This paper describes the change of emphasis that occurred in the teaching of ethics to small groups of clinical students. Although the original focus of the course was on the analysis of ethical dilemmas associated with individual patients known to the students, it soon became evident that there were, for the students themselves, more fundamental ethical dilemmas in their new role as clinical students. These included worries about how to respond when patients asked questions which their consultants had previously deceived (...) them about, worries about inflicting pain on patients, as with intravenous cannulation, and the role of the medical student in the clinical team. We emphasise the need to explore student experiences as part of the process of ethics teaching. (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)

Pediatric oncology has a strong research culture. Most pediatric oncologists are investigators, involved in clinical care as well as research. As a result, a remarkable proportion of children with cancer enrolls in a trial during treatment. This paper discusses the ethical consequences of the unprecedented integration of research and care in pediatric oncology from the perspective of parents and physicians. An empirical ethical approach, combining (1) a narrative review of (primarily) qualitative studies on parents' and physicians' experiences of the pediatric (...) oncology research practice, and (2) comparison of these experiences with existing theoretical ethical concepts about (pediatric) research. The use of empirical evidence enriches these concepts by taking into account the peculiarities that ethical challenges pose in practice. Analysis of the 22 studies reviewed revealed that the integration of research and care has consequences for the informed consent process, the promotion of the child's best interests, and the role of the physician (doctor vs. scientist). True consent to research is difficult to achieve due to the complexity of research protocols, emotional stress and parents' dependency on their child's physician. Parents' role is to promote their child's best interests, also when they are asked to consider enrolling their child in a trial. Parents are almost never in equipoise on trial participation, which leaves them with the agonizing situation of wanting to do what is best for their child, while being fearful of making the wrong decision. Furthermore, a therapeutic misconception endangers correct assessment of participation, making parents inaccurately attribute therapeutic intent to research procedures. Physicians prefer the perspective of a therapist over a researcher. Consequently they may truly believe that in the research setting they promote the child's best interests, which maintains the existence of a therapeutic misconception between them and parents. Due to the integration of research and care, their different ethical perspectives become intertwined in the daily practice of pediatric oncology. Increasing awareness of what this means for the communication between parents and physicians is essential. Future research should focus on efforts that overcome the problems that the synchronicity of research and care evokes. (shrink)

Originally published in 1988, M. C. Dillon's classic study of Merleau-Ponty is now available in a revised second edition containing a new preface and a new ...

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)

Two approaches have emerged to resolve discrepancies between predictions and observations at galactic and cosmological scales: introducing dark matter or modifying the laws of gravity. Practitioners of each approach claim to better satisfy a different explanatory ideal, either unification or simplicity. In this chapter, we take a closer look at the ideals and at the successes of these approaches in achieving them. Not only are these ideals less divisive than assumed, but moreover we argue that the approaches are focusing on (...) different aspects of the same ideal. This realisation opens up the possibility of a more fruitful trading zone between dark matter and modified gravity communities. (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)

Dispositions are essential to our understanding of the world. Dispositions: A Debate is an extended dialogue between three distinguished philosophers - D.M. Armstrong, C.B. Martin and U.T. Place - on the many problems associated with dispositions, which reveals their own distinctive accounts of the nature of dispositions. These are then linked to other issues such as the nature of mind, matter, universals, existence, laws of nature and causation.

'Why did the window break when it was hit by the stone? Because the window is brittle and the stone is hard; hardness and brittleness are powers, dispositional properties or dispositions.' Dispositions are essential to our understanding of the world. This book is a record of the debate on the nature of dispositions between three distinguished philosophers - D. M. Armstrong, C. B. Martin and U. T. Place - who have been thinking about dispositions all their working lives. Their (...) distinctive accounts cover many of the issues surrounding dispositions such as the nature of mind, matter, universals, existence, laws of nature and causation. Dispositions illuminates this central topic in analytic philosophy and at the same time highlights deeper concerns of metaphysics. (shrink)

BackgroundFor many decades, the debate on children’s competence to give informed consent in medical settings concentrated on ethical and legal aspects, with little empirical underpinnings. Recently, data from empirical research became available to advance the discussion. It was shown that children’s competence to consent to clinical research could be accurately assessed by the modified MacArthur Competence Assessment Tool for Clinical Research. Age limits for children to be deemed competent to decide on research participation have been studied: generally children of 11.2 (...) years and above were decision-making competent, while children of 9.6 years and younger were not. Age was pointed out to be the key determining factor in children’s competence. In this article we reflect on policy implications of these findings, considering legal, ethical, developmental and clinical perspectives.DiscussionAlthough assessment of children’s competence has a normative character, ethics, law and clinical practice can benefit from research data. The findings may help to do justice to the capacities children possess and challenges they may face when deciding about treatment and research options. We discuss advantages and drawbacks of standardized competence assessment in children on a case-by-case basis compared to application of a fixed age limit, and conclude that a selective implementation of case-by-case competence assessment in specific populations is preferable. We recommend the implementation of age limits based on empirical evidence. Furthermore, we elaborate on a suitable model for informed consent involving children and parents that would do justice to developmental aspects of children and the specific characteristics of the parent-child dyad.SummaryPrevious research outcomes showed that children’s medical decision-making capacities could be operationalized into a standardized assessment instrument. Recommendations for policies include a dual consent procedure, including both child as well as parents, for children from the age of 12 until they reach majority. For children between 10 and 12 years of age, and in case of children older than 12 years in special research populations of mentally compromised patients, we suggest a case-by-case assessment of children’s competence to consent. Since such a dual consent procedure is fundamentally different from a procedure of parental permission and child assent, and would imply a considerable shift regarding some current legislations, practical implications are elaborated. (shrink)

As of October 23, 2020, almost 42 million cases of COVID-19 have been reported globally. Although many different treatments have been applied in infected...

