Bioethicists have long been concerned that seriously ill patients entering early phase (‘phase I’) treatment trials are motivated by therapeutic benefit even though the likelihood of benefit is low. In spite of these concerns, consent forms for phase I studies involving seriously ill patients generally employ indeterminate benefit statements rather than unambiguous statements of unlikely benefit. This seeming mismatch between attitudes and actions suggests a need to better understand research ethics committee members’ attitudes toward communication of potential benefits and risks (...) of early phase studies to potential subjects. We surveyed the members of two U.S. research ethics committees using a phase I gene transfer study scenario, and compared the results to a previous survey of potential subjects’ perceptions and attitudes toward benefit and risk for the same protocol. The results show that there is indeed a gap between the subjects’ perceptions and the committee members’ views on what is appropriate to be communicated to research subjects. This discrepancy is the product of both the commonly assumed optimism of the subjects and to a “protective pessimism” of the research ethics committee members. We discuss this discrepancy using “frameworks of trust” and demonstrate the need to incorporate these frameworks into the existing model of informed consent. (shrink)

Epigenetic research has brought several important technological achievements, including identifying epigenetic clocks and signatures, and developing epigenetic editing. The potential military applications of such technologies we discuss are stratifying soldiers’ health, exposure to trauma using epigenetic testing, information about biological clocks, confirming child soldiers’ minor status using epigenetic clocks, and inducing epigenetic modifications in soldiers. These uses could become a reality. This article presents a comprehensive literature review, and analysis by interdisciplinary experts of the scientific, legal, ethical, and societal issues (...) surrounding epigenetics and the military. Notwithstanding the potential benefit from these applications, our findings indicate that the current lack of scientific validation for epigenetic technologies suggests a careful scientific review and the establishment of a robust governance framework before consideration for use in the military. In this article, we highlight general concerns about the application of epigenetic technologies in the military context, especially discrimination and data privacy issues if soldiers are used as research subjects. We also highlight the potential of epigenetic clocks to support child soldiers’ rights and ethical questions about using epigenetic engineering for soldiers’ enhancement and conclude with considerations for an ethical framework for epigenetic applications in the military, defense, and security contexts. (shrink)

Subjects enrolled in studies testing high risk interventions for incurable or progressive brain diseases may be vulnerable to deficiencies in informed consent, such as the therapeutic misconception. However, the definition and measurement of the therapeutic misconception is a subject of continuing debate. Our qualitative pilot study of persons enrolled in a phase I trial of gene transfer for Parkinson disease suggests potential avenues for both measuring and preventing the therapeutic misconception. Building on earlier literature on the topic, we developed and (...) tested an interview guide that focuses on how the subjects decided to participate, emphasizing the integration of subjects’ various statements that are relevant to assessing the therapeutic misconception, rather than evaluating them as isolated statements. The results indicate that a subject’s understanding of the purpose of research is best explored in juxtaposition to the subject’s motivation for participating. (shrink)

Subjects enrolled in studies testing high risk interventions for incurable or progressive brain diseases may be vulnerable to deficiencies in informed consent, such as the therapeutic misconception. However, the definition and measurement of the therapeutic misconception is a subject of continuing debate. Our qualitative pilot study of persons enrolled in a phase I trial of gene transfer for Parkinson disease suggests potential avenues for both measuring and preventing the therapeutic misconception. Building on earlier literature on the topic, we developed and (...) tested an interview guide that focuses on how the subjects decided to participate, emphasizing the integration of subjects’ various statements that are relevant to assessing the therapeutic misconception, rather than evaluating them as isolated statements. The results indicate that a subject’s understanding of the purpose of research is best explored in juxtaposition to the subject’s motivation for participating. (shrink)

