We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

Parental reading to young children is well-established as being positively associated with child cognitive development, particularly their language development. Research indicates that a particular, “intersubjective,” form of using books with children, “Dialogic Book-sharing”, is especially beneficial to infants and pre-school aged children, particularly when using picture books. The work on DBS to date has paid little attention to the theoretical and empirical underpinnings of the approach. Here, we address the question of what processes taking place during DBS confer benefits to (...) child development, and why these processes are beneficial. In a novel integration of evidence, ranging from non-human primate communication through iconic gestures and pointing, archaeological data on Pre-hominid and early human art, to experimental and naturalistic studies of infant attention, cognitive processing, and language, we argue that DBS entails core characteristics that make it a privileged intersubjective space for the promotion of child cognitive and language development. This analysis, together with the findings of DBS intervention studies, provides a powerful intellectual basis for the wide-scale promotion of DBS, especially in disadvantaged populations. (shrink)

This book collects some of the most exciting pioneering work in perceptual and cognitive psychology. The authors' quantitative approach to the study of mental images and their representation is clearly depicted in this invaluable volume of research which presents, interprets, evaluates, and extends their work. The selections are preceded by a thorough review of the history of their experiments, and all of the articles have been updated with reviews of the current literature. The book's first part focuses on mental rotation; (...) the second includes other, more complex transformations and sequences of transformations. A third part describes work on rotational transformations in the context of the perceptual illusion of &"apparent motion.&" Roger N. Shepard is Professor of Psychology, Stanford University. Lynn A. Cooper is Professor of Psychology, University of Arizona. A Bradford Book. (shrink)

The Plant Ontology (PO) is a community resource consisting of standardized terms, definitions, and logical relations describing plant structures and development stages, augmented by a large database of annotations from genomic and phenomic studies. This paper describes the structure of the ontology and the design principles we used in constructing PO terms for plant development stages. It also provides details of the methodology and rationale behind our revision and expansion of the PO to cover development stages for all plants, particularly (...) the land plants (bryophytes through angiosperms). As a case study to illustrate the general approach, we examine variation in gene expression across embryo development stages in Arabidopsis and maize, demonstrating how the PO can be used to compare patterns of expression across stages and in developmentally different species. Although many genes appear to be active throughout embryo development, we identified a small set of uniquely expressed genes for each stage of embryo development and also between the two species. Evaluating the different sets of genes expressed during embryo development in Arabidopsis or maize may inform future studies of the divergent developmental pathways observed in monocotyledonous versus dicotyledonous species. The PO and its annotation databasemake plant data for any species more discoverable and accessible through common formats, thus providing support for applications in plant pathology, image analysis, and comparative development and evolution. (shrink)

The relation between sex hormones and responses to partner infidelity was explored in two studies reported here. The first confirmed the standard sex difference in relationship jealousy, that males (n=133) are relatively more distressed by a partner’s sexual infidelity and females (n=159) by a partner’s emotional infidelity. The study also revealed that females using hormone-based birth control (n=61) tended more toward sexual jealousy than did other females, and reported more intense affective responses to partner infidelity (n=77). In study two, 47 (...) females were assessed four times across one month. Patterns of response to partner infidelity did not vary by week of menstrual cycle, but significant relations between salivary estradiol level and jealousy responses were obtained during the time of rising and high fertility risk. The implications, at least for females, are that any evolved psychological, affective, or behavioral dispositions regarding reproduction-related relationships are potentially moderated by estradiol, and that the use of synthetic hormones may disrupt this relation. (shrink)

