The Last Gift is an observational HIV cure-related research study conducted with people with HIV at the end of life (EOL) at the University of California San Diego. Participants agree to voluntarily donate blood and other biospecimens while living and their bodies for a rapid research autopsy postmortem to better understand HIV reservoir dynamics throughout the entire body. The Last Gift study was initiated in 2017. Since then, 30 volunteers were enrolled who are either (1) terminally ill with a concomitant (...) condition and have a prognosis of 6 months or less or (2) chronically ill with multiple comorbidities and nearing the EOL.Multiple ethical and logistical challenges have been revealed during this time; here, we share our lessons learnt and ethical analysis. Issues relevant to healthcare research include surrogate informed consent, personal and professional boundaries, challenges posed conducting research in a pandemic, and clinician burnout and emotional support. Issues more specific to EOL and postmortem research include dual roles of clinical care and research teams, communication between research personnel and clinical teams, legally required versus rapid research autopsy, identification of next of kin/loved ones and issues of inclusion. Issues specific to the Last Gift include logistics of body donation and rapid research autopsy, and disposition of the body as a study benefit.We recommend EOL research teams to have clear provisions around surrogate informed consent, rotate personnel to maintain boundaries, limit direct contact with staff associated with clinical care and have a clear plan for legally required versus research autopsies, among other recommendations. (shrink)

BackgroundThe pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research.MethodsWe conducted a scoping review of the growing HIV cure (...) research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021. We extracted and summarized key developments in the ethics of HIV cure research. Twelve community advocates actively engaged in HIV cure research provided input on this summary and suggested areas warranting further ethical inquiry and foresight via email exchange and video conferencing.DiscussionDespite substantial scholarship related to the ethics of HIV cure research, additional attention should focus on emerging issues in six categories of ethical issues: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation).ConclusionHIV cure research ethics has an unfinished agenda. Scientific research and bioethics should work in tandem to advance ethical HIV cure research. Because the science of HIV cure research will continue to rapidly advance, ethical considerations of the major themes we identified will need to be revisited and refined over time. (shrink)

BackgroundOne of the next frontiers in HIV research is focused on finding a cure. A new priority includes people with HIV (PWH) with non-AIDS terminal illnesses who are willing to donate their bodies at the end-of-life (EOL) to advance the search towards an HIV cure. We endeavored to understand perceptions of this research and to identify ethical and practical considerations relevant to implementing it.MethodsWe conducted 20 in-depth interviews and 3 virtual focus groups among four types of key stakeholders in the (...) United States (PWH, biomedical HIV cure researchers, HIV clinicians, and bioethicists) to obtain triangulated viewpoints because little was known about the ethics of this topic. Each group was queried as to ethical considerations, safeguards, and protections for conducting HIV cure-related research at the EOL to ensure this research remains acceptable.ResultsAll four key stakeholder groups generally supported HIV cure-related research conducted at the EOL because of the history of altruism within the PWH community and the potential for substantial scientific knowledge to be gained. Our informants expressed that: (1) Strong stakeholder and community involvement are integral to the ethical and effective implementation, as well as the social acceptability of this research; (2) PWH approaching the EOL should not inherently be considered a vulnerable class and their autonomy must be respected when choosing to participate in HIV cure-related research at the EOL; (3) Greater diversity among study participants, as well as multi-disciplinary research teams, is necessitated by HIV cure-related research at the EOL; (4) The sensitive nature of this research warrants robust oversight to ensure a favorable risk/benefit balance and to minimize the possibility of therapeutic misconception or undue influence; and (5) Research protocols should remain flexible to accommodate participants’ comfort and needs at the EOL.ConclusionBecause of the ethical issues presented by HIV cure-related research at the EOL, robust ethical safeguards are of utmost importance. The proposed ethical and practical considerations presented herein is a first step in determining the best way to maximize this research’s impact and social value. More much inquiry will need to be directed towards understanding context-specific and cultural considerations for implementing EOL HIV cure research in diverse settings. (shrink)

