A wide range of biological processes, in all eukaryotes and in some prokaryotes, are controlled by rhythms with a period close to 24 hours. The circadian oscillator, which is responsible for generating these rhythms, is controlled by light signals that maintain its synchrony with the environmental day/night cycle. Higher plants exhibit many circadian rhythms, including rhythms in the transcription of specific genes. Molecular tools derived from such clock‐controlled genes have led to the identification of several circadian rhythm mutants in the (...) genetic model, Arabidopsis thaliana. The extensive understanding of photoperception in this species will make it a powerful system with which to investigate the light regulation of circadian rhythms. We compare Arabidopsis rhythms to the results from other systems, and discuss these data with respect to the current phototransduction models. (shrink)

Management buyouts occur when incumbent managers (typically in association with third party investors) purchase all of a firm's outstanding stock and remove it from public trading. Prior ethical analyses of such activities have ignored the fact that large numbers of such buyouts return to public trading. The ethical implications of management buyout activity can be more fully understood if the entire buyout process is considered, beginning with the time the firm is taken private until it is returned to public trading. (...) Using a widely employed strategic management ethical framework developed by Hosmer (1994), this paper examines the ethics of the complete buyout cycle. (shrink)

The rapid rise of international collaborative science has enabled access to genomic data. In this article, it is argued that to move beyond mapping genomic variation to understanding its role in complex disease aetiology and treatment will require extending data sharing for the purposes of clinical research translation and implementation.

The language of “participant-driven research,” “crowdsourcing” and “citizen science” is increasingly being used to encourage the public to become involved in research ventures as both subjects and scientists. Originally, these labels were invoked by volunteer research efforts propelled by amateurs outside of traditional research institutions and aimed at appealing to those looking for more “democratic,” “patient-centric,” or “lay” alternatives to the professional science establishment. As mainstream translational biomedical research requires increasingly larger participant pools, however, corporate, academic and governmental research programs (...) are embracing this populist rhetoric to encourage wider public participation. We examine the ethical and social implications of this recruitment strategy. We begin by surveying examples of “citizen science” outside of biomedicine, as paradigmatic of the aspirations this democratizing rhetoric was originally meant to embody. Next, we discuss the ways these aspirations become articulated in the biomedical context, with a view to drawing out the multiple and potentially conflicting meanings of “public engagement” when citizens are also the subjects of the science. We then illustrate two uses of public engagement rhetoric to gain public support for national biomedical research efforts: its post-hoc use in the “care.data” project of the National Health Service in England, and its proactive uses in the “Precision Medicine Initiative” of the United States White House. These examples will serve as the basis for a normative analysis, discussing the potential ethical and social ramifications of this rhetoric. We pay particular attention to the implications of government strategies that cultivate the idea that members of the public have a civic duty to participate in government-sponsored research initiatives. We argue that such initiatives should draw from policy frameworks that support normative analysis of the role of citizenry. And, we conclude it is imperative to make visible and clear the full spectrum of meanings of “citizen science,” the contexts in which it is used, and its demands with respect to participation, engagement, and governance. (shrink)

The work of Jacques Ellul is useful in understanding and evaluating the implications of rapidly changing technologies for human values and democracy. Ellul developed three powerful theses about technology: technological autonomy, technological determinism, and technological bluff. In this essay, the authors explicate these views of technology, and place the work of Ellul in dialogue with the ides of other important theorists of technology. Ellul’s too-often overlooked theses about technology are relevant to our present technological society.

We present a comprehensive study of the axiom schemas IΣ - n , BΣ - n (induction and collection schemas for parameter free Σ n formulas) and some closely related schemas.