International organisations are actors capable of bearing moral responsibilities and ought to be accountable for their failures in doing so. However, we should understand these responsibilities and respond to their failures in the light of fuller considerations about morality and the common good. The article argues that the international community should ensure victims are attended to, but also that defaulting institutions may themselves need rehabilitation for different kinds of international common purposes to be achievable. Further, the ways in which both (...) goals are agreed and undertaken must recognise multiple perspectives, else the possibilities for durable peaceable cooperation internationally will be damaged. Even in a world of plural views, we can find sufficient proximity on matters of ‘good’ and ‘bad’ to move toward further agreement. Drawing on Braithwaite, Rawls, and Sunstein, the article argues we should search out and build on such ‘islands of agreement’ on wrongs in international life and on mutually respectful ways of responding to them. (shrink)

This article revisits the "harmony doctrine" school of economics and its distinctive understanding of how ethics and economics intersect. Harmony doctrine thinkers staked out a “natural” understanding of economic phenomena that in many ways fused the classical political economy of Adam Smith with the earlier French Physiocratic School. Their metaphysically grounded interpretation was largely eclipsed by the developments of utilitarian and marginalist schools by the end of the nineteenth century. Yet harmony doctrine thinking adhered to a distinct understanding of how (...) ethical processes and outcomes play out within the economic sphere that has to date gone under examined by business ethicists. This paper outlines three characteristics of harmony doctrine views: the belief in curative forces empowered to "heal" the economic order, a dichotomous interpretation of the economic realm that distinguishes the “natural” from the “artificial,” and an overarching belief in a harmonious social order actualized by cooperative interdependencies within economic enterprises. Despite falling into obscurity in the economic discipline, all these ideas found new life in intellectual currents of organizational and political thought at the turn of the twentieth century. After surveying these historical developments, this article concludes by demonstrating how harmony doctrine thinking helpfully illuminates persisting metaphysical dimensions of contemporary business ethics. (shrink)

The primary purpose of this study was to examine the effects of perceptions of product harm and consumer vulnerability on ethical evaluations of target marketing strategies. We first established whether subjects are able to accurately judge the harmfulness of a product through labeling alone, and whether they could differentiate consumers who were more or less vulnerable. The results suggest that without the presence of a prime, subjects who depended on implicit memory or guess were able to detect differences in “sin” (...) and “non-sin” products and consumer vulnerability, but were far less likely to be able to distinguish among high and low levels of product harm and consumer vulnerability. The inability to accurately identify high and low levels of product harm and consumer vulnerability impacted their perceptions of the ethicality of target marketing strategies, such that only four out of 18 target marketing strategies were judged as unethical. Thus, our findings contradict previous research that found subjects judged many more of the integrated strategies as unethical [Smith and Cooper- Martin, J Market 61 1]. Our results suggest that assessing ethical evaluations of strategies varying in product harm, and consumer vulnerability may only be relevant if consumers can accurately identify product harm. (shrink)

Autobiographical memory plays a key role in psychological well-being, and the field has been investigated from multiple perspectives for over thirty years. One large body of research has examined the basic mechanisms and characteristics of autobiographical memory during general cognition, and another body has studied what happens to it during psychological disorders, and how psychological therapies targeting memory disturbances can improve psychological well-being. This edited collection reviews and integrates current theories on autobiographical memory when viewed in a clinical perspective. It (...) presents an overview of basic applied and clinical approaches to autobiographical memory, covering memory specificity, traumatic memories, involuntary and intrusive memories, and the role of self-identity. The book discusses a wide range of psychological disorders, including depression, post-traumatic stress disorder, borderline personality disorder and autism, and how they affect autobiographical memory. It will be of interest to students of psychology, clinicians and therapists alike. (shrink)