BackgroundHIV cure research involving cell and gene therapy has intensified in recent years. There is a growing need to identify ethical standards and safeguards to ensure cell and gene therapy (CGT) HIV cure research remains valued and acceptable to as many stakeholders as possible as it advances on a global scale.MethodsTo elicit preliminary ethical and practical considerations to guide CGT HIV cure research, we implemented a qualitative, in-depth interview study with three key stakeholder groups in the United States: (1) biomedical (...) HIV cure researchers, (2) bioethicists, and (3) community stakeholders. Interviews permitted evaluation of informants’ perspectives on how CGT HIV cure research should ethically occur, and were transcribed verbatim. We applied conventional content analysis focused on inductive reasoning to analyze the rich qualitative data and derive key ethical and practical considerations related to CGT towards an HIV cure.ResultsWe interviewed 13 biomedical researchers, 5 community members, and 1 bioethicist. Informants generated considerations related to: perceived benefits of CGT towards an HIV cure, perceived risks, considerations necessary to ensure an acceptable benefit/risk balance, CGT strategies considered unacceptable, additional ethical considerations, and considerations for first-in-human CGT HIV cure trials. Informants also proposed important safeguards to developing CGT approaches towards an HIV cure, such as the importance of mitigating off-target effects, mitigating risks associated with long-term duration of CGT interventions, and mitigating risks of immune overreactions.ConclusionOur study identified preliminary considerations for CGT-based HIV cure across three key stakeholder groups. Respondents identified an ideal cure strategy as one which would durably control HIV infection, protect the individual from re-acquisition, and eliminate transmission to others. Known and unknown risks should be anticipated and perceived as learning opportunities to preserve and honor the altruism of participants. Preclinical studies should support these considerations and be transparently reviewed by regulatory experts and peers prior to first-in-human studies. To protect the public trust in CGT HIV cure research, ethical and practical considerations should be periodically revisited and updated as the science continues to evolve. Additional ethics studies are required to expand stakeholder participation to include traditionally marginalized groups and clinical care providers. (shrink)

With precision and profundity born of 30 years of devoted study, John Boyle offers an essential introduction to St. Thomas Aquinas on Scripture, shedding helpful light on the goals, methods, and commitments that animate the Angelic Doctor's engagement with the sacred page. Because the genius of St. Thomas's approach to the Bible lies not so much in its novelty but rather in the fidelity and clarity with which he recapitulates the riches of the preceding interpretive Tradition, this initiation into (...) St. Thomas's vision of Scripture is itself an orientation to the Church's vision of Scripture, from the Fathers through and beyond the Middle Ages. St. Thomas's embeddedness within the Church's Tradition and his own historical context is integral to his approach to Scripture, yet it sets him at some distance from modern readers, for whom his interpretive vision may seem perplexing or even impenetrable. In this Primer, Boyle first provides an acclimation to this medieval context through a survey and explanation of pertinent technical terminology used by St. Thomas and characteristic of the scholastic theology of the time. With an eye to the medieval practice of considering Scripture according to the fourfold division of causes, Boyle builds on this initial foundation by exploring in turn St. Thomas's accounts of the end or use of Scripture (final cause), its divine and human authorship (efficient cause), its order and division (material cause), and its literary styles or genres (formal cause). Drawing on writings from across St. Thomas's corpus, but especially his work On the Commendation and Division of Sacred Scripture and the prologues to his biblical commentaries, Boyle masterfully elucidates both the hermeneutical principles and deep wisdom of the Angelic Doctor's approach to Scripture, imparting invaluable guidance not only for reading and understanding St. Thomas and other great masters of the Tradition, but also-and ultimately-for understanding Scripture in light of this Tradition and reading it with greater benefit and joy. (shrink)

The notion of proof is central to mathematics yet it is one of the most difficult aspects of the subject to teach and master. In particular, undergraduate mathematics students often experience difficulties in understanding and constructing proofs. Understanding Mathematical Proof describes the nature of mathematical proof, explores the various techniques that mathematicians adopt to prove their results, and offers advice and strategies for constructing proofs. It will improve students’ ability to understand proofs and construct correct proofs of their own. The (...) first chapter of the text introduces the kind of reasoning that mathematicians use when writing their proofs and gives some example proofs to set the scene. The book then describes basic logic to enable an understanding of the structure of both individual mathematical statements and whole mathematical proofs. It also explains the notions of sets and functions and dissects several proofs with a view to exposing some of the underlying features common to most mathematical proofs. The remainder of the book delves further into different types of proof, including direct proof, proof using contrapositive, proof by contradiction, and mathematical induction. The authors also discuss existence and uniqueness proofs and the role of counter examples. (shrink)

