© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

Brock Macdonald1, Evi Vakiani2, Rhonda K Yantiss3, Jun Lee4, Robert S Brown Jr5, Samuel H Sigal61Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA, 2Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, 3Department of Pathology and Laboratory Medicine, New York Weill Cornell Medical College, New York, NY, 4Division of Nephrology, Department of Medicine, Weill Cornell Medical College, New York, NY, 5Division of Gastroenterology, Department of Medicine, Columbia University College of Physicians and Surgeons, New (...) York, NY, 6Division of Gastroenterology and Hepatology, Department of Medicine, New York University, New York, NY, USA: The use of sirolimus as an alternative to calcineurin inhibitors for posttransplant immunosuppression is associated with a variety of inflammatory conditions. In this report, we describe the case of a 34-year-old man who developed abnormal liver tests 6 years after live-donor kidney transplantation and 5 years after initiation of sirolimus-based immunosuppression. Elevated aminotransferase levels persisted after withdrawal of potentially hepatotoxic medications, and serologic evaluation for viral hepatitis, autoimmune disease, and genetic disorders was unrevealing. Liver biopsy revealed prominent hepatocellular injury associated with a mixed inflammatory infiltrate and liver tests normalized within 2 weeks of discontinuation of sirolimus. In this report, we review previous reports of sirolimus hepatotoxicity and propose a unifying hypothesis for the various inflammatory conditions that have been attributed to sirolimus.Keywords: sirolimus, immunosuppression, transplant, inflammatory conditions, hepatotoxicity. (shrink)

In the face of environmental crises such as climate change, pollution and biodiversity loss—which all adversely impact on health—Gils-Schmidt and Salloch explore whether physicians can be justified in taking climate issues into account in clinical care.1 While their approach centres on the ‘climate-sensitive’ decisions, physicians can carry out on the micro-level of clinical decision-making, they encourage further discussions on how climate-related issues can be included across different levels of decision-making in healthcare. We propose a list of tasks and a model (...) to assist with navigating the range of factors and structural elements an environmentally sensitive ethics must address. Stephen Gardiner’s notion of a perfect moral storm is central to understanding these issues.2 Gardiner describes how a perfect moral storm occurs in the centre of three overlapping conditions for human action and policymaking in the face of climate change. This storm is driven by: (1) a lack of interest among current generations to meet global needs and accommodate the well-being of future generations, (2) a lack of ecological concerns for other parts of nature than humans and (3) weak ethical and political theories and institutions shaping policy decisions on issues with severe implications across borders and generations. Moreover, these conditions are embedded in the existing, complex world of ethically unjustified power imbalances and social injustice. The growing awareness of healthcare’s climate footprint has amplified and accelerated global, grassroots action to make healthcare more environmentally friendly. This includes incorporating environmental impacts into quality improvement methodologies, building communities of practice to explore how to make …. (shrink)

This article discusses the meanings of “creativity”—tvorchestvo—as we encounter it in Georges Florovsky’s thought, first and foremost in his magnum opus Ways of Russian Theology (1937). Tvorchestvo had by this time become a key concept in Russian pre-revolutionary and later émigré thought. It is associated above all with Nikolai Berdyaev’s philosophy, but it also plays an important role in Sergei Bulgakov’s philosophy of economy. In both cases, it stands for the human response to divine creation. Moreover, and somewhat less famously, (...) it was also an epistemological concept in the religious idealism of Vladimir Solovyov as well as in Russian neo-Kantianism (Fyodor Stepun), where it stood for the active, synthetic faculty of our minds. Florovsky, meanwhile, used it as a description of how we should relate to the patristic heritage, but also to history more generally: Our attitude should be “creative,” active, as well as both backward- and forward-looking. This “return to the Fathers” was a central component of Florovsky’s neopatristic program, but, interestingly, in order to conceptualize this return, Florovsky took over a concept from traditions that his own approach otherwise firmly criticized. By analyzing Florovsky’s use of tvorchestvo, this article addresses the broader question as to the differences and parallels between the neopatristic movement and the legacy of the Russian Renaissance (Silver Age). (shrink)

Hermann von Helmholtz’s work on perceptual science had a fundamental impact on Neo-Kantian movements in the late nineteenth century, and his influence continues to be felt in psychology and analytic philosophy of perception. As is widely acknowledged, Helmholtz denied that we can perceive mind-independent properties of external objects, a view I label Ignorance. Given his commitment to Ignorance, Helmholtz might seem to be committed to a subjectivism according to which we only perceive properties of our own representations. Against this, I (...) argue that for Helmholtz, the properties we perceive are not monadic properties of either the subject or the object. Rather, Helmholtz endorsed a relationalism about the properties we perceive: the properties of objects we perceive are all relational properties. I then suggest that once we take into account oft-neglected terminological distinctions in Helmholtz’s corpus, we are better able to make sense of his commitment to relationalism. (shrink)