The National Center for Biomedical Ontology is a consortium that comprises leading informaticians, biologists, clinicians, and ontologists, funded by the National Institutes of Health (NIH) Roadmap, to develop innovative technology and methods that allow scientists to record, manage, and disseminate biomedical information and knowledge in machine-processable form. The goals of the Center are (1) to help unify the divergent and isolated efforts in ontology development by promoting high quality open-source, standards-based tools to create, manage, and use ontologies, (2) to create (...) new software tools so that scientists can use ontologies to annotate and analyze biomedical data, (3) to provide a national resource for the ongoing evaluation, integration, and evolution of biomedical ontologies and associated tools and theories in the context of driving biomedical projects (DBPs), and (4) to disseminate the tools and resources of the Center and to identify, evaluate, and communicate best practices of ontology development to the biomedical community. Through the research activities within the Center, collaborations with the DBPs, and interactions with the biomedical community, our goal is to help scientists to work more effectively in the e-science paradigm, enhancing experiment design, experiment execution, data analysis, information synthesis, hypothesis generation and testing, and understand human disease. (shrink)

"Corpus Anima" is a collection of previously published essays written for professional Jungian journals about the unity of psyche and soma, spirit and matter, body and soul. There are also two chapters of more personal reflections, previously unpublished, including a series of articles on the mid-Atlantic Azorean Archipelago. The essays on psyche and soma come from the direct experience of their unity. We live, life moves, at the confluence of these polarities of spirit and matter, body and soul, where through (...) the capacity to hold contradiction and paradox we can become whole. Included in this collection is a published essay (Routledge) on the Portuguese poet and writer, Fernando Pessoa (1888-1935). His particular paradoxical expression of the soul and its life in the world is radically inspiring. The lines below are written on his tomb in Lisbon, resting in the same national monument with Vasco de Gama (c. 1460s-1524), world oceanic explorer. Pessoa was an explorer of inner worlds. He is, posthumously, a national treasure. I am nothing. I shall always be nothing. I cannot want to be anything. But I have in me all the dreams of the world. Cedrus Monte, PhD, is a Jungian Analyst, graduate of the C.G. Jung Institute in Switzerland (1995) where she now resides. She is originally from Northern California. Her roots lie there, even her heart; but even deeper roots, soul roots, lie in the Azores and Madeira, both autonomous island regions of Portugal. An uprooted wanderer of many lands, she has grounded herself as much as possible in the one constant earth, the body. (shrink)

Some recent discussions of narrative structure consider the narrative as a sequence of events, and assume that the structure is what is manifested by the relation between any given event and the event 1, or perhaps the whole sequence from the first event up to the th event in the book. In the present discussion this approach will be modified in two ways. It will be modified, later on, by considering what would be happening if the writer were revising his (...) work into the final version, out of a penultimate version which was, as it were, a next-most complex version: one to which some final "complexifying" process had not yet been applied. The other way in which the present discussion will modify that approach is that it will consider narrative not as one sequence of events but as an interrelated set of sequences. · 1. E.g., R. Barthes, "Introduction à l'analyse structurale du récit," Communications, no. 8 , pp.1-27. John Holloway, professor of Modern English at the University of Cambridge, has written The Victorian Sage, The Charted Mirror, The Story of the Night, Blake: The Lyric Poetry, and five volumes of verse, such as New Poems. He is presently completing a book on poetic modes from Milton to Hardy and coediting a four-volume series on English and Irish street ballads. His other contribution to Critical Inquiry," Supposition and Supersession: A Model of Analysis for Narrative Structure" appeared in the Autumn 1976 issue. (shrink)

Kinetic demixing in quaternary mixed oxides has not been investigated previously, either theoretically or experimentally. In this theoretical study, we derive simple and exact analytical expressions that describe the steady-state cation concentration profiles resulting from kinetic demixing in mixed oxides of the O type. The concentration profiles are expressed in terms of cation-vacancy exchange frequency ratios. We assume a random distribution of cations and make use of the Moleko-Allnatt exact sum-rule expression relating the phenomenological coefficients in the ternary random alloy (...) to the vacancy mechanism operative. We employ Monte Carlo simulation of kinetic demixing to verify the result of the analysis. We discuss how kinetic demixing profiles can be processed to obtain atom-vacancy exchange frequency ratios. We also discuss how atom-vacancy exchange frequencies themselves might be obtained from available diffusivities in the quaternary oxide. (shrink)

