The growing recognition by cognitive neuroscientists that areas of vertebrate brains may be reused for multiple purposes either functionally during development or during evolution echoes a similar realization made by neuroscientists working on invertebrates. Because of these animals' relatively more accessible nervous systems, neuronal reuse can be examined at the level of individual identified neurons and fully characterized neural circuits.

We compare several methods of implementing the display (sequent) calculus RA for relation algebra in the logical frameworks Isabelle and Twelf. We aim for an implementation enabling us to formalise within the logical framework proof-theoretic results such as the cut-elimination theorem for RA and any associated increase in proof length. We discuss issues arising from this requirement.

We describe how we used the interactive theorem prover Isabelle to formalise and check the laws of the Timed Interval Calculus (TIC). We also describe some important corrections to, clarifications of, and flaws in these laws, found as a result of our work.

Although aesthetics began with an interest in a teleological order, the classical question was largely disparaged and rejected in mainstream academic circles by the twentieth century. The two dogmas of musical modernism were the presumption of formalism and the assertion of aestheticism. Historically, philosophers defending the objectivity of aesthetic value focused on the question of Beauty per se. But what if beauty is descriptive of something else? Our conviction of justice runs deeper than convictions of beauty. This essay explores the (...) significance of human anticipation concerning justice and how moral conviction relates to music as an encounter with teleological convictions. Music is fundamentally an individualized philosophical experience engaging the question of order, based upon a universal teleological presupposition. We do not find the arts to be meaningful because we believe them to be beautiful; we ascribe beauty to that which we find to be deeply meaningful--a way-it-should-be. (shrink)

We use a deep embedding of the display calculus for relation algebras ÆRA in the logical framework Isabelle /HOL to formalise a machine-checked proof of cut-admissibility for ÆRA. Unlike other “implementations”, we explicitly formalise the structural induction in Isabelle /HOL and believe this to be the first full formalisation of cutadmissibility in the presence of explicit structural rules.

We re-express our theorem on the strong-normalisation of display calculi as a theorem about the well-foundedness of a certain ordering on first-order terms, thereby allowing us to prove the termination of systems of rewrite rules. We first show how to use our theorem to prove the well-foundedness of the lexicographic ordering, the multiset ordering and the recursive path ordering. Next, we give examples of systems of rewrite rules which cannot be handled by these methods but which can be handled by (...) ours. Finally, we show that our method can also prove the termination of the Knuth-Bendix ordering and of dependency pairs. Keywords: rewriting, termination, well-founded ordering, recursive path ordering.. (shrink)

This essay examines the strategies that Berkeley and Dharmakīrti utilize to deny that idealism entails solipsism. Beginning from similar arguments for the non-existence of matter, the two philosophers employ markedly different strategies for establishing the existence of other minds. This difference stems from their responses to the problem of intersubjective agreement. While Berkeley’s reliance on his Cartesian inheritance does allow him to account for intersubjective agreement without descending into solipsism, it nevertheless prevents him from establishing the existence of other finite (...) minds. I argue that Dharmakīrti, in accounting for intersubjective agreement causally, is able to avoid Berkeley’s shortcoming. I conclude by considering a challenge to Dharmakīrti’s use of inference that Ratnakīrti, a Buddhist successor of Dharmakīrti, advances in his “Disproof of the Existence of Other Minds” and briefly exploring a possible response that someone who wants to advocate an idealist position could give. (shrink)

Identity leadership (IL) describes that the effectiveness of a leader will depend upon his capacity to represent a given group, to make the group go forward, to create a group identity, and to make the group matter. An identity leader may increase commitment among his followers by increasing the perception of shared identity and giving more weight in the decision process to his followers. We aim to explore the mechanisms through which a leader who creates a shared group identity can (...) increase organizational commitment. In the first study, we plan to conduct a cross-cultural correlational study where we aim to test if the relationship between IL and organizational commitment is mediated by team identification and mediated-moderated by participation in decision making (PDM) and collective efficacy. In the second study, we aim to explore the direction of the causality between IL and PDM. To test this hypothesis, we will conduct an experimental study in which (1) we will manipulate IL to test its influence on the perception of PDM and (2) we will manipulate PDM to test its influence on the perception of IL. Thus, we will be able to identify the role of IL and the perception of PDM on organizational commitment. (shrink)

