It has long been recognized that cancer onset and progression represent a type of reversion to an ancestral quasi‐unicellular phenotype. This general concept has been refined into the atavistic model of cancer that attempts to provide a quantitative analysis and testable predictions based on genomic data. Over the past decade, support for the multicellular‐to‐unicellular reversion predicted by the atavism model has come from phylostratigraphy. Here, we propose that cancer onset and progression involve more than a one‐off multicellular‐to‐unicellular reversion, and are (...) better described as a series of reversionary transitions. We make new predictions based on the chronology of the unicellular‐eukaryote‐to‐multicellular‐eukaryote transition. We also make new predictions based on three other evolutionary transitions that occurred in our lineage: eukaryogenesis, oxidative phosphorylation and the transition to adaptive immunity. We propose several modifications to current phylostratigraphy to improve age resolution to test these predictions. Also see the video abstract here: https://youtu.be/3unEu5JYJrQ. (shrink)

Recent magnetic resonance imaging and pathological studies have indicated that axonal loss is a major contributor to disease progression in multiple sclerosis. 1 H magnetic resonance spectroscopy, through measurement of N -acetyl aspartate, a neuronal marker, provides a unique tool to investigate this. Patients with primary progressive multiple sclerosis have few lesions on conventional MRI, suggesting that changes in normal appearing white matter, such as axonal loss, may be particularly relevant to disease progression in this group. To test this hypothesis (...) NAWM was studied with MRS, measuring the concentration of N -acetyl derived groups. Single-voxel MRS using a water-suppressed PRESS sequence was carried out in 24 patients with primary progressive multiple sclerosis and in 16 age-matched controls. Ratios of metabolite to creatine concentration were calculated in all subjects, and absolute concentrations were measured in 18 patients and all controls. NA/Cr was significantly lower in NAWM in patients than in controls, as was the absolute concentration of NA. There was no significant difference in the absolute concentration of creatine between the groups. This study supports the hypothesis that axonal loss occurs in NAWM in primary progressive multiple sclerosis and may well be a mechanism for disease progression in this group. (shrink)

BackgroundCentral to ethically justified clinical trial design is the need for an informed consent process responsive to how potential subjects actually comprehend study participation, especially study goals, risks, and potential benefits. This will be particularly challenging when studying deep brain stimulation and whether it impedes symptom progression in Parkinson’s disease, since potential subjects will be Parkinson’s patients for whom deep brain stimulation will likely have therapeutic value in the future as their disease progresses.MethodAs part of an expanded informed consent process (...) for a pilot Phase I study of deep brain stimulation in early stage Parkinson’s disease, an ethics questionnaire composed of 13 open-ended questions was distributed to potential subjects. The questionnaire was designed to guide potential subjects in thinking about their potential participation.ResultsWhile the purpose of the study (safety and tolerability) was extensively presented during the informed consent process, in returned responses 70 percent focused on effectiveness and 91 percent included personal benefit as potential benefit from enrolling. However, 91 percent also indicated helping other Parkinson’s patients as motivation when considering whether or not to enroll.ConclusionsThis combination of responses highlights two issues to which investigators need to pay close attention in future trial designs: (1) how, and in what ways, informed consent processes reinforce potential subjects’ preconceived understandings of benefit, and (2) that potential subjects see themselves as part of a community of Parkinson’s sufferers with responsibilities extending beyond self-interest. More importantly, it invites speculation that a different paradigm for informed consent may be needed. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Journal of the History of Philosophy 41.2 (2003) 277-278 [Access article in PDF] John Hedley Brooke, Margaret J. Osler, and Jitse M. van der Meer, editors. Science in Theistic Contexts: Cognitive Dimensions. Chicago: University of Chicago Press Journals Division, 2001. Pp. xiii + 376. Cloth, $39.00. Paper, $25.00. Some twenty years ago, when I submitted a dissertation proposal to explore connections between theologies of creation and views of scientific (...) knowledge in the seventeenth century, my doctoral committee was not initially enthusiastic—my idea might make a good dissertation in religion, but was it really history of science? I doubt I would have a similar experience today. Not only has the "warfare" thesis of science and religion been laid permanently to rest, historians have begun seriously to question whether it makes sense even to treat "religion" and "science" in an essentialist manner as separate ways of thinking that do not ordinarily interact. Many detailed case studies demonstrating a variety of fascinating, often important connections between science and religion have appeared from leading scholars in the past two decades. This trend continues in the latest volume of Osiris, which contains sixteen essays documenting various ways in which religious beliefs have influenced the actual content and presentation of science.The volume opens with two companion essays laying out the terrain. First, Brooke engages the new methodological and conceptual problems that confront historians following the demise of the "warfare" thesis. Then Stephen Wykstra offers criteria for sorting out the various roles for metaphysical and religious beliefs (which he distinguishes) in shaping scientific knowledge. The case studies begin with E. Jamil Ragep's essay on medieval Islamic astronomy, arguing that religion sometimes had a constructive role—a rather novel claim for Islamic science, he points out. Noah J. Efron and Menachem Fisch show how early modern Jewish exegetical practices influenced David b. Solomon Gans's interpretations of astronomical texts, and quite possibly his interpretation of nature also. A Christian astronomer is next, as Peter Barker and Bernard R. Goldstein detail how Johannes Kepler's theology contributed directly to the discovery of scientific laws. Maurice A. Finnocchiaro then reviews various accounts of the Galileo affair, finding far more conflict in the subsequent historiography of the events than in the trial itself.Moving from astronomy to natural philosophy, Margaret G. Cook's essay on Robert Boyle examines the web of connections between theology, the mechanical philosophy, and [End Page 277] "the Aristotelian philosophy that he sought to replace." She demonstrates that Boyle used the classical art/nature distinction "to interpret the biblical account of the Creation and to argue that chemical techniques offered experimental confirmation that the world, created by art, worked by the same mechanical principles as artificial objects, not by the inherent agency of Aristotelian nature" (136). Margaret J. Osler also writes about Boyle. Contrary to the traditional view that final causes were expunged from science by the mechanical philosophy—a view that originated in the "positivism and scientific optimism" of the postwar period (168)—she proves that final causality remained central to the thought of Boyle and Pierre Gassendi. The essay by Stephen D. Snobelen presents substantial evidence that the famous General Scholium, appended to the second edition of Isaac Newton's Principia, was a carefully worded declaration of Newton's heterodox theology. "A Trinitarian," Snobelen concludes, "could not have written the General Scholium" (186). He also shows the degree to which Newton's theology shaped his overall natural philosophy, decisively debunking the late Richard S. Westfall's view that such influences could not be found.The final seven essays are mainly devoted to nineteenth-century science. Michael J. Crowe documents several ways in which Christian beliefs about divine goodness and the Incarnation affected astronomy. Martin Fichman shows how Alfred Russel Wallace's theism—not merely a vague spiritualism, as traditional accounts claim—"shaped the cognitive content of his mature evolutionary synthesis, which included a theoretical reconceptualization of the scope of natural selection" (227). In a revisionist account of Charles Darwin's philosophy of "nature," Phillip R. Sloan challenges the received view that... (shrink)