The article discusses the notion of culture as it appears and is conceptualized in the works of G.P. Fedotov. The analysis focuses on two articles by Fedotov published in Russian migr journals, "The Holy Spirit in Nature and Culture" of 1932 and "Eschatology and culture" of 1938, and in his magnum opus in a Western context, The Russian Religious Mind of 1946. The author proposes to analyze Fedotov's ideas as a theology of culture due to the profoundly religious meaning the (...) Russian migr thinker attributed to cultural products and production, regardless of their religious intention. By implication, Fedotov understood culture in a religious framework as the human experience of and response to the divine, though not necessarily as dependent on firm belief. Viewing Fedotov as a theologian of culture enables us, furthermore, to compare him with other thinkers across the West-East cultural gradient, most notably Paul Tillich. This approach contextualizes Fedotov in a post-Schellingian pan-European idealist tradition, to which Russian thinkers' analyses of religious experience and imagination have made seminal contributions, in particular from Vladimir Solov'ev on. The article discusses these issues within the framework of the perspectives of global intellectual history, entangled history, and transnationalized Russian studies. (shrink)

Evert van der Zweerde’s book is the most recent result of the author’s long-time study of Russian philosophy and Russian philosophical culture. The latter concept has been one of Zweerde’s main con...

Many philosophers believe that there is a causal condition on perception, and that this condition is a conceptual truth about perception. A highly influential argument for this claim is based on intuitive responses to Gricean style thought experiments. Do the folk share the intuitions of philosophers? Roberts et al. (2016) presented participants with two kinds of cases: Blocker cases (similar to Grice’s case involving a mirror and a pillar) and Non-Blocker cases (similar to Grice’s case involving a clock and brain (...) stimulation). They found that a substantial minority agreed that seeing occurs in the Non-Blocker cases, and that in the Blocker cases significantly less agreed that seeing occurs. They thus hypothesized that folk intuitions better align with a no blocker condition than with a causal condition. This paper continues this line of enquiry with two new experiments. The paper investigates the generality and robustness of Roberts et al.’s findings by expanding the sense modalities tested from only vision to audition and olfaction as well. The paper also uses Gricean style thought experiments as a case study for investigating the “reflection defense” against the negative project in experimental philosophy. Our results replicate and extend Roberts et al.’s study and support their hypothesis that folk intuitions better align with a no blocker condition. They also provide an empirical reason to doubt the reflection defense. (shrink)

This is the first edition of Plato's Republic to be based on an exhaustive examination of all the textual evidence - manuscripts, including papyri; quotations and allusions in ancient authors; translations into Coptic, Arabic and Hebrew. The three primary manuscripts have been examined with particular care. Many new readings have been introduced in the text and a critical apparatus gives details for all relevant textual evidence.

The author, who pioneered this argument in 1961, here places it in the context of traditional discussions of the problem, and answers various criticisms that have been made.

Heidegger’s early project aims to articulate the form of our being as Dasein, and he says that for this usually hidden form to become accessible, a certain kind of “mood” is required of the philosopher. This “ground-mood” he identifies in Sein und Zeit as anxiety. He also, however, presents anxiety as a mood anyone, philosopher or not, experiences when there is some significant breakdown in the living of her life. I argue here that there are largely unrecognized problems with this (...) conflation of methodological and “existential” moods, but that there is nevertheless a compelling methodological account of anxiety that can be teased apart from the existentialist one: methodologically understood, anxiety is a self-affected state of the ontologist, one that results from her asking ontological questions of herself, and, by imagining crisis or breakdown, withdrawing from her determinate situation to a position where she can see the form of her own activity as questioner and imaginer. I draw out some consequences this has for how we should understand the place of ontological understanding in living one’s life, and I conclude by briefly showing how my reading helps us see Heidegger as developing key elements in the work of Descartes and Kant. (shrink)

