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)

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.

Agricultural diversification in the Midwestern Corn Belt has the potential to improve socioeconomic and environmental outcomes by buffering farmers from environmental and economic shocks and improving soil, water, and air quality. However, complex barriers related to agricultural markets, individual behavior, social norms, and government policy constrain diversification in this region. This study examines farmer perspectives regarding the challenges and opportunities for both corn and soybean production and agricultural diversification strategies. We analyze data from 20 focus groups with 100 participants conducted (...) in Indiana, Illinois, and Iowa through a combined inductive and deductive approach, drawing upon interpretive grounded theory. Our results suggest that when identifying challenges and opportunities, participants center economics and market considerations, particularly income, productivity, and market access. These themes are emphasized both as benefits of the current corn-soybean system, as well as challenges for diversification. Additionally, logistical, resource and behavioral hurdles– including the comparative difficulty and time required to diversify, and constraints in accessing land, labor, and technical support– are emphasized by participants as key barriers to diversification. Agricultural policies shape these challenges, enhancing the comparative advantage and decreasing the risk of producing corn and soybeans as compared to diversified products. Meanwhile, alternative marketing arrangements, farmer networks, family relationships, and improved soil health are highlighted as important opportunities for diversification. We contextualize our findings within the theories of reasoned action and diffusion of innovation, and explore their implications for farmer engagement, markets, and agricultural policy, and the development of additional resources for business and technical support. (shrink)

The practice of modern craniomaxillofacial surgery has been defined by emergent technologies allowing for the acquisition, storage, utilization, and transfer of massive amounts of sensitive and identifiable patient data. This alone has thrust providers into an unlikely and unprecedented role as the stewards of vast databases of digital information. This data powers the potent surgical tool of virtual surgical planning, a method by which craniomaxillofacial surgeons plan and simulate procedural outcomes in a digital environment. Further complicating this new terrain is (...) the involvement of third‐party contractors—a necessary presence in bringing raw data to bear in the office, virtual space, and operating room. The individual privileges and responsibilities of patients, providers, and vendors towards data are situated within the most recent U.S. court rulings and regulations. This paper offers guidance for overseeing the safe and responsible transfer to third‐party contractors, and provides suggestions for negotiating the trinary relationship between physicians, their patients, and the vendors offering this transformative technology. (shrink)

Polarization is a topic of intense interest among social scientists, but there is significant disagreement regarding the character of the phenomenon and little understanding of underlying mechanics. A first problem, we argue, is that polarization appears in the literature as not one concept but many. In the first part of the article, we distinguish nine phenomena that may be considered polarization, with suggestions of appropriate measures for each. In the second part of the article, we apply this analysis to evaluate (...) the types of polarization generated by the three major families of computational models proposing specific mechanisms of opinion polarization. (shrink)

Artists, art critics, art historians, and cognitive psychologists have asserted that visual artists perceive the world differently than nonartists and that these perceptual abilities are the product of knowledge of techniques for working in an artistic medium. In support of these claims, Kozbelt (2001) found that artists outperform nonartists in visual analysis tasks and that these perceptual advantages are statistically correlated with drawing skill. We propose a model to explain these results that is derived from a diagnostic framework for object (...) recognition and recent research in cognitive neuroscience on selective visual attention. This research demonstrates that endogenous shifts of visual attention enhance the encoding of expected features in the visual field and inhibit the perception of potential distracters. Moreover, it demonstrates complementary roles for spatial schemata and motor plans in visual attention. We argue that artists develop novel spatial schemata, which enable them to recognize and reproduce stimulus features sufficient for adequate artistic production in a medium, and that these schemata become encoded as motor plans as artists develop technical proficiency in a medium. We hypothesize that artists' perceptual advantages can therefore, be explained by the role spatial schemata and motor plans play in selective attention. (shrink)