Unrealistic optimism is a bias that leads people to believe, with respect to a specific event or hazard, that they are more likely to experience positive outcomes and/or less likely to experience negative outcomes than similar others. The phenomenon has been seen in a range of health-related contexts—including when prospective participants are presented with the risks and benefits of participating in a clinical trial. In order to test for the prevalence of unrealistic optimism among participants of early-phase oncology trials, we (...) conducted a survey with patients over 18 years of age who were enrolled in a phase I, phase I/II, or phase II clinical cancer trial in the New York City area between August 2008 and October 2009. Participants in our study were asked to compare their own chances of experiencing a range of risks and benefits related to the trial they were enrolled in with the chances of the other trial participants. We found a significant optimistic bias in their responses. Respondents tended to overestimate the benefits of the trial they were enrolled in and underestimate its risks. In addition, we found no significant relationship between respondents’ understanding of the trial’s purpose and how susceptible they were to unrealistic optimism. Our findings suggest that improving the consent process for oncology studies requires more than addressing deficits in understanding. (shrink)

If people sometimes participate in research because of altruism—because they want to help in the search for treatments—should we revise our views about what kinds of experiments are ethical? If participants act out of altruism, we might let them accept greater risks than we would if they are motivated only by a desire for personal gain. But how can we know when participants are genuinely altruistic?

Drawing the line on physician assistance in physician-assisted death continues to be a contentious issue in many legal jurisdictions across the USA, Canada and Europe. PAD is a medical practice that occurs when physicians either prescribe or administer lethal medication to their patients. As more legal jurisdictions establish PAD for at least some class of patients, the question of the proper scope of this practice has become pressing. This paper presents an argument for restricting PAD to the terminally ill that (...) can be accepted by defenders as well as critics of PAD for the terminally ill. The argument appeals to fairness-based paternalism and the social meaning of medical practice. These two considerations interact in various ways, as the paper explains. The right way to think about the social meaning of medical practice bears on fair paternalism as it relates to PAD and vice versa. The paper contends that these considerations have substantial force when directed against proposals to extend PAD to non-terminally ill patients, but considerably less force when directed against PAD for the terminally ill. The paper pays special attention to the case of non-terminally ill patients who suffer from treatment-resistant depression, as these patients present a potentially strong case for extending PAD beyond the terminally ill. (shrink)

The allocation of vaccines and therapeutics for Covid‐19 obviously raises ethical questions, and physicians and ethicists have begun to address them. Writers have identified various criteria that should guide allocation decisions, but the criteria often conflict and need to be balanced against one another. This article proposes a model for thinking about how different considerations that are relevant to the distribution of vaccines and scarce treatments for Covid‐19 could be integrated into an allocation procedure. The model employs the construct of (...) a weighted lottery, which is a construct that has been employed in other contexts that involve the distribution of scarce resources. The article highlights the advantages of applying a weighted lottery to the Covid‐19 context and offers an illustration for how it might work in practice. The primary aim of the article is to articulate the structural features of a weighted lottery for this context and to bring out its advantages over other methods for allocating Covid‐19 medications. (shrink)

The term “exploitation” has gained wide currency in recent discussions of biomedical and research ethics. This is due in no small measure to the influence of Alan Wertheimer’s path-breaking work on the topic (Wertheimer 1999, 2011). Wertheimer presented a clear and compelling non-Marxist account of the concept of exploitation—one that stressed the connection between exploitation and unfair distributive outcomes. On this account, when one party exploits another, she takes advantage of the other to gain unfairly. A number of contemporary bioethicists (...) have accepted Wertheimer’s account of exploitation and have proceeded to apply it to a range of issues in research ethics (Hawkins and Emanuel 2008; Miller and Brody .. (shrink)

Recent years have witnessed a growing concern that terminally illpatients are needlessly suffering in the dying process. This has ledto demands that physicians become more attentive in the assessment ofsuffering and that they treat their patients as `whole persons.'' Forthe most part, these demands have not fallen on deaf ears. It is nowwidely accepted that the relief of suffering is one of the fundamentalgoals of medicine. Without question this is a positive development.However, while the importance of treating suffering has generally (...) beenacknowledged, insufficient attention has been paid to the question ofwhether different types of terminal suffering require differnt responsesfrom health care professionals. In this paper we introduce a distinctionbetween two types of suffering likely to be present at the end of life,and we argue that physicians must distinguish between these types if theyare to respond appropriately to the suffering of their terminally illpatients. After introducing this distinction and explaining its basis,we further argue that the distinction informs a (novel) principle ofproportionality, one that should guide physicians in balancing theircompeting obligations in responding to terminal suffering. As weexplain, this principle is justified by reference to the intereststerminally ill patients have in restoration, as well as in therelief of suffering, at the end of life. (shrink)

