The major challenge in complex disease genetics is to understand the fundamental features of this complexity and why functional alterations at multiple independent genes conspire to lead to an abnormal phenotype. We hypothesize that the various genes involved are all functionally united through gene regulatory networks (GRN), and that mutant phenotypes arise from the consequent perturbation of one or more rate‐limiting steps that affect the function of the entire GRN. Understanding a complex phenotype thus entails unraveling the details of each (...) GRN, namely, the transcription factors that bind to cis regulatory elements affected by sequence variants altering transcription of specific genes, and their mutual feedback relationships. These GRNs can be identified through their rate‐limiting steps and are best uncovered by genomic analyses of rare, extreme phenotype families, thus providing a coherent molecular basis to complex traits and disorders. (shrink)

Sex chromosomes are advantageous to mammals, allowing them to adopt a genetic rather than environmental sex determination system. However, sex chromosome evolution also carries a burden, because it results in an imbalance in gene dosage between females (XX) and males (XY). This imbalance is resolved by X dosage compensation, which comprises both X chromosome inactivation and X chromosome upregulation. X dosage compensation has been well characterized in the soma, but not in the germ line. Germ cells face a special challenge, (...) because genome wide reprogramming erases epigenetic marks responsible for maintaining the X dosage compensated state. Here we explain how evolution has influenced the gene content and germ line specialization of the mammalian sex chromosomes. We discuss new research uncovering unusual X dosage compensation states in germ cells, which we postulate influence sexual dimorphisms in germ line development and cause infertility in individuals with sex chromosome aneuploidy. (shrink)

Despite its effectiveness, limited research has examined the provision of telemental health and how practices may vary according to treatment paradigm. We surveyed 276 community mental health providers registered with a commercial telemedicine platform. Most providers reported primarily offering TMH services to adults with anxiety, depression, and trauma-and stressor-related disorders in individual therapy formats. Approximately 82% of TMH providers reported endorsing the use of Cognitive Behavioral Therapy in their remote practice. The most commonly used in-session and between-session exercises included coping (...) and emotion regulation, problem solving, mindfulness, interpersonal skills, relaxation, and modifying and addressing core beliefs. CBT TMH providers had a higher odds of using in-session and homework exercises and assigning them through postal mail, email or fax methods, as compared to non-CBT TMH providers. TMH providers, regardless of treatment paradigm, felt that assigning homework was neither easy nor difficult and they believed their patients were somewhat-to-moderately compliant to their assigned exercises. CBT TMH providers also collected clinical information from their patients more often than non-CBT TMH providers. They reported being less satisfied with their method, which was identified most often as paper-based surveys and forms. Overall, TMH providers employ evidence-based treatments to their patients remotely, with CBT TMH providers most likely to do so. Findings highlight the need for innovative solutions to improve how TMH providers that endorse following the CBT treatment paradigm remotely assign homework and collect clinical data to increase their satisfaction via telemedicine. (shrink)

Aims. Currently, methylphenidate (MPH, trade name Ritalin) is the most widely prescribed medication for attention deficit/hyperactivity disorder (ADHD). We examined the ability of repeated MPH administration to produce a sensitized appetitive eagerness type response in laboratory rats, as indexed by 50-kHz ultrasonic vocalizations (50-kHz USVs). We also examined the ability of MPH to reduce play behavior in rats which may be partially implicated in the clinical efficacy of MPH in ADHD. Design. 56 adolescent rats received injections of either 5.0 mg/kg (...) MPH, or vehicle each day for 8 consecutive days, and a week later received a challenge injection of either MPH or vehicle. Measurements. Both play behavior (pins) and 50-kHz USVs were recorded after each drug or vehicle administration. Results. MPH challenge produced a substantial 73% reduction in play behavior during the initial treatment phase, and during the last test (1 week post drug), 50-kHz USVs were elevated approximately threefold only in animals with previous MPH experience. Conclusions. These data suggest that MPH treatment may lead to psychostimulant sensitization in young animals, perhaps by increasing future drug-seeking tendencies due to an elevated eagerness for positive incentives. Further, we hypothesize that MPH may be reducing ADHD symptoms, in part, by blocking playful tendencies, whose neuro-maturational and psychological functions remain to be adequately characterized. (shrink)

