We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

“Losing Thomas & Ella” presents a research comic about one father’s perinatal loss of twins. The comic recounts Paul’s experience of the hospital and the babies’ deaths, and it details the complex grieving process afterward, including themes of anger, distance, relationship stress, self-blame, religious challenges, and resignation. A methodological appendix explains the process of constructing the comic and provides a rationale for the use of comics-based research for illness, death, and grief among practitioners, policy makers, and the bereaved.

In an attempt to improve upon Alexander Pruss’s work (The principle of sufficient reason: A reassessment, pp. 240–248, 2006), I (Weaver, Synthese 184(3):299–317, 2012) have argued that if all purely contingent events could be caused and something like a Lewisian analysis of causation is true (per, Lewis’s, Causation as influence, reprinted in: Collins, Hall and paul. Causation and counterfactuals, 2004), then all purely contingent events have causes. I dubbed the derivation of the universality of causation the “Lewisian argument”. The (...) Lewisian argument assumed not a few controversial metaphysical theses, particularly essentialism, an incommunicable-property view of essences (per Plantinga’s, Actualism and possible worlds, reprinted in: Davidson (ed.) Essays in the metaphysics of modality, 2003), and the idea that counterfactual dependence is necessary for causation. There are, of course, substantial objections to such theses. While I think a fight against objections to the Lewisian argument can be won, I develop, in what follows, a much more intuitive argument for the universality of causation which takes as its inspiration a result from Frederic B. Fitch’s work (J Symb Logic 28(2):135–142, 1963) [with credit to who we now know was Alonzo church’s, Referee Reports on Fitch’s Definition of value, in: (Salerno (ed.), New essays on the knowability paradox, 2009)] that if all truths are such that they are knowable, then (counter-intuitively) all truths are known. The resulting Church–Fitch proof for the universality of causation is preferable to the Lewisian argument since it rests upon far weaker formal and metaphysical assumptions than those of the Lewisian argument. (shrink)

This paper introduces the notion of syntactic feature to provide a unified treatment of earlier model theoretic proofs of both the compactness and interpolation theorems for a variety of two valued logics including sentential logic, first order logic, and a family of modal sentential logic includingM,B,S 4 andS 5. The compactness papers focused on providing a proof of the consequence formulation which exhibited the appropriate finite subset. A unified presentation of these proofs is given by isolating their essential feature and (...) presenting it as an abstract principle about syntactic features. The interpolation papers focused on exhibiting the interpolant. A unified presentation of these proofs is given by isolating their essential feature and presenting it as a second abstract principle about syntactic features. This second principle reduces the problem of exhibiting the interpolant to that of establishing the existence of a family of syntactic features satisfying certain conditions. The existence of such features is established for a variety of logics (including those mentioned above) by purely combinatorial arguments. (shrink)

In (Weaver 2021), I showed that Boltzmann’s H-theorem does not face a significant threat from the reversibility paradox. I argue that my defense of the H-theorem against that paradox can be used yet again for the purposes of resolving the recurrence paradox without having to endorse heavy-duty statistical assumptions outside of the hypothesis of molecular chaos. As in (Weaver 2021), lessons from the history and foundations of physics reveal precisely how such resolution is achieved.

A Dedekind algebra is an ordered pair (B, h), where B is a non-empty set and h is a similarity transformation on B. Among the Dedekind algebras is the sequence of the positive integers. From a contemporary perspective, Dedekind established that the second-order theory of the sequence of the positive integers is categorical and finitely axiomatizable. The purpose here is to show that this seemingly isolated result is a consequence of more general results in the model theory of second-order languages. (...) Each Dedekind algebra can be decomposed into a family of disjoint, countable subalgebras called the configurations of the algebra. There are ?0 isomorphism types of configurations. Each Dedekind algebra is associated with a cardinal-valued function on ? called its configuration signature. The configuration signature counts the number of configurations in each isomorphism type that occurs in the decomposition of the algebra. Two Dedekind algebras are isomorphic iff their configuration signatures are identical. The second-order theory of any countably infinite Dedekind algebra is categorical, and there are countably infinite Dedekind algebras whose second-order theories are not finitely axiomatizable. It is shown that there is a condition on configuration signatures necessary and sufficient for the second-order theory of a Dedekind algebra to be finitely axiomatizable. It follows that the second-order theory of the sequence of the positive integers is categorical and finitely axiomatizable. (shrink)