Early life stress precedes alterations to neuro-immune activation, which may mediate an increased risk for stress-related psychiatric disorders, potentially through alterations of central kynurenine pathway metabolites, the latter being relatively unexplored. We hypothesized that ELS in a non-human primate model would lead to a reduction of neuroprotective and increases of neurotoxic KP metabolites. Twelve adult female bonnet macaques reared under conditions of maternal variable foraging demand were compared to 27 age- and weight-matched non-VFD-exposed female controls. Baseline behavioral observations of social (...) affiliation were taken over a 12-week period followed by the first cerebrospinal fluid sample. Subjects were then either exposed to a 12-week repeated separation paradigm or assigned to a “no-RSP” condition followed by a second CSF. We used high-performance liquid chromatography for kynurenine, tryptophan, 5-hydroxyindoleacetic acid, kynurenic acid, and anthranilic acid as a proxy for quinolinic acid determination. At baseline, social affiliation scores were reduced in VFD-reared versus control subjects. CSF log KYNA and log KYNA/KYN ratio were lower in VFD-reared versus control subjects. CSF log KYNA/KYN was positively correlated with CSF log ANTH in VFD only. Controlling for log KYNA/KYN, log ANTH was elevated in VFD-reared subjects versus controls. CSF log KYNA/KYN obtained post-RSP was positively correlated with mean social affiliation scores during RSP, specifically in VFD. ELS is associated with a reduced neuroprotective and increased neurotoxic pathway products. That the two contrasting processes are paradoxically correlated following ELS suggests a cross-talk between two opposing KP enzymatic systems. (shrink)

A challenge of performing research in the paediatric emergency and acute care setting is obtaining valid prospective informed consent from parents. The ethical issues are complex, and it is important to consider the perspective of participants, health care workers and researchers on research without prospective informed consent while planning this type of research. We performed a systematic review according to PRISMA guidelines, of empirical evidence relating to the process, experiences and acceptability of alternatives to prospective informed consent, in the paediatric (...) emergency or acute care setting. Major medical databases and grey sources were searched and results were screened and assessed against eligibility criteria by 2 authors, and full text articles of relevant studies obtained. Data were extracted onto data collection forms and imported into data management software for analysis. Thirteen studies were included in the review consisting of nine full text articles and four abstracts. Given the heterogeneity of the methods, results could not be quantitatively combined for meta-analysis, and qualitative results are presented in narrative form, according to themes identified from the data. Major themes include capacity of parents to provide informed consent, feasibility of informed consent, support for alternatives to informed consent, process issues, modified consent process, child death, and community consultation. Our review demonstrated that children, their families, and health care staff recognise the requirement for research without prior consent, and are generally supportive of enrolling children in such research with the provisions of limiting risk, and informing parents as soon as possible. Australian data and perspectives of children are lacking and represent important knowledge gaps. (shrink)

Newborn screening (NBS) began in the 1960s by testing all newborns for a single condition—phenylketonuria, or PKU—which, when identified and treated early, significantly reduces morbidity. Over the...

Quality and service improvement (QSI) research employs a broad range of methods to enhance the efficiency of healthcare delivery. QSI research differs from traditional healthcare research and poses unique ethical questions. Since QSI research aims to generate knowledge to enhance quality improvement efforts, should it be considered research for regulatory purposes? Is review by a research ethics committee required? Should healthcare providers be considered research participants? If participation in QSI research entails no more than minimal risk, is consent required? The (...) lack of consensus on answers to these questions highlights the need for ethical guidance. Three distinct approaches to classifying QSI research in accordance with existing ethical principles and regulations can be found in the literature. In the first approach, QSI research is viewed as distinct from other types of healthcare research and does not require regulation. In the second approach, QSI research falls within regulatory guidelines but is exempt from research ethics committee review. In the third approach, QSI research is deemed to be part of the learning healthcare system and, as such, is subject to a different set of ethical principles entirely. In this paper, we critically assess each of these views. While none of these approaches is entirely satisfactory, we argue that use of the ethical principles governing research provides the best means of addressing the numerous questions posed by QSI research. (shrink)

