Plato's Republic has proven to be of astounding influence and importance. Justly celebrated as Plato's central text, it brings together all of his prior works, unifying them into a comprehensive vision that is at once theological, philosophical, political and moral. The essays in this volume provide a picture of the most interesting aspects of the Republic, and address questions that continue to puzzle and provoke, such as: Does Plato succeed in his argument that the life of justice is the most (...) attractive one? Is his tripartite analysis of the soul coherent and plausible? Why does Plato seem to have to force his philosopher-guardians to rule when they know this is something that they ought to do? What is the point of the strange and complicated closing Myth of Er? This volume will be essential to those looking for thoughtful and detailed excursions into the problems posed by Plato's text and ideas. (shrink)

v. 1. Nicomachean ethics. Politics. The Athenian Constitution. Rhetoric. On Poetics.--v. 2. Logic.--v. 3. Physics. Metaphysics. On the soul. Short physical treaties.--v. 4. On the heavens. On generation and corruption. Meteorology. Biological treatises.

A substantial body of evidence suggests that autobiographical recollection and simulation of future happenings activate a shared neural network. Many of the neural regions implicated in this network are affected in patients with bipolar disorder , showing altered metabolic functioning and/or structural volume abnormalities. Studies of autobiographical recall in BD reveal overgeneralization, where autobiographical memory comprises primarily factual or repeated information as opposed to details specific in time and in place and definitive of re-experiencing. To date, no study has examined (...) whether these deficits extend to future event simulation. We examined the ability of patients with BD and controls to imagine positive, negative and neutral future events using a modified version of the Autobiographical Interview that allowed for separation of episodic and non-episodic details. Patients were selectively impaired in imagining future positive, negative, and neutral episodic details; simulation of non-episodic details was equivalent across groups. (shrink)

This paper presents a theoretical elaboration of the ethical framework of classical capitalism as formulated by Adam Smith in reaction to the dominant mercantilism of his day. It is seen that Smith's project was profoundly ethical and designed to emancipate the consumer from a producer and state dominated economy. Over time, however, the various dysfunctions of a capitalist economy — e.g., concentration of wealth, market power — became manifest and the utilitarian ethical basis of the system eroded. Contemporary capitalism, dominated (...) as it is by large corporations, entrenched political interests and persistent social pathologies, bears little resemblance to the system which Smith envisioned would serve the common man. Most critiques of capitalism are launched from a Marxian-based perspective. We find, however, that by illustrating the wide gap between the reality of contemporary capitalism and the model of amoral political economy developed by Smith, the father of capitalism proves to be the most trenchant critic of the current order. (shrink)

While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

Chi sites are examples of special sites enhancing homologous recombination in their region of the chromosome. Chi, 5′ G‐C‐T‐G‐G‐T‐G‐G3′, is a recognition site for the RecBC enzyme, which nicks DNA near Chi as it unwinds DNA. A molecular model of genetic recombination incorporating these features is reviewed.

This introduction to the Common Knowledge symposium titled “Comparative Relativism” outlines a variety of intellectual contexts where placing the unlikely companion terms comparison and relativism in conjunction offers analytical purchase. If comparison, in the most general sense, involves the investigation of discrete contexts in order to elucidate their similarities and differences, then relativism, as a tendency, stance, or working method, usually involves the assumption that contexts exhibit, or may exhibit, radically different, incomparable, or incommensurable traits. Comparative studies are required to (...) treat their objects as alike, at least in some crucial respects; relativism indicates the limits of this practice. Jensen argues that this seeming paradox is productive, as he moves across contexts, from Lévi-Strauss's analysis of comparison as an anthropological method to Peter Galison's history of physics, and on to the anthropological, philosophical, and historical examples offered in symposium contributions by Barbara Herrnstein Smith, Eduardo Viveiros de Castro, Marilyn Strathern, and Isabelle Stengers. Comparative relativism is understood by some to imply that relativism comes in various kinds and that these have multiple uses, functions, and effects, varying widely in different personal, historical, and institutional contexts that can be compared and contrasted. Comparative relativism is taken by others to encourage a “comparison of comparisons,” in order to relativize what different peoples—say, Western academics and Amerindian shamans—compare things “for.” Jensen concludes that what is compared and relativized in this symposium are the methods of comparison and relativization themselves. He ventures that the contributors all hope that treating these terms in juxtaposition may allow for new configurations of inquiry. (shrink)

