The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been acknowledged for many years and validated by the clinical use of several drugs. Recently, the crystal structures of all but one of the enzymes in the pathway from GTP to dihydrofolate have been determined. Given that structure‐based drug design strategies are now widely employed, these recent developments have prompted a re‐evaluation of the potential of each of the enzymes in the pathway as (...) a target for development of specific inhibitors. Here, we review the current knowledge of the structure and mechanism of each enzyme in the bacterial folic acid biosynthesis pathway from GTP to dihydrofolate and draw conclusions regarding the potential of each enzyme as a target for therapeutic intervention. BioEssays 24:637–648, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Regulating affective responses to acute stress has the potential to improve health, performance, and well-being outcomes. Using the biopsychosocial model of challenge and threat as an organizing framework, we review how appraisals inform affective responses and highlight research that demonstrates how appraisals can be used as regulatory tools. Arousal reappraisal, specifically, instructs individuals on the adaptive benefits of stress arousal so that arousal is conceptualized as a coping resource. By reframing the meaning of signs of arousal that accompany stress, it (...) is possible to break the link between stressful situations, and malignant physiological responses and experiences of negative affect. Applications of arousal reappraisal for academic contexts and clinical science, and directions for future research are discussed. (shrink)

The biopsychosocial model of challenge and threat posits that resource and demand appraisals interact in situations of acute stress to determine affective responses, and concomitant physiological responses, motivation, and decisions/behaviors. Regulatory approaches that alter appraisals to regulate challenge and threat affective states have the potential to facilitate coping. This reply clarifies the conceptualization of one such regulatory approach, arousal reappraisal, and suggests avenues for future research. However, it is important to note that arousal reappraisal is not a “silver bullet” for (...) improving stress outcomes, nor should this strategy be expected to positively impact all individuals. More work is needed to better elucidate how psychological and biological stress processes interact to shape health. (shrink)

Accounting for the Commandments in Medieval Judaism explores the discursive formation of the commandments as a generative matrix of Jewish thought and life in the posttalmudic period. Each study sheds light on how medieval Jews crafted the commandments out of theretofore underdetermined material. By systematizing, representing, or interrogating the amorphous category of commandment, medieval Jewish authors across both the Islamic and Christian spheres of influence sought to explain, justify, and characterize Israel's legal system, divine revelation, the cosmos, and even the (...) divine order. This volume correlates bodies of knowledge-such as jurisprudence, philosophy, ethics, pietism, and kabbalah-that are normally treated in isolation into a single conversation about a shared constitutional concern. (shrink)

This article engages the question—what is the right business‐society relationship? We consider three perspectives that seek to address the relationship: corporate social responsibility (CSR), social entrepreneurship (SE), and conscious capitalism (CC). We take a macroapproach considering how commentary about these approaches establishes a direction for corporate practice and its relationship to key stakeholder groups. We argue that these perspectives are ‘D'iscourses that provide arguments for and articulations about the direction of corporate practice and the business‐society relationship. To organize our review (...) of each perspective, and focus our critique, for each we highlight (a) drivers and influencers, (b) core assumptions and defining features, and (c) approaches and exemplars. Although distinct, all emphasize effective business practices as key to meeting social needs. CSR suggests legitimizing business practice; SE relocates business practices; and CC seeks to reimagine/rehabilitate business for social good. Ultimately, we conclude that these Discourses lack a clear communicative focus in terms of decision making within these organizations. We attend to this and other implications, and offer avenues for further research. (shrink)

For 15 years, former assistant football coach Jerry Sandusky used his Penn State University perquisites to lure young and fatherless boys by offering them special access to one of the most revered football programs in the country. He repeatedly used the football locker room as a space to groom, molest, and rape his victims. In February 2001, an eye-witness alerted Penn State’s top leaders that Sandusky was caught sexually assaulting a young boy in the showers. Instead of taking swift action (...) against Sandusky, leaders began a cover-up that is considered one of the worst scandals in sports history. While public outcry has focused on the leaders’ silence, we focus on the talk that occurred within the organization by key personnel. Drawing from court documents and internal investigative reports, we examine two euphemism clusters that unfolded in the scandal. The first cluster comprises reporting euphemisms, in which personnel used coded language to report the assault up the chain of command. The second cluster comprises responding euphemisms, in which Penn State’s top leaders relied on an innocuous, but patently false, interpretation of earlier euphemisms as a decision-making framework to chart their course of action. We use this case to demonstrate how euphemistic language impairs ethical decision-making, particularly by framing meaning and visibility of acts, encouraging mindless processing of moral considerations, and providing a shield against psychological and material consequences. Further, we argue that euphemism may serve as a disguised retort to critical upward communication in organizations. (shrink)