I critically explore various forms of the language of thought (LOT) hypothesis. Many considerations, including the complexity of representational content and the systematicity of language understanding, support the view that some, but not all, of our mental representations occur in a language. I examine several arguments concerning sententialism and the propositional attitudes, Fodor's arguments concerning infant and animal thought, and Fodor's argument for radical concept nativism and show that none of these considerations require us to postulate a LOT that is (...) innate or otherwise distinct from spoken languages. Instead, I suggest that we maintain the more conservative hypothesis, supported by introspection, that some of our thoughts occur in the languages that we speak. (shrink)

This book is a comprehensive exposition of the Transcendental Deduction of the Categories in both editions of Kant’s Critique of Pure Reason.

Despite its focus on consent the new Human Tissue Act 2004 allows for testing without consent where a relative could benefitIn recognition of the fact that genetic test results in people can have implications for close relatives, the new Human Tissue Act 2004 allows for a direction to access a person’s tissue so that testing can be carried out for the benefit of a relative, without the consent of that person. Clinical practice governed by common law and statute, before this (...) act, acknowledged that the disclosure, without consent, of the results of a genetic test, is ethically permissible in extreme situations for the benefit of a relative. New testing for the benefit of a relative without donor consent challenges the principle that informed or adequate consent should be obtained before a genetic test with considerable predictive powers is carried out. The debate surrounding the analogous situation of HIV testing concluded that in very rare cases, disclosure of an HIV result without consent may be justified, but testing without consent is a professional misconduct. This part of the legislation is controversial and deserves further debate. The Human Tissue Authority should take measures to limit the potential harm that can be caused by this provision.IntroductionAfter much debate, the new Human Tissue Act 2004 was passed by parliament in November 2004. Implementation of this act may be staggered, but it will be fully operational in May 2006. This act has several provisions that have implications in clinical practice for the use of stored tissue or samples containing cells. These provisions allow the Human Tissue Authority to permit access to human tissue for the purpose of obtaining scientific or medical information about a person for the benefit of another family member, without the consent of the donor . …. (shrink)

As in other countries, the traditional doctor-patient relationship in the Japanese healthcare system has often been characterised as being of a paternalistic nature. However, in recent years there has been a gradual shift towards a more participatory-patient model in Japan. With advances in technology, the possibility to use digital technologies to improve patient interactions is growing and is in line with changing attitudes in the medical profession and society within Japan and elsewhere. The implementation of an online patient engagement platform (...) is being considered by the Myotonic Dystrophy Registry of Japan. The aim of this exploratory study was to understand patients’ views and attitudes to using digital tools in patient registries and engagement with medical research in Japan, prior to implementation of the digital platform. We conducted an exploratory, cross-sectional, self-completed questionnaire with a sample of myotonic dystrophy patients attending an Open Day at Osaka University, Japan. Patients were eligible for inclusion if they were 18 years or older, and were diagnosed with MD. A total of 68 patients and family members attended the Open Day and were invited to participate in the survey. Of those, 59 % submitted a completed questionnaire. The survey showed that the majority of patients felt that they were not receiving the information they wanted from their clinicians, which included recent medical research findings and opportunities to participate in clinical trials, and 88 % of patients indicated they would be willing to engage with digital technologies to receive relevant medical information. Patients also expressed an interest in having control over when and how they received this information, as well as being informed of how their data is used and shared with other researchers. Overall, the findings from this study suggest that there is scope to develop a digital platform to engage with patients so that they can receive information about medical care and research opportunities. While this study group is a small, self-selecting population, who suffer from a particular condition, the results suggest that there are interested populations within Japan that would appreciate enhanced communication and interaction with healthcare teams. (shrink)

Fodor and others who think that scientific, computational psychology will vindicate commonsense belief-desire psychology have maintained that belief can be identified with the explicit storage of a token with appropriate content. I review and develop problems for the explicit storage view and show that a more plausible account identifies belief with the disposition to use a token with appropriate content in explicit reasoning and planning processes and as a basis for action. I argue that this type of inner disposition account (...) will also apply to most other common sense attitudes. The result is a realism about commonsense belief-desire psychology that is more modest than Fodor's: While such inner dispositions probably do exist, these states will probably not be the main focus of scientific psychological theories. (shrink)

