It was, until recently, accepted that the two classes of acetylcholine (ACh) receptors are distinct in an important sense: muscarinic ACh receptors signal via heterotrimeric GTP binding proteins (G proteins), whereas nicotinic ACh receptors (nAChRs) open to allow flux of Na+, Ca2+, and K+ ions into the cell after activation. Here we present evidence of direct coupling between G proteins and nAChRs in neurons. Based on proteomic, biophysical, and functional evidence, we hypothesize that binding to G proteins modulates the activity (...) and signaling of nAChRs in cells. It is important to note that while this hypothesis is new for the nAChR, it is consistent with known interactions between G proteins and structurally related ligand‐gated ion channels. Therefore, it underscores an evolutionarily conserved metabotropic mechanism of G protein signaling via nAChR channels.Also watch the Video Abstract. (shrink)

It was, until recently, accepted that the two classes of acetylcholine (ACh) receptors are distinct in an important sense: muscarinic ACh receptors signal via heterotrimeric GTP binding proteins (G proteins), whereas nicotinic ACh receptors (nAChRs) open to allow flux of Na+, Ca2+, and K+ ions into the cell after activation. Here we present evidence of direct coupling between G proteins and nAChRs in neurons. Based on proteomic, biophysical, and functional evidence, we hypothesize that binding to G proteins modulates the activity (...) and signaling of nAChRs in cells. It is important to note that while this hypothesis is new for the nAChR, it is consistent with known interactions between G proteins and structurally related ligand‐gated ion channels. Therefore, it underscores an evolutionarily conserved metabotropic mechanism of G protein signaling via nAChR channels.Also watch the Video Abstract. (shrink)

This paper presents a new theory of modal reasoning, i.e. reasoning about what may or may not be the case, and what must or must not be the case. It postulates that individuals construct models of the premises in which they make explicit only what is true. A conclusion is possible if it holds in at least one model, whereas it is necessary if it holds in all the models. The theory makes three predictions, which are corroborated experimentally. First, conclusions (...) correspond to the true, but not the false, components of possibilities. Second, there is a key interaction: it is easier to infer that a situation is possible as opposed to impossible, whereas it is easier to infer that a situation is not necessary as opposed to necessary. Third, individuals make systematic errors of omission and of commission. We contrast the theory with theories based on formal rules. (shrink)

Increasing public concern for the welfare of fish species that human beings use and exploit has highlighted the need for better understanding of the cognitive status of fish and of their ability to experience negative emotions such as pain and fear. Moreover, studying emotion and cognition in fish species broadens our scientific understanding of how emotion and cognition are represented in the central nervous system and what kind of role they play in the organization of behavior. For instance, on a (...) macro neuro-architecture level the brains of fish species look dramatically different from those of mammals, while such a dramatic difference does not (always) occur at the level of emotion- and cognition-related behavior. Here, therefore, we discuss the evidence of emotion and cognition in fish species related to underlying neuro-architecture and the role that emotion and cognition play in the organization of behavior. To do so we use a framework encompassing a number of steps allowing a systematic approach to these issues. Emotion and cognition confer on human and non-human animals the capacity to compliment and/or override immediate reflexes to stimuli and so allow a large degree of flexibility in behavior. Systematic research on behavior that in mammals is indicative of emotion and cognition has been conducted in only a few fish species. The data thus far indicate that in these species brain-behavior relationships are not fundamentally different from those observed in mammals. Furthermore, data from other studies show evidence that behavior patterns related to emotion and cognition vary between fish species as well within fish species, related to sex and life history stage for example. From a welfare perspective, knowledge of such variability will potentially help us to design optimal living conditions for fish species kept by humans. (shrink)