Despite recurring efforts, a gap exists across a variety of contexts between the protection of patients' safety in theory and in practice. This timely Research Handbook highlights these critical issues and suggests both legal and policy changes are necessary to better protect patients' safety. Multidisciplinary in nature, this Research Handbook features contributions from eminent academics, policy makers and medical practitioners from the Global North and South, discussing the essential facets concerning patient safety and the law. It highlights how the role (...) of legislation and case law has the potential to influence, both positively and negatively, medical practice and the quality of care. Chapters explore patient safety and the global health agenda; physiotherapy; 'non-therapeutic' clinical research with children; patient safety awareness in healthcare education; and the increasing use of robotics and artificial intelligence in healthcare. Outlining a wide range of international perspectives on patient safety and the law, this Research Handbook will appeal to academics and researchers specialising in health and medical law, human rights and healthcare regulation. It will also serve as a valuable resource for legal and medical practitioners alike, as well as clinicians and professionals working in healthcare governance. (shrink)

In this paper, I show that the availability of what some authors have called the weak reading and the strong reading of donkey sentences with relative clauses is systematically related to monotonicity properties of the determiner. The correlation is different from what has been observed in the literature in that it concerns not only right monotonicity, but also left monotonicity (persistence/antipersistence). I claim that the reading selected by a donkey sentence with a double monotone determiner is in fact the one (...) that validates inference based on the left monotonicity of the determiner. This accounts for the lack of strong reading in donkey sentences with MON determiners, which have been neglected in the literature. I consider the relevance of other natural forms of inference as well, but also suggest how monotonicity inference might play a central role in the actual process of interpretation. The formal theory is couched in dynamic predicate logic with generalized quantifiers. (shrink)

Some formal properties of enriched systems of Lambek calculus with analogues of conjunction and disjunction are investigated. In particular, it is proved that the class of languages recognizable by the Lambek calculus with added intersective conjunction properly includes the class of finite intersections of context-free languages.

Though the revised edition of A Theory of Justice, published in 1999, is the definitive statement of Rawls's view, so much of the extensive literature on Rawls's theory refers to the first edition. This reissue makes the first edition once again available for scholars and serious students of Rawls's work.

Theories of discourse bring to realism new ideas about how knowledge develops and how representations of reality are influenced. We gain an understanding of the conceptual aspect of social life and the processes by which meaning is produced. This collection reflects the growing interest realist critics have shown towards forms of discourse theory and deconstruction. The diverse range of contributions address such issues as the work of Derrida and deconstruction, discourse theory, Eurocentrism and poststructuralism. What unites all of the contributions (...) is a sense that it is essential to provide a realist alternative to the hitherto dominance of social constructionism, hermeneutics and postmodernism, over many of the issues discussed. By developing a realist perspective the different authors attempt to embed discourse within the structured nature of the reality of the world. Realism can situate language, discourse and ideology within context specific, or 'causally efficacious' circumstances. Realism can help to uncover issues of power, representation, and subjectivity and how discursive and other social practices produce real effects. This can help us understand the manner in which social structures are reproduced through various forms of ideology and discourse. And by knowing this, we can start to address questions concerning human emancipation and how the world is to be transformed. (shrink)

This book continues and revises the ideas of justice as fairness that John Rawls presented in _A Theory of Justice_ but changes its philosophical interpretation in a fundamental way. That previous work assumed what Rawls calls a "well-ordered society," one that is stable and relatively homogenous in its basic moral beliefs and in which there is broad agreement about what constitutes the good life. Yet in modern democratic society a plurality of incompatible and irreconcilable doctrines--religious, philosophical, and moral--coexist within (...) the framework of democratic institutions. Recognizing this as a permanent condition of democracy, Rawls asks how a stable and just society of free and equal citizens can live in concord when divided by reasonable but incompatible doctrines? This edition includes the essay "The Idea of Public Reason Revisited," which outlines Rawls ' plans to revise _Political Liberalism,_ which were cut short by his death. "An extraordinary well-reasoned commentary on _A Theory of Justice_...a decisive turn towards political philosophy." --_Times Literary Supplement_. (shrink)

