Some metabolic pathways are nearly ubiquitous among organisms: the genes encoding the enzymes for such pathways must therefore be ancient and essential. De novo pyrimidine biosynthesis is an example of one such metabolic pathway. In animals a single protein called CADAbbreviations: CAD, trifunctional protein catalyzing the first three steps of de novo pyrimidine biosynthesis in higher eukaryotes; CPS, carbamyl phosphate synthetase domain; CPSase, carbamyl phosphate synthetase activity; ATC, aspartate transcarbamylase domain; ATCase, aspartate transcarbamylase activity; DHO, dihydroorotase domain; DHOase, dihydroorotase activity; (...) GLN, glutaminase subdomain or subunit of carbamyl phosphate synthetase, GL Nase, glutaminase activity; SYN, synthetase subdomain or subunit of carbamyl phosphate synthetase; SYNase, synthetase activity. carries the first three steps of this pathway. The same three enzymes in prokaryotes are associated with separate proteins. The CAD gene appears to have evolved through a process of gene duplication and DNA rearrangement, leading to an in‐frame gene fusion encoding a chimeric protein. A driving force for the creation of eukaryotic genes encoding multienzymatic proteins such as CAD may be the advantage of coordinate expression of enzymes catalyzing steps in a biosynthetic pathway. The analogous structure in bacteria is the operon. Differences in the translational mechanisms of eukaryotes and prokaryotes may have dictated the different strategies used by organisms to evolve coordinately regulated genes. (shrink)

This article begins with discussing challenges encountered while managing the epistemology of legal modes of thinking and social science, and the limits of relying on discipline-based methodologies for the advancement of empirical legal scholarship. In then discusses two approaches to empirical legal training employed in New York. Through this, it seeks to demonstrate the strengths of collaborative research with illustrations of a cross-national collaboration. Empirical research on law is a multi-method phenomenon. Ideally, empirical legal training means that students need and (...) can further foster a background in a broad range of social science methods and in a set of methods that can use triangulation or juxtaposition to capture the factors that explain law as a social phenomenon. (shrink)

One factor that impedes medical students from speaking up about ethical situations is the lack of sufficient knowledge and skills in conflict resolution. This may also affect students’ decision and timing to intervene. This article will provide practical ways to effectively and efficiently address the medical student’s ethical case presented in August A. Culbert et al.’s “Navigating Informed Consent and Patient Safety in Surgery: Lessons for Medical Students and Junior Trainees.”.

© JNCCN-Journal of the National Comprehensive Cancer Network.Background: Next-generation tumor sequencing panels, which include multiple established and novel targets across cancers, are emerging in oncology practice, but lack formal positive coverage by US payers. Lack of coverage may impact access and adoption. This study identified challenges of NGTS coverage by private payers.Methods: We conducted semi-structured interviews with 14 NGTS experts on potential NGTS benefits, and with 10 major payers, representing more than 125,000,000 enrollees, on NGTS coverage considerations. We used the (...) framework approach of qualitative research for study design and thematic analyses and simple frequencies to further describe findings.Results: All interviewed payers see potential NGTS benefits, but all noted challenges to formal coverage: 80% state that inherent features of NGTS do not fit the medical necessity definition required for coverage, 70% view NGTS as a bundle of targets versus comprehensive tumor characterization and may evaluate each target individually, and 70% express skepticism regarding new evidence methods proposed for NGTS. Fifty percent of payers expressed sufficient concerns about NGTS adoption and implementation that will preclude their ability to issue positive coverage policies.Conclusions: Payers perceive that NGTS holds significant promise but, in its current form, poses disruptive challenges to coverage policy frameworks. Proactive multidisciplinary efforts to define the direction for NGTS development, evidence generation, and incorporation into coverage policy are necessary to realize its promise and provide patient access. This study contributes to current literature, as possibly the first study to directly interview US payers on NGTS coverage and reimbursement. (shrink)

