Graphical AbstractGene editing with engineered nucleases introduce double-strand breaks that are repaired by error-prone nonhomologous end-joining (NHEJ). In article number 1900126, Sara G. Trimidal et al. propose that the length and type or resulting indels can now be controlled by editing with different engineered nucleases or by manipulating the expression of NHEJ genes.

Genome editing with engineered nucleases (GEENs) introduce site‐specific DNA double‐strand breaks (DSBs) and repairs DSBs via nonhomologous end‐joining (NHEJ) pathways that eventually create indels (insertions/deletions) in a genome. Whether the features of indels resulting from gene editing could be customized is asked. A review of the literature reveals how gene editing technologies via NHEJ pathways impact gene editing. The survey consolidates a body of literature that suggests that the type (insertion, deletion, and complex) and the approximate length of indel edits (...) can be somewhat customized with different GEENs and by manipulating the expression of key NHEJ genes. Structural data suggest that binding of GEENs to DNA may interfere with binding of key components of DNA repair complexes, favoring either classical‐ or alternative‐NHEJ. The hypotheses have some limitations, but if validated, will enable scientists to better control indel makeup, holding promise for basic science and clinical applications of gene editing. Also see the video abstract here https://youtu.be/vTkJtUsLi3w. (shrink)

Dr. Brown, a hospitalist, admits Mark, a patient transferred from a local jail for management of cellulitis. The patient, who was taken into custody two days prior to hospital admission, has a history of intravenous heroin use. Mark explains that he had been prescribed buprenorphine-naloxone maintenance therapy for opioid use disorder for several years prior to being arrested and had not used other opioids during that time. As a policy, the jail where Mark is detained does not prescribe opioid agonists, (...) and his maintenance therapy was stopped upon his arrival there. Dr. Brown discovers that Mark is diaphoretic and appears distressed. Mark's symptoms suggest to Dr. Brown that, in addition to having cellulitis, Mark is actively withdrawing from opioids. Mark tells Dr. Brown that he has felt “horrible” since his buprenorphine-naloxone therapy was stopped and that he now has intense cravings for opioids. He asks Dr. Brown to help alleviate the withdrawal symptoms. Dr. Brown, who is accustomed to treating opioid withdrawal with opioid replacement therapy, wonders if she should initiate ORT for Mark while he is in the hospital. (shrink)

“We get wise by asking questions, and even if these are not answered, we get wise; for a well packed question carries its answer on its back as a snail carries its shell.” These lines from James Stephens’ Irish Fairy Tales are an appropriate introduction, for Singer takes the question, ‘How shall I live if I would have of life the best it has to offer?’ as the departure for his ethics, or perhaps it would be fairer to say, (...) for his reflections on ethical matters. This brief essay is expository and interpretive rather than critical and brings together material from various essays, particularly “Progress,” “On The Contented Life,” and “Old Ways and New Beginnings of Science and of Morals.”. (shrink)

Through an examination of a variety of cultural forms and texts, Sexy Bodies investigates the ways in which sexual bodies, sexual practices and sexualities are produced.Are bodies sexy? How? In what sorts of ways? Sexy Bodies investigates the production of sexual bodies and sexual practices, of sexualities which are dyke, bi, transracial, and even hetero. It celebrates lesbian and queer sexualities but also explores what runs underneath and within all sexualities, discovering what is fundamentally weird and strange about all bodies, (...) all carnalities.Looking at a pleasurable variety of cultural forms and texts, the contributors consider the particular charms of girls and horses, from National Velvet to Marnie; discuss figures of the lesbian body from vampires to tribades to tomboys; uncover 'virtual' lesbians in the fiction of Jeanette Winterson; track desire in the music of legendary Blues singers; and investigate the ever-scrutinised and celebrated body of Elizabeth Taylor. The collection includes two important pieces of fiction by Mary Fallon and Nicole Brossard. (shrink)

