The scope of noninvasive prenatal testing (NIPT) could expand in the future to include detailed analysis of the fetal genome. This will allow for the testing for virtually any trait with a genetic contribution, including “non-medical” traits. Here we discuss the potential use of NIPT for these traits. We outline a scenario which highlights possible inconsistencies with ethical decision-making. We then discuss the case against permitting these uses. The objections include practical problems; increasing inequities; increasing the burden of choice; negative (...) impacts on the child, family, and society; and issues with implementation. We then outline the case for permitting the use of NIPT for these traits. These include arguments for reproductive liberty and autonomy; questioning the labeling of traits as “non-medical”; and the principle of procreative beneficence. This summary of the case for and against can serve as a basis for the development of a consistent and coherent ethical framework. (shrink)

The scope of noninvasive prenatal testing (NIPT) could expand in the future to include detailed analysis of the fetal genome. This will allow for the testing for virtually any trait with a genetic contribution, including “non-medical” traits. Here we discuss the potential use of NIPT for these traits. We outline a scenario which highlights possible inconsistencies with ethical decision-making. We then discuss the case against permitting these uses. The objections include practical problems; increasing inequities; increasing the burden of choice; negative (...) impacts on the child, family, and society; and issues with implementation. We then outline the case for permitting the use of NIPT for these traits. These include arguments for reproductive liberty and autonomy; questioning the labeling of traits as “non-medical”; and the principle of procreative beneficence. This summary of the case for and against can serve as a basis for the development of a consistent and coherent ethical framework. (shrink)

While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

An equivalence between the category of MV-algebras and the category \ is given in Castiglioni et al. :67–92, 2014). An integral residuated lattice with bottom is an MV-algebra if and only if it satisfies the equations \ \vee = 1}\) and \ = a \wedge b}\). An object of \ is a residuated lattice which in particular satisfies some equations which correspond to the previous equations. In this paper we extend the equivalence to the category whose objects are pairs, where (...) A is an MV-algebra and I is an ideal of A. (shrink)

An equivalence between the category of MV-algebras and the category $${{\rm MV^{\bullet}}}$$ MV ∙ is given in Castiglioni et al. :67–92, 2014). An integral residuated lattice with bottom is an MV-algebra if and only if it satisfies the equations $${a = \neg \neg a, \vee = 1}$$ a = ¬ ¬ a, ∨ = 1 and $${a \odot = a \wedge b}$$ a ⊙ = a ∧ b. An object of $${{\rm MV^{\bullet}}}$$ MV ∙ is a residuated lattice which in (...) particular satisfies some equations which correspond to the previous equations. In this paper we extend the equivalence to the category whose objects are pairs, where A is an MV-algebra and I is an ideal of A. (shrink)

This book explores in detail the relation between ontology and ethics in the early work of Ludwig Wittgenstein, notably the _Tractatus Logico-Philosophicus_ and, to a lesser extent, the _Notebooks 1914-1916_. Self-contained and requiring no prior knowledge of Wittgenstein's thought, it is the first book-length argument that his views on ethics decisively shaped his ontological and semantic thought. The book's main thesis is twofold. It argues that the ontological theory of the _Tractatus_ is fundamentally dependent on its logical and linguistic doctrines: (...) the tractarian world is the world as it appears in language and thought. It also maintains that this interpretation of the ontology of the _Tractatus_ can be argued for not only on systematic grounds, but also via the contents of the ethical theory that it offers. Wittgenstein's views on ethics presuppose that language and thought are but one way in which we interact with reality. Although detailed studies of Wittgenstein's ontology and ethics exist, this book is the first thorough investigation of the relationship between them. As an introduction to Wittgenstein, it sheds new light on an important aspect of his early thought. (shrink)

BackgroundPreprint usage is growing rapidly in the life sciences; however, questions remain on the relative quality of preprints when compared to published articles. An objective dimension of quality that is readily measurable is completeness of reporting, as transparency can improve the reader’s ability to independently interpret data and reproduce findings.MethodsIn this observational study, we initially compared independent samples of articles published in bioRxiv and in PubMed-indexed journals in 2016 using a quality of reporting questionnaire. After that, we performed paired comparisons (...) between preprints from bioRxiv to their own peer-reviewed versions in journals.ResultsPeer-reviewed articles had, on average, higher quality of reporting than preprints, although the difference was small, with absolute differences of 5.0% [95% CI 1.4, 8.6] and 4.7% [95% CI 2.4, 7.0] of reported items in the independent samples and paired sample comparison, respectively. There were larger differences favoring peer-reviewed articles in subjective ratings of how clearly titles and abstracts presented the main findings and how easy it was to locate relevant reporting information. Changes in reporting from preprints to peer-reviewed versions did not correlate with the impact factor of the publication venue or with the time lag from bioRxiv to journal publication.ConclusionsOur results suggest that, on average, publication in a peer-reviewed journal is associated with improvement in quality of reporting. They also show that quality of reporting in preprints in the life sciences is within a similar range as that of peer-reviewed articles, albeit slightly lower on average, supporting the idea that preprints should be considered valid scientific contributions. (shrink)

