Now widely adopted, SCID newborn screening has proven effective for early identification and treatment of SCID. In addition, screening has improved our understanding of SCID and related disorders, which are more diverse than originally believed. Newborn screening for SCID illustrates how adding new disorders to newborn screening panels can be enormously beneficial if evidence‐based guidelines are adhered to and if mechanisms are in place to track outcomes and learn along the way. These lessons should guide all additions to newborn screening, (...) including those involving sequencing. (shrink)

Human severe combined immune deficiency (SCID) is the most serious inherited immunological deficit. Recent work has revealed defects in the predominant pathway for double‐strand break repair called nonhomologous DNA end joining, or NHEJ. Progress in the biochemistry and genetics of NHEJ and of human SCID has proven to be synergistic between these two fields in a manner that covers the range from biochemical etiology to considerations about possible gene therapy for the B− SCID patients. BioEssays 25:1061–1070, 2003. © (...) 2003 Wiley Periodicals, Inc. (shrink)

In this paper, we apply the perspective of intra-organismal ecology by investigating a family of ecological models suitable to describe a gene therapy to a particular metabolic disorder, the adenosine deaminase deficiency (ADA-SCID). The gene therapy is modeled as the prospective ecological invasion of an organ (here, bone marrow) by genetically modified stem cells, which then operate niche construction in the cellular environment by releasing an enzyme they synthesize. We show that depending on the chosen order (a choice that cannot (...) be made on \textit{a priori} assumptions), different kinds of dynamics are expected, possibly leading to different therapeutic strategies. This drives us to discuss several features of the extension of ecology to intra-organismal ecology. (shrink)

Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to (...) genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50, which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1, showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED. (shrink)

During the last two decades, neonatal screening in Europe and North America has expanded substantially. This article examines two recent suggestions for expanding neonatal screening: severe combined immunodeficiency and X-linked adrenoleukodystrophy. With reference to well-established risk-benefit based rationales for screening, it is argued that the case for introducing SCID in neonatal screening is considerably stronger than for introducing X-ALD. For instance, the majority of those screened for X-ALD most likely have a negative risk-benefit ratio of screening: they (...) develop milder symptoms or perhaps no symptoms at all, while still being monitored for a long time. This argument is used as a vehicle for making some general points regarding justified expansions of neonatal screening. First, when considering the expansion of neonatal screening, we should look at a condition specific case-by-case basis. Moreover, future expansions of neonatal screening should stick to the well-established rationales for screening while avoiding risk-benefit slippage. Otherwise, more strict procedures of informed consent are warranted in neonatal screening, procedures that, in the end, risk undermining the benefits of current neonatal screening programmes. (shrink)

A pathogenic connection between autoreactive T cells, fungal infection, and carcinogenesis has been demonstrated in studies of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy as well as in a mouse model in which kinase-dead Ikkα knock-in mice develop impaired central tolerance, autoreactive T cell–mediated autoimmunity, chronic fungal infection, and esophageal squamous cell carcinoma, which recapitulates APECED. IκB kinase α is one subunit of the IKK complex required for NF-κB activation. IKK/NF-κB is essential for central tolerance establishment by regulating the development of medullary thymic (...) epithelial cells that facilitate the deletion of autoreactive T cells in the thymus. In this review, we extensively discuss the pathogenic roles of inborn errors in the IKK/NF-κB loci in the phenotypically related diseases APECED, immune deficiency syndrome, and severe combined immunodeficiency; differentiate how IKK/NF-κB components, through mTEC, T cells/leukocytes, or epithelial cells, contribute to the pathogenesis of infectious diseases, autoimmunity, and cancer; and highlight the medical significance of IKK/NF-κB in these diseases. IKK/NF-κB regulates the expression of many genes that encode proteins involved in many crucial biological functions, such as immunity, tissue homeostasis, and fungal/bacterial/viral infections. Also, IKKα plays anti-tumor activities in many organs independently of NF-κB pathways. Thus, an inborn error in one of these gene loci can cause severe human diseases through these complicated mechanisms. (shrink)

All organisms possess mechanisms to repair double strand breaks (dsbs) generated in their DNA by damaging agents. Site‐specific dsbs are also introduced during V(D)J recombination. Four complementation groups of radiosensitive rodent mutants are defective in the repair of dsbs, and are unable to carry out V(D)J recombination effectively. The immune defect in Severe Combined Immunodeficient (scid) mice also results from an inability to undergo effective V(D)J recombination, and scid cell lines display a repair defect and belong to one (...) of these complementation groups. These findings indicate a mechanistic overlap between the processes of DNA repair and V(D)J recombination. Recently, two of the genes defined by these complementation groups have been identified and shown to encode components of DNA‐dependent protein kinase (DNA‐PK). We review here the three fields which have become linked by these findings, and discuss the involvement of DNA‐PK in dsb rejoining and in V(D)J recombination. (shrink)

