Heterogeneity within MDD has hampered identification of biological markers (e.g., intermediate phenotypes, IPs) that might increase risk for the disorder or reflect closer links to the genes underlying the disease process. The newer characterizations of dimensions of MDD within Research Domain Criteria (RDoC) domains may align well with the goal of defining IPs. We compare a sample of 25 individuals with MDD compared to 29 age and education matched controls in multimodal assessment. The multimodal RDoC assessment included the primary IP (...) biomarker, positron emission tomography (PET) with a selective radiotracer for 5-HT1A ([11C]WAY-100635), as well as event-related functional MRI with a Go/No-go task targeting the Cognitive Control network, neuropsychological assessment of affective perception, negative memory bias and Cognitive Control domains. There was also an exploratory genetic analysis with the serotonin transporter (5-HTTLPR) and monamine oxidase A (MAO-A) genes. In regression analyses, lower 5-HT1A binding potential (BP) in the MDD group was related to diminished engagement of the Cognitive Control network, slowed resolution of interfering cognitive stimuli, one element of Cognitive Control. In contrast, higher/normative levels of 5-HT1A BP in MDD (only) was related to a substantial memory bias toward negative information, but intact resolution of interfering cognitive stimuli and greater engagement of Cognitive Control circuitry. The serotonin transporter risk allele was associated with lower 1a BP and the corresponding imaging and cognitive IPs in MDD. Lowered 5HT 1a BP was present in half of the MDD group relative to the control group. Lowered 5HT 1a BP may represent a subtype including decreased engagement of Cognitive Control network and impaired resolution of interfering cognitive stimuli. Future investigations might link lowered 1a BP to neurobiological pathways and markers, as well as probing subtype-specific treatment targets. (shrink)

Genomic research results and incidental findings with health implications for a research participant are of potential interest not only to the participant, but also to the participant's family. Yet investigators lack guidance on return of results to relatives, including after the participant's death. In this paper, a national working group offers consensus analysis and recommendations, including an ethical framework to guide investigators in managing this challenging issue, before and after the participant's death.

In 2004, the United States Sentencing Commission amended the Federal Sentencing Guidelines to allow firms that create “effective compliance and ethics programs” to receive better treatment if prosecuted for fraud. Effective compliance and ethics, however, appear to be limited to activities focused on complying with the firms’ internal legal and ethical standards. We explored a potential connection between the firms’ external corporate social responsibility (CSR) behaviors and internal compliance: Is there an organizationally valid relationship between these two firm activities? That (...) is, when organizations demonstrate CSR with behaviors external to the firm, such as employee volunteerism, are their employees more likely to demonstrate uncompromised legal and ethical compliance behavior internally? We collected data from 164 working professionals enrolled in a top-tier MBA program in the southeastern United States regarding their employer-sponsored volunteer activities and their intentions to comply in various organizational compliance vignettes. We found that employer-sponsored volunteerism is associated with uncompromised compliance choices in one of the three vignettes. This finding indicates preliminary support for further inquiry into the relationship within the firm between external CSR behaviors and policies regarding organizational compliance. Post hoc analyses suggest that employer-sponsored volunteerism is strongly associated with a positive organizational identity, but organizational identity is not associated with the significant compliance vignette. This evidence suggests that the underlying mechanism that connects external CSR behaviors and internal compliance intentions is complex and requires future study. (shrink)

Health care reform proposals threaten to exacerbate tensions physicians already face in trying to balance traditional duties to individual patients against increasing pressure to serve broader societal and institutional goals. To cope with reform, medical ethics must clarify physicians' moral obligations, change existing ethical codes, and develop an ethics of institutions.

The current explosion of genetic knowledge and the rapid proliferation of genetic tests has rightly provoked concern that we are approaching a future in which people will be labeled and disadvantaged based on genetic information. Indeed, some have already suffered harm, including denial of health insurance. This concern has prompted an outpouring of analysis. Yet almost all of it approaches the problem of genetic disadvantage under the rubric of “genetic discrimination.”This rubric is woefully inadequate to the task at hand. It (...) ignores years of commentary on race and gender demonstrating the limits of antidiscrimination analysis as an analytic framework and corrective tool. Too much discussion of genetic disadvantage proceeds as if scholars of race and gender had not spent decades critiquing and developing antidiscrimination theory.Indeed, there are multiple links among race, gender, and genetics. Dorothy Roberts has discussed the historical links between racism and genetics, while she and others have begun to map connections between gender and genetics. (shrink)

