Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to (...) genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50, which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1, showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED. (shrink)

While rooted in careful study of Mead’s original writings and transcribed lectures and the historical context in which that work was carried out, the papers in this volume have brought Mead’s work to bear on contemporary issues in metaphysics, epistemology, cognitive science, and social and political philosophy.

The general problem of visual search can be shown to be computationally intractable in a formal, complexity-theoretic sense, yet visual search is extensively involved in everyday perception, and biological systems manage to perform it remarkably well. Complexity level analysis may resolve this contradiction. Visual search can be reshaped into tractability through approximations and by optimizing the resources devoted to visual processing. Architectural constraints can be derived using the minimum cost principle to rule out a large class of potential solutions. The (...) evidence speaks strongly against bottom-up approaches to vision. In particular, the constraints suggest an attentional mechanism that exploits knowledge of the specific problem being solved. This analysis of visual search performance in terms of attentional influences on visual information processing and complexity satisfaction allows a large body of neurophysiological and psychological evidence to be tied together. (shrink)

I was in manufacturing for over thirty years and a manager for nearly twenty-five. During that time it never occurred to me that the consequentialist, utilitarian framework I used was inadequate as a conceptual framework for making decisions to ensure organisational viability and success.1 The framework gave three criteria which enabled me to construct a rational approach to issues associated with my role as a manager: To show that this framework is adequate as a basis for managerial decision making I (...) want to spell out the logical implications of the three criteria and show that they are necessary and jointly sufficient to provide an epistemically sound framework for managerial decisions. I will argue that we can look to managerial practice for examples which can serve as paradigms for constructing a pragmatic approach to management decision making, one that — when employed correctly — will result in the best moral outcome for all those affected by a decision.2 This approach is derived from, and ultimately justified by, the primary role responsibility of a manager to create and implement a healthy work environment. This is one designed to be viable so that the organisation can compete successfully in the marketplace and meet the morally minimal standard that we ought not to cause unnecessary and avoidable harm to innocent people. Because the approach is goal directed, it is teleological and consequential in nature. I maintain that a workplace, or organisation, is healthy when all the components that constitute it are working coherently together to achieve legitimate organisational goals designed to ensure the best chances of being viable and competitive. Such an organisation is what I term optimally functional.3. (shrink)

The general problem of visual search can be shown to be computationally intractable in a formal, complexity-theoretic sense, yet visual search is extensively involved in everyday perception, and biological systems manage to perform it remarkably well. Complexity level analysis may resolve this contradiction. Visual search can be reshaped into tractability through approximations and by optimizing the resources devoted to visual processing. Architectural constraints can be derived using the minimum cost principle to rule out a large class of potential solutions. The (...) evidence speaks strongly against bottom-up approaches to vision. In particular, the constraints suggest an attentional mechanism that exploits knowledge of the specific problem being solved. This analysis of visual search performance in terms of attentional influences on visual information processing and complexity satisfaction allows a large body of neurophysiological and psychological evidence to be tied together. (shrink)

Inspired by Goffman and Mead Social Interactionism theory and Ghanaian traditional leadership model, this article interprets Mark 7:24-30 as text that re-imagines alternative leadership practice. The study suggest that social interactionism theory tenants of ritual making, people processing, characterisation, frame making and dramaturgy provide a alternative heuristic tools to understand Jesus' view of leadership. Seemingly and for Jesus, leadership is a product of social interaction derived from the manner one interacts with various people. This study proposes that the Ghanaian Akan (...) traditional notion of leadership based on social interaction provides analogical model that complements social interactionism theory in interpreting Jesus' leadership practices. Therefore, the study explains social interactionism theory and then illustrated it through Akan leadership model analogue. The story of the Syrophoenician woman in Mark 7:24-30 gives the social interaction, people processing, characterisation, frame making and dramaturgy that informs Jesus' leadership model to be modelled by the Church. (shrink)