Our understanding of the nature and processing of figurative language is central to several important issues in cognitive science, including the relationship of language and thought, how we process language, and how we comprehend abstract meaning. Over the past fifteen years, traditional approaches to these issues have been challenged by experimental psychologists, linguists, and other cognitive scientists interested in the structures of the mind and the processes that operate on them. In Figurative Language and Thought, internationally recognized experts in the (...) field of figurative language, Albert Katz, Mark Turner, Raymond W. Gibbs Jr., and Cristina Cacciari, provide a coherent and focused debate on the subject. The book's authors discuss a variety of fundamental questions, including: What can figures of speech tell us about the structure of the conceptual system? If and how should we distinguish the literal from the nonliteral in our theories of language and thought? Are we primarily figurative thinkers and consequently figurative language users or the other way around? Why do we prefer to speak metaphorically in everyday conversation, when literal options may be available for use? Is metaphor the only vehicle through which we can understand abstract concepts? What role do cultural and social factors play in our comprehension of figurative language? These and related questions are raised and argued in an integrative look at the role of nonliteral language in cognition. This volume, a part of Counterpoints series, will be thought-provoking reading for a wide range of cognitive psychologists, linguists, and philosophers. (shrink)

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to (...) existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource providing details on the people, policies, and issues being addressed in association with OBI. (shrink)

Previous research on the moral foundations of transformational leadership has focused primarily on stage of justice reasoning; this study focuses on developmental mode of care reasoning. Multilevel regression analyses were conducted on data coded from interviews with a sample of Canadian public sector managers ( N = 58) and survey responses from their subordinates ( N = 119). Results indicated that managers’ developmental mode of care reasoning significantly and positively predicted subordinates’ reports of transformational (but not transactional) leadership, with significant (...) differences in follower reports of transformational leadership between those using more versus less advanced modes of care reasoning. Conceptual implications for understanding transformational leadership and the ethics of leadership, directions for future research, and suggestions for leadership interventions are discussed. (shrink)

This article provides ethical guidance on using race in health research as a variable or in defining the study population. To this end, a plain, non-exhaustive checklist is provided for researchers and research ethics committees, preceded by a brief introduction on the need for justification when using race as a variable or in defining a study population, the problem of exoticism, that distinctions pertain between race, ethnicity and ancestry, the problematic naming of races, and that race does not serve well (...) as a presumed biological construct in genetic research. (shrink)

BackgroundMedical ethics has recently seen a drive away from multiple prescriptive approaches, where physicians are inundated with guidelines and principles, towards alternative, less deontological perspectives. This represents a clear call for theory building that does not produce more guidelines. Phronesis (practical wisdom) offers an alternative approach for ethical decision-making based on an application of accumulated wisdom gained through previous practice dilemmas and decisions experienced by practitioners. Phronesis, as an ‘executive virtue’, offers a way to navigate the practice virtues for any (...) given case to reach a final decision on the way forward. However, very limited empirical data exist to support the theory of phronesis-based medical decision-making, and what does exist tends to focus on individual practitioners rather than practice-based communities of physicians.MethodsThe primary research question was: What does it mean to medical practitioners to make ethically wise decisions for patients and their communities? A three-year ethnographic study explored the practical wisdom of doctors (n = 131) and used their narratives to develop theoretical understanding of the concepts of ethical decision-making. Data collection included narrative interviews and observations with hospital doctors and General Practitioners at all stages in career progression. The analysis draws on neo-Aristotelian, MacIntyrean concepts of practice- based virtue ethics and was supported by an arts-based film production process.ResultsWe found that individually doctors conveyed many different practice virtues and those were consolidated into fifteen virtue continua that convey the participants’ ‘collective practical wisdom’, including the phronesis virtue. This study advances the existing theory and practice on phronesis as a decision-making approach due to the availability of these continua.ConclusionGiven the arguments that doctors feel professionally and personally vulnerable in the context of ethical decision-making, the continua in the form of a video series and app based moral debating resource can support before, during and after decision-making reflection. The potential implications are that these theoretical findings can be used by educators and practitioners as a non-prescriptive alternative to improve ethical decision-making, thereby addressing the call in the literature, and benefit patients and their communities, as well. (shrink)