Developing ethical standards for clinical use of large-scale genome and exome sequencing has proven challenging, in part due to the inevitability of incidental or secondary findings. Policy of the American College of Medical Genetics and Genomics has evolved but remains problematic. In 2013, ACMG issued policy recommending mandatory analysis of 56 extra genes whenever sequencing was ordered for any indication, in order to ascertain positive findings in pathogenic and actionable genes. Widespread objection yielded a 2014 amendment allowing patients to opt-out (...) from analysis of the extra genes. In 2015, ACMG published the amended policy, providing that patients could opt out of the full set of extra genes, but not a subset. In 2016, ACMG enlarged the set and indicated planned expansion of the roster of extra genes to include pharmacogenetic findings. ACMG policy does not protect the respect for patient choice that prevails in other domains of clinical medicine, where informed consent allows patients to opt in to desired testing. By creating an expanding domain of genomic testing that will be routinely conducted unless patients reject the entire set of extra tests, ACMG creates an exceptional domain clinical practice that is not supported by ethics or science. (shrink)

The everyday experience of someone, or something, getting in one’s face reveals a depth that is the difference between a world that is intrusive and a world that is respectful. This depth, I argue, should be conceived, not in feet and inches, but in terms of violation and honor. I explore three factors that contribute to this depth’s emergence. First, I examine our body’s capacity, at the level of sense experience, for giving the world a figure/ground structure; this structure insures (...) that most of the world we are in constant contact with, nonetheless, keeps its distance as background. I demonstrate the importance of this figure/ground structure to the depth of our world by considering the experience of people with autism; for those with autism, this structure seems to be, if not entirely missing, at least substantially less robust than our own. Next, I examine our body’s ability, at the level of more personal experience, to handle the world; our handling of the world, which rests on the acquisition of specific skills, transforms things that could easily assault us into the usually motionless objects we tend to take for granted. I demonstrate the importance of these skills to the depth of our world by considering the experience of Gregg Mozgalla; until recently, Mozgalla, who has cerebral palsy, could only lurch, rather than walk, through the world. Finally, I draw on the work of the artist Mierle Ukeles to examine the maintenance work that other people, at a broader social level, perform; other’s maintenance work keeps in good condition a world that, by falling into bad condition, could easily intrude on us. (shrink)

Kant objects on principle to any duty of moral self-perfection that would aim at the moral self-perfection of another person. Yet, despite the apparent barrier posed by the introspective technique of self-perfecting effort, I argue that such a duty is both possible and desirable as a part of moral friendship. Through mutual sincere efforts at self-disclosure, we escape the prison of mutual distrust which otherwise characterizes social life and consolidate the very sincerity necessary for moral improvement.

Participant-driven research is a burgeoning domain of research innovation, often facilitated by mobile technologies. Return of results and data are common hallmarks, grounded in transparency and data democracy. PDR has much to teach traditional research about these practices and successful engagement. Recommendations calling for new state laws governing research with mHealth modalities common in PDR and federal creation of review mechanisms, threaten to stifle valuable participant-driven innovation, including in return of results.

The phenotype of some spontaneous mutations in Drosophila can be modified by mutations at unlinked loci. The affected alleles are caused by the insertion of retroviral transposable elements. The idiosyncratic functional and structural properties of these elements play a key role in determining the expression characteristics of the genes into which they are inserted. These phenotypes are reversed or intensified by the allelic state of suppressor and enhancer loci through changes in the transcriptional properties of the transposable elements.

This study investigates the effectiveness of pedagogical practices used to teach business ethics. The business community has greatly increased its demands for better ethics education in business programs. Educators have generally agreed that the ethical principles of business people have declined. It is important, then, to examine how common methods of instruction used in business ethics could contribute to the development of higher levels of moral judgment competence for students. To determine the effectiveness of these methods, moral judgment competence levels (...) for undergraduate and graduate students from three institutions were measured and compared based upon the pedagogical method used in a business class. Significant differences were found for moral reasoning and moral competence scores depending on the method used for ethics instruction. Students in classes with more highly integrated ethics coverage scored higher in moral reasoning and moral competence. (shrink)