: In light of information uncovered about human radiation experiments conducted during the Cold War, an important charge for the Advisory Committee on Human Radiation Experiments was to assess the current state of protections for human research subjects. This assessment was designed to enhance the Committee's ability to make informed recommendations for the improvement of future policies and practices for the protection of research subjects. The Committee's examination of current protections revealed great improvement over those from the past, yet some (...) problems remain. Although the data collected by the Committee highlight specific areas in need of attention, the Committee's work should be viewed in part as the beginning of a series of ongoing assessments of the adequacy and effectiveness of the protections afforded to human subjects. (shrink)

Recent legislation, such as the Patient Self-Determination Act, establishes advance directives as an acceptable procedural means of incorporating patients’ preferences for life-sustaining treatments into their medical care. Advance directives can enhance medical decision making since they provide patients with an opportunity to communicate their preferences before suffering from an acute illness that may preclude their ability to do so.Although patients expect discussions about life-sustaining therapies to be initiated by their physicians, very little is known about what prompts physicians to discuss (...) advance directives with their patients. As in other areas of clinical decision making, there is evidence that patients’ sociodemographic factors influence whether discussions about advance directives occur between patients and their physicians. In one study of persons with the acquired immunodeficiency syndrome, those who had not had discussions about advance directives with their physicians tended to be non-white, have no prior hospitalization, and were more likely to have been cared for in a health maintenance organization than in a teaching hospital. (shrink)

We are less optimistic than Madole & Harden that family-based genome-wide association studies (GWASs) will lead to significant second-generation causal knowledge. Despite bearing some similarities, family-based GWASs and randomised controlled trials (RCTs) are not identical. Most RCTs assess a relatively homogenous causal stimulus as a treatment, whereas GWASs assess highly heterogeneous causal stimuli. Thus, GWAS results will not translate so easily into second-generation causal knowledge.

Biomedical and behavioral research may affect strongly held social values and thereby create significant controversy over whether such research should be permitted in the first place. Institutional review boards responsible for protecting the rights and welfare of participants in research are sometimes faced with review of protocols that have significant implications for social policy and the potential for negative social consequences. Although IRB members often raise concerns about potential long-term social implications in protocol review, federal regulations strongly discourage IRBs from (...) considering them in their decisions. Yet IRBs often do consider the social implications of research protocols and sometimes create significant delays in initiating or even prevent such research. The social implications of research are important topics for public scrutiny and professional discussion. This article examines the reasons that the federal regulations preclude IRBs from assessing the social risks of research, and examines alternative approaches that have been used with varying success by national advisory groups to provide such guidance. The article concludes with recommendations for characteristics of a national advisory group that could successfully fulfill this need, including sustainability, independence, diverse and relevant expertise, and public transparency. (shrink)