In response to adverse events in retroviral gene therapy clinical trials conducted in France to correct for X-linked severe combined immune deficiency disorder (X-SCID), an advisory committee of the Food and Drug Administration convened in October 2002, February 2003, and March 2005, to deliberate and provide recommendations for similarly sponsored research in the United States. A similar National Institutes of Health committee met in February 2003. In this article, I review the transcripts and/or minutes of these meetings to (...) evaluate the extent to which the ethical dimension of the research was engaged even as the molecular and clinical evidence was reviewed. I then provide representative ethical arguments to demonstrate the sort of ethical reasoning that should be included as part of the agenda of such committee meetings. (shrink)

This book explores a neglected philosophical question: How do groups of interacting minds relate to singular minds? Could several of us, by organizing ourselves the right way, constitute a single conscious mind that contains our minds as parts? And could each of us have been, all along, a group of mental parts in close cooperation? Scientific progress seems to be slowly revealing that all the different physical objects around us are, at root, just a matter of the right parts put (...) together in the right ways: How far could the same be true of minds? This book argues that we are too used to seeing the mind as an indivisible unity and that understanding our place in nature requires being willing to see minds as composite systems, simultaneously one conscious whole and many conscious parts. In thinking through the implications of such a shift of perspective, the book relates the question of mental combination to a range of different theories of the mind (in particular panpsychism, functionalism, and Neo-Lockeanism about personal identity) and identifies, clarifies, and addresses a wide array of philosophical objections (concerning personal identity, the unity of consciousness, the privacy of experience, and other issues) that have been raised against the idea of composite minds. The result is an account of the metaphysics of composition and consciousness that can illuminate many different debates in philosophy of mind, concerning split brains, collective intentionality, and the combination problem, among others. (shrink)

Using a longitudinal case study design, we have tracked the recovery of motor function following severe traumatic brain injury (TBI) through a multimodal neuroimaging approach. In 2006, Canadian Soldier Captain (retired) Trevor Greene (TG) was attacked with an axe to the head while on tour in Afghanistan. TG continues intensive daily rehabilitation, which recently included the integration of physical therapy (PT) with neuromodulation using translingual neurostimulation (TLNS) to facilitate neuroplasticity. Recent findings with PT+TLNS demonstrated that recovery of motor function (...) occurred beyond conventional time limits, currently extending past 14-years post-injury. To investigate whether PT+TLNS similarly resulted in associated cognitive function improvements, we examined event-related potentials (ERPs) with the brain vital signs framework. In parallel with motor function improvements, brain vital signs detected significant increases in basic attention (as measured by P300 response amplitude) and cognitive processing (as measured by contextual N400 response amplitude). These objective cognitive improvements corresponded with TG’s self-reported improvements, including a noteworthy and consistent reduction in ongoing symptoms of post-traumatic stress disorder (PTSD). The findings provide valuable insight into the potential importance of non-invasive neuromodulation in cognitive rehabilitation, in addition to initial indications for physical rehabilitation. (shrink)

Panpsychism has often been motivated on the grounds that any attempt to account for experience and consciousness in organisms in purely physical, nonexperiential terms faces severe difficulties. The “combination problem” charges that attributing phenomenal properties to the basic constituents of organisms, as panpsychism proposes, likewise fails to provide a satisfactory basis for experience in humans and other organisms. This paper evaluates a recent attempt to understand, and solve, the combination problem. This approach, due to Sam Coleman, is premised on (...) a distinction between mere aggregates and genuine unities, and the purported inability of subjects to constitute a unity. In response, I first argue that it may not be incumbent upon the panpsychist to explain how microphenomenal properties could constitute a unity in the way that Coleman supposes. I then argue that even if such a burden does fall on the panpsychist, it is far from clear that a plurality subjects cannot constitute such a unity. Finally, I argue that if one adopts a functionalist account of macrosubjects, as Coleman does, there is little reason to think that a plurality of subjects could not constitute a macrosubject. In these ways, I argue that the force of the combination problem does not turn on whether microphenomenal properties require minds or subjects that have them. (shrink)

Although a very recent topic in contemporary logic, the subject of combinations of logics has already shown its deep possibilities. Besides the pure philosophical interest offered by the possibility of defining mixed logic systems in which distinct operators obey logics of different nature, there are also several pragmatical and methodological reasons for considering combined logics. We survey methods for combining logics (integration of several logic systems into a homogeneous environment) as well as methods for decomposing logics, showing their interesting (...) properties and applications. (shrink)

This paper investigates modular combinations of temporal logic systems. Four combination methods are described and studied with respect to the transfer of logical properties from the component one-dimensional temporal logics to the resulting combined two-dimensional temporal logic. Three basic logical properties are analyzed, namely soundness, completeness, and decidability. Each combination method comprises three submethods that combine the languages, the inference systems, and the semantics of two one-dimensional temporal logic systems, generating families of two-dimensional temporal languages with varying expressivity and (...) varying degrees of transfer of logical properties. The temporalization method and the independent combination method are shown to transfer all three basic logical properties. The method of full join of logic systems generates a considerably more expressive language but fails to transfer completeness and decidability in several cases. So a weaker method of restricted join is proposed and shown to transfer all three basic logical properties. (shrink)

