We highlight the various domains of the flavivirus virulence factor NS1 and speculate on potential implications of the NS1 3D structure in understanding its role in flavivirus pathogenesis. Flavivirus non‐structural protein 1 (NS1) is a virulence factor with dual functions in genome replication and immune evasion. Crystal structures of NS1, combined with reconstructions from electron microscopy (EM), provide insight into the architecture of dimeric NS1 on cell membranes and the assembly of a secreted hexameric NS1‐lipid complex found in patient sera. (...) Three structural domains of NS1 likely have distinct roles in membrane association, replication complex assembly, and immune system avoidance. A conserved hydrophobic inner face is sequestered either on the membrane or in the interior of the secreted hexamer and contains regions implicated in viral replication. The exposed variable outer face is presented to cellular and secreted components of the immune system in infected patients and contains candidate regions for immune system modulation. We anticipate that knowledge of the distinct NS1 domains and assembly will lead to advances in elucidating virus‐host interactions mediated through NS1 and in dissecting the role of NS1 in viral genome replication. (shrink)

Background Families whose child has unexplained intellectual or developmental differences often hope that a genetic diagnosis will lower barriers to community-based therapeutic and support services. However, there is little known about efforts to mobilize genetic information outside the clinic or how socioeconomic disadvantage shapes and constrains outcomes.Methods We conducted an ethnographic study with predominantly socioeconomically disadvantaged families enrolled in a multi-year genomics research study, including clinic observations and in-depth interviews in English and Spanish at multiple time points. Coding and thematic (...) development were used to collaboratively interpret fieldnotes and transcripts.Results Thirty-two families participated. Themes included familial expectations that a genetic diagnosis could be translated into information, understanding, and assistance to improve the quality of a child’s day-to-day life. After sequencing, however, genetic information was not readily converted into improved access to services beyond the clinic, with families often struggling to use a genetic diagnosis to advocate for their child.Conclusion Families’ ability to use a genetic diagnosis as an effective advocacy tool beyond the clinic was limited by the knowledge and resources available to them, and by the eligibility criteria used by therapeutic service providers’ – which focused on clinical diagnosis and functional criteria more than etiologic information. All families undertaking genomic testing, particularly those who are disadvantaged, need additional support to understand the limits and potential benefits of genetic information beyond the clinic. (shrink)

The central role played by Darwin's analogy between selection under domestication and that under nature has been adequately appreciated, but I have indicated how important the domesticated organisms also were to other elements of Darwin's theory of evolution-his recognition of “the constant principle of change,” for instance, of the imperfection of adaptation, and of the extent of variation in nature. The further development of his theory and its presentation to the public likewise hinged on frequent reference to domesticates.We have seen (...) that Darwin's reliance on the analogy between domesticated varieties and wild species was a bold and original step, in light of contemporary views on the nature of domesticates. However, as Darwin undoubtedly foresaw, his reliance on the analogy created difficulties as well as solving problems, and these began with his Malthusian codiscoverer of the principle of natural selection, Alfred Russel Wallace. Wallace's paper “On the Tendency of Varieties to Depart Indefinitely from the Original Type,” presented to the Linnean Scoiety along with the first public unveiling of Darwin's theory, states: We see, then, that no inferences as to varieties in a state of nature can be deduced from the observation of those occurring among domestic animals. The two are so much opposed to each other in every circumstance of their existence, that what applies to the one is almost sure not to apply to the other. Domestic animals are abnormal, irregular, artificial; they are subject to varieties which never occur and never can occur in a state of nature.62Much has been made of the similarity of views of Darwin and Wallace, but this quotation surely reveals how utterly different their views were on what to Darwin was an important matter. Several critics of the Origin saw Darwin's reliance on the domesticates as his Achilles heel. As Young has pointed out, Samuel Wilberforce included the following passage in his attack on the Origin: Nor must we pass over unnoticed the transference of the argument from the domesticated to the untamed animals. Assuming that man as the selector can do much in a limited time, Mr. Darwin argues that Nature, a more powerful, a more continuous power, working over vastly extended ranges of time, can do more. But why should Nature, so uniform and persistent in all her operations, tend in this instance to change? Why should she become a selector of varieties?63Another critic, Fleeming Jenkin, found the analogy a weakness in Darwin's theory because of the limited extent of variation in any one direction in domestic animals and plants.64 We have already seen that Darwin had confided a similar view to his notebook thirty years earlier, but changed his mind as a result of his profound study of domesticates. De Beer's reference to “an English country gentleman's knowledge of domestic plants and animals and their breeding”65 fails totally to recognize the originality and depth of Darwin's knowledge of domesticates.Why did Darwin, against the currents of his time, rely so heavily on mankind's experience with domesticated organisms to shape his theory about species in nature? On reason is that only with domesticates was an approach that came close to experimental verification possible. Darwin fully realized the inadequacies of the experiment, as is emphasized by his repeated contrasting of selection under nature and selection by man. Yet the extensive experience and data of plant and animal breeders offered the only reliable base against which Darwin could continually challenge his views. As he wrote in the introduction to Variation, with domestication, “man ... may be said to have been trying an experiment on a gigantic scale.”66 Given Darwin's high opinion of the quantitative work of Malthus and Quetelet (as emphasized by Schweber),67 and his unremitting efforts to secure data by which to test his theories, it was inevitable that he should attach high significance to domesticated varieties. John Tyndall, in his Belfast address of 1874, said: “The strength of the doctrine of Evolution consists, not in experimental demonstration (for the subject is hardly accessible to this mode of proof), but in its general harmony with scientific thought.”68 Darwin would have agreed with the latter thought, but I think he would have challenged the preceding one on the grounds that long experience with domesticated varieties did provide an element of experimental demonstration. It gave him confidence in his theory, and he used his vast knowledge of artificial selection boldly and creatively. (shrink)