A Dedekind Algebra is an ordered pair (B,h) where B is a non-empty set and h is an injective unary function on B. Each Dedekind algebra can be decomposed into a family of disjoint, countable subalgebras called configurations of the Dedekind algebra. There are N0 isomorphism types of configurations. Each Dedekind algebra is associated with a cardinal-valued function on omega called its configuration signature. The configuration signature of a Dedekind algebra counts the number of configurations in the decomposition of the (...) algebra in each isomorphism type.The configuration signature of a Dedekind algebra encodes the structure of that algebra in the sense that two Dedekind algebras are isomorphic iff their configuration signatures are identical. Configuration signatures are used to establish various results in the first-order model theory of Dedekind algebras. These include categoricity results for the first-order theories of Dedekind algebras and existence and uniqueness results for homogeneous, universal and saturated Dedekind algebras. Fundamental to these results is a condition on configuration signatures that is necessary and sufficient for elementary equivalence. (shrink)

A Dedekind algebra is an order pair (B, h) where B is a non-empty set and h is a similarity transformation on B. Each Dedekind algebra can be decomposed into a family of disjoint, countable subalgebras called the configurations of the algebra. There are 0 isomorphism types of configurations. Each Dedekind algebra is associated with a cardinal-valued function on called its configuration signature. The configuration signature counts the number of configurations in each isomorphism type which occur in the decomposition of (...) the algebra. Two Dedekind algebras are isomorphic iff their configuration signatures are identical. It is shown that configuration signatures can be used to characterize the homogeneous, universal and homogeneous-universal Dedekind algebras. This characterization is used to prove various results about these subclasses of Dedekind algebras. (shrink)

M. Oaksford and N. Chater presented a Bayesian analysis of the Wason selection task in which they proposed that people choose cards in order to maximize expected information gain as measured by reduction in uncertainty in the Shannon-Weaver information theory sense. It is argued that the EIG measure is both psychologically implausible and normatively inadequate as a measure of epistemic utility. The article is also concerned with the descriptive account of findings in the selection task literature offered by Oaksford (...) and Chater. First, it is shown that their analysis data reported in the recent article of K. N. Kirby is unsound; second, an EIG analysis is presented of the experiments of P. Pollard and J. St. B. T. Evans that provides a strong empirical disconfirmation of the theory. (shrink)

We propose a way in which Barsalou could strengthen his position and at the same time make a considerable dent in the category/abstraction problem (that he suggests remains unsolved). There exists a class of connectionist models that solves this problem parsimoniously and provides a mechanistic underpinning for the promising high-level architecture he proposes.

In this paper, I consider a variety of objections against the covering-law model of scientific explanation, show that Aristotle was already aware of them and had solutions for them, and argue that these solutions are correct. These solutions involve the notions of nonHumean causality and of essential properties. There are a great many familiar objections, both methodological and epistemological, to introducing these concepts into the methodology of science, but I show that these objections are based upon misunderstandings of these concepts.

A number of recent arguments purport to show that imprecise credences are incompatible with accuracy-first epistemology. If correct, this conclusion suggests a conflict between evidential a...

Background: Clinical genomic implementation studies pose challenges for informed consent. Consent forms often include complex language and concepts, which can be a barrier to diverse enrollment, and these studies often blur traditional research-clinical boundaries. There is a move toward self-directed, web-based research enrollment, but more evidence is needed about how these enrollment approaches work in practice. In this study, we developed and evaluated a literacy-focused, web-based consent approach to support enrollment of diverse participants in an ongoing clinical genomic implementation study. (...) Methods: As part of the Cancer Health Assessments Reaching Many (CHARM) study, we developed a web-based consent approach that featured plain language, multimedia, and separate descriptions of clinical care and research activities. CHARM offered clinical exome sequencing to individuals at high risk of hereditary cancer. We interviewed CHARM participants about their reactions to the consent approach. We audio recorded, transcribed, and coded interviews using a deductively and inductively derived codebook. We reviewed coded excerpts as a team to identify overarching themes. Results: We conducted 32 interviews, including 12 (38%) in Spanish. Most (69%) enrolled without assistance from study staff, usually on a mobile phone. Those who completed enrollment in one day spent an average of 12 minutes on the consent portion. Interviewees found the information simple to read but comprehensive, were neutral to positive about the multimedia support, and identified increased access to testing in the study as the key difference from clinical care. Conclusions: This study showed that interviewees found our literacy-focused, web-based consent approach acceptable; did not distinguish the consent materials from other online study processes; and valued getting access to testing in the study. Overall, conducting empirical bioethics research in an ongoing clinical trial was useful to demonstrate the acceptability of our novel consent approach but posed practical challenges. (shrink)

