Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

Ethological theory standardly attributes representational content to animal signals. In this article I first assess whether Ruth Millikan’s teleosemantic theory accounts for the content of animal signals. I conclude that it does not, because many signals do not exhibit the required sort of cooperation between signal‐producing and signal‐consuming devices. It is then argued that Kim Sterelny’s proposal, while not requiring cooperation, sometimes yields the wrong content. Finally, I outline an alternative view, according to which consumers alone are responsible for conferring (...) representational status and determining content. I suggest that consumer‐based teleosemantics reconstruct the content of both cooperative and noncooperative signals and explain how a given trait can mean different things to different consumers. †To contact the author, please write to: Department of Philosophy, King’s College London, Strand, London WC2R 2LS, U.K.; e‐mail: ulrich[email protected]. (shrink)

Abstract In order to illuminate the role of information in biology, Bergstrom and Rosvall (Biol Philos 26:159–176, 2011a ; Biol Philos 26:195–200, 2011b ) propose a ‘transmission sense of information’ which builds on Shannon’s theory. At the core of the transmission sense is an appeal to the reduction in uncertainty in receivers and to etiological function. I explore several ways of cashing out uncertainty reduction as well as the consequences of appealing to function. Content Type Journal Article Pages 1-4 DOI (...) 10.1007/s10539-012-9310-x Authors Ulrich E. Stegmann, School of Divinity, History and Philosophy, University of Aberdeen, Old Brewery, High Street, Aberdeen, AB24 3UB UK Journal Biology and Philosophy Online ISSN 1572-8404 Print ISSN 0169-3867. (shrink)

One approach to assess the explanatory power of natural selection is to ask what type of facts it can explain. The standard list of explananda includes facts like trait frequencies or the survival of particular organisms. Here, I argue that this list is incomplete: natural selection can also explain a specific kind of individual-level fact that involves traits. The ability of selection to explain this sort of fact vindicates the explanatory commitments of empirical studies on microevolution. Trait facts must be (...) distinguished from a closely related kind of fact, that is, the fact that a particular individual x has one trait rather than another. Whether or not selection can explain the latter type of fact is highly controversial. According to the so-called ‘Negative View’ it cannot be explained by selection. I defend the Negative View against Nanay’s objection. (shrink)

A central idea of developmental systems theory is ‘parity’ or ‘symmetry’ between genes and non-genetic factors of development. The precise content of this idea remains controversial, with different authors stressing different aspects and little explicit comparisons among the various interpretations. Here I characterise and assess several influential versions of parity.

The genetic code has been regarded as arbitrary in the sense that the codon-amino acid assignments could be different than they actually are. This general idea has been spelled out differently by previous, often rather implicit accounts of arbitrariness. They have drawn on the frozen accident theory, on evolutionary contingency, on alternative causal pathways, and on the absence of direct stereochemical interactions between codons and amino acids. It has also been suggested that the arbitrariness of the genetic code justifies attributing (...) semantic information to macromolecules, notably to DNA. I argue that these accounts of arbitrariness are unsatisfactory. I propose that the code is arbitrary in the sense of Jacques Monod's concept of chemical arbitrariness: the genetic code is arbitrary in that any codon requires certain chemical and structural properties to specify a particular amino acid, but these properties are not required in virtue of a principle of chemistry. This notion of arbitrariness is compatible with several recent hypotheses about code evolution. I maintain that the code's chemical arbitrariness is neither sufficient nor necessary for attributing semantic information to nucleic acids. (shrink)

