Ion channels are transport proteins present in the lipid bilayers of biological membranes. They are involved in many physiological processes, such as the generation of nerve impulses, hormonal secretion, and heartbeat. Conformational changes in the ion channel-forming protein allow the opening or closing of pores to control the ionic flux through the cell membranes. The opening and closing of the ion channel have been classically treated as a random kinetic process, known as a Markov process. Here the time the channel (...) remains in a given state is assumed to be independent of the condition it had in the previous state. More recently, however, several studies have shown that this process is not random but a deterministic one, where both the open and closed dwell-times and the ionic current flowing through the channel are history-dependent. This property is called long memory or long-range correlation. However, there is still much controversy regarding how this memory originates, which region of the channel is responsible for this property, and which models could best reproduce the memory effect. In this article, we provide a review of what is, where it is, its possible origin, and the mathematical methods used to analyze the long-term memory present in the kinetic process of ion channels. (shrink)

IntroductionTranscranial magnetic stimulation is a consolidated procedure for the treatment of depression, with several meta-analyses demonstrating its efficacy. Theta-burst stimulation is a modification of TMS with similar efficacy and shorter session duration. The geriatric population has many comorbidities and a high prevalence of depression, but few clinical trials are conducted specifically for this age group. TBS could be an option in this population, offering the advantages of few side effects and no pharmacological interactions. Therefore, our aim is to investigate the (...) efficacy of TBS in geriatric depression.Clinical trial registration[https://clinicaltrials.gov/ct2/], identifier [NCT04842929]. (shrink)

Making research data readily accessible during a public health emergency can have profound effects on our response capabilities. The moral milieu of this data sharing has not yet been adequately explored. This article explores the foundation and nature of a duty, if any, that researchers have to share data, specifically in the context of public health emergencies. There are three notable reasons that stand in opposition to a duty to share one’s data, relating to: (i) data property and ownership, (ii) (...) just distribution of benefits and burdens and (iii) the contemporary ethos of science. We argue each reason can be successfully met with corresponding rationale in favour of data sharing. Further support for data sharing has been echoed in policies of health agencies, funding bodies and academic institutions; in documents on the ethical conduct of biomedical research; and in discussions on the nature of public health. From this, we ascertain that sharing data is the morally sound default position. This article then highlights the key roles reciprocity and solidarity play in supporting the practice of data sharing. We conclude with recommendations to regard public health research data as a common-pool resource in order to build a framework for stable data sharing management. (shrink)

The coronavirus disease pandemic fundamentally disrupted humans’ social life and behavior. Public health measures may have inadvertently impacted how people care for each other. This study investigated prosocial behavior, its association well-being, and predictors of prosocial behavior during the first COVID-19 pandemic lockdown and sought to understand whether region-specific differences exist. Participants from eight regions clustering multiple countries around the world responded to a cross-sectional online-survey investigating the psychological consequences of the first upsurge of lockdowns in spring 2020. Prosocial behavior (...) was reported to occur frequently. Multiple regression analyses showed that prosocial behavior was associated with better well-being consistently across regions. With regard to predictors of prosocial behavior, high levels of perceived social support were most strongly associated with prosocial behavior, followed by high levels of perceived stress, positive affect and psychological flexibility. Sociodemographic and psychosocial predictors of prosocial behavior were similar across regions. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

The aim of this study was to analyze the association between coaches’ experience and their perceptions on the implementation of a long-term athletic development model created in 2016 by the Portuguese Swimming Federation. Eighty-six swimming coaches were assembled in groups according to their experience level: “novice”, “intermediate”, and “experienced”, and they answered a questionnaire with the following items: awareness of the existing model acceptance usefulness for practice, and implementation of this model by their peers. Regardless of experience, ~67% of the (...) coaches were aware of the model. Among those, a large number showed acceptance and confidence in its usefulness for their daily practice. Most coaches showed concerns about the fact that their peers do not respect the model frameworks, declaring the search for their swimmers’ immediate success as the main cause for such behavior. The results also showed an association between experience and knowledge about the model’s existence [χ2 = 10.223, p < 0.01, V = 0.345], and experienced coaches exhibited better knowledge than their intermediate [χ2 = 9.555, p < 0.01, V = 0.393] or novice [χ2 = 5.926, p = 0.02, V = 0.314] counterparts. While there was an association between the coaches’ experience and knowledge about the LTAD model’s existence, this situation does not seem to influence the way coaches accept and understand the usefulness of the model for their daily practice. (shrink)

A obra Consequências da liberdade, publicada no ano de 2011 pela Editora Universitária da UFPE, é primeira obra do escritor e filósofo Geraldo Euclides da Silva, e que certamente se firmará no cenário de exegese das pesquisas sobre o pensamento existencialista de corte sartreano.