Significant associations have been found between specific human leukocyte antigen (HLA) alleles and organ transplant rejection, autoimmune disease development, and the response to infection. Traditional searches for disease associations have conventionally measured risk associated with the presence of individual HLA alleles. However, given the high level of HLA polymorphism, the pattern of amino acid variability, and the fact that most of the HLA variation occurs at functionally important sites, it may be that a combination of variable amino acid sites shared (...) by several alleles (shared epitopes) are better descriptors of the actual causative genetic variants. Here we describe a novel approach to genetic association analysis in which genes/proteins are broken down into smaller sequence features and then variant types defined for each feature, allowing for independent analysis of disease association with each sequence feature variant type. We have used this approach to analyze a cohort of systemic sclerosis patients and show that a sequence feature composed of specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk for systemic sclerosis. (shrink)

While valuable work has been done addressing clinical ethics within established healthcare systems, we anticipate that the projected growth in acquisitions of community hospitals and facilities by large tertiary hospitals will impact the field of clinical ethics and the day-to-day responsibilities of clinical ethicists in ways that have yet to be explored. Toward the goal of providing clinical ethicists guidance on a range of issues that they may encounter in the systematization process, we discuss key considerations and potential challenges in (...) implementing system-wide ethics consultation services. Specifically, we identify four models for organizing, developing, and enhancing ethics consultation activities within a system created through acquisitions: train-the-trainer, local capacity-building, circuit-riding, and consolidated accountability. We note each model’s benefits and challenges. To our knowledge, this is the first paper to consider the broader landscape of issues affected by consolidation. We anticipate that clinical ethicists, volunteer consultants, and hospital administrators will benefit from our recommendations. (shrink)

Introduction, W G Runciman Social Evolution in Primates: The Role of Ecological Factors and Male Behaviour, Carel P van Schaik Determinants of Group Size in Primates: A General Model, R I M Dunbar Function and Intention in the Calls of Non-Human Primates, Dorothy L Cheney & Robert M Seyfarth Why Culture is Common, but Cultural Evolution is Rare, Robert Boyd & Peter J Richerson An Evolutionary and Chronological Framework for Human Social Behaviour, Robert A Foley Friendship and the Banker?s Paradox: (...) Other Pathways to the Evolution of Adaptations for Altruism, John Tooby & Leda Cosmides The Early Prehistory of Human Social Behaviour: Issues of Archaeological Inference and Cognitive Evolution, Steven Mithen The Emergence of Biologically Modern Populations in Europe: A Social and Cognitive ?Revolution??, Paul Mellars Responses to Environmental Novelty: Changes in Men?s Marriage Strategies in a Rural Kenyan Community, Monique Borgerhoff Mulder Genetic Language Impairment: Unruly Grammars, M Gopnik, J Dalalakis, S E Fukuda, S Fukuda & E Kehayia The Emergence of Cultures among Wild Chimpanzees, Christophe Boesch Terrestriality, Bipedalism and the Origin of Language, Leslie C Aiello Conclusions, John Maynard Smith. (shrink)

© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

Clinical ethics consultation is largely outside the scope of regulation and oversight, despite its importance. For decades, the bioethics community has been unable to reach a consensus on whether there should be accountability in this work, as there is for other clinical activities that influence the care of patients. The American Society for Bioethics and Humanities, the primary society of bioethicists and scholars in the medical humanities and the organizational home for individuals who perform CEC in the United States, has (...) initiated a two‐step quality attestation process as a means to assess clinical ethics consultants and help identify individuals who are qualified to perform this role. This article describes the process. (shrink)

This book's importance is derived from three sources: careful conceptualization of teacher induction from historical, methodological, and international perspectives; systematic reviews of research literature relevant to various aspects of teacher induction including its social, cultural, and political contexts, program components and forms, and the range of its effects; substantial empirical studies on the important issues of teacher induction with different kinds of methodologies that exemplify future directions and approaches to the research in teacher induction.

Throughout the biological and biomedical sciences there is a growing need for, prescriptive ‘minimum information’ (MI) checklists specifying the key information to include when reporting experimental results are beginning to find favor with experimentalists, analysts, publishers and funders alike. Such checklists aim to ensure that methods, data, analyses and results are described to a level sufficient to support the unambiguous interpretation, sophisticated search, reanalysis and experimental corroboration and reuse of data sets, facilitating the extraction of maximum value from data sets (...) them. However, such ‘minimum information’ MI checklists are usually developed independently by groups working within representatives of particular biologically- or technologically-delineated domains. Consequently, an overview of the full range of checklists can be difficult to establish without intensive searching, and even tracking thetheir individual evolution of single checklists may be a non-trivial exercise. Checklists are also inevitably partially redundant when measured one against another, and where they overlap is far from straightforward. Furthermore, conflicts in scope and arbitrary decisions on wording and sub-structuring make integration difficult. This presents inhibit their use in combination. Overall, these issues present significant difficulties for the users of checklists, especially those in areas such as systems biology, who routinely combine information from multiple biological domains and technology platforms. To address all of the above, we present MIBBI (Minimum Information for Biological and Biomedical Investigations); a web-based communal resource for such checklists, designed to act as a ‘one-stop shop’ for those exploring the range of extant checklist projects, and to foster collaborative, integrative development and ultimately promote gradual integration of checklists. (shrink)