Over the past decade, there has been an extensive debate about whether researchers have an obligation to disclose genetic research findings, including primary and secondary findings. There appears to be an emerging (but disputed) view that researchers have some obligation to disclose some genetic findings to some research participants. The contours of this obligation, however, remain unclear. -/- As this paper will explore, much of this confusion is definitional or conceptual in nature. The extent of a researcher’s obligation to return (...) secondary and other research findings is often limited by reference to terms and concepts like “incidental,” “analytic validity,” “clinical validity,” “clinical relevance,” “clinical utility,” “clinical significance,” “actionability,” and “desirability.” These terms are used in different ways by different writers to describe obligations in different sorts of cases. -/- Underneath this definitional confusion is a general notion, supported by much of the literature, that findings only need to be disclosed when they surpass certain presumably objective or measureable thresholds, such as medical importance or scientific reproducibility. The problem is that there is significant variability in the way that these terms and concepts are used in the literature and, as such, in defining the scope of an obligation to return findings that surpasses the relevant thresholds. -/- The goal of this paper is to analyze the definitional muddle underlying the debate about returning genetic research findings, with the hope of answering a few questions. First, what is the range of definitions being used in this debate? Based on an extensive literature review, Part 1 will lay out a range of articulated definitions for each relevant term, with the goal of categorizing them into a handful of distinct types. Part 2 explains the definitional redundancy and confusion in the current literature, and, drawing from the terminological patterns identified in Part 1, outlines more cohesive building blocks to inform the development of future disclosure frameworks.Our minimum goal in articulating these conceptual building blocks is to promote clearer articulations of, and distinctions between, future disclosure frameworks. More ambitiously, we suggest which definitions and conceptualizations we consider most appropriate to use in future disclosure frameworks. Here, we seek to balance benefits to participants through the disclosure of important information with the minimization of undue burdens on individual researchers and the research enterprise more generally. -/- Our analysis builds upon the central philosophical distinction between concepts and conceptions. The basic idea is that the “concept” of X refers to the general (and relatively uncontroversial) structure/shape of X, while various “conceptions” of X are more particular, filled out, and controversial elaborations of the concept. In other words, “concepts” of X will be formal representations of X, while “conceptions” of X will be substantive interpretations of the key elements and relationships operating within that formal framework. (Implicit in this distinction is an important point about the nature of disagreement – namely, that in order for two or more parties to “disagree” about X as opposed to simply talk past one another, there must be at least enough shared agreement about X to know that the parties are referring to the same thing. A concept of X provides this point of common agreement, while competing conceptions of X mark the areas where disagreement arises.) In this paper, we will employ this distinction in a fundamental way to clarify exactly where the primary disagreements arise in the debate over disclosing genetic research findings. -/- We propose that, underlying all the seeming confusion and disagreement, there are three central and widely agreed upon concepts at work in this debate—validity, value, and volition. The first two concepts concern the nature of the information itself. An obligation to disclose only exists when findings are valid and have value but there are competing conceptions of how to determine or define validity and valuableness. The third concept—volition—pertains not to the information but rather to the person to whom it will be disclosed. Does that person want or not want the information, and what is the best way of determining this? Here, too, competing conceptions arise. Our key point, though, is that almost all of the ethical disagreement arises because of competing conceptions of these three concepts. Understanding and appreciating this key point can help to refocus the substantive debate by providing some common ground to start from in determining how best to interpret these shared concepts. This refocusing can, ideally, produce more productive debate and facilitate some progress in resolving it. (shrink)

It is widely assumed that informing prospective subjects about the risks and possible benefits of research not only protects their rights as autonomous decisionmakers, but also empowers them to protect their own interests. Yet interviews with patient‐subjects conducted under the auspices of the Advisory Committee on Human Radiation Experiments suggest this is not always the case. Patient‐subjects often trust their physician to guide them through decisions on research participation. Clinicians, investigators, and IRBs must assure that such trust is not misplaced.

