In this review, we discuss how two evolutionarily conserved pathways at the interface of DNA replication and repair, template switching and break-induced replication, lead to the deleterious large-scale expansion of trinucleotide DNA repeats that cause numerous hereditary diseases. We highlight that these pathways, which originated in prokaryotes, may be subsequently hijacked to maintain long DNA microsatellites in eukaryotes. We suggest that the negative mutagenic outcomes of these pathways, exemplified by repeat expansion diseases, are likely outweighed by their positive role in (...) maintaining functional repetitive regions of the genome such as telomeres and centromeres. Break-induced replication and template switching are conserved mechanisms of replication fork restart. They do not cause microsatellite instability in prokaryotes, but promote repeat expansion in eukaryotes. We suggest that TS and BIR persisted in eukaryotes despite their mutagenic potential because they help maintain long repetitive telomeres and centromeres. (shrink)

This course book serves an undergraduate course in introduction to legal reasoning. It is designed to initiate students in the legal methods of case law analysis and statutory interpretation, prompting students to take a critical distance from the wielding of the methods. It helps students acquire or refine the techniques of close reading, analogizing, distinguishing, positing related fact patterns, and criticizing judicial and legislative exposition and logic.

The first 1000 days of life, from conception to 2 years, are a critical window for the influence of environmental exposures on the assembly of the oral microbiome, which is the precursor to dental caries (decay), one of the most prevalent microbially induced disorders worldwide. While it is known that the human microbiome is susceptible to environmental exposures, there is limited understanding of the impact of prenatal and early childhood exposures on the oral microbiome trajectory and oral health. A barrier (...) has been the lack of technology to directly measure the foetal "exposome", which includes nutritional and toxic exposures crossing the placenta. Another barrier has been the lack of statistical methods to account for the high dimensional data generated by‐omic assays. Through identifying which early life exposures influence the oral microbiome and modify oral health, these findings can be translated into interventions to reduce dental decay prevalence. (shrink)

This article tracks Corporate Social Responsibility (CSR) as an emergent organizational process that places the employee at its center. Predominantly, research on CSR tends to focus on external pressures and outcomes leading to a neglect of CSR as a dynamic and developing process that relies on the involvement of the employee as a major stakeholder in its co-creation and implementation. Utilizing case study data drawn from a study of a large multinational energy company, we explore how management relies on employees' (...) interaction with CSR as the process of initiation → implementation → maturation develops. Employee involvement grows from a minor element in the CSR initiation stage to a vital contributory factor in CSR's success in the later stages of the process. The article offers new insights into a processual and interactional approach to CSR that accounts for the actions of different actors involved at each stage. Most unusually, it also recognizes the dual impact this has on broader issues concerning the management and involvement of employees through CSR actions, and gaining legitimacy in the eyes of not only external stakeholders but internal too. (shrink)

While simulation has been a staple of Social Studies curricula since the 1960s, few current studies have sought to understand the mechanisms behind how simulations may influence students’ learning and behavior. Learning theories around student engagement – specifically interest development theory (Hidi & Renninger, 2006) – may help explain students’ commitment to future political action. To incorporate this theory into the democratic education literature, this study asks: Do situational interest and simulation frequency uniquely contribute to students’ commitment to vote in (...) the future? Data included 260 students from 19 classrooms, 9 teachers, in 9 schools, recruited as part of a larger mixed-methods study on Project Based Learning. Hierarchical Linear Modeling (HLM) techniques were used to examine the relationship between individual outcomes and predictors across different classrooms and teachers. Analysis of data suggests both frequency of simulations and situational interest directly predict students’ commitment to vote but do not uniquely contribute to the outcome. Findings suggest situational interest may play an important role in influencing students’ learning and future political behavior. (shrink)

The need for better incorporation of the construct emotional intelligence (EI) into counterproductive work behavior (CWB) research may be achieved via a unified conceptual framework. Accordingly, the purpose of this paper is to use the Profile Analysis via Multidimensional Scaling (PAMS) approach, a conceptual framework that unifies motivational process with antecedents and outcomes, to assess differences in EI concerning a variety of constructs: organizational justice, CWB, emotional exhaustion, job satisfaction, and intrinsic motivation. Employing established scales within a framework unifying CWB, (...) intrinsic motivation, EI, organizational justice, and outcome constructs, two EI-based profiles displayed associations with CWB based on responses from 3,293 employees. Both the first core profile, high overall justice and low emotional intelligence, and the second core profile, high emotional intelligence and low work motivation, displayed associations with interpersonal deviance and organizational deviance, as well as emotional exhaustion and job satisfaction. The results are discussed with respect to possible underlying theory and an overarching unified motivation framework that incorporates goal choice, intrinsic motivation, antecedents, and outcomes. We also provide directions for future research and implications for managers in the workplace based on heuristic conceptual frameworks that combine multiple motivational perspectives into a unified model. (shrink)