Controversial Harlem-born rapper/singer, songwriter, and provocateuse Azealia Banks is the most famous, vocal, and visible proponent of Black Atlantic traditions in recent times—making a critical reckoning well overdue. I begin here by tracing Banks's engagement with Afro-Diasporic religions as a trajectory from vamp to bruja [witch]/santera to mayombera. A review of Banks's public statements reveals her growing commitment to championing “so-called voodoo” and urging other African Americans to do so as well. I argue that the release of Beyoncé's Lemonade (...) in 2016 catalyzed Banks's advocacy for Kongo-inspired Palo Mayombe, long overshadowed by Yorùbá-based orisha worship. I further demonstrate that Banks's espousal of Palo Mayombe has been bound up with her identity as a Womanist and dark-skinned, cisgender femme fatale. More than a political program, however, Banks's discursive constructions amount to a Black Atlantic metaphysics. Drawing on Irene Lara's formulation of “bruja positionalities,” I propose that the theoretical scaffolding for her metaphysics should be designated Brujx Womanism. Missteps notwithstanding, Banks emerges as a metaphysician, aspiring to repair Black bodies by re-membering Kongo traditions. In closing, I suggest that Banks's Brujx Womanism may contribute to the conceptualization of Conjure Feminism in four crucial respects. (shrink)

In this timely collection, some of the world's leading ethicists grapple with the variety of issues posed by human embryonic stem cell research. Investigates the moral status of the embryo including the creation of chimeras and paying for gametes (eggs and sperm) and embryos for research purposes Provides a thorough evaluation of the ethics and politics of regulating hESC research, and the privacy, confidentiality, and informed consent in the conduct of research and clinical investigations Essential reading for scientists, philosophers, policy (...) makers, and all who are interested in the ethical conduct of science Contributors include David DeGrazia, Lori Gruen, Elizabeth Harman, John Harris, Jeff McMahan, Don Marquis and Peter Singer. (shrink)

In 1972, the young philosopher Peter Singer published "Famine, Affluence and Morality," which rapidly became one of the most widely discussed essays in applied ethics. Through this article, Singer presents his view that we have the same moral obligations to those far away as we do to those close to us. He argued that choosing not to send life-saving money to starving people on the other side of the earth is the moral equivalent of neglecting to save drowning (...) children because we prefer not to muddy our shoes. If we can help, we must--and any excuse is hypocrisy. Singer's extreme stand on our moral obligations to others became a powerful call to arms and continues to challenge people's attitudes towards extreme poverty. Today, it remains a central touchstone for those who argue we should all help others more than we do. As Bill and Melinda Gates observe in their foreword, in the age of today's global philanthropy, Singer's essay is as relevant now as it ever was. This attractively packaged, concise edition collects the original article, two of Singer's more recent popular writings on our obligations to others around the world, and a new introduction by Singer that discusses his current thinking. (shrink)

In a thoughtful reassessment of the meaning of life and death, a noted philosopher offers a new definition for life that contrasts a world dependent on biological maintenance with one controlled by state-of-the-art medical technology. Tour.

Public discussions of political and social issues are often characterized by deep and persistent polarization. In social psychology, it’s standard to treat belief polarization as the product of epistemic irrationality. In contrast, we argue that the persistent disagreement that grounds political and social polarization can be produced by epistemically rational agents, when those agents have limited cognitive resources. Using an agent-based model of group deliberation, we show that groups of deliberating agents using coherence-based strategies for managing their limited resources tend (...) to polarize into different subgroups. We argue that using that strategy is epistemically rational for limited agents. So even though group polarization looks like it must be the product of human irrationality, polarization can be the result of fully rational deliberation with natural human limitations. (shrink)