The question of how concepts are formed was central for positivist and operationalist philosophers concerned to root scientific thought directly in experience. Although the positivist program has been abandoned, the current interest in the philosophy of scientific discovery shows the need for a theory of conceptual development. This paper offers a theory of how new concepts can arise, not by abstraction from experience or by definition, but by conceptual combination. Such combination produces a new concept as a non-linear, non-definitional amalgam (...) of existing concepts. After proposing rules intended to account for a variety of mundane cases of conceptual combination, the paper presents several illustrations of how scientific concepts have arisen through combination. (shrink)

Society Semantics, introduced by W. Carnielli and M. Lima-Marques, is a method for obtaining new logics from the combination of agents of a given logic. The goal of this paper is to present several generalizations of this method, as well as to show some applications to many-valued logics. After a reformulation of Society Semantics in a wider setting, we develop in detail two examples of application of the new formalism, characterizing a hierarchy of paraconsistent logics called Pn and a hierarchy (...) of paracomplete logics In. We also propose three further generalizations, obtaining Society Semantics for several many-valued logics, including a hierarchy of logics called In Pk which are both paraconsistent and paracomplete. (shrink)

BackgroundProfessional guidelines have addressed ethical dilemmas posed by a few types of nontraditional procreative arrangements, but many questions arise regarding how providers view and make decisions about these and other such arrangements.MethodsThirty-seven ART providers and 10 patients were interviewed in-depth for approximately 1 h each. Interviews were systematically analyzed.ResultsProviders faced a range of challenges and ethical dilemmas concerning both the content and the process of decisions about requests for unconventional interfamilial and other reproductive combinations. Providers vary in how they respond (...) — what they decide, who exactly decides, and how — often undergoing complex decision-making processes. These combinations can involve creating or raising the child, and can shift over time — from initial ART treatment through to the child’s birth. Patients’ requests can vary from fully established to mere possibilities. Arrangements may also be unstable, fluid, or unexpected, posing challenges. Difficulties emerge concerning not only familial but social, combinations. These arrangements can involve blurry and confusing roles, questions about the welfare of the unborn child, and unanticipated and unfamiliar questions about how to weigh competing moral and scientific concerns — e.g., the autonomy of the individuals involved, and the potential risks and benefits. Clinicians may feel that these requests do not “smell right”; and at first respond with feelings of “yuck,” and only later, carefully and explicitly consider the ethical principles involved. Proposed arrangements may, for instance, initially be felt to involve consanguineous individuals, but not in fact do so. Obtaining and verifying full and appropriate informed consent can be difficult, given implicit familial and/or cultural expectations and senses of duty. Social attitudes are changing, yet patients’ views of these issues may also vary, based on their cultural backgrounds.ConclusionsThese data, the first to examine how clinicians make decisions about unconventional reproductive arrangements, highlight several critical ethical questions and ambiguities, and variations in clinicians’ responses. While several professional guidelines exist, the current data highlight additional challenges, and have vital implications for improving future guidelines, practice, education and research.Trial registrationNot applicable. (shrink)

The definition of biological individuality is one of the most discussed topics in philosophy of biology, but current debate has focused almost exclusively on evolution-based accounts. Moreover, several participants in this debate consider the notions of a biological individual and an organism as equivalent. In this paper, I show that the debates would be considerably enriched and clarified if philosophers took into account two elements. First, physiological fields are crucial for the understanding of biological individuality. Second, the category of biological (...) individuals should be divided into two subcategories: physiological individuals and evolutionary individuals, which suggests that the notions of organism and biological individual should not be used interchangeably. I suggest that the combination of an evolutionary and a physiological perspective will enable biologists and philosophers to supply an account of biological individuality that will be both more comprehensive and more in accordance with scientific practices. (shrink)

The success of social robots in achieving natural coexistence with humans depends on both their level of autonomy and their interactive abilities. Although a lot of robotic architectures have been suggested and many researchers have focused on human–robot interaction, a robotic architecture that can effectively combine interactivity and autonomy is still unavailable. This paper contributes to the research efforts toward this architecture in the following ways. First a theoretical analysis is provided that leads to the notion of co-evolution between the (...) agent and its environment and with other agents as the condition needed to combine both autonomy and interactivity. The analysis also shows that the basic competencies needed to achieve the required level of autonomy and the envisioned level of interactivity are similar but not the same. Secondly nine specific requirements are then formalized that should be achieved by the architecture. Thirdly a robotic architecture that tries to achieve those requirements by utilizing two main theoretical hypothesis and several insights from social science, developmental psychology and neuroscience is detailed. Lastly two experiments with a humanoid robot and a simulated agent are reported to show the potential of the proposed architecture. (shrink)

As Children’s Laureate 2013–2015, Malorie Blackman raised awareness of the lack of racial diversity in children’s fiction. Underrepresentation of ethnic minorities in fiction and the publishing industry’s infrastructure is a severe problem in the world of children’s books, as illuminated by research into the publishing environment of the past 15 years, and the books populating current bestseller charts. Pierre Bourdieu’s theory of economic and symbolic capital is important to understanding how diversity is highlighted in the contemporary literary field, but (...) his polarization of the different form of capital as motivation for creating art is reductive. Storytelling is about combining voices and experiences, and publishers can, and should, combine economic and symbolic motivations in publishing diverse fiction for children. Publishing a book because it will be successful economically and because it is the right thing to do are not mutually exclusive; in publishing diverse children’s fiction, both motives can and should inspire us. (shrink)