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:A Treatise on Efficacy: Between Western and Chinese ThinkingJeremy E. HenkelA Treatise on Efficacy: Between Western and Chinese Thinking. By François Jullien, translated by Janet Lloyd. Honolulu: University of Hawai'i Press, 2004. Pp. x + 202. $22.00.In A Treatise on Efficacy: Between Western and Chinese Thinking François Jullien argues that the different ways Chinese and Western thinkers have dealt with warfare and diplomacy reflect important differences in how (...) the two cultures understand human action in the world. When Chinese texts such as the Sunzi and the Guiguzi are set up as counterpoints to the Europeans Clausewitz and Machiavelli, Jullien argues that the Aristotelian inheritance of the latter pair is shown to be the cause of their inability to provide clean theories with the consistent predictive power they desired. Chinese strategists, by contrast, meet with no such limitations in the realm of human interaction. The basic difference between Western and Chinese thought that Jullien seeks to demonstrate is that "one constructs a model that is then projected onto the situation, which implies that the situation is momentarily 'frozen.' The other relies on the situation as on a disposition that is known to be constantly evolving" (p. 189; italics in original).Jullien's regular use of the generic terms "Western" and "Chinese" in constructing his comparison will likely give many comparative philosophers pause. But this [End Page 347] need not be a source of worry, as he is careful not to essentialize the two world-views. While he is pointing out patterns and tendencies in the thinking of Europe and China, he is not positing an essential incommensurable difference between them. Rather, he is pointing out that "what remains underdeveloped in the one context is more developed in the other" (p. 145). He goes on to say, "The purpose of our foray into China is not to imagine-let alone fabricate-other 'mentalities'.... It is simply to make use of other possible sources of intelligibility" (ibid.).Jullien begins by showing that Western thought regards human action as something that imposes itself on the world in order to bring about a predetermined goal. This is a natural consequence of the belief that the world is created: belief in creation implies something existing outside that creation, thus an intention behind that creation, and thus a transcendent norm toward which things within that creation aim. This two-leveled ontology of creator and creation yields a distinction between theory and practice, wherein practice always aims-and ultimately fails-at implementing an ideal that is established by theory. This worldview has led to demonstrable success in the sciences but meets with frequent frustration in the arena of human interaction. This limitation has been recognized by strategists in the West but has never been successfully resolved.Aristotle was the first to identify and try to resolve this problem. He posited phronesis as the skill that enables an individual to apply a model to the world successfully. For Aristotle such successful action consists of first identifying one's desired end and then reasoning back to one's present situation in order to establish the best means to achieve that end. Jullien's analysis shows that Clausewitz was working with the same model more than two thousand years later. Clausewitz believed that earlier attempts at creating a general theory of warfare had failed to achieve their goal-namely, to provide a model of warfare that a general could use to ensure victory-because the opponent's actions are unpredictable. The system that the military strategist is dealing with, then, is not mechanistic, and consequently plans are easily frustrated by ever-changing circumstances. But Clausewitz was unable to conceive of strategy as based on anything other than plans.For Clausewitz, warfare is composed of distinct engagements, separate moments in time where an army seeks to impose a plan on the world. Seeing warfare as composed of distinct moments means that time is an opponent, for time brings with it change and uncertainty and thus a greater chance that one's plans will be frustrated. Opportunity, then, is something unexpected-a chance happening at a specific moment that can be taken advantage of only... (shrink)

Acceptance of elderly or marginal health individuals as kidney donors is debated, with practices varying between centres. Transplant recipients, live kidney donors and health-care professionals caring for patients with renal failure were surveyed regarding their views on live donor kidney transplantation (LDKT) of marginal health (diabetes, hypertension, atherosclerosis, obesity, etc.) and elderly donors. Participants were recruited within a tertiary renal and transplant centre and invited to participate in focus groups and structured interviews. They also completed an anonymous questionnaire. Of 464 (...) participants who completed the questionnaire (36% health-care professionals and 64% patients), 49% and 64%, respectively, stated that marginal and elderly donors should be accepted for LDKT. In the structured interviews, emphasis was given to presenting to donor, recipient and their respective families a calculated risk regarding the effect that either a nephrectomy or transplant has on long-term quality of life. Participants stated that an independent third party in addition to the transplant team should discuss involved risks. Issues of ‘how desperate’ the recipient's situation is should also be considered. Health-care professionals stated that regardless of the strength of will of an individual to donate a kidney (despite age, health problems or personal risk), they should always have the right to say ‘no’ if performing a specific LDKT was against their professional and ethical values. About half of those surveyed considered that marginal health and elderly donors were acceptable for LDKT. Emphasis was given to the explanation to donors and recipients of the risks involved in such transplantation. (shrink)

Participants in clinical research sometimes view participation as therapy or exaggerate potential benefits, especially in phase I or phase II trials. We conducted this study to discover what methods might improve cancer patients’ understanding of early-phase clinical trials. We randomly assigned 130 cancer patients from three U.S. medical centers who were considering enrollment in a phase I or phase II cancer trial to receive either a multimedia intervention or a National Cancer Institute pamphlet explaining the trial and its purpose. Intervention (...) participants were 32 times more likely to believe that the trial’s purpose was to examine safety and 60 % less likely to believe they would experience long-term benefit or cure. There was no difference in enrollment decision. However, while patients’ understanding of the trial’s purpose improved and expectations of long-term benefit diminished, half the respondents still believed they would experience long-term benefit or cure from participation. Therefore, we conclude that multimedia interventions such as this one may help oncologists to explain the risks and benefits of early-phase cancer trials in a way that patients can more easily understand, helping them to make more informed decisions about participation. But further research into other factors that influence patients’ beliefs about the outcome of enrollment is needed, both to modify the interventions and to determine how malleable patient beliefs are. (shrink)

Zygon®, Volume 56, Issue 4, Page 960-970, December 2021.

