Socrates is one of the most important yet enigmatic philosophers of all time; his fame has endured for centuries despite the fact that he never actually wrote anything. In 399 B.C.E., he was tried on the charge of impiety by the citizens of Athens, convicted by a jury, and sentenced to death (ordered to drink poison derived from hemlock). About these facts there is no disagreement. However, as the sources collected in this book and the scholarly essays that follow them (...) show, several of even the most basic facts about these events were controversial in antiquity, and the questions persist today: How and why was Socrates brought to trial? Why did the jurors, members of the world's first democracy, find him guilty? When he was given an opportunity to escape execution, why did he refuse to do so and instead accept the punishment that he and his friends agreed was unjustly assigned to him? How exactly did Socrates die? Differences of opinion on these and other issues continue to arouse our curiosity and to challenge new generations of students and scholars. The Trial and Execution of Socrates: Sources and Controversies is the first work to collect in one place all of the major ancient sources on Socrates' death--those of both his critics and his defenders--as well as recent scholarly views. Part I includes new translations of Plato's Euthyphro, Apology, Crito, and the death scene from Phaedo, as well as other ancient sources that shed light on Socrates' trial and execution. Part II features some of the most influential recent scholarship on this historically momentous event with work by M. F. Burnyeat, Robert Parker, Mark L. McPherran, Thomas C. Brickhouse and Nicholas D. Smith, Richard Kraut, Christopher Gill, and Enid Bloch (whose essay is published here for the first time). Ideal for undergraduate surveys of ancient Greek philosophy and upper-level courses on Socrates and Socratic philosophy, this unique collection provides an unprecedented look into the many perplexing questions surrounding the trial and execution of this remarkable man. (shrink)

Plato's Euthyrphro, Apology, andCrito portray Socrates' words and deeds during his trial for disbelieving in the Gods of Athens and corrupting the Athenian youth, and constitute a defense of the man Socrates and of his way of life, the philosophic life. The twelve essays in the volume, written by leading classical philosophers, investigate various aspects of these works of Plato, including the significance of Plato's characters, Socrates's revolutionary religious ideas, and the relationship between historical events and Plato's texts.

BackgroundIn the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.MethodsBetween 2013 and 2019, 8252 participants (...) (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported.ResultsSevere structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy.ConclusionThe management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/nct02220582. (shrink)

