Adenosine transport in cultured human umbilical vein endothelial cells (HUVEC) was characterized and shown to be mediated by a single facilitated diffusion mechanism. Initial rates of adenosine influx at 22 degrees C were saturable [apparent Michaelis constant, 69 +/- 10 mu M; maximum velocity (V-max), 600 +/- 70 pmol.10(6) cells(-1).s(-1)] and inhibited by nitrobenzylthioinosine (NBMPR). Formycin B had an unusually high affinity [inhibitory constant K-i), 18 +/- 4.3 mu M], whereas inosine had a low affinity (K-i, 440 +/- 68 mu (...) M) and nucleobases were without effect on adenosine influx. The number of transporters (1.2 x 10(6) sites/cell) was estimated by NBMPR equilibrium binding (apparent dissociation constant, 0.11 +/- 0.01 nM; maximum binding, 2.0 +/- 0.15 pmol/10(6) cells). In addition, we compared these endothelial cells with those obtained from cords from pregnancies complicated by diabetes (HUVEC-D), since embriopathy may occur in these conditions. HUVEC-D exhibited a 2.3-fold reduction in both the V-max for adenosine influx and the maximum number of NBMPR binding sites (260 +/- 40 pmol.10(6) cells(-1).s(-1) and 0.86 +/- 0.08 pmol/10(6) cells, respectively). However, the turnover number for each nucleoside transporter in normal and diabetic HUVEC was similar (approximate to 300 adenosine molecules/s). Adenosine metabolism at 10 mu M in HUVEC-D was modified compared with normal cells. Intracellular phosphorylation (> 90%) was the predominant pathway in normal HUVEC, whereas in HUVEC-D, substantial levels of adenine and adenosine were detected. The present results demonstrate therefore the downregulation of the NBMPR-sensitive nucleoside transporter and changes in adenosine metabolism in HUVEC from diabetic pregnancies. (shrink)

Polyclonal antibodies raised against the human erythrocyte nucleoside transporter were used to investigate the distribution of the nucleoside transporters in the placenta. Immunoblots of brush-border membranes isolated from the human syncytiotrophoblast revealed a cross-reactive species that co-migrated with the erythrocyte nucleoside transporter as a broad band of apparent M 55,000. In contrast, no labelling was detected in basal membranes containing a similar number of equilibrative nucleoside transporters as assessed by nitrobenzylthioinosine -binding. The absence of cross-reactive epitopes in basal membranes and (...) their presence in brush-border membranes was confirmed by confocal immunofluorescence microscopy. The results suggest that at least two isoforms of the NBMPR-sensitive nucleoside transporter are present in the human placenta. The lumenal surfaces of fetal capillaries, small placental vessels and umbilical vein ware also strongly labelled by the antibody, a finding that suggests that the high fetal-placental adenosine uptake previously reported is due to endothelial transporters. (shrink)

Almost traditionally, it seems, accounts of the development of the concepts of work and energy have tended to describe them within the classical framework of Newtonian mechanics. They are seen as the end products of the celebratedvis-vivadispute in the eighteenth century: the outcome of a debate within the confines of the science of rational mechanics. I would like to suggest that this may be to take too narrow a view of the case. It is to project backwards our present specialist (...) arrangement of scientific knowledge, our present divisions between the sciences, and to assume that past development was strictly guided by these divisions. And this is to make questionable historical and sociological assumptions. (shrink)

