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)

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

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)

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)

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)

Scepticism about ought simpliciter is the view that there is no such thing as what one ought simpliciter to do. Instead, practical deliberation is governed by a plurality of normative standpoints, each authoritative from their own perspective but none authoritative simpliciter. This paper aims to resist such scepticism. After setting out the challenge in general terms, I argue that scepticism can be resisted by rejecting a key assumption in the sceptic’s argument. This is the assumption that standpoint-relative ought judgments bring (...) with them a commitment to act in accordance with those judgments. Instead, I propose an alternative account of our normative concepts according to which only ought simpliciter judgments commit one to acting in accordance with those judgments. In addition to answering the sceptical challenge, the proposal offers an independently motivated account of what makes a concept normatively authoritative. (shrink)

This paper examines the general prospects for conceptual role expressivism, expressivist theories that embrace conceptual role semantics. It has two main aims. The first aim is to provide a general characterisation of the view. The second aim is to raise a challenge for the general view. The challenge is to explain why normative concepts are not a species of defective concepts, where defective concepts are those that cannot meaningfully embed and participate in genuine inference. After rejecting existing attempts to answer (...) the challenge, I propose an alternative solution. However, the solution leaves conceptual role expressivism a far less distinctive and interesting position than its proponents claim. I conclude that we should be sceptical about how much expressivists gain by appealing to conceptual role semantics. (shrink)

Emerging adult newlywed couples often experience many demands on their time, and three common problems may surface as couples try to balance these demands—problems related to finances, sleep, and sex. We used two waves of dyadic data from 1,001 emerging adult newlywed couples to identify four dyadic latent profiles from husbands’ and wives’ financial management behaviors, sexual satisfaction, and sleep quality: Flounderers, Financially Challenged Lovers, Drowsy Budgeters, and Flourishers. We then examined how husbands’ and wives’ marital satisfaction, in relation to (...) profile membership, varied at a later wave. We found that Financially Challenged Lovers and Flourishers had significantly higher marital satisfaction than Drowsy Budgeters and Flounderers. Whereas, Financially Challenged Lovers and Flourishers did not differ in terms of marital satisfaction, Drowsy Budgeters seemed to have slightly higher marital satisfaction than Flounderers for wives only. However, we did not find evidence that these connections meaningfully differed by sex. Implications for the efforts of clinicians and educators are discussed. (shrink)

It describes and explains the patient-centered model examining and evaluating qualitative and quantitative research. It comprehensively covers the evolution and the six interactive components of the patient-centered clinical method, taking the reader through the relationships between the patient and doctor and the patient and clinician. All the editors are professors in the Department of Family Medicine at the University of Western Ontario, London, Canada.

Legal decision-support systems have the potential to improve access to justice, administrative efficiency, and judicial consistency, but broad adoption of such systems is contingent on development of technologies with low knowledge-engineering, validation, and maintenance costs. This paper describes two approaches to an important form of legal decision support—explainable outcome prediction—that obviate both annotation of an entire decision corpus and manual processing of new cases. The first approach, which uses an attention network for prediction and attention weights to highlight salient case (...) text, was shown to be capable of predicting decisions, but attention-weight-based text highlighting did not demonstrably improve human decision speed or accuracy in an evaluation with 61 human subjects. The second approach, termed semi-supervised case annotation for legal explanations, exploits structural and semantic regularities in case corpora to identify textual patterns that have both predictable relationships to case decisions and explanatory value. (shrink)

Heisenberg'sgendanken experiments in quantum mechanics have given rise to a widespread belief that the indeterminacy relations holding for the variables of a quantal system can be explained quasiclassically in terms of a disturbance suffered by the system in interaction with a quantal measurement, or state preparation, agent. There are a number of criticisms of this doctrine in the literature, which are critically examined in this article and found to be ininconclusive, the chief error being the conflation of this disturbance with (...) the projection postulate. We present a critique of the disturbance theory based on the fact that the required disturbance will in general depend on the interaction time of the system and state-preparer. This point is exploited in the construction of a spin-interaction model which acts as a counterexample to the disturbance doctrine, while remaining faithful to the spirit of Heisenberg'sgedanken experiments. Several consequences of this result are discussed. (shrink)