Cyclic adenosine monophosphate (cAMP) and cAMP‐dependent protein kinase A (PKA) are evolutionary conserved molecules with a well‐established position in the complex network of signal transduction pathways. cAMP/PKA‐mediated signaling pathways are implicated in many biological processes that cooperate in organ development including the motility, survival, proliferation and differentiation of epithelial cells. Cell surface polarity, here defined as the anisotropic organisation of cellular membranes, is a critical parameter for most of these processes. Changes in the activity of cAMP/PKA elicit a variety of (...) effects on intracellular membrane dynamics, including membrane sorting and trafficking. One of the most intriguing aspects of cAMP/PKA signaling is its evolutionary conserved abundance on the one hand and its precise spatial–temporal actions on the other. Here, we review recent developments with regard to the role of cAMP/PKA in the regulation of intracellular membrane trafficking in relation to the dynamics of epithelial surface domains. BioEssays 30:146–155, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Despite the proliferation of research on ethical leadership, there remains a limited understanding of how specifically the assumingly moral component of this leadership style affects employee behavior. Taking an identity perspective, we integrate the ethical leadership literature with research on the dynamics of the moral self-concept to posit that ethical leadership will foster a sense of moral identity among employees, which then inspires followers to adopt more ethical actions, such as increased organization citizenship behavior. We further argue that these identity (...) effects should be more pronounced when leaders are perceived to be group prototypical, as their actions then speak louder to followers’ sense of identity. Two studies—a scenario experiment with 138 participants and a field study with 225 employees—provided support for our hypothesized moderated mediation model. Perceived ethical leadership positively affected OCB via followers’ moral identity but only under conditions of high perceived leader group prototypicality. We discuss how the identity pathway of ethical leadership can facilitate novel theorizing about moral transference. Our findings also suggest that, when hiring external ethical leaders or training internal managers, practitioners are well advised to consider that these individuals may only be effective in morally transforming followers when they are perceived as prototypical for the group. (shrink)

Vraagt onze samenleving om een nieuwe politieke formule, om met Alexis de Tocqueville (1805-1859) te spreken? Op het eerste gezicht niet. De democratie is stevig verankerd in de Grondwet en verdragen en is ingebed in de rechtsstaat, en zowel democratie als rechtsstaat maken deel uit van ons collectieve bewustzijn. Toch is er wat aan de hand in de verhouding tussen overheid, samenleving en individu, zoals de inmiddels structurele onvrede met het publieke domein laat zien. Dat vraagt om een richtinggevende doordenking (...) van de vooronderstellingen van ons democratisch bestel en de fundamenten waarop het berust. Dat is wat dit boek zich ten doel stelt. Het biedt toekomstgerichte ideeën voor ons publieke domein aan de hand van kernbegrippen als legitimiteit, staat, politiek, instituties, identiteit, burgerschap, kerk en theologie. Het gedachtegoed van Tocqueville, die geldt als een van de grootste en meest interessante denkers over de moderne democratie, de democratische samenleving en de democratische mens, vormt daarvoor de inspiratiebron. (shrink)

Introduction: The Dutch Euthanasia Act states that euthanasia is not punishable if the attending physician acts in accordance with the statutory due care criteria. These criteria hold that: there should be a voluntary and well-considered request, the patient’s suffering should be unbearable and hopeless, the patient should be informed about their situation, there are no reasonable alternatives, an independent physician should be consulted, and the method should be medically and technically appropriate. This study investigates whether physicians experience problems with these (...) criteria in medical practice.Methods: In 2006, questionnaires were sent to a random, stratified sample of 2100 Dutch physicians . Physicians were asked about problems in their decision-making related to requests for euthanasia or assisted suicide after enforcement of the 2002 Euthanasia Act.Results: Of all physicians who had received a request for euthanasia or assisted suicide , 25% had experienced problems in the decision-making with regard to at least one of the criteria of due care. Physicians who had experienced problems mostly indicated to have had problems related to evaluating whether or not the patient’s suffering was unbearable and hopeless and whether or not the patient’s request was voluntary or well considered .Discussion: Physicians in The Netherlands most frequently reported problems related to aspects in which they have to evaluate the patient’s subjective perspective. However, it can be questioned whether placing emphasis on these subjective aspects is an adequate fulfilment of the duties imposed on physicians, as laid down in the Dutch Euthanasia Act. (shrink)

