Johanna Knapstein,1 Daniel Grimm,1 Marcus A Wörns,1 Peter R Galle,1 Hauke Lang,2 Tim Zimmermann111st Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany; 2Department of General, Visceral and Transplantation Surgery, Johannes Gutenberg-University, Mainz, GermanyIntroduction: Hepatitis C virus reinfection occurs universally after liver transplantation, with accelerated cirrhosis rates of up to 30% within 5 years after liver transplantation. Dual antiviral therapy with pegylated interferon-2a and ribavirin only reaches sustained virological response rates of ~30% after liver transplantation. With the approval of viral (...) NS3/4A protease inhibitors telaprevir, boceprevir, and simeprevir and the NS5B polymerase inhibitor sofosbuvir, combination therapy offers new therapeutic options for HCV-infected patients, resulting in considerably higher sustained virological response rates in the nontransplant setting. Case presentation: We report three cases of TVR-based triple antiviral therapy in HCV genotype 1 reinfected patients after liver transplantation, of whom a 57-year-old Caucasian female and a 43-year-old Caucasian male were therapy naïve, and a 49-year-old Caucasian male patient was pretreated ineffectively. After 4 weeks of therapy, viral load decreased one to three log10 and became negative in weeks 6 to 8 in the therapy naïve patients. The pretreated patient showed a negative viral load in week 4. TVR was administered over 12 weeks, 750 mg thrice daily. Doses of immunosuppression with cyclosporine were reduced four to six fold. Initial peg-IFN and RBV doses ranged from 135–180 µg/week and 800–1,200 mg/day, according to the patient's body weight. Doses of peg-IFN and RBV were adapted to 90–135 µg/week and 400–800 mg/day after 2 to 12 weeks of protease inhibitor therapy. Dual therapy was continued for 36 weeks with total treatment duration of 48 weeks in the therapy naïve patients leading to a sustained virological response 12 weeks after the end of therapy. In the pretreated patient a breakthrough was detected in week 24 and therapy was discontinued. Overall, antiviral therapy was well tolerated. Side effects included dysgeusia and anemia leading to erythropoietin application and blood transfusions. Conclusion: This case series emphasizes that triple therapy with TVR is an efficient treatment for therapy naïve HCV genotype 1 reinfected patients after liver transplantation. But therapeutic options for pretreated patients require improvement. Keyword: cyclosporine, interferon, ribavirin, hepatitis C, protease inhibitor. (shrink)

On Buddhist metaphsical approach to suffering; a study, with some reference to George Grimm's works.

Exposure of man to chemical agents can occur intentionally, as in the treatment of disease, or inadvertently because the environment contains a wide range of synthetic or naturally occurring chemicals. The alkylating agents are a diverse group of compounds (Fig. 1) and comprise a good example of such xenobiotics, since much is known about their occurrence, and their biological effects include carcinogenicity, mutagenicity, toxicity and teratogenicity.Exposure to potentially carcinogenic alkylating agents such as nitrosamines may occur occupationally, from cigarette smoke, from (...) certain foodstuffs and even endogenously through the ingestion of the appropriate precursor chemicals.1 At the other extreme, the cytotoxic effects of agents such as the chloroethylating nitrosamides or mustards have been exploited in the design of certain antitumour drugs.2 The effectiveness of antitumour agents and the other, mostly adverse, biological effects of alkylating agents have been ascribed to their ability to damage cellular macromolecules, in particular DNA. This review concentrates on investigations carried out over the past two years on the role of DNA damage in carcinogenesis, but we shall see how recent advances in this area of research have also led to a better understanding of the mechanisms of the cytotoxic effects of alkylating antitumour agents. (shrink)

An important contribution to the foundations of probability theory, statistics and statistical physics has been made by E. T. Jaynes. The recent publication of his collected works provides an appropriate opportunity to attempt an assessment of this contribution.