The increased incidence of morbidity and mortality due to Clostridium difficile infection, had led to the emergence of fecal microbial transplantation (FMT) as a highly successful treatment. From this, a 32 strain stool substitute has been derived, and successfully tested in a pilot human study. These approaches could revolutionize not only medical care of infectious diseases, but potentially many other conditions linked to the human microbiome. But a second revolution may be needed in order for regulatory agencies, society and medical (...) practitioners to accept and utilize these interventions, monitor their long term effects, have a degree of control over their use, or at a minimum provide guidelines for donors and recipients. (shrink)

Being Arising:. Review of Going on Bdngby Mark Epstein and The Positive Psychology of Buddhism and Yoga by Martin Levine.

This paper provides a method for characterizing space events using the framework of conceptual spaces. We focus specifically on estimating and ranking the likelihood of collisions between space objects. The objective is to design an approach for anticipatory decision support for space operators who can take preventive actions on the basis of assessments of relative risk. To make this possible our approach draws on the fusion of both hard and soft data within a single decision support framework. Contextual data is (...) also taken into account, for example data about space weather effects, by drawing on the Space Domain Ontologies, a large system of ontologies designed to support all aspects of space situational awareness. The framework is coupled with a mathematical programming scheme that frames a mathematically optimal approach for decision support, providing a quantitative basis for ranking potential for collision across multiple satellite pairs. The goal is to provide the broadest possible information foundation for critical assessments of collision likelihood. (shrink)

Although workplace bullying is common and has universally harmful effects on employees’ outcomes, little is known about workplace bullies. To address this gap in knowledge, we draw from the tenets of social exchange and displaced aggression theories in order to develop and test a model of workplace bullying that incorporates the effects of employees’ individual differences, perceptions of their work environments, and perceptions of supervisory treatment on their tendencies to bully coworkers. The results of mediated moderation analyses that examine responses (...) from two samples of working adults support our hypotheses. Specifically, we find evidence of an indirect relationship between entitlement and coworker bullying through perceptions of abusive supervision that is stronger for employees who report lower levels of felt accountability than employees who report higher levels of felt accountability. This study makes important theoretical and practical contributions to abusive supervision research, bullying research, and organizational efforts to promote ethical work environments devoid of interpersonal mistreatment by providing novel insight into how employees’ entitlement and felt accountability combine to influence their tendencies to perceive themselves as victims of abusive supervision and culprits of coworker bullying. (shrink)

This paper describes an AFOSR-supported basic research program that focuses on developing a new framework for combining hard with soft data in order to improve space situational awareness. The goal is to provide, in an automatic and near real-time fashion, a ranking of possible threats to blue assets (assets trying to be protected) from red assets (assets with hostile intentions). The approach is based on Conceptual Spaces models, which combine features from traditional associative and symbolic cognitive models. While Conceptual Spaces (...) are revolutionary, they lack an underlying mathematical framework. Several such frameworks have attempted to represent Conceptual Spaces, but by far the most robust is the model developed by Holender. His model utilizes integer linear programming in order to obtain an overall similarity value between observations and concepts that support the formation of hypotheses. This paper will describe a method for building Conceptual Spaces models for threats that utilizes ontologies as a means to provide a clear semantic foundation for this inferencing process; in particular threat ontologies and space domain ontologies are developed and employed in this approach. A space situational awareness use-case is presented involving a kinetic kill scenario and results are shown to assess the performance of this fusion-based inferencing framework. (shrink)