The present research seeks to better understand research conditions in laboratory research, with special attention paid to the informed consent process and experimenter characteristics. The first study tested the impact of language perspective and experimenter demeanor upon participant retention of the informed consent information, attitudes toward the research project, and performance on experimental tasks. The second study examined the impact of experimenter attire. Across the two studies, our results suggest that there was no impact of language perspective, whereas the number (...) of other participants in the laboratory, experimenter attire, and experimenter demeanor influence participant behaviors in the laboratory. (shrink)

Self-criticism is a trait associated with increased psychopathology, but self-criticism is also a personality state reflecting an action that people do in moments of time. In the current study, we explored factors associated with heightened self-criticism in daily life. Participants (N = 197) received five random prompts per day for one week on their mobile phones, where they reported their current affect (negative and positive affect), willpower self-efficacy, distress intolerance, degree of support and criticism from others, current context (location, activity, (...) hunger, tiredness) and momentary self-criticism. We first demonstrated that self-criticism varies over time and across contexts, and is associated with heightened trait self-criticism. Then, using multilevel modelling, we explored the contextual factors associated with greater self-criticism. We found that self-criticism was higher when people were at home, and more tired. We also found higher self-criticism to be associated with greater negative and lower positive affect, greater distress intolerance, lower willpower and greater perceived criticism from others. In addition, self-criticism predicted subsequent distress intolerance, willpower and positive affect in lagged analyses. This study provides evidence that both environmental and psychological factors are associated with the dynamics of self-critical thoughts. (shrink)

La pensée du jurisconsulte anglais Jeremy Bentham (1748-1832) se prête particulièrement bien à une approche interdisciplinaire telle que celle qui est menée dans le présent ouvrage. Si Bentham, en effet, a consacré l'essentiel de ses travaux à des projets de réforme de la société anglaise de son temps par le biais de la codification des lois, il n'a cessé d'enrichir cette réflexion par des emprunts faits à d'autres disciplines, dans lesquelles il était également passé maître, telles la morale, la (...) psychologie, la logique, la théorie du langage, l'économie ou la politique. Cette pensée, à la fois plurielle et ambiguë (est-elle conservatrice, réformiste, révolutionnaire ou utopique? est-elle descriptive, explicative ou normative?), révèle aujourd'hui son étonnante actualité. Il est peu de thèmes juridiques contemporains qui ne trouvent en effet leur place dans l'œuvre de Bentham : ainsi les questions de l'utilité, de la balance des intérêts, de la constitution d'une science du droit et d'une logique déontique; ainsi les concepts de système juridique, de codification, de déontologie, de contrôle social, d'opinion publique et de majorité politique. L'intérêt de cette " relecture " de la pensée de Bentham réside dès lors sans doute moins dans l'exégèse de ses multiples détours que dans la mise en lumière de ses ambiguïtés et de ses limites qui, pour une large part, sont aussi les nôtres. Parmi celles-ci, l'oscillation constante, déjà inscrite dans les textes benthamiens, entre deux figures de l'État moderne (État libéral et État-providence), n'est sans doute pas la moins actuelle. (shrink)

The lives of few mathematicians offer the drama that is presented by the life of L. E. J. Brouwer, correctly identified on the cover of this book as a topologist, intuitionist, and philosopher, and before we go any further, it will be worth indicating why.It is not just that Brouwer would rank high among mathematicians for his work in topology alone: he set standards for rigour and created a theory of dimension for topological spaces, and his fixed-point theorem is of (...) great importance. Nor is it just that his philosophy of intuitionism created a new and vibrant branch of logic, that is, arguably, the only viable alternative to naïve, classical logic outside the enclave of professional logicians. Rather, it is that there is a tension, popularly taken to amount to a contradiction, in the fundamental ideas behind his topology and his intuitionism. Added to that, he took a highly principled stand on mathematical issues that led him into confrontations with major figures and a certain degre .. (shrink)

