Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disorder treated with bone marrow transplantation or enzyme replacement therapy with laronidase, a high-cost orphan drug. Laronidase was approved by the US Food and Drug Administration and the European Medicines Agency in 2003 and by the Brazilian National Health Surveillance Agency in 2005. Many Brazilian MPS I patients have been receiving laronidase despite the absence of a governmental policy regulating access to the drug. Epidemiological and treatment data concerning MPS I (...) are scarce. This study aims to present a demographic profile of Brazilian patients with MPS I, describe the routes of access to laronidase in Brazil, and discuss associated ethical issues relating to public funding of orphan drugs. (shrink)

Since at least Hume and Kant, philosophers working on the nature of aesthetic judgment have generally agreed that common sense does not treat aesthetic judgments in the same way as typical expressions of subjective preferences—rather, it endows them with intersubjective validity, the property of being right or wrong regardless of disagreement. Moreover, this apparent intersubjective validity has been taken to constitute one of the main explananda for philosophical accounts of aesthetic judgment. But is it really the case that most people (...) spontaneously treat aesthetic judgments as having intersubjective validity? In this paper, we report the results of a cross‐cultural study with over 2,000 respondents spanning 19 countries. Despite significant geographical variations, these results suggest that most people do not treat their own aesthetic judgments as having intersubjective validity. We conclude by discussing the implications of our findings for theories of aesthetic judgment and the purpose of aesthetics in general. (shrink)

The immune system can generate an almost infinite number of different antibody specificities, the sum of which is the antibody repertoire. This article considers aspects of the mechanism and control of immunoglobulin variable (V) region gene assembly with a focus on how these factors may affect generation of the antibody repertoire in normal and disease states. New model systems to study the mechanism and control of V gene assembly are described, in particular the introduction of V gene recombination substrates into (...) Abelson murine leukemia virus‐transformed pre‐B cells. Finally, a model is presented which suggests that control of V gene assembly is mediated by regulating accessibility of substrate gene segments to recombinational machinery. (shrink)

Background Regionalised models of health care delivery have important implications for people with disabilities and chronic illnesses yet the ethical issues surrounding disability and regionalisation have not yet been explored. Although there is ethics-related research into disability and chronic illness, studies of regionalisation experiences, and research directed at improving health systems for these patient populations, to our knowledge these streams of research have not been brought together. Using the Canadian province of Ontario as a case study, we address this gap (...) by examining the ethics of regionalisation and the implications for people with disabilities and chronic illnesses. The critical success factors we provide have broad applicability for guiding and/or evaluating new and existing regionalised health care strategies. Discussion Ontario is in the process of implementing fourteen Local Health Integration Networks (LHINs). The implementation of the LHINs provides a rare opportunity to address systematically the unmet diverse care needs of people with disabilities and chronic illnesses. The core of this paper provides a series of composite case vignettes illustrating integration opportunities relevant to these populations, namely: (i) rehabilitation and services for people with disabilities; (ii) chronic illness and cancer care; (iii) senior's health; (iv) community support services; (v) children's health; (vi) health promotion; and (vii) mental health and addiction services. For each vignette, we interpret the governing principles developed by the LHINs – equitable access based on patient need, preserving patient choice, responsiveness to local population health needs, shared accountability and patient-centred care – and describe how they apply. We then offer critical success factors to guide the LHINs in upholding these principles in response to the needs of people with disabilities and chronic illnesses. Summary This paper aims to bridge an important gap in the literature by examining the ethics of a new regionalisation strategy with a focus on the implications for people with disabilities and chronic illnesses across multiple sites of care. While Ontario is used as a case study to contextualize our discussion, the issues we identify, the ethical principles we apply, and the critical success factors we provide have broader applicability for guiding and evaluating the development of – or revisions to – a regionalised health care strategy. (shrink)