Adult-based suicide theories have determined much of what we know about suicidal ideation. Here, we investigate the extent to which elements of theIntegrated Motivational-Volitional(IMV) model generalize to adolescence, a period when rates of suicidal ideation increase dramatically. In a sample of community-based adolescents (n= 74), we tested whether defeat and entrapment related to suicidal ideation, and whether poor positive future thinking abilities exacerbated this association. Consistent with the IMV model, we found that defeat/entrapment was associated specifically with history of suicidal (...) ideation, and not with history of suicide attempt. Defeat/entrapment was related to baseline suicidal ideation severity above and beyond depressive symptoms. While defeat/entrapment predicted future suicidal ideation controlling for history of ideation, it did not do so controlling for depressive symptoms. Counter to the IMV model, we initially found that the association between defeat/entrapment and suicidal ideation was strongest among adolescents withgreaterpositive future thinking abilities. This was driven by the tendency to imagine more positive future events, particularly those that are less realistic and achievable. These findings call for a more nuanced understanding of defeat/entrapment and positive future thinking among adolescents, particularly in how they interact to predict recurrent suicidal ideation. (shrink)

The interdisciplinary field of neurorobotics looks to neuroscience to overcome the limitations of modern robotics technology, to robotics to advance our understanding of the neural system’s inner workings, and to information technology to develop tools that support those complementary endeavours. The development of these technologies is still at an early stage, which makes them an ideal candidate for proactive and anticipatory ethical reflection. This article explains the current state of neurorobotics development within the Human Brain Project, originating from a close (...) collaboration between the scientific and technical experts who drive neurorobotics innovation, and the humanities and social sciences scholars who provide contextualising and reflective capabilities. This article discusses some of the ethical issues which can reasonably be expected. On this basis, the article explores possible gaps identified within this collaborative, ethical reflection that calls for attention to ensure that the development of neurorobotics is ethically sound and socially acceptable and desirable. (shrink)

Thirty-eight individuals (mean age: 34.8 years old) participating in a 3-month yoga and meditation retreat were assessed before and after the intervention for psychometric measures, brain derived neurotrophic factor (BDNF), circadian salivary cortisol levels, and pro- and anti-inflammatory cytokines. Participation in the retreat was found to be associated with decreases in self-reported anxiety and depression as well as increases in mindfulness. As hypothesized, increases in the plasma levels of BDNF and increases in the magnitude of the cortisol awakening response (CAR) (...) were also observed. The normalized change in BDNF levels was inversely correlated with BSI-18 anxiety scores at both the pre-retreat (r = 0.40, p < 0.05) and post-retreat (r = 0.52, p < 0.005) such that those with greater anxiety scores tended to exhibit smaller pre- to post-retreat increases in plasma BDNF levels. In line with a hypothesized decrease in inflammatory processes resulting from the yoga and meditation practices, we found that the plasma level of the anti-inflammatory cytokine Interleukin-10 was increased and the pro-inflammatory cytokine Interleukin-12 was reduced after the retreat. Contrary to our initial hypotheses, plasma levels of other pro-inflammatory cytokines, including Interferon Gamma (IFN-γ), Tumor Necrosis Factor (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and Interleukin-8 (IL-8) were increased after the retreat. Given evidence from previous studies of the positive effects of meditative practices on mental fitness, autonomic homeostasis and inflammatory status, we hypothesize that these findings are related to the meditative practices throughout the retreat; however, some of the observed changes may also be related to other aspects of the retreat such as physical exercise-related components of the yoga practice and diet. We hypothesize that the patterns of change observed here reflect mind-body integration and well-being. The increased BDNF levels observed is a potential mediator between meditative practices and brain health, the increased CAR is likely a reflection of increased dynamic physiological arousal, and the relationship of the dual enhancement of pro- and anti-inflammatory cytokine changes to healthy immunologic functioning is discussed. (shrink)