What is ethics? Where do moral standards come from? Are they based on emotions, reason, or some innate sense of right and wrong? For many scientists, the key lies entirely in biology---especially in Darwinian theories of evolution and self-preservation. But if evolution is a struggle for survival, why are we still capable of altruism? In his classic study The Expanding Circle, Peter Singer argues that altruism began as a genetically based drive to protect one's kin and community members but (...) has developed into a consciously chosen ethic with an expanding circle of moral concern. Drawing on philosophy and evolutionary psychology, he demonstrates that human ethics cannot be explained by biology alone. Rather, it is our capacity for reasoning that makes moral progress possible. In a new afterword, Singer takes stock of his argument in light or recent research on the evolution of morality.--Publisher's description. (shrink)

Disability is primarily a social phenomenon -- a way of being a minority, a way of facing social oppression, but not a way of being inherently or intrinsically worse off. This is how disability is understood in the Disability Rights and Disability Pride movements; but there is a massive disconnect with the way disability is typically viewed within analytic philosophy. The idea that disability is not inherently bad or sub-optimal is one that many philosophers treat with open skepticism, and sometimes (...) even with scorn. The goal of this book is to articulate and defend a version of the view of disability that is common in the Disability Rights movement. To be physically disabled is not to have a defective body, but simply to have a minority body. (shrink)

Since its original publication in 1975, this groundbreaking work has awakened millions of people to the existence of "speciesism"—our systematic disregard of nonhuman animals—inspiring a worldwide movement to transform our attitudes to animals and eliminate the cruelty we inflict on them. In Animal Liberation, author Peter Singer exposes the chilling realities of today’s "factory farms" and product-testing procedures—destroying the spurious justifications behind them, and offering alternatives to what has become a profound environmental and social as well as moral issue. (...) An important and persuasive appeal to conscience, fairness, decency, and justice, it is essential reading for the supporter and the skeptic alike. (shrink)

In the Brazilian film "Central Station," Dora is a retired schoolteacher who makes ends meet by sitting at the station writing letters for illiterate people. Suddenly she has an opportunity to pocket $1,000. All she has to do is persuade a homeless 9-year-old boy to follow her to an address she has been given. (She is told he will be adopted by wealthy foreigners.) She delivers the boy, gets the money, spends some of it on a television set and settles (...) down to enjoy her new acquisition. Her neighbor spoils the fun, however, by telling her that the boy was too old to be adopted —he will be killed and his organs sold for transplantation. Perhaps Dora knew this all along, but after her neighbor's plain speaking, she spends a troubled night. In the morning Dora resolves to take the boy back. (shrink)

For thirty years, Peter Singer's Practical Ethics has been the classic introduction to applied ethics. For this third edition, the author has revised and updated all the chapters and added a new chapter addressing climate change, one of the most important ethical challenges of our generation. Some of the questions discussed in this book concern our daily lives. Is it ethical to buy luxuries when others do not have enough to eat? Should we buy meat from intensively reared animals? (...) Am I doing something wrong if my carbon footprint is above the global average? Other questions confront us as concerned citizens: equality and discrimination on the grounds of race or sex; abortion, the use of embryos for research and euthanasia; political violence and terrorism; and the preservation of our planet's environment. This book's lucid style and provocative arguments make it an ideal text for university courses and for anyone willing to think about how she or he ought to live. (shrink)

Social constructionism is often considered a form of anti-realism. But in contemporary feminist philosophy, an increasing number of philosophers defend views that are well-described as both realist and social constructionist. In this paper, I use the work of Sally Haslanger as an example of realist social constructionism. I argue: that Haslanger is best interpreted as defending metaphysical realism about social structures; that this type of metaphysical realism about the social world presents challenges to some popular ways of understanding metaphysical realism.