Nietzsche declara em uma carta de 1881 que sua filosofia e a de Espinosa partilham de uma “idêntica tendência geral”, resumida na fórmula: “fazer do conhecimento o afeto mais potente”. Contudo, em anotações do mesmo período da carta declara que se para Espinosa o conhecimento é um afeto para ele o conhecimento é uma paixão. O que significa, em Espinosa, definir o conhecimento como afeto e, em Nietzsche, o conhecimento como paixão? Para responder a esta questão delimitamos dois objetivos. Primeiro: (...) compreender porque Espinosa define na Parte V da Ética o conhecimento de terceiro gênero como o afeto mais potente e não um paixão. Para tanto, precisamos verificar: 1. a distinção entre os termos paixão e afeto no contexto da teoria dos afetos ; 2. a relação entre a teoria dos três gêneros do conhecimento e a teoria dos afetos. Segundo: examinar o que significa, para Nietzsche, o conhecimento como paixão. Delimitamos essa pesquisa aos textos do período da carta tendo por fio condutor as expressões: “paixão do conhecimento” e “nova paixão”. (shrink)

In the 1960’s, both Montague (e.g. 1970, 222) and Grice (1975, 24) famously declared that natural languages were not so different from the formal languages of logic as people had thought. Montague sought to comprehend the grammars of both within a single theory, and Grice sought to explain away apparent divergences as due to the fact that the former, but not the latter, were used for conversation. But, if we confine our concept of logic to first order predicate logic (or (...) FOPL) with identity (that is, omitting everything which is not required for the pursuit of mathematical truth), then there are of course many other aspects, in addition to its use in conversation, which distinguish natural language from logic. Conventional implicature, information structure (including presupposition), tense and time reference, and the expression of causation and inference are several of these, which combine as well with syntactic complexities which are unnecessary in first order predicate logic. In this paper I will argue that such distinguishing aspects should be more fully exploited to explain the differences between the material conditional of logic and the indicative conditional of one natural language (English). (shrink)

Populizmus dnes predstavuje často skloňovaný pojem tak na akademickej pôde, ako i na samotnej politickej scéne, v médiách a medzi laickou verejnosťou. Skutočnosťou je, že hoci v našej spoločnosti tento pojem používa takmer každý, len málokto vie, čo vlastne znamená. V tomto článku sa preto budeme zaoberať otázkou, ktorá sa stala predmetom analýz mnohých teoretikov, otázkou, čo je to populizmus. Jedným z tých teoretikov je Ernesto Laclau (1935–2014), ktorý populizmus nechápe ako ideológiu, ale ako istú stratégiu resp. spôsob komunikácie. V (...) prvej časti nášho článku vymedzíme pojem „populizmus“, pričom upozorníme na jeho viaceré rozličné interpretácie ako aj na to, aké je jeho spoločné základné analytické jad­ro. V nasledujúcich častiach článku sa už zameriame na analýzu populizmu podľa Ernesta Laclaua. Cieľom nášho článku je teda analýza teórie populizmu podľa E. Laclaua v kontexte súčas­nej situácie na domácej i svetovej, nielen politickej scéne. (shrink)

BackgroundDouble-blind peer review has been proposed as a possible solution to avoid implicit referee bias in academic publishing. The aims of this study are to analyse the demographics of corresponding authors choosing double-blind peer review and to identify differences in the editorial outcome of manuscripts depending on their review model.MethodsData includes 128,454 manuscripts received between March 2015 and February 2017 by 25 Nature-branded journals. We investigated the uptake of double-blind review in relation to journal tier, as well as gender, country, (...) and institutional prestige of the corresponding author. We then studied the manuscripts’ editorial outcome in relation to review model and author’s characteristics. The gender (male, female, or NA) of the corresponding authors was determined from their first name using a third-party service (Gender API). The prestige of the corresponding author’s institutions was measured from the data of the Global Research Identifier Database (GRID) by dividing institutions in three prestige groups with reference to the 2016 Times Higher Education (THE) ranking. We employed descriptive statistics for data exploration, and we tested our hypotheses using Pearson’s chi-square and binomial tests. We also performed logistic regression modelling with author update, out-to-review, and acceptance as response, and journal tier, author gender, author country, and institution as predictors.ResultsAuthor uptake for double-blind submissions was 12% (12,631 out of 106,373). We found a small but significant association between journal tier and review type (p value < 0.001, Cramer’s V = 0.054, df = 2). We had gender information for 50,533 corresponding authors and found no statistically significant difference in the distribution of peer review model between males and females (p value = 0.6179). We had 58,920 records with normalised institutions and a THE rank, and we found that corresponding authors from the less prestigious institutions are more likely to choose double-blind review (p value < 0.001, df = 2, Cramer’s V = 0.106). In the ten countries with the highest number of submissions, we found a large significant association between country and review type (p value < 0.001, df = 10, Cramer’s V = 0.189). The outcome both at first decision and post review is significantly more negative (i.e. a higher likelihood for rejection) for double-blind than single-blind papers (p value < 0.001, df = 1, Cramer’s V = 0.112 for first decision; p value < 0.001; df = 1, Cramer’s V = 0.082 for post-review decision).ConclusionsThe proportion of authors that choose double-blind review is higher when they submit to more prestigious journals, they are affiliated with less prestigious institutions, or they are from specific countries; the double-blind option is also linked to less successful editorial outcomes. (shrink)