Child poly-victimization is a risk factor for psychopathology in adulthood, such as anxiety and depression. Despite that, there is minus investment regarding psychotic symptoms and the mechanisms explaining the relationship between poly-victimization and psychoticism. The purpose of this study is to investigate these variables and explain how they might be associated. A sample of 246 adults participated in this study, aged between 18 and 68 years (M = 37.5, SD = 12.5) and mostly females (76.8%). The results revealed a significant (...) mediating effect of anxiety and depression in the relationship between childhood victimization and psychoticism (b =.12, p =.011), but not a significant moderating effect of gender, Δχ2(5) = 3.87, p =.568. The affective pathway was supported by our findings. These results suggest the need of additional efforts on prevention of child victimization, as well as of intervention programs aiming to prevent its cumulative effect. (shrink)

Although various scholars underscore the importance of innovating responsibly in view of today's societal challenges, less attention has been paid to the entrepreneurial skillset, that is, the range of individual skills and organizational capabilities, that innovation-based organizations mobilize to deliver new responsible products and services. This paper thus explores the relationships between the entrepreneurial skillsets of 16 Canadian and Brazilian for-profit and not-for-profit organizations producing Responsible Innovations in Health (RIH) and their degree of responsibility. Our mixed methods study includes interviews (...) with entrepreneurs (n = 23) and fieldnotes as well as quantitative results from the RIH Assessment Tool. Our findings identify four skillset orientations—Technical, Technical + Business, Social, and Social + Business—that not only reflect (co)founders' training and entrepreneurial motivations but also a proclivity toward the consolidation of either “Technical” or “Social” skills and capabilities. Such consolidation is made possible by recruiting high-level executives with diverse backgrounds or by tapping on external knowledge sources (e.g., boards of directors, incubators, or volunteers). As five enterprises had no formal business skills, patterns associated to their overall RIH score (ranging from 1 to 5) reveal intriguing results. Organizations with a Social + Business skillset have a slightly lower RIH score (4.1) than those with a Social skillet (4.4) and those with a Technical + Business skillset have a slightly higher score (3.5) than those with a Technical skillset (3.0). The presence of business skills thus appears to mediate the relationship between entrepreneurial skillsets and the degree of responsibility, which may be linked to the distinct roles of ordinary (“doing things right”) and dynamic capabilities (“doing the right things”). These exploratory findings have scholarly and practical implications. First, the tensions and synergies characterizing responsible value creation should be approached by examining the complementary skills and capabilities that need to be assembled and consolidated. Second, the eight cases with a Social + Business skillset clarify the unique capabilities needed to produce highly responsible health innovations. Third, entrepreneurs with a scientific or engineering background should recognize that a Technical skillset is not enough. Fourth, recognizing that “falling in love with the cause” of RIH is not sufficient, investors and boards of directors should adequately support responsible entrepreneurs towards the proper orchestration of skills and capabilities that can reconcile economic and social goals. (shrink)

Background: Debates over legalisation of physician-assisted suicide or euthanasia often warn of a “slippery slope”, predicting abuse of people in vulnerable groups. To assess this concern, the authors examined data from Oregon and the Netherlands, the two principal jurisdictions in which physician-assisted dying is legal and data have been collected over a substantial period.Methods: The data from Oregon comprised all annual and cumulative Department of Human Services reports 1998–2006 and three independent studies; the data from the Netherlands comprised all four (...) government-commissioned nationwide studies of end-of-life decision making and specialised studies. Evidence of any disproportionate impact on 10 groups of potentially vulnerable patients was sought.Results: Rates of assisted dying in Oregon and in the Netherlands showed no evidence of heightened risk for the elderly, women, the uninsured , people with low educational status, the poor, the physically disabled or chronically ill, minors, people with psychiatric illnesses including depression, or racial or ethnic minorities, compared with background populations. The only group with a heightened risk was people with AIDS. While extralegal cases were not the focus of this study, none have been uncovered in Oregon; among extralegal cases in the Netherlands, there was no evidence of higher rates in vulnerable groups.Conclusions: Where assisted dying is already legal, there is no current evidence for the claim that legalised PAS or euthanasia will have disproportionate impact on patients in vulnerable groups. Those who received physician-assisted dying in the jurisdictions studied appeared to enjoy comparative social, economic, educational, professional and other privileges. (shrink)