Conversational interfaces are becoming ubiquitous in an increasing number of application domains as Artificial Intelligence, Natural Language Processing and Machine Learning methods associated with the recognition, understanding and generation of natural language advance by leaps and bounds. However, designing the dialog model of these systems is still a very demanding task requiring a great deal of effort given the number of information sources to be considered related to the analysis of user utterances, interaction context, information repositories, etc. In this paper, (...) we present a general framework for increasing the quality of the system responses by combining a statistical dialog management technique and a deep learning-based intention recognizer that allow replacing the system responses initially selected by the statistical dialog model with other presumably better candidates. This approach is portable to different task-oriented domains, a diversity of methodologies for dialog management and intention estimation techniques. We have evaluated our two-step proposal using two conversational systems, assessed several intention recognition methodologies and used the developed modules to dynamically select the system responses. The results of the evaluation show that the proposed framework achieves satisfactory results by making it possible to reduce the number of non-coherent dialog responses by replacing them by more coherent alternatives. (shrink)

t Intentional sampling methods are non-randomized procedures that select a group of individuals for a sample with the purpose of meeting specific prescribed criteria. In this paper we extend previous works related to intentional sampling, and address the problem of sequential allocation for clinical trials with few patients. Roughly speaking, patients are enrolled sequentially, according to the order in which they start the treatment at the clinic or hospital. The allocation problem consists in assigning each new patient to one, and (...) only one, of the alternative treatment arms. The main requisite is that the profiles in the alternative arms remain similar with respect to some relevant patients’ attributes (age, gender, disease, symptom severity and others). We perform numerical experiments based on a real case study and discuss how to conveniently set up perturbation parameters, in order to yield a suitable balance between optimality – the similarity among the relative frequencies of patients in the several categories for both arms, and decoupling – the absence of a tendency to allocate each pair of patients consistently to the same arm. (shrink)

Intergenerational justice not only requires the adoption of best practices and policies; but also the prevention and repression of deleterious and morally blameworthy human behaviour which have severe impacts on the long-term health; safety and means of survival of groups of individuals. While many international crimes have indirect consequences on the well-being of present and future generations; it cannot be said that existing international criminal law is currently well-placed to directly and clearly protect intergenerational rights. As such; the development (...) of a new type of international crime; crimes against future generations; may be a promising avenue for implementing intergenerational justice. Such a crime would penalise acts or conduct that amount to serious violations of existing international law regarding economic; social and cultural rights or the environment. (shrink)

I will introduce and motivate eliminativist super-relationism. This is the conjunction of relationism about spacetime and eliminativism about material objects. According to the view, the universe is a big collection of spatio-temporal relations and natural properties, and no substance (material or spatio-temporal) exists in it. The view is original since eliminativism about material objects, when understood as including not only ordinary objects like tables or chairs but also physical particles, is generally taken to imply substantivalism about spacetime: if properties are (...) directly instantiated by spacetime without the mediation of material objects, then, surely, spacetime has to be a substance. After introducing briefly the two debates about spacetime (§1) and material objects (§2), I will present Schaffer's super-substantivalism (§3), the conjunction of substantivalism about spacetime and eliminativism about material objects at the fundamental level. I shall then expose and discuss the assumption from which the implication from eliminativism to substantivalism is drawn, and discuss the compatibility of eliminativism with relationism: if spacetime is not a substance, and if material objects are not real, how are we to understand the instantiation of properties (§4)? And what are the relata of spatio-temporal relations (§5)? I then show that each argument in favor of super-substantivalism offered by Schaffer also holds for super-relationism (§6) and examine several metaphysical consequences of the view (§7). I conclude that both super-substantivalism and super-relationism are compatible with Schaffer's priority monism (§8). (shrink)

We evaluate whether evidence from conceptual combination supports the relational priming model of analogy. Representing relations implicitly as patterns of activation distributed across the semantic network provides a natural and parsimonious explanation of several key phenomena observed in conceptual combination. Although an additional mechanism for role resolution may be required, relational priming offers a promising approach to analogy.