We apply an online optimization process based on machine learning to the production of Bose-Einstein condensates. BEC is typically created with an exponential evaporation ramp that is optimal for ergodic dynamics with two-body s-wave interactions and no other loss rates, but likely sub-optimal for real experiments. Through repeated machine-controlled scientific experimentation and observations our ’learner’ discovers an optimal evaporation ramp for BEC production. In contrast to previous work, our learner uses a Gaussian process to develop a statistical model of the (...) relationship between the parameters it controls and the quality of the BEC produced. We demonstrate that the Gaussian process machine learner is able to discover a ramp that produces high quality BECs in 10 times fewer iterations than a previously used online optimization technique. Furthermore, we show the internal model developed can be used to determine which parameters are essential in BEC creation and which are unimportant, providing insight into the optimization process of the system. (shrink)

Introduction In 2007, a national review committee was instituted in The Netherlands to review cases of active ending of life for newborns. It was expected that 15–20 cases would be reported. To date, however, only one case has been reported to this committee. Reporting is essential to obtain societal control and transparency; the possible explanations for this lack of reporting were therefore explored. Methods Data on end-of-life decision-making were scrutinised from Dutch nation-wide studies (1995, 2001 and 2005), before institution of (...) the committee. Physicians received a questionnaire about their medical decision-making for stratified samples of deceased infants up to 1 year, drawn from the central death registry. Results In 2005, 58% of all deaths were preceded by an end-of-life decision, compared with 68% in 2001 and 62% in 1995. The use of drugs with a possible life-shortening effect tended to be lower. In 2005, all four cases in the study in which an infants' life was actively ended were preceded by a decision to forego life-prolonging treatment. In three cases, the infant's life expectancy was short; one case involved a longer life expectancy. Discussion The expected number of cases is probably an overestimation due to changes in medical practice such as the tendency to attribute less life-shortening effects to opioids. The lack of reports is probably also associated with requirements in the regulation; it may be difficult to fulfil them due either to time constraints or the nature of the suffering that is addressed. If societal control of active ending of life is considered useful, changes in the regulation may be needed. (shrink)

Theoria , the international Swedish philosophy journal, was founded in 1935. Its contributors in the first 75 years include the major Swedish philosophers from this period and in addition a long list of international philosophers, including A. J. Ayer, C. D. Broad, Ernst Cassirer, Hector Neri Castañeda, Arthur C. Danto, Donald Davidson, Nelson Goodman, R. M. Hare, Carl G. Hempel, Jaakko Hintikka, Saul Kripke, Henry E. Kyburg, Keith Lehrer, Isaac Levi, David Lewis, Gerald MacCallum, Richard Montague, Otto Neurath, Arthur N. (...) Prior, W. V. Quine, Nicholas Rescher, Ernest Sosa, Robert C. Stalnaker, P. F. Strawson, Patrick Suppes, Johan van Benthem, Georg Henrik von Wright and many others. Hempel's confirmation paradoxes, Ross's deontic paradox, Montague's universal grammar and Lindström's theorem are among the contributions to philosophy that were first published in Theoria. (shrink)

The Hutchinsonian movement exercised considerable influence on thought about various topics of importance in England's Enlightenment/Counter-Enlightenment debates. Its epistemological stance, derived from a group of Irish writers of the early eighteenth century, places the movement at the centre of these debates and does much to explain its attraction to contemporaries. The article emphasises the persistence of Hutchinsonian thought and the continuing importance of its epistemological underpinnings into the early nineteenth century, drawing attention particularly to the writings of Bishop William Van (...) Mildert. (shrink)