: Some commentators have recently proposed that "clinical equipoise," although widely accepted, is not necessary for morally acceptable research on human subjects. If this concept is rejected, however, we may find that trials not in the best medical interests of their subjects--bad deal trials--could be justified. To avoid exploiting participants, we must find a way to distribute the risks fairly, even if it means embracing radical changes in the way clinical research is conducted.

In this paper, we defend the ethics of clinical research against the charge of paternalism. We do so not by denying that the ethics of clinical research is paternalistic, but rather by defending the legitimacy of paternalism in this context. Our aim is not to defend any particular set of paternalistic restrictions, but rather to make a general case for the permissibility of paternalistic restrictions in this context. Specifically, we argue that there is no basic liberty-right to participate in clinical (...) research and that considerations of distributive fairness justify some paternalistic protections of research subjects. (shrink)

The ethical standards that regulate clinical research have multiple rationales. Among them is the need to protect potential subjects from making imprudent decisions, which extends beyond the soft paternalistic concern to protect people from making uninformed decisions to participate in trials. This article argues that a plausible risk/benefit restriction on clinical trials is presumptively justified by hard paternalism, which in turn is supported by a deeper fairness-based rationale. This presumptive case for hard paternalism in research is not defeated by the (...) alleged right to participate in clinical trials, by concerns about insult or status, by the need to conduct early phase trials that promise little to no benefit to participants, or by the recognition that some potential subjects are altruistically motivated. (shrink)

: "Clinical pragmatism" is an important new method of moral problem solving in clinical practice. This method draws on the pragmatic philosophy of John Dewey and recommends an experimental approach to solving moral problems in clinical practice. Although the method may shed some light on how clinicians and their patients ought to interact when moral problems are at hand, it nonetheless is deficient in a number of respects. Clinical pragmatism fails to explain adequately how moral problems can be solved experimentally, (...) it underestimates the relevance and importance of judgment in clinical ethics, and it presents a questionable account of the role that moral principles should play in moral problem solving. (shrink)

Ethical research on human subjects requires that subjects, if they have the capacity to do so, give free and informed consent to participate in the trials in which they are enrolled. This requirement, which is commonly referred to as the principle of informed consent, was prominently endorsed by the authors of the Belmont Report in 1978, and it remains widely accepted today. Yet while the principle of informed consent is by now almost universally accepted, the responsibilities that it imposes on (...) those who conduct research on human subjects is a more contentious matter. New challenges to securing informed consent have emerged since the publication of the Belmont Report, and responding to these challenges requires... (shrink)

Some commentators have recently proposed that “clinical equipoise,” although widely accepted, is not necessary for morally acceptable research on human subjects. If this concept is rejected, however, we may find that trials not in the best medical interests of their subjects—”bad deal trials”—could be justified. To avoid exploiting participants, we must find a way to distribute the risks fairly, even if it means embracing radical changes in the way clinical research is conducted.

The movement in bioethics toward disclosure of financial conflicts of interest is well and good, most of the time. But in some cases, disclosure is not only unnecessary but destructive. When bioethicists advance arguments whose premises and logical moves are open to scrutiny, disclosure—far from clearing the air of bias—introduces bias.