In this, the first of two ground-breaking volumes on the nature of language in the light of the way it evolved, James Hurford looks at how the world first came to have a meaning in the minds of animals and how in humans this meaning eventually came to be expressed as language. He reviews a mass of evidence to show how close some animals, especially primates and more especially apes, are to the brink of human language. Apes may not talk (...) to us but they construct rich cognitive representations of the world around them, and here, he shows, are the evolutionary seeds of abstract thought - the means of referring to objects, the memory of events, even elements of the propositional thinking philosophers have hitherto reserved for humans. What then, he asks, is the evolutionary path between the non-speaking minds of apes and our own speaking minds? Why don't apes communicate the richness of their thoughts to each other? Why do humans alone have a unique disposition to reveal their thoughts in complex detail? Professor Hurford searches a wide range of evidence for the answers to these central questions, including degrees of trust, the role of hormones, the ability to read minds, and the willingness to cooperate. Expressing himself congenially in consistently colloquial language the author builds up a vivid picture of how mind, language, and meaning evolved over millions of years. His book is a landmark contribution to the understanding of linguistic and thinking processes, and the fullest account yet published of the evolution of language and communication."A wonderful read - lucid, informative, and entertaining, while at the same time never talking down to the reader by sacrificing argumentation for the sake of 'simplicity'. Likely to be heralded as the major publication dealing with language evolution to date. Frederick J. Newmeyer, University of Washington. (shrink)

Further examines the sense in which moral judgements are universalizable. Distinguishes between moral and logical theses of universalizability and shows how the moral does not follow from the logical. Universalizability, in the form maintained in this book, is a logical, not a moral, thesis; furthermore, nothing substantially moral follows from the logical thesis. The chapter presents the exact import of the thesis and considers the role of moral principles.

On the example of the online game Akinator, the basic principles on which programs of this type are built are considered. Effective technics have been proposed by which artificial intelligence systems can build logical inferences that allow to identify an unknown subject from its description. To confirm the considered hypotheses, the terminological analysis of definition of the program "Akinator" offered by the author is carried out. Starting from the assumptions given by the author's definition, the article complements their definitions presented (...) by other researchers and analyzes their constituent theses. Finally, some proposals are made for the next steps in improving the program. The Akinator program, at one time, became one of the most famous online games using artificial intelligence. And although this was not directly stated, it was clear to the experts in the field of artificial intelligence that the program uses the techniques of expert systems and is built on inference rules. At the moment, expert systems have lost their positions in comparison with the direction of neural networks in the field of artificial intelligence, however, in the case considered in the article, we are talking about techniques using both directions – hybrid systems. Games for filling semantics interact with the user, expanding their semantic base and use certain strategies to achieve the best result. The playful form of such semantics filling programs is beneficial for researchers by involving a large number of players. The article examines the techniques used by the Akinator program, and also suggests possible modifications to it in the future. This study, first of all, focuses on how the knowledge base of the Akinator program is built, it consists of incomplete sets, which can be filled and adjusted as a result of further iterations of the program launches. It is important to note our assumption that the order of questions used by the program during the game plays a key role, because it determines its strategy. It was identified that the program is guided by the principles of nonmonotonic logic – the assumptions constructed by the program are not final and can be rejected by it during the game. The three main approaches to acquisite semantics proposed by Jakub Šimko and Mária Bieliková are considered, namely, expert work, crowdsourcing and machine learning. Paying attention to machine learning, the Akinator program using machine learning to build an effective strategy in the game presents a class of hybrid systems that combine the principles of two main areas in artificial intelligence programs – expert systems and neural networks. (shrink)

William Hasker and I have a friendly disagreement over the doctrine of the Trinity. We both reject classical theistic attributes like divine timelessness and divine simplicity. Instead, we affirm that God is temporal and unified. Further, we reject so-called Latin models of the Trinity, and prefer social models of the Trinity. Where we disagree is over the doctrine of the processions of the Trinitarian persons. In this essay, I articulate some problems for the doctrine of the processions.

Discusses an important objection to the view that moral judgements are prescriptive: the existence of cases in which people act in ways that they know to be wrong. The objection is that if moral judgements are prescriptive, it is impossible to accept a moral judgement and yet act contrary to it; therefore prescriptivism must be wrong. It is argued that cases of moral weakness do not constitute a counterexample to prescriptivism.

Leslie Graves, Barbara Horan and Alex Rosenberg (1999) have argued that the process of evolution is really deterministic, so we should be instrumentalists about our probabilistic evolutionary theory. I criticize the consistency of their view. I argue that because they are realists towards multiple theories (quantum mechanics and macrophysics) their arguments against realism for another scientific theory fail. The main point of this paper is critical, but in order to set up this criticism I explore the ramifications of realism for (...) multiple theories. Finally, I offer a brief metaphysical justification for realism about multiple theories. This view justifies realism for evolutionary theory, which has been defended by Robert Brandon and Scott Carson (1996). (shrink)

Sam Lebens offers an intriguing set of arguments from theism to idealism. In this paper, I shall focus on the argument from perfect rationality to Hassidic Idealism. I will offer a critical analysis of this argument and draw out a series of conflicts between Hassidic Idealism and divine freedom, the divine ideas, and creation ex nihilo.