Significant associations have been found between specific human leukocyte antigen (HLA) alleles and organ transplant rejection, autoimmune disease development, and the response to infection. Traditional searches for disease associations have conventionally measured risk associated with the presence of individual HLA alleles. However, given the high level of HLA polymorphism, the pattern of amino acid variability, and the fact that most of the HLA variation occurs at functionally important sites, it may be that a combination of variable amino acid sites shared (...) by several alleles (shared epitopes) are better descriptors of the actual causative genetic variants. Here we describe a novel approach to genetic association analysis in which genes/proteins are broken down into smaller sequence features and then variant types defined for each feature, allowing for independent analysis of disease association with each sequence feature variant type. We have used this approach to analyze a cohort of systemic sclerosis patients and show that a sequence feature composed of specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk for systemic sclerosis. (shrink)

BackgroundThe ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines are widely endorsed but compliance is limited. We sought to determine whether journal-requested completion of an ARRIVE checklist improves full compliance with the guidelines.MethodsIn a randomised controlled trial, manuscripts reporting in vivo animal research submitted to PLOS ONE (March–June 2015) were randomly allocated to either requested completion of an ARRIVE checklist or current standard practice. Authors, academic editors, and peer reviewers were blinded to group allocation. Trained reviewers performed outcome adjudication (...) in duplicate by assessing manuscripts against an operationalised version of the ARRIVE guidelines that consists 108 items. Our primary outcome was the between-group differences in the proportion of manuscripts meeting all ARRIVE guideline checklist subitems.ResultsWe randomised 1689 manuscripts (control: n = 844, intervention: n = 845), of which 1269 were sent for peer review and 762 (control: n = 340; intervention: n = 332) accepted for publication. No manuscript in either group achieved full compliance with the ARRIVE checklist. Details of animal husbandry (ARRIVE subitem 9b) was the only subitem to show improvements in reporting, with the proportion of compliant manuscripts rising from 52.1 to 74.1% (X2 = 34.0, df = 1, p = 2.1 × 10−7) in the control and intervention groups, respectively.ConclusionsThese results suggest that altering the editorial process to include requests for a completed ARRIVE checklist is not enough to improve compliance with the ARRIVE guidelines. Other approaches, such as more stringent editorial policies or a targeted approach on key quality items, may promote improvements in reporting. (shrink)

Saeculum: Gedenkschrift für Heinrich Otten anlässlich seines 100. Geburtstags. Edited by Andreas Müller-Karpe; Elisabeth Rieken; and Walter Sommerfeld. Studien zu den Boǧazköy-Texten, vol. 58. Wiesbaden: Harrassowitz Verlag, 2015. Pp. xi + 316, illus. €84.

It is argued that the so-called fitting attitude- or buck-passing pattern of analysis may be applied to personal values too if the analysans is fine-tuned in the following way: An object has personal value for a person a, if and only if there is reason to favour it for a’s sake. One benefit with it is its wide range: different kinds of values are analysable by the same general formula. Moreover, by situating the distinguishing quality in the attitude rather than (...) the reason part, the analysis admits that personal value is recognizable as a value not only by the person for whom it has personal value, but for everyone else too. We thereby avoid facing two completely different notions of value, viz., one pertaining to impersonal value, and another to personal value. The analysis also elucidates why we are justified in our concern for objects that are valuable for us; if value just is, as it is suggested, the existence of reasons for such a concern, the justification is immediately forthcoming. (shrink)

Chemical structures are among the trademarks of our profession, as surely chemical as flasks, beakers and distillation columns. When someone sees one of us busily scribbling formulas or structures, he or she has no trouble identifying a chemist. Yet these familiar objects, which accompany our work from start to end, from the initial doodlings (Fig. I) to the final polished artwork in a publication (Fig. II), are deceptively simple. They raise interesting and difficult questions about representation. It is the intent (...) of this article to reflect upon molecular graphics. (shrink)

This distinction has sometimes been read as purely epistemic, resting not on things, but on our knowledge of them: there is one world, not two, though it may be apprehended in two ways. But this view is patently at odds with the text. Knowledge and opinion are δυνάμεις, "faculties," to be distinguished and defined by their objects, no less than by the state of mind they produce, and Plato clearly states that the fallibility and unclearness of opinion is rooted in (...) the relative unreality of opinables. (shrink)