In lieu of an abstract, here is a brief excerpt of the content:Theoretical Remarks on Combined Creative and Scholarly PhD Degrees in the Visual ArtsJames Elkins (bio)The PhD in visual arts is inescapable: it is on the horizon. In just a few years, there will be a number of such programs in the United States, and if the trend mirrors the expansion of MFAs after the mid-1960s, then in a few decades the PhD will be the consensus "terminal" degree (...) for artists. Given that, it is pressing to consider how the degree might be theorized. In Australia and the United Kingdom, where the degrees already exist, their growth has been dictated in large measure by the existing educational structures and by the inevitable quest for funding. (In the United Kingdom, university departments get a disproportionate increase in their funding if they offer doctorate programs, and the same pattern occurs in state schools in America.) As a result, existing programs simply grow by exonomic necessity or opportunity, and so far they have not been well theorized apart from models already in use elsewhere in the university. Private universities and art schools in the United States are therefore well positioned to rethink the conceptual foundations of combined studio and scholarly PhDs, because they are largely freed of the temptation of increased funding and the obligation to fit the new programs into existing structures. In this essay, I propose eight configurations that such degrees might take. I close with three general observations about the future of such programs.Three pieces of background are necessary as introduction. First, the School of the Art Institute, Chicago, where I teach, is currently running an four-year undergraduate major in visual studies. Soon we will be expanding it into an MA and, in a few years, a PhD. At the BA level our program already has a large studio component. For that reason we have been looking at programs that offer comparable combinations of creative and scholarly work at the PhD level. Our own program, we hope, will be a place [End Page 22] where the possibilities of other programs can be kept open and continuously questioned.Second, this essay was originally a reader's report for a creative-arts PhD thesis called "Beyond the Surface: The Contemporary Experience of the Italian Renaissance," written by Jo-Anne Duggan for the University of Technology, Sydney. In fall 2003 Duggan was a candidate for the "DCA," Doctorate of Creative Arts." She is a photographer, and her special interest is photographing inside museums; her thesis explores the history and theory of that practice. The report I wrote for her was the basis of this essay, because I found that her thesis is a mixture of what I think are the eight principal possibilities for combining PhD-level scholarship and creative work.Third, this essay is the outgrowth of several colloquia that have been held at the College Art Association and at the Association of Independent Colleges of Art and Design/National Association of Schools of Art and Design (AICAD/NASAD) conferences (organizations of art school administrators). These ad hoc forums have been, so far, the only places where the new programs have been debated. I hope this essay can contribute to a more detailed discussion.Here are the eight configurations. The first five are (or will be) common, and the last two are rare but preferable.1. The thesis is art history, intended to inform the art practice. The most obvious relation between scholarship and creative work is that the former informs the latter. The artist positions her scholarship so that it supports her art practice. Within this possibility, perhaps the most common option would be to write an art historical thesis, covering the history of practices that lead up to the writer's own practice. Among the advantages would be that, in theory, the candidate would be able to go on to teach in a department of art history. In terms of her practice, the idea would be that historical knowledge strengthens art practice: a debatable point, if only because so many artists have done so well by ignoring or distorting the relevant history. In Canberra in summer 2003, I met a recent PhD whose thesis was on... (shrink)

Satisfaction systems and reductions between them are presented as an appropriate context for analyzing the satisfiability and the validity problems. The notion of reduction is generalized in order to cope with the meet-combination of logics. Reductions between satisfaction systems induce reductions between the respective satisfiability problems and (under mild conditions) also between their validity problems. Sufficient conditions are provided for relating satisfiability problems to validity problems. Reflection results for decidability in the presence of reductions are established. The validity problem in (...) the meet-combination is proved to be decidable whenever the validity problem for the components are decidable. Several examples are discussed, namely, involving modal and intuitionistic logics, as well as the meet-combination of modal logic and intuitionistic logic. (shrink)

Business activity can be analyzed through a ‘risk awareness’ perspective and a ‘responsibility awareness’ perspective. However, risk and responsibility are actually interdependent. Risk-taking triggers responsibility issues and taking responsibility means risking being asked critical questions. This article suggests some first steps for combining these two perspectives conceptually. After several introductory illustrations showing how risk and responsibility issues are intertwined, the article looks separately each at risk and at responsibility. Then the argument that such perspectives could be usefully combined is (...) elaborated further from a theoretical angle and from a practical angle, by looking at various ethical issues and by presenting paradigmatic examples of balancing or sharing risk and responsibility related to leadership, to ERM and to insurance. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Theoretical Remarks on Combined Creative and Scholarly PhD Degrees in the Visual ArtsJames Elkins (bio)The PhD in visual arts is inescapable: it is on the horizon. In just a few years, there will be a number of such programs in the United States, and if the trend mirrors the expansion of MFAs after the mid-1960s, then in a few decades the PhD will be the consensus "terminal" degree (...) for artists. Given that, it is pressing to consider how the degree might be theorized. In Australia and the United Kingdom, where the degrees already exist, their growth has been dictated in large measure by the existing educational structures and by the inevitable quest for funding. (In the United Kingdom, university departments get a disproportionate increase in their funding if they offer doctorate programs, and the same pattern occurs in state schools in America.) As a result, existing programs simply grow by exonomic necessity or opportunity, and so far they have not been well theorized apart from models already in use elsewhere in the university. Private universities and art schools in the United States are therefore well positioned to rethink the conceptual foundations of combined studio and scholarly PhDs, because they are largely freed of the temptation of increased funding and the obligation to fit the new programs into existing structures. In this essay, I propose eight configurations that such degrees might take. I close with three general observations about the future of such programs.Three pieces of background are necessary as introduction. First, the School of the Art Institute, Chicago, where I teach, is currently running an four-year undergraduate major in visual studies. Soon we will be expanding it into an MA and, in a few years, a PhD. At the BA level our program already has a large studio component. For that reason we have been looking at programs that offer comparable combinations of creative and scholarly work at the PhD level. Our own program, we hope, will be a place [End Page 22] where the possibilities of other programs can be kept open and continuously questioned.Second, this essay was originally a reader's report for a creative-arts PhD thesis called "Beyond the Surface: The Contemporary Experience of the Italian Renaissance," written by Jo-Anne Duggan for the University of Technology, Sydney. In fall 2003 Duggan was a candidate for the "DCA," Doctorate of Creative Arts." She is a photographer, and her special interest is photographing inside museums; her thesis explores the history and theory of that practice. The report I wrote for her was the basis of this essay, because I found that her thesis is a mixture of what I think are the eight principal possibilities for combining PhD-level scholarship and creative work.Third, this essay is the outgrowth of several colloquia that have been held at the College Art Association and at the Association of Independent Colleges of Art and Design/National Association of Schools of Art and Design (AICAD/NASAD) conferences (organizations of art school administrators). These ad hoc forums have been, so far, the only places where the new programs have been debated. I hope this essay can contribute to a more detailed discussion.Here are the eight configurations. The first five are (or will be) common, and the last two are rare but preferable.1. The thesis is art history, intended to inform the art practice. The most obvious relation between scholarship and creative work is that the former informs the latter. The artist positions her scholarship so that it supports her art practice. Within this possibility, perhaps the most common option would be to write an art historical thesis, covering the history of practices that lead up to the writer's own practice. Among the advantages would be that, in theory, the candidate would be able to go on to teach in a department of art history. In terms of her practice, the idea would be that historical knowledge strengthens art practice: a debatable point, if only because so many artists have done so well by ignoring or distorting the relevant history. In Canberra in summer 2003, I met a recent PhD whose thesis was on... (shrink)