The purpose of this note is to examine the notion of obligations to future generations, a notion that finds increasing use in discussions of social policies and programs, particularly as concerns population distribution and control and environment control. Thus, it may be claimed, the solution of problems in these areas is not merely a matter of enhancing our own good, improving our own conditions of life, but is also a matter of discharging an obligation to future generations.

The purpose of this essay is to investigate and critically analyse some of the formative factors which led to the spiritual maturation of a leading Vīraśaiva saint, Basava. This inquiry focuses on a single event in the life of this great reformer of medieval times, i.e. his spiritual conflict leading to his rejection of the upanayana ceremony. The study will proceed through an investigation of the earliest and subsequent sources which veil the personality of Basava. The traditional view will be (...) challenged as one-sided. By critically comparing the sources, a more comprehensive and plausible account will be suggested. (shrink)

This white paper aims to identify an open problem in 'Quantum Physics and the Nature of Reality' -namely whether quantum theory and special relativity are formally compatible-, to indicate what the underlying issues are, and put forward ideas about how the problem might be addressed.

** The primary topic of this dissertation is the study of the relationships between parts and wholes as described by particular physical theories, namely generalized probability theories in a quasi-classical physics framework and non-relativistic quantum theory. ** A large part of this dissertation is devoted to understanding different aspects of four different kinds of correlations: local, partially-local, no-signaling and quantum mechanical correlations. Novel characteristics of these correlations have been used to study how they are related and how they can be (...) discerned via Bell-type inequalities that give non-trivial bounds on the strength of the correlations. ** The study of quantum correlations has also prompted us to study a) the multi-partite qubit state space with respect to its entanglement and separability characteristics, and b) the differing strength of the correlations in separable and entangled qubit states. Results include a novel classification of multipartite (partial) separability and entanglement, strong constraints on the monogamy of entanglement and of non-local correlations, and many new entanglement detection criteria that are directly experimentally accessible. ** Because of the generality of the investigation these results also have strong foundational as well as philosophical repercussions for the different sorts of physical theories as a whole; notably for the viability of hidden variable theories for quantum mechanics, for the possibility of doing experimental metaphysics, for the question of holism in physical theories, and for the classical vs. quantum dichotomy. (shrink)

Although Alston believed epistemically circular arguments were able to justify their conclusions, he was also disquieted by them. We will argue that Alston was right to be disquieted. We explain Alston’s view of epistemic circularity, the considerations that led him to accept it, and the purposes he thought epistemically circular arguments could serve. We then build on some of Alston’s remarks and introduce further limits to the usefulness of such arguments and introduce a new problem that stems from those limits. (...) The upshot is that adopting Alston’s view that epistemically circular arguments can be used to justify their conclusions is more costly than even he thought. (shrink)

The traditional paradox of the stone may be interpreted as posing a competition between a pair of omnipotent beings, represented by God at two different times. The new paradox poses a question about simultaneous competition between a pair of omnipotent beings. We make use of an attractive Thomistic response to the former paradox in arguing that the latter situation is logically possible.

A obra Consequências da liberdade, publicada no ano de 2011 pela Editora Universitária da UFPE, é primeira obra do escritor e filósofo Geraldo Euclides da Silva, e que certamente se firmará no cenário de exegese das pesquisas sobre o pensamento existencialista de corte sartreano.

Like the virtue it purports to explain, St Thomas Aquinas' treatment of modestia in the Summa Theologiae is something that can easily be overlooked. Such neglect is unfortunate, for it is liable to obscure the surprising character of Aquinas' account, departing as it does from many of his philosophical sources , to say nothing of our own contemporary assumptions. This novel treatment is especially significant given its potential value in addressing the social and political needs of the current age, for (...) rather than being the virtue least fitted for contemporary life, the modesty that emerges in Thomas' moral theology may have an enduring civic significance. This essay therefore begins with an exegesis of Aquinas' account of modestia and concludes with an analysis of its political dimensions. (shrink)

The target article “Bounded Justice, Inclusion, and the Hyper/Invisibility of Race in Precision Medicine” is a welcome addition to the corpus on inclusion in genomics and precision medicine (Ferrym...