0-categorical o-minimal structures were completely described by Pillay and Steinhorn 565–592), and are essentially built up from copies of the rationals as an ordered set by ‘cutting and copying’. Here we investigate the possible structures which an 0-categorical weakly o-minimal set may carry, and find that there are some rather more interesting examples. We show that even here the possibilities are limited. We subdivide our study into the following principal cases: the structure is 1-indiscernible, in which case all possibilities are (...) classified up to binary structure; the structure is 2-indiscernible, classified up to ternary structure; the structure is 3-indiscernible, in which case we show that it is k-indiscernible for every finite k. We also make some remarks about the possible structures of higher arities which an 0-categorical weakly o-minimal structure may carry. (shrink)

In this paper we shall introduce the variety FWHA of frontal weak Heyting algebras as a generalization of the frontal Heyting algebras introduced by Leo Esakia in [ 10 ]. A frontal operator in a weak Heyting algebra A is an expansive operator τ preserving finite meets which also satisfies the equation $${\tau(a) \leq b \vee (b \rightarrow a)}$$, for all $${a, b \in A}$$. These operators were studied from an algebraic, logical and topological point of view by Leo Esakia (...) in [ 10 ]. We will study frontal operators in weak Heyting algebras and we will consider two examples of them. We will give a Priestley duality for the category of frontal weak Heyting algebras in terms of relational spaces $${\langle X, \leq, T, R \rangle}$$ where $${\langle X, \leq, T \rangle}$$ is a WH -space [ 6 ], and R is an additional binary relation used to interpret the modal operator. We will also study the WH -algebras with successor and the WH -algebras with gamma. For these varieties we will give two topological dualities. The first one is based on the representation given for the frontal weak Heyting algebras. The second one is based on certain particular classes of WH -spaces. (shrink)

Living donation provides important access to organ transplantation, which is the optimal therapy for patients with end-stage liver or kidney failure. Paired exchanges have facilitated thousands of kidney transplants and enable transplantation when the donor and recipient are incompatible. However, frequently willing and otherwise healthy donors have contraindications to the donation of the organ that their recipient needs. Trans-organ paired exchanges would enable a donor associated with a kidney recipient to donate a lobe of liver and a donor associated with (...) a liver recipient to donate a kidney. This article explores some of the ethical concerns that trans-organ exchange might encounter including unbalanced donor risks, the validity of informed consent, and effects on deceased organ donation. (shrink)

BackgroundUnderstanding representations of disease in various art genres provides insights into how patients and health care providers view the diseases. It can also be used to enhance patient care and stimulate patient self-management.MethodsThis paper reviews how cardiovascular diseases are represented in novels, films, and paintings: myocardial infarction, aneurysm, hypertension, stroke, heart transplantation, Marfan’s disease, congestive heart failure. Various search systems and definitions were used to help identify sources of representations of different cardiovascular diseases. The representations of the different diseases were (...) considered separately. The Common Sense Model was used a theoretical model to outline illness perceptions and self-management in the various identified novels, films, and paintings.ResultsMyocardial infarction followed by stroke were the most frequently detailed diseases in all three art genres. This reflects their higher prevalence. Representations ranged from biomedical details through to social and psychological consequences of the diseases.ConclusionsArtistic representations of cardiovascular diseases reflect cognitions, emotions, and images of prevalent disease. These representations shape views and behaviour of ill and healthy persons regarding heart diseases. As these representations are amenable to change, they deserve further research, which may be instrumental in improving the quality of life of persons struck by cardiovascular diseases. Changing illness perceptions appears to be a method to improve self-management and thereby quality of life in patients with various cardiovascular diseases. (shrink)

This book applies Augustine's thought to current questions of teaching and learning. The essays are written in an accessible style and is not intended just for experts on Augustine or church history.

This volume consists of 21 essays on Marsilio Ficino (1433-99), the Florentine scholar-philosopher-magus-priest who was the architect of Renaissance Platonism.

This study expands the application of deonance theory into organizations’ upper echelons by examining how CEOs imprinted with a sense of duty can influence managerial decision-making. We hypothesize an imprint of bounded autonomy, an ought-force that constrains their decision-making and understanding of behavioral freedom, influences duty-bound CEOs to self-report errors in past financial reporting. We test deonance theory propositions of instrumentality for behavioral expansion, namely loss avoidance and gain attainment, related to institutional ownership concentration and CEO equity ownership. We use (...) CEOs that are graduates of U.S. service academies as a proxy for duty-bound executives and find firms they lead are more likely to issue a financial restatement to correct a previous reporting error. This finding is robust to alternate explanations such as being error-prone, earnings management, auditor oversight, and risk behaviors. We also find evidence that deonance may be subject to behavioral expansion. The likelihood of issuing a restatement decreases as institutional ownership concentration and CEO equity ownership increases. This study shows imprinted deonance within the C-suite influences important organizational outcomes. (shrink)

1 Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2 During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for (...) generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3 The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4 The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5 Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible. (shrink)

A sense of agency over wilful actions is thought to be dependent on the level of choice and the nature of the outcome. In a preregistered study, we manipulated choice and valence of outcome to assess the relationship between SoA across the depression and psychosis continuum. Participants completed a Libet Clock task, in which they had either a free or forced choice to press one of two buttons and received either a rewarding or punishing outcome. Participants also completed questionnaires on (...) depressive and psychosis-like traits. Rewarding outcomes increased intentional binding. The evidence favoured no effect of choice on average, but this was influenced by inter-individual differences. Individuals reporting more depressive traits had less of a difference in intentional binding between free and forced choice conditions. We show that implicit SoA is sensitive to outcome valence and the effect of choice differs across the depression continuum. (shrink)