Religion and the external world -- Projection, religion, and the external world -- The senses, reason and the imagination -- Realism, meaning and justification : the external world and religious belief -- Modality, projection and realism -- 'Our profound ignorance' : causal realism, and the failure to detect necessity -- Spreading the mind : projection, necessity and realism -- Into the labyrinth : persons, modality, and Hume's undoing -- Value, projection, and realism -- Gilding : projection, value and secondary qualities (...) -- The gold : good, evil, belief and desire -- The golden : relational values, realism and a moral sense. (shrink)

Theism, according to David O'Connor, has in recent centuries been on trial for its life, the charge being that the existence of so much evil in the world is incompatible with belief in a benevolent creator. But this trial, he claims is incapable of producing a reasoned verdict.

Multidisciplinary healthcare committees meet regularly to discuss patients’ candidacy for emerging functional neurosurgical procedures, such as Deep Brain Stimulation . Through debate and discussion around the surgical candidacy of particular patients, functional neurosurgery programs begin to mold practice and policy supported both by scientific evidence and clear value choices. These neurosurgical decisions have special considerations not found in non-neurologic committees. The professional time used to resolve these conflicts provides opportunities for the emergence of careful, ethical practices simultaneous with the expansion (...) of therapy applications. (shrink)

This article draws from theories of business-government relations and Austrian economics to develop a model relating firm performance to the firm’s market and nonmarket actions. Nonmarket actions represent one mechanism for the implementation of firm strategies. The model is tested using an original data set covering airlines serving international routes in the North Atlantic region. Results suggest that nonmarket actions have a positive and significant impact on performance, measured in three ways: profits, market share, and capacity utilization.

This essay engages Mary Shelley’s Frankenstein or The Modern Prometheus as a salient intervention into modern political theory. I analyze the work as a cipher for the tensions inhabiting Euro-modernity’s stitched together fictions of racial determinism and racial dynamism legible in slavery, assimilationist projects and White fears reverberating throughout. Adapting the mythical ancient Prometheus as one who steals fire from the gods to create humans and civilization, Frankenstein dramatizes the risks and monstrous results of White imperial masculinity as a Euro-colonial (...) Promethean project of subject formation and race-making. Viewed through the prism of the Modern Prometheus, modernity in general and liberal humanism in particular are recast as monster-making projects. The European “discovery” of Indigenous peoples amplified Promethean aspirations to create subjects through civilizational processes of religious conversion, the infusion of Enlightenment rationality, and assimilation into whiteness. Politically, the Promethean capacity to engineer humans and proto-humans using Native peoples as raw material allowed progressives to argue against outright extermination in favor of cultural genocide. Seeking to create a subserviant species, Victor Frankenstein confronts a revolting insurrection of his own making—a Creature who refuses slavery, claims mastery over his creator and demands a female companion. Yet Frankenstein’s fear of creating “a race of devils” betrays a terror of what Whites know, but refuse to acknowledge, about themselves and racial others. (shrink)

Layers of complexity arise when a person arrives in an Intensive Care Unit (ICU) due to self-harm intended to end their life and when there is known past personal trauma. We highlight three importa...

In his paper ‘Has the Ontological Argument Been Refuted?’, 97–110) William F. Vallicella argues that my attempt to show that the Ontological Argument begs the question is unsuccessful. 1 I believe he is wrong about this, but before endeavouring to vindicate my position I must first make clear what precisely is the point at issue between us. The Ontological Argument is not a single argument, but a family of arguments. Newly devised formulations of the argument are frequently put forward by (...) philosophers in an effort to avoid difficulties that have been pointed out in previous versions. As a consequence there is no possibility of a conclusive proof that every form of the argument embodies the same fallacy. Nevertheless, one can, I believe, prove that all the standard versions of the argument embody a certain fallacy and that, given the nature of the argument, it is therefore unlikely that the argument can be formulated in such a way as to avoid this difficulty. What I tried to show in my paper is that the six best-known versions of the argument all beg the question and that they do so at the same point in the argument, namely when it is asserted that it is possible that an absolutely perfect being exists. It is difficult to see how an ontological argument could be formulated without including this claim as one of its premises, since the distinguishing badge of the argument is the inference from the possibility of an absolutely perfect being to its actuality. It must be unlikely then, if my criticism of these six versions is correct, that there is any way of formulating the argument that avoids this fallacy. (shrink)

Inleidend overzicht van de wijsgerige ethiek.