This essay explores the role of informal logicand its application in the context of currentdebates regarding evidence-based medicine. This aim is achieved through a discussion ofthe goals and objectives of evidence-basedmedicine and a review of the criticisms raisedagainst evidence-based medicine. Thecontributions to informal logic by StephenToulmin and Douglas Walton are explicated andtheir relevance for evidence-based medicine isdiscussed in relation to a common clinicalscenario: hypertension management. This essayconcludes with a discussion on the relationshipbetween clinical reasoning, rationality, andevidence. It is argued that (...) informal logic hasthe virtue of bringing explicitness to the roleof evidence in clinical reasoning, and bringssensitivity to understanding the role ofdialogical context in the need for evidence inclinical decision making. (shrink)

In this paper I consider how thinking emerges out of human infants' relatedness towards the personal and non-personal world. I highlight the contrast between cognitive aspects and cognitive components of psychological functioning, and propose that even when thinking has become a partly separable component of the mind, affective and conative aspects inhere in its nature. I provide illustrative evidence from recent research on the developmental psychopathology of autism. In failing to adopt a developmental perspective, contemporary theorizing has displaced thinking from (...) where it is properly situated - intimately woven with feeling as well as action, and infused with qualities of interpersonal relatedness from which its structure is derived. (shrink)

We generalize two well-known model-theoretic characterization theorems from propositional modal logic to first-order modal logic. We first study FML-definable frames and give a version of the Goldblatt–Thomason theorem for this logic. The advantage of this result, compared with the original Goldblatt–Thomason theorem, is that it does not need the condition of ultrafilter reflection and uses only closure under bounded morphic images, generated subframes and disjoint unions. We then investigate Lindström type theorems for first-order modal logic. We show that FML has (...) the maximal expressive power among the logics extending FML which satisfy compactness, bisimulation invariance and the Tarski union property. (shrink)

Given a structure for a first-order language L, two objects of its domain can be indiscernible relative to the properties expressible in L, without using the equality symbol, and without actually being the same. It is this relation that interests us in this paper. It is called Leibniz equality. In the paper we study systematically the problem of its definibility mainly for classes of structures that are the models of some equality-free universal Horn class in an infinitary language Lκκ, where (...) κ is an infinite regular cardinal. (shrink)

For all the time and effort expended on empowerment and participation ‘programmes’, many fail each year. This paper argues that the cause is a faulty view of communication widespread among managers and their teachers: the conduit, transmission model. It frustrates participation and is an ideology of management control. It rests on untenable beliefs about meaning and how language relates to the world. The paper proposes a new model of communication in terms of ‘communicating other/wise’ and offers examples of how it (...) can be practised in management education and by managers aiming to bring empowered and participatory workplaces into being. (shrink)

In the coverage of the problems of war and peace in Catholicism, researchers sometimes omit the regional component of their manifestation. We are talking about local traditions in Catholicism, which have their own specific approach to solving this problem and sometimes may differ significantly from the "conventional" position. The study of this field is necessary because in the delineated field the position of those theologians who were on the "outskirts" of Catholicism in the intercultural dialogue, on the one hand, led (...) to a deviation from the humanistic orientation about Catholicism. the war. An example would be the concept of a "holy war" of the Crusades, which had the anti-Islamic rhetoric generated not only in the West but also in the East. (shrink)

Before talking about the vision of Orikhov's essence of the relationship between the church and the state, one must first determine what the church is about - Catholic or Orthodox. After all, the thinker lived in Poland when there were still strong, even parity positions of both denominations. He himself was brought up in a family where his father was Catholic and his mother was Orthodox. This was reflected in his mentality: he repeatedly publicly stated the benefits of certain tenets (...) of the Orthodox faith. But most of all he settled on the problem of relations between the Catholic Church and the state. (shrink)

This chapter argues that the objection that Socrates makes against diviners, poets, and rhapsodies having knowledge is an example of what has come to be known as an opacity objection: that is, some aspect of what would be required for them to know is unrecognised by them. This chapter contends that the opacity is of a different kind than what contemporary epistemologists have considered, and claims that Socrates’ specific version should have a place in contemporary theory of knowledge.

ABSTRACT R. P. Wolff has argued that there is an irreconcilable conflict between the distinguishing mark of every state, viz. supreme authority over all its citizens, and the primary obligation of rational beings, viz. to act autonomously by taking moral responsibility for all of their actions. Utilitarian and consent theories which seek to justify the state's claim to possess a monopoly of the rightful use of force are shown to fail and the concept of a ‘legitimate state’to be morally incoherent. (...) However, Wolff's version of individualist anarchism does not follow. Human beings are by no means equally rational or homogeneously autonomous. There are ‘states’which have a contingent and variable right to enforce obedience over an indefinitely large number of their ‘subjects’, although not over those who are autonomous because rational in high degree. (shrink)