Randomized controlled trial trial designs exist on an explanatory-pragmatic spectrum, depending on the degree to which a study aims to address a question of efficacy or effectiveness. As conceptualized by Schwartz and Lellouch in 1967, an explanatory approach to trial design emphasizes hypothesis testing about the mechanisms of action of treatments under ideal conditions, whereas a pragmatic approach emphasizes testing effectiveness of two or more available treatments in real-world conditions. Interest in, and the number of, pragmatic trials has grown substantially (...) in recent years, with increased recognition by funders and stakeholders worldwide of the need for credible evidence to inform clinical decision-making. This increase has been accompanied by the onset of learning healthcare systems, as well as an increasing focus on patient-oriented research. However, pragmatic trials have ethical challenges that have not yet been identified or adequately characterized. The present study aims to explore the views of key stakeholders with respect to ethical issues raised by the design and conduct of pragmatic trials. It is embedded within a large, four-year project that seeks to develop guidance for the ethical design and conduct of pragmatic trials. As a first step, this study will address important gaps in the current empirical literature with respect to identifying a comprehensive range of ethical issues arising from the design and conduct of pragmatic trials. By opening up a broad range of topics for consideration within our parallel ethical analysis, we will extend the current debate, which has largely emphasized issues of consent, to the range of ethical considerations that may flow from specific design choices. Semi-structured interviews with key stakeholders, across multiple jurisdictions, identified based on their known experience and/or expertise with pragmatic trials. We expect that the study outputs will be of interest to a wide range of knowledge users including trialists, ethicists, research ethics committees, journal editors, regulators, healthcare policymakers, research funders and patient groups. All publications will adhere to the Tri-Agency Open Access Policy on Publications. (shrink)

For forty years, Harvey Mansfield has been worth reading. Whether plumbing the depths of MachiavelliOs Discourses or explaining what was at stake in Bill ClintonOs impeachment, MansfieldOs work in political philosophy and political science has set the standard. In Educating the Prince, twenty-one of his students, themselves distinguished scholars, try to live up to that standard. Their essays offer penetrating analyses of Machiavellianism, liberalism, and America., all of them informed by MansfieldOs own work. The volume also includes a bibliography of (...) MansfieldOs writings. (shrink)

In another paper, one of us argued that emergence and reduction are compatible, and presented four examples illustrating both. The main purpose of this paper is to develop this position for the example of phase transitions. We take it that emergence involves behaviour that is novel compared with what is expected: often, what is expected from a theory of the system's microscopic constituents. We take reduction as deduction, aided by appropriate definitions. Then the main idea of our reconciliation of emergence (...) and reduction is that one makes the deduction after taking a limit of an appropriate parameter $N$. Thus our first main claim will be that in some situations, one can deduce a novel behaviour, by taking a limit $N\to\infty$. Our main illustration of this will be Lee-Yang theory. But on the other hand, this does not show that the $N=\infty$ limit is physically real. For our second main claim will be that in such situations, there is a logically weaker, yet still vivid, novel behaviour that occurs before the limit, i.e. for finite $N$. And it is this weaker behaviour which is physically real. Our main illustration of this will be the renormalization group description of cross-over phenomena. (shrink)