ABSTRACT This article distinguishes nine senses of polarization and provides formal measures for each one to refine the methodology used to describe polarization in distributions of attitudes. Each distinct concept is explained through a definition, formal measures, examples, and references. We then apply these measures to GSS data regarding political views, opinions on abortion, and religiosity—topics described as revealing social polarization. Previous breakdowns of polarization include domain-specific assumptions and focus on a subset of the distribution’s features. This has conflated multiple, (...) independent features of attitude distributions. The current work aims to extract the distinct senses of polarization and demonstrate that by becoming clearer on these distinctions we can better focus our efforts on substantive issues in social phenomena. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:The Apocalypse of Wisdom: Louis Bouyer's Theological Recovery of the Cosmos by Keith LemnaAaron WilliamsThe Apocalypse of Wisdom: Louis Bouyer's Theological Recovery of the Cosmos by Keith Lemna (Brooklyn, NY: Angelico, 2019), xxx + 488 pp.Keith Lemna has done the theological world a great service. In The Apocalypse of Wisdom: Louis Bouyer's Theological Recovery of the Cosmos, he offers the English-speaking world for the first time a monograph (...) on the thought of the Oratorian Louis Bouyer. Bouyer is undoubtedly one of the theological giants of the twentieth century. Born in Paris in 1913, he was ordained a Lutheran pastor in 1936. After only three years as a Lutheran clergyman, he was received into the Catholic Church at the Benedictine Abbey of Saint Wandrille. Then ordained as an Oratorian priest in 1944, he taught from 1946 to 1962 at the Institut Catholique de Paris and abroad for the three decades following.1 He is most well-known for his work on the liturgy both before and after the Second Vatican Council. With fifty books to his name, including a nine-part synthesis on Christian doctrine, the breadth of his theological vision and work is astounding. In France he is considered one of the four preeminent theologians of the post-World War II era, and his theological contemporaries in Europe, such as Hans Urs von Balthasar and Joseph Ratzinger / Benedict XVI, always held the Oratorian in high regard.2 Yet, in the English-speaking world, much of his work has gone without comment.3 Thankfully, into the void steps this excellent work by Lemna. [End Page 1353]Anyone familiar with the Bouyerian corpus knows the challenge of approaching it. With its vast array of subject matter, ranging from biblical to liturgical to historical to spiritual to speculative theology, one wonders whether there is any one thread woven throughout the varied strands, a single theme around which the whole sprawling corpus can be understood. In fact, there is, and Lemna has deftly identified it. For Bouyer, the fundamental question of theology is the world's relation to God.4 The structure of the first six books of his nine-part treatise on systematic theology attest to the priority of the question with the first three works addressing the question of the world, or the economy of creation and salvation, and the latter three works addressing the question of God, or theology properly speaking: the doctrine of the Trinitarian God. Interestingly, though Bouyer's work on theological cosmology, Cosmos, is the third book in the series, it was, in fact, the last of the six to be written. In this sense, as Lemna points out, "Cosmos is a capstone monograph... summarizing in important ways the decisive first six volumes" (xiv). Theological cosmology fully illuminates the God–world relation as Bouyer sees it, and since this relation sits at the heart of his thought, Cosmos is for Bouyer both his "most personal, as well as most speculative work" and indeed, "opens up the meaning of his other writings" beyond the dogmatic sphere (25). One could, then, scarcely choose a better entry point into the wide theological world of this "mind with a very special character," as Joseph Ratzinger saw him.5The Apocalypse of Wisdom is an expansive commentary on Bouyer's cosmology at the heart of which is a liturgical, even nuptial, vision of the whole of creation known and loved in the mind of God from all eternity, as the uncreated Wisdom of God. In creation God freely gives existence to the world ex nihilo, so that it might return to him in a liturgical song of praise and thanksgiving, as the Bride of his eternal Son, the eschatological and cosmic Church, created wisdom now made glorious and radiant through the indwelling of the Holy Spirit. As Lemna puts it, "Bouyer shows that cosmology should be a pursuit of wisdom, but that Wisdom is ultimately a gift revealed or uncovered by means of apokalypsis in the re-creative interventions of the divine Word and Holy Spirit in history" (xvii). The wisdom of man seeking a unified vision of the whole of reality [End... (shrink)

ABSTRACT Between 1920 and 1922, the University of Bristol biochemist, Maximilian Nierenstein, published four papers in a series exploring the structure of catechin in the Journal of the Chemical Society. The Society then abruptly refused to accept any more of his papers on catechin, or any other subject. It provided him with no reasons for the embargo until 1925. It then transpired that Nierenstein was boycotted because it was deemed that he had not responded adequately to criticisms of his work (...) made by his rival in catechin research, the German natural products chemist, Karl Freudenberg. It was not until 1929 that, as a result of a petition by a group of his former Bristol pupils and friends, that Nierenstein was again permitted to publish in the Society’s journal. The paper explores the Chemical Society’s treatment of Nierenstein in detail, sheds new light on his career and his reaction to the Society’s unprecedented boycott, examines some of the structural chemistry involved in the disputes, and discusses whether Nierenstein’s research deserves the label of ‘bad science’. (shrink)

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)

Agent-based models have played a prominent role in recent debates about the merits of democracy. In particular, the formal model of Lu Hong and Scott Page and the associated “diversity trumps ability” result has typically been seen to support the epistemic virtues of democracy over epistocracy (i.e., governance by experts). In this paper we first identify the modeling choices embodied in the original formal model and then critique the application of the Hong-Page results to philosophical debates on the relative merits (...) of democracy. In particular we argue that the “best-performing agents” in Hong-Page model should not be interpreted as experts. We next explore a closely related model in which best-performing agents are more plausibly seen as experts and show that the diversity trumps ability result fails to hold. However, with changes in other parameters (such as the deliberation dynamic) the diversity trumps ability result is restored. The sensitivity of this result to parameter choices illustrates the complexity of the link between formal modeling and more general philosophical claims; we use this debate as a platform for a more general discussion of when and how agent-based models can contribute to philosophical discussions. (shrink)

This volume examines some of the most contentious social justice issues present in the corpus of Augustine's writings. Whether one is concerned with human trafficking and the contemporary slave trade, the global economy, or endless wars, these essays further the conversation on social justice as informed by the writings of Augustine of Hippo.