Plagiarism and other transgressions of the norms of academic integrity appear to be a persistent problem among upper secondary students. Numerous surveys have revealed high levels of infringement of what appear to be clearly stated rules. Less attention has been given to students’ understanding of academic integrity, and to the potential misconceptions and false beliefs that may make it difficult for them to comply with existing rules and handle complex real-life situations.In this paper we report findings from a survey of (...) European upper secondary students’ views on issues relating to academic integrity. We relate these findings to the students’ training about academic integrity, self-reported level of questionable behavior and country of study.A total of 1654 students at 51 institutions located in 6 European countries participated in the study. The participants generally believed they had a good understanding of the rules applying to them and knew how to behave in compliance with norms of academic integrity. The results indicate, however, that often, in practice, this belief was mistaken. Many students had an inadequate understanding of core elements of academic integrity. They were uncertain about how to act, and they struggled in the handling of complex situations that require context-sensitive judgement. While some differences between countries were identified, they were modest and exhibited no clear pattern. Our results also suggest that reducing students’ level of uncertainty and, to a lesser degree, improving their level of knowledge could lead them to engage less in certain types of questionable behaviours. Surprisingly, the effect of academic training is modest and ambiguous. The study also confirms that perception of peer behaviour has the strongest association with student engagement in questionable behaviours. Thus, academic integrity at the upper secondary level cannot be explained simply in terms of individual ethics or knowledge. (shrink)

Marcel Beaufils fut un pedagogue exceptionnel qui exerca une influence decisive sur l'evolution de l'esthetique musicale en France, a partir des annees 50. Or, parmi ses ouvrages, Musique du son, musique du verbe est tres certainement celui qui porte le plus fortement la marque de son activite d'enseignant au Conservatoire National Superieur de Musique de Paris ; cette mission, il semblait l'entendre davantage comme celle d'un declencheur d'idees, catalyseur, plutot que du transmetteur d'un savoir fige une fois pour toutes. Bouleversant (...) toute tentative de classification academique, toute certitude acquise, ce livre laisse des pointilles ; un grand souffle traverse son ecriture. N'en deplaise aux musicographes, il s'agit la d'un ouvrage de creation, qui nous rappelle que Marce Beaufils etait egalement un ecrivain qui savait manier le verbe a la fois en tant que dramaturge et en tant que poete. (shrink)

There is limited knowledge about cancer patients' experiences of uncertainty while waiting for genome sequencing results, and whether prolonged uncertainty contributes to psychological factors in this context. To investigate uncertainty in patients with a cancer of likely hereditary origin while waiting for genome sequencing results, we collected questionnaire and interview data at baseline, and at three and 12 months follow up. Participants had negative attitudes towards uncertainty at baseline, and low levels of uncertainty at three and 12 months. Uncertainty about (...) genome sequencing did not change significantly over time [t = 0.660, p = 0.510]. Greater perceived susceptibility for cancer [r = 0.14, p < 0.01], fear of cancer recurrence [r = 0.19, p < 0.01], perceived importance of genome sequencing [r = 0.24, p < 0.01], intention to change behavior if a gene variant indicating risk is found [r = 0.29, p < 0.01], perceived ability to cope with results [r = 0.36, p < 0.01], and satisfaction with decision to have genome sequencing [r = 0.52, p < 0.01] were significantly correlated with negative attitudes towards uncertainty at baseline. Multiple primary cancer diagnoses [B = −2.364 [−4.238, −0.491], p = 0.014], lower perceived ability to cope with results [B = −0.1.881 [−3.403, −0.359], p = 0.016] at baseline, greater anxiety about genome sequencing [B = 0.347 [0.148, 0.546], p = 0.0012] at 3 months, and greater perceived uncertainty about genome sequencing [B = 0.494 [0.267, 0.721] p = 0.000] at 3 months significantly predicted greater perceived uncertainty about genome sequencing at 12 months. Greater perceived uncertainty about genome sequencing at 3 months significantly predicted greater anxiety about genome sequencing at 12 months [B = 0.291 [0.072, 0.509], p = 0.009]. Semi-structured interviews revealed that while participants were motivated to pursue genome sequencing as a strategy to reduce their illness and risk uncertainty, genome sequencing generated additional practical, scientific and personal uncertainties. Some uncertainties were consistently discussed over the 12 months, while others emerged over time. Similarly, some uncertainty coping strategies were consistent over time, while others emerged while patients waited for their genome sequencing results. This study demonstrates the complexity of uncertainty generated by genome sequencing for cancer patients and provides further support for the inter-relationship between uncertainty and anxiety. Helping patients manage their uncertainty may ameliorate psychological morbidity. (shrink)

Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need (...) to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent. (shrink)

Existing research on the formation of employee ethical climate perceptions focuses mainly on organization characteristics as antecedents, and although other constructs have been considered, these constructs have typically been studied in isolation. Thus, our understanding of the context in which ethical climate perceptions develop is incomplete. To address this limitation, we build upon the work of Rupp to develop and test a multi-experience model of ethical climate which links aspects of the corporate social responsibility, ethics, justice, and trust literatures and (...) helps to explain how employees’ ethical climate perceptions form. We argue that in forming ethical climate perceptions, employees consider the actions or characteristics of a complex web of actors. Specifically, we propose that employees look outward at how communities are impacted by their organization’s actions, upward to make inferences about the ethicality of leaders in their organizations, and inward at their own propensity to trust others as they form their perceptions. Using a multiple-wave field study conducted at a privately held US corporation, we find substantial evidence in support of our model. (shrink)

Good academic practice is more than the avoidance of clear-cut cheating. It also involves navigation of the gray zones between cheating and good practice. The existing literature has left students’ understanding of gray zone practices largely unexplored. To begin filling in this gap, we present results from a questionnaire study involving N = 1639 undergraduate students from seven European countries representing all major disciplines. We show that large numbers of these students are unable to identify gray area issues and lack (...) sensitivity to the context dependence of these. We also show that a considerable proportion of students have a poor understanding of concepts like plagiarism and falsification, not only in gray zone scenarios, but also in cases of relatively clear-cut cheating. Our results are similar across the faculties and countries of study, and even for students who have attended academic integrity training. We discuss the implications of this for academic integrity training. (shrink)

This article provides current Schwartz Values Survey (SVS) data from samples of business managers and professionals across 50 societies that are culturally and socioeconomically diverse. We report the society scores for SVS values dimensions for both individual- and societal-level analyses. At the individual-level, we report on the ten circumplex values sub-dimensions and two sets of values dimensions (collectivism and individualism; openness to change, conservation, self-enhancement, and self-transcendence). At the societal-level, we report on the values dimensions of embeddedness, hierarchy, mastery, affective (...) autonomy, intellectual autonomy, egalitarianism, and harmony. For each society, we report the Cronbach’s α statistics for each values dimension scale to assess their internal consistency (reliability) as well as report interrater agreement (IRA) analyses to assess the acceptability of using aggregated individual level values scores to represent country values. We also examined whether societal development level is related to systematic variation in the measurement and importance of values. Thus, the contributions of our evaluation of the SVS values dimensions are two-fold. First, we identify the SVS dimensions that have cross-culturally internally reliable structures and within-society agreement for business professionals. Second, we report the society cultural values scores developed from the twenty-first century data that can be used as macro-level predictors in multilevel and single-level international business research. (shrink)

Over twenty years have passed since JLME published “The Girl Who Cried Pain: A Bias Against Women in the Treatment of Pain.” This article revisits the conclusions drawn in that piece and explores what we have learned in the last two decades regarding the experience of men and women who have chronic pain and whether women continue to be treated less aggressively for their pain than men.

In this study, we comprehensively examine the relationships between ethical leadership, social exchange, and employee commitment. We find that organizational and supervisory ethical leadership are positively related to employee commitment to the organization and supervisor, respectively. We also find that different types of social exchange relationships mediate these relationships. Our results suggest that the application of a multifoci social exchange perspective to the context of ethical leadership is indeed useful: As hypothesized, within-foci effects (e.g., the relationship between organizational ethical leadership (...) and commitment to the organization) are stronger than cross-foci effects (e.g., the relationship between supervisory ethical leadership and commitment to the organization). In addition, in contrast to the “trickle down” model of ethical leadership (Mayer et al. in Org Behav Hum Decis Process 108:1–13, 2009), our results suggest that organizational ethical leadership is both directly and indirectly related to employee outcomes. (shrink)

