BackgroundThe rise of Big Data-driven health research challenges the assumed contribution of medical research to the public good, raising questions about whether the status of such research as a common good should be taken for granted, and how public trust can be preserved. Scandals arising out of sharing data during medical research have pointed out that going beyond the requirements of law may be necessary for sustaining trust in data-intensive health research. We propose building upon the use of a social (...) licence for achieving such ethical governance.Main textWe performed a narrative review of the social licence as presented in the biomedical literature. We used a systematic search and selection process, followed by a critical conceptual analysis. The systematic search resulted in nine publications. Our conceptual analysis aims to clarify how societal permission can be granted to health research projects which rely upon the reuse and/or linkage of health data. These activities may be morally demanding. For these types of activities, a moral legitimation, beyond the limits of law, may need to be sought in order to preserve trust. Our analysis indicates that a social licence encourages us to recognise a broad range of stakeholder interests and perspectives in data-intensive health research. This is especially true for patients contributing data. Incorporating such a practice paves the way towards an ethical governance, based upon trust. Public engagement that involves patients from the start is called for to strengthen this social licence.ConclusionsThere are several merits to using the concept of social licence as a guideline for ethical governance. Firstly, it fits the novel scale of data-related risks; secondly, it focuses attention on trustworthiness; and finally, it offers co-creation as a way forward. Greater trust can be achieved in the governance of data-intensive health research by highlighting strategic dialogue with both patients contributing the data, and the public in general. This should ultimately contribute to a more ethical practice of governance. (shrink)

A longitudinal, epidemiological study was carried out in a rural area of Kenya with a population of about 28,000 between 1974 and 1980. Population registration during this time showed that population growth was very high between 1974 and 1978 (4·4% per year) and much lower in 1979 and 1980 (1·1%). Natural increase was nearly as high as in Kenya as a whole (3·7%) in this period. Fertility was somewhat lower than in all Kenya (the crude birth rate was 46 per (...) 1000) while mortality was substantially lower (7 per 1000). Evidence is presented supporting the argument that these low mortality rates are genuine. Levels of temporary and permanent migration are high and probably characteristic for many parts of Kenya. The change in population growth in 1979 and 1980 is probably due to changes in economic conditions leading in particular to less in-migration and to more out-migration. (shrink)

This volume contains papers and abstracts of papers delivered at the colloquium at Tihany, Hungary in 1962. There were seven sections; mathematical logic, computers and automata theory, circuit theory, mathematical linguistics, computers and programming, applications of computers in economics, artificial intelligence. Among the more interesting—to the reviewer—were these papers: one by Church concerning an independence problem in recursive arithmetic; Muller—characterizing classes of recursive functions; a long and philosophically stimulating study by Watanabe on a formalization of inductive logic; Kiefer—applications of (...) set theoretic techniques in linguistics; Abraham and Salapina—recognition of synonymity by machine; Gelernter—problem-solving graphs and heuristic programming. A number of papers which were read are not included in this volume.—P. J. M. (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)

The success of deep brain stimulation (DBS) for movement disorders and the improved understanding of the neurobiologic and neuroanatomic bases of psychiatric diseases have led to proposals to expand current DBS applications. Recent preclinical and clinical work with Alzheimer's disease and obsessive-compulsive disorder, for example, supports the safety of stimulating regions in the hypothalamus and nucleus accumbens in humans. These regions are known to be involved in addiction and overeating associated with obesity. However, the use of DBS targeting these areas (...) as a treatment modality raises common ethical considerations, which include informed consent, coercion, enhancement, threat to personhood, and manipulation of the reward center. Pilot studies for both of these conditions are currently investigational. If these studies show promise, then there is a need to address the ethical concerns related to the initiation of clinical trials including the reliability of preclinical evidence, patient selection, study design, compensation for participation and injury, cost-effectiveness, and the need for long-term follow-up. Multidisciplinary teams are necessary for the ethical execution of such studies. In addition to establishing safety and efficacy, the consideration of these ethical issues is vital to the adoption of DBS as a treatment for these conditions. We offer suggestions about the pursuit of future clinical trials of DBS for the treatment of addiction and overeating associated with obesity and provide a framework for addressing ethical concerns related to treatment. (shrink)

Current theories of breast cancer progression have been greatly influenced by the development and refinement of mouse transgenic and gene targeting technologies. Early transgenic mouse models confirmed the involvement of oncogenes, previously implicated in human breast cancer, by establishing a causal relationship between overexpression or activation of these genes and mammary tumorigenesis. More recently, the importance of genes located at sites of loss of heterozygosity in human breast cancer have been examined in mice by their targeted disruption via homologous recombination. (...) The union of these two approaches allows the generation of complex animal models that more accurately reflect the multistep nature of human breast cancer. This review will examine how the study of transgenic mice has increased our understanding of the molecular events responsible for oncogenic transformation of the mammary gland. BioEssays 22:554–563, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

fusion theory challenges efforts to see theory as inhibiting by presenting an approach that is innovative, eclectic, and subtle in order to draw out competing and constellating ideas and opinions. This collected volume of essays examines fusion theory and demonstrates how the theory can be applied to the reading of various works of Indian English novelists.