The idea that the form of a word reflects information about its meaning has its roots in Platonic philosophy, and has been experimentally investigated for concrete, sensory-based properties since the early 20th century. Here, we provide evidence for an abstract property of ‘boundedness’ that introduces a systematic, iconic bias on the phonological expectations of a novel lexicon. We show that this abstract property is general across events and objects. In Experiment 1, we show that subjects are systematically more likely to (...) associate sign language signs that end with a gestural boundary with telic verbs (denoting events with temporal boundaries, e.g., die, arrive) and with count nouns (denoting objects with spatial boundaries, e.g., ball, coin). In Experiments 2–3, we show that this iconic mapping acts on conceptual representations, not on grammatical features. Specifically, the mapping does not carry over to psychological nouns (e.g. people are not more likely to associate a gestural boundary with idea than with knowledge). Although these psychological nouns are still syntactically encoded as either count or mass, they do not denote objects that are conceived of as having spatial boundaries. The mapping bias thus breaks down. Experiments 4–5 replicate these findings with a new set of stimuli. Finally, in Experiments 6–11, we explore possible extensions to a similar bias for spoken language stimuli, with mixed results. Generally, the results here suggest that ‘boundedness’ of words' referents (in space or time) has a powerful effect on intuitions regarding the form that the words should take. (shrink)

In crafting our paper on addressing the ethical challenges in HIV prevention research with people who inject drugs,1 we had hoped to stimulate further discussion and deliberation about the topic. We are pleased that three commentaries on our paper have begun this process.2 3 4 The commentaries rightly bring up important issues relating to community engagement and problems in translating research into practice in the fraught environments in which PWID face multiple risks. These risks include acquisition of HIV as well (...) as criminalisation, stigma and lack of access to needed healthcare, prevention and social services. We take this opportunity to respond to the excellent points raised by the commentators. All of the commentaries support our emphasis on robust community engagement with PWID and other stakeholders in designing and conducting HIV prevention research, but urge us to go farther. Wolfe highlights the difficulty of even engaging with community members in oppressive settings, where authorities severely restrict civil liberties of PWID so that even discussing issues related to drug use and enforcement may place individuals at risk. To overcome such limitations, he appropriately suggests interviewing confidentially those who have previously been detained in closed settings as part of the community engagement process. Similarly, Wolfe observes that critical issues can be overlooked with a narrow focus on study procedures if contextual factors before, during or after a study are ignored. For example, he cites the risk of overdose for study participants who have been abstinent during a study and subsequently resume injecting when the study concludes. These kinds of risks may not be obvious …. (shrink)

Background Pragmatic randomized controlled trials are designed to evaluate the effectiveness of interventions in real-world clinical conditions. However, these studies raise ethical issues for researchers and regulators. Our objective is to identify a list of key ethical issues in pragmatic RCTs and highlight gaps in the ethics literature. Methods We conducted a scoping review of articles addressing ethical aspects of pragmatic RCTs. After applying the search strategy and eligibility criteria, 36 articles were included and reviewed using content analysis. Results Our (...) review identified four major themes: 1) the research-practice distinction; 2) the need for consent; 3) elements that must be disclosed in the consent process; and 4) appropriate oversight by research ethics committees. 1) Most authors reject the need for a research-practice distinction in pragmatic RCTs. They argue that the distinction rests on the presumptions that research participation offers patients less benefit and greater risk than clinical practice, but neither is true in the case of pragmatic RCTs. 2) Most authors further conclude that pragmatic RCTs may proceed without informed consent or with simplified consent procedures when risks are low and consent is infeasible. 3) Authors who endorse the need for consent assert that information need only be disclosed when research participation poses incremental risks compared to clinical practice. Authors disagree as to whether randomization must be disclosed. 4) Finally, all authors view regulatory oversight as burdensome and a practical impediment to the conduct of pragmatic RCTs, and argue that oversight procedures ought to be streamlined when risks to participants are low. Conclusion The current ethical discussion is framed by the assumption that the function of research oversight is to protect participants from risk. As pragmatic RCTs commonly involve usual care interventions, the risks may be minimal. This leads many to reject the research-practice distinction and question the need for informed consent. But the function of oversight should be understood broadly as protecting the liberty and welfare interest of participants and promoting public trust in research. This understanding, we suggest, will focus discussion on questions about appropriate ethical review for pragmatic RCTs. (shrink)

We report on the small-scale (0.5 13 h - 1M, a large-scale bias of ~2.0 and a satellite fraction of 12 ± 2 per cent. Thus, these galaxies occupy haloes with average masses in between those of the higher redshift BOSS CMASS sample and the original SDSS I/II luminous red galaxy sample © 2012 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society © doi:10.1093/mnras/sts314.

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)