America’s unfinished revolution The_revolutionary spirit that runs through American history and whose_founding_father and greatest advocate was Thomas Paine is fiercely traced in Thomas Paine and the Promise of America ._Showing how Paine turned Americans into radicals—and how we have remained radicals at heart ever since—Harvey J. Kaye presents the nation’s democratic story with wit, subtlety, and, above all, passion. Paine was one of the most remarkable political writers of the modern world and the greatest radical of a radical age._Through (...) writings like Common Sense —and words such as “The sun never shined on a cause of greater worth,” “We have it in our power to begin the world over again,” and “These are the times that try men’s souls”—he not only turned America’s colonial rebellion into a revolutionary war but, as Kaye demonstrates, articulated an American identity charged with exceptional purpose and promise. Beginning with Paine’s life and ideas and following their vigorous influence through to our own day, Thomas Paine and the Promise of America reveals how, while the powers that be repeatedly sought to suppress, defame, and most recently co-opt Paine’s memory, generations of radical and liberal Americans turned to Paine for inspiration as they endeavored to expand American freedom, equality, and democracy. (shrink)

Fodor has argued that, because concept acquisition relies on the use of concepts already possessed by the learner, all concepts that cannot be definitionally reduced are innate. Since very few reductive definitions are available, it appears that most concepts are innate. After noting the reasons why we find such radical concept nativism implausible, I explicate Fodor's argument, showing that anyone who is committed to mentalistic explanation should take it seriously. Three attempts at avoiding the conclusion are examined and found to (...) be unsuccessful. I then present an alternative way around Fodor's nativism; I maintain that concepts at a given level of explanation can be semantically primitive, yet at least partially acquired if some of the conditions at a lower level of explanation that are responsible for the concept's presence are themselves acquired. (shrink)

Clinicians, as well as other health-care professionals in genetics clinics, may find themselves in the position where they must consider whether it would be appropriate to offer a diagnostic genetic test to an adolescent. While a clinician's decision to offer a diagnostic genetic test may be straightforward in clinical terms, the dynamics of family interaction and circumstances may make the decision-making process more complicated. Disagreement between parent and child place clinicians in a difficult position and they must be clear about (...) the scope of their professional responsibility and obligations, to both parents and the adolescent. The purpose of this paper is to discuss the Gillick principles and statutory requirements regarding the genetic testing of adolescents. While I will discuss the clinician's obligations, these legal requirements also have applicability to other health-care professionals, such as genetic counsellors, working in genetics clinics. (shrink)

The language of “participant-driven research,” “crowdsourcing” and “citizen science” is increasingly being used to encourage the public to become involved in research ventures as both subjects and scientists....

I propose, develop and defend the view that theories of meaning — for instance, a theory specifying the logical form or truth conditions of natural language sentences — should be naturalized to scientific psychological inquiry. This involves both psychologism — the claim that semantics characterizes psychological states — and scientific naturalism — the claim that semantics will depend on the data and theories of scientific psychology. I argue that scientific psychologism is more plausible than the traditional alternative, the view that (...) a theory of meaning is a priori. After defending scientific psychologism against several objections, I offer a speculative proposal that shows how a theory of meaning can be integrated into scientific psychology. (shrink)

BackgroundInnovations in technology have contributed to rapid changes in the way that modern biomedical research is carried out. Researchers are increasingly required to endorse adaptive and flexible approaches to accommodate these innovations and comply with ethical, legal and regulatory requirements. This paper explores how Dynamic Consent may provide solutions to address challenges encountered when researchers invite individuals to participate in research and follow them up over time in a continuously changing environment.MethodsAn interdisciplinary workshop jointly organised by the University of Oxford (...) and the COST Action CHIP ME gathered clinicians, researchers, ethicists, lawyers, research participants and patient representatives to discuss experiences of using Dynamic Consent, and how such use may facilitate the conduct of specific research tasks. The data collected during the workshop were analysed using a content analysis approach.ResultsDynamic Consent can provide practical, sustainable and future-proof solutions to challenges related to participant recruitment, the attainment of informed consent, participant retention and consent management, and may bring economic efficiencies.ConclusionsDynamic Consent offers opportunities for ongoing communication between researchers and research participants that can positively impact research. Dynamic Consent supports inter-sector, cross-border approaches and large scale data-sharing. Whilst it is relatively easy to set up and maintain, its implementation will require that researchers re-consider their relationship with research participants and adopt new procedures. (shrink)