It is proved that for any k, the class of classical categorial grammars that assign at most k types to each symbol in the alphabet is learnable, in the Gold (1967) sense of identification in the limit from positive data. The proof crucially relies on the fact that the concept known as finite elasticity in the inductive inference literature is preserved under the inverse image of a finite-valued relation. The learning algorithm presented here incorporates Buszkowski and Penn's (1990) algorithm for (...) determining categorial grammars from input consisting of functor-argument structures. (shrink)

A Norton Library edition of Locke's Second Treatise of Government, edited by A. John Simmons.

Every language recognized by the Lambek calculus with brackets is context-free. This is shown by combining an observation by Jäger with an entirely straightforward adaptation of the method Pentus used for the original Lambek calculus. The case of the variant of the calculus allowing sequents with empty antecedents is slightly more complicated, requiring a restricted use of the multiplicative unit.

Much as we would like to conceive empirical thought as rationally grounded in experience, pitfalls await anyone who tries to articulate this position, and ...

Hirschi and Gottfredson (1983) claim that the relationship between age and crime is similar in all social and cultural conditions and that no current sociological or criminological theory can account for this similarity. We introduce the new field of evolutionary psychology and extend Daly and Wilson's (1988) work on homicide to construct a general theory of male criminality, which explains why men commit violent and property crimes. The theory can also explain the age-crime curve. It might also account for some (...) empirical anomalies such as why physically smaller boys are more delinquent, and why violent criminals desist more slowly. (shrink)

Previous edition, 1st, published in 1971.

"What is a military aircraft? John Law shows in his beautiful analysis that it is a constant oscillation between multiplicity and singularity.

John Searle's Speech Acts (1969) and Expression and Meaning (1979) developed a highly original and influential approach to the study of language. But behind both works lay the assumption that the philosophy of language is in the end a branch of the philosophy of the mind: speech acts are forms of human action and represent just one example of the mind's capacity to relate the human organism to the world. The present book is concerned with these biologically fundamental capacities, (...) and, though third in the sequence, in effect it provides the philosophical foundations for the other two. Intentionality is taken to be the crucial mental phenomenon, and its analysis involves wide-ranging discussions of perception, action, causation, meaning, and reference. In all these areas John Searle has original and stimulating views. He ends with a resolution of the 'mind-body' problem. (shrink)

Building on Ben-Avi and Winter’s (2007) work, this paper provides a general “intensionalization” procedure that turns an extensional semantics for a language into an intensionalized one that is capable of accommodating “truly intensional” lexical items without changing the compositional semantic rules. We prove some formal properties of this procedure and clarify its relation to the procedure implicit in Montague’s (1973) PTQ.

Though the revised edition of A Theory of Justice, published in 1999, is the definitive statement of Rawls's view, so much of the extensive literature on Rawls's theory refers to the first edition.

Combined with recent evolutionary psychological theories, Crespi & Badcock's (C&B's) intragenomic conflict theory of the social brain suggests that schizophrenics are more religious, and autistics are less religious, than the normal population. Combined with the generalized Trivers-Willard hypothesis (gTWH), it suggests that schizophrenics have more daughters, and autistics have more sons, than expected.

I present a new syntactical method for proving the Interpolation Theorem for the implicational fragment of intuitionistic logic and its substructural subsystems. This method, like Prawitz’s, works on natural deductions rather than sequent derivations, and, unlike existing methods, always finds a ‘strongest’ interpolant under a certain restricted but reasonable notion of what counts as an ‘interpolant’.