This paper explores John Maynard Smith’s conceptual work on animal signals. Maynard Smith defined animal signals as traits that (1) change another organism’s behaviour while benefiting the sender, that (2) are evolved for this function, and that (3) have their effects through the evolved response of the receiver. Like many ethologists, Maynard Smith assumed that animal signals convey semantic information. Yet his definition of animal signals remains silent on the nature of semantic information and on the conditions determining its content. (...) I therefore compare three ways to specify the semantic content of animal signals. The first suggestion models semantic content on Maynard Smith’s theory of genetic information. On the second proposal, semantic content is equated with a condition identified by conventional content ascriptions. The third suggestion is to explain semantic content in terms of consumer-based teleosemantics. I show how these accounts equate semantic content with distinct kinds of conditions and how they differ with respect to the kinds of traits that qualify as carrying semantic information. (shrink)

This paper assesses Sarkar's ([2003]) deflationary account of genetic information. On Sarkar's account, genes carry information about proteins because protein synthesis exemplifies what Sarkar calls a ‘formal information system’. Furthermore, genes are informationally privileged over non-genetic factors of development because only genes enter into arbitrary relations to their products (in virtue of the alleged arbitrariness of the genetic code). I argue that the deflationary theory does not capture four essential features of the ordinary concept of genetic information: intentionality, exclusiveness, asymmetry, (...) and causal relevance. It is therefore further removed from what is customarily meant by genetic information than Sarkar admits. Moreover, I argue that it is questionable whether the account succeeds in demonstrating that information is theoretically useful in molecular genetics. Introduction Sarkar's Information System The Pre-theoretic Features of Genetic Information 3.1 Intentionality 3.2 Exclusiveness 3.3 Asymmetry 3.4 Causal relevance Theoretical Usefulness Conclusion CiteULike Connotea Del.icio.us What's this? (shrink)

Much recent work on natural information has focused on probabilistic theories, which construe natural information as a matter of probabilistic relations between events or states. This paper assesses three variants of probabilistic theories (due to Millikan, Shea, and Scarantino and Piccinini). I distinguish between probabilistic theories as (1) attempts to reveal why probabilistic relations are important for human and non-human animals and as (2) explications of the information concept(s) employed in the sciences. I argue that the strength of probabilistic theories (...) lies in the first project. Probability-raising can enable organisms to draw specific inferences they otherwise could not entertain and I show how exactly they help to explain the behaviour of organisms. In addition, probability-raising warrants inferences by providing incremental inductive support. (shrink)

ABSTRACT Theodor Herzl once contemptuously remarked that he regards Freiland as a joke. This statement surprises if one compares his novel Altneuland to Theodor Hertzka's Freiland. To say the least, both utopias share many themes and narratives structures. While Altneuland became the world-renowned manifesto of Zionism, Freiland cherished popularity only at the time of its publication. Both novels are products of Vienna's fin-de-siècle modernism. Herzl's utopia is set in Palestine, Hertzka places Freiland in the empty space of East Africa. His (...) vision of a new civilization in Africa coincided with European colonialism, nationalism and the surge of anti-Semitism in Vienna. In the following, the essay investigates if Hertzka merely criticizes the culture of fin-de-siècle Vienna, or, if he produces a unique alternative? (shrink)

The literatures on both authentic leadership and behavioral integrity have argued that leader integrity drives follower performance. Yet, despite overlap in conceptualization and mechanisms, no research has investigated how authentic leadership and behavioral integrity relate to one another in driving follower performance. In this study, we propose and test the notion that authentic leadership behavior is an antecedent to perceptions of leader behavioral integrity, which in turn affects follower affective organizational commitment and follower work role performance. Analysis of a survey (...) of 49 teams in the service industry supports the proposition that authentic leadership is related to follower affective organizational commitment, fully mediated through leader behavioral integrity. Next, we found that authentic leadership and leader behavioral integrity are related to follower work role performance, fully mediated through follower affective organizational commitment. These relationships hold when controlling for ethical organizational culture. (shrink)

The concept of genetic information is controversial because it attributes semantic properties to what seem to be ordinary biochemical entities. I argue that nucleic acids contain information in a semantic sense, but only about a limited range of effects. In contrast to other recent proposals, however, I analyze genetic information not in terms of a naturalized account of biological functions, but instead in terms of the way in which molecules determine their products during processes known as template-directed syntheses. I argue (...) that determining an outcome in a certain way is constitutive for being an instruction. On this account, the content of genetic information is identified with the template's properties, which determine the product in the way constitutive for instructions. (shrink)

The Individual and the Political Order examines major theoretical perspectives, both historical and contemporary, in major issues in social and political philosophy. It combines accessibility with appreciation of philosophical complexity and discusses applied issues, such as morality and war, as well as theoretical approaches to justice, rights, and democratic liberal thought.