ABSTRACT When applying moral principles to concrete cases, we assume a background shared understanding of the boundaries of the persons to whom the principles apply. In most contexts, this assumption is unproblematic. However, in end‐of‐life contexts, when patients are receiving ‘artificial’ life‐support, judgments about where a person's self begins and ends can become controversial. To illustrate this possibility, this paper presents a case in which a decision must be made whether to deactivate a patient's pacemaker as a means to hasten (...) his death. After discussing some common moral principles that are often applied to resolve ethical problems at the end of life and after explaining why they are of no help here, the paper argues that the correct analysis of this case, and of cases of this sort, turns on considerations that relate to the constitution of the self. These considerations, the paper further argues, sometimes resist resolution. The constitution of the self is fixed in large measure by our concepts and social conventions, and these do not always provide determinate grounds for delimiting the boundaries of the self. (shrink)

We are currently in the midst of a revival of interest in thevirtues. A number of contemporary moral philosophers havedefended a virtue-based approach to ethics. But does thisrenewal of interest in the virtues have much to contributeto medical ethics and medical practice? This paper criticallydiscusses this question. It considers and rejects a number ofimportant arguments that purport to establish the significanceof the virtues for medical practice. Against these arguments,the paper seeks to show that while the virtues have a genuinerole to (...) play in medical ethics, it is a limited role, one thatis subordinate to the role that other moral concepts such asrules and principles play. (shrink)

We are currently in the midst of a revival of interest in thevirtues. A number of contemporary moral philosophers havedefended a virtue-based approach to ethics. But does thisrenewal of interest in the virtues have much to contributeto medical ethics and medical practice? This paper criticallydiscusses this question. It considers and rejects a number ofimportant arguments that purport to establish the significanceof the virtues for medical practice. Against these arguments,the paper seeks to show that while the virtues have a genuinerole to (...) play in medical ethics, it is a limited role, one thatis subordinate to the role that other moral concepts such asrules and principles play. (shrink)

In recent years, a number of writers have proposed voluntary stopping of eating and drinking as an alternative to physician-assisted suicide. This paper calls attention to and discusses some of the ethical complications that surround the practice of voluntary stopping of eating and drinking. The paper argues that voluntary stopping of eating and drinking raises very difficult ethical questions. These questions center on the moral responsibility of clinicians who care for the terminally ill as well as the nature and limits (...) of the authority they exercise over them. (shrink)

There is broad agreement among research ethicists that investigators have a duty to obtain the informed consent of all subjects who participate in their research trials. On a common view, the duty to obtain this informed consent follows from the need to respect persons and their autonomous decisions. However, the nature of informed consent and the demands it places on investigators are open to dispute and recently have been challenged. Respect for persons, it has been claimed, does not require investigators (...) to guarantee that the subjects enrolled in their trials comprehend the risk/benefit information disclosed to them or even that they appreciate the difference between research and therapy. According to this critique, the significance of defects in informed consent, like therapeutic misconception or unrealistic optimism, has been greatly exaggerated. This article reevaluates informed consent in clinical research in light of this critique. It not only rebuts the main points the critics raise, but also shows that other points they raise can be accepted by a doctrine of informed consent that resembles the common view in maintaining that autonomous authorization is central to informed consent. (shrink)

When patients enrolled in early‐phase cancer treatment trials are asked later to explain their decision to participate, they often reveal unrealistically high expectations for therapeutic benefit from participation. This phenomenon has given rise to a complex and ongoing debate over the quality and validity of informed consent to these trials. Bioethicists and researchers must better understand these expectations and why research participants so often have them. This article presents a new explanation for this phenomenon by drawing on social psychology research (...) on mindsets and, in particular, on a distinction between deliberative and implementation mindsets. (shrink)