In May 2011, the clinical ethics group of the Center for Ethics at Washington Hospital Center launched a 40-hour, three and one-half day Clinical Ethics Immersion Course. Created to address gaps in training in the practice of clinical ethics, the course is for those who now practice clinical ethics and for those who teach bioethics but who do not, or who rarely, have the opportunity to be in a clinical setting. “Immersion” refers to a high-intensity clinical ethics experience in a (...) busy, urban, acute care hospital. During the Immersion Course, participants join clinical ethicists on working rounds in intensive care units and trauma service. Participants engage in a videotaped role-play conversation with an actor. Each simulated session reflects a practical, realistic clinical ethics case consultation scenario. Participants also review patients’ charts, and have small group discussions on selected clinical ethics topics. As ethics consultation requests come into the center, Immersion Course participants accompany clinical ethicists on consultations.Specific to this pilot, because participants’ evaluations and course faculty impressions were positive, the Center for Ethics will conduct the course twice each year. We look forward to improving the pilot and establishing the Immersion Course as one step towards addressing the gap in training opportunities in clinical ethics. (shrink)

This text demonstrates that symbolic representation and related problem-solving methods offer significant opportunities to clarify and articulate concepts of design.

The non-financial effects (NFE) antitakeover amendment addresses the duties of company directors and management when faced with a possible takeover bid. The NFE amendment either permits or requires managers to consider the interests of the company's stakeholders during takeover bids. Other types of antitakeover devices have been viewed as protecting either stockholder or management interests. The NFE amendment would appear to protect a broad spectrum of interests including those of company employees, creditors, and the community in which the company operates. (...) Positive market returns to the adoption of NFE amendments provide some evidence that investors approve. The percent of both management and institutional ownership are positively related to the market reaction to the NFE amendment adoption. To the extent that institutional ownership proxies for the broad spectrum of stakeholder interest, NFE devices, unlike some other amendments that have been studied, appear to be in the interests of more than a single interest group. (shrink)