People often judge it unacceptable to directly harm a person, even when this is necessary to produce an overall positive outcome, such as saving five other lives. We demonstrate that similar judgments arise when people consider damage to owned objects. In two experiments, participants considered dilemmas where saving five inanimate objects required destroying one. Participants judged this unacceptable when it required violating another’s ownership rights, but not otherwise. They also judged that sacrificing another’s object was less acceptable as a means (...) than as a side-effect; judgments did not depend on whether property damage involved personal force. These findings inform theories of moral decision-making. They show that utilitarian judgment can be decreased without physical harm to persons, and without personal force. The findings also show that the distinction between means and side-effects influences the acceptability of damaging objects, and that ownership impacts utilitarian moral judgment. (shrink)

The Bible has influenced contemporary culture both positively and negatively. The present volume is a collection of papers that were discussed at an international colloquium on the use of the Bible in Ethics in the Department of Biblical Studies at the University of Sheffield in April 1995. Participants came from many parts of the world and from different backgrounds, and the papers reflect their varied interests and the contexts in which they work. The contributors, in addition to the three editors, (...) are John Barton, Bruce Birch, Mark Brett, Mark Chapman, David Clines, Philip Davies, Cheryl Exum, Stephen Fowl, Norman Gottwald, John Haldane, Walter Houston, Sharon Ringe, Chrisopher Rowland, Lisa Sowle Cahill and Gerald West. (shrink)

In “Potential Subjects’ Responses to an Ethics Questionnaire in a Phase I Study of Deep-Brain Stimulation in Early Parkinson’s Disease,” Finder, Bliton, Gill, Davis, Konrad, and Charles undertake informed consent research on what they describe as a Phase I trial of deep brain stimulation (DBS) for Parkinson’s disease. We argue that the authors should have more carefully characterized the nature of the DBS study at the start of their clinical study.

Should engineering ethics be taught? Despite the obvious truism that we all want our students to be moral engineers who practice virtuous professional behavior, I argue, in this article that the question itself obscures several ambiguities that prompt preliminary resolution. Upon clarification of these ambiguities, and an attempt to delineate key issues that make the question a philosophically interesting one, I conclude that engineering ethics not only should not, but cannot, be taught if we understand “teaching engineering ethics” to mean (...) training engineers to be moral individuals (as some advocates seem to have proposed). However, I also conclude that there is a justification to teaching engineering ethics, insofar as we are able to clearly identify the most desirable and efficacious pedagogical approach to the subject area, which I propose to be a case study-based format that utilizes the principle of human cognitive pattern recognition. (shrink)