Informed by Critical Race Theory, this quantitative study supports civic educators in understanding the role of classroom climate and racial identity in students’ civic engagement during a statewide middle school civics mandate (n = 4707). Findings reveal that students of color experience higher civic engagement and lower civic attitude scores than white-identifying peers, after controlling for school, classroom, and affluence indicators. Students’ perception of whiteness (or perhaps majority status) appeared to correlate with positive civic knowledge and civic attitude, but relative (...) civic inaction. These findings suggest differences in civic outcomes as early as middle school between white-identifying students and students of color. Such differences offer implications for civic education interventions that address not only effective instruction, but civic inequities, students’ perceived agency, and curricular content. (shrink)

This book is an annotated translation, with introduction and commentary, of the correspondence between Yi Hwang (T'oegye, 1500-1570) and Ki Taesung (Kobong, 1527-1572) and between Yi I (Yulgok, 1536-1584) and Song Hon (Ugye, 1535-1598), known as the Four-Seven Debate, the most famous philosophical controversy in Korean Neo-Confucian thought. The most complex issues and difficult tensions in the great Neo-Confucian synthesis are at the juncture between the metaphysics of the cosmos and the human psyche. The Four-Seven Debate is perhaps the most (...) searching examination of this tension ever carried out. (shrink)

Are mechanisms for social attention influenced by culture? Evidence that social attention is triggered automatically by bottom-up gaze cues and is uninfluenced by top-down verbal instructions may suggest it operates in the same way everywhere. Yet considerations from evolutionary and cultural psychology suggest that specific aspects of one's cultural background may have consequence for the way mechanisms for social attention develop and operate. In more interdependent cultures, the scope of social attention may be broader, focusing on more individuals and relations (...) between those individuals. We administered a multi-gaze cueing task requiring participants to fixate a foreground face flanked by background faces and measured shifts in attention using eye tracking. For European Americans, gaze cueing did not depend on the direction of background gaze cues, suggesting foreground gaze alone drives automatic attention shifting; for East Asians, cueing patterns differed depending on whether the foreground cue matched or mismatched background cues, suggesting foreground and background gaze information were integrated. These results demonstrate that cultural background influences the social attention system by shifting it into a narrow or broad mode of operation and, importantly, provides evidence challenging the assumption that mechanisms underlying automatic social attention are necessarily rigid and impenetrable to culture. (shrink)

The Council on Ethical and Judicial Affairs of the American Medical Association examines physicians’ professional ethical responsibility in the event that the security of patients’ electronic records is breached.

A crisis continues to brew within the pharmaceutical research and development (R&D) enterprise: productivity continues declining as costs rise, despite ongoing, often dramatic scientific and technical advances. To reverse this trend, we offer various suggestions for both the expansion and broader adoption of modeling and simulation (M&S) methods. We suggest strategies and scenarios intended to enable new M&S use cases that directly engage R&D knowledge generation and build actionable mechanistic insight, thereby opening the door to enhanced productivity. What M&S requirements (...) must be satisfied to access and open the door, and begin reversing the productivity decline? Can current methods and tools fulfill the requirements, or are new methods necessary? We draw on the relevant, recent literature to provide and explore answers. In so doing, we identify essential, key roles for agent-based and other methods. We assemble a list of requirements necessary for M&S to meet the diverse needs distilled from a collection of research, review, and opinion articles. We argue that to realize its full potential, M&S should be actualized within a larger information technology framework—a dynamic knowledge repository—wherein models of various types execute, evolve, and increase in accuracy over time. We offer some details of the issues that must be addressed for such a repository to accrue the capabilities needed to reverse the productivity decline. (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)

One of the problems in economics that economists have devoted a considerable amount of attention in prevalent years has been to ensure consistency in the models they employ. Assuming markets to be generally in some state of equilibrium, it is asked under what circumstances such equilibrium is possible. The fundamental mathematical tools used to address this concern are fixed point theorems: the conditions under which sets of assumptions have a solution. This book gives the reader access to the mathematical techniques (...) involved and goes on to apply fixed point theorems to proving the existence of equilibria for economics and for co-operative and noncooperative games. Special emphasis is given to economics and games in cases where the preferences of agents may not be transitive. The author presents topical proofs of old results in order to further clarify the results. He also proposes fresh results, notably in the last chapter, that refer to the core of a game without transitivity. This book will be useful as a text or reference work for mathematical economists and graduate and advanced undergraduate students. (shrink)