Increasing public concern for the welfare of fish species that human beings use and exploit has highlighted the need for better understanding of the cognitive status of fish and of their ability to experience negative emotions such as pain and fear. Moreover, studying emotion and cognition in fish species broadens our scientific understanding of how emotion and cognition are represented in the central nervous system and what kind of role they play in the organization of behavior. For instance, on a (...) macro neuro-architecture level the brains of fish species look dramatically different from those of mammals, while such a dramatic difference does not (always) occur at the level of emotion- and cognition-related behavior. Here, therefore, we discuss the evidence of emotion and cognition in fish species related to underlying neuro-architecture and the role that emotion and cognition play in the organization of behavior. To do so we use a framework encompassing a number of steps allowing a systematic approach to these issues. Emotion and cognition confer on human and non-human animals the capacity to compliment and/or override immediate reflexes to stimuli and so allow a large degree of flexibility in behavior. Systematic research on behavior that in mammals is indicative of emotion and cognition has been conducted in only a few fish species. The data thus far indicate that in these species brain-behavior relationships are not fundamentally different from those observed in mammals. Furthermore, data from other studies show evidence that behavior patterns related to emotion and cognition vary between fish species as well within fish species, related to sex and life history stage for example. From a welfare perspective, knowledge of such variability will potentially help us to design optimal living conditions for fish species kept by humans. (shrink)

Our objective is to understand how parents and children perceive their roles in decision making about research participation. Forty-five children (ages 4-15 years) with or without a chronic condition and 21 parents were the participants. A semistructured interview assessed perceptions of up to 4 hypothetical research scenarios with varying levels of risk, benefit, and complexity. Children were also administered the Peabody Picture Vocabulary Test, Third Edition, to assess verbal ability, as a proxy for the child's cognitive development. The audiotaped interviews (...) were transcribed and analyzed for themes related to parent and child decision-making roles. Both parents and children varied in their perceptions of decision-making roles. Child perceptions of parental influence on decision making as knowledge-based increased with cognitive development, whereas perceptions of parental influence as power-based decreased. Both children and parents commented that they would collaborate with each other when making decisions. Collaborative decision making appeared to increase with cognitive development. These findings suggest that approaches to child assent and parent permission should consider the parent-child relationship and how children and families typically make decisions. Future research is necessary to explain variation in the process of research decision making across children and families, explore the role of collaboration on children's decision-making skills, and understand developmental trajectories and mechanisms related to research decision making. (shrink)

This narrative review summarizes the empirical literature on children's competence for consent and assent in research and treatment settings. Studies varied widely regarding methodology, particularly in the areas of participant sampling, situational context studied (e.g., psychological versus medical settings), procedures used (e.g., lab-based vs. real-world approaches), and measurement of competence. This review also identified several fundamental dilemmas underlying approaches to children's informed consent. These dilemmas, including autonomy versus best interests approaches, legal versus psychological or ethical approaches, child- versus family-based approaches, (...) and approaches that emphasize consent versus those that emphasize assent, have implications for the measurement of children's competence and interpretation of findings. Recommendations for future research in the area of children's informed consent include the use of diverse samples and control groups, development of multidimensional and standardized measures of competence, utilization of observational methods and longitudinal designs, examination of noncognitive aspects of children's competence, and comparison of children's competence for treatment and research decisions. (shrink)

When listening to degraded speech, such as speech delivered by a cochlear implant, listeners make use of top-down linguistic knowledge to facilitate speech recognition. Lexical knowledge supports speech recognition and enhances the perceived clarity of speech. Yet, the extent to which lexical knowledge can be used to effectively compensate for degraded input may depend on the degree of degradation and the listener’s age. The current study investigated lexical effects in the compensation for speech that was degraded via noise-vocoding in younger (...) and older listeners. In an online experiment, younger and older normal-hearing listeners rated the clarity of noise-vocoded sentences on a scale from 1 to 7. Lexical information was provided by matching text primes and the lexical content of the target utterance. Half of the sentences were preceded by a matching text prime, while half were preceded by a non-matching prime. Each sentence also consisted of three key words of high or low lexical frequency and neighborhood density. Sentences were processed to simulate CI hearing, using an eight-channel noise vocoder with varying filter slopes. Results showed that lexical information impacted the perceived clarity of noise-vocoded speech. Noise-vocoded speech was perceived as clearer when preceded by a matching prime, and when sentences included key words with high lexical frequency and low neighborhood density. However, the strength of the lexical effects depended on the level of degradation. Matching text primes had a greater impact for speech with poorer spectral resolution, but lexical content had a smaller impact for speech with poorer spectral resolution. Finally, lexical information appeared to benefit both younger and older listeners. Findings demonstrate that lexical knowledge can be employed by younger and older listeners in cognitive compensation during the processing of noise-vocoded speech. However, lexical content may not be as reliable when the signal is highly degraded. Clinical implications are that for adult CI users, lexical knowledge might be used to compensate for the degraded speech signal, regardless of age, but some CI users may be hindered by a relatively poor signal. (shrink)