This book presents 18 essays by leading scholars covering mortuary analysis, the archaeology of foraging and agricultural societies, cultural evolution, and archaeological method and theory, which transcend the processual/postprocessual debate in archaeology and provide examples of how archaeologists think about, and go about, studying the past. As archaeology encounters the 21st century, debate over the nature of the discipline dominates professional discourse. Archaeologists are embattled over isms: processualism, postprocessualism, scientism, and humanism are ubiquitous buzzwords in the literature. Yet archaeology is (...) a craft practiced by individuals, learned from and influenced by other individuals. Sometimes a peson, through sheer force of intellectual spirit, rises above the debate to make a mark on the field in ways that cross out schools, paradigms, and factions. It is fitting to look back at the influence one such individual has had on archaeological methods, theory, data collection, and syntheses over the last half century. This volume draws on the experience of students and colleagues who worked with and were strongly influenced by James A. Brown's approach to the past. The volume is divided into five categories, each reflecting one distinctive facet of Brown's affect on archaeology: mortuary analysis, foraging and horticultural societies, complex agriculturalists, proto-historic and historic societies, and method and theory. These diverse categories, with articles by archaeologists of many backgrounds, are drawn together by the threads of Brown's intellectual legacy. Not all authors here are in agreement with Brown's views on their subjects, but all acknolwedge that his work in the area sets a standard that needs to be met if one is to succeed. (shrink)

The underrepresentation of females in mathematics-related fields may be explained by gender differences in mathematics self-concept (rather than ability) favoring males. Mathematics self-concept typically declines with student age, differs with student ethnicity, and is sensitive to teacher influence in early schooling. We investigated whether change in mathematics self-concept occurred within the context of a longitudinal intervention to raise and sustain teacher expectations of student achievement. This experimental study was conducted with a large sample of New Zealand primary school students and (...) their teachers. Data were analyzed using longitudinal multilevel modelling with mathematics self-concept as the dependent variable and time (which represents students’ increasing age each year), gender, and ethnicity entered as predictors and achievement in mathematics included as a control variable. Interaction terms were also explored to investigate changes over time for different groups. All students demonstrated a small increase in mathematics self-concept over the three-year period of the current study but mathematics self-concept was consistently greater for boys than girls. Māori, Asian, and Other students’ initial mathematics self-concept was higher than that of New Zealand European and Pacific Islanders’ (after controlling for achievement differences). However, a statistically significant decline in mathematics self-concept occurred for Māori students alone by the end of the study. The expected age-related reduction over time in student mathematics self-concept appeared to be mitigated in association with the longitudinal study. Nevertheless, the demonstration of a comparatively lower mathematics self-concept remained for girls overall and declined for Māori. Our results reinforce implications for future research into mathematics self-concept as a possible determinant of female student career choices. (shrink)

There is a widespread assumption that the universe in general, and life in particular, is 'getting more complex with time'. This book brings together a wide range of experts in science, philosophy and theology and unveils their joint effort in exploring this idea. They confront essential problems behind the theory of complexity and the role of life within it: what is complexity? When does it increase, and why? Is the universe evolving towards states of ever greater complexity and diversity? If (...) so, what is the source of this universal enrichment? This book addresses those difficult questions, and offers a unique cross-disciplinary perspective on some of the most profound issues at the heart of science and philosophy. Readers will gain insights in complexity that reach deep into key areas of physics, biology, complexity science, philosophy and religion. (shrink)

In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target‐the‐weakness strategy. Our most detailed example involves the immune system. The absence of adaptive immunity in immunosuppressed (...) tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target‐the‐weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation. (shrink)

An indispensable and comprehensive resource for students and scholars of philosophy of religion.

Of laws in general -- Of laws directly derived from the nature of government -- Of the principles of the three kinds of government -- That the laws of education ought to be relative to the principles of government -- That the laws given by the legislator ought to be relative to the nature of government -- Consquences of the principles of different governments, with respect to the simplicity of civil and criminal laws, the form of judgements, and inflicting of (...) punishments -- Consquences of the different principles of the three governments, with respect to sumptuary laws, luxury, and the condition of women -- Of the corruption of the principles of the three governments -- Of the laws in the relation they bear to defensive force -- Of laws, in the relation they bear to offensive force. (shrink)

Of laws in general -- Of laws directly derived from the nature of government -- Of the principles of the three kinds of government -- That the laws of education ought to be relative to the principles of government -- That the laws given by the legislator ought to be relative to the nature of government -- Consquences of the principles of different governments, with respect to the simplicity of civil and criminal laws, the form of judgements, and inflicting of (...) punishments -- Consquences of the different principles of the three governments, with respect to sumptuary laws, luxury, and the condition of women -- Of the corruption of the principles of the three governments -- Of the laws in the relation they bear to defensive force -- Of laws, in the relation they bear to offensive force. (shrink)

Three experiments investigated the relationship between subjective experience and attentional lapses during sustained attention. These experiments employed two measures of subjective experience to examine how differences in awareness correspond to variations in both task performance and psycho-physiological measures . This series of experiments examine these phenomena during the Sustained Attention to Response Task . The results suggest we can dissociate between two components of subjective experience during sustained attention: task unrelated thought which corresponds to an absent minded disengagement from the (...) task and a pre-occupation with one's task performance that seems to be best conceptualised as a strategic attempt to deploy attentional resources in response to a perception of environmental demands which exceed ones ability to perform the task. The implications of these findings for our understanding of how awareness is maintained on task relevant material during periods of sustained attention are discussed. (shrink)