The overall goal of the approach developed in this paper is to estimate the likelihood of a given kinetic kill scenario between hostile spacebased adversaries using the mathematical framework of Complex Conceptual Spaces Single Observation. Conceptual spaces are a cognitive model that provide a method for systematically and automatically mimicking human decision making. For accurate decisions to be made, the fusion of both hard and soft data into a single decision framework is required. This presents several challenges to this data (...) fusion framework. The first is the challenge involved in handling multiple complex terminologies, which is addressed by drawing on a set of Space Domain Ontologies. Another challenge is the complex combinatorics involved when considering all possible feature combinations. This can be mitigated by using integer linear programming optimization that is outlined by the Complex Conceptual Spaces Single Observation mathematical model framework. A third challenge is the complicated physics that is involved in a spacecraft collision that must be addressed to obtain a better understanding of threat assessment. Overcoming these various challenges allows for a quantitative ranking for the potential of a kinetic kill collision across multiple spacecraft pairs. In addition to overcoming these challenges this paper will break down threat assessment into four domains and identify a ranking of threat both for each individual domain and for the four domains combined. Simulation results are shown to verify the developed concepts. (shrink)

Research that examines unethical interpersonal treatment has received a great deal of attention from scholars and practitioners in recent years due to the remarkable impact of mistreatment in the workplace. However, the literature is incomplete because we have an inadequate understanding of insubordination, which we define as “subordinates’ disobedient behaviors that intentionally exhibit a defiant refusal of their supervisors’ authority.” In our study, we integrate social exchange theory and the advantageous comparison component of moral disengagement within the integrative model of (...) experiencing and responding to mistreatment at work. Then, we explain why subordinates disengage from moral control as they balance experiencing abusive supervision with perpetrating insubordination within negative supervisor–subordinate social exchange relationships. In Studies 1–4, we validate a five-item measure of insubordination and demonstrate its content, convergent, discriminant, criterion-related, and predictive validity. In Study 5, we demonstrate that there is a positive indirect effect of abusive supervision on insubordination through negative social exchange relationship quality that strengthens for subordinates who perceive higher levels of supervisors’ task performance than others. Overall, our study advances the conversation in the business ethics literature by creating a solid conceptual, empirical, and theoretical foundation for a cohesive program of insubordination research that meaningfully builds on prior findings in unethical interpersonal treatment research. (shrink)

The ability to take others’ perspectives on the self has important psychological implications. Yet the logically and developmentally prior question is how children develop the capacity to take others’ perspectives. We discuss the development of joint attention in infancy as a rudimentary form of perspective taking and critique examples of biological and individualistic approaches to the development of joint attention. As an alternative, we present an activity-based relational perspective according to which infants develop the capacity to coordinate attention with others (...) by differentiating the perspectives of self and other from shared activity. Joint attention is then closely related to language development, which makes further social development possible. We argue that the ability to take the perspective of others on the self gives rise to the possibility of language, rationality and culture. (shrink)

The ability to take others’ perspectives on the self has important psychological implications. Yet the logically and developmentally prior question is how children develop the capacity to take others’ perspectives. We discuss the development of joint attention in infancy as a rudimentary form of perspective taking and critique examples of biological and individualistic approaches to the development of joint attention. As an alternative, we present an activity-based relational perspective according to which infants develop the capacity to coordinate attention with others (...) by differentiating the perspectives of self and other from shared activity. Joint attention is then closely related to language development, which makes further social development possible. We argue that the ability to take the perspective of others on the self gives rise to the possibility of language, rationality and culture. (shrink)

Evidence-based medicine has always required integration of patient values with ‘best’ clinical evidence. It is widely recognized that scientific practices and discoveries, including those of EBM, are value-laden. But to date, the science of EBM has focused primarily on methods for reducing bias in the evidence, while the role of values in the different aspects of the EBM process has been almost completely ignored.

Beyond Consent examines the concept of justice, and its application to human subject research, through the different lenses of various research populations: children, the vulnerable sick, captive and convenient populations, women, people of colour, and subjects in international settings. Separate chapters address the evolution of research policies, implications of the concept of justice for the future of human subject research, and the ramifications of this concept throughout the research enterprise.