The history of the dyestuffs industry during the period 1775–1860 is interesting for three reasons. In the first place it was in connection with the manufacture of synthetic dyestuffs, begun in 1856, that the industrial research laboratory and the organization scientist first unmistakably appeared in the last decades of the nineteenth century. Secondly, there are the enigmas of W. H. Perkin, the man who discovered and manufactured the first coal-tar colours, but who retired somewhat abruptly from the industry in 1874: (...) just after the synthesis of alizarine. Thirdly, the dyestuffs industry was in intimate association with the textile industries which had for a long time been subject to frequent radical scientific and technological innovation. Among the most important of these we may mention John Smeaton's classic paper of 1759 on the maximum work obtainable from a given fall of water: a problem important not only for the abstract science of mechanics, but also for the design of waterwheels—the main source of power for the early textile mills. (The waterwheel was not, during the eighteenth century, the epitome of the quaint and picturesque: it was in the van of scientific and technical progress.) Again, the textile industries were quick to employ the Watt rotative engine; previously a two cylinder Newcomen engine had been tried out. Bleaching powders, based on Scheele's discovery of chlorine and its properties, were rapidly adopted: in this context one cannot help contrasting the indifference of medical science to Davy's early suggestion of using nitrous oxide as an anaesthetic; or Faraday's comment in 1818 on the anaesthetic power of sulphuric ether. The textile industries saw, over this period, a rapid succession of new machines, the pace of invention being so hot that in 1832 Charles Babbage reported that machines became obsolete long before they wore out. A Salford cotton mill was the first industrial establishment to use gas lighting: James Thomson, calico printer, introduced gas lighting to the town of Clitheroe when he installed it in his works. And there were many other important technical and scientific innovations. It was to supply these industries, so well accustomed to change, that the synthetic coal-tar dyestuffs were introduced from 1856 onwards. It is interesting that, so far as we can see, the appearance of these synthetic dyestuffs was the last in the series of major innovations in the textiles and related industries: at least until recent times. (shrink)

For several decades, higher education systems have undergone continuous waves of reform, driven by a combination of concerns about the changing labour needs of the economy, competition within the global-knowledge economy, and nationally competitive positioning strategies to enhance the performance of higher education systems. Yet, despite far-ranging international pressures, including the emergence of an international higher education market, enormous growth in cross-border student mobility, and pressures to achieve universities of world class standing, boost research productivity and impact, and compete in (...) global league tables, the suites of policy, policy designs and sector outcomes continue to be marked as much by hybridity as they are of similarity or convergence. This volume explores these complex governance outcomes from a theoretical and empirical comparative perspective, addressing those vectors precipitating change in the modalities and instruments of governance, and how they interface at the systemic and institutional levels, and across geographic regions. (shrink)

Background: Demand for organisational ethics capacity is growing in health organisations, particularly among managers. The role of clinical ethicists in, and perspective on, organisational ethics has not been well described or documented in the literature. Objective: To describe clinical ethicists’ perspectives on organisational ethics issues in their hospitals, their institutional role in relation to organisational ethics, and their perceived effectiveness in helping to address organisational ethics issues. Design and Setting: Qualitative case study involving semi-structured interviews with 18 clinical ethicists across (...) 13 health organisations in Toronto, Canada. Results: From the clinical ethicists’ perspective, the most pressing organisational ethics issues in their organisations are: resource allocation, staff moral distress linked to the organisation’s moral climate, conflicts of interest, and clinical issues with a significant organisational dimension. Clinical ethicists were consulted in particular on issues related to staff moral distress and clinical issues with an organisational dimension. Some ethicists described being increasingly consulted on resource allocation, conflicts of interest, and other corporate decisions. Many clinical ethicists felt they lacked sufficient knowledge and understanding of organisational decision-making processes, training in organisational ethics, and access to organisational ethics tools to deal effectively with the increasing demand for organisational ethics support. Conclusion: Growing demand for organisational ethics expertise in healthcare institutions is reshaping the role of clinical ethicists. Effectiveness in organisational ethics entails a re-evaluation of clinical ethics training to include capacity building in organisational ethics and organisational decision-making processes as a complement to traditional clinical ethics education. (shrink)

This paper provides a brief overview and critique of the dominant objectivist understanding and use of illness narrative in Enlightenment (scientific) medicine and ethics, as well as several revisionist accounts, which reflect the evolution of this approach. In light of certain limitations and difficulties endemic in the objectivist understanding of illness narrative, an alternative phronesis approach to medical ethics influenced by Charles Taylor’s account of the interpretive nature of human agency and language is examined. To this end, the account of (...) interpretive medical responsibility previously described by Schultz and Carnevale as "clinical phronesis" (based upon Taylor’s notion of "strong" or "radical evaluation") is reviewed and expanded. The thesis of this paper is that illness narrative has the ability to benefit patients as well as the potential to cause harm or iatrogenic effects. This benefit or harm is contingent upon how the story is told and understood. Consequently, these tales are not simply "nice stories," cathartic gestures, or mere supplements to scientific procedures and decision making, as suggested by the objectivist approach. Rather, they open the agent to meanings that provide a context for explanation and evaluation of illness episodes and therapeutic activities. This understanding provides indicators (guides) for right action. Hence, medical responsibility as clinical phronesis involves, first, the patient and provider’s coformulation and cointerpretation of what is going on in the patient’s illness narrative, and second, the patient and provider’s response to interpretation of the facts of illness and what they signify–not simply a response to the brute facts of illness, alone. The appeal to medical responsibility as clinical phronesis thus underscores the importance of getting the patient’s story of illness right. It is anticipated that further elaboration concerning the idea of clinical phronesis as interpretive illness narrative will provide a new foundation for medical ethics and decision making. (shrink)