Dynamic Consent is both a model and a specific web-based tool that enables clear, granular communication and recording of participant consent choices over time. The DC model enables individuals to know and to decide how personal research information is being used and provides a way in which to exercise legal rights provided in privacy and data protection law. The DC tool is flexible and responsive, enabling legal and ethical requirements in research data sharing to be met and for online health (...) information to be maintained. DC has been used in rare diseases and genomics, to enable people to control and express their preferences regarding their own data. However, DC has never been explored in relationship to historical collections of bioscientific and genetic heritage or to contexts involving Aboriginal and Torres Strait Islander people.In response to the growing interest by First Peoples throughout Australia in genetic and genomic research, and the increasing number of invitations from researchers to participate in community health and wellbeing projects, this article examines the legal and ethical attributes and challenges of DC in these contexts. It also explores opportunities for including First Peoples' cultural perspectives, governance, and leadership as a method for defining DC on cultural terms that engage best practice research and data analysis as well as respect for meaningful and longitudinal individual and family participation. (shrink)

There is a vast literature that seeks to uncover features underlying moral judgment by eliciting reactions to hypothetical scenarios such as trolley problems. These thought experiments assume that participants accept the outcomes stipulated in the scenarios. Across seven studies, we demonstrate that intuition overrides stipulated outcomes even when participants are explicitly told that an action will result in a particular outcome. Participants instead substitute their own estimates of the probability of outcomes for stipulated outcomes, and these probability estimates in turn (...) influence moral judgments. Our findings demonstrate that intuitive likelihoods are one critical factor in moral judgment, one that is not suspended even in moral dilemmas that explicitly stipulate outcomes. Features thought to underlie moral reasoning, such as intention, may operate, in part, by affecting the intuitive likelihood of outcomes, and, problematically, moral differences between scenarios may be confounded with non-moral intuitive probabilities. (shrink)

Biobanks are increasingly being created specifically for research purposes. Concomitantly, we are seeing significant and evolving shifts in research ethics in relation to biobanking. Three discrete shifts are identified in this article. The first extends the ethical focus beyond the protection of human subjects to the promotion of broader community benefits of research utilizing biobanked resources, and an expectation that these benefits will be shared. The second involves the evolution of the traditional consent paradigm for future research uses of biobanks (...) resources that are not in contemplation at the time of donation. The third involves a move away from single project management to more dynamic governance accountability to research participants and the public. These shifts may take different local and institutional forms but share common recognizable elements. (shrink)

PDZ (also called DHR or GLGF) domains are found in diverse membraneassociated proteins including members of the MAGUK family of guanylate kinase homologues, several protein phosphatases and kinases, neuronal nitric oxide synthase, and several dystrophin‐associated proteins, collectively known as syntrophins. Many PDZ domain‐containing proteins appear to be localised to highly specialised submembranous sites, suggesting their participation in cellular junction formation, receptor or channel clustering, and intracellular signalling events. PDZ domains of several MAGUKs interact with the C‐terminal polypeptides of a subset (...) of NMDA receptor subunits and/or with Shaker‐type K+ channels. Other PDZ domains have been shown to bind similar ligands of other transmembrane receptors. Recently, the crystal structures of PDZ domains, with and without ligand, have been determined. These demonstrate the mode of ligand‐binding and the structural bases for sequence conservation among diverse PDZ domains. (shrink)