The National Institutes of Health (NIH) invests over $37 billion per year in support of research to improve human health. All research funded by NIH that involves human subjects is subject to regulatory oversight, requiring institutions to staff and manage Institutional Review Boards (IRBs). IRB members, chairs, and the many associated human subjects protections oversight professionals who support the work of the IRB must navigate complex federal regulations issued by multiple agencies. This book is the industry standard reference work for (...) the research oversight community, providing comprehensive, understandable interpretations of the regulations, clear descriptions of the ethical principles on which the regulations are based, and practical best-practices guidelines for effectively implementing regulatory oversight. (shrink)

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5-6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor (...) evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation. (shrink)

We develop an axiomatic set theory — the Theory of Hyperfinite Sets THS— which is based on the idea of the existence of proper subclasses of large finite sets. We demonstrate how theorems of classical continuous mathematics can be transfered to THS, prove consistency of THS, and present some applications.

One approach to the analysis of ethical dilemmas in medical practice uses the “four principles plus scope” approach. These principles are: respect for autonomy, beneficence, non-maleficence and justice, along with concern for their scope of application. However, conflicts between the different principles are commonplace in psychiatric practice, especially in forensic psychiatry, where duties to patients often conflict with duties to third parties such as the public. This article seeks to highlight some of the specific ethical dilemmas encountered in forensic psychiatry: (...) the excessive use of segregation for the protection of others, the ethics of using mechanical restraint when clinically beneficial and the use of physical treatment without consent. We argue that justice, as a principle, should be paramount in forensic psychiatry, and that there is a need for a more specific code of ethics to cover specialised areas of medicine like forensic psychiatry. This code should specify that in cases of conflict between different principles, justice should gain precedence over the other principles. (shrink)

CRISPR‐Cas technology accelerates development of fast, accurate, and portable diagnostic tools, typified by recent applications in COVID‐19 diagnosis. Parasitic helminths cause devastating diseases afflicting 1.5 billion people globally, representing a significant public health and economic burden, especially in developing countries. Currently available diagnostic tests for worm infection are neither sufficiently sensitive nor field‐friendly for use in low‐endemic or resource‐poor settings, leading to underestimation of true prevalence rates. Mass drug administration programs are unsustainable long‐term, and diagnostic tools – required to be (...) rapid, specific, sensitive, cost‐effective, and user‐friendly without specialized equipment and expertise – are urgently needed for rapid mapping of helminthic diseases and monitoring control programs. We describe the key features of the CRISPR‐Cas12/13 system and emphasise its potential for the development of effective tools for the diagnosis of parasitic and other neglected tropical diseases (NTDs), a key recommendation of the NTDs 2021–2030 roadmap released by the World Health Organization. (shrink)

Was Descartes a Cartesian Dualist? In this controversial study, Gordon Baker and Katherine J. Morris argue that, despite the general consensus within philosophy, Descartes was neither a proponent of dualism nor guilty of the many crimes of which he has been accused by twentieth century philosophers. In lively and engaging prose, Baker and Morris present a radical revision of the ways in which Descartes' work has been interpreted. Descartes emerges with both his historical importance assured and his philosophical importance (...) redeemed. (shrink)

This is a new edition of the first volume of G.P.Baker and P.M.S. Hacker’s definitive reference work on Wittgenstein’s _Philosophical Investigations_. New edition of the first volume of the monumental four-volume _Analytical Commentary on the Philosophical Investigations._ Takes into account much material that was unavailable when the first edition was written. Following Baker’s death in 2002, P.M.S. Hacker has thoroughly revised the first volume, rewriting many essays and sections of exegesis completely. Part One - the Essays - now includes two (...) completely new essays: 'Meaning and Use' and 'The Recantation of a Metaphysician'. Part Two - Exegesis §§1-184 - has been thoroughly revised in the light of the electronic publication of Wittgenstein’s _Nachlass_, and includes many new interpretations of the remarks, a history of the composition of the book, and an overview of its structure. The revisions will ensure that this remains the definitive reference work on Wittgenstein’s masterpiece for the foreseeable future. (shrink)