Altruism is a deep and complex phenomenon that is analysed by scholars of various disciplines, including psychology, philosophy, biology, evolutionary anthropology and experimental economics. Much confusion arises in current literature because the term altruism covers variable concepts and processes across disciplines. Here we investigate the sense given to altruism when used in different fields and argumentative contexts. We argue that four distinct but related concepts need to be distinguished: (a) psychological altruism , the genuine motivation to improve others’ interests and (...) welfare; (b) reproductive altruism , which involves increasing others’ chances of survival and reproduction at the actor’s expense; (c) behavioural altruism , which involves bearing some cost in the interest of others; and (d) preference altruism , which is a preference for others’ interests. We show how this conceptual clarification permits the identification of overstated claims that stem from an imprecise use of terminology. Distinguishing these four types of altruism will help to solve rhetorical conflicts that currently undermine the interdisciplinary debate about human altruism. (shrink)

Consider a typical fear episode. You are strolling down a lonely mountain lane when suddenly a huge wolf leaps towards you. A number of different interconnected elements are involved in the fear you experience. First, there is the visual and auditory perception of the wild animal and its movements. In addition, it is likely that given what you see, you may implicitly and inarticulately appraise the situation as acutely threatening. Then, there are a number of physiological changes, involving a variety (...) of systems controlled by the autonomic nervous system. Your heart races, your breathing becomes strained and your start trembling. These changes are accompanied by an expression of fear on your face: your mouth opens and your eyes widen while you stare at the wolf. There is also a kind of experience that you undergo. You are likely to feel a sort of pang, something that might consist in the perception of the physiological changes you are going through. Moreover, a number of thoughts are likely to cross your mind. You might think that the wild beast is about to tear you into pieces and that you’ll never escape from this. In addition to this, your attention focuses on the wolf and its movement, as well as, possibly, ways of escaping or defending yourself. Last, but not least, your fear is likely to come with a motivation, such as an urge to run away or to strike back. Whatever the details of the story, it is clear that a typical emotion episode involves a number of different components. Roughly, these components are a) a sensory perception or more generally an informational component, b) a kind of appraisal, d) physiological changes, c) conscious feelings, d) cognitive and attentional processes, and e) an actiontendency or more generally a motivational component. One central question in the theory of emotion is which, if any, of these components, constitute the emotion.. (shrink)

I evaluate two claims; that (a) Jesus’ message as recorded in the gospels implies exclusivism with respect to salvation and that, correspondingly, (b) Christians should be exclusivists with respect to salvation. I evaluate these claims through a cataloguing and evaluation of the logical condition involved in each of the claims regarding conditions for salvation made by Jesus in the Gospel of John. As a result, I argue that (a) is false and that, correspondingly, so is (b).

The broaden‐and‐build theory (CitationFredrickson, 1998, Citation2001) hypothesises that positive emotions broaden the scope of attention and thought‐action repertoires. Two experiments with 104 college students tested these hypotheses. In each, participants viewed a film that elicited (a) amusement, (b) contentment, (c) neutrality, (d) anger, or (e) anxiety. Scope of attention was assessed using a global‐local visual processing task (Experiment 1) and thought‐action repertoires were assessed using a Twenty Statements Test (Experiment 2). Compared to a neutral state, positive emotions broadened the scope (...) of attention in Experiment 1 and thought‐action repertoires in Experiment 2. In Experiment 2, negative emotions, relative to a neutral state, narrowed thought‐action repertoires. Implications for promoting emotional well‐being and physical health are discussed. (shrink)

There remains only the obligation to thank those who have helped me with specific suggestions and the editors who have kindly granted permission to reprint material which first appeared in the pages of their journals. To the former group belong Alan B. Brinkley and Max O. Hocutt Portion of chap ters I and VI were published in Philosophy of Science; of chapters IV and V in Perspectives in Biology and Medicine; of chapter VIII in Dialectica; of chapter IX in The (...) British lournal for the Philosophy of Science; and of chapter XIII in Synthese. J.K.F. New Orleans, 1971 PREFACE In this book I have tried to describe the scientific method, understood as the hypothetico-experimental technique of investigation which has been prac ticed so successfully in the physical sciences. It is the first volume of a three-volume work on the philosophy of science, each of which, however, is complete and independent. A second volume will contain an account of the domain in which the method operates and a history of empiricism. A third volume will be devoted to the philosophy of science proper: the metaphysics and epistemology presupposed by the method, its logical structure, and the ethical implications of its results. (shrink)

