Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23, selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are released from perfused tracheas of mutant and wild-type mice at the (...) same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 min after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 min of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to WT mice, consistent with these functions depending on baseline secretion that is fully compensated. (shrink)

Background The use of lengthy, detailed, and complex informed consent forms is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in (...) biomedical research. Methods This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 to 5. Results Of the 2484 questionnaires distributed, 2113 were returned. The majority of respondents considered most elements required in the ICF to be ‘moderately important’ to ‘very important’ for their decision making. Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF. Conclusions Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF. (shrink)

Although there are various studies comparing Greek and Indian philosophy and religion, and Chinese and Western philosophy and religion, Brahman and Dao: Comparatives Studies in Indian and Chinese Philosophy and Religion is a first of its kind that brings together Indian and Chinese philosophies and religions. Brahman and Dao helps close the gap on a much needed examination on the rich history of Buddhist transmission to China, and the many generations of Indian Buddhist missionaries to China and Chinese Buddhist pilgrims (...) to India, including the legendary Bodhidharma, and Faxian and Xuanzang. (shrink)

In this study, we attempt to explain the divergent results found in the relationships between supervisor–subordinate guanxi and employee work outcomes. Specifically, we propose that the relationships between supervisor–subordinate guanxi and participatory management, turnover intentions, and organizational commitment are mediated by job satisfaction. Based on the data collected from a sample of 196 employees of three local manufacturing firms in Zhejiang Province, China, we found that job satisfaction fully mediated the effects of supervisor–subordinate guanxi on participatory management and intentions to (...) leave, but partially mediated the relationship between supervisor–subordinate guanxi and organizational commitment. Theoretical and practical implications are discussed. (shrink)

In recent times, daily, ordinary medical practices have incontrovertibly been developing under the condition of complexity. Complexity jeopardizes the moral core of practicing medicine: helping people, with their illnesses and suffering, in a medically competent way. Practical wisdom (a modification of the Aristotelian phronèsis) has been proposed as part of the solution to navigate complexity, aiming at the provision of morally good care. Practical wisdom should help practitioners to maneuver in complexity, where the presupposed linear ways of operating prove to (...) be insufficient. However, this solution is unsatisfactory, because the proposed versions of practical wisdom are too individualistic of nature, while physicians are continuously operating in varying teams, and dealing with complicated technologies and pressing structures. A second point of critique is, that these versions are theory based, and thus insufficiently attuned to the actual context of everyday medical practices. Now, our proposal is to use an approach of practical wisdom that enables medical practices to counter the complexity issue and to re-invent the moral core of medical practicing as well. This implies a practice oriented approach, as thematized by practice theory, qualitative empirical research from the inside, and abduction from actual performed practical wisdom towards an apt understanding of phronèsis. (shrink)

Moral case deliberation (MCD) is a form of clinical ethics support in which the ethicist as facilitator aims at supporting professionals with a structured moral inquiry into their moral issues from practice. Cases often affect clients, however, their inclusion in MCD is not common. Client participation often raises questions concerning conditions for equal collaboration and good dialogue. Despite these questions, there is little empirical research regarding client participation in clinical ethics support in general and in MCD in particular. This article (...) aims at describing the experiences and processes of two MCD groups with client participation in a mental healthcare institution. A responsive evaluation was conducted examining stakeholders’ issues concerning client participation. Findings demonstrate that participation initially creates uneasiness. As routine builds up and client participants meet certain criteria, both clients and professionals start thinking beyond ‘us-them’ distinctions, and become more equal partners in dialogue. Still, sentiments of distrust and feelings of not being safe may reoccur. Client participation in MCD thus requires continuous reflection and alertness on relational dynamics and the quality of and conditions for dialogue. Participation puts the essentials of MCD (i.e., dialogue) to the test. Yet, the methodology and features of MCD offer an appropriate platform to introduce client participation in healthcare institutions. (shrink)

High-dose chemotherapy and autologous stem cell transplantation is used to treat some advanced malignancies. It is a traumatic procedure, with a high complication rate and significant mortality. ASCT patients and their carers draw on many sources of information as they seek to understand the procedure and its consequences. Some seek information from beyond orthodox medicine. Alternative beliefs and practices may conflict with conventional understanding of the theory and practice of ASCT, and ‘contested understandings’ might interfere with patient adherence to the (...) strict and demanding protocols required for successful ASCT.The present study, conducted in Sydney, Australia, examines narrative-style interviews with 10 sequentially recruited ASCT patients and nine of their carers conducted at the time of transplant and three months later. Transcripts were read for instances of mention of alternative advice, and for instances of contested understanding of information relevant to the transplant.Patients and carer pairs expressed closely concordant views about alternative advice. Five pairs were consulting alternative practitioners. Contested understanding was expressed in four domains—understandings of the transplant itself and its underlying theory, of the relationship between the components of the ‘transplant’, of the nature and role of stem cells, and of beliefs about bodily function and life-style. Contested understandings of the transplant treatment were expressed as predominantly personal interpretations of orthodox informationPatients and carers seemed to recognise that alternative and conventional systems were discordant, yet they were able to separate the two, and adhere to each practice without prejudicing their medical treatment. A single case of late, post-transplant repudiation of Western medicine is discussed to emphasise some of the possible determinants of dissonance when it does occur. (shrink)

Background If trials of therapeutic interventions are to serve society's interests, they must be of high methodological quality and must satisfy moral commitments to human subjects. The authors set out to develop a clinical - trials compendium in which standards for the ethical treatment of human subjects are integrated with standards for research methods. Methods The authors rank-ordered the world's nations and chose the 31 with >700 active trials as of 24 July 2008. Governmental and other authoritative entities of the (...) 31 countries were searched, and 1004 English-language documents containing ethical and/or methodological standards for clinical trials were identified. The authors extracted standards from 144 of those: 50 designated as ‘core’, 39 addressing trials of invasive procedures and a 5% sample of the remainder. As the integrating framework for the standards we developed a coherent taxonomy encompassing all elements of a trial's stages. Findings Review of the 144 documents yielded nearly 15 000 discrete standards. After duplicates were removed, 5903 substantive standards remained, distributed in the taxonomy as follows: initiation, 1401 standards, 8 divisions; design, 1869 standards, 16 divisions; conduct, 1473 standards, 8 divisions; analysing and reporting results, 997 standards, four divisions; and post-trial standards, 168 standards, 5 divisions. Conclusions The overwhelming number of source documents and standards uncovered in this study was not anticipated beforehand and confirms the extraordinary complexity of the clinical trials enterprise. This taxonomy of multinational ethical and methodological standards may help trialists and overseers improve the quality of clinical trials, particularly given the globalisation of clinical research. (shrink)

In moral case deliberation (MCD), healthcare professionals meet to reflect upon their moral questions supported by a structured conversation method and non-directive conversation facilitator. An increasing number of Dutch healthcare institutions work with MCD to (1) deal with moral questions, (2) improve reflection skills, interdisciplinary cooperation and decision-making, and (3) develop policy. Despite positive evaluations of MCD, organization and implementation of MCD appears difficult, depending on individuals or external experts. Studies on MCD implementation processes have not yet been published. The (...) aim of this study is to describe MCD implementation processes from the perspective of nurses who co-organize MCD meetings, so called ‘ local coordinators ’. Various qualitative methods were used within the framework of a responsive evaluation research design. The results demonstrate that local coordinators work hard on the pragmatic implementation of MCD. They do not emphasize the ethical and normative underpinnings of MCD, but create organizational conditions to foster a learning process, engagement and continuity. Local coordinators indicate MCD needs firm back-up from management regulations. These pragmatic action-oriented implementation strategies are as important as ideological reasons for MCD implementation. Advocates of clinical ethics support should pro-actively facilitate these strategies for both practical and ethical reasons. (shrink)

This paper develops an incomplete information model of extended deterrence relationships. It postulates players who are fully informed about the costs of war and all other relevant variables, save for the values their opponents place on the issues at stake, i.e., the pawn. We provide consistent and intuitively satisfying parallel definitions for two types of players, Hard and Soft, in terms of the parameters of our model. We also answer several particular questions about the strategy choices of players in an (...) extended deterrence relationship and, by identifying all the Perfect Bayesian Equilibria of the game model we construct, specify typical behavior patterns.Our most general finding is that an Extended Deterrence Game always has a unique Perfect Bayesian Equilibrium with a rather simple form. A challenger initiates for certain if the pawn is valuable enough to it and never challenges otherwise, Likewise, a defender always resists if the pawn is valuable enough and never resists otherwise. (shrink)

Hooglands commentaar op mijn ‘Pluralisme’ komt hierop neer dat levensbeschouwelijke neutraliteit niet mogelijk is, noch voor de overheid, noch voor de individuele burger. We kunnen geen radicale buitenstaanderspositie innemen tegenover de levensbeschouwing die we erop nahouden. Dat zou een vorm van hybris zijn. Wie niettemin levensbeschouwelijke neutraliteit bepleit en deze identificeert met tolerantie voor de levensbeschouwingen van anderen, pretendeert in feite dat het eigen tolerante standpunt moreel superieur is aan het standpunt van al diegenen die aan hun levensbeschouwing vastgeklonken zitten. (...) Dat is moreel verwerpelijk. (shrink)