C endorses the doctrine of Composition as Identity, which holds that a composite object is identical to its many parts, and entails that one object can be identical to several others. In this dialogue, N argues that many‐one identity, and thus composition as identity, is conceptually confused. In particular, N claims it violates two conceptual truths: that existence facts fix identity facts, and that identity is no addition to being. In response to pressure from C, N considers several candidate interpretations (...) of the first slogan. Each interpretation imagines God issuing a divine existential decree that counts as ‘fixing the existence facts’, and then considers what questions about identity are left open by it. N eventually hits on an appealing interpretation of the slogan that C can neither undermine nor accommodate, and uses it to interpret the second slogan as well. (shrink)

Al-Maʾmūn, the Inquisition, and the Quest for Caliphal Authority. By John Abdallah Nawas. Resources in Arabic and Islamic Studies, vol. 4. Atlanta: Lockwood Press, 2015. Pp. xvi + 340. $45.

C endorses the doctrine of Composition as Identity, which holds that a composite object is identical to its many parts, and entails that one object can be identical to several others. In this dialogue, N argues that many‐one identity, and thus composition as identity, is conceptually confused. In particular, N claims it violates two conceptual truths: that existence facts fix identity facts, and that identity is no addition to being. In response to pressure from C, N considers several candidate interpretations (...) of the first slogan. Each interpretation imagines God issuing a divine existential decree that counts as ‘fixing the existence facts’, and then considers what questions about identity are left open by it. N eventually hits on an appealing interpretation of the slogan that C can neither undermine nor accommodate, and uses it to interpret the second slogan as well. (shrink)

It is a common complaint that sociology has little regard for history. One important exception to this standard criticism is the sociology of religion of Robert N. Bellah and his ‘revival’ of Karl Jasper’s notion of the axial age. In this article, Bellah’s evolutionary notions of religion are explored within a debate about historical disjunctures and continuities. A significant challenge to the idea of the continuity of axial-age religions comes from the notion of an Anthropocene. Our relationship to nature has (...) fundamentally changed and the possibilities for ‘improving’ the human body create a significant ontological challenge to the continuity/preservation of embodied practice as the underpinning of axial-age religions. The Anthropocene age presents a turning away from the religious legacies of the past, because biotechnical developments change not only our relationship to nature but they presage a radical change to the human body. Can the axial-age religions as our contemporaries survive the construction of hybrid post-bodies? In conclusion, insofar as there has been a ‘protestantization’ of religions with modernity involving an erosion of habitualized religion, an individualized and dis-embodied religiosity may be compatible with our anthropocenic future, but this possibility represents a discontinuity with the past and not a continuity. (shrink)

The N ational Assembly held in the Frankfurt Paulskirche in 1848, which opened w ith high hopes for the unification o f Germ any on parliam entary constitutional principles, was left to die a year later, in the telling phrase o f D onoso Cortes, ‘like a street w om an in the gu tter’. In the period o f reaction that followed, during w hich the Paulskirche convention came to be described as the ‘parliam ent o f pro­ fessors’, (...) one o f its m em bers, Georg G ottfried Gervinus, was accused, in a trial for high treason, o f attem pting to prove the historical inevitability o f the supersession o f monarchical forms by republican forms. This was Gervinus’s second experience as a professorial m artyr. In 1837 he had been one o f the professors at the U niversity o f G ottingen, the ‘Gottingen Seven’, w ho protested the revocation o f the H anoverian constitution. For this he had been banished and given three days to leave the kingdom. The lesson he, and m any other liberal thinkers, learned from these experiences was that the Germ an middle classes were incapable o f perform ing the historical role assigned to them; they lacked the political will to establish a republican order. (shrink)