Introduction to, and overview of, the contents of the Symposium on consent and confidentialityThe papers in this symposium are based on a meeting held by the Academy of Medical Sciences in London on 12 February 2002. The decision to hold this meeting, and to explore in detail these important and contentious issues, arose from a number of concerns that the Academy felt about what may reasonably be called “impediments to medical research”.These include: The regulations arising from the implementation of the (...) European data protection directive and their effect on the gathering and holding of data needed for disease surveillance as well as for research. Phil Boyd, in his paper, presents the views and the work of the Information Commission, the responsible UK body in this area. The “Source Informatics” case where the Department of Health requested a judicial review on the use, by this company, of anonymised prescribing data from general practitioner records for informing the pharmaceutical industry about patterns of drug use. Mr Justice Latham ruled that the use of even this anonymised data for commercial purposes could be a breach of patients' rights to confidentiality. The Court of Appeal, however, emphatically reversed his decision and, no further appeal having been made to the House of Lords, the law of the land is now clear that there is no breach of confidentiality in the use of anonymised data. It did seem to us, …. (shrink)

Joel Feinberg and Dan Brock have independently developed a solution to the Problem of Nonidentity as it occurs in cases where a mother's negligent act of conception causes her child to be born with a severe disability. I display three problems in the Feinberg‐Brock proposal and develop an alternative view that explains both cases of wrongful conception and additional instances of the Problem of Nonidentity presented by Derek Parfit and others.

This paper first considers why it is important to give children genetic information about hereditary conditions in the family, which will go on to affect their lives in a salient way. If it is important to inform children that they are at risk for an adult-onset disease that exists in the family, why should they not also grow up knowing whether they actually carry the genetic mutation? Central to this discussion is the importance of the process of disclosure and the (...) environment in which genetic information is divulged. It is concluded that the reasons given for defending disclosure of genetic conditions in the family to children are also important reasons to cautiously defend predictive genetic testing of children for adult-onset diseases. (shrink)

The dossier of decrees concerning the Deceleans and the Demotionidae of Athens presents fascinating problems and has attracted plentiful discussion. For a long time there has been a division between the view of Wilamowitz and his followers, that the Demotionidae were a phratry and the Deceleans a privileged genos within it, and that of Wade–Gery refined by Andrewes, that the Deceleans were a phratry and the Demotionidae a privileged genos within it.3 Each of these interpretations gave rise to problems; and (...) since the work of Bourriot and Roussel on the gene there has been a reluctance to believe in gene as aristocratic clans able to control their phratries. Recently Hedrick has argued that the Demotionidae were the phratry and the Deceleans the members of the deme of Decelea; and Lambert has argued that the Demotionidae were the phratry and the Deceleans a genos–like body which formed a semi–independent group within the phratry and which in these decrees was extending its independence further. These interpretations also give rise to problems: in this paper I attempt to continue the debate and to show that an interpretation on Wade–Gery′s lines is after all the most likely to be right. (shrink)

Natural duty theorists of political obligation try to base a moral duty to obey the law on some natural duty, such as the duty to promote justice. Their critics say they confront an insurmountable obstacle in the particularity problem: Since natural duties do not bind us to some persons and institutions more strongly than to others, they cannot support a duty to one particular state or society. I solve the particularity problem, by developing a version of the political obligation thesis, (...) giving a natural duty argument for it and showing that the particularity problem does not arise for the argument. I reply to some likely objections to my view. (shrink)

Hume's 'Natural History of Religion' offers a naturalized account of the causes of religious thought, an investigation into its 'origins' rather than its 'foundation in reason'. Hume thinks that if we consider only the causes of religious belief, we are provided with a reason to suspend the belief. I seek to explain why this is so, and what role the argument plays in Hume's wider campaign against the rational acceptability of religious belief. In particular, I argue that the work threatens (...) a form of fideism which maintains that it is rationally permissible to maintain religious belief in the absence of evidence or of arguments in its favour. I also discuss the 'argument from common consent', and the relative superiority of Hume's account of the origins of religious belief. (shrink)