This article provides ethical guidance on using race in health research as a variable or in defining the study population. To this end, a plain, non-exhaustive checklist is provided for researchers and research ethics committees, preceded by a brief introduction on the need for justification when using race as a variable or in defining a study population, the problem of exoticism, that distinctions pertain between race, ethnicity and ancestry, the problematic naming of races, and that race does not serve well (...) as a presumed biological construct in genetic research. (shrink)

We investigated, by means of the Reverse Correlation Task, visual representations of the culturally dominating group of local people held by sojourners as a function of their degree of cross-cultural adaptation. In three studies, using three different methods with three independent samples of sojourners and seven independent samples of Portuguese and US-American raters, we gathered clear evidence that poor adaptation goes along with more negative representations of locals. This indicates that sojourner adaptation is reflected, at a social-cognitive level, in the (...) valence of outgroup representations. (shrink)

Argumentation as the public exchange of reasons is widely thought to enhance deliberative interactions that generate and justify reasonable public policies. Adopting an argumentation-theoretic perspective, we survey the norms that should govern public argumentation and address some of the complexities that scholarly treatments have identified. Our focus is on norms associated with the ideals of correctness and participation as sources of a politically legitimate deliberative outcome. In principle, both ideals are mutually coherent. If the information needed for a correct deliberative (...) outcome is distributed among agents, then maximising participation increases information diversity. But both ideals can also be in tension. If participants lack competence or are prone to biases, a correct deliberative outcome requires limiting participation. The central question for public argumentation, therefore, is how to strike a balance between both ideals. Rather than advocating a preferred normative framework, our main purpose is to illustrate the complexity of this theme. (shrink)

Take the following version of scientific realism: we have good reason to believe that (some of the) current scientific theories tell us something specific about the underlying, i.e. unobservable, structures of the world, for instance that there are electrons with a certain electric charge, or that there are viruses that cause certain diseases. Popper, the rationalist, would not have adhered to the proposed formulation of scientific realism in terms of the rationality of existential beliefs concerning unobservables. Popper did not believe (...) in belief. According to Van Fraassen, the empiricist, one may yet have a rational existential belief concerning unobservables, given a liberal notion of rationality of belief. In this paper I will investigate to what extent a reassessment of both Popper’s rejection of the rationality of belief and Van Fraassen’s reformulation of the rationality of belief, points towards a new and pragmatist dissolution of the ‘problem of scientific realism’. (shrink)

SummaryTake the following version of scientific realism: we have good reason to believe that (some of the) current scientific theories tell us something specific about the underlying, i.e. unobservable, structures of the world, for instance that there are electrons with a certain electric charge, or that there are viruses that cause certain diseases. Popper, the rationalist, would not have adhered to the proposed formulation of scientific realism in terms of the rationality of existential beliefs concerning unobservables. Popper did not believe (...) in belief. According to Van Fraassen, the empiricist, one may yet have a rational existential belief concerning unobservables, given a liberal notion of rationality of belief. In this paper I will investigate to what extent a reassessment of both Popper’s rejection of the rationality of belief and Van Fraassen’s reformulation of the rationality of belief, points towards a new and pragmatist dissolution of the ‘problem of scientific realism’. (shrink)