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)

In the original publication of the article, the Acknowledgement section was inadvertently not included. The Acknowledgement is given in this Correction.

The FDA's new table of surrogate endpoints used for drug approvals is an important step forward for overseeing the use of biomarkers in clinical trials. Nevertheless, we present several ways in which the table can be improved.

While visiting relatives in northern England in October 1865 the London chemist William Crookes witnessed firsthand the economic devastation of farming communities blighted by the cattle plague that had been sweeping Britain since June. Crookes delayed his return to London for several months and obtained official permission to begin experimenting on eradicating the disease with a new disinfectant, carbolic acid. In his report to the British government in 1866, Crookes was explicit that his experiments had been based on a (...) germ or contagion theory of the disease. Germs were considered to be airborne particles that might either be “living” material that “germinated” in the soil of animal flesh and blood or chemical poisons that decomposed flesh and blood.In the opening chapter of this fine study of the construction of British germ theories between the 1860s and 1900, Michael Worboys makes it clear that the cattle plague was a keystone in the long process of germ theory construction. Rinderpest was readily accepted by veterinary surgeons as a contagious disease to be controlled by wholesale culling with the poleax. On the other hand, they ignored or actively opposed the practical implications of a germ theory—disinfection , vaccination, and laboratory research—because these procedures posed a threat to the power and control of the veterinary profession. Plus ça change? In Britain, we are currently witnessing a similar example of party interest as a powerful Farmers' Union culls millions of cattle and sheep but prevents the use of vaccination in fighting a foot and mouth epidemic.Although a number of studies have celebrated the germ theory as the key development in producing scientific medicine in the late nineteenth century, this is the first critical book‐length study of its diffusion. The separate professional communities of veterinary practitioners, surgeons, and sanitarians are disarmingly shown to have developed different germ theories and differed over the practical consequences of their commitments. The closed subcultures inhabited by these groups meant that it took several decades before the germs of sanitarians were linked with those of surgeons and with the bacteria of microbiologists. Anyone who made a connection, such as the physicist John Tyndall, was dismissed as an inexpert interloper. Clearly, the singular specific disease germ theory was evolutionary in construction, not revolutionary.Worboys's ambitious monograph offers many fresh insights, including a finely tuned account of Joseph Lister's vacillating ideas and practices concerning wound management, and a splendid analysis of the problematic identification of specific germs causing cholera, smallpox, tuberculosis, diphtheria, typhoid fever, and scarlet fever. His meticulous survey of the contemporary literature unravels the deep uncertainty over whether “germs” were living organisms or chemicals, spontaneously generated or ancestral, causes or concomitants of disease. The fact that unpleasant wounds and the sick sometimes recovered spontaneously made sense only if patients constitutionally differed as an appropriate or inappropriate “soil” for “germ seeds” to blossom or perish. In this way ontological germ theories complemented the traditional medical concepts of constitutional strength and weakness and the healing power of nature. This insight underlines one of the strengths of the book, namely, its recognition of continuities in the construction of disease concepts and practices.Worboys successfully challenges the view that the British medical communities acted largely as onlookers while French and German practitioners honed a laboratory‐based medicine for the twentieth century. Overall, Worboys's monograph is a challenging and extremely readable medical history of germs. It will be essential reading for students taking history of medicine programs. (shrink)

Epistemic justifications for democracy have been offered in terms of two different aspects of decision-making: voting and deliberation, or ‘votes’ and ‘talk.’ The Condorcet Jury Theorem is appealed to as a justification in terms votes, and the Hong-Page “Diversity Trumps Ability” result is appealed to as a justification in terms of deliberation. Both of these, however, are most plausibly construed as models of direct democracy, with full and direct participation across the population. In this paper, we explore how these results (...) hold up if we vary the model so as to reflect the more familiar democratic structure of a representative hierarchy. We first recount extant analytic work that shows that representation inevitably weakens the voting results of the Condorcet Jury Theorem, but we question the ability of that result to shine light on real representative systems. We then show that, when we move from votes to talk, as modeled in Hong-Page, representation holds its own and even has a slight edge. (shrink)

A first take, matured in later work, in modeling belief polarization.

