Rare genetic diseases collectively impact millions of individuals in the United States. These patients and their families share many challenges including delayed diagnosis, lack of knowledgeable providers, and limited economic incentives to develop new therapies for small patient groups. As such, rare disease patients and families often must rely on advocacy, including both self-advocacy to access clinical care and public advocacy to advance research. However, these demands raise serious concerns for equity, as both care and research for a given disease (...) can depend on the education, financial resources, and social capital available to the patients in a given community. In this article, we utilize three case examples to illustrate ethical challenges at the intersection of rare diseases, advocacy and justice, including how reliance on advocacy in rare disease may drive unintended consequences for equity. We conclude with a discussion of opportunities for diverse stakeholders to begin to address these challenges. (shrink)

The epistemological premises and scientific viability of Stoffregen & Bardy's ecological perspective are evaluated by analyzing the concept of direct perception of global invariants vis-à-vis (1) behavioral evidence that perception is based on the integration of modal sources of information and (2) neurophysiological aspects of the integration of sensory signals.

Research on motivation has mainly concentrated on the role of goal orientation and self?evaluation in conducting learning activities. In this paper, we examine the relative importance of teachers? teaching and their efficacy beliefs to explain variation in student motivation. Questionnaires were used to measure the well?being, academic self?efficacy, mastery goal orientation, performance avoidance, intrinsic motivation and school investment of students (n = 3462) and the teaching practices and teachers? sense of self?efficacy (n = 194) in primary schools. Results of the (...) multi?level analyses show that connection to the students? world and cooperative learning methods had a positive effect on students? motivation, while process?oriented instruction by the teacher had a negative effect on motivational behaviour and motivational factors of students. Finally, the results lend credence to the argument that teachers? sense of self?efficacy has an impact on both teachers? teaching and students? motivation to learn. (shrink)

This article addresses the ability of Parallel Distributed Processing (PDP) networks to generate stagewise cognitive development in accordance with Piaget's theory of cognitive epigenesis. We carried out a replication study of the simulation experiments by McClelland (1989) and McClelland and Jenkins (1991) in which a PDP network learns to solve balance scale problems. In objective tests motivated from catastrophe theory, a mathematical theory of transitions in epigenetical systems, no evidence for stage transitions in network performance was found. It is concluded (...) that PDP networks lack the ability to recover the positive outcomes of analogous catastrophe analyses of real cognitive developmental data. In an attempt to further characterize the learning behaviour of PDP networks, we carried out a second simulation study using the discrimination‐shift paradigm. The results thus obtained indicate that PDP learning is compatible with the learning of stimulus‐response relationships, not with the acquisition of mediating rules such as conceived in (neo‐)Piagetian theory. In closing, we speculate about the feasibility of simulating stagewise development with alternative network architectures. (shrink)

In this paper we generalize the pigeonhole principle by using isols as our fundamental counting tool.

A nonnegative interger is called a number, a collection of numbers a set and a collection of sets a class. We write ε for the set of all numbers, o for the empty set, N(α) for the cardinality of $\alpha, \subset$ for inclusion and $\subset_+$ for proper inclusion. Let α, β 1 ,...,β k be subsets of some set ρ. Then α' stands for ρ-α and β 1 ⋯ β k for β 1 ∩ ⋯ ∩ β k . For (...) subsets α 1 ,..., α r of ρ we write: $\alpha_\sigma - \{x \in v \ (\nabla i) \lbrack i \in \sigma \Rightarrow x \in \alpha_i\rbrack\} \text{for} \sigma \subset (1, \ldots, r),\\ s_i = \sum \{N(\alpha_\sigma) \mid \sigma \subset (1,\ldots, r) \& N(\sigma) = i\}, \text{for} 0 \leqq i \leqq r$ . Note that α 0 = v, hence s 0 = N(v). If the set v is finite, the classical inclusion-exclusion principle (abbreviated IEP) states $(a) N(\alpha_1 \cup \cdots \cup \alpha_r) = \sum^r_{t=1} (-1)^{t-1} s_t = \sum_{o \subset_+\sigma \subset (1,\ldots,r)}$ (b) N(α' 1 ⋯ α' r ) = ∑ r t=0 (-1) t s t = ∑ (-1) N(σ) N (α σ ). In this paper we generalize (a) and (b) to the case where α 1 ,⋯, α r are subsets of some countable but isolated set v. Then the role of the cardinality N(α) of the set α is played by the RET (recursive equivalence type) Req α of α. These generalization of (a) and (b) are proved in § 3. Since they involve recursive distinctness, this notion is discussed in § 2. In § 4l we consider a natural extension of "the sum of the elements of a finite set σ" to the case where σ is countable. § 5 deals with valuations, i.e., certain mappings μ from classes of isolated sets into the collection λ of all isols which permit us to further generalize IEP by substituting μ(α) for $\operatorname{Req} \alpha$. (shrink)

