of embodied cognition research are described and some thoughts on the future of embodied cognition offered.

This paper argues that it has been widely assumed by philosophers of science that the cumulative retention of explanatory success is a "sine qua non" for making judgements about the progress or rational preferability of one theory over another. It has also been assumed that it is impossible to make objective, Comparative judgements of the acceptability of rival theories unless all the statements of both theories could be translated into a common language. This paper seeks to show that both these (...) dogmas are mistaken; that progress without cumulativity and comparability without commensurability are both viable. (shrink)

This article asks whether personal ventilators should be redistributed to maximize lives saved in emergency condition, like the COVID-19 pandemic. It begins by examining extant claims that items like ventilators are literally parts of their user’s bodies. Arguments in favor of incorporation for ventilators fail to show that they meet valid sufficient conditions to be body parts, but arguments against incorporation also fail to show that they fail to meet clearly valid necessary conditions. Further progress on this issue awaits clarification (...) of difficult normative, conceptual, and metaphysical questions about the possible boundaries of a person’s body. Rather than relying solely on incorporation arguments, we propose an argument against reallocation from widely accepted anti-discrimination principles. Possession of a personal ventilator is an obvious marker of disability identity; thus, reallocating ventilators from those that already possess them discriminates on the basis of a stigmatized trait – a paradigm case of presumptively wrongful discrimination. This discrimination claim, taken together with uncertainty about the bodily status of ventilators, yields a strong presumption against personal ventilator reallocation. (shrink)

abstract Some day, perhaps soon, we may have genetic enhancements enabling us to conquer aging. Should we do so, if we can? I believe the topic is both interesting and important, and that it behoves us to think about it. Doing so may yield important insights about what we do care about, what we should care about, and how we should seek to live our lives, both individually and collectively. My central question is this: Is living longer, living better? My (...) paper does not offer a sustained argument for a single, considered, thesis. Rather, it offers a number of snippets of often-unconnected thoughts relevant to the issues my question raises. The paper contains seven sections. Part one is introductory. Part two comments on some current longevity research. Part three indicates the attitudes towards death and science with which I approach these questions. Parts four and five, respectively, discuss some worries about immortality raised by Leon Kass and Bernard Williams. Part six points to some practical, social, and moral concerns that might arise if society's members lived super long lives. Part seven concludes by suggesting that we should favour living well over living longer, and ongoing reproduction over immortality; correspondingly, I suggest that we should think long and hard before proceeding with certain lines of longevity research. (shrink)

This paper develops and draws the consequences of an etiological analysis of goal-directedness modeled on one that functions centrally in Charles Taylor's work on action. The author first presents, criticizes, and modifies Taylor's formulation, and then shows his modified formulation accounts easily for much of the fine-structure of teleological concepts and conceptualizations. Throughout, the author is at pains to show that teleological explanations are orthodox from an empiricist's point of view: they require nothing novel methodologically.

Being a patient and living a life -- Clinical space and traits of healing -- False starts and frequent failures -- Three journeys : A.'Ibuprofen and love', B. 'Staying tuned up', C. 'We all want the same things' -- Being a patient : the moral field -- Rethinking healthcare ethics : the patient's moral authority.

The Covid‐19 pandemic has concentrated bioethics attention on the “lifeboat ethics” of rationing and fair allocation of scarce medical resources, such as testing, intensive care unit beds, and ventilators. This focus drives ethics resources away from persistent and systemic problems—in particular, the structural injustices that give rise to health disparities affecting disadvantaged communities of color. Bioethics, long allied with academic medicine and highly attentive to individual decision‐making, has largely neglected its responsibility to address these difficult “upstream” issues. It is time (...) to broaden our teaching, research, and practice to match the breadth of the field in order to help address these significant societal inequities and unmet health needs. (shrink)

We recall the characterisation of positive definite polynomial functions over a real closed ring due to Dickmann, and give a new proof of this result, based upon ideas of Abraham Robinson. In addition we isolate the class of convexly ordered valuation rings for which this characterisation holds.