In this paper I outline an approach to managerial decision making that incorporates the important role that metaphors and moral imagination play in our moral reasoning coupled with an organisational moral concept I call the Health of the Organisation. I have used this concept in my managerial (and philosophical) career to interpret and evaluate potential, and actual, courses of action. I have concluded that this concept fits in nicely with Mark Johnson’s analysis of the metaphor of morality is health, which (...) he argues is one of the central moral metaphors in the conceptual framework that we use to interpret and evaluate actions from a reasonable moral point of view. He argues that metaphors are the essential components in defining the rational mental framework utilised in interpreting, evaluating, predicting likely outcomes from various alternatives, and choosing morally acceptable courses of action. I argue that the metaphor morality is health explicated as the Health of the Organisation can serve as an antidote to the unimaginative moral decision making processes that Patricia Werhane has shown can result in bad moral decisions. I do this by demonstrating that a healthy organisation is one that is optimally functional. This means that the components that make up the organisation are so structured that there is no better possible organisational arrangement available for achieving the goals designed to ensure successful performance in the marketplace. (shrink)

The 14 chapters in _Ethics at the End of Life: New Issues and Arguments_, all published here for the first time, focus on recent thinking in this important area, helping initiate issues and lines of argument that have not been explored previously. At the same time, a reader can use this volume to become oriented to the established questions and positions in end of life ethics, both because new questions are set in their context, and because most of the chapters—written (...) by a team of experts—survey the field as well as add to it. Each chapter includes initial summaries, final conclusions, and a Related Topics section. TABLE OF CONTENTS John K. Davis, "Introduction" Geoffrey Scarre, "Is it possible to be better off dead?" Taylor W. Cyr, "How Does Death Harm the Deceased?" Benjamin Mitchell-Yellin, "The Significance of an Afterlife" Jens Johansson, "The Severity of Death" John K. Davis, "Defining Death" James Stacey Taylor, "Autonomy, Competence, and End of Life" Eric Vogelstein, "Deciding for the Incompetent" Paul T. Menzel, "Change of Mind: An Issue for Advance Directives" Nancy S. Jecker, "Medical Futility and Respect for Patient Autonomy" Paul T. Menzel, "Refusing Lifesaving Medical Treatment and Food and Water by Mouth" Thomas S. Huddle, "Suicide, Physician-Assisted Suicide, the Doing-Allowing Distinction and Double Effect" Michael Cholbi, "Grief and End of Life Surrogate Decision-making" Bruce Jennings, "Solidarity near the End of Life: The Promise of Relational Decision-making in the Care of the Dying" Colin Farrelly, "Justice and the Aging of the Human Species". (shrink)

The 14 chapters in _Ethics at the End of Life: New Issues and Arguments_, all published here for the first time, focus on recent thinking in this important area, helping initiate issues and lines of argument that have not been explored previously. At the same time, a reader can use this volume to become oriented to the established questions and positions in end of life ethics, both because new questions are set in their context, and because most of the chapters—written (...) by a team of experts—survey the field as well as add to it. Each chapter includes initial summaries, final conclusions, and a Related Topics section. TABLE OF CONTENTS John K. Davis, "Introduction" Geoffrey Scarre, "Is it possible to be better off dead?" Taylor W. Cyr, "How Does Death Harm the Deceased?" Benjamin Mitchell-Yellin, "The Significance of an Afterlife" Jens Johansson, "The Severity of Death" John K. Davis, "Defining Death" James Stacey Taylor, "Autonomy, Competence, and End of Life" Eric Vogelstein, "Deciding for the Incompetent" Paul T. Menzel, "Change of Mind: An Issue for Advance Directives" Nancy S. Jecker, "Medical Futility and Respect for Patient Autonomy" Paul T. Menzel, "Refusing Lifesaving Medical Treatment and Food and Water by Mouth" Thomas S. Huddle, "Suicide, Physician-Assisted Suicide, the Doing-Allowing Distinction and Double Effect" Michael Cholbi, "Grief and End of Life Surrogate Decision-making" Bruce Jennings, "Solidarity near the End of Life: The Promise of Relational Decision-making in the Care of the Dying" Colin Farrelly, "Justice and the Aging of the Human Species". (shrink)

