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)

Endochondral bone formation can take place in the embryo, during fracture healing, or in postnatal animals after induction by implanted demineralized bone matrix. This matrix‐induced bone formation recapitulates the embryonic sequence of bone formation morphologically and biochemically. The steps in bone formation in both systems include differentiation of cartilage from mesenchyme, cartilage maturation, invasion of the cartilage by blood vessels and marrow precursors, and formation of bone and bone marrow. Recently, bone inductive molecules from demineralized bone matrix have been purified, (...) sequenced and produced as recombinant proteins. While there are similarities between bone development in the embryo and that after induction by these purified molecules, the molecules responsible for bone induction in the embryo have not yet been defined. Because of similarities between the two methods of bone formation, studies of Bone induction by demineralized bone matrix may help to elucidate mechanisms of embryonic bone induction. (shrink)

This paper aims, firstly, to bridge debates on human rights and Transnational Corporations within practical philosophy and those within the business and human rights literature and, secondly, to determine the extent to which human rights duties can be assigned to TNCs. To justifiably assign human rights duties to TNCs, it is argued that these duties need to be grounded in moral theory. Through assessment of two approaches from practical philosophy, it is argued that positive duties cannot be assigned to TNCs (...) because their bindingness cannot be grounded in moral theory. A positive argument is introduced to interpret TNCs’ human rights duties as corresponding to virtues rather than rights. Though such duties are indeterminate regarding what constitutes adequate performance, they can be made more determinate through legal instruments outside of positive human rights law. An approach is introduced exemplifying how such approaches can achieve the end of TNCs compliance with human rights norms. (shrink)

Biodefense and emerging infectious disease animal research aims to avoid or ameliorate human disease, suffering, and death arising, or potentially arising, from natural outbreaks or intentional deployment of some of the world’s most dreaded pathogens. Top priority research goals include finding vaccines to prevent, diagnostic tools to detect, and medicines for smallpox, plague, ebola, anthrax, tularemia, and viral hemorrhagic fevers, among many other pathogens (National Institute of Allergy and Infectious Diseases [NIAID] priority pathogens). To this end, increased funding for conducting (...) research, developing research facilities, and purchasing (stockpiling) developed vaccines, diagnostic tools, and therapeutics .. (shrink)

In this article, we query binaries of mobility and immobility in language studies via an empirical focus on language/social practices in a site that bridges the global North and global South. To do so, we work from a Southern praxis perspective to analyze discourses/knowledges informing the performance of accounts from Cambodian men, interviewed about transactional same-sex relationship practices between (ostensibly immobile) local men and (ostensibly mobile) male tourists to Cambodia from the global North. The analysis focuses on a process in (...) which participants’ chronotopic awareness of language shapes a negotiation of power, knowledge, and action with respect to these relationships. Encompassing the discursive positioning of selves and others through the deployment of relevant and affective chronotopes, the talk from these Cambodian men allows us to challenge assumptions about (im)mobility, awareness, agency, sexuality, and power, and demonstrate how these are accessed in multiple ways at this site of North/South contact. (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 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)

In some practical uncertain situations decision makers are presented with described events that are out of sequence when having to make a causal attribution. A theoretical perspective concerning the causal coherence of the explanation is developed to predict the effect of this on causal attribution. Three experiments investigated the effect on causal judgement when the described order of events did not correspond to their causal order. Participants had to judge the relative probability of two possible causes of an outcome in (...) scenarios in which presentation order varied. All three experiments found that there was a preference to judge that the cause associated with events described in causal order was more responsible for the outcome when events associated with one cause were interleaved in their presentation order with those from a second cause. This occurred when there was a strong causal relationship between events. The results were consistent with the causal coherence explanation. (shrink)

CHAPTER I THE FRAMEWORK OF SELF-PERFECTION 1. Buddhism and Ethics Anyone who has read even a very little in the early Buddhist Scriptures is aware that from ...

