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)

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)

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.

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)

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)

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)

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)

In phase I clinical trials, healthy volunteers are dosed with investigational drugs and subjected to blood draws and other bodily monitoring procedures. In exchange, they are paid. Healthy volunteers are, in a very direct sense, selling access to their bodies for pharmaceutical companies and their associates to run drugs through. In his ethnographic study of socalled professional guinea pigs, Roberto Abadie writes, "Paid volunteers are well aware of the demand for an idealized, perfectly healthy volunteer. They also realize that their (...) body is a valued commodity in clinical trials research". It is perhaps surprising, then, that commodification is little discussed in the bioethics literature on phase I... (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)

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)

O’Loughlin and Thagard (2000) present a specific computational implementation of the idea that the problems encountered by a child with autism in classic False Belief tasks derive from a failure to maintain coherence among multiple propositions. They argue that this failure can be explained as a structural feature of a connectionist network attempting to maintain coherence. The current paper criticizes this implementation because it falsely predicts that the same children will have a parallel problem with the False Photographs task. The (...) fact that the content of representations makes a difference while the structure remains constant casts doubt upon their claim. (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)

Here we present and develop the hypothesis that the derepression of endogenous retrotransposable elements (RTEs) – “genomic parasites” – is an important and hitherto under‐unexplored molecular aging process that can potentially occur in most tissues. We further envision that the activation and continued presence of retrotransposition contribute to age‐associated tissue degeneration and pathology. Chromatin is a complex and dynamic structure that needs to be maintained in a functional state throughout our lifetime. Studies of diverse species have revealed that chromatin undergoes (...) extensive rearrangements during aging. Cellular senescence, an important component of mammalian aging, has recently been associated with decreased heterochromatinization of normally silenced regions of the genome. These changes lead to the expression of RTEs, culminating in their transposition. RTEs are common in all kingdoms of life, and comprise close to 50% of mammalian genomes. They are tightly controlled, as their activity is highly destabilizing and mutagenic to their resident genomes. (shrink)