The non-financial effects (NFE) antitakeover amendment addresses the duties of company directors and management when faced with a possible takeover bid. The NFE amendment either permits or requires managers to consider the interests of the company's stakeholders during takeover bids. Other types of antitakeover devices have been viewed as protecting either stockholder or management interests. The NFE amendment would appear to protect a broad spectrum of interests including those of company employees, creditors, and the community in which the company operates. (...) Positive market returns to the adoption of NFE amendments provide some evidence that investors approve. The percent of both management and institutional ownership are positively related to the market reaction to the NFE amendment adoption. To the extent that institutional ownership proxies for the broad spectrum of stakeholder interest, NFE devices, unlike some other amendments that have been studied, appear to be in the interests of more than a single interest group. (shrink)

Background Empirical studies of surrogate decision-making tend to assume that surrogates should make only a 'substituted judgement'—that is, judge what the patient would want if they were mentally competent. Objectives To explore what people want in a surrogate decision-maker whom they themselves select and to test the assumption that people want their chosen surrogate to make only a substituted judgement. Methods 30 undergraduate students were recruited. They were presented with a hypothetical scenario about their expected loss of mental capacity in (...) the future and asked to answer some questions about their choice of surrogate. These data were analysed qualitatively using thematic content analysis. Results Most respondents talked about choosing someone who was caring and competent in certain ways, giving interesting evidence for their judgements. Surprisingly few highlighted how well they thought their chosen surrogate knew their preferences and would be able to make a substituted judgement. Moreover, few specified that their chosen surrogate had similar attitudes and values to their own and so would make a similar decision to theirs in the circumstances presented. Some respondents also referred to the social role of their chosen surrogate or the social dynamics of their situation which influenced their choices, as well as to ideas of reciprocity and characteristics of honesty and loyalty. Conclusion In the event that they lose mental capacity, many people will not select a surrogate to decide about medical treatments on their behalf solely on the basis that they expect their surrogate to make a substituted judgement. (shrink)

Proceedings of a conference held in the fall of 2005 at the University of Notre Dame.

Glowacki offers many new directions for understanding and even eliminating the problem of war, especially creating positive interdependencies with out-group members. We develop Glowacki's intriguing proposition that in-group dynamics provide a route to peace by describing a prosocial motivational system, the caregiving system, that aligns individual interests and eliminates the need to use coercion to achieve mutually beneficial outcomes.

Depue & Morrone-Strupinsky (D&M-S) do not address how a reward system accommodates the motivational dilemmas associated with (a) the decision to approach versus avoid conspecifics, and (b) self versus other tradeoffs inherent in behaving altruistically toward bonded relationship partners. We provide an alternative evolutionary view that addresses motivational conflict, and discuss implications for the neurobiological study of affiliative bonds.

It is commonly held that early career experiences influence ethical behavior. One way early career experiences might operate is to influence the decisions people make when presented with problems that raise ethical concerns. To test this proposition, 102 first-year doctoral students were asked to complete a series of measures examining ethical decision making along with a series of measures examining environmental experiences and climate perceptions. Factoring of the environmental measure yielded five dimensions: professional leadership, poor coping, lack of rewards, limited (...) competitive pressure, and poor career direction. Factoring of the climate inventory yielded four dimensions: equity, interpersonal conflict, occupational engagement, and work commitment. When these dimensions were used to predict performance on the ethical decision-making task, it was found that the environmental dimensions were better predictors than the climate dimensions. The implications of these findings for research on ethical conduct are discussed. (shrink)

Retractions have traditionally been reserved for correcting the scientific record and discouraging research misconduct. Nonetheless, the potential for actual societal harm resulting from accurately reported published scientific findings, so-called information hazards, has been the subject of several recent article retractions. As these instances increase, the extent of support for such decisions among the scientific community and lay public remains unclear. Undergraduates (Study 1) and federally funded researchers (Study 2) reported their support for retraction decisions described as due to misconduct, honest (...) errors, or potential information hazards. Participants supported retraction on the former two grounds more than the latter. Despite limited support, women remained more receptive to retractions based on information hazards. Activist tendencies additionally predicted undergraduate men’s receptivity. Receptivity toward retraction due to information hazards was unrelated to scientists’ engagement in activism, suggesting that formal scientific training affords researchers an ability to separate personal and professional values in scientific discourse. Findings could inform the development of educational materials that may aid less experienced scientists and the lay public in understanding retraction ethics. (shrink)