For a century and a half, the artists and intellectuals of Europe have scorned the bourgeoisie. And for a millennium and a half, the philosophers and theologians of Europe have scorned the marketplace. The bourgeois life, capitalism, Mencken’s “booboisie” and David Brooks’s “bobos”—all have been, and still are, framed as being responsible for everything from financial to moral poverty, world wars, and spiritual desuetude. Countering these centuries of assumptions and unexamined thinking is Deirdre McCloskey’s _The Bourgeois Virtues_, a magnum opus (...) that offers a radical view: capitalism is good for us. McCloskey’s sweeping, charming, and even humorous survey of ethical thought and economic realities—from Plato to Barbara Ehrenreich—overturns every assumption we have about being bourgeois. Can you be virtuous and bourgeois? Do markets improve ethics? Has capitalism made us better as well as richer? Yes, yes, and yes, argues McCloskey, who takes on centuries of capitalism’s critics with her erudition and sheer scope of knowledge. Applying a new tradition of “virtue ethics” to our lives in modern economies, she affirms American capitalism without ignoring its faults and celebrates the bourgeois lives we actually live, without supposing that they must be lives without ethical foundations. _High Noon_, Kant, Bill Murray, the modern novel, van Gogh, and of course economics and the economy all come into play in a book that can only be described as a monumental project and a life’s work. _The Bourgeois Virtues _is nothing less than a dazzling reinterpretation of Western intellectual history, a dead-serious reply to the critics of capitalism—and a surprising page-turner. (shrink)

This study examines the family environments and hormone profiles of 316 individuals aged 2 months-58 years residing in a rural village on the east coast of Dominica, a former British colony in the West Indies. Fieldwork was conducted over an eight-year period (1988–1995). Research methods and techniques include radioimmunoassay of cortisol and testosterone from saliva samples (N=22,340), residence histories, behavioral observations of family interactions, extensive ethnographic interview and participant observation, psychological questionnaires, and medical examinations.Analyses of data indicate complex, sex-specific effects (...) of family environment on endocrine function. Male endocrine profiles exhibit greater sensitivity to presence of father than do female endocrine profiles. Father-absent males tend to have (a) low cortisol levels during infancy, (b) high or abnormal cortisol profiles during childhood and adolescence, and (c) high cortisol and low testosterone levels during adulthood compared with those of males raised with a resident father. These results indicate that early family environment has significant effects on endocrine response throughout male life histories. (shrink)

Çağımızın seçkin kültür ve düşünce tarihçilerinden Frank Turner’ın Yale Üniversite’sinde verdiği derslerden oluşan Rousseau’dan Nietzsche’ye Avrupa Düşünce Tarihi, Aydınlanma döneminden yirminci yüzyılın başına dek Avrupa’da yaşanan radikal değişimi fikir akımları ve öncü figürler üzerinden anlatıyor. Oxford Today’in editörü Richard Lofthouse tarafından derlenen bu dersler, farklı disiplinleri ustaca bir araya getirerek döneme dair kapsamlı bir bakış açısı sunuyor. Yale’in en sevilen hocalarından Turner’ın açık, akıcı ve öğretici üslubu sayesinde düşünce tarihinin zorlu dönemeçlerinde kolaylıkla yol alacak, dersler bittikten sonra kitabın (...) sonundaki okuma listesini takip ederek daha fazlasını öğrenmek isteyeceksiniz. (shrink)