Book Information The Myths We Live By. The Myths We Live By Mary Midgley , London: Routledge , 2003 , 175 , US$29.95 ( cloth ) By Mary Midgley. London: Routledge. Pp. 175. US$29.95 (cloth:).

v. 1. Theory of continuous Fokker-Planck systems -- v. 2. Theory of noise induced processes in special applications -- v. 3. Experiments and simulations.

Speech unfolds over time, and the cues for even a single phoneme are rarely available simultaneously. Consequently, to recognize a single phoneme, listeners must integrate material over several hundred milliseconds. Prior work contrasts two accounts: (a) a memory buffer account in which listeners accumulate auditory information in memory and only access higher level representations (i.e., lexical representations) when sufficient information has arrived; and (b) an immediate integration scheme in which lexical representations can be partially activated on the basis of early (...) cues and then updated when more information arises. These studies have uniformly shown evidence for immediate integration for a variety of phonetic distinctions. We attempted to extend this to fricatives, a class of speech sounds which requires not only temporal integration of asynchronous cues (the frication, followed by the formant transitions 150–350 ms later), but also integration across different frequency bands and compensation for contextual factors like coarticulation. Eye movements in the visual world paradigm showed clear evidence for a memory buffer. Results were replicated in five experiments, ruling out methodological factors and tying the release of the buffer to the onset of the vowel. These findings support a general auditory account for speech by suggesting that the acoustic nature of particular speech sounds may have large effects on how they are processed. It also has major implications for theories of auditory and speech perception by raising the possibility of an encapsulated memory buffer in early auditory processing. (shrink)

In the paper, a philosophical and methodological analysis of the evolution of cybernetics in the context of the development of scientific rationality is carried out. The evolution of cybernetics is represented as a movement from the methodology of “observable systems” and to the methodology of “observing systems” and to the methodology of self-developing reflexive-active environments. Special attention is paid to the formation of a new promising direction for post-non-classical cybernetics of self-developing poly-subject environments, which, given the correlation with previous stages (...) of cybernetics development, we define as thirdorder cybernetics. The analysis of the basics of the formation of third-order cybernetics was carried out with consideration of interrelated aspects: philosophical, methodological, theoretical, and methodical. We also provide model of self-developing poly-subject environments as well as a system of ontologies, defining the mechanisms of functioning of such self-organizing poly-subject environments and active elements that organize the communication space. The ontology system also makes it possible to integrate cybernetics of the first, second, and third order. Some sociohumanitarian trends in the development of cybernetics are considered: from an external observer to a distributed observer; from monodisciplinary to transdisciplinary approaches; from activity approach to subject-activity one, and further to subject-oriented approach; from information to active knowledge; from ethics of goals to ethics of strategic subjects. Potential opportunities for using third-order cybernetics are described, in order to improve the quality of solving a number of important scientific and practical problems of controlling social systems. Information is provided on the directions of approbation of a third-order cybernetics concept for improving state administration, based on a system of distributed situational centers, and there is its approbation at international scientific conferences. (shrink)