Recent political developments and disclosures of serious adverse events in human gene therapy (HGT) with the death of 18‐year old Jesse Gelsinger in the USA have shown that the clinical application of HGT raises some severe ethical issues. These have either been neglected or not yet been discussed to a satisfactory extent. In this paper, we will address this deficiency and develop strategies for a safer application of HGT. Such a study must first look closely at the science of HGT (...) itself. We will evaluate the latest preclinical research, especially data on the viruses that are used as vectors and on modes of administration of vectors. We will put forward new arguments concerning the toxicity assessment of so‐called ‘gene drugs‘, the tissue and cell type specificity of the vectors, and the duration and on‐set of gene expression. Secondly, we will look at procedural aspects of applied research ethics on the way to clinical application of HGT. There, informed consent (IC) and the patient‐researcher relationship are of utmost concern. Furthermore, we will explore the problem of expertise in risk assessment and will show how current regulations foster conflicts of interests that create dilemma situations even for those researchers who act in the best interest of the patients. We will conclude the article with a set of questions for ethicists who have to decide about the quality of HGT protocols. This may contribute to the safety of patients participating in HGT trials and to achieving the aim of efficient application of HGT. (shrink)

Promoting translational research as a means to overcoming chasms in the translation of knowledge through successive fields of research from basic science to public health impacts and back is a central challenge for research managers and policymakers. Organizational leaders need to assess baseline conditions, identify areas needing improvement, and to judge the impact of specific initiatives to sustain or improve translational research practices at their institutions. Currently, there is a lack of such an assessment tool addressing the specific context of (...) translational biomedical research. To close this gap, we have developed a new survey for assessing theorganizational climate for translational research. This self-assessment tool measures employees’ perceptions of translational research climate and underlying research practices in organizational environments and builds on the established Survey of Organizational Research Climate, assessing research integrity. Using this tool, we show that scientists at a large university hospital (Charité Berlin) perceive translation as a central and important component of their work. Importantly, local resources and direct support are main contributing factors for the practical implementation of translation into their own research practice. We identify and discuss potential leverage points for an improvement of research climate to foster successful translational research. (shrink)

Philosophers have recently paid more attention to the physical aspects of scientific models. The attention is motivated by the prospect that a model’s physical features strongly affect its use and that this suggests re-thinking modelling in terms of extended or distributed cognition. This paper investigates two ways in which physical features of scientific models affect their use and it asks whether modelling is an instance of extended cognition. I approach these topics with a historical case study, in which scientists kept (...) records not only of their findings, but also of some the mental operations that generated the findings. The case study shows how scientists can employ a physical model as an external information store, which allows alternating between mental manipulations, recording the outcome externally, and then feeding the outcome back into subsequent mental manipulations. The case study also demonstrates that a models’ physical nature allows replacing explicit reasoning with visuospatial manipulations. I argue, furthermore, that physical modelling does not need to exemplify a strong kind of extended cognition, the sort for which external features are mereological parts of cognition. It can exemplify a weaker kind, instead. (shrink)

This collection of essays considers a variety of educational ideas and programs from the perspective of governmentality, integrating conceptual and theoretical insights and empirical investigation of policy documents, and government technologies. Considers different educational ideas of enlightenment, creativity, participation, inclusion, learning, and critique Offers an overview of French philosopher Michel Foucault’s theory on governmentality and how his ideas apply to current developments in society and education Investigates the intrinsic relationship between intellectual and practical educational technologies A study of how educational (...) practice and educational theory have played a constitutive role in practices of subjectivity which are crucial to ‘learning societies’. (shrink)

