Mechanical stimulation has a critical role in the development and maintenance of the skeleton. This function requires the perception of extracellular stimuli as well as their conversion into intracellular biochemical responses. This process is called mechanotransduction and is mediated by a plethora of molecular events that regulate bone metabolism. Indeed, mechanoreceptors, such as integrins, G protein‐coupled receptors, receptor protein tyrosine kinases, and stretch‐activated Ca2+ channels, together with their downstream effectors coordinate the transmission of load‐induced signals to the nucleus and the (...) expression of bone‐related genes. During the past decade, scientists have gained increasing insight into the molecular networks implicated in bone mechanotransduction. In the present paper, we consider the major signaling cascades and transcription factors that control bone and cartilage mechanobiology and discuss the influence of the mechanical microenvironment on the determination of skeletal morphology. (shrink)

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Living Organ Donors’ Stories: (Unmet) Expectations about Informed Consent, Outcomes, and CareElisa J. Gordon, Symposium EditorKeywordsEthics, informed consent, kidney, liver, living donor, narrative, transplantationLiving donor organ transplantation has become standard treatment for patients with end-stage kidney or end-stage liver disease. Live donors comprised approximately 5,769 (34%) and 247 (4%) of all kidney and liver transplants in 2011, respectively (OPTN/UNOS). The reasons why people donate, the perception that donating does (...) not entail a decision per se, and the attendant fears and anxieties living donors feel about donating, have all been previously well investigated (Lennerling, Forsberg, Meyer, & Nyberg, 2004; Papachristou, Walter, Frommer, & Klapp, 2010). But much less is known about how donors experienced the overall donation process including the donor evaluation, preparation, appreciation of risks, decision-making, informed consent, post-operative, recovery processes, and the impact of donating on all aspects of their life, from their point of view. Thus, a narrative approach is essential for gaining insights into these less well known phenomena.There is good reason to remain concerned about the safety and ethical basis of living donation considering that living donors undergo serious health risks for no direct medical benefit to themselves (Ethics Committee of the Transplantation Society, 2004; Laird, 2012; Neergaard, 2011; Ratner & Sandoval, 2010; Shelton, 2011). The situation raises serious ethical questions specifically about nonmaleficence and informed consent, and more broadly about using people as a means to an end. The absence of long-term information may not undermine a willing donor’s commitment to save a loved one’s life, but is certainly cause for concern among transplant clinicians who want to be sure to disclose information that may be material for donors in order to provide adequate informed consent. In other words, the disjuncture between what transplant clinicians find important to disclose to donors and what prospective donors need to know—which follows along the lines of what Elliot Mishler referred to as the ‘voice of medicine’ versus the ‘voice of the lifeworld’(1984)—seems to complicate donors’ preparation for donation. Donors’ stories are important for addressing these concerns by identifying risks that typically do not get reported in the scientific literature—perhaps owing to a different [End Page 1] conceptualization of what should be construed as noteworthy risks—as well as by demonstrating how personal situations can enhance or detract from the experience overall.This issue of Narrative Inquiry in Bioethics (NIB) affords a unique entrée into both the often heard and unheard stories of living organ donors. A set of topical areas were presented for the authors’ consideration that relate to the donation process in general and the informed consent process more specifically: whether donors were prepared to donate; comprehended what they were told; could have understood the process better, as well as, the impact of donation on health, employment, finances, and personal relationships (Table 1). When soliciting donors’ stories, every effort was made to include a full range of experiences—both good and bad—from a variety of donors: kidney donation, liver donation, adult-to-adult and adult-to-child donation, related, unrelated, directed and anonymous (also known as ‘altruistic’ or ‘good Samaritan’ donors), paired chain exchange, and list exchange (Table 2)—in order to present a balanced perspective on live donation. Additionally, this issue includes a full breadth of stories about the donor experience, ranging from positive to mixed to negative (Table 3). While donors were given tremendous leeway in what stories they told, they were asked to focus their narratives on the lesser known dimensions of donation—the experience of it. While additional stories from liver donors would have helped to underscore common concerns among liver donors, we only received a few. Some of the donors are themselves health care professionals, active in the United Network for Organ Sharing (UNOS) or their local OPO, or have leveraged their experiences to help others by becoming a donor buddy or donor advocate. Given that we received more stories than Click for larger view View full resolutionTable 1.Topical areas to address[End Page 2] Click for larger view View full resolutionTable 2.Forms of Living Donation Click for larger view View... (shrink)

Information can be public among a group. Whether or not information is public matters, for example, for accounts of interdependent rational choice, of communication, and of joint intention. A standard analysis of public information identifies it with (some variant of) common belief. The latter notion is stipulatively defined as an infinite conjunction: for p to be commonly believed is for it to believed by all members of a group, for all members to believe that all members believe it, and so (...) forth. This analysis is often presupposed without much argument in philosophy. Theoretical entrenchment or intuitions about cases might give some traction on the question, but give little insight about why the identification holds, if it does. The strategy of this paper is to characterize a practical-normative role for information being public, and show that the only things that play that role are (variants of) common belief as stipulatively characterized. In more detail: a functional role for “taking a proposition for granted” in non-isolated decision making is characterized. I then present some minimal conditions under which such an attitude is correctly held. The key assumption links this attitude to beliefs about what is public. From minimal a priori principles, we can argue that a proposition being public among a group entails common commitment to believe among that group. Later sections explore partial converses to this result, the factivity of publicity and publicity from the perspective of outsiders to the group, and objections to the aprioricity of the result deriving from a posteriori existential presuppositions. (shrink)