"The fixed person for fixed duties, who in older societies was such a godsend, in the future ill be a public danger." Twenty years ago, a single legal metaphor accurately captured the role that American society accorded to physicians. The physician was "c- tain of the ship." Physicians were in charge of the clinic, the Operating room, and the health care team, responsible - and held accountabl- for all that happened within the scope of their supervision. This grant of responsibility (...) carried with it a corresponding grant of authority; like the ship's captain, the physician was answerable to no one regarding the practice of his art. However compelling the metaphor, few would disagree that the mandate accorded to the medical profession by society is changing. As a result of pressures from a number of diverse directions - including technological advances, the development of new health professionals, changes in health care financing and delivery, the recent emphasis on consumer choice and patients' rights - what our society expects phy- cians to do and to be is different now. The purpose of this volume is to examine and evaluate the conceptual foundations and the moral imp- cations of that difference. Each of the twelve essays of this volume assesses the current and future validity of the "captain of the ship" metaphor from a different perspective. The essays are grouped into four sections. In Section I, Russell Maulitz explores the physician's role historically. (shrink)

Learners exposed to an artificial language recognize its abstract structural regularities when instantiated in a novel vocabulary (e.g., Gómez, Gerken, & Schvaneveldt, 2000; Tunney & Altmann, 2001). We asked whether such sensitivity accelerates subsequent learning, and enables acquisition of more complex structure. In Experiment 1, pre-exposure to a category-induction language of the form aX bY sped subsequent learning when the language is instantiated in a different vocabulary. In Experiment 2, while naíve learners did not acquire an acX bcY language, in (...) which aX and bY co-occurrence regularities were separated by a c-element, prior experience with an aX bY language provided some benefit. In Experiment 3 we replicated this finding with a 24-hour delay between learning phases, and controlled for prior experience with the aX bY language's prosodic and phonological characteristics. These findings suggest that learners, and the structure they can acquire, change as a function of experience. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. These factors include the short-term and (...) long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. These factors include the short-term and (...) long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. These factors include the short-term and (...) long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. These factors include the short-term and (...) long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

Repetitive thinking predicts and maintains depression and anxiety, yet the role of RT in the perinatal context has been under-researched. Further, the content and themes that emerge during RT in the perinatal period have been minimally investigated. We recruited an online community sample of women who had their first baby within the past 12 months. Participants completed a battery of self-report questionnaires which included four open-ended questions about the content of their RT. Responses to the latter were analyzed using an (...) inductive thematic analysis approach. Participants reported RT about a range of unexpected emotional responses to becoming a new mother, impact on their sleep and cognitive functioning, as well as the impact on their identity, sense of self, lifestyle, achievements, and ability to function. RT was commonly experienced in first-time mothers, and the themes that emerged conveyed an overall sense of discrepancy between expectations and reality, as well as adjustment to profound change. By providing insight into the content of RT in new mothers, the findings of our study have scope to inform the content of interventions that seek to prevent and treat postnatal mental health problems, particularly those which target key psychological processes such as RT. (shrink)

In this exploratory paper, we investigate the extension of Haidt’s :814–834, 2001, The righteous mind: Why good people are divided by politics and religion, 2012) Moral foundations theory, operationalized as the MFQ30 questionnaire, from a sample of the general public across many countries to a sample of business students. MFT posits that people rely on five major concerns, or foundations, when making moral judgments. The five concerns are care/harm, fairness/cheating, loyalty/betrayal, respect/authority, and purity/degradation. In addition, Haidt suggests that intuition, rather (...) than reasoning, leads to moral judgment. We replicate Haidt’s measurement model and find that the measurement model based on our sample is consistent. This indicates support for MFT. Further, we find structural differences in the measurement model between the genders and between areas of study. Our findings suggest that all students in the sample focus substantially on the fairness foundation. Ethics education and research may seek to expand the number of moral foundations individuals consider when discerning whether something is right or wrong. (shrink)

