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)

Thousands of youth suffering from acquired brain injury or other early-life neurological disease live, mature, and learn with only limited communication and interaction with their world. Such cognitively capable children are ideal candidates for brain-computer interfaces. While BCI systems are rapidly evolving, a fundamental gap exists between technological innovators and the patients and families who stand to benefit. Forays into translating BCI systems to children in recent years have revealed that kids can learn to operate simple BCI with proficiency akin (...) to adults. BCI could bring significant boons to the lives of many children with severe physical impairment, supporting their complex physical and social needs. However, children have been neglected in BCI research and a collaborative BCI research community is required to unite and push pediatric BCI development forward. To this end, the pediatric BCI Canada collaborative network was formed, under a unified goal to cooperatively drive forward pediatric BCI innovation and impact. This article reflects on the topics and discussions raised in the foundational BCI-CAN meeting held in Toronto, ON, Canada in November 2019 and suggests the next steps required to see BCI impact the lives of children with severe neurological disease and their families. (shrink)

In Bester’s article (2018) challenging the use of the harm principle and advocating sole reliance on the use of a best interest standard (BIS) in pediatric decision-making, we believe that the auth...

New targets for brain tumor therapies may be identified by mutations that cause hereditary microcephaly. Brain growth depends on the repeated proliferation of stem and progenitor cells. Microcephaly syndromes result from mutations that specifically impair the ability of brain progenitor or stem cells to proliferate, by inducing either premature differentiation or apoptosis. Brain tumors that derive from brain progenitor or stem cells may share many of the specific requirements of their cells of origin. These tumors may therefore be susceptible to (...) disruptions of the protein products of genes that are mutated in microcephaly. The potential for the products of microcephaly genes to be therapeutic targets in brain tumors are highlighted hereby reviewing research on EG5, KIF14, ASPM, CDK6, and ATR. Treatments that disrupt these proteins may open new avenues for brain tumor therapy that have increased efficacy and decreased toxicity. -/- . (shrink)

Really statistical explanation is a hitherto neglected form of noncausal scientific explanation. Explanations in population biology that appeal to drift are RS explanations. An RS explanation supplies a kind of understanding that a causal explanation of the same result cannot supply. Roughly speaking, an RS explanation shows the result to be mere statistical fallout.

This book's importance is derived from three sources: careful conceptualization of teacher induction from historical, methodological, and international perspectives; systematic reviews of research literature relevant to various aspects of teacher induction including its social, cultural, and political contexts, program components and forms, and the range of its effects; substantial empirical studies on the important issues of teacher induction with different kinds of methodologies that exemplify future directions and approaches to the research in teacher induction.

Grady and colleagues (2008) have provided a major contribution to the field of bioethics, and their research should lend a significant hand to the oft-neglected ethics needs of professional nurses....

The explicit objective for the 2014 Symposium hosted by the University of North Florida, which serves as the basis for this collection of papers, was to explore the relationship and potential for mutual support between the disciplines of child rights and pediatric bioethics in advancing the health and well-being of children in the United States and around the world. The U.N. Convention on the Rights of the Child served as the locus for this discussion. A significant question emerged in the (...) Symposium about whether the CRC could serve any beneficial purpose in the United States, where it has not yet been ratified. Further, there was.. (shrink)

The excellent quality and depth of the various essays make [the book] an invaluable resource....It is likely to become essential reading in its field.—CHOICE.

Children tend to view equal resource distributions as more fair than unequal ones, but will sometimes view even unequal distributions as fair. However, less is known about how children form judgments about inequality when different procedures are used. In the present study, we investigated children’s consideration of procedures, outcomes, and emotions when judging the fairness of unequal resource distributions. Participants were introduced to a Fair Coin and an Unfair Coin. In two between-subjects conditions, they watched a researcher flip either the (...) Fair or Unfair Coin in order to distribute resources unequally between two child recipients. Participants then rated the fairness of this event, provided verbal justifications for their ratings, and rated the emotional state of each recipient. Results revealed that participants rated the event as more fair in the Fair Coin than the Unfair Coin condition. References to the outcome in children’s justifications predicted lower fairness ratings, while references to the procedure only predicted lower ratings in the Unfair Coin condition. Greater Emotion Difference Scores predicted lower fairness ratings, and this effect increased with age. Together, these results show that children consider procedures, outcomes, and emotions when judging the fairness of inequality. Moreover, results suggest age-related increases in consideration of recipients’ emotions makes inequality seem less fair, even when fair procedures are used. Implications for the development of fairness are discussed. (shrink)

This paper proposes several concepts of efficient solutions for multicriteria decision problems under uncertainty. We show how alternative notions of efficiency may be grounded on different decision ‘contexts’, depending on what is known about the Decision Maker's (DM) preference structure and probabilistic anticipations. We define efficient sets arising naturally from polar decision contexts. We investigate these sets from the points of view of their relative inclusions and point out some particular subsets which may be especially relevant to some decision situations.