"This book maps the moral terrain in the grounded reality of human experience without relying on theories or systems of ethics as the primary orienting strategy. Moral awareness needs first to be appreciated for what it is before it is made to conform to theories or systems. And moral consciousness is not a steady or stable set of perceptions; as we change so do the moral challenges that most concern us"--.

In I. Kecskes & L. Horn (eds.) Explorations in Pragmatics: Linguistic, Cognitive, and Interculural Aspects. Mouton: 39-69.

Much has been written about the importance of narrative in teaching ethics and humanities to medical students and residents, as well as the value of narratives in clinical care. Relatively little has been said about the essential role of narrative in bioethics consultations. For most consults, the interpretation of narratives is the central moral feature, and the ethics consultant is inevitably one of the narrators. In a recent consult in which I participated, at least three narratives were in play. The (...) medical record itself was a narrative, or really, a variety of narratives. A second distinct narrative was the story of why this case had come to be categorized as an ethical concern for the medical team. A third narrative was the tentative sketch running through my mind as a consultant‐partly factual, partly anticipatory and conjectural, inevitably personal‐about what was going on here. (shrink)

In March 1996, the General Accounting Office (GAO) issued the reportScientific Research: Continued Vigilance Critical to Protecting Human Subjects.It stated that “an inherent conflict of interest exists when physician-researchers include their patients in research protocols. If the physicians do not clearly distinguish between research and treatment in their attempt to inform subjects, the possible benefits of a study can be overemphasized and the risks minimized.” The report also acknowledged that “the line between research and treatment is not always cleartoclinicians. Controversy (...) exists regarding whether certain medical procedures should be categorized as research.”This problem currently plagues gene transfer research. A few months prior to the GAO report, an ad hoc committee appointed by National Institutes of Health (NIH) Director Harold Varmus expressed similar concerns in its assessment of NIH investment in research on gene therapy. (shrink)

In March 1996, the General Accounting Office (GAO) issued the reportScientific Research: Continued Vigilance Critical to Protecting Human Subjects.It stated that “an inherent conflict of interest exists when physician-researchers include their patients in research protocols. If the physicians do not clearly distinguish between research and treatment in their attempt to inform subjects, the possible benefits of a study can be overemphasized and the risks minimized.” The report also acknowledged that “the line between research and treatment is not always cleartoclinicians. Controversy (...) exists regarding whether certain medical procedures should be categorized as research.”This problem currently plagues gene transfer research. A few months prior to the GAO report, an ad hoc committee appointed by National Institutes of Health (NIH) Director Harold Varmus expressed similar concerns in its assessment of NIH investment in research on gene therapy. (shrink)

In a recent article in The Journal of Clinical Ethics, David Wendler argues that worries about the therapeutic misconception (TM) are not only misconceived, but detract from the larger agenda of a proper informed consent for subjects involved in clinical research. By contrast, we argue that Wendler mischaracterizes those who support TM research, and that his arguments are fragmentary, often illogical, and neglect a critical difference between clinical care and clinical research. A clear explanation about the chief aim of research (...) is, in fact, what gives the other elements in a consent process their meaning. We argue that informed consent must be both trial-specific and context-sensitive, and that concern about the TM is needed now more than ever. (shrink)

In March 1996, the General Accounting Office issued the report Scientific Research: Continued Vigilance Critical to Protecting Human Subjects. It stated that “an inherent conflict of interest exists when physician-researchers include their patients in research protocols. If the physicians do not clearly distinguish between research and treatment in their attempt to inform subjects, the possible benefits of a study can be overemphasized and the risks minimized.” The report also acknowledged that “the line between research and treatment is not always clear (...) to clinicians. Controversy exists regarding whether certain medical procedures should be categorized as research.”This problem currently plagues gene transfer research. A few months prior to the GAO report, an ad hoc committee appointed by National Institutes of Health Director Harold Varmus expressed similar concerns in its assessment of NIH investment in research on gene therapy. (shrink)