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

In the recent past, several papers have pointed to the possibility that tumour removal generates a permissive environment in which tumour growth is potentiated. This phenomenon has been coined “perioperative tumour growth” and whilst it represents a departure in terms of our attitude to the surgical process, this concept was first hinted at by Paget1Sir James Paget (1814–1899) was a surgeon and physiologist who is widely held (along with Rudolph Virchow) to be the father of the science of pathology. Paget (...) described Paget's disease of the nipple as well as Paget's disease of bone. himself. Despite this, the time interval immediately before and after cancer surgery (i.e. the perioperative period) remains an underutilised interval during which chemotherapeutic regimens are rarely implemented. Herein, we present a summarised review of the literature that supports the concept that tumour removal may potentiate the growth of residual neoplastic disease. We also outline current knowledge regarding underlying mechanisms and in this manner highlight potential therapeutic entry points. Finally, we emphasise the urgent need for trials of agents that could protect patients against the harmful host–tumour interactions that may occur during the perioperative period. BioEssays 28: 433–437, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:When an Arab Laughs in Toledo: Cervantes’s Interpellation of Early Modern Spanish OrientalismE. C. Graf (bio)My purpose has been to place in the plaza of our republic a game table which everyone can approach to entertain themselves without fear of being harmed by the rods; by which I mean without harm to spirit or body, because honest and agreeable exercises are always more likely to do good than harm.—Miguel (...) de Cervantes Saavedra, Prologue to Novelas ejemplares [my translation]We are engaged in a technical enterprise at the species scale.—Jacques Lacan, “L’agressivité en psychanalyse” [my translation]While I was all intent on watching him, he looked at me, and with his hands he spread his chest and said: “See how I split myself!”!—Dante Alighieri, Inferno 28.28–30 Click for larger view View full resolutionFigure 1.Sandro Botticelli, The Virgin and Child (c. 1490). Courtesy of the Fogg Art Museum, Harvard University; ©1999 President and Fellows of Harvard College. Click for larger view View full resolutionFigure 2.Salvador Dalí, Dream Caused by the Flight of a Bee around a Pomegranate One Second Before Awakening (1941). Courtesy of Museo Thyssen-Bornemisza, Madrid; ©1999 Artists' Rights Society (ARS), New York.For much of this century, Hispanists have labored in an effort to elevate Miguel de Cervantes Saavedra’s El ingenioso hidalgo don Quijote de la Mancha (1605, 1615) to the coveted status of the “first modern novel.” Today this kind of criticism may strike our postmodern sensibilities as a rather traditional enterprise, the kind more interested in establishing an elite hierarchy of literary tastes than in saying anything new about an author or text. For many, the study of literature is still an aesthetic beauty pageant in which “great books” like Laurence Sterne’s Tristram Shandy (1767) or Marie de la Vergne de La Fayette’s La princesse de Clèves (1678) are paraded across the stage in a contest to seduce the Western intelligentsia. 1 The postmodern student of literature may not have much concern for this age-old territorial contest, but she might be interested to learn that the fallout from Hispanism’s quest for the “first modern novel” has involved so much attention to, indeed complication of, Don Quixote, that the book now resembles more a postmodern text than an early modern one. At the turn of the century, we have been left with what Jorge Luis Borges would recognize as an “aleph”: an infinite ideological labyrinth that reflects and/or cannibalizes all forms, thereby escaping all attempts [End Page 68] to describe it. 2 Whatever we currently mean by “Cervantes” (an author, a collection of texts, an ideological construction, and so forth) carries with it an impressive range of critical responses. Cervantes has been labeled converso (Castro, Canavaggio), Christian humanist (Castro, Bataillon, Forcione, Herrero, Vilanova), disillusioned secularist (Lukács, Cascardi), precapitalist (Johnson), anti-essentialist (Wilson), anti-Eusebian (Presberg), Menippean (Bakhtin), feminist (El Saffar, Rabin, Cruz), sadist (Nabokov), ethnocentric imperialist (Mariscal), medieval (Gorfkle), homophobic (Martín), non-organicist Aristotelian (Read), and either discursively or actually homosexual (Combet, Rossi, Smith, Arrabal). This list is nowhere near complete, but the reader will grasp the robust effects of the plurality of perspectives on Cervantes.Each of these interpretations is valid to varying degrees within various contexts, but at present I am interested in reading Cervantes as the author of a multicultural manifesto on behalf of the Moriscos of Southern Spain. 3 Within the contexts of French Marxist philosopher Louis Althusser and Palestinian postcolonial literary critic Edward Said, materialist, postcolonial, and multicultural critiques of various forms of power and their ideologies can be seen as the fundamental propositions of Cervantes’s Don Quixote. 4 Cervantes’s ultimate orientation may perhaps be inescapably Eurocentric, but his responses to the European experience of the rise and expansion of an ethnocentric militaristic nation state are relatively centrifugal when compared to the attitudes of many of his contemporaries.In surveying some of the antihegemonic details of Cervantes’s novel, I am also interested in dispelling the popular myth of Don Quixote. Especially in the English-speaking world, and particularly in the United States, Don Quixote remains captive to a... (shrink)

Biological ontologies are used to organize, curate, and interpret the vast quantities of data arising from biological experiments. While this works well when using a single ontology, integrating multiple ontologies can be problematic, as they are developed independently, which can lead to incompatibilities. The Open Biological and Biomedical Ontologies Foundry was created to address this by facilitating the development, harmonization, application, and sharing of ontologies, guided by a set of overarching principles. One challenge in reaching these goals was that the (...) OBO principles were not originally encoded in a precise fashion, and interpretation was subjective. Here we show how we have addressed this by formally encoding the OBO principles as operational rules and implementing a suite of automated validation checks and a dashboard for objectively evaluating each ontology’s compliance with each principle. This entailed a substantial effort to curate metadata across all ontologies and to coordinate with individual stakeholders. We have applied these checks across the full OBO suite of ontologies, revealing areas where individual ontologies require changes to conform to our principles. Our work demonstrates how a sizable federated community can be organized and evaluated on objective criteria that help improve overall quality and interoperability, which is vital for the sustenance of the OBO project and towards the overall goals of making data FAIR. Competing Interest StatementThe authors have declared no competing interest. (shrink)