The COVID-19 pandemic has presented a global threat to physical and mental health worldwide. Research has highlighted adverse impacts of COVID-19 on wellbeing but has yet to offer insights as to how wellbeing may be protected. Inspired by developments in wellbeing science and guided by our own theoretical framework, we examined the role of various potentially protective factors in a sample of 138 participants from the United Kingdom. Protective factors included physical activity, tragic optimism, gratitude, social support, and nature connectedness. (...) Initial analysis involved the application of one-sample t-tests, which confirmed that wellbeing in the current sample was significantly lower compared to previous samples. Protective factors were observed to account for up to 50% of variance in wellbeing in a hierarchical linear regression that controlled for a range of sociostructural factors including age, gender, and subjective social status, which impact on wellbeing but lie beyond individual control. Gratitude and tragic optimism emerged as significant contributors to the model. Our results identify key psychological attributes that may be harnessed through various positive psychology strategies to mitigate the adverse impacts of hardship and suffering, consistent with an existential positive psychology of suffering. (shrink)

We examined the development of children's understanding of beliefs and emotions in relation to parental talk about the psychological world. We considered the relations between parent–child talk about the emotions of characters depicted in a picture book, false belief understanding and emotion understanding. Seventy-eight primarily Caucasian and middle-class parents and their 3- to 5-year-old children participated (half boys and half girls). The emotions talked about were relatively simple, but the complexity of the situation varied in terms of whether or not (...) an understanding of beliefs was required to understand the emotion. Talk about the belief-dependent aspects of the emotions of picture book characters predicted children's false belief understanding, whereas talk about non-belief-dependent aspects of these emotions predicted children's emotion understanding. We argue that these data suggest that the development of children's understanding of beliefs and emotions is intertwined with learning to talk about the psychological world. (shrink)

Many contextualist accounts in epistemology appeal to ordinary language and everyday practice as grounds for positing a low-standards knowledge (knowledgeL) that contrasts with high-standards prevalent in epistemology (knowledgeH). We compare these arguments to arguments from the height of “ordinary language” philosophy in the mid 20th century and find that all such arguments face great difficulties. We find a powerful argument for the legitimacy and necessity of knowledgeL (but not of knowledgeH). These appeals to practice leave us with reasons to accept (...) knowledgeL in the face of radical doubts raised by skeptics. We conclude by arguing that by relegating knowledgeH to isolated contexts, the contextualist fails to deal with the skeptical challenge head-on. KnowledgeH and knowledgeL represent competing, incompatible intuitions about knowledge, and we must choose between them. A fallibilist conception of knowledge, formed with proper attention to radical doubts, can address the skeptical challenge without illicit appeal to everyday usage. (shrink)

Strategies for disclosing investigators' financial interests to potential research participants have been adopted by many research institutions. However, little is known about how decisions are made regarding disclosures of financial interests to potential research participants, including what is disclosed and the rationale for making these determinations. We sought to understand the attitudes, beliefs, and practices of institutional review board chairs, conflict of interest committee chairs, and investigators regarding disclosure of financial interests to potential research participants. Several themes emerged, including general (...) attitudes toward conflicts of interest, circumstances in which financial interests should be disclosed, rationales and benefits of disclosure, what should be disclosed, negative effects of and barriers to disclosure, and timing and presentation of disclosure. Respondents cited several rationales for disclosure, including enabling informed decision making, promoting trust in researchers and research institutions, and reducing legal liability. There was general agreement that disclosure should happen early in the consent process. Respondents disagreed about whether to disclose the amounts of particular financial interests. Clarifying the goals of disclosure and understanding how potential research participants use the information will be critical in efforts to ensure the integrity of clinical research and to protect the rights and interests of participants. (shrink)

Investigator and institutional financial conflicts of interest have raised concerns about both the integrity of clinical research and protecting the rights and welfare of research participants. In response, professional groups and governmental bodies have issued guidance for managing conflicts of interest to minimize their potential untoward effects. Although a variety of approaches have been offered, a common protection is to disclose financial interests in research to potential research participants as part of the recruitment and informed consent process. This approach reinforces (...) a basic norm of candor, ideally allowing potential research participants to evaluate whether financial interests should affect their decision to participate in research. Disclosure to potential research participants is viewed as an alternative to having regulators or research institutions limit or prohibit all financial interests in research, assuming that not all such interests are unacceptable. (shrink)

The paper investigates the various factors from a socio-cultural perspective that have a bearing on the intercultural couple’s marital satisfaction in Westerner and non-Westerner relationships, and how cultural differences may potentially amplify the difficulties, which non-intercultural couples themselves are already likely to face. These factors include acculturation, language and communication, attitudes toward marriage, individual traits and behaviours, support of the family, societal views, gender roles, managing of the household finances and child rearing. Certain theories are also highlighted in an attempt (...) to explain why these cultural differences have such a profound effect on the marital satisfaction of intercultural couples. (shrink)

Presents a plethora of approaches to developing human potential in areas not conventionally addressed. Organized in two parts, this international collection of essays provides viable educational alternatives to those currently holding sway in an era of high-stakes accountability.