Background Investigative genetic genealogy (IGG) is a technique that involves uploading genotypes developed from perpetrator DNA left at a crime scene, or DNA from unidentified remains, to public genetic genealogy databases to identify genetic relatives and, through the creation of a family tree, the individual who was the source of the DNA. As policymakers demonstrate interest in regulating IGG, it is important to understand public perspectives on IGG to determine whether proposed policies are aligned with public attitudes.Methods We conducted eight (...) focus groups with members of the public (N = 72), sampled from four geographically diverse US regions, to explore general attitudes and perspectives regarding aspects of IGG practices, applications, and policies. Five major topics were explored in each focus group: when IGG should be used; who should perform IGG; how to approach consent for genetic database users; what systems of oversight should govern IGG practitioners; and whether to notify database users if their data are involved in law enforcement (LE) matching.Results Participants were supportive of IGG in most scenarios, especially for cold and violent cases. The favorable attitudes toward IGG were, however, tempered by distrust of law enforcement among some participants. All participants agreed that databases must inform users if IGG is allowed, but they did not agree on how individual database users should be allowed to opt out or whether to notify them if their data are involved in specific investigations. All participants agreed that IGG should be subject to some prescriptive guidelines, regulations, or accountability mechanisms.Conclusions These findings suggest broad public support for IGG, and interest in developing systems of accountability for its practice. Our study provides useful insight for policy makers, genomic database stewards, law enforcement, and other stakeholders in IGG’s practice, and suggests multiple directions for future research. (shrink)

The article "Picking and Choosing Among Phase I Trials", written by Jill A. Fisher, Torin Monahan and Rebecca L. Walker, was originally published Online First without Open Access. After publication in volume 16, issue 4, page 535-549 the author decided to opt for Open Choice and to make the article an Open Access publication.

The development of new effective but expensive medical treatments leads to discussions about whether and how such treatments should be funded in solidarity-based healthcare systems. Solidarity is often seen as an elusive concept; it appears to be used to refer to different sets of concerns, and its interrelations with the concept of justice are not well understood. This paper provides a conceptual analysis of the concept of solidarity as it is used in discussions on the allocation of healthcare resources and (...) the funding of expensive treatments. It contributes to the clarification of the concept of solidarity by identifying in the literature and discussing four uses of the concept: (1) assisting patients in need, (2) upholding the solidarity-based healthcare system, (3) willingness to contribute and (4) promoting equality. It distinguishes normative and descriptive uses of the concept and outlines the overlap and differences between solidarity and justice. Our analysis shows that the various uses of the concept of solidarity point to different, even conflicting, ethical stances on whether and how access to effective, expensive treatments should be provided. We conclude that the concept of solidarity has a role to play in discussions on the accessibility and funding of newly approved medical treatments. It requires, for instance, that healthcare policies promote and maintain both societal willingness to contribute to the care of others and the value of providing care to vulnerable patients through public funding. (shrink)

The development of new effective but expensive medical treatments leads to discussions about whether and how such treatments should be funded in solidarity-based healthcare systems. Solidarity is often seen as an elusive concept; it appears to be used to refer to different sets of concerns, and its interrelations with the concept of justice are not well understood. This paper provides a conceptual analysis of the concept of solidarity as it is used in discussions on the allocation of healthcare resources and (...) the funding of expensive treatments. It contributes to the clarification of the concept of solidarity by identifying in the literature and discussing four uses of the concept: (1) assisting patients in need, (2) upholding the solidarity-based healthcare system, (3) willingness to contribute and (4) promoting equality. It distinguishes normative and descriptive uses of the concept and outlines the overlap and differences between solidarity and justice. Our analysis shows that the various uses of the concept of solidarity point to different, even conflicting, ethical stances on whether and how access to effective, expensive treatments should be provided. We conclude that the concept of solidarity has a role to play in discussions on the accessibility and funding of newly approved medical treatments. It requires, for instance, that healthcare policies promote and maintain both societal willingness to contribute to the care of others and the value of providing care to vulnerable patients through public funding. (shrink)

Phase 1 healthy volunteer clinical trials—which financially compensate subjects in tests of drug toxicity levels and side effects—appear to place pressure on each joint of the moral framework justifying research. In this article, we review concerns about phase 1 trials as they have been framed in the bioethics literature, including undue inducement and coercion, unjust exploitation, and worries about compromised data validity. We then revisit these concerns in light of the lived experiences of serial participants who are income-dependent on phase (...) 1 trials. We show how participant experiences shift attention from discrete exchanges, behaviors, and events in the research enterprise to the ongoing and dynamic patterns of serial participation in which individual decision-making is embedded in collective social and economic conditions and shaped by institutional policies. We argue in particular for the ethical significance of structurally diminished voluntariness, routine powerlessness in setting the terms of exchange, and incentive structures that may promote pharmaceutical interests but encourage phase 1 healthy volunteers to skirt important rules. (shrink)