An attempt is made to show that Wittgenstein's later philosophy of logic is not the kind of conventionalism which is often ascribed to him. On the contrary, Wittgenstein gives expression to a “mixed” theory which is not only interesting but tends to resolve the perplexities usually associated with the question of the a priori character of logical truth. I try to show that Wittgenstein is better understood not as denying that there are such things as “logical rules” nor as denying (...) that the results of applying such rules are “logically necessary,” but as trying to understand what it is to appeal to a logical rule and what it means to say that the results of applying such a rule are “necessary.” He is not so much overthrowing standard accounts of logical necessity as discovering the limits of the concept. (shrink)

Objective To determine the attitudes of Egyptian patients regarding their participation in research and with the collection, storage and future use of blood samples for research purposes. Design Cross-sectional survey. Study population Adult Egyptian patients (n=600) at rural and urban hospitals and clinics. Results Less than half of the study population (44.3%) felt that informed consent forms should provide research participants the option to have their blood samples stored for future research. Of these participants, 39.9% thought that consent forms should (...) include the option that future research be restricted to the illness being studied. A slight majority (66.2%) would donate their samples for future genetic research. Respondents were more favourable towards having their blood samples exported to other Arab countries (62.0%) compared with countries in Europe (41.8%, p<0.001) and to the USA (37.2%, p<0.001). Conclusions This study shows that many individuals do not favour the donation of a blood sample for future research. Of those who do approve of such future research, many favour a consent model that includes an option restricting the future research to the illness being studied. Also, many Egyptians were hesitant to have their blood samples donated for genetic research or exported out of the Arab region to the USA and European countries. Further qualitative research should be performed to determine the underlying reasons for many of our results. (shrink)

In this text, a variety of modal logics at the sentential, first-order, and second-order levels are developed with clarity, precision and philosophical insight. All of the S1-S5 modal logics of Lewis and Langford, among others, are constructed. A matrix, or many-valued semantics, for sentential modal logic is formalized, and an important result that no finite matrix can characterize any of the standard modal logics is proven. Exercises, some of which show independence results, help to develop logical skills. A separate sentential (...) modal logic of logical necessity in logical atomism is also constructed and shown to be complete and decidable. On the first-order level of the logic of logical necessity, the modal thesis of anti-essentialism is valid and every de re sentence is provably equivalent to a de dicto sentence. An elegant extension of the standard sentential modal logics into several first-order modal logics is developed. Both a first-order modal logic for possibilism containing actualism as a proper part as well as a separate modal logic for actualism alone are constructed for a variety of modal systems. Exercises on this level show the connections between modal laws and quantifier logic regarding generalization into, or out of, modal contexts and the conditions required for the necessity of identity and non-identity. Two types of second-order modal logics, one possibilist and the other actualist, are developed based on a distinction between existence-entailing concepts and concepts in general. The result is a deeper second-order analysis of possibilism and actualism as ontological frameworks. Exercises regarding second-order predicate quantifiers clarify the distinction between existence-entailing concepts and concepts in general. Modal Logic is ideally suited as a core text for graduate and undergraduate courses in modal logic, and as supplementary reading in courses on mathematical logic, formal ontology, and artificial intelligence. (shrink)

In order to slow down the inexorable increase in spending on health care, the British government has implemented an initiative proposed by Griffiths. This initiative is designed to make doctors more accountable for the decisions they may take. In this essay I argue first, that the conflation of two decisions (financial and clinical) leads to unnecessary ethical dilemmas and secondly, that as psychologically it is difficult to take two decisions simultaneously, inevitably the clinician is forced to name either the financial (...) or the clinical decision as the prior problem. To decide for the former inevitably strains the traditional doctor/patient relationship of mutual trust. (shrink)

This paper describes the perspectives of stakeholders within the North American dairy industry on key issues affecting the welfare of dairy cattle. Five heterogeneous focus groups were held during a dairy cattle welfare meeting in Guelph, Canada in October 2012. Each group contained between 7 and 10 participants and consisted of a mix of dairy producers, veterinarians, academics, students, and dairy industry specialists. The 1-h facilitated discussions were audio-recorded and transcribed verbatim. Content analysis of the resulting transcripts showed that participants (...) across all stakeholder categories identified lameness as the most important welfare issue facing dairy cattle. Other prominent issues of concern included cow comfort, disease, on-farm mortality, stockmanship, painful procedures, injuries, cull cow management, calf management, and restriction of behavioural freedoms. Participants typically gave several reasons for why they considered issues problematic. Underlying reasons were grouped according to animal-centered concerns [at both the individual and at the herd level ] and industry-centered concerns . This analysis identified areas of shared concern among diverse stakeholder groups, which should aid in the development of standards and policies that satisfy stakeholders within and external to the dairy industry. (shrink)