For decades, the discussion on children’s competence to consent to medical issues has concentrated around normative concerns, with little progress in clinical practices. Decision-making competence is an important condition in the informed consent model. In pediatrics, clinicians need to strike a proper balance in order to both protect children’s interests when they are not fully able to do so themselves and to respect their autonomy when they are. Children’s competence to consent, however, is currently not assessed in a standardized way. (...) Moreover, the correlation between competence to give informed consent and age in children has never been systematically investigated, nor do we know which factors exactly contribute to children’s competence. (shrink)

First Philosophy: Knowing and Being brings together over thirty classic and contemporary readings in epistemology and metaphysics. Mindful of the intrinsic difficulty of the material, the editors provide comprehensive introductions both to each topic and to each individual selection. By presenting a detailed discussion of the historical and intellectual background to each piece, the editors enable readers to approach the material without unnecessary barriers to understanding. A brief introduction to arguments is included, as are appendices on terminology and philosophical puzzles (...) and paradoxes. (shrink)

This white paper outlines the plans of the History Philosophy Culture Working Group of the Next Generation Event Horizon Telescope Collaboration.

The removal of water from mines was one of the key issues that former miners had to deal with. Roman colonists brought new technology to the Iberian Peninsula that addressed this problem. However, they did not invent this technology because it had already been applied to the growth of other endeavours in the Hellenistic society throughout the Eastern Mediterranean. In the mine, the Archimedes screw, waterwheels, bucket pulleys, and Ctesibius pumps were the primary drainage systems. In this essay, the primary (...) characteristics, and modes of operation of machines are examined. Without leaving out the most significant finds made in the southwest of the Iberian Peninsula, one of the regions with the longest history of mining exploitation. To serve as a foundation for future research in this field, this work compares the primary mining mechanisms in ancient Huelva on a qualitative and quantitative level by the implementation of a TOPSIS methodology, a multi-criteria decision analysis method. (shrink)

Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences of (...) parents/patients at enrolment, documented by a questionnaire, with preferences developed during follow-up by an interview-study to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study. This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug, currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. (shrink)

Andrew Bailey's highly-regarded introductory anthology has been revised and updated in this new concise edition. First Philosophy : Knowing and Being brings together over thirty classic and contemporary readings in epistemology and metaphysics. Mindful of the intrinsic difficulty of the material, the editors provide comprehensive introductions both to each topic and to each individual selection. By presenting a detailed discussion of the historical and intellectual background to each piece, the editors enable readers to approach the material without unnecessary barriers to (...) understanding. A brief introduction to arguments is included, as are appendices on terminology and philosophical puzzles and paradoxes. (shrink)

Peter Abelard (1079–1142 ce) was the most wide‐ranging philosopher of the twelfth century. He quickly established himself as a leading teacher of logic in and near Paris shortly after 1100. After his affair with Heloise, and his subsequent castration, Abelard became a monk, but he returned to teaching in the Paris schools until 1140, when his work was condemned by a Church Council at Sens. His logical writings were based around discussion of the “Old Logic”: Porphyry's Isagoge, aristotle'S Categories and (...) On Interpretation and boethius'S textbook on topical inference. They comprise a freestanding Dialectica (“Logic”; probably c.1116), a set of commentaries (known as the Logica [Ingredientibus], c. 1119) and a later (c. 1125) commentary on the Isagoge (Logica Nostrorum Petititoni Sociorum or Glossulae). In a work Abelard called his Theologia, issued in three main versions (between 1120 and c.1134), he attempted a logical analysis of trinitarian relations and explored the philosophical problems surrounding God's claims to omnipotence and omniscience. The Collationes (“Debates,” also known as “Dialogue between a Christian, a Philosopher and a Jew”; probably c.1130) present a rational investigation into the nature of the highest good, in which the Christian and the Philosopher (who seems to be modeled on a philosopher of pagan antiquity) are remarkably in agreement. The unfinished Scito teipsum (“Know thyself,” also known as the “Ethics”; c.1138) analyses moral action. (shrink)

Inspired by Martin Buber's I and Thou, the author holds that the self is neither mind nor body, but rather the "I" which engages in dialogues with itself, with its fellows, and with God. Philosophers and scientists are criticized for their "reductionism" with regard to the self, and the Hellenic tendency to view history and the self as "structured artifacts" is rejected. The author calls for renewed allegiance to the Hebraic heritage of Western culture, and for a more religious (...) view of the self and its role in history. He is perhaps less explicit than one might wish concerning the positive contributions which such a view could make.--C. M. (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)

We introduce and study a natural extension of Marcus external contextual grammars. This mathematically simple mechanism which generates a proper subclass of simple matrix languages, known to be mildly context-sensitive ones, is still mildly context-sensitive. Furthermore, we get an infinite hierarchy of mildly context-sensitive families of languages. Then we attempt to fill a gap regarding the linguistic relevance of these mechanisms which consists in defining a tree structure on the strings generated by many-dimensional external contextual grammars, and investigate some related (...) issues. Several open problems are finally discussed. (shrink)