The central claim of a Consummation Anyway model is that God could bring about eschatological consummation sans the fall—the intended telos of created humanity—apart from the incarnation of Christ. As such, the CA model is an alternative to an Incarnation Anyway model, according to which Christ’s incarnation is a necessary means by which a state of eschatological glory would be achieved sans the fall. This essay seeks to propose an argument for the CA model by drawing from the covenant theology (...) of the Reformed tradition, and it moves in four steps. Firstly, I shall summarize Marc Cortez’s recent arguments for IA, homing in on the major moves that are most relevant for sketching a CA model. Secondly, I will highlight the challenges Cortez has offered against those interested in defending a CA model. Thirdly, I shall sketch a Reformed account of the CA model that seeks to address Cortez’s objections. Fourthly, then, I’ll consider two potential objections against the sketch I have offered for CA, inspired by a recent argument offered by James T. Turner. Finally, I close with a brief conclusion that summarizes some salient features of the proposed thesis. This paper thus proposes at least one way in which the CA thesis could remain a real and live option within this debate. (shrink)

The N‐terminal domain of histone H4 has been implicated in various nuclear functions, including gene silencing and activation and replication‐linked chromatin assembly. Many of these have been identified by using H4 mutants in the yeast S. cerevisiae. In a recent paper, Megee et al.(1) use this approach to show that mutants in which all four N‐terminal H4 lysines are substituted with glutamines accumulate increased levels of DNA damage. A single lysine, but not an arginine, anywhere in the N‐terminal domain suppresses (...) this phenotype. It is suggested that histone H4 plays a role in maintaining genome integrity through the cell cycle, possibly by a mechanism involving lysine acetylation. (shrink)

This empirical investigation showed that contrary to the popular notion that apologies signify weakness, the victims of mistakes made by leaders consistently perceived leaders who apologized as more transformational than those who did not apologize. In a field experiment (Study 1), male referees who were perceived as having apologized for mistakes made officiating hockey games were rated by male coaches (n = 93) as more transformational than when no apology was made. Studies 2 (n = 50) and 3 (n = (...) 224) replicated this effect in two vignette studies to enhance internal and ecological validity. Contrary to expectations in Study 3, there were no apology×leader gender interactions. Theoretical and practical implications are discussed. (shrink)

Denys Turner argues that there are reasons of faith why the existence of God should be thought rationally demonstrable and that it is worthwhile revisiting the theology of Thomas Aquinas to see why. The proposition that the existence of God is demonstrable by rational argument is doubted by nearly all philosophical opinion today and is thought by most Christian theologians to be incompatible with Christian faith. Turner's robust challenge to the prevailing orthodoxies will be of interest to believers (...) as well as non-believers. (shrink)

Incompatibilists believe free will is impossible if determinism is true, and they often claim that this view is supported by ordinary intuitions. We challenge the claim that incompatibilism is intuitive to most laypersons and discuss the significance of this challenge to the free will debate. After explaining why incompatibilists should want their view to accord with pretheoretical intuitions, we suggest that determining whether incompatibilism is in fact intuitive calls for empirical testing. We then present the results of our studies, which (...) put significant pressure on the claim that incompatibilism is intuitive. Finally, we consider and respond to several potential objections to our approach. (shrink)

The concept of "practices"--whether of representation, of political or scientific traditions, or of organizational culture--is central to social theory. In this book, Stephen Turner presents the first analysis and critique of the idea of practice as it has developed in the various theoretical traditions of the social sciences and the humanities. Understood broadly as a tacit understanding "shared" by a group, the concept of a practice has a fatal difficulty, Turner argues: there is no plausible mechanism by which (...) a "practice" is transmitted or reproduced. The historical uses of the concept, from Durkheim to Kripke's version of Wittgenstein, provide examples of the contortions that thinkers have been forced into by this problem, and show the ultimate implausibility of the idea. Turner's conclusion sketches a picture of what happens when we do without the notion of a shared practice, and how this bears on social theory and philosophy. It explains why social theory cannot get beyond the stage of constructing fuzzy analogies, and why the standard constructions of the contemporary philosophical problem of relativism depend upon this defective notion. This first book-length critique of practice theory is sure to stir discussion and controversy in a wide range of fields, from philosophy and science studies to sociology, anthropology, literary studies, and political and legal theory. (shrink)

The human spark -- Catch a fire -- The idea of you -- The idea of I -- Forbidden ideas -- Artful ideas -- Vast ideas -- Tight ideas -- Recurring ideas -- Future ideas.