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)

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 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)

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)

The doctrine of double effect (DOE) has its origins in Roman Catholic thought and has been held to have widespread applications in bioethics. Its applications range over issues of maternal-fetal conflict, organ donation and transplant, euthanasia, and resource allocation, among other controversial issues. Recently, Joseph Boyle, the foremost proponent of the DOE over the past few decades, has argued that the DOE is required by the absolutist context of the Catholic tradition, and, further, that anyone who rejects this particular context (...) is not entitled to use the doctrine. In this essay, I will focus exclusively on the intention condition of the DOE and its central distinction, i.e., intention/side effect. I will proceed by considering in turn (1) Boyle's argument that the absolutist moral framework of the Catholic tradition requires the intention/side effect distinction; (2) the ways in which that framework is made vulnerable by this requirement; and (3) just why the DOE should be viable even outside of the Catholic tradition if it turns out that a feature of (l) is correct and the challenges of (2) can be met. (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.

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)

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)

_The purpose _of the article is to introduce into scientific circulation works by Ukrainian scholar Taras Zakydalsky on the philosophy of Hryhorii Skovoroda. Taras Zakydalsky is a representative of the Ukrainian diaspora, philosopher, and member of Canadian NTSh (Shevchenko Scientific Society of Canada). _Theoretical basis._ We consider the uniqueness of H. Skovoroda’s philosophy, which stimulates not only intellectually but also spiritually enlightens the reader. The reasons for the complex perception and interpretation of Hryhorii Skovoroda’s philosophy are highlighted. We have verified (...) the main methods of its interpretation given in the works by Dmytro Chyzhevskyi. The influence of philosophical thought of thinkers of Antiquity and the Middle Ages: Aristotle, Epicurus, the Church Fathers, and Tertullian has been studied. We have comprehended H. Skovoroda’s interpretation of the Bible as a two-layer existence, the symbolic world that makes the foundation of his philosophy. The peculiarity of the thinker’s division of the heart into "internal" and "external" is analyzed. Hryhorii Skovoroda’s position on the Good and the evil is stated. The Good is identified with God, and the evil – with the real world, the man can choose between the two. Much attention is paid to the understanding of man as a microcosm – rational thinking, and thought is the fundamental cause of human activity, which generates all existence. Hryhorii Skovoroda’s philosophy of metaphysics as the existence of three worlds is highlighted: the first is the macrocosm (the whole surrounding world), the second is the microcosm (the man), and the third is the symbolic world (the Bible). "Monodualism" as a characteristic feature of H. Skovoroda’s work is analyzed. We have highlighted H. Skovoroda’s attitude to the transcendence of God, which is not separated from the world but is present in it directly. The understanding of faith as a forced act of self-love is analyzed because by loving ourselves we love God. The criteria for true and false faith have been clarified. The significance of H. Skovoroda’s aphorism that _what is necessary is useful, and not useful is unnecessary_ is considered. Examples of ethical principles in H. Skovoroda’s philosophy are considered. Peculiarities of the concept HAPPINESS are revealed. This concept is a universal means of existence of the Good, its source is gratitude to God. _Originality_ of the article is in the systematic presentation of the philosophy of the heart by Hryhorii Skovoroda and the analysis of the integrity of the "inner man", the true meaning of life as interpreted by Taras Zakydalsky. _Conclusions_ summarize the "anthropological pragmatism" of the philosopher, whose main idea is to apply practical skills for the benefit of society. (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.

The civil war which ended in the victory of Octavian and the suicide of Antony and Cleopatra is one of the most exciting but most obscure periods of Roman history, obscure mainly because the victor succeeded in imposing bis version of affairs upon his countrymen and through them on posterity. That is not to say that his version is necessarily completely false: the danger that threatened Rome was a real one, the national feeling that resulted in the coniuratio totius Italiae (...) of 32 B.C. and that inspired Virgil and Horace later was not an artificial growth, though it was carefully tended. But in kindling the requisite war-feeling and in rousing the necessary enthusiasm both sides had to propagand for themselves, and in ancient times propaganda often became a matter of personal abuse and mud-slinging. In this Octavian's agents were perhaps more successful, though few nowadays would accept the conventional portraits of Antony and Cleopatra as anywhere near the truth. But Antony's propaganda, though not so effective, was not obliterated by Octavian's victory; indeed a great deal of it is still preserved and masquerades as fact in histories of the period, where Octavian's personal character suffers badly. (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 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...

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 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.