My paper is motivated by two thoughts: that there’s significant overlap between J. G. Herder’s romanticism and, what I call, the ‘late’ conceptualism of John McDowell; that recognizing this helps to settle a dispute in contemporary epistemology concerning the contents of perception. I argue, on the basis of that overlap, that “romantic conceptualism” avoids two pressing criticisms of conceptualism: It offers a reply to the argument from the fineness of grain of perceptual experience and it explains the relationship between human (...) perceptual experience and the perceptual experiences of non-human animals. I start with the interpretation of McDowell’s views, tracing the significant revisions in the period following the publication of Mind and World; then I try to compare his views with Herder’s, trying to establish a framework for responding to the more trenchant criticisms of McDowell’s non-conceptualist opponents, and the explanatory force of conceptualist hypotheses beyond the context of contemporary epistemology. The first arc of the paper, therefore, traces the evolution of McDowell’s thought concerning perceptual contents. The second attempts to demonstrate where that view converges with a romantic philosophy of mind. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

In a recent study, Becker and Elliott [Becker, C., & Elliott, M. A. . Flicker induced color and form: Interdependencies and relation to stimulation frequency and phase. Consciousness & Cognition, 15, 175–196] described the appearance of subjective experiences of color and form induced by stimulation with intermittent light. While there have been electroencephalographic studies of similar hallucinatory forms, brain activity accompanying the appearance of hallucinatory colors was never measured. Using a priming procedure where observers were required to indicate the presence (...) of one of eight target colors we compared electrophysiological correlates of hallucinatory color with brain states associated with other visual phenomena. Different target colors were accompanied by different patterns of EEG activation. However, in general, we found that the appearance of hallucinatory colors is preceded by a power decrease in the lower alpha band alongside an increase in gamma band frequencies. We argue that decreasing activity in the lower alpha band acts as a gating mechanism, inducing a switch in perception between different colors. The increasing gamma activation may correlate with the formation of a coherent conscious percept. (shrink)

This is the first really comprehensive treatment to appear in modern times of the great Alexandrian theologian's life and doctrine. Like his better known contemporaries, Fr. Chr. Baur, J. Müller, and Dorner, Redepenning also united the great heritage of intense speculative interest with the full armor of nineteenth century historical scholarship. In spite of his many footnotes he has a clear and rich style, focusing on major theological and historical questions. He has sense enough to leave some highly specialized issues (...) to a number of appendices. The first volume is devoted to Origen's early doctrines in their historical context. The second volume has two major sections: one deals in the fashion of the first volume with the development of Origen's later doctrines. The other treats in a systematic manner the whole of Origen's doctrines in terms of God, the fallen world, and the redemption. These are the most important chapters of the book but they must be read as Redepenning intended: only after the historical sections. This beautifully printed book is an indispensable instrument to any further study of the history of Patristic thought.--M. J. V. (shrink)

CONSCIOUSNESS AND THE BRAIN SELF-REGULATION PARADOX The relationship of consciousness to biology has intrigued mankind thoroughout recorded history. However, little progress has been made not only in understanding these issues but also in raising fundamental questions central to the problem. As Davidson and Davidson note in their introduction, William James suggested, almost a century ago in his Principles of Psychology, that the brain was the organ of mind and be havior. James went so far as to suggest that the remainder (...) of the Principles was but a "footnote" to this central thesis. This volume brings together diverse biobehavioral scientists who are addressing the various aspects of the mindlbrainlbodylbehavior issue. Although some of the authors have previously published together in other volumes, by and large the particular combination of authors and topics selected by the editors makes this volume unique and timely. Unlike the Consciousness and Self-Regulation series (Schwartz & Shapiro, 1976, 1978), also published by Plenum, this volume is devoted entirely to a psychobiological approach to consciousness. Although readers will differ in their interest in specific chapters, the well-rounded investigator who is concerned with the psychobiology of consciousness will want to become intimately acquainted with all the views presented in this volume. As noted by the individual contributors, the topic of this volume stimulates fundamental questions which, on the surface, may appear trivial, yet, on further reflection, turn out to have deep significance. (shrink)

SummaryIt is shown that the concept of understanding cannot be reduced to a combination of knowing that, knowing how, and knowledge by acquaintence. First, it is shown that understanding and knowledge have different objects. Then “understanding what” is analyzed along Aristotelian lines. In the central part of the paper it is shown that understanding objects defined by constitutive rules involves a non‐propositional component. This notion of “understanding” is shown to cut across the humanist‐scientist dichotomy.

Despite optimistic reports about the results of amputation for advanced vascular disease, the patient’s assessment of advantages and disadvantages is seldom acknowledged. A detailed social study of 67 amputees has revealed considerable disparity between the patient’s views and those of the medical staff. About a third of the patients are forced to retire from active work by the amputation; about three-quarters report a serious decline in their social activities; only about half are really independent with prostheses in the long term; (...) a quarter report severe and intractable symptoms related to their amputation stumps; only about a quarter feel that the amputation was definitely beneficial; and only about one in five feel that the medical staff have provided adequate support during their hospital stay. Amputees face physical and financial disability, isolation, and discomfort. Every effort must be made to explain the implications of amputation honestly and realistically and to ensure continuing patient assessment and support. (shrink)