Genetic testing poses fundamental questions for insurance. Testing can predict a low probability of future illness and disability, which can help promote the insurability of individuals with a family history of genetic risk, but it can also invite insurers to reject applicants, increase premiums, exclude people with certain illnesses and disabilities, and otherwise adjust the underwriting processes for individuals with certain genotypes. In the workplace, these issues may cause employers who offer or pay for insurance to alter their hiring behavior, (...) either by selecting those with desirable genetic makeup or rejecting, dismissing, or reassigning those who carry an unwanted risk, ultimately threatening employability and the safety net that insurance is intended to provide. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Hume Studies Volume XXIII, Number 2, November 1997, pp. 195-212 The Moral Self and the Indirect Passions SUSAN M. PURVIANCE David Hume1 and Immanuel Kant are celebrated for their clear-headed rejection of dogmatic metaphysics, Hume for rejecting traditional metaphysical positions on cause and effect, substance, and personal identity, Kant for rejecting all judgments of experience regarding the ultimate ground of objects and their relations, not just judgments of (...) cause and substantiality. Nevertheless, each argues that practical activity is not compromised by the rejection of metaphysical claims that others had taken to be crucial. Kant and Hume thought that political and moral life did not depend upon theoretical knowlege of the nature of the self, free will, or knowledge of the true motives of actions or the character of the agent. Because the grounds of morality and politics were too important to leave to the mercies of speculative metaphysics, each moved their foundations to higher ground, insulating the grounds of practical activity from the threat of metaphysical turmoil and skepticism. Contemporary philosophers have generally followed Hume and Kant in this regard, but often select very different strategies. Some think that the best way to avoid the problems associated with contemporary scientific ontologies is to separate ethics from the factual domain entirely. Some give moral and political language a noncognitivist interpretation, and others have interpreted values as a projection of the passions and affections of the subject or as the constructions of suitably situated practical reasoners.2 At the same time there has been a resurgence of interest in moral realism. Moral realists think that the objectivity of moral discourse, and hence the Susan M. Purviance is at the Department of Philosophy, The University of Toledo, Toledo OH 43606-3390 USA. 196 Susan M. Purviance possibility of moral truth, depend upon the existence of moral facts.3 Moral realists have tended to concentrate on the role of facts in establishing the truth of general moral principles, or the Tightness or moral value of particular individual actions. For moral realists, moral facts are the states of affairs that make general moral principles or particular moral judgments true. Whether these facts are of a naturalistic sort or not, whether they are literally on a par with natural facts, or whether they simply play the same role in practical knowledge that natural facts play in theoretical knowledge, is an open question. Moral realists often are naturalists, like David O. Brink and Jonathan Dancy, but they may be nonnaturalists, like G. E. Moore.4 Ethical naturalism accounts for moral motivation and the cultivation of good character in terms of moral qualities, and many hope to ground it in (or at least show that it is compatible with) the scientific understanding of objects and their relations and qualities. Naturalism is only one option, but realism has received support because it is not clear that antirealists have developed a convincing alternative to the grounding of concepts of moral agency and moral judgment in some sort of moral facts. Questions abound about what it means to ascribe responsibility to a moral self and how we can defend a notion of enduring character. Although moral realists have paid less attention to the ontological status of virtues and character traits than to moral principles, their status is equally important. Here the concern is with the sort of metaphysics of the self thought to be necessary to account for moral agency, responsibility, praise, and blame. I shall argue that there is a class of moral facts that justify or perhaps merely vindicate the ascription of moral powers to agents, and that these are the sorts of facts another sort of theorist is interested in, whereas the states of affairs that make moral judgments true are the sorts of facts that moral realists have been interested in. In order to distinguish this use of moral facts I shall call this sort of theory a Fact of Agency Theory, and it is a version of this theory that can be found in Hume's discussion of the problem of the self and the indirect passions. A realist metaphysics of morals needs to address two questions, the question of the reality of the... (shrink)

_Hegel or Spinoza_ is the first English-language translation of the modern classic _Hegel ou Spinoza._ Published in French in 1979, it has been widely influential, particularly in the work of the philosophers Alain Badiou, Antonio Negri, and Gilles Deleuze. _Hegel or Spinoza_ is a surgically precise interrogation of the points of misreading of Spinoza by Hegel. Pierre Macherey explains the necessity of Hegel’s misreading in the kernel of thought that is “indigestible” for Hegel, which makes the Spinozist system move in (...) a way that Hegel cannot grasp. In doing so, Macherey exposes the limited and situated truth of Hegel’s perspective—which reveals more about Hegel himself than about his object of analysis. Against Hegel’s characterization of Spinoza’s work as immobile, Macherey offers a lively alternative that upsets the accepted historical progression of philosophical knowledge. He finds in Spinoza an immanent philosophy that is not subordinated to the guarantee of an a priori truth. Not simply authorizing a particular reading—a “good” Spinoza against a “bad” Hegel—_Hegel or Spinoza_ initiates an encounter that produces a new understanding, a common truth that emerges in the interval that separates the two. (shrink)

This collection of essays examines how philosophers in the Western tradition have viewed and written about children through the ages. (Philosophy).

