It is estimated that 300,000 children 0–14 years of age are diagnosed with cancer worldwide each year. While the absolute risk of cancer in children is low, it is the leading cause of death due to disease in children in high‐income countries. In spite of this, the etiologies of pediatric cancer are largely unknown. Environmental exposures have long been thought to play an etiologic role. However, to date, there are few well‐established environmental risk factors for pediatric malignancies, likely due to (...) technical barriers in collecting biological samples prospectively in pediatric populations for direct measurements. In this review, we propose the use of novel or underutilized biospecimens (dried blood spots and teeth) and molecular approaches for exposure assessment (epigenetics, metabolomics, and somatic mutational profiles). Future epidemiologic studies of pediatric cancer should incorporate novel exposure assessment methodologies, data on molecular features of tumors, and a more complete assessment of gene‐environment interactions. (shrink)

BackgroundIn the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.MethodsBetween 2013 and 2019, 8252 participants (...) (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported.ResultsSevere structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy.ConclusionThe management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/nct02220582. (shrink)

Michael J. Zimmerman explores whether and how our ignorance about ourselves and our circumstances affects what our moral obligations and moral rights are. He rejects objective and subjective views of the nature of moral obligation, and presents a new case for a 'prospective' view.

Much has been published about the ethical issues encountered by clinicians in genetics/genomics, but those experienced by clinical laboratory scientists are less well described. Clinical laboratory scientists now frequently face navigating ethical problems in their work, but how they should be best supported to do this is underexplored. This lack of attention is also reflected in the ethics tools available to clinical laboratory scientists such as guidance and deliberative ethics forums, developed primarily to manage issues arising within the clinic.We explore (...) what ethical issues are being experienced by clinical scientists, how they think such issues could be best analysed and managed, and whether their practice might be enhanced by more situated approaches to ethics deliberation and practice such as ethical preparedness. From thematic analysis of cases presented by clinical scientists at a specially convened meeting of the UK Genethics Forum, we derived three main ethical themes: (1) the redistribution of labour and responsibilities resulting from the practice of genomic medicine; (2) the interpretation and certainty of results and (3) the proposal that better standardisation and consistency of ethical approaches (for example, more guidelines and policy) could resolve some of the challenges arising.We argue that although standardisation is important for promoting shared understandings of good (including ethical) practice, supplementary approaches to enhance and sustain ethical preparedness will be important to help clinical scientists and others in the recently expanded genetic/genomic medicine environment foster quality ethical thinking. (shrink)

Jian Zhou,* Weiqiang Ju,* Xiaopeng Yuan, Xiaofeng Zhu, Dongping Wang, Xiaoshun HeOrgan Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contributed equally to this work: Hyperosmolar nonketotic hyperglycemic coma is a serious, rare complication induced by methylprednisolone pulse therapy for acute rejection after orthotopic liver transplantation. Herein, we report an unusual case of a 58-year-old woman who experienced acute rejection at 30 months after OLT, only one case in which HNKHC resulted in MP (...) pulse therapy for acute rejection in all 913 recipients in our center. The general morbidity of HNKHC was 1.09‰ in this study. HNKHC is characterized by rapid onset, rapid progression, and a lack of specific clinical manifestations. High-dose MP management was a clear risk factor. The principle of treatment included rapid rehydration, low-dose insulin infusion, and correcting disorders of electrolytes and acidosis. In conclusion, clinicians considering MP pulse therapy after OLT should be alert to the occurrence of HNKHC. Keywords: liver transplantation, complications, hyperosmolar nonketotic hyperglycemic coma, methylprednisolone pulse therapy, principle of treatment. (shrink)

This essay is written on the following premises and argues for them. “Enlightenment” is a word or signifier, and not a single or unifiable phenomenon which it consistently signifies. There is no single or unifiable phenomenon describable as “the Enlightenment,” but it is the definite article rather than the noun which is to be avoided. In studying the intellectual history of the late seventeenth century and the eighteenth, we encounter a variety of statements made, and assumptions proposed, to which the (...) term “Enlightenment” may usefully be applied, but the meanings of the term shift as we apply it. The things are connected, but not continuous; they cannot be reduced to a single narrative; and we find ourselves using the word “Enlightenment” in a family of ways and talking about a family of phenomena, resembling and related to one another in a variety of ways that permit of various generalizations about them. We are not, however, committed to a single root meaning of the word “Enlightenment,” and we do not need to reduce the phenomena of which we treat to a single process or entity to be termed “the” Enlightenment. It is a reification that we wish to avoid, but the structure of our language is such that this is difficult, and we will find ourselves talking of “the French” or “the Scottish,” “the Newtonian” or the “the Arminian” Enlightenments, and hoping that by employing qualifying adjectives we may constantly remind ourselves that the keyword “Enlightenment” is ours to use and should not master us. (shrink)

This manuscript reports on a landmark symposium on the ethical, legal and technical challenges of xenotransplantation in the UK. King’s College London, with endorsement from the British Transplantation Society (BTS), and the European Society of Organ Transplantation (ESOT), brought together a group of experts in xenotransplantation science, ethics and law to discuss the ethical, regulatory and technical challenges surrounding translating xenotransplantation into the clinical setting. The symposium was the first of its kind in the UK for 20 years. This paper (...) summarises the content of the expert lectures showcasing the progress which has been made in xenotransplantation including—the history of xenotransplantation, advances in gene edited animals and progress towards clinical xenotransplantation. We then set out the ethical and legal issues still to be resolved. Finally, we report the themes of the roundtable discussion highlighting areas of consensus and controversy. While the detail of the legal discussion was directed towards the UK, the principles and summary reported here are intended to be applicable to any jurisdiction seeking to implement clinical xenotransplantation. (shrink)

The first English translation of Fichte’s second set of 1804 lectures on the Wissenschaftslehre.

On its first appearance in 1960, J.O. Urmson's Concise encyclopedia of Western philosophy and philosophers established itself as a classic. Its contributors included many of the leading philosophers of the English-speaking world: Ryle, Hare, Strawson, Ayer, Dummett, Williams and many others. They wrote with an authority and individuality which made the Encyclopedia into a lively and engaging introduction to philosophy as well as a convenient reference work. For this edition, supervised by Jonathan Rée, the original articles have been revised and (...) updated, and eighty articles by thirty one new authors have been added. The additions take account of recent developments in philosophy, of literary, historical and political issues in philosophy, and of developments in continental thought, including in Marxism, psychoanalysis, phenomenology, existentialism, structuralism, post-structuralism and deconstruction. There is a clear, integral cross-referencing system which allows the reader to identify points of overlap between philosophical traditions and their personalities at a glance. (shrink)