In ‘Wittgenstein on Language and Rules’, Professor N. Malcolm took us to task for misinterpreting Wittgenstein's arguments on the relationship between the concept of following a rule and the concept of community agreement on what counts as following a given rule. Not that we denied that there are any grammatical connections between these concepts. On the contrary, we emphasized that a rule and an act in accord with it make contact in language. Moreover we argued that agreement in judgments and (...) in definitions is indeed necessary for a shared language. But we denied that the concept of a language is so tightly interwoven with the concept of a community of speakers as to preclude its applicabilty to someone whose use of signs is not shared by others. Malcolm holds that ‘This is an unwitting reduction of Wittgenstein's originality. That human agreement is necessary for “shared” language is not so striking a thought as that it is essential for language simpliciter .’ Though less striking, we believe that it has the merit of being a true thought. We shall once more try to show both that it is correct, and that it is a correct account of Wittgenstein's arguments. (shrink)

Of course, as scholars have long known, this example has serious limitations. For one thing, a substantial form, as the scholastics understood it, is much more dynamic than a mere shape. For example, the substantial form of an oak tree somehow explains how and why an oak tree can do everything that it does. So the substantial form of an oak tree could not be something as simple or crude as its shape. Nevertheless, the example of the bronze statue does (...) have the virtue of illustrating one of the chief advantages of hylomorphism as a philosophy of the human person. Although we can talk about the bronze and the shape of the statue, respectively, it still seems correct to say that the statue is exactly one thing, not two things. Likewise, although we can talk about the matter and the form of a human being, the hylomorphist insists that a human being is exactly one thing, not two things accidentally conjoined. (shrink)

Analytical commentary -- Fruits upon one tree -- The continuation of the early draft into philosophy of mathematics -- Hidden isomorphism -- A common methodology -- The flatness of philosophical grammar -- Following a rule 185-242 -- Introduction to the exegesis -- Rules and grammar -- The tractatus and rules of logical syntax -- From logical syntax to philosophical grammar -- Rules and rule-formulations -- Philosophy and grammar -- The scope of grammar -- Some morals -- Exegesis 185-8 -- Accord (...) with a rule -- Initial compass bearings -- Accord and the harmony between language and reality -- Rules of inference and logical machinery -- Formulations and explanations of rules by examples -- Interpretations, fitting and grammar -- Further misunderstandings -- Exegesis 189-202 -- Following rules, mastery of techniques and practices -- Following a rule -- Practices and techniques -- Doing the right thing and doing the same thing -- Privacy and the community view -- On not digging below bedrock -- Private linguists and private linguists : Robinson Crusoe sails again -- Is a language necessarily shared with a community of speakers? -- Innate knowledge of a language -- Robinson Crusoe sails again -- Solitary cavemen and monolinguists -- Private languages and private languages -- Exegesis 203-37 -- Agreement in definitions, judgements, and form of life -- The scaffolding of facts -- The role of our nature -- Forms of life -- Agreement : consensus of human beings and their actions -- Exegesis 238-42 -- Grammar and necessity -- Setting the stage -- Leitmotifs -- External guidelines -- Necessary propositions and norms of representation -- Concerning the truth and falsehood of necessary propositions -- What necessary truths are about illusions of correspondence : ideal objects, kinds of reality, and ultra-physics -- The psychology of the A priori -- Knowledge -- Belief -- Certainty -- Surprise -- Discoveries and conjectures -- Compulsion -- Propositions of logic and laws of thought -- Alternative forms of representation -- The arbitrariness of grammar -- A kinship to the non-arbitrary -- Proof in mathematics -- Conventionalism. (shrink)

This is a much revised and extended new edition of _Part I_ of the first volume of the monumental four-volume _Analytical Commentary on the Philosophical Investigations_. Takes into account much new material that was unavailable when the first edition was written Following Baker’s death in 2002, P.M.S. Hacker has rewritten many essays completely _Part I: Essays_ now includes two completely new essays: 'Meaning and Use' and 'The Recantation of a Metaphysician'; the essays: ‘The Augustinian Conception of Language’, ‘The Language-Game Method’, (...) ‘Contextual Dicta and Contextual Principles’, ‘Philosophy’, ‘Surveyability and Surveyable Representations’, and ‘Truth and the General Propositional Form’ are redrafted and expanded, incorporating new source materials and new arguments, as well as taking into account debates of the last quarter of a century The accompanying _Part II: Exegesis §§1-184_ - has been thoroughly revised in the light of the electronic publication of Wittgenstein’s _Nachlass_, and includes many new interpretations of the remarks, a history of the composition of the _Philosophical Investigations_ and an overview of its structure. The revisions will ensure that this remains the definitive reference work on Wittgenstein’s masterpiece for the foreseeable future. (shrink)