The quality of the products coming from different lines of production requires some tests called comparative life tests. For lines having the same facility, the lifetime of the product is distributed by Burr XII, the lifetime distribution, and units are tested under type-I generalized hybrid censoring scheme. The observed censoring data are used under maximum likelihood and the Bayes method to estimate the model parameters. The theoretical results are discussed and assessed through data analysis and Monte Carlo simulation study. (...) Finally, we reported some brief comments obtained from numerical computation. (shrink)

Multitrait-multimethod (MTMM) analysis is one of the most frequently employed methods to examine the validity of psychological measures. Confirmatory factor analysis (CFA) is a commonly used analytic tool for examining MTMM data through the specification of trait and method latent variables. Most contemporary CFA-MTMM models either do not allow estimating correlations between the trait and method factors or they are restricted to linear trait-method relationships. There is no theoretical reason why trait and method relationships should always be linear, and quadratic (...) relationships are frequently proposed in the social sciences. In this article, we present two approaches for examining quadratic relations between traits and methods through extended latent difference and latent means CFA-MTMM models (Pohl et al., 2008; Pohl and Steyer, 2010). An application of the new approaches to a multi-rater study of the nine inattention symptoms of attention-deficit/hyperactivity disorder in children (N = 752) and the results of a Monte Carlo study to test the applicability of the models under a variety of data conditions are described. (shrink)

Background: Mental healthcare needs person-tailored interventions. Experience Sampling Method (ESM) can provide daily life monitoring of personal experiences. This study aims to operationalize and test a measure of momentary reward-related Quality of Life (rQoL). Intuitively, quality of life improves by spending more time on rewarding experiences. ESM clinical interventions can use this information to coach patients to find a realistic, optimal balance of positive experiences (maximize reward) in daily life. rQoL combines the frequency of engaging in a relevant context (a (...) ‘behavior setting’) with concurrent (positive) affect. High rQoL occurs when the most frequent behavior settings are combined with positive affect or infrequent behavior settings co-occur with low positive affect. Methods: Resampling procedures (Monte Carlo experiments) were applied to assess the reliability of rQoL using various behavior setting definitions under different sampling circumstances, for real or virtual subjects with low-, average- and high contextual variability. Furthermore, resampling was used to assess whether rQoL is a distinct concept from positive affect. Virtual ESM beep datasets were extracted from 1058 valid ESM observations for virtual and real subjects. Results: Behavior settings defined by Who-What contextual information were most informative. Simulations of at least 100 ESM observations are needed for reliable assessment. Virtual ESM beep datasets of a real subject can be defined by Who-What-Where behavior setting combinations. Large sample sizes are necessary for reliable rQoL assessments, except for subjects with low contextual variability. rQoL is distinct from positive affect. Conclusion: rQoL is a feasible concept. Monte Carlo experiments should be used to assess the reliable implementation of an ESM statistic. Future research in ESM should asses the behavior of summary statistics under different sampling situations. This exploration is especially relevant in clinical implementation, where often only small datasets are available. (shrink)

clusions are only probably correct. On the other hand, algorithmic information theory provides a precise mathematical definition of the notion of random or patternless sequence. In this paper we shall describe conditions under which if the sequence of coin tosses in the Solovay– Strassen and Miller–Rabin algorithms is replaced by a sequence of heads and tails that is of maximal algorithmic information content, i.e., has maximal algorithmic randomness, then one obtains an error-free test for primality. These results are only of (...) theoretical interest, since it is a manifestation of the G¨ odel incompleteness phenomenon that it is impossible to “certify” a sequence to be random by means of a proof, even though most sequences have this property. Thus by using certified random sequences one can in principle, but not in practice, convert probabilistic tests for primality into deterministic ones. (shrink)