We maximally extend the quantum‐mechanical results of Muller and Saunders ( 2008 ) establishing the ‘weak discernibility’ of an arbitrary number of similar fermions in finite‐dimensional Hilbert spaces. This confutes the currently dominant view that ( A ) the quantum‐mechanical description of similar particles conflicts with Leibniz’s Principle of the Identity of Indiscernibles (PII); and that ( B ) the only way to save PII is by adopting some heavy metaphysical notion such as Scotusian haecceitas or Adamsian primitive thisness. We (...) take sides with Muller and Saunders ( 2008 ) against this currently dominant view, which has been expounded and defended by many. *Received July 2008; revised May 2009. †To contact the authors, please write to: F. A. Muller, Faculty of Philosophy, Erasmus University Rotterdam, Burg. Oudlaan 50, H5–16, 3062 PA Rotterdam, The Netherlands; e‐mail: [email protected] , and Institute for the History and Foundations of Science, Utrecht University, Budapestlaan 6, IGG–3.08, 3584 CD Utrecht, The Netherlands; e‐mail: [email protected] . M. P. Seevinck, Institute for the History and Foundations of Science, Utrecht University, Budapestlaan 6, IGG–3.08, 3584 CD Utrecht, The Netherlands; e‐mail: [email protected]. (shrink)

Although Frege is now one of the most important figures in analytical philosophy, there are virtually no full-length studies available. Walker does not try to present all of Frege—that would be a monumental undertaking—but only to consider the philosophical aspects of his thought. Frege's theory of functions, concepts, and objects is first studied; then naming and describing are related to predication and thence to concepts; the notion of the sense of words and expressions, and then the notion of truth, especially (...) as picture-truth, is analyzed with their assistance. The last sections view Frege's general idea of the use of language and symbols, the nature of scientific laws, and the nature of numbers. The author sees Frege as tending to shift his interest from logic to ordinary language and so to the problems of expression in general; this view is reflected in the book itself. The affinities which the author sees with the work of Frege and Wittgenstein is only occasionally treated, but he does make it clear that the Tractatus owes much to Frege. Generally, this compact work will serve well in the study and interpretation of the work of the nineteenth century's greatest logician.—P. J. M. (shrink)

This concise work is a study of the semantical aspects of various paradoxes arising in formal logic. The author constructs a second-order system T with an interpretation in order to provide apparatus for stating and dodging the antinomies. After presenting a number of paradoxes, the author discusses a semantic vicious-circle principle, and provides a clarification of the problems by its application. He then discusses semantic aspects of some classical meta-mathematical results of Gödel, Tarski, Kleene, and Turing on unsolvable problems. Also (...) treated is the topic of impredicative definition in mathematics, especially as it relates to the vicious-circle principle.—P. J. M. (shrink)

In this paper I hope to show that a conception of human rights requires a view of the social ideal and the good life, and requires a view of the nature of human community. But what I say in favor of these points hardly amounts to a demonstration. Instead I try to exhibit how we think and talk about rights in general, and what the presuppositions of such thought and talk are. Throughout, I emphasize the pragmatic side of rights-discourse and (...) I try to establish some of the contexts in which such discourse can be significantly employed. Much of what I say is motivated by the consideration that an historically important factor in the generation of various rights, their acknowledgement and implementation, and their extension to increasingly larger segments of the population, has been the claims put forward and the demands made by individuals and groups against individuals and groups. This factor constitutes a suggestive clue for the development of a theory of rights. The treatment here, however, is largely programmatic and fragmentary. The space allotted does not permit more. Moreover, I lead up to—but do not go into—the social ideal and the human community. The title of this essay indicates its limited scope. The above points are, of course, hardly novel; many older writers laid great stress upon them. But of late they have not received the attention that they in my view deserve. What does it mean for someone to maintain a conception of human rights? How is this conception given any concrete content? The answers to these questions, I believe, ultimately lead to a consideration of social ideals and the human community. What follows is meant to stimulate new thinking on these old-fashioned topics. (shrink)