The advent of writing in the Greek polis administration resulted in the appointment of officials responsible for document management. These were known as grammateis (secretaries). The need for records connected to judicial proceedings led to the involvement of secretaries in the polis legal procedure. Although there remains little evidence of this, in Athens secretarial support was certainly connected with almost every use of writing in a judicial context. Secretaries appear to have received suits, published notifications of trials and recorded fines, (...) but their most well-attested duty is that of the reading of documents brought as evidence in the courtroom. The study of references to secretaries in a judicial context demonstrates that their duties were essential to the persons involved in the administration of justice. By keeping track of judicial documents secretaries helped the officials to keep accurate records for the sake of accountability, while the reading of legal texts enabled the Athenian citizen-judges to get to know verbatim the texts of the state laws and avoid manipulation by litigants who produced their own interpretations of a law. The purpose of this article is to present all the relevant cases of secretarial support in the justice system of Athens and to discuss the contribution made by the secretaries to the Athenian legal procedure. (shrink)

Could Greek philosophers-Plato, Aristotle, Plotinus, Proclus-be considered as guardians and schoolmasters that brought humanity to Christ in a way similar to the Law of the Old Testament according to Saint Paul (Gal. 3,24)??he philosophical project of Platonism had five fundamental tenets, namely monism, transcendence, participation, ethics of purification, and the relevant notion of evil as non-being. Dr. Dionysios Skliris is both theologian and philosopher, and he sees that all of these philosophical demands were realized in the theology of the (...) Fathers in the most radical way, yet "in another form" (Mark 16,12). After Christ, transcendence means that God is uncreated and creates a contingent world out of free love. Monism coexists with a Trinity of Persons since God is love in His own transcendent being and not only in relation to the world. On every page, Skliris shows us the true implications of purification: it leads to transformation and evil is non-being not as a "fading away" of light, but as a historical closedness to God that cannot survive in the eschaton. (shrink)

This book examines the place of physical bodies, a major topic of natural philosophy that has occupied philosophers since antiquity. Aristotle's conceptions of place (topos) and the void (kenon), as expounded in the 'Physics', were systematically repudiated by John Philoponus (ca. 485-570) in his philosophical commentary on that work. The primary philosophical concern of the present study is the in-depth investigation of the concept of place established by Philoponus, putting forward the claim that the latter offers satisfactory solutions to problems (...) raised by Aristotle and the Aristotelian tradition regarding the nature of place. Philoponus' account proposes a specific physical model of how physical bodies exist and move in place, and regards place as an intrinsic reality of the physical cosmos. Due to exactly this model, his account may be considered as strictly pertaining to the study of physics, thereby constituting a remarkable episode in the history of philosophy and science. (shrink)

The paper examines the status of ambiguity in the thought of Plotinus (c. 204/205-270). Even though ambiguity should be regarded as the enemy of the philosopher and as pertaining rather to the rhetorical tradition and not the philosophical one as it was especially established by Plato and Aristotle, one can argue that the particularly Neoplatonist philosophical project permitted an important place to it due to some fundamental inherent aspects that it contained. Most importantly, the ambiguity in the generation of the (...) Intellect from the One is examined in this paper as related to the dialectic between existence and being. In such a perspective, ambiguity is initiated by the fact that being is both one in order to exist and not one in order to be a being. Thus, it can be explained only in dialectic with an ontological reality beyond it, namely an absolute One. This means that, in turn, its generation as Intellect from the latter is necessarily a two-fold movement: Both a distribution of existence by procession and a reverting contemplative act for acquisition of substantial definition. This dialectic does not only concern the highest ontological level of the relation of the Being to the One, but is a permanent ontological vacillation in the system of Plotinus. The paper observes this valorization of ambiguity as an original and dynamic feature of Plotinian ontology that arguably paved the way for Modernity. (shrink)

In this paper we offer a critical account of Aristotelian theory of time. After a brief presentation of the main views of Aristotle on the infinite, we focus the attention to the status of points with respect to the potentiality-actuality distinction. Then we address Aristotle’s views on time on the basis of the Aristotelian notion of continuity. We construe the “nows” as potentialities awaiting to be actualized. We show that it is the intervention of an agent, who, through finitely many (...) unitary mental acts of noticing or perceiving, guarantees the actualization of particular “nows”, constructs or brings into existence time intervals and through their comparison measures them, so producing what Aristotle calls time. (shrink)

This collection of original papers by an international group of distinguished philosophers of science impressively demonstrates the links among the philosophic points of view, areas of focus, and methods of treatment used in examining the many facets of scientific inquiry. It will be an indispensable collection for philosophers of science and scientists of various disciplines, including physicists, neuroscientists, and psychologists.