This is the second volume of analytical commentary on Wittgenstein's masterpiece, the Philosophical Investigations. Like the first, it consists of philosophical essays and critical exegesis. The six essays deal comprehensively with various themes in Wittgenstein''s philosophy: the relationship between his mathematics and his philosophy of mind; his conception of grammar and rules of grammar; the relation between a rule and what accords with a rule; the characterization of rule-following as mastery of a technique manifest in practice; his notion of a (...) form of life, and of agreement in definitions and judgements; a comprehensive investigation into his account of logical and mathematical necessity and other topics. (shrink)

Wittgenstein remarked 'What we do is to bring words back from their metaphysical to their everyday use' (PI §116). On this basis, his 'later philosophy' is generally regarded as a version of 'ordinary language philosophy'. He is taken to criticize philosophers for making ('metaphysical') statements which deviate in different ways from the everyday use of some of their component expressions. I marshal textual evidence for another reading of this remark, and show that he used 'metaphysical' in a traditional way, namely, (...) to describe philosophical attempts to delineate the essence of things by establishing necessities and impossibilities. On his conception, 'everyday' simply means 'non-metaphysical' (in this precise sense). Comparisons of philosophical utterances with non-philosophical uses of words are meant to call attention to this crucial distinction. (shrink)

Early in this century, only a few biologists accepted that natural selection was the chief cause of evolution, until the independent calculations of John Burdon Sanderson Haldane (1892–1964), Sewall Wright and R. A. Fisher demonstrated that ideal populations subject to Mendel's laws could behave as Darwin had said they would. Evolutionary theorist John Maynard Smith, a student of Haldane's, has raised the question of why Haldane, who was no naturalist, took up the subject of evolution, and he suggests that the (...) answer may have to do with Haldane's lively interest in religion. In fact Maynard Smith's answer has much more evidence in its favour than he knew. (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)

Arguing against the prevailing view that Cartesian dualism is fundamental to understanding Descartes' philosophy, Gordon Baker and Katherine Morris present a controversial examination of Descartes' philosophy. As the first full-length study of Descartes' conception of the person, Baker and Morris depart radically from traditional representations of Descartes'argument about the persona, the cogito, and the alleged "mind/body" dualism. Contesting the nearly institutionalized view that Cartesian duality is central to understanding Descartes, Baker and Morris illuminate how this "reading" has been ascribed (...) mistakenly and erroneously to Descartes. Controversially, they show how this interpretation has led to abuse both within philosophy and beyond it. Refusing to draw a distinction between the mind and the body in traditional ways, Baker and Morris open up interesting ways of conceptualizing both ourselves and philosophy itself. (shrink)

"Arranged into four main parts, the book begins by selecting readings from classical theorists in order to review formative ideas on the transition to modern society. It then moves on to address, at length, the modernizationists' discussion of how development changes people and the response from dependency and world-system theorists. A final section assembles eight of the most influential writings on the social effects of globalization."--Jacket.

The first horn of the Responsibilism Dilemma turns on the fact that the concept of responsibility is neutral between positive appraisal and negative appraisal. To say that someone is responsible is not ipso facto to say whether she is praiseworthy or blameworthy. Being responsible for something is simply a matter of having the appropriate sort of control over it, regardless of whether that control is exercised well or badly. So responsibility is, at most, a necessary, but not a sufficient condition (...) for positive appraisal. Now, the concept of epistemic justification obviously entails a positive appraisal. So if responsibility, as such, is neutral between positive and negative appraisal, whereas epistemic justification entails a positive appraisal, then obviously there is a conceptual gap between mere responsibility and epistemic justification. It seems obvious to me that Hetherington is right about this. However, it seems just as obvious that it is innocuous to the responsibilist to concede that responsibility is only a necessary, and not a sufficient condition for justification. That is because responsibility, thus understood, is simply a matter of having control, regardless of whether that control is exercised well or badly. Only control that is exercised properly could be sufficient for a positive epistemic status. All of this seems rather mundane. (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)

The goal of this paper is twofold. First, we argue that the understanding one has of a proposition or a propositional content of a representational vehicle is a species of what contemporary epistemologists characterise as objectual understanding. Second, we demonstrate that even though this type of understanding differs from linguistic understanding, in many instances of successful communication, these two types of understanding jointly contribute to understanding a communicated thought.