Charles Darwin, in his species notebooks, engaged seriously with the quinarian system of William Sharp Macleay. Much of the attention given to this engagement has focused on Darwin’s attempt to explain, in a transmutationist framework, the intricate patterns that characterized the quinarian system. Here, I show that Darwin’s attempt to explain these quinarian patterns primarily occurred before he had read any work by Macleay. By the time Darwin began reading Macleay’s writings, he had already arrived at a skeptical view (...) of the reality of these patterns. What most interested Darwin, as he read Macleay, was not the quinarian system itself. Rather, Darwin’s notes on his reading primarily concerned certain background principles animating Macleay’s work, in particular: the non-existence of a saltus between human and animal minds, the difficulty of establishing boundaries between species and varieties, and Macleay’s method of variation. Darwin’s interest in the last of these left a mark on his discussion of taxonomic methodology in the Origin. (shrink)

Aaron Zimmerman presents a new pragmatist account of belief, in terms of information poised to guide our more attentive, controlled actions. And he explores the consequences of this account for our understanding of the relation between psychology and philosophy, the mind and brain, the nature of delusion, faith, pretence, racism, and more.

The behavioral sciences have flourished by studying how traditional and/or rational behavior has been governed throughout most of human history by relatively well-informed individual and social learning. In the online age, however, social phenomena can occur with unprecedented scale and unpredictability, and individuals have access to social connections never before possible. Similarly, behavioral scientists now have access to “big data” sets – those from Twitter and Facebook, for example – that did not exist a few years ago. Studies of human (...) dynamics based on these data sets are novel and exciting but, if not placed in context, can foster the misconception that mass-scale online behavior is all we need to understand, for example, how humans make decisions. To overcome that misconception, we draw on the field of discrete-choice theory to create a multiscale comparative “map” that, like a principal-components representation, captures the essence of decision making along two axes: aneast–westdimension that represents the degree to which an agent makes a decision independently versus one that is socially influenced, and anorth–south dimensionthat represents the degree to which there is transparency in the payoffs and risks associated with the decisions agents make. We divide the map into quadrants, each of which features a signature behavioral pattern. When taken together, the map and its signatures provide an easily understood empirical framework for evaluating how modern collective behavior may be changing in the digital age, including whether behavior is becoming more individualistic, as people seek out exactly what they want, or more social, as people become more inextricably linked, even “herdlike,” in their decision making. We believe the map will lead to many new testable hypotheses concerning human behavior as well as to similar applications throughout the social sciences. (shrink)

Population-level biomedical research offers new opportunities to improve population health, but also raises new challenges to traditional systems of research governance and ethical oversight. Partly in response to these challenges, various models of public involvement in research are being introduced. Yet, the ways in which public involvement should meet governance challenges are not well understood. We conducted a qualitative study with 36 experts and stakeholders using the World Café method to identify key governance challenges and explore how public involvement can (...) meet these challenges. This brief report discusses four cross-cutting themes from the study: the need to move beyond individual consent; issues in benefit and data sharing; the challenge of delineating and understanding publics; and the goal of clarifying justifications for public involvement. The report aims to provide a starting point for making sense of the relationship between public involvement and the governance of population-level biomedical research, showing connections, potential solutions and issues arising at their intersection. We suggest that, in population-level biomedical research, there is a pressing need for a shift away from conventional governance frameworks focused on the individual and towards a focus on collectives, as well as to foreground ethical issues around social justice and develop ways to address cultural diversity, value pluralism and competing stakeholder interests. There are many unresolved questions around how this shift could be realised, but these unresolved questions should form the basis for developing justificatory accounts and frameworks for suitable collective models of public involvement in population-level biomedical research governance. (shrink)

In a profile in the November, 2012 issue of the magazine Architect, activist-architect Raphael Sperry, a founder of the group Architects Planners & Designers for Social Responsibility discussed his petition to amend the AIA’s Code of Ethics and Professional Conduct to include a prohibition on “the design of spaces intended for long-term solitary isolation and execution.”1 This issue is both serious and timely. It deserves contemplative attention before any action is taken. The purpose of this letter is to provide the (...) the architecture profession a condensed analysis of the possible justification for taking the action Mr. Sperry advocates. After review and consideration, we are persuaded that Mr. Sperry’s proposal does merit action by the AIA. (shrink)

The authors respond to a letter by Mitchell Berger in the March‐April 2024 issue of the Hastings Center Report concerning their essay “Securing the Trustworthiness of the FDA to Build Public Trust in Vaccines.”.

The Hong and Page ‘diversity trumps ability’ result has been used to argue for the more general claim that a diverse set of agents is epistemically superior to a comparable group of experts. Here we extend Hong and Page’s model to landscapes of different degrees of randomness and demonstrate the sensitivity of the ‘diversity trumps ability’ result. This analysis offers a more nuanced picture of how diversity, ability, and expertise may relate. Although models of this sort can indeed be suggestive (...) for diversity policies, we advise against interpreting such results overly broadly. (shrink)