What makes for a good education? What does one need to count as well-educated? Knowledge, to be sure. But knowledge is easily forgotten, and today's knowledge may be obsolete tomorrow. Skills, particularly in critical thinking, are crucial as well. But absent the right motivation, graduates may fail to put their skills to good use. In this book, Nathan King argues that intellectual virtues-traits like curiosity, intellectual humility, honesty, intellectual courage, and open-mindedness-are central to any education worthy of the name. (...) Further, such virtues are crucial to our functioning well in everyday life, in areas as diverse as personal relationships, responsible citizenship, civil discourse, and personal success. Our struggles in these areas often result from a failure to think virtuously. Drawing upon recent work in philosophy and psychology, King paints a portrait of virtuous intellectual character-and of the vices such a character opposes. Filled with examples and applications, this book introduces readers to the intellectual virtues: what they are, why they matter, and how we can grow in them. (shrink)

Background The ethical use both of human and non-human animals in research is predicated on the assumption that it is of a high quality and its projected benefits are more significant than the risks and harms imposed on subjects. Yet questions remain about whether and how IRBs and IACUCs should consider the scientific value of proposed research studies.Methods We draw upon 45 interviews with IRB and IACUC members and researchers with oversight experience about their perceptions of their own roles in (...) reviewing the quality and value of scientific protocols. Interview transcripts were memoed to highlight specific findings, which were then used to identify key themes through an iterative process.Results IRB and IACUC members expressed broad trust in the need for and value of research, and they often assumed that protocols had social value or that prior review, especially when associated with funding, affirmed both the rigor and merit of those protocols. Some oversight members also took an explicit stance against scientific review by stating that such review is not within the regulatory mandates governing their parts in the oversight system. Yet other interviewees expressed uneasiness about the current paradigm for evaluating the quality and overall value of science, suggesting that IRB and IACUC members perceive gaps in the oversight systems.Conclusions These findings reveal many similarities in how IRB and IACUC members understand the roles and limitations of their respective oversight committees. We conclude with a discussion of how the lack of a clear mandate regarding scientific review within US federal regulations may undermine ethical engagement of whether human and animal research is scientifically justified, resulting in a “mission lapse” wherein no organizational body is clearly responsible for ensuring that the research being conducted has the potential to advance science and benefit society. (shrink)

Much recent work in virtue epistemology has focused on the analysis of such intellectual virtues as responsibility, conscientiousness, honesty, courage, open-mindedness, firmness, humility, charity, and wisdom. Absent from the literature is an extended examination of perseverance as an intellectual virtue. The present paper aims to fill this void. In Sect. 1, I clarify the concept of an intellectual virtue, and distinguish intellectual virtues from other personal characters and properties. In Sect. 2, I provide a conceptual analysis of intellectually virtuous perseverance (...) that places perseverance in opposition to its vice -counterparts, intransigence and irresolution. The virtue is a matter of continuing in one’s intellectual activities for an appropriate amount of time, in the pursuit of intellectual goods, despite obstacles to one’s attainment of those goods. In Sect. 3, I explore relations between intellectually virtuous perseverance and other intellectual virtues. I argue that such perseverance is necessary for the possession and exercise of several other intellectual virtues, including courage. These connections highlight the importance of perseverance in a comprehensive account of such virtues. (shrink)

Contemporary Western culture is experiencing a heightened awareness of religious diversity. This article surveys a range of possible responses to such diversity, and distinguishes between responses that concern the salvation or moral transformation of persons (soteriological views) and those that concern the alethic or epistemic status of religious beliefs (doctrinal views). After providing a brief taxonomy of these positions and their possible relations to one another, the article focuses primarily on competing views about the truth and rationality of religious beliefs (...) (e.g., pluralism, exclusivism, and skepticism). Here a heavy emphasis is placed on arguments for and against the rationality and moral propriety of retaining one's religious beliefs in the face of disagreement. The article surveys some of the more prominent arguments from the literature on this topic and closes with suggestions for further research. (shrink)