This paper evaluates and criticises the developmental systems conception of evolution and develops instead an extension of the gene's eye conception of evolution. We argue (i) Dawkin's attempt to segregate developmental and evolutionary issues about genes is unsatisfactory. On plausible views of development it is arbitrary to single out genes as the units of selection. (ii) The genotype does not carry information about the phenotype in any way that distinguishes the role of the genes in development from that other factors. (...) (iii) There is no simple and general causal criterion which distinguishes the role of genes in development and evolution. (iv) There is, however, an important sense in which genes but not every other developmental factor represent the phenotype. (v) The idea that genes represent features of the phenotype forces us to recognise that genes are not the only, or almost the only, replicators. Many mechanisms of replication are involved in both development and evolution. (vi) A conception of evolutionary history which recognises both genetic and non-genetic replicators, lineages of replicators and interactors has advantages over both the radical rejection of the replicator/interactor distinction and the conservative restriction of replication to genetic replication. (shrink)

This question is the theme uniting all these essays by lead Chinese and Western philosophers.

Volume 19, Issue 10, October 2019, Page 57-59.

Nursing programs are complex systems that articulate values of relationality and holism, while developing curriculums that privilege metric‐driven competency‐based pedagogies. This study used an interpretive approach to analyze interviews from 20 nursing students at two Canadian Baccalaureate programs to understand how nursing's educational context, including its hidden curriculums, impacted student writing activities. We viewed this qualitative data through the lens of activity theory. Students spoke about navigating a rigid writing context. This resulted in a hyper‐focus on “figuring out” the teacher (...) with minimal focus on the act of writing. Students used a form of behavioral “code‐switching” to maximize their grade while considering how their “valuing” of the assignment fit within their writing motives. Hidden curriculum messages taught students that academic success was assured whether their writing mirrored instructor preferences. Instructional practices of rigidity reinforced unequal social conditions for some minority students. Faculty can counteract the impact of the hidden curriculum through encouragement of choice and independent thinking about writing activities. Acknowledging power relationships and their influence on how students navigate writing assignments and nursing discourse may relieve pressures on students who fear penalties for countering norms and result in a more flexible learning environment. (shrink)

With aims to both increase organ supply and better reflect individual donation preferences, many nations worldwide have shifted from ‘opt‐in’ to ‘opt‐out’ systems for post‐mortem organ donation (PMOD). In such countries, while a prospective donor's willingness to donate their organs/tissues for PMOD was previously ascertained—at least partially—by their having recorded positive donation preferences on an official register prior to death, this willingness is now presumed or inferred—at least partially—from their not having recorded an objection to PMOD—on an official organ donation (...) register. Using evidence regarding the presence and prevalence of selective donation preferences, and via exploration of how appeals to donation preferences are used to both motivate and legitimate shifts to opt‐out frameworks, this paper draws attention to a set of previously unexplored problems for opt‐out organ donation arising in contexts where: (a) individuals demonstrate selective post‐mortem organ/tissue donation preferences, (b) legislation provides prospective donors with the opportunity to selectively permit/refuse the donation of certain organs/tissues in line with these preferences. While selective preferences pose few problems for opt‐in systems where a selective occasion is built into the process of signing the donor register, this is not the case for opt‐out systems. The loss of this selective occasion can cause significant problems where appeals to preferences motivate/legitimate shifts to opt‐out but evidence regarding variable preferences does not feed into determinations regarding organ/tissue exclusions. The nature of these problems depends on how the authorization aspect of ‘opt‐out’ systems is framed (e.g. as presumed consent, deemed consent or, given the role of familial consent in many jurisdictions as consent in name only). (shrink)

Previous work has reported that children creatively make syntactic errors that are ungrammatical in their target language, but are grammatical in another language. One of the most well‐known examples is medial wh‐question errors in English‐speaking children's wh‐questions (e.g., What do you think who the cat chased? from Thornton, 1990). The evidence for this non‐target‐like structure in both production and comprehension has been taken to support the existence of innate, syntactic parameters that define all possible grammatical variation, which serve as a (...) top‐down constraint guiding children's language acquisition process. The present study reports new story‐based production and comprehension experiments that challenge this interpretation. While we replicated previous observations of medial wh‐question errors in children's sentence production (Experiment 1), we saw a reduction in evidence indicating that English‐speaking children assign interpretations that conform to the medial wh‐question pattern (Experiment 2). Crucially, we found no correlation between production and comprehension errors (Experiment 3). We suggest that these errors are the result of children's immature sentence production mechanisms rather than immature grammatical knowledge. (shrink)