The 14 chapters in Ethics at the End of Life: New Issues and Arguments, all published here for the first time, focus on recent thinking in this important area, helping initiate issues and lines of argument that have not been explored previously. At the same time, a reader can use this volume to become oriented to the established questions and positions in end of life ethics, both because new questions are set in their context, and because most of the chapters--written (...) by a team of experts--survey the field as well as add to it. Each chapter includes initial summaries, final conclusions, and a Related Topics section. TABLE OF CONTENTS John K. Davis, "Introduction" Geoffrey Scarre, "Is it possible to be better off dead?" Taylor W. Cyr, "How Does Death Harm the Deceased?" Benjamin Mitchell-Yellin, "The Significance of an Afterlife" Jens Johansson, "The Severity of Death" John K. Davis, "Defining Death" James Stacey Taylor, "Autonomy, Competence, and End of Life" Eric Vogelstein, "Deciding for the Incompetent" Paul T. Menzel, "Change of Mind: An Issue for Advance Directives" Nancy S. Jecker, "Medical Futility and Respect for Patient Autonomy" Paul T. Menzel, "Refusing Lifesaving Medical Treatment and Food and Water by Mouth" Thomas S. Huddle, "Suicide, Physician-Assisted Suicide, the Doing-Allowing Distinction and Double Effect" Michael Cholbi, "Grief and End of Life Surrogate Decision-making" Bruce Jennings, "Solidarity near the End of Life: The Promise of Relational Decision-making in the Care of the Dying" Colin Farrelly, "Justice and the Aging of the Human Species". (shrink)

Relativism and contextualism are the most popular accounts of faultless disagreement, but Crispin Wright once argued for an account I call divergentism. According to divergentism, parties who possess all relevant information and use the same standards of assessment in the same context of utterance can disagree about the same proposition without either party being in epistemic fault, yet only one of them is right. This view is an alternative to relativism, indexical contextualism, and nonindexical contextualism, and has advantages over those (...) views. Wright eventually abandoned this view in favor of relativism for reasons related to a conciliationist view of disagreement between epistemic peers. I argue that he gave up on divergentism too soon. (shrink)

Does respect for autonomy imply respect for precedent autonomy? The principle of respect for autonomy requires us to respect a competent patient’s treatment preference, but not everyone agrees that it requires us to respect preferences formed earlier by a now‐incapacitated patient, such as those expressed in an advance directive. The concept of precedent autonomy, which concerns just such preferences, is problematic because it is not clear that we can still attribute to a now‐incapacitated patient a preference which that patient never (...) disaffirmed but can no longer understand. If we cannot make that attribution, then perhaps we should not respect precedent autonomy – after all, how can you respect patient autonomy by giving patients what they no longer want, even if they never disaffirmed those wants? I argue that whether an earlier preference can still be attributed to a now‐incapacitated patient depends on the reasons behind the preference, for a preference includes (and is not merely supported by) the reasons behind it. When the considerations that served as reasons no longer exist, neither does the preference which included those reasons. In particular, if the considerations that served as reasons for the patient exist only under conditions where the patient retains full mental capacity, then once that capacity is lost, so are those reasons and the preference based upon them. I use this analysis of precedent autonomy to ascertain the merits of various approaches to advance medical decisionmaking, including Nancy Rhoden’s approach, approaches based on a Parfitian personal identity analysis, approaches based on soft paternalism, and approaches based on the stability and longevity of preferences. Despite the apparent absurdity of respecting patient autonomy by giving patients what they no longer prefer but have never disaffirmed, I conclude with some programmatic remarks on when and why respect for (precedent) autonomy nonetheless requires us to respect former preferences. (shrink)

I note that the logics of the relevant group most closely tied to the research programme in paraconsistency are those without the contraction postulate(A.AB).AB and its close relatives. As a move towards gaining control of the contraction-free systems I show that they are prime (that wheneverA B is a theorem so is eitherA orB). The proof is an extension of the metavaluational techniques standardly used for analogous results about intuitionist logic or the relevant positive logics.

Honoring a living will typically involves treating an incompetent patient in accord with preferences she once had, but whose objects she can no longer understand. How do we respect her precedent autonomy by giving her what she used to want? There is a similar problem with subsequent consent: How can we justify interfering with someone''s autonomy on the grounds that she will later consent to the interference, if she refuses now?Both problems arise on the assumption that, to respect someone''s autonomy, (...) any preferences we respect must be among that person''s current preferences. I argue that this is not always true. Just as we can celebrate an event long after it happens, so can we respect someone''s wishes long before or after she has that wish. In the contexts of precedent autonomy and subsequent consent, the wishes are often preferences about which of two other, conflicting preferences to satisfy. When someone has two conflicting preferences, and a third preference on how to resolve that conflict, to respect his autonomy we must respect that third preference. People with declining competence may have a resolution preference earlier, favoring the earlier conflicting preference (precedent autonomy), whereas those with rising competence may have it later, favoring the later conflicting preference (subsequent consent). To respect autonomy in such cases we must respect not a current, but a former or later preference. (shrink)