Combinatory logic and lambda-conversion were originally devised in the 1920s for investigating the foundations of mathematics using the basic concept of 'operation' instead of 'set'. They have now developed into linguistic tools, useful in several branches of logic and computer science, especially in the study of programming languages. These notes form a simple introduction to the two topics, suitable for a reader who has no previous knowledge of combinatory logic, but has taken an undergraduate course in predicate calculus and recursive (...) functions. The key ideas and basic results are presented, as well as a number of more specialised topics, and man), exercises are included to provide manipulative practice. (shrink)

The notion of a severe test has played an important methodological role in the history of science. But it has not until recently been analyzed in any detail. We develop a generally Bayesian analysis of the notion, compare it with Deborah Mayo’s error-statistical approach by way of sample diagnostic tests in the medical sciences, and consider various objections to both. At the core of our analysis is a distinction between evidence and confirmation or belief. These notions must be kept (...) separate if mistakes are to be avoided; combined in the right way, they provide an adequate understanding of severity. Those who think that the weight of the evidence always enables you to choose between hypotheses “ignore one of the factors (the prior probability) altogether, and treat the other (the likelihood) as though it ...meant something other than it actually does. This is the same mistake as is made by someone who has scruples about measuring the arms of a balance (having only a tape measure at his disposal ...), but is willing to assert that the heavier load will always tilt the balance (thereby implicitly assuming, although without admitting it, that the arms are of equal length!). (Bruno de Finetti, Theory of Probability)2. (shrink)

We consider a deterministic rewrite system for combinatory logic over combinators , and . Terms will be represented by graphs so that reduction of a duplicator will cause the duplicated expression to be "shared" rather than copied. To each normalizing term we assign a weighting which is the number of reduction steps necessary to reduce the expression to normal form. A lambda-expression may be represented by several distinct expressions in combinatory logic, and two combinatory logic expressions are considered equivalent if (...) they represent the same lambda-expression (up to --equivalence). The problem of minimizing the number of reduction steps over equivalent combinator expressions (i.e., the problem of finding the "fastest running" combinator representation for a specific lambda-expression) is proved to be NP-complete by reduction from the "Hitting Set" problem. (shrink)

Often the only treatment available for patients suffering from diseased and injured organs is whole organ transplant. However, there is a severe shortage of donor organs for transplantation. The goal of organ engineering is to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Recent progress in stem cell biology, biomaterials, and processes such as organ decellularization and electrospinning has resulted in the generation of bioengineered blood vessels, heart valves, livers, kidneys, bladders, and (...) airways. Future advances that may have a significant impact for the field include safe methods to reprogram a patient's own cells to directly differentiate into functional replacement cell types. The subsequent combination of these cells with natural, synthetic and/or decellularized organ materials to generate functional tissue substitutes is a real possibility. This essay reviews the current progress, developments, and challenges facing researchers in their goal to create replacement tissues and organs for patients. (shrink)