Cancer is a singular cellular state, the emergence of which destabilises the homeostasis reached through the evolution to multicellularity. We present the idea that the onset of the cellular disobedience to the metazoan functional and structural architecture, known as the cancer phenotype, is triggered by changes in the cell's external environment that occur with ageing: what ensues is a breach of the social contract of multicellular life characteristic of metazoans. By integrating old ideas with new evidence, we propose that with (...) ageing the environmental information that maintains a multicellular organisation is eroded, rewiring internal processes of the cell, and resulting in an internal shift towards an ancestral condition resulting in the pseudo‐multicellular cancer phenotype. Once that phenotype emerges, a new local social contract is built, different from the homeostatic one, leading to tumour formation and the foundation of a novel local ecosystem. (shrink)

In their paper “Research approvals iceberg: how a ‘low-key’ study in England needed 89 professionals to approve it and how we can do better” Petrova and Barclay highlight concerns with the health research regulatory environment in the UK. As long-standing chairs of NHS research ethics committees, researchers, and also academics in research ethics, we are also often frustrated with the regulatory process in the UK. However, we think that Petrova and Barclay’s analysis is misleading because it conflates research ethics with (...) governance and funding processes, thus failing to adequately distinguish between the national coordinating function of the Health Research Authority, local research governance processes, and interactions with research sponsors and/or the Clinical Research Network. (shrink)

Diagrams can serve as representational models in scientific research, yet important questions remain about how they do so. I address some of these questions with a historical case study, in which diagrams were modified extensively in order to elaborate an early hypothesis of protein synthesis. The diagrams’ modelling role relied mainly on two features: diagrams were modified according to syntactic rules, which temporarily replaced physico-chemical reasoning, and diagram-to-target inferences were based on semantic interpretations. I then explore the lessons for the (...) relative roles of syntax, semantics, external marks, and mental images, for justifying diagram-to-target inferences, and for the “artefactual approach” to scientific models. (shrink)

The Covid-19 pandemic has intensified interest in animals with superior antiviral defences. I argue that the role of such animals in biomedical research contrasts with the role of disease models.

Context: This paper outlines how radical constructivist theory has led to a particular methodological technique, developing second-order models of student thinking, that has helped mathematics educators to be more effective teachers of their students. Problem: The paper addresses the problem of how radical constructivist theory has been used to explain and engender more viable adaptations to the complexities of teaching and learning. Method: The paper presents empirical data from teaching experiments that illustrate the process of second-order model building. Results: The (...) result of the paper is an illustration of how second-order models are developed and how this process, as it progresses, supports teachers to be more effective. Implications: This paper has the implication that radical constructivism has the potential to impact practice. Key Words: Second-order model, radical constructivism, teaching, mathematics education. (shrink)

Organizations increasingly rely on algorithm-based HR decision-making to monitor their employees. This trend is reinforced by the technology industry claiming that its decision-making tools are efficient and objective, downplaying their potential biases. In our manuscript, we identify an important challenge arising from the efficiency-driven logic of algorithm-based HR decision-making, namely that it may shift the delicate balance between employees’ personal integrity and compliance more in the direction of compliance. We suggest that critical data literacy, ethical awareness, the use of participatory (...) design methods, and private regulatory regimes within civil society can help overcome these challenges. Our paper contributes to literature on workplace monitoring, critical data studies, personal integrity, and literature at the intersection between HR management and corporate responsibility. (shrink)