Using the infamous research studies in Tuskegee and Guatemala, the article examines the difference between victims and bystanders. The victims can include families, sexual partners, and children not just the participants. There are also the bystanders in the populations who are affected, even vaguely, decades after the initial studies took place. Differing reparations for victims and bystanders through lawsuits and historical acknowledgments has to be part of broader discussions of historical justice, and the weighing of the impact of racism and (...) imperial research endeavors. (shrink)

This study examined self-recognition processing in both the auditory and visual modalities by determining how comparable hearing a recording of one’s own voice was to seeing photograph of one’s own face. We also investigated whether the simultaneous presentation of auditory and visual self-stimuli would either facilitate or inhibit self-identification. Ninety-one participants completed reaction-time tasks of self-recognition when presented with their own faces, own voices, and combinations of the two. Reaction time and errors made when responding with both the right and (...) left hand were recorded to determine if there were lateralization effects on these tasks. Our findings showed that visual self-recognition for facial photographs appears to be superior to auditory self-recognition for voice recordings. Furthermore, a combined presentation of one’s own face and voice appeared to inhibit rather than facilitate self-recognition and there was a left-hand advantage for reaction time on the combined-presentation tasks. (shrink)

Human genomics is a translational field spanning research, clinical care, public health, and direct-to-consumer testing. However, law differs across these domains on issues including liability, consent, promoting quality of analysis and interpretation, and safeguarding privacy. Genomic activities crossing domains can thus encounter confusion and conflicts among these approaches. This paper suggests how to resolve these conflicts while protecting the rights and interests of individuals sequenced. Translational genomics requires this more translational approach to law.

The problem of incidental findings in human subjects research—findings of potential health importance to the research participant that the researcher stumbles upon while pursuing the aims of the research—may at first seem of minor significance. The number and potential gravity of incidental findings force researchers to face difficult questions. The most fundamental of these is whether researchers have any duty to identify, evaluate, and disclose these findings to the research participant. This is a profound challenge to the structure of bioethics (...) and health law. Both fields approach the world of research and the world of medical care very differently. Neuroimaging research can yield a high number of incidental findings. Bioethics and health law must now reconstitute the traditional vision of researcher duties to bring the researcher back into a relationship with the research participant. (shrink)

Mouse models of human genetic disorders provide a valuable resource for investigating the pathogenesis of genetic disease and for testing potential therapies. The high degree of resolution of linkage mapping in the mouse allows mutant phenotypes to be mapped precisely which, combined with the accurate definition of areas of homology between the mouse and human genomes, greatly facilitates the identification of mouse models. We describe here mouse models of human single gene disorders dividing them into three categories depending on the (...) information available; phenotypic similarities, comparative mapping and identification of the underlying genetic lesion. (shrink)

Oversight of human gene transfer research presents an important model with potential application to oversight of nanobiology research on human participants. Gene therapy oversight adds centralized federal review at the National Institutes of Health's Office of Biotechnology Activities and its Recombinant DNA Advisory Committee to standard oversight of human subjects research at the researcher's institution and at the federal level by the Office for Human Research Protections. The Food and Drug Administration's Center for Biologics Evaluation and Research oversees human gene (...) transfer research in parallel, including approval of protocols and regulation of products. This article traces the evolution of this dual oversight system; describes how the system is already addressing nanobiotechnology in gene transfer: evaluates gene therapy oversight based on public opinion, the literature, and preliminary expert elicitation; and offers lessons of the gene therapy oversight experience for oversight of nanobiotechnology. (shrink)

Is the lower rate of kidney transplantation into African Americans medically and ethically justifiable? Or is it a form of racial discrimi nation comparable to if not worse than denial of employment opportunities, housing, and educational opportunities? This essay focusses on the medical problems associated with matching antigens in donors and recipients, and the implications of those problems for social justice.1 Racially discriminatory practices in bank lending, education, and hiring provide a context for understanding how medical criteria treat black recipients (...) unfairly. Although antigen matching is only one aspect of the general problem of finding medically suitable black recipients, it presents an especially interesting challenge for theories of justice, as well as for medical research. (shrink)