There remains only the obligation to thank those who have helped me with specific suggestions and the editors who have kindly granted permission to reprint material which first appeared in the pages of their journals. To the former group belong Alan B. Brinkley and Max O. Hocutt Portion of chap ters I and VI were published in Philosophy of Science; of chapters IV and V in Perspectives in Biology and Medicine; of chapter VIII in Dialectica; of chapter IX in The (...) British lournal for the Philosophy of Science; and of chapter XIII in Synthese. J.K.F. New Orleans, 1971 PREFACE In this book I have tried to describe the scientific method, understood as the hypothetico-experimental technique of investigation which has been prac ticed so successfully in the physical sciences. It is the first volume of a three-volume work on the philosophy of science, each of which, however, is complete and independent. A second volume will contain an account of the domain in which the method operates and a history of empiricism. A third volume will be devoted to the philosophy of science proper: the metaphysics and epistemology presupposed by the method, its logical structure, and the ethical implications of its results. (shrink)

What is the primary function of consciousness in the nervous system? The answer to this question remains enigmatic, not so much because of a lack of relevant data, but because of the lack of a conceptual framework with which to interpret the data. To this end, we have developed Passive Frame Theory, an internally coherent framework that, from an action-based perspective, synthesizes empirically supported hypotheses from diverse fields of investigation. The theory proposes that the primary function of consciousness is well-circumscribed, (...) serving the 'somatic nervous system[. For this system, consciousness serves as a frame that constrains and directs skeletal muscle output, thereby yielding adaptive behavior. The mechanism by which consciousness achieves this is more counterintuitive, passive, and “low level” than the kinds of functions that theorists have previously attributed to consciousness. Passive frame theory begins to illuminate (a) what consciousness contributes to nervous function, (b) how consciousness achieves this function, and (c) the neuroanatomical substrates of conscious processes. Our untraditional, action-based perspective focuses on olfaction instead of on vision and is 'descriptive' (describing the products of nature as they evolved to be) rather than 'normative' (construing processes in terms of how they should function). Passive frame theory begins to isolate the neuroanatomical, cognitive-mechanistic, and representational (e.g., conscious contents) processes associated with consciousness. (shrink)

The generally agreed upon principle that legality and ethics can come apart is frequently overlooked in our professional ethics education and decision-making procedures. The crux of the issue is that we teach in our philosophy classes that the law can sometimes be unethical, but then clearly state in nursing codes of ethics that students should always follow the law. The law could no doubt give us some reason to choose action A over action B, but in professional contexts we frequently (...) treat the law as a side-constraint that limits the logical space of choices to exclude even consideration of action B. If B is the mandatory action, this in effect forces professionals to do something unethical by preventing them from ever seeing the ethical action as an option. This is a problem. Ultimately we concede that there might be an irresolvable tension in competing normative interests in ethics and the law, though we suggest that a more nuanced approach to ethical code formation could help alleviate the issue somewhat. (shrink)

The broaden‐and‐build theory (CitationFredrickson, 1998, Citation2001) hypothesises that positive emotions broaden the scope of attention and thought‐action repertoires. Two experiments with 104 college students tested these hypotheses. In each, participants viewed a film that elicited (a) amusement, (b) contentment, (c) neutrality, (d) anger, or (e) anxiety. Scope of attention was assessed using a global‐local visual processing task (Experiment 1) and thought‐action repertoires were assessed using a Twenty Statements Test (Experiment 2). Compared to a neutral state, positive emotions broadened the scope (...) of attention in Experiment 1 and thought‐action repertoires in Experiment 2. In Experiment 2, negative emotions, relative to a neutral state, narrowed thought‐action repertoires. Implications for promoting emotional well‐being and physical health are discussed. (shrink)