© 2015 NATCO, The Organization for Transplant Professionals.Despite the known benefits of kidney transplant, less than 30% of the 615 000 patients living with end-stage renal disease in the United States have received a transplant. More than 100 000 people are presently on the transplant waiting list. Although the shortage of kidneys for transplant remains a critical factor in explaining lower transplant rates, another important and modifiable factor is patients' lack of comprehensive education about transplant. The purpose of this article (...) is to provide an overview of known best practices from the broader literature that can be used as an evidence base to design improved education for ESRD patients pursuing a kidney transplant. Best practices in chronic disease education generally reveal that education that is individually tailored, understandable for patients with low health literacy, and culturally competent is most beneficial. Effective education helps patients navigate the complex health care process successfully. Recommendations for how to incorporate these best practices into transplant education design are described. Providing more ESRD patients with transplant education that encompasses these best practices may improve their ability to make informed health care decisions and increase the numbers of patients interested in pursuing transplant. (shrink)

Contents: John A. HALL and Ian JARVIE: Preface. John A. HALL and Ian JARVIE: The Life and Times of Ernest Gellner. PART 1 INTELLECTUAL BACKGROUND. Ji_i MUSIL: The Prague Roots of Ernest Gellner's Thinking. Chris HANN: Gellner on Malinowski: Words and Things in Central Europe. Tamara DRAGADZE: Ernest Gellner in the Soviet East. PART 2 NATIONS AND NATIONALISM. Brendan O'LEARY: On the Nature of Nationalism: An Appraisal of Ernest Gellner's Writings on Nationalism. Kenneth MINOGUE: Ernest Gellner and the Dangers of (...) Theorising Nationalism. Anthony D. SMITH: History and Modernity: Reflection on the Theory of Nationalism. Michael MANN: The Emergence of Modern European Nationalism. Nicholas STARGARDT: Gellner's Nationalism: The Spirit of Modernisation? PART 3 PATTERNS OF DEVELOPMENT. Peter BURKE: Reflections on the History of Encyclopaedias. Alan MACFARLANE: Ernest Gellner and the Escape to Modernity. Ronald DORE: Sovereign Individuals. Shmuel EISENSTADT: Japan: Non-Axial Modernity. Marc FERRO: l'Indépendance Telescopée: De la Décolonisation a l'Impérialisme Multinational. PART 4 ISLAM. Abdellah HAMMOUDI: Segmentarity, Social Stratification, Political Power and Sainthood: Reflections on Gellner's Theses. Henry MUNSON, Jr.: Rethinking Gellner's Segmentary Analysis of Morocco's Ait cAtta. Jean BAECHLER: Sur le charisme. Charles LINDHOLM: Despotism and Democracy: State and Society in the Premodern Middle East. Henry MUNSON, Jr.: Muslim and Jew in Morocco: Reflections on the Distinction between Belief and Behavior. Talal ASAD: The Idea of an Anthropology of Islam. PART 5 SCIENCE AND DISENCHANTMENT. Perry ANDERSON: Science, Politics, Enchantment. Ralph SCHROEDER: From the Big Divide to the Rubber Cage: Gellner's Conception of Science and Technology. John DAVIS: Irrationality in Social Life. PART 6 RELATIVISM AND UNIVERSALS. John SKORUPSKI: The Post-Modern Hume: Ernest Gellner's 'Enlightenment Fundamentalism'. John WETTERSTEN: Ernest Gellner: A Wittgensteinian Rationalist. Ian JARVIE: Gellner's Positivism. Raymond BOUDON: Relativising Relativism: When Sociology Refutes the Sociology of Science. Rod AYA: The Devil in Social Anthropology; or, the Empiricist Exorcist; or, the Case Against Cultural Relativism. PART 7 PHILOSOPHY OF HISTORY. William MCNEILL: A Swan Song for British Liberalism? Andrus PARK: Gellner and the Long Trends of History. Eero LOONE: Marx, Gellner, Power. Rosaire LANGLOIS: Coercion, Cognition and Production: Gellner's Challenge to Historical Materialism and Postmodernism. Ernest GELLNER: Reply to Critics. Ian JARVIE: Complete Bibliography of Gellner's Work. Name index. Subject index. (shrink)