Telling a patient that the outcome of his illness is not good, or even hopeless, requires sensitivity and the ability to communicate with him in the setting of a hospital which is an unnatural environment divorced from family and friends. It is a task which must be taught and learned by doctors and nurses.

The achievements of the textile industry in Roman Britain are often underestimated as a result of the meagreness of our available evidence. The Edict on maximum prices issued by Diocletian in A.D. 301 shows that British capes commanded high prices on the markets of the Empire, and that in the late third century A.D. British rugs were the best in the world. In view of the competition from the traditional centres of rug manufacture in the East, this is an astonishing (...) achievement. (shrink)

The received translation and interpretation of many of the technical terms current in the textile industry of the Roman Empire are inaccurate, because lexicographers have either fought shy of being precise, or have thought that they recognized in the ancient world technical processes which originated at a much later date. The evidence is often equivocal or insufficient, but may still yield details that have been overlooked. The textile expression scutulatus, to take an example, deserves more attention than Blümner has devoted (...) to it. When it refers to the appearance of a garment, Lewis and Short, s.v. scutulatus, translate ‘diamond or lozenge-shaped, checkered’. It seems worth while to attempt a more precise translation, and, if possible, to estimate the significance in context of the goods so designated. (shrink)

Living out of silence, out of a fully functioning, lovingly attentive mind, and not just out of thought, out of a partially functioning mind, is requisite for depth or profundity in living or relating. A fully attentive, truly silent or meditative mind sees that there is real dualism of time and the timeless and that time and the timeless each has its own unique value. The timeless, or real silence, that which alone can make for depth in one's living and (...) relating, can be there only when, in one's awareness, time and all that is related to time, have come to an end. An examination of a wide variety of statements made by writers, both past and present, shows that these understandings are seldom there in contemporary writings, just as they were not there in writings that have come down to us from the past. 'Living beyond the One and the Many' invites readers to consider the possibility that what is presented in it can bring deep meaning to one's way of living in the world"--Publisher's description, back cover. (shrink)

If the world itself is metaphysically indeterminate in a specified respect, what follows? In this paper, we develop a theory of metaphysical indeterminacy answering this question.

Husserlian phenomenology, as the study of conscious experience, has often been accused of solipsism. Husserl’s method, it is argued, does not have the resources to provide an account of consciousness of other minds. This chapter will address this issue by providing a brief overview of the multiple angles from which Husserl approached the theme of intersubjectivity, with specific focus on the details of his account of the concrete interpersonal encounter – “empathy.” Husserl understood empathy as a direct, quasi-perceptual form of (...) intentionality through which the sense of the Other is constituted. Furthermore, his account of empathy is holistically integrated with his overall theory of intersubjectivity, including his discussions of the objectivity of nature, and the social, historical, and communal aspects of subjectivity. Husserl’s theory of empathy continues to cast a long shadow, influencing both the analytic and continental approaches to the problem of other minds, as well as contemporary account of social cognition in the cognitive sciences. (shrink)

An Essay on Human Action seeks to provide a comprehensive, detailed, enlightening, and (in its detail) original account of human action. This account presupposes a theory of events as abstract, proposition-like entities, a theory which is given in the first chapter of the book. The core-issues of action-theory are then treated: what acting in general is (a version of the traditional volitional theory is proposed and defended); how actions are to be individuated; how long actions last; what acting intentionally is; (...) what doing one thing by doing another is; what basic action is; and what omitting to do something is. Attention is also given to the concepts of causation, intention, volition, deciding, choosing, and trying. Finally, a libertarian account of free action is tentatively proposed and defended. (shrink)

We develop and apply a multi-dimensional conception of explanatory depth towards a comparative analysis of inflationary and bouncing paradigms in primordial cosmology. Our analysis builds on earlier work due to Azhar and Loeb (2021) that establishes initial condition fine-tuning as a dimension of explanatory depth relevant to debates in contemporary cosmology. We propose dynamical fine-tuning and autonomy as two further dimensions of depth in the context of problems with instability and trans-Planckian modes that afflict bouncing and inflationary approaches respectively. In (...) the context of the latter issue, we argue that the recently formulated trans-Planckian censorship conjecture leads to a trade-off for inflationary models between dynamical fine-tuning and autonomy. We conclude with the suggestion that explanatory preference with regard to the different dimensions of depth is best understood in terms of differing attitudes towards heuristics for future model building. (shrink)

Global Media Ethics is the first comprehensive cross-cultural exploration of the conceptual and practical issues facing media ethics in a global world. A team of leading journalism experts investigate the impact of major global trends on responsible journalism. The first full-length, truly global textbook on media ethics; Explores how current global changes in media promote and inhibit responsible journalism; Includes relevant and timely ethical discussions based on major trends in journalism and global media; Questions existing frameworks in media ethics in (...) light of the impact of global media; Contributors are leading experts in global journalism and communication. (shrink)

The existential analysis -- The death of dasein -- The timeliness of dasein -- The derivation of time -- The time of being.