We motivate a picture of social epistemology that sees forgetting as subject to epistemic evaluation. Using computer simulations of a simple agent-based model, we show that how agents forget can have as large an impact on group epistemic outcomes as how they share information. But, how we forget, unlike how we form beliefs, isn’t typically taken to be the sort of thing that can be epistemically rational or justified. We consider what we take to be the most promising argument for (...) this claim and find it lacking. We conclude that understanding how agents forget should be as central to social epistemology as understanding how agents form beliefs and share information with others. (shrink)

Much of the literature on the relationship between belief and credence has focused on the reduction question: that is, whether either belief or credence reduces to the other. This debate, while important, only scratches the surface of the belief-credence connection. Even on the anti-reductive dualist view, belief and credence could still be very tightly connected. Here, I explore questions about the belief-credence connection that go beyond reduction. This paper is dedicated to what I call the independence question: just how independent (...) are belief and credence? I look at this question from two angles: a descriptive one (as a psychological matter, how much can belief and credence come apart?) and a normative one (for a rational person, how closely connected are belief and credence?) Ultimately, I suggest that the two attitudes are more independent than one might think. (shrink)

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

Women as commercial baby factories, nature as an economic resource, life as one big shopping mall: This is what we get when we use the market as a common ...

This new and important study of semantic change examines how new meanings arise through language use, especially the various ways in which speakers and writers experiment with uses of words and constructions in the flow of strategic interaction with addressees. In the last few decades there has been growing interest in exploring systemicities in semantic change from a number of perspectives including theories of metaphor, pragmatic inferencing, and grammaticalization. Like earlier studies, these have for the most part been based on (...) data taken out of context. This book is the first detailed examination of semantic change from the perspective of historical pragmatics and discourse analysis. Drawing on extensive corpus data from over a thousand years of English and Japanese textual history, Traugott and Dasher show that most changes in meaning originate in and are motivated by the associative flow of speech and conceptual metonymy. (shrink)

In this project I am concerned with the extent to which conceptual engineering happens in domains outside of philosophy, and if so, what that might look like. Specifically, I’ll argue that...

Feminist epistemology has often been understood as the study of feminine "ways of knowing." But feminist epistemology is better understood as the branch of naturalized, social epistemology that studies the various influences of norms and conceptions of gender and gendered interests and experiences on the production of knowledge. This understanding avoids dubious claims about feminine cognitive differences and enables feminist research in various disciplines to pose deep internal critiques of mainstream research.

In a recent paper, Barry Loewer attempts to defend Humeanism about laws of nature from a charge that Humean laws are not adequately explanatory. Central to his defense is a distinction between metaphysical and scientific explanations: even if Humeans cannot offer further metaphysical explanations of particular features of their “mosaic,” that does not preclude them from offering scientific explanations of these features. According to Marc Lange, however, Loewer’s distinction is of no avail. Defending a transitivity principle linking scientific explanantia to (...) their metaphysical grounds, Lange argues that a charge of explanatory inadequacy resurfaces once this intuitive principle is in place. This paper surveys, on behalf of the Humean, three strategies for responding to Lange’s criticism. The ready availability of these strategies suggests that Lange’s argument may not bolster anti-Humean convictions, since the argument rests on premises that those not antecedently sharing these convictions may well reject. The three strategies also correspond to three interesting ways of thinking about relations of grounding linking Humean laws and their instances, all of which are consistent with theses of Humean supervenience, and some of which have been heretofore overlooked. (shrink)

The book's primary readership remains teachers and students of ethics whether in philosophy or some other branch of the humanities or social sciences. However, such is the clarity of the book's style and structure that it should interest any thinking person concerned with the most difficult social problems facing us as we approach the twenty-first century.