This volume is an outgrowth of the second Workshop on Logic, Language and Computation held at Stanford in the spring of 1993. The workshop brought together researchers interested in natural language to discuss the current state of the art at the borderline of logic, linguistics and computer science. The papers in this collection fall into three central research areas of the nineties, namely quantifiers, deduction, and context. Each contribution reflects an ever-growing interest in a more dynamic approach to meaning, which (...) focuses on inference patterns and the interpretation of sentences in the context of a larger discourse. The papers apply either current logical machinery - such as linear logic, generalised quantifier theory, dynamic logic - or formal analyses of the notion of context in discourse to classical linguistic issues, with original and thought-provoking results deserving of a wide audience. (shrink)

Second-order abstract categorial grammars (de Groote in Association for computational linguistics, 39th annual meeting and 10th conference of the European chapter, proceedings of the conference, pp. 148–155, 2001) and hyperedge replacement grammars (Bauderon and Courcelle in Math Syst Theory 20:83–127, 1987; Habel and Kreowski in STACS 87: 4th Annual symposium on theoretical aspects of computer science. Lecture notes in computer science, vol 247, Springer, Berlin, pp 207–219, 1987) are two natural ways of generalizing “context-free” grammar formalisms for string and tree (...) languages. It is known that the string generating power of both formalisms is equivalent to (non-erasing) multiple context-free grammars (Seki et al. in Theor Comput Sci 88:191–229, 1991) or linear context-free rewriting systems (Weir in Characterizing mildly context-sensitive grammar formalisms, University of Pennsylvania, 1988). In this paper, we give a simple, direct proof of the fact that second-order ACGs are simulated by hyperedge replacement grammars, which implies that the string and tree generating power of the former is included in that of the latter. The normal form for tree-generating hyperedge replacement grammars given by Engelfriet and Maneth (Graph transformation. Lecture notes in computer science, vol 1764. Springer, Berlin, pp 15–29, 2000) can then be used to show that the tree generating power of second-order ACGs is exactly the same as that of hyperedge replacement grammars. (shrink)

The savanna theory of happiness proposes that, due to evolutionary constraints on the human brain, situations and circumstances that would have increased our ancestors’ happiness may still increase our happiness today, and those that would have decreased their happiness then may still decrease ours today. It further proposes that, because general intelligence evolved to solve evolutionarily novel problems, this tendency may be stronger among less intelligent individuals. Because humans are a diurnal species that cannot see in the dark, darkness always (...) represented danger to our ancestors and may still decrease our happiness today. Consistent with this prediction, the analysis of the National Longitudinal Study of Adolescent to Adult Health (Add Health) data shows that exposure to sunlight was associated with happiness but the association was significantly weaker among more intelligent individuals. (shrink)

John Searle's Speech Acts (1969) and Expression and Meaning (1979) developed a highly original and influential approach to the study of language. But behind both works lay the assumption that the philosophy of language is in the end a branch of the philosophy of the mind: speech acts are forms of human action and represent just one example of the mind's capacity to relate the human organism to the world. The present book is concerned with these biologically fundamental capacities, (...) and, though third in the sequence, in effect it provides the philosophical foundations for the other two. Intentionality is taken to be the crucial mental phenomenon, and its analysis involves wide-ranging discussions of perception, action, causation, meaning, and reference. In all these areas John Searle has original and stimulating views. He ends with a resolution of the 'mind-body' problem. (shrink)

The latest volume in the Oxford Readings in Philosophy series, this work brings together some of the best and most influential recent philosophical scholarship on Nietzsche. Opening with a substantial introduction by John Richardson, it covers: Nietzsche's views on truth and knowledge, his 'doctrines' of the eternal recurrence and will to power, his distinction between Apollinian and Dionysian art, his critique of morality, his conceptions of agency and self-creation, and his genealogical method. For each of these issues, the papers (...) show Nietzsche's continuing philosophical importance. Giving a clear and accessible overview, while retaining an analytical philosophical approach throughout, this volume is essential reading for all students of Nietzsche. (shrink)

This chapter addresses the issues that motivate representationalist accounts, and it describes the different versions of representationalism as responses to these issues. It argues that the representationalist views do not adequately respond to the epistemological problems that motivate them and that they engender some ontological problems. The chapter presents an alternative ‘presentationalist’ account that preserves the straightforward sense of the mind's openness to the world. While representationalism and presentationalism agree that the relation between mental events or states is direct but (...) mediated, they radically differ in their views of the nature of the mediation involved in the mind's intentional directedness to the world. This difference and the preferability of the presentationalist account are explored. (shrink)