Sometimes the mentally ill have sufficient mental capacity to refuse treatment competently, and others have a moral duty to respect their refusal. However, those with episodic mental disorders may wish to precommit themselves to treatment, using Ulysses contracts known as “mental health advance directives.” How can health care providers justify enforcing such contracts over an agent’s current, competent refusal? I argue that providers respect an agent’s autonomy not retrospectively—by reference to his or her past wishes—and not merely synchronically—so that the (...) agent gets what he or she wants right now—but diachronically and prospectively, acting so that the agent can shape his or her circumstances as the agent wishes over time, for the agent will experience the consequences of providers’ actions over time. Mental health directives accomplish this, so they are a way of respecting the agent’s autonomy even when providers override the agent’s current competent refusal. (shrink)

"Sheriff’s text moves the "guess" to a new level of understanding, while integrating much of Peirce’s philosophy, and provokes many questions." —Society for the Advancement of American Philosophy Newletter "The purpose of Sheriff’s work is to expound Peirce’s unified theory of the universe—from cosmology to semiotic—and to discuss its ramifications for how we should live. He concludes that Peirce has given us a theory we can live with. The book makes an important contribution to philosophy of life and to the (...) humanities in general."—Nathan Houser "In clear and concise prose, Sheriff describes Peirce’s ‘theory of everything,’ a vision of cosmic and human meaning that offers a positive alternative to popular pessimistic and relativistic approaches to life and meaning." —Peirce Project Newsletter. (shrink)

Patients sometimes request procedures their doctors find morally objectionable. Do doctors have a right of conscientious refusal? I argue that conscientious refusal is justified only if the doctor's refusal does not make the patient worse off than she would have been had she gone to another doctor in the first place. From this approach I derive conclusions about the duty to refer and facilitate transfer, whether doctors may provide 'moral counseling,' whether doctors are obligated to provide objectionable procedures when no (...) other doctor is available, why the moral consensus among doctors seems relevant even though it does not determine whether something is morally acceptable, and whether doctors should stay out of fields whose standard procedures they find morally unacceptable. (shrink)

Moral and legal judgments sometimes depend on personal traits in this sense: the subject offers good reasons for her judgment, but if she had a different social or ideological background, her judgment would be different. If you would judge the constitutionality of restrictions on abortion differently if you were not a secular liberal, is your judgment really based on the arguments you find convincing, or do you find them so only because you are a secular liberal? I argue that a (...) judgment can be based on the considerations the subject claims as justification even when it depends on personal traits. (shrink)

Some moral disagreements are so persistent that we suspect they are deep : we would disagree even when we have all relevant information and no one makes any mistakes. The possibility of deep disagreement is thought to drive cognitivists toward relativism, but most cognitivists reject relativism. There is an alternative. According to divergentism, cognitivists can reject relativism while allowing for deep disagreement. This view has rarely been defended at length, but many philosophers have implicitly endorsed its elements. I will defend (...) it. (shrink)

The worst possible way to resolve this issue is to leave it up to individual choice. There is no known social good coming from the conquest of death (Bailey, 1999). - Daniel Callahan Dramatically extending the human lifespan seems increasingly possible. Many bioethicists object that life-extension will have Malthusian consequences as new Methuselahs accumulate, generation by generation. I argue for a Life-Years Response to the Malthusian Objection. If even a minority of each generation chooses life-extension, denying it to them deprives (...) them of many years of extra life, and their total extra life-years are likely to exceed the total life-years of a majority who do not want life-extension. This is a greater harm to those who want extended life than the Malthusian harms to those who refuse extended life, both because losing an extra year of life is worse than enduring a year of Malthusian conditions, and because the would-be Methuselahs have more life-years at stake. Therefore, even if life-extension seems likely to cause severe overcrowding and resource shortages, that threat is not sufficient to justify society in restricting the development or availability of life-extension. (shrink)