Studies suggest that when a language requires grammatical marking of future events, speakers prefer immediate payoffs and engage in less future-oriented behavior. If future costs of tax avoidance are non-trivial, we posit that strong future time reference in languages would lower managers’ perceptions about costs, encouraging more tax avoidance. Using a large sample of 56,243 firm-year observations across 31 countries, we find that tax avoidance is higher where FTR in the language is strong. We also find that tax avoidance is (...) more prevalent in Swiss regions with strong FTR and in US firms whose CEOs were born in countries with strong FTR. Collectively, our evidence suggests that costs of tax avoidance can be non-trivial, and that linguistically driven time perception helps explain the cross-country variation in tax avoidance. (shrink)

Background: Empirical ethics inquiry works from the notion that stakeholder perspectives are necessary for gauging the ethical acceptability of human studies and assuring that research aligns with societal expectations. Although common, studies involving different populations often entail comparisons of trends that problematize the interpretation of results. Using graphical model selection—a technique aimed at transcending limitations of conventional methods—this report presents data on the ethics of clinical research with two objectives: (1) to display the patterns of views held by ill and (...) healthy individuals in clinical research as a test of the study's original hypothesis and (2) to introduce graphical model selection as a key analytic tool for ethics research. Methods: In this institutional review board (IRB)-approved, National Institutes of Health-funded project, data were collected from 60 mentally ill and 43 physically ill clinical research protocol volunteers, 47 healthy protocol-consented participants, and 29 healthy individuals without research protocol experience. Respondents were queried on the ethical acceptability of research involving people with mental and physical illness (i.e., cancer, HIV, depression, schizophrenia, and posttraumatic stress disorder) and non-illness-related sources of vulnerability (e.g., age, class, gender, ethnicity). Using a statistical algorithm, we selected graphical models to display interrelationships among responses to questions. Results: Both mentally and physically ill protocol volunteers revealed a high degree of connectivity among ethically salient perspectives. Healthy participants, irrespective of research protocol experience, revealed patterns of views that were not highly connected. Conclusions: Between ill and healthy protocol participants, the pattern of views was vastly different. Experience with illness was tied to dense connectivity, whereas healthy individuals expressed views with sparse connections. In offering a nuanced perspective on the interrelation of ethically relevant responses, graphical model selection has the potential to bring new insights to the field of ethics. (shrink)

Little is known about how individuals with and without mood disorders perceive the inherent risks and helpfulness of participating in innovative psychiatric research, or about the factors that influence their willingness to participate. We conducted an online survey with 80 individuals (self-reported mood disorder [n = 25], self-reported good health [n = 55]) recruited via MTurk. We assessed respondents’ perceptions of risk and helpfulness in study vignettes associated with two innovative research projects (intravenous ketamine therapy and wearable devices), as well (...) as their willingness to participate in these projects. Respondents with and without mood disorders perceived risk similarly across projects. Respondents with no mood disorders viewed both projects as more helpful to society than to research volunteers, while respondents with mood disorders viewed the projects as equally helpful to volunteers and society. Individuals with mood disorders perceived ketamine research, and the two projects on average, as more helpful to research volunteers than did individuals without mood disorders. Our findings add to a limited empirical literature on the perspectives of volunteers in innovative psychiatric research. (shrink)

Since its founding in 1943, Medievalia et Humanistica has won worldwide recognition as the first scholarly publication in America to devote itself entirely to medieval and Renaissance studies. Since 1970, a new series, sponsored by the Modern Language Association of America and edited by an international board of distinguished scholars and critics, has published interdisciplinary articles. In yearly hardbound volumes, the new series publishes significant scholarship, criticism, and reviews treating all facets of medieval and Renaissance culture: history, art, literature, music, (...) science, law, economics, and philosophy. (shrink)

Over the past 20 years or so, a small but growing literature has emerged with the aim of modeling agents who are unaware of certain things. In this paper we compare two different approaches to modeling unawareness: the object-based approach of Board and Chung (Object-based unawareness: theory and applications. University of Minnesota, Mimeo, 2008) and the subjective-state-space approach of Heifetz et al. (J Econ Theory 130: 78-94,2006). In particular, we show that subjectivestate-space models (henceforth HMS structures) can be embedded within (...) object-based models (henceforth OBU structures), demonstrating that the latter are at least as expressive. As long as certain restrictions are imposed on the form of the OBU structure, the embedding can also go the other way. A generalization of HMS structures (relaxing the partitional properties of knowledge) gives us a full converse. (shrink)