Our primary focus is on analysis of the concept of voluntariness, with a secondary focus on the implications of our analysis for the concept and the requirements of voluntary informed consent. We propose that two necessary and jointly sufficient conditions must be satisfied for an action to be voluntary: intentionality, and substantial freedom from controlling influences. We reject authenticity as a necessary condition of voluntary action, and we note that constraining situations may or may not undermine voluntariness, depending on the (...) circumstances and the psychological capacities of agents. We compare and evaluate several accounts of voluntariness and argue that our view, unlike other treatments in bioethics, is not a value-laden theory. We also discuss the empirical assessment of individuals? perceptions of the degrees of noncontrol and self-control. We propose use of a particular Decision Making Control Instrument. Empirical research using this instrument can provide data that will help establish appropriate policies and procedures for obtaining voluntary consent to research. (shrink)

We show that the theory, consisting of the usual axioms of but with the power set axiom removed—specifically axiomatized by extensionality, foundation, pairing, union, infinity, separation, replacement and the assertion that every set can be well‐ordered—is weaker than commonly supposed and is inadequate to establish several basic facts often desired in its context. For example, there are models of in which ω1 is singular, in which every set of reals is countable, yet ω1 exists, in which there are sets of (...) reals of every size, but none of size, and therefore, in which the collection axiom fails; there are models of for which the Łoś theorem fails, even when the ultrapower is well‐founded and the measure exists inside the model; there are models of for which the Gaifman theorem fails, in that there is an embedding of models that is Σ1‐elementary and cofinal, but not elementary; there are elementary embeddings of models whose cofinal restriction is not elementary. Moreover, the collection of formulas that are provably equivalent in to a Σ1‐formula or a Π1‐formula is not closed under bounded quantification. Nevertheless, these deficits of are completely repaired by strengthening it to the theory, obtained by using collection rather than replacement in the axiomatization above. These results extend prior work of Zarach. (shrink)

Though the publication of Kuhn's 'Structure of Scientific Revolutions' seemed to herald the advent of a unified study of the history and philosophy of science, it is a hard fact that history of science and philosophy of science have increasingly grown apart. Recently, however, there has been a series of workshops on both sides of the Atlantic (called '&HPS') to bring historians and philosophers of science together to discuss integrative approaches. This is therefore an especially appropriate time to explore the (...) problems with and prospects for integrating history and philosophy of science. The original essays in this volume, all from specialists in the history of science or philosophy of science, offer such an exploration from a wide variety of perspectives. The volume combines general reflections on the current state of history and philosophy of science with discussion of the relation between the two disciplines in specific historical and scientific cases"--Publisher's description, back cover. (shrink)

As in other countries, the traditional doctor-patient relationship in the Japanese healthcare system has often been characterised as being of a paternalistic nature. However, in recent years there has been a gradual shift towards a more participatory-patient model in Japan. With advances in technology, the possibility to use digital technologies to improve patient interactions is growing and is in line with changing attitudes in the medical profession and society within Japan and elsewhere. The implementation of an online patient engagement platform (...) is being considered by the Myotonic Dystrophy Registry of Japan. The aim of this exploratory study was to understand patients’ views and attitudes to using digital tools in patient registries and engagement with medical research in Japan, prior to implementation of the digital platform. We conducted an exploratory, cross-sectional, self-completed questionnaire with a sample of myotonic dystrophy patients attending an Open Day at Osaka University, Japan. Patients were eligible for inclusion if they were 18 years or older, and were diagnosed with MD. A total of 68 patients and family members attended the Open Day and were invited to participate in the survey. Of those, 59 % submitted a completed questionnaire. The survey showed that the majority of patients felt that they were not receiving the information they wanted from their clinicians, which included recent medical research findings and opportunities to participate in clinical trials, and 88 % of patients indicated they would be willing to engage with digital technologies to receive relevant medical information. Patients also expressed an interest in having control over when and how they received this information, as well as being informed of how their data is used and shared with other researchers. Overall, the findings from this study suggest that there is scope to develop a digital platform to engage with patients so that they can receive information about medical care and research opportunities. While this study group is a small, self-selecting population, who suffer from a particular condition, the results suggest that there are interested populations within Japan that would appreciate enhanced communication and interaction with healthcare teams. (shrink)