Antibodies that are specific for DNA provide an excellent system for studying the protein‐nucleic acid interactions that allow proteins to recognize specific DNA structures or sequences.

Evidentialism is the thesis that epistemic justification for belief supervenes on evidential support. However, we claim there are cases in which, even though two subjects have the same evidential support for a proposition, only one of them is justified. What make the difference are pragmatic factors, factors having to do with our cares and concerns. Our argument against evidentialism is not based on intuitions about particular cases. Rather, we aim to provide a theoretical basis for rejecting evidentialism by defending a (...) “pragmatic” necessary condition on epistemic justification. We argue for the following necessary condition for justification: S is justified in believing that p only if S is rational to prefer (and, hence, act) as if p. In light of this necessary condition, the price of evidentialism is skepticism, or something close to it. (shrink)

BackgroundAlthough the number of reporting guidelines has grown rapidly, few have gone through an updating process. The STARD statement (Standards for Reporting Diagnostic Accuracy), published in 2003 to help improve the transparency and completeness of reporting of diagnostic accuracy studies, was recently updated in a systematic way. Here, we describe the steps taken and a justification for the changes made.ResultsA 4-member Project Team coordinated the updating process; a 14-member Steering Committee was regularly solicited by the Project Team when making critical (...) decisions. First, a review of the literature was performed to identify topics and items potentially relevant to the STARD updating process. After this, the 85 members of the STARD Group were invited to participate in two online surveys to identify items that needed to be modified, removed from, or added to the STARD checklist. Based on the results of the literature review process, 33 items were presented to the STARD Group in the online survey: 25 original items and 8 new items; 73 STARD Group members (86 %) completed the first survey, and 79 STARD Group members (93 %) completed the second survey.Then, an in-person consensus meeting was organized among the members of the Project Team and Steering Committee to develop a consensual draft version of STARD 2015. This version was piloted in three rounds among a total of 32 expert and non-expert users. Piloting mostly led to rewording of items. After this, the update was finalized. The updated STARD 2015 list now consists of 30 items. Compared to the previous version of STARD, three original items were each converted into two new items, four original items were incorporated into other items, and seven new items were added.ConclusionsAfter a systematic updating process, STARD 2015 provides an updated list of 30 essential items for reporting diagnostic accuracy studies. (shrink)

The present edition of 'Of the Limits of the Penal Branch of Jurisprudence' supersedes 'Of Laws in General,' edited by H.L.A. Hart and published by the Athlone Press in 1970, as a volume in The Collected Works of Jeremy Bentham." --P. xi.

Dorr et al. present a case that poses a challenge for a number of plausible principles about knowledge and objective chance. Implicit in their discussion is an interesting new argument against KK, the principle that anyone who knows p is in a position to know that they know p. We bring out this argument, and investigate possible responses for defenders of KK, establishing new connections between KK and various knowledge-chance principles.

This paper offers a new argument that your reasons for believing or acting need not be true. It proceeds indirectly through an account of what it takes to be happy that p. To be happy that p is for p to be among your reasons for being happy. That’s because questions about why you’re happy and what you’re happy is the case are interchangeable. But, I argue, it is possible to be happy that p even when p is false. In (...) cases in which you believe falsely that p and sincerely assert that you are happy that p, you are still expressing happiness about something. To be happy about something is to be happy that some proposition is the case. In the cases in question, it is implausible that the proposition you are happy is the case is a proposition about the evidence or how things seem or what you believe. The only other option is that the proposition you are happy is the case is p itself. Along the way, I discuss linguistic data that seems to counter the view that you can be happy that falsehoods are true. Though initially suggesting a more principled argument that you can only be happy about truths, both the linguistic data and the principled argument can ultimately be defused. A similar principled argument for the factivity of ‘knows,’ however, remains happily untouched. (shrink)