Precision targeting of specific white matter bundles that traverse the subcallosal cingulate has been linked to efficacy of deep brain stimulation for treatment resistant depression. Methods to confirm optimal target engagement in this heterogenous region are now critical to establish an objective treatment protocol. As yet unexamined are the time-frequency features of the SCC evoked potential, including spectral power and phase-clustering. We examined these spectral features—evoked power and phase clustering—in a sample of TRD patients with implanted SCC stimulators. Electroencephalogram was (...) recorded during wakeful rest. Location of electrical stimulation in the SCC target region was the experimental manipulation. EEG was analyzed at the surface level with an average reference for a cluster of frontal sensors and at a time window identified by prior study. Morlet wavelets generated indices of evoked power and inter-trial phase clustering. Enhanced phase clustering at theta frequency was observed in every subject and was significantly correlated with SCC-EP magnitude, but only during left SCC stimulation. Stimulation to dorsal SCC evinced stronger phase clustering than ventral SCC. There was a weak correlation between phase clustering and white matter density. An increase in evoked delta power was also coincident with SCC-EP, but was less consistent across participants. DBS evoked time-frequency features index mm-scale changes to the location of stimulation in the SCC target region and correlate with structural characteristics implicated in treatment optimization. Results also imply a shared generative mechanism between evoked potentials evinced by electrical stimulation and evoked potentials evinced by auditory/visual stimuli and behavioral tasks. Understanding how current injection impacts downstream cortical activity is essential to building new technologies that adapt treatment parameters to individual differences in neurophysiology. (shrink)

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Biomedical Informatics: We Are What We Publish", written by Peter L. Elkin, Steven H. Brown, and Graham Wright. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the Elkin et al. paper. In subsequent issues the discussion can continue through letters to the editor.

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)

The fusion of law and equity in common law systems was a crucial moment in the development of the modern law. In this volume leading scholars assess the significance of the fusion of law and equity from comparative, doctrinal, historical and theoretical perspectives.

Socrates is one of the most important yet enigmatic philosophers of all time; his fame has endured for centuries despite the fact that he never actually wrote anything. In 399 B.C.E., he was tried on the charge of impiety by the citizens of Athens, convicted by a jury, and sentenced to death. About these facts there is no disagreement. However, as the sources collected in this book and the scholarly essays that follow them show, several of even the most basic (...) facts about these events were controversial in antiquity, and the questions persist today: How and why was Socrates brought to trial? Why did the jurors, members of the world's first democracy, find him guilty? When he was given an opportunity to escape execution, why did he refuse to do so and instead accept the punishment that he and his friends agreed was unjustly assigned to him? How exactly did Socrates die? Differences of opinion on these and other issues continue to arouse our curiosity and to challenge new generations of students and scholars. The Trial and Execution of Socrates: Sources and Controversies is the first work to collect in one place all of the major ancient sources on Socrates' death--those of both his critics and his defenders--as well as recent scholarly views. Part I includes new translations of Plato's Euthyphro, Apology, Crito, and the death scene from Phaedo, as well as other ancient sources that shed light on Socrates' trial and execution. Part II features some of the most influential recent scholarship on this historically momentous event with work by M. F. Burnyeat, Robert Parker, Mark L. McPherran, Thomas C. Brickhouse and Nicholas D. Smith, Richard Kraut, Christopher Gill, and Enid Bloch. Ideal for undergraduate surveys of ancient Greek philosophy and upper-level courses on Socrates and Socratic philosophy, this unique collection provides an unprecedented look into the many perplexing questions surrounding the trial and execution of this remarkable man. (shrink)

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that (...) has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. (shrink)