This is a new edition of the first volume of G.P.Baker and P.M.S. Hacker’s definitive reference work on Wittgenstein’s _Philosophical Investigations_. Takes into account much material that was unavailable when the first edition was written. Following Baker’s death in 2002, P.M.S. Hacker has thoroughly revised the first volume, rewriting many essays and sections of exegesis completely. Part One – the Essays – now includes two completely new essays: 'Meaning and Use' and 'The Recantation of a Metaphysician'. Part Two – Exegesis (...) §§1–184 – has been thoroughly revised in the light of the electronic publication of Wittgenstein’s _Nachlass_, and includes many new interpretations of the remarks, a history of the composition of the book, and an overview of its structure. The revisions will ensure that this remains the definitive reference work on Wittgenstein’s masterpiece for the foreseeable future. (shrink)

A comprehensive look at the intellectual and cultural innovations of the Weimar period During its short lifespan, the Weimar Republic witnessed an unprecedented flowering of achievements in many areas, including psychology, political theory, physics, philosophy, literary and cultural criticism, and the arts. Leading intellectuals, scholars, and critics—such as Hannah Arendt, Walter Benjamin, Ernst Bloch, Bertolt Brecht, and Martin Heidegger—emerged during this time to become the foremost thinkers of the twentieth century. Even today, the Weimar era remains a vital resource for (...) new intellectual movements. In this incomparable collection, Weimar Thought presents both the specialist and the general reader a comprehensive guide and unified portrait of the most important innovators, themes, and trends of this fascinating period. The book is divided into four thematic sections: law, politics, and society; philosophy, theology, and science; aesthetics, literature, and film; and general cultural and social themes of the Weimar period. The volume brings together established and emerging scholars from a remarkable array of fields, and each individual essay serves as an overview for a particular discipline while offering distinctive critical engagement with relevant problems and debates. Whether used as an introductory companion or advanced scholarly resource, Weimar Thought provides insight into the rich developments behind the intellectual foundations of modernity. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

The process-dissociation procedure was used to estimate the influence of spatial and form-based processing in the Simon task. Subjects made manual responses to the direction of arrows . The results provide evidence that the form and spatial location of a single stimulus can have functionally independent effects on performance. They also indicate the existence of two kinds of automaticity—an associative component that reflects prior S-R mappings and a nonassociative component that reflects the correspondence between stimulus and response codes.

This is a much revised and extended new edition of _Part II_ of the first volume of the monumental four-volume _Analytical Commentary on the Philosophical Investigations_. Takes into account much new material that was unavailable when the first edition was written Following Baker’s death in 2002, P.M.S. Hacker has rewritten many sections of exegesis completely _Part II: Exegesis §§1-184_ has been thoroughly revised in the light of the electronic publication of Wittgenstein’s _Nachlass_, and includes many new interpretations of the remarks, (...) a history of the composition of the _Philosophical Investigations_ and an overview of its structure The accompanying _Part I: Essays_ now includes two completely new essays: 'Meaning and Use' and 'The Recantation of a Metaphysician'; the essays: ‘The Augustinian Conception of Language’, ‘The Language-Game Method’, ‘Contextual Dicta and Contextual Principles’, ‘Philosophy’, ‘Surveyability and Surveyable Representations’, and ‘Truth and the General Propositional Form’ are redrafted and expanded, incorporating new source materials and new arguments, as well as taking into account debates of the last quarter of a century The revisions will ensure that this remains the definitive reference work on Wittgenstein’s masterpiece for the foreseeable future. (shrink)

The Second Edition of _Wittgenstein: Rules, Grammar and Necessity_ now includes extensively revised and supplemented coverage of the Wittgenstein's complex and controversial remarks on following rules. Includes thoroughly rewritten essays and the addition of one new essay on communitarian and individualist conceptions of rule-following Includes a greatly expanded essay on Wittgenstein’s conception of logical, mathematical and metaphysical necessity Features updates to the textual exegesis as the result of taking advantage of the search engine for the Bergen edition of the _Nachlass_ (...) Reflects the results of scholarly debates on rule-following that have raged over the past 20 years. (shrink)

On March 17, 2015, Brill was informed that the article by Francisco Gómez Camacho S. J., “Later Scholastics: Spanish Economic Thought in the XVIth and XVIIth Centuries,” in _Ancient and Medieval Economic Ideas and Concepts of Social Justice_, ed. S. Todd Lowry and Barry Gordon, pp. 503–561 suffers from serious citation problems and that in some cases the original sources are never mentioned at all. It goes without saying that Brill strongly disapproves of such practices, which represent a serious (...) breach of publication integrity. Brill condemns any violation of the authors’ rights and the copyrights of the publishers, and distances itself from these practices. As a result Brill cannot stand behind the noted material as originally contained in this volume and for these reasons formally retracts the article by Francisco Gómez Camacho and also the volume. The volume will no longer be available in its current form. (shrink)