In this article, we examine how the U.N. Convention on the Rights of the Child can be useful in pediatric bioethics. Adopted in 1989, the CRC reflects norms that have been deliberated upon for a long period of time and endorsed by most nations. The United States is now the only country that has not ratified the CRC.1 International human rights law shares many key moral concepts with clinical pediatric bioethics, and the CRC provides a considered language common to many (...) jurisdictions that can assist bioethicists in their daily practice and help health-care organizations in their policy development and international interactions. There may, however, be practical challenges with using the CRC in the practice of.. (shrink)

Owen Barfield--philosopher, author, poet, and critic--was a founding member of the Inklings, the private Oxford society that included the leading literary figures C.S. Lewis, J.R.R. Tolkien, and Charles Williams. Lewis, who was greatly affected by Barfield during their long friendship, wrote of their many heated debates: "I think he changed me a good deal more than I him." Simon Blaxland-de Lange's biography (the first to be published on Owen Barfield) was written with the active cooperation of Barfield himself who, before (...) his death in 1997, gave numerous interviews to the author and shared many of his papers and manuscripts. The fruit of this collaboration is a book that penetrates deeply into the life and thought of one of the most important figures of the twentieth century. It studies two pf Barfield's influences--the Romantic poet Coleridge and the philosopher Rudolf Steiner--and elaborates on his profound personal connection with C.S. Lewis. This biography also features a sketch in his own words (based on interviews with the author), describing Barfield's strong relationship with North America and his two professions as lawyer and writer. This updated edition features important new material, including Owen Barfield's own "Psychography" (1948) and four pages of color plates. (shrink)

Let R be a real closed field. An integer part I for R is a discretely ordered subring such that for every \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${r \in R}$$\end{document}, there exists an \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${i \in I}$$\end{document} so that i ≤ r < i + 1. Mourgues and Ressayre (J Symb Logic 58:641–647, 1993) showed that every real closed field has an integer part. The procedure of Mourgues and (...) Ressayre appears to be quite complicated. We would like to know whether there is a simple procedure, yielding an integer part that is \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\Delta^0_2(R)}$$\end{document} —limit computable relative to R. We show that there is a maximal Z-ring \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${I \subseteq R}$$\end{document} which is \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\Delta^0_2(R)}$$\end{document}. However, this I may not be an integer part for R. By a result of Wilkie (Logic Colloquium ’77), any Z-ring can be extended to an integer part for some real closed field. Using Wilkie’s ideas, we produce a real closed field R with a Z-ring \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${I \subseteq R}$$\end{document} such that I does not extend to an integer part for R. For a computable real closed field, we do not know whether there must be an integer part in the class \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\Delta^0_2}$$\end{document}. We know that certain subclasses of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\Delta^0_2}$$\end{document} are not sufficient. We show that for each \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${n \in \omega}$$\end{document}, there is a computable real closed field with no n-c.e. integer part. In fact, there is a computable real closed field with no n-c.e. integer part for any n. (shrink)

Using an analogy between moths and men, in 1916, Richard Goldschmidt proposed that homosexuality was a case of genetic intersexuality. As he strove to create a unified theory of sex determination that would encompass animals ranging from moths to men, Goldschmidt's doubts grew concerning the association of homosexuality with intersexuality until, in 1931, he dropped homosexuality from his theory of intersexuality. Despite Goldschmidt's explicit rejection of his theory of homosexuality, Theo Lang, a researcher in the Genealogical-Demographic Department of the (...) Institute for Psychiatric Research in Munich, revived it, maintained Goldschmidt's association with it, and argued on its behalf in publications from 1936 to 1960. Lang's appropriation of Goldschmidt's theory did not depend on his resolution of the difficulties Goldschmidt had found with his own theory. Lang and Goldschmidt, I argue, had fundamentally different scientific and social commitments that allowed one to reject this theory of homosexuality and the other to accept it. (shrink)

As R. Sorabji says in his general introduction, "The 15,000 pages of the Ancient Greek Commentaries on Aristotle are the largest corpus of Ancient Greek philosophy that has not yet been translated into English or other modern European languages". Besides its considerable intrinsic interest, this corpus is an important source of late Greek philosophy, and a thorough acquaintance with it underlies the development of Arabic philosophy, whence it becomes a "silent partner" in Latin philosophy after 1200.

What is the origin of the concept of a law of nature? How much does it owe to theology and metaphysics? To what extent do the laws of nature permit contingency? Are there exceptions to the laws of nature? Is it possible to give a reductive analysis of lawhood, or is it a primitive? -/- Twelve brand-new essays by an international team of leading philosophers take up these and other central questions on the laws of nature, whilst also examining some (...) of the most important intuitions and assumptions that have guided the debate over laws of nature since the concept's invention in the seventeenth century. -/- Laws of Nature spans the history of philosophy and of science, contemporary metaphysics, and contemporary philosophy of science. Contents: 1. Intuitions and Assumptions in the Debate over Laws of Nature, Walter Ott and Lydia Patton 2. Early Modern Roots of the Philosophical Concept of a Law of Nature, Helen Hattab 3. Laws of Nature and the Divine Order of Things: Descartes and Newton on Truth in Natural Philosophy, Mary Domski 4. Leges sive natura: Bacon, Spinoza, and a Forgotten Concept of Law, Walter Ott 5. Laws and Powers in the Frame of Nature, Stathis Psillos 6. Laws and Ideal Unity, Angela Breitenbach 7. Becoming Humean, John W. Carroll 8. A Perspectivalist Better Best System Account of Lawhood, Michela Massimi 9. Laws: An Invariance Based Account, James Woodward 10. How the Explanations of Natural Laws Make Some Reducible Physical Properties Natural and Explanatorily Powerful, Marc Lange 11. Laws and their Exceptions, Stephen Mumford 12. Are laws of nature consistent with contingency?, Nancy Cartwright and Pedro Merlussi. (shrink)