This collection of essays considers a variety of educational ideas and programs from the perspective of governmentality, integrating conceptual and theoretical insights and empirical investigation of policy documents, and government technologies. Considers different educational ideas of enlightenment, creativity, participation, inclusion, learning, and critique Offers an overview of French philosopher Michel Foucault’s theory on governmentality and how his ideas apply to current developments in society and education Investigates the intrinsic relationship between intellectual and practical educational technologies A study of how educational (...) practice and educational theory have played a constitutive role in practices of subjectivity which are crucial to ‘learning societies’. (shrink)

The literature on deep brain stimulation (DBS) and adaptive DBS (aDBS) raises concerns that these technologies may affect personality, mood, and behavior. We conducted semi-structured interviews with researchers (n = 23) involved in developing next-generation DBS systems, exploring their perspectives on ethics and policy topics including whether DBS/aDBS can cause such changes. The majority of researchers reported being aware of personality, mood, or behavioral (PMB) changes in recipients of DBS/aDBS. Researchers offered varying estimates of the frequency of PMB changes. A (...) smaller majority reported changes in personality specifically. Some expressed reservations about the scientific status of the term ‘personality,’ while others used it freely. Most researchers discussed negative PMB changes, but a majority said that DBS/aDBS can also result in positive changes. Several researchers viewed positive PMB changes as part of the therapeutic goal in psychiatric applications of DBS/aDBS. Finally, several discussed potential causes of PMB changes other than the device itself. (shrink)

Language’s intentional nature has been highlighted as a crucial feature distinguishing it from other communication systems. Specifically, language is often thought to depend on highly structured intentional action and mutual mindreading by a communicator and recipient. Whilst similar abilities in animals can shed light on the evolution of intentionality, they remain challenging to detect unambiguously. We revisit animal intentional communication and suggest that progress in identifying analogous capacities has been complicated by (i) the assumption that intentional (that is, voluntary) production (...) of communicative acts requires mental-state attribution, and (ii) variation in approaches investigating communication across sensory modalities. To move forward, we argue that a framework fusing research across modalities and species is required. We structure intentional communication into a series of requirements, each of which can be operationalised, investigated empirically, and must be met for purposive, intentionally communicative acts to be demonstrated. Our unified approach helps elucidate the distribution of animal intentional communication and subsequently serves to clarify what is meant by attributions of intentional communication in animals and humans. (shrink)

This article reconsiders the theoretical role of the genetic code. By drawing on published and unpublished sources from the 1950s, I analyse how the code metaphor was actually employed by the scientists who first promoted its use. The analysis shows that the term ‘code’ picked out mechanism sketches, consisting of more or less detailed descriptions of ordinary molecular components, processes, and structural properties of the mechanism of protein synthesis. The sketches provided how-possibly explanations for the ordering of amino acids by (...) nucleic acids. I argue that employing the code metaphor was justified in virtue of its descriptive-denotational and explanatory roles, and because it highlighted a similarity with conventional codes that was particularly salient at the time. 1 Introduction2 Coding Schemes in the 1950s2.1 The research problem: Determining amino acid sequences2.2 The solution: Mapping schemes or ‘codes’3 The Code Metaphor Played Descriptive and Explanatory Roles4 Theness of Codes and the Expendability of the Code Metaphor5 The Role of Arbitrariness6 Conclusions. (shrink)

Guilt and shame are self-conscious emotions with implications for mental health, social and occupational functioning, and the effectiveness of sports practice. To date, the assessment and role of athlete-specific guilt and shame has been under-researched. Reporting data from 174 junior elite cricketers, the present study utilized exploratory factor analysis in validating the Athletic Perceptions of Performance Scale, assessing three distinct and statistically reliable factors: athletic shame-proneness, guilt-proneness, and no-concern. Conditional process analysis indicated that APPS shame-proneness mediated the relationship between general (...) and athlete-specific distress. While APPS domains of guilt-proneness and no-concern were not significant mediators, they exhibited correlations in the expected direction with indices of psychological distress and well-being. The APPS may assist coaches and support staff identify players who may benefit from targeted interventions to reduce the likelihood of experiencing shame-prone states. (shrink)