SummaryJohn Dalton's atomic theory, with its postulate of compound formation through atom-to-atom combination, brought a new perspective to weight relationships in chemical reactions. A presumed one-to-one combination of atoms A and B to form a simple compound AB allowed Dalton to construct his first table of relative atomic weights from literature analyses of appropriate binary compounds. For such simple binary compounds, the atomic theory had little advantages over affinity theory as an explanation of fixed proportions by weight. For ternary compounds (...) of the form AB2, however, atomic theory made quantitative predictions that were not deducible from affinity theory. Atomic theory required that the weight of B in the compound AB2 be exactly twice that in the compound AB. Dalton, Thomas Thomson and William Hyde Wollaston all published within a few years of each other experimental data that claimed to give the predicted results with the required accuracy. There are nonetheless several experimental barriers to obtaining the desired integral multiple proportions. In this paper I will discuss replication experiments which demonstrate that only Wollaston's results are experimentally reliable. It is likely that such replicability explains why Wollaston's experiments were so influential. (shrink)

The purposes of this article were to obtain mechanical properties of the dry femur cortical bone samples through a tensile load and stress concentration factor approach and to provide simulations to predict experimental behaviors based on manipulations of certain properties and parameters of the biomaterial. Since bone samples have characteristics and geometries, the development of a mathematical model was necessary to describe the combination of stresses interacting in the bone when a tension load is applied. The samples have average diameters (...) and lengths of 0.5 and 2 inches respectively and were tested using a 10 kN Universal Tensile Machine to determine mechanical properties such as yield and ultimate stress, young module, and fracture, among others. Several simulations were conducted to evaluate failure criteria like “Von Mises”, “Tresca” and “Tsai-Wu”. Finally, was concluded that 83% of the data obtained from the 22 samples observed in the “Stress-Strain” charts showed a directly proportional relationship. (shrink)

Mental fictionalism is not the benign view that we may better understand the mind if we think of mental states as something like useful fictions, but the more radical view that mental states just are useful fictions. This paper argues that, if one were to treat mental states as a kind of fiction, the genre of fiction best suited to this purpose would be fantasy make-believe, in which magic is a central feature. After defending a promising fictionalist account of mental (...) discourse as a kind of prop-oriented make believe against recent criticism, the paper ultimately concludes that mental fictionalism faces further, potentially insurmountable, challenges. Most significantly, there is a problematic disanalogy between folk psychology and fiction: our mental state attributions aim to track truth, and this crucial aspect of our mental discourse cannot be captured if we interpret it as a kind of fictional discourse. For this and other reasons, the cost of adopting mental fictionalism likely outweighs its benefits. Whether or not these problems can be resolved, there is still much to be gained from taking mental fictionalism seriously: in doing so we may illuminate several important features of our own folk psychology that often go unnoticed. (shrink)

There is a discrepancy between Stoffregen & Bardy's concept with experimental work on human self-motion perception. We suggest an alternative: (1) higher brain centers are informed by a given sensory cue in a direct and rapid way (direct perception), and (2) this information is then used to prime and shape a more complex mechanism that usually involves several cues and processing steps (inferential).

Robert Deltete and Anastasios Brenner have provided a thorough examination of my translation of Duhem’s Le mixte et la combinaison chimique (1902) and associated essays. I am very grateful for their efforts and gratified that such competent reviewers should be generally positive. They provide an overview of relevant aspects of Duhem’s life and work, which may serve to introduce him to readers of this journal and promote interest in Duhem studies. They also raise and answer some questions about the interpretation (...) and evaluation of Duhem’s work, make some points of criticism of my choice of material and question certain points of translation. The editor has suggested that I make a response, and I shall take up some issues in these three areas. Since Duhem’s views play a central role in the development of the concept of chemical substance which I have worked on in recent years, I will make several references to my own publications. (shrink)

This paper develops a new framework for combining propositional logics, called "juxtaposition". Several general metalogical theorems are proved concerning the combination of logics by juxtaposition. In particular, it is shown that under reasonable conditions, juxtaposition preserves strong soundness. Under reasonable conditions, the juxtaposition of two consequence relations is a conservative extension of each of them. A general strong completeness result is proved. The paper then examines the philosophically important case of the combination of classical and intuitionist logics. Particular attention is (...) paid to the phenomenon of collapse. It is shown that there are logics with two stocks of classical or intuitionist connectives that do not collapse. Finally, the paper briefy investigates the question of which rules, when added to these logics, lead to collapse. (shrink)

The objectives of this study are to survey, post the latest Combined Code, current board practice concerning the appointment, evaluation and development of directors and performance evaluation of boards and their committees. The Company Secretaries of all FTSE 100 and 250 companies were invited to complete, online or on paper, a survey questionnaire designed to investigate several aspects of the performance of their Boards of Directors, including the impact of relevant parts of the latest Combined Code. The more (...) positive findings are that: the Code's principles yield discernible benefits for board and company performances; board performance is most affected by new appointments which has implications for director induction; New Directors' roles and competencies are well articulated by Nomination Committees; a majority use explicit performance criteria; a majority of directors commit 3 5 days per annum to their professional development. Areas for attention suggested by the findings are as follows: a minority translate explicit performance criteria into specific improvement targets; some ambivalence characterises public disclosure of board evaluation results; evaluation of Committees' performance is less rigorous than for Main Boards; the powers and responsibilities of Subsidiary/Divisional boards are not well defined; only a minority of Nomination Committees focus on Descriptors of High Performance; traditional methods of Director selection and induction prevail; Non-Executive Directors' suitability to coach their Executive Director colleagues or other members of the executive team; only one in seven boards uses External Facilitators to assist in benchmarking their performance. The implications of these results are discussed. (shrink)