Many evidentialists are impermissivists. But there’s no in-principle reason for this. In this paper, I examine and motivate permissivist evidentialism. Not only are permissivism and evidentialism compatible but there are unique benefits that arise for this combination of views. In particular, permissivist evidentialism respects the importance of evidence while capturing its limitations and provides a plausible and attractive explanation of the relationship between the epistemic and non-epistemic. Permissivist evidentialism is thus an attractive option in logical space that hasn’t received enough (...) attention. (shrink)

Credences are similar to levels of confidence, represented as a value on the [0,1] interval. This chapter sheds light on questions about credence, including its relationship to full belief, with an eye toward the empirical relevance of credence. First, I’ll provide a brief epistemological history of credence and lay out some of the main theories of the nature of credence. Then, I’ll provide an overview of the main views on how credences relate to full beliefs. Finally, I’ll turn to the (...) empirical, and suggest some ways that cognitive science does and could answer questions about credence, such as what credences one has, how credences relate to beliefs, and the extent to which we can control our credences. (shrink)

Philosophical theories of gender are typically understood as theories of what it is to be a woman, a man, a nonbinary person, and so on. In this paper, I argue that this is a mistake. There’s good reason to suppose that our best philosophical theory of gender might not directly match up to or give the extensions of ordinary gender categories like ‘woman’.

This book is composed of research presented at the fourth international Queering Paradigms Conference (QP4), held in Rio de Janeiro, Brazil. It intends to contribute to building a queer postcolonial critique of the current politics of queer activism and of queer knowledge production and circulation.

More than forty years have passed since Congress, in response to the Civil Rights Movement, enacted sweeping antidiscrimination laws in the Civil Rights Act of 1964, the Voting Rights Act of 1965, and the Fair Housing Act of 1968. As a signal achievement of that legacy, in 2008, Americans elected their first African American president. Some would argue that we have finally arrived at a postracial America, butThe Imperative of Integration indicates otherwise. Elizabeth Anderson demonstrates that, despite progress toward (...) racial equality, African Americans remain disadvantaged on virtually all measures of well-being. Segregation remains a key cause of these problems, and Anderson skillfully shows why racial integration is needed to address these issues. Weaving together extensive social science findings--in economics, sociology, and psychology--with political theory, this book provides a compelling argument for reviving the ideal of racial integration to overcome injustice and inequality, and to build a better democracy. -/- Considering the effects of segregation and integration across multiple social arenas, Anderson exposes the deficiencies of racial views on both the right and the left. She reveals the limitations of conservative explanations for black disadvantage in terms of cultural pathology within the black community and explains why color blindness is morally misguided. Multicultural celebrations of group differences are also not enough to solve our racial problems. Anderson provides a distinctive rationale for affirmative action as a tool for promoting integration, and explores how integration can be practiced beyond affirmative action. -/- Offering an expansive model for practicing political philosophy in close collaboration with the social sciences, this book is a trenchant examination of how racial integration can lead to a more robust and responsive democracy. (shrink)

Intention is one of the masterworks of twentieth-century philosophy in English. First published in 1957, it has acquired the status of a modern philosophical classic. The book attempts to show in detail that the natural and widely accepted picture of what we mean by an intention gives rise to insoluble problems and must be abandoned. This is a welcome reprint of a book that continues to grow in importance.

Metaphysical orthodoxy maintains that the relation of ontological dependence is irreflexive, asymmetric, and transitive. The goal of this paper is to challenge that orthodoxy by arguing that ontological dependence should be understood as non- symmetric, rather than asymmetric. If we give up the asymmetry of dependence, interesting things follow for what we can say about metaphysical explanation— particularly for the prospects of explanatory holism.

The aim of this paper is to (i) examine the concept of epistemic paternalism and (ii) explore the consequences of normative questions one might ask about it. I begin by critically examining several definitions of epistemic paternalism that have been proposed, and suggesting ways they might be improved. I then contrast epistemic and general paternalism and argue that it’s difficult to see what makes epistemic paternalism an epistemic phenomenon at all. Next, I turn to the various normative questions one might (...) ask about epistemic paternalism and discuss the literature’s assumptions of epistemic consequentialism and veritism. I close by comparing and contrasting epistemic paternalism with other topics in social epistemology, such as disagreement or testimony. (shrink)

Do other living creatures alienate themselves from their own species with only selfish concern for material successes and external achievement? ...