Plagiarism is a serious, yet widespread type of research misconduct, and is often neglected in developing countries. Despite its far-reaching implications, plagiarism is poorly acknowledged and discussed in the academic setting, and insufficient evidence exists in Latin America and developing countries to inform the development of preventive strategies. In this context, we present a longitudinal case study of seven instances of plagiarism and cheating arising in four consecutive classes of an Epidemiology Masters program in Lima, Peru, and describes the implementation (...) and outcomes of a multifaceted, “zero-tolerance” policy aimed at introducing research integrity. Two cases involved cheating in graded assignments, and five cases correspond to plagiarism in the thesis protocol. Cases revealed poor awareness of high tolerance to plagiarism, poor academic performance, and widespread writing deficiencies, compensated with patchwriting and copy-pasting. Depending on the events’ severity, penalties included course failure and separation from the program. Students at fault did not engage in further plagiarism. Between 2011 and 2013, the Masters program sequentially introduced a preventive policy consisting of: intensified research integrity and scientific writing education, a stepwise, cumulative writing process; honor codes; active search for plagiarism in all academic products; and a “zero-tolerance” policy in response to documented cases. No cases were detected in 2014. In conclusion, plagiarism seems to be widespread in resource-limited settings and a greater response with educational and zero-tolerance components is needed to prevent it. (shrink)

ObjectiveCo-morbid insomnia and sleep apnea is a common and debilitating condition that is more difficult to treat compared to insomnia or sleep apnea-alone. Emerging evidence suggests that cognitive behavioral therapy for insomnia is effective in patients with COMISA, however, those with more severe sleep apnea and evidence of greater objective sleep disturbance may be less responsive to CBTi. Polysomnographic sleep study data has been used to predict treatment response to CBTi in patients with insomnia-alone, but not in patients with COMISA. (...) We used randomized controlled trial data to investigate polysomnographic predictors of insomnia improvement following CBTi, versus control in participants with COMISA.MethodsOne hundred and forty five participants with insomnia and sleep apnea [apnea-hypopnea index ≥ 15] were randomized to CBTi or no-treatment control. Mixed models were used to investigate the effect of pre-treatment AHI, sleep duration, and other traditional, and novel [quantitative electroencephalography ] polysomnographic predictors of between-group changes in Insomnia Severity Index scores from pre-treatment to post-treatment.ResultsCompared to control, CBTi was associated with greater ISI improvement among participants with; higher AHI, less wake after sleep onset, and less N3 sleep. No quantitative electroencephalographic, or other traditional polysomnographic variables predicted between-group ISI change.DiscussionAmong participants with COMISA, higher OSA severity predicted a greater treatment-response to CBTi, versus control. People with COMISA should be treated with CBTi, which is effective even in the presence of severe OSA and objective sleep disturbance. (shrink)

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Biomedical Informatics: We Are What We Publish", written by Peter L. Elkin, Steven H. Brown, and Graham Wright. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the Elkin et al. paper. In subsequent issues the discussion can continue through letters to the editor.

Moral distress (MD) is well-documented within the nursing literature and occurs when constraints prevent a correct course of action from being implemented. The measured frequency of MD has increased among nurses over recent years, especially since the COVID-19 Pandemic. MD is less understood among nurse leaders than other populations of nurses. A qualitative systematic review was conducted with the aim to synthesize the experiences of MD among nurse leaders. This review involved a search of three databases (Medline, CINAHL, and APA (...) PsychINFO) which resulted in the retrieval of 303 articles. PRISMA review criteria guided authors during the article review and selection process. Following the review, six articles were identified meeting review criteria and quality was assessed using the Critical Appraisal Skills Programme (CASP) Checklist for qualitative studies. No ethical review was required for this systematic review. The six studies included in this review originated from the United States, Brazil, Turkey, and Iran. Leadership roles ranged from unit-based leadership to executive leadership. Assigned quality scores based upon CASP criteria ranged from 6 to 9 (moderate to high quality). Three analytical themes emerged from the synthesis: (1) moral distress is consuming; (2) constrained by the system; and (3) adapt to overcome. The unique contributors of MD among nurse leaders include the leadership role itself and challenges navigating moral situations as they arise. The nurse leader perspective should be considered in the development of future MD interventions. (shrink)