Traditional approaches to measurement of violations of academic integrity may overestimate the magnitude and severity of cheating and confound panic with planned cheating. Differences in the severity and level of premeditation of academic integrity violations have largely been unexamined. Results of a study based on a combined sample of business students showed that students are more likely to commit minor cheating offenses and engage in panic-based cheating as compared to serious and planned cheating offenses. Results also indicated there is (...) a significant interaction between severity and type of cheating. We hypothesized serious and planned cheating offenses would be related to justifications and found the largest differences were between panic and planned. Finally, panic and minor cheating were associated with two self-control-related personality traits. Implications for cheating research are discussed. (shrink)

Antoine Arnauld and Pierre Nicole were philosophers and theologians associated with Port-Royal Abbey, a centre of the Catholic Jansenist movement in seventeenth-century France. Their enormously influential Logic or the Art of Thinking, which went through five editions in their lifetimes, treats topics in logic, language, theory of knowledge and metaphysics, and also articulates the response of 'heretical' Jansenist Catholicism to orthodox Catholic and Protestant views on grace, free will and the sacraments. In attempting to combine the categorical theory of the (...) proposition with a Cartesian account of knowledge, their Logic represents the classical view of judgment which inspired the modern transformation in logic and semantic theory by Frege, Russell, Wittgenstein and recent philosophers. This edition presents a new translation of the text, together with a historical introduction and suggestions for further reading. (shrink)

In this contribution, we use the connection between stable polynomials and orthogonal polynomials on the real line to construct sequences of Hurwitz polynomials that are robustly stable in terms of several uncertain parameters. These sequences are constructed by using properties of orthogonal polynomials, such as the well-known three-term recurrence relation, as well as by considering linear combinations of two orthogonal polynomials with consecutive degree. Some examples are presented.

Defenders of patient autonomy have successfully supported the legal adoption of advance directives. More recently, some defenders of patient autonomy have also supported the legalization of voluntary active euthanasia. This paper explores the wisdom of combining both practices. If euthanasia were to become legal, should it be permitted by advance directives? The paper juxtaposes the most significant doubts about advance directives, with the most significant doubts about euthanasia. It argues that the doubts together raise more concern about the combined (...) practices than about either euthanasia or advance directives separately. Not all cases of voluntary euthanasia by advance directive are equally problematic, however. Advance directives can help in the defense of euthanasia for patients who make the request in advance and reaffirm it under circumstances of severe suffering. Keywords: advance directives, durable power of attorney, euthanasia, living will, patient interests CiteULike Connotea Del.icio.us What's this? (shrink)

This article elucidates a unique metaethical theory implicit in the work of several thinkers associated with the Stone-Campbell Restoration Movement. After positioning that theory within a broader landscape of metaethical positions endorsed by several prominent contemporary Christian philosophers and theologians, we address the concern that, when attending to the Euthyphro dilemma, the Restoration-inspired combination metaethical theory inevitably collapses into either an unalloyed divine command theory or an unalloyed natural law theory. In explaining how this sort of worry can be mitigated, (...) we offer reason to think that the nonreductive, combination metaethical theory in question constitutes potentially fertile territory for further scholarly work in Christian ethics. (shrink)

In order to improve the translation quality of complex English sentences, this paper investigated unknown words. First, two baseline models, the recurrent neural machine translation (RNMT) model and the transformer model, were briefly introduced. Then, the unknown words were identified and replaced based on WordNet and the semantic environment and input to the neural machine translation (NMT) model for translation. Finally, experiments were conducted on several National Institute of Standards and Technology (NIST) datasets. It was found that the transformer model (...) significantly outperformed the RNMT model, its average bilingual evaluation understudy (BLEU) value was 42.14, which was 6.96 higher than the RNMT model, and its translation error rate (TER) was also smaller. After combining the intelligent algorithm, the BLEU values of both models improved, and the TER became smaller; the average BLEU value of the transformer model combined with the intelligent algorithm was 43.7, and the average TER was 57.68. The experiment verifies that the transformer model combined with the intelligent algorithm is reliable in translating complex sentences and can obtain higher-quality translation results. (shrink)

This article introduces a theoretical framework that combines institutional and stakeholder theories to explain how firms choose their corporate social responsibility (CSR) strategy. Organizational researchers have identified several distinct CSR strategies (e.g., obstructionist, defensive, accommodative, and proactive), but did not explain the sources of divergence. This article argues that the divergence comes from the variability in the configuration of external influences that consists of institutional and stakeholder pressures. While institutions affect firms’ social behavior by shaping the macro-level incentive structure and (...) sources of legitimacy (distal mechanisms), firms’ stakeholders can amplify or buffer the institutional forces by acting as mediators (proximate mechanisms). The two dimensions are interdependent in that stakeholders draw legitimacy and power from institutions, and institutions are often actualized through stakeholder mechanisms. Together, they form a particular configuration of external influences that shapes how focal firms construct their CSR strategy. (shrink)