Basic issues in the recent ‘death-of-God’ movement can be illuminated by comparison and contrast with the relevant ideas of two American philosophers, John Dewey and William James. Dewey is an earlier spokesman for ideas that are central to the ‘radical theology’ of Thomas J. J. Altizer, William Hamilton, and Paul Van Buren. His reasons for rejecting theism closely resemble propositions maintained by these ‘death-of-God’ theologians. James, on the other hand, points toward a theological alternative. He takes cognizance of ideas (...) similar to those in the ‘radical theology’, but he does not opt for either a metaphorical or real elimination of God. Thus, the contentions of this paper are that there has been a version of the ‘death-of-God’ perspective in American thought before, and that there are resources in the American tradition that suggest a viable option to this perspective. (shrink)

The paper describes two practical exercises (and their learning outcomes) requiring students to consider certain concrete decisions made by managers in business and professional life. The first exercise requires students to consider that competitive economic exchange inevitably puts managers in situations where they cannot accurately predict the outcomes of their decisions, and often results in harm to innocent people. In this practical exercise, seven discussion situations are described and students are asked to make decisions that take into account the individuals (...) affected by these managerial decisions. Students are asked to consider various ethical theories and devise creative solutions so as to avoid unnecessary harm. The second exercise places students in roles that represent shareholders and stakeholders and asks them to consider the relocation of a manufacturing company to their community. (shrink)

The world into which Jesus was born in Galilee was thoroughly Jewish. It was also divided along social and economic lines and by the manner in which Jews dealt with gentiles. This is evident from different ways in which Jewish identity was conceived and differing attitudes toward land and temple. Jesus' teaching reflects this social context and interacts with it.

Moral decision procedures such as principlism or casuistry require intuition at certain junctures, as when a principle seems indeterminate, or principles conflict, or we wonder which paradigm case is most relevantly similar to the instant case. However, intuitions are widely thought to lack epistemic justification, and many ethicists urge that such decision procedures dispense with intuition in favor of forms of reasoning that provide discursive justification. I argue that discursive justification does not eliminate or minimize the need for intuition, or (...) constrain our intuitions. However, this is not a problem, for intuitions can be justified in easy or obvious cases, and decision procedures should be understood as heuristic devices for reaching judgments about harder cases that approximate the justified intuitions we would have about cases under ideal conditions, where hard cases become easy. Similarly, the forms of reasoning which provide discursive justification help decision procedures perform this heuristic function not by avoiding intuition, but by making such heuristics more accurate. Nonetheless, it is possible to demand too much justification; many clinical ethicists lack the time and philosophical training to reach the more elaborate levels of discursive justification. We should keep moral decision procedures simple and user-friendly so that they will provide what justification can be achieved under clinical conditions, rather than trying to maximize our epistemic justification out of an overstated concern about intuition. (shrink)

Genocide is evil or nothing could be. It raises a host of questions about humanity, rights, justice, and reality, which are key areas of concern for philosophy. Strangely, however, philosophers have tended to ignore genocide. Even more problematic, philosophy and philosophers bear more responsibility for genocide than they have usually admitted. In Genocide and Human Rights: A Philosophical Guide, an international group of twenty-five contemporary philosophers work to correct those deficiencies by showing how philosophy can and should repsond to genocide, (...) particularly in ways that defend human rights. (shrink)

It is shown that there are exactly six normal DeMorgan monoids generated by the identity element alone. The free DeMorgan monoid with no generators but the identity is characterised and shown to have exactly three thousand and eighty-eight elements. This result solves the "Ackerman constant problem" of describing the structure of sentential constants in the logic R.

A growing number of patients make up their minds about some medical issue before they see their provider, either by googling their symptoms or asking a friend. They’ve made up their minds before coming in, and they resist their provider’s recommendations even after receiving information and advice from their provider. This is a new kind of medical autonomy problem; it differs from cases of standard consent, futility, or conscientious refusal. Providers sometimes call this problem “Dr. Google.” I call it premature (...) consent. Providers may wonder whether these patient decisions command the same deference and respect as other patient decisions. The answer is “no,” for these patients are neither fully competent nor properly informed. They typically appear to be competent, but competence includes the ability to deliberate, and they are not deliberating well when they make up their minds before consulting a qualified provider. They seem informed, especially after talking to their provider, but they are misinformed about what sources of medical advice to trust. Moreover, being informed requires believing the information one has received, and these patients sometimes don’t believe the information their provider gives them. (shrink)