This article addresses the ability of Parallel Distributed Processing (PDP) networks to generate stagewise cognitive development in accordance with Piaget's theory of cognitive epigenesis. We carried out a replication study of the simulation experiments by McClelland (1989) and McClelland and Jenkins (1991) in which a PDP network learns to solve balance scale problems. In objective tests motivated from catastrophe theory, a mathematical theory of transitions in epigenetical systems, no evidence for stage transitions in network performance was found. It is concluded (...) that PDP networks lack the ability to recover the positive outcomes of analogous catastrophe analyses of real cognitive developmental data. In an attempt to further characterize the learning behaviour of PDP networks, we carried out a second simulation study using the discrimination‐shift paradigm. The results thus obtained indicate that PDP learning is compatible with the learning of stimulus‐response relationships, not with the acquisition of mediating rules such as conceived in (neo‐)Piagetian theory. In closing, we speculate about the feasibility of simulating stagewise development with alternative network architectures. (shrink)

Through discourse with international groups of physicians, we conducted a cross-cultural analysis of the types of ethical dilemmas physicians face. Qualitative analysis was used to categorise the dilemmas into seven themes, which we compared among the physicians by country of practice. These themes were a-theoretically-driven and grounded heavily within the text. We then subjected the dilemmas to an analysis of moral intensity, which represents an important theoretical perspective of ethical decision making. These constructs represent salient determinants of ethical behaviour and (...) our cross-cultural sample afforded us the opportunity to consider both the pragmatic aspects of culture, as they are perceived by physicians, as well as the theory-driven concept of moral intensity. By examining both culture and moral intensity, we hope to better elucidate the complexities of ethical decision-making determinants among physicians in their daily practice. Doing so may potentially have practical implications for ethics training of medical students and foreign physicians. (shrink)

This paper deals primarily with countable, simple, connected graphs and the following two conditions which are trivially satisfied if the graphs are finite: (a) there is an edge-recognition algorithm, i.e., an effective procedure which enables us, given two distinct vertices, to decide whether they are adjacent, (b) there is a shortest path algorithm, i.e., an effective procedure which enables us, given two distinct vertices, to find a minimal path joining them. A graph $G = \langle\eta, \eta\rangle$ with η as set (...) of vertices and η as set of edges is an α-graph if it satisfies (a); it is an ω-graph if it satisfies (b). G is called r.e. (isolic) if the sets ν and η are r.e. (isolated). While every ω-graph is an α-graph, the converse is false, even if G is r.e. or isolic. Several basic properties of finite graphs do not generalize to ω-graphs. For example, an ω-tree with more than one vertex need not have two pendant vertices, but may have only one or none, since it may be a 1-way or 2-way infinite path. Nevertheless, some elementary propositions for finite graphs $G = \langle\nu, \eta\rangle$ with $n = \operatorname{card}(\nu), e = \operatorname{card}(\eta)$ , do generalize to isolic ω-graphs, e.g., n - 1 ≤ e ≤ n(n - 1)/2. Let N and E be the recursive equivalence types of ν and η respectively. Then we have for an isolic α-tree $G = \langle\nu, \eta\rangle: N = E + 1$ iff G is an ω-tree. The theorem that every finite graph has a spanning tree has a natural, effective analogue for ω-graphs. The structural difference between isolic α-graphs and isolic ω-graphs will be illustrated by: (i) every infinite graph is isomorphic to some isolic α-graph; (ii) there is an infinite graph which is not isomorphic to any isolic ω-graph. An isolic α-graph is also called a twilight graph. There are c such graphs, c denoting the cardinality of the continuum. (shrink)

Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences of (...) parents/patients at enrolment, documented by a questionnaire, with preferences developed during follow-up by an interview-study to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study. This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug, currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. (shrink)