Inception module is one of the most used variants in convolutional neural networks. It has a large portfolio of success cases in computer vision. In the past years, diverse inception flavours, differing in the number of branches, the size and the number of the kernels, have appeared in the scientific literature. They are proposed based on the expertise of the practitioners without any optimization process. In this work, an implementation of population-based incremental learning is proposed for automatic optimization of the (...) hyperparameters of the inception module. This hyperparameters optimization undertakes classification of the MNIST database of handwritten digit images. This problem is widely used as a benchmark in classification, and therefore, the learned best configurations for the Inception module will be of wide use in the deep learning community. In order to reduce the carbon footprint of the optimization process, policies for reducing the redundant evaluations have been undertaken. As a consequence of this work, an evaluation of configurations of the inception module and a mechanism for optimizing hyperparameters in deep learning architectures are stated. (shrink)

Integrating large language models (LLMs) like GPT-4 into medical ethics is a novel concept, and understanding the effectiveness of these models in aiding ethicists with decision-making can have significant implications for the healthcare sector. Thus, the objective of this study was to evaluate the performance of GPT-4 in responding to complex medical ethical vignettes and to gauge its utility and limitations for aiding medical ethicists. Using a mixed-methods, cross-sectional survey approach, a panel of six ethicists assessed LLM-generated responses to eight (...) ethical vignettes.The main outcomes measured were relevance, reasoning, depth, technical and non-technical clarity, as well as acceptability of GPT-4’s responses. The readability of the responses was also assessed. Of the six metrics evaluating the effectiveness of GPT-4’s responses, the overall mean score was 4.1/5. GPT-4 was rated highest in providing technical (4.7/5) and non-technical clarity (4.4/5), whereas the lowest rated metrics were depth (3.8/5) and acceptability (3.8/5). There was poor-to-moderate inter-rater reliability characterised by an intraclass coefficient of 0.54 (95% CI: 0.30 to 0.71). Based on panellist feedback, GPT-4 was able to identify and articulate key ethical issues but struggled to appreciate the nuanced aspects of ethical dilemmas and misapplied certain moral principles.This study reveals limitations in the ability of GPT-4 to appreciate the depth and nuanced acceptability of real-world ethical dilemmas, particularly those that require a thorough understanding of relational complexities and context-specific values. Ongoing evaluation of LLM capabilities within medical ethics remains paramount, and further refinement is needed before it can be used effectively in clinical settings. (shrink)

La mayoría de interpretaciones sobre la noción de comunidad en Hannah Arendt, han pasado por alto el esfuerzo por parte de la autora de deslindarse de lo que ella considera -la tradición de la filosofía política-. Arendt encuentra que dicha tradición ha sido incapaz de reconocer la pluralidad y contingencia propias de los asuntos humanos. Este libro se propone buscar en el pensamiento de la autora una posible noción de Comunidad que conciba la pluralidad como -ley de la tierra-, y (...) vea en la acción esa puesta en escena de dicha pluralidad. (shrink)

The author is the recipient of the Herman Halperin Electric Transmission and Distribution Award, IEEE; United States Activities Board Professional Leadership Award, IEEE; United States Activities Board Citation of Honor, IEEE; Philip Sporn Award, Cigré; Atwood Associate, Cigré. J.A. Casazza has established the Peter Cooper Fund for Advancing Government Technical Competitions at Cooper Union.

Questions about how to negotiate belief and non-belief in social and public spheres are attracting an