Purpose Recent research has found unrealistic optimism among patient-subjects in early-phase oncology trials. Our aim was to investigate the cognitive and motivational factors that evoke this bias in this context. We expected perceptions of control to be a strong correlate of unrealistic optimism. Methods A study of patient-subjects enrolled in early-phase oncology trials was conducted at two sites in the USA. Respondents completed questionnaires designed to assess unrealistic optimism and several risk attribute variables that have been found to evoke the (...) bias in other contexts. Results One hundred and seventy-one patient-subjects agreed to be interviewed for our study. Significant levels of perceived controllability were found with respect to all nine research-related questions. Perceptions of control were found to predict unrealistic optimism. Two other risk attribute variables, awareness of indicators and mental image, were correlated with unrealistic optimism. However, in multivariate regression analysis, awareness and mental image dropped out of the model and perceived controllability was the only factor independently associated with unrealistic optimism. Conclusion Patient-subjects reported that they can, at least partially, control the benefits they receive from participating in an early-phase oncology trial. This sense of control may underlie unrealistic optimism about benefiting personally from trial participation. Effective interventions to counteract unrealistic optimism may need to address the psychological factors that give rise to distorted risk/benefit processing. (shrink)

Recent empirical work on the concept of intentionality suggests that people’s assessments of whether an action is intentional are subject to uncertainty. Some researchers have gone so far as to claim that different people employ different concepts of intentional action. These possibilities have motivated a good deal of work in the relatively new field of experimental philosophy. The findings from this empirical research may prove to be relevant to medical ethics. In this article, we address this issue head on. We (...) first describe a study we conducted on intention ascription. Drawing on recent work in experimental philosophy, we investigated the possibility that the ascription of intentions to clinical actors in clinical settings is influenced by prior judgments about the goodness or badness of the consequences of the action in question. Our study was modeled on experimental studies in other contexts that have shown that people, when presented with a range of scenarios, are more likely to classify a side effect of an action as intended if the side effect is negative or reflects poorly on the actor than if it is positive or reflects well on the actor. We investigated whether this asymmetry in intention ascriptions was also present among physicians who were asked to ascribe intentions to clinical actors in certain well-defined clinical scenarios. After describing the study and its results, we discuss its implications for medical ethics. (shrink)

The common variety of incandescent light bulb has been in use for over a century, and although perhaps manufactured by highly technological systems, it is not a "high tech" device. Light bulbs are also found in nearly every home and business in this country. Because of these characteristics, the light bulb lends itself to use as a symbol of material things in modem industrial culture.

This article critically analyzes the principle of beneficence and the principle of nonmaleficence in clinical medical ethics. It resists some recent skepticism about the principle of nonmaleficence, and then seeks to explain its role in medicine. The article proposes that the two principles are informed by different accounts of what is in the patient’s best interests. The principle of beneficence is tied to the patient’s best overall interests, whereas the principle of nonmaleficence is tied to the patient’s best medical interests (...) only. The article argues that the principle of nonmaleficence takes priority over the principle of beneficence in that it filters the treatment options that are appropriately subject to the principle of beneficence. Understanding how both principles can play an important role in medical practice, and how they relate when they come into conflict, can help clinicians to avoid certain mistakes in thinking about their duties to their patients. (shrink)

Informed consent is a central concept in the literature on the ethics of clinical care and human subjects research. There is a broad consensus that ethical practice in these domains requires the informed consent of patients and subjects. The requirements of informed consent in these domains, however, are matters of considerable controversy. Some argue that the requirements of informed consent have been inflated, others that they have not been taken seriously enough. This essay argues that both sides are partly right. (...) To advance this argument, the essay distinguishes a general doctrine of informed consent from what it characterizes as “models of informed consent.” A general doctrine articulates a set of requirements for informed consent and then adjusts these requirements to fit the context in which they are to be applied. In contrast, different models of informed consent impose different requirements in different contexts. The essay contends that different models of informed consent are needed for clinical care and clinical research. It outlines these two models, articulates the rationale for distinguishing them, and considers and rebuts the objection that clinical care and clinical research are too deeply intertwined in contemporary medicine for the models approach to apply to them. (shrink)

Death in the Clinic fills a gap in contemporary medical education by explicitly addressing the concrete clinical realities about death with which practitioners, patients, and their families continue to wrestle. Visit our website for sample chapters!