This is a new edition of the first volume of G.P.Baker and P.M.S. Hacker’s definitive reference work on Wittgenstein’s _Philosophical Investigations_. Takes into account much material that was unavailable when the first edition was written. Following Baker’s death in 2002, P.M.S. Hacker has thoroughly revised the first volume, rewriting many essays and sections of exegesis completely. Part One – the Essays – now includes two completely new essays: 'Meaning and Use' and 'The Recantation of a Metaphysician'. Part Two – Exegesis (...) §§1–184 – has been thoroughly revised in the light of the electronic publication of Wittgenstein’s _Nachlass_, and includes many new interpretations of the remarks, a history of the composition of the book, and an overview of its structure. The revisions will ensure that this remains the definitive reference work on Wittgenstein’s masterpiece for the foreseeable future. (shrink)

BackgroundKinarm Standard Tests is a suite of upper limb tasks to assess sensory, motor, and cognitive functions, which produces granular performance data that reflect spatial and temporal aspects of behavior. We have previously used principal component analysis to reduce the dimensionality of multivariate data using the Kinarm End-Point Lab. Here, we performed PCA using data from the Kinarm Exoskeleton Lab, and determined agreement of PCA results across EP and EXO platforms in healthy participants. We additionally examined whether further dimensionality reduction (...) was possible by using PCA across behavioral tasks.MethodsHealthy participants were assessed using the Kinarm EXO and EP. Four behavioral tasks were performed that quantified arm sensory and motor function, including position sense [Arm Position Matching ] and three motor tasks [Visually Guided Reaching, Object Hit, and Object Hit and Avoid ]. The number of components to include per task was determined from scree plots and parallel analysis, and rotation type was decided on a per-task basis. To assess agreement, we compared principal components across platforms using distance correlation. We additionally considered inter-task interactions in EXO data by performing PCA across all six behavioral assessments.ResultsBy applying PCA on a per task basis to data collected using the EXO, the number of behavioral parameters were substantially reduced by 58–75% while accounting for 76–87% of the variance. These results compared well to the EP analysis, and we found good-to-excellent agreement values between PCs from the EXO and those from the EP. Finally, we were able to reduce the dimensionality of the EXO data across tasks down to 16 components out of a total of 76 behavioral parameters, which represents a reduction of 79% while accounting for 73% of the total variance.ConclusionPCA of Kinarm robotic assessment appears to capture similar relationships between kinematic features in healthy individuals and is agnostic to the robotic platform used for collection. Further work is needed to investigate the use of PCA-based data reduction for the characterization of neurological deficits in clinical populations. (shrink)

The co-occurrence of stress-induced posttraumatic stress disorder and obesity is common, particularly among military personnel but the link between these conditions is unclear. Individuals with comorbid PTSD and obesity manifest other physical and psychological problems, which significantly diminish their quality of life. Current understanding of the pathways connecting stress to PTSD and obesity is focused largely on behavioral mediators alone with little consideration of the biological regulatory mechanisms that underlie their co-occurrence. In this work, we leverage prior knowledge to systematically (...) highlight such bio-behavioral mechanisms and inform on the design of confirmatory pilot studies. We use natural language processing to extract documented regulatory interactions involved in the metabolic response to stress and its impact on obesity and PTSD from over 8 million peer-reviewed papers. The resulting network describes the propagation of stress to PTSD and obesity through 34 metabolic mediators using 302 documented regulatory interactions supported by over 10,000 citations. Stress jointly affected both conditions through 21 distinct pathways involving only two intermediate metabolic mediators out of a total of 76 available paths through this network. Moreover, oxytocin, Neuropeptide-Y, and cortisol supported an almost direct propagation of stress to PTSD and obesity with different net effects. Although stress upregulated both NPY and cortisol, the downstream effects of both markers are reported to relieve PTSD severity but exacerbate obesity. The stress-mediated release of oxytocin, however, was found to concurrently downregulate the severity of both conditions. These findings highlight how a network-informed approach that leverages prior knowledge might be used effectively in identifying key mediators like OXT though experimental verification of signal transmission dynamics through each path will be needed to determine the actual likelihood and extent of each marker’s participation. (shrink)