Two decades of research on euthanasia in the Netherlands have resulted into clear insights in the frequency and characteristics of euthanasia and other medical end-of-life decisions in the Netherlands. These empirical studies have contributed to the quality of the public debate, and to the regulating and public control of euthanasia and physician-assisted suicide. No slippery slope seems to have occurred. Physicians seem to adhere to the criteria for due care in the large majority of cases. Further, it has been shown (...) that the majority of physicians think that the euthanasia Act has improved their legal certainty and contributes to the carefulness of life-terminating acts. In 2005, eighty percent of the euthanasia cases were reported to the review committees. Thus, the transparency envisaged by the Act still does not extend to all cases. Unreported cases almost all involve the use of opioids, and are not considered to be euthanasia by physicians. More education and debate is needed to disentangle in these situations which acts should be regarded as euthanasia and which should not. Medical end-of-life decision-making is a crucial part of end-of-life care. It should therefore be given continuous attention in health care policy and medical training. Systematic periodic research is crucial for enhancing our understanding of end-of-life care in modern medicine, in which the pursuit of a good quality of dying is nowadays widely recognized as an important goal, in addition to the traditional goals such as curing diseases and prolonging life. (shrink)

Background Since the enactment of the euthanasia law in the Netherlands, there has been a lively public debate on assisted dying that may influence the way patients talk about euthanasia and physician-assisted suicide with their physicians and the way physicians experience the practice of EAS. Aim To show what developments physicians see in practice and how they perceive the influence of the public debate on the practice of EAS. Methods We conducted a secondary analysis of in-depth interviews with 28 Dutch (...) physicians who had experience with a complex case of EAS. Respondents were recruited both by the network of physicians working for SCEN as well as via a national questionnaire, wherein participating physicians could indicate their willingness to be interviewed. Results Three themes came up in analysing the interviews. First, the interviewed physicians experienced a change in what patients would expect from them: from a role as an involved caregiver to being the mere performer of EAS. Second, interviewees said that requests for EAS based on non-medical reasons came up more frequently and wondered if EAS was the right solution for these requests. Last, respondents had the impression that the standards of EAS are shifting and that the boundaries of the EAS regulation were stretched. Conclusions The perceived developments could make physicians less willing to consider a request for EAS. Our results also raise questions about the role of physicians and of EAS in society. (shrink)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

BackgroundResearch ethics committees (RECs) are tasked to assess the risks and the benefits of a trial. Currently, two procedure-level approaches are predominant, the Net Risk Test and the Component Analysis.DiscussionBy looking at decision studies, we see that both procedure-level approaches conflate the various risk-benefit tasks, i.e., risk-benefit assessment, risk-benefit evaluation, risk treatment, and decision making. This conflation makes the RECs’ risk-benefit task confusing, if not impossible. We further realize that RECs are not meant to do all the risk-benefit tasks; instead, (...) RECs are meant to evaluate risks and benefits, appraise risk treatment suggestions, and make the final decision.ConclusionAs such, research ethics would benefit from looking beyond the procedure-level approaches and allowing disciplines like decision studies to be involved in the discourse on RECs’ risk-benefit task. (shrink)

Background: Issues concerning legislation and regulation with respect to the role of nurses in euthanasia and physician-assisted suicide gave the Minister for Health reason to commission a study of the role of nurses in medical end-of-life decisions in hospitals, home care and nursing homes.Aim: This paper reports the findings of a study of the role of nurses in euthanasia and physician-assisted suicide, conducted as part of a study of the role of nurses in medical end-of-life decisions. The findings for hospitals, (...) home care and nursing homes are described and compared.Method: A questionnaire was sent to 1509 nurses, employed in 73 hospitals, 55 home care organisations and 63 nursing homes. 1179 responses were suitable for analysis. The questionnaire was pilot-tested among 106 nurses, with a response rate of 85%.Results: In 37.0% of cases, the nurse was the first person with whom patients discussed their request for euthanasia or physician-assisted suicide. Consultation between physicians and nurses during the decision-making process took place quite often in hospitals and nursing homes and less frequently in home care situations . In some cases , nurses administered the euthanatics.Conclusions: The results show substantial differences between the intramural sector and the extramural sector , which are probably linked to the organisational structure of the institutions. Consultation between physicians and nurses during the decision-making process needs improvement, particularly in home care. Some nurses had administered euthanatics, although this task is by law exclusively reserved to physicians. (shrink)