Ethical guidance for genomic research is increasingly sought and perceived to be necessary. Although there are pressing ethical issues in genomic research – concerning for example the recruitment of patients/participants; the process of taking consent; data sharing; and returning results to patients/participants – there is still limited useful guidance available for researchers/clinicians or for the research ethics committees who review such projects. This report outlines the ethical principles and guidance for genomic research co-produced with stakeholders during two workshops which took (...) place in the UK between November 2016 and May 2017. The stakeholders involved in these workshops included: healthcare professionals, genomic research teams, academics, patients, biobank managers, and representatives from the Health Research Authority, NHS Research Ethics Committees, patient support groups, pharmaceutical industry, and health policy think tanks. The co-produced principles and guidance are specifical... (shrink)

Background -/- Ontology Design Patterns (ODPs) are representational artifacts devised to offer solutions for recurring ontology design problems. They promise to enhance the ontology building process in terms of flexibility, re-usability and expansion, and to make the result of ontology engineering more predictable. In this paper, we analyze ODP repositories and investigate their relation with upper-level ontologies. In particular, we compare the BioTop upper ontology to the Action ODP from the NeOn an ODP repository. In view of the differences in (...) the respective approaches, we investigate whether the Action ODP can be embedded into BioTop. We demonstrate that this requires re-interpreting the meaning of classes of the NeOn Action ODP in the light of the precepts of realist ontologies. -/- Results -/- As a result, the re-design required clarifying the ontological commitment of the ODP classes by assigning them to top-level categories. Thus, ambiguous definitions are avoided. Classes of real entities are clearly distinguished from classes of information artifacts. The proposed approach avoids the commitment to the existence of unclear future entities which underlies the NeOn Action ODP. Our re-design is parsimonious in the sense that existing BioTop content proved to be largely sufficient to define the different types of actions and plans. -/- Conclusions -/- The proposed model demonstrates that an expressive upper-level ontology provides enough resources and expressivity to represent even complex ODPs, here shown with the different flavors of Action as proposed in the NeOn ODP. The advantage of ODP inclusion into a top-level ontology is the given predetermined dependency of each class, an existing backbone structure and well-defined relations. Our comparison shows that the use of some ODPs is more likely to cause problems for ontology developers, rather than to guide them. Besides the structural properties, the explanation of classification results were particularly hard to grasp for 'self-sufficient' ODPs as compared with implemented and 'embedded' upper-level structures which, for example in the case of BioTop, offer a detailed description of classes and relations in an axiomatic network. This ensures unambiguous interpretation and provides more concise constraints to leverage on in the ontology engineering process. (shrink)

High-spin states in the odd-odd N = Z nucleus Co-54 have been investigated by the fusion-evaporation reaction Si-28(S-32,1 alpha 1p1n)Co-54. Gamma-ray information gathered with the Ge detector array Gammasphere was correlated with evaporated particles detected in the charged particle detector system Microball and a 1 pi neutron detector array. A significantly extended excitation scheme of Co-54 is presented, which includes a candidate for the isospin T = 1, 6(+) state of the 1f(7/2)(-2) multiplet. The results are compared to large-scale shell-model (...) calculations in the fp shell. Effective interactions with and without isospin-breaking terms have been used to probe isospin symmetry and isospin mixing. A quest for deformed high-spin rotational cascades proved negative. This feature is discussed by means of cranking calculations. (shrink)