Psychiatric disorders present distinct clinical challenges which are partly attributable to their multifactorial aetiology and the absence of laboratory tests that can be used to confirm diagnosis or predict risk. Psychiatric disorders are highly heritable, but also polygenic, with genetic risk conferred by interactions between thousands of variants of small effect that can be summarized in a polygenic risk score. We discuss four areas in which the use of polygenic risk scores in psychiatric research and clinical contexts could have ethical (...) implications. First, there is concern that clinical use of polygenic risk scores may exacerbate existing health inequities. Second, research findings regarding polygenic risk could be misinterpreted in stigmatising or discriminatory ways. Third, there are concerns associated with testing minors as well as eugenics concerns elicited by prenatal polygenic risk testing. Fourth, potential challenges that could arise with the feedback and interpretation of high polygenic risk for a psychiatric disorder would require consideration. While there would be extensive overlap with the challenges of feeding back genetic findings in general, the potential clinical use of polygenic risk scoring warrants discussion in its own right, given the recency of this possibility. To this end, we discuss how lay interpretations of risk and genetic information could intersect. Consideration of these factors would be necessary for ensuring effective and constructive communication and interpretation of polygenic risk information which, in turn, could have implications for the uptake of any therapeutic recommendations. Recent advances in polygenic risk scoring have major implications for its clinical potential, however, care should be taken to ensure that communication of polygenic risk does not feed into problematic assumptions regarding mental disorders or support reductive interpretations. (shrink)

Current UK legislation is impacting upon the feasibility and cost-effectiveness of medical record-based research aimed at benefiting the NHS and the public heath. Whereas previous commentators have focused on the Data Protection Act 1998, the Health and Social Care Act 2001 is the key legislation for public health researchers wishing to access medical records without written consent. The Act requires researchers to apply to the Patient Information Advisory Group for permission to access medical records without written permission. We present a (...) case study of the work required to obtain the necessary permissions from PIAG in order to conduct a large scale public health research project. In our experience it took eight months to receive permission to access basic identifying information on individuals registered at general practices, and a decision on whether we could access clinical information in medical records without consent took 18 months. Such delays pose near insurmountable difficulties to grant funded research, and in our case £560 000 of public and charitable money was spent on research staff while a large part of their work was prohibited until the third year of a three year grant. We conclude by arguing that many of the current problems could be avoided by returning PIAG’s responsibilities to research ethics committees, and by allowing “opt-out” consent for many public health research projects. (shrink)

Current UK legislation is impacting upon the feasibility and cost-effectiveness of medical record-based research aimed at benefiting the NHS and the public heath. Whereas previous commentators have focused on the Data Protection Act 1998, the Health and Social Care Act 2001 is the key legislation for public health researchers wishing to access medical records without written consent. The Act requires researchers to apply to the Patient Information Advisory Group for permission to access medical records without written permission. We present a (...) case study of the work required to obtain the necessary permissions from PIAG in order to conduct a large scale public health research project. In our experience it took eight months to receive permission to access basic identifying information on individuals registered at general practices, and a decision on whether we could access clinical information in medical records without consent took 18 months. Such delays pose near insurmountable difficulties to grant funded research, and in our case £560 000 of public and charitable money was spent on research staff while a large part of their work was prohibited until the third year of a three year grant. We conclude by arguing that many of the current problems could be avoided by returning PIAG’s responsibilities to research ethics committees, and by allowing “opt-out” consent for many public health research projects. (shrink)

Public policy issues around access to networked information are explored and examined. Long viewed as the quintessential public good, information has evolved into a critically important market commodity in little more than a generation. New technologies and a political climate in which the meaning of universal access to information is no longer commonly understood and in which its importance is no longer taken for granted pose significant challenges for American society. Libraries, as information commons, offer the means of meeting those (...) challenges. Historical, economical, and professional factors that shape the conflict are described and discussed. (shrink)

A role of perirhinal cortex (PrC) in recognition memory for objects has been well established. Contributions of parahippocampal cortex (PhC) to this function, while documented, remain less well understood. Here, we used fMRI to examine whether the organization of item-based recognition memory signals across these two structures is shaped by object category, independent of any difference in representing episodic context. Guided by research suggesting that PhC plays a critical role in processing landmarks, we focused on three categories of objects that (...) differ from each other in their landmark suitability as confirmed with behavioral ratings (buildings > trees > aircraft). Participants made item-based recognition-memory decisions for novel and previously studied objects from these categories, which were matched in accuracy. Multi-voxel pattern classification revealed category-specific item-recognition memory signals along the long axis of PrC and PhC, with no sharp functional boundaries between these structures. Memory signals for buildings were observed in the mid to posterior extent of PhC, signals for trees in anterior to posterior segments of PhC, and signals for aircraft in mid to posterior aspects of PrC and the anterior extent of PhC. Notably, item-based memory signals for the category with highest landmark suitability ratings were observed only in those posterior segments of PhC that also allowed for classification of landmark suitability of objects when memory status was held constant. These findings provide new evidence in support of the notion that item-based memory signals for objects are not limited to PrC, and that the organization of these signals along the longitudinal axis that crosses PrC and PhC can be captured with reference to landmark suitability. (shrink)

This paper argues that research on normative issues in the life sciences will benefit from a tighter integration of philosophy of science. We examine research on ethical, legal and social issues in the life sciences (“ELSI”) and discuss three illustrative examples of normative issues that arise in different areas of the life sciences. These examples show that important normative questions are highly dependent on epistemic issues which so far have not been addressed sufficiently in ELSI, RRI and related areas of (...) research. Accordingly, we argue for the integration of research on the epistemic aspects of the relevant areas of science into ELSI research to provide a better basis for addressing normative questions. (shrink)

Inequities in access to oncology care among Indigenous peoples in Canada are well documented. Access to oncology care is mediated by a range of factors; however, emerging evidence suggests that healthcare providers, including nurses, play a significant role in shaping healthcare access. The purpose of this study was to critically examine access to oncology care among Indigenous peoples in Canada from the perspective of oncology nurses. Guided by postcolonial theoretical perspectives, interpretive descriptive and critical discourse analysis methodologies informed study design (...) and data analysis. Oncology nurses were recruited from across Canada to complete an online survey (n = 78). Nurses identified a range of barriers experienced by Indigenous peoples when accessing oncology care, yet located these barriers primarily at the individual and systems levels. Nurses perceived themselves as mediators of access to oncology care; however, their efforts to facilitate access to care were constrained by the dominance of biomedicine within healthcare. Nurses' constructions of access to oncology care highlight the embedded narrative of individualism within nursing practice and the relative invisibility of racism as a determinant of equitable access to care among Indigenous peoples. This suggests a need for oncology nurses to better understand and incorporate structural determinants of health perspectives. (shrink)

The Institute of Medicine's report, the American Medical Association's project, the Open Society Institute's and the initiative sponsored by the Robert Wood Johnson Foundation have focused attention on improving the care of dying patients. These efforts include advance care planning and the use of written advance directives. Although previous studies have provided quantitative descriptions of patient preferences for life-sustaining treatment, including those documented in written ADs, to our knowledge open-ended written preferences have not been studied. Studies of these open-ended preferences (...) could highlight issues with respect to quality end-of-life care. The purpose of this study was to explore the open-ended proxy, health, and personal care preferences of people with HIV as expressed in a written AD form. (shrink)

Introducing Philosophy: A Text with Integrated Readings, Tenth Edition is a thorough introduction to the core problems of philosophy, including explanations and background by the authors along with generous excerpts from the philosophers under discussion. Organized topically, the chapters present alternative perspectives-including analytic, continental, feminist, and non-Western viewpoints-alongside the historical works of major philosophers. The text provides the course materials that allow instructors and students to focus on a variety of philosophical problems and perspectives. Spanning 2,500 years, the selections range (...) from the oldest known fragments to cutting-edge contemporary essays. (shrink)

This comprehensive new collection is designed as a complete introduction to philosophy for students and general readers. Consisting of eleven extended essays, specially commissioned for this volume from leading philosophers, the book surveys all of the major areas of philosophy and offers an accessible but sophisticated guide to the main debates. An extended introduction provides general context and explains how the different subjects are related. The first part of the book deals with the foundations of philosophical inquiry: epistemology, philosophical logic, (...) methodology, metaphysics, and the philosophy of mind. The second part offers historical chapters, two on ancient philosophy and two on modern philosophy. Finally, two chapters deal with questions of value, ethics and aesthetics. Each chapter has a full bibliography. The contributors include Bernard Williams, Roger Scruton, Martin Davies, David Wiggins, Christopher Janaway, David Papineau, and Mark Sainsbury. Designed to be as useful to the third-year student as to the beginner, this exciting new text will give each reader a unique sense of involvement in philosophy as it is practiced today. (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)

We point out that current belief revision operations can be used to revise non-monotonic theories and we propose a new operation, called permissive belief revision. The underlying idea of permissive belief revision consists of instead of abandoning some beliefs during a revision, transforming those beliefs into weaker ones, while still keeping the resulting belief set consistent. This framework allows us to keep more beliefs than what is usual using existing belief base-based revision theories.

Media increasingly accuse firms of exploiting suppliers, and these allegations often result in lurid headlines that threaten the reputations and therefore business successes of these firms. Neither has the phenomenon of supplier exploitation been investigated from a rigorous, ethical standpoint, nor have answers been provided regarding why some firms pursue exploitative approaches. By systemically contrasting economic liberalism and just prices as two divergent perspectives on supplier exploitation, we introduce a distinction of common business practice and unethical supplier exploitation. Since supplier (...) exploitation is based on power, we elucidate several levels of power as antecedents and investigate the role of ethical climate as a moderator. This study extends Victor and Cullen’s ethical climate matrix according to a supply chain dimension and is summarized in an integrated, conceptual model of five propositions for future theory testing. Results provide a frame of reference for executives and scholars, who can now delineate unethical exploitation and understand important antecedents of the phenomenon better. (shrink)

In this article the Reformer Martin Luther is to be situated against the backdrop of his medieval theological context – considering especially Bernard of Clairvaux. It is well-known that he held in great esteem Bernard and the theology he represented. First of all, Luther's relationship to Bernard is to be investigated by way of a historiographic review of the research that was done in the past 150 years. How did one consider Luther’s attitude toward Bernard, and how did Luther (...) research specifically value this attitude? In this research, denominational positions appear to have played a important role. Secondly, the attempt is made here to sketch Bernard’s place in Luther’s own tradition. Next to the medieval scholastic theology, there were diverse other influences that became important for the young Luther. Bernard’s specific place within the complexity of medieval traditions is to be determined. This is being explained by presenting seven significant texts mainly from Luther’s works, which are added to this article. Finally, the attempt is made to determine more closely Bernard’s place in Luther’s theology between Scholasticism and Mysticism. If one wants to do justice to Bernard in Luther's works, one must take into consideration the way in which Luther has perceived him, namely as a theologian of the Scriptures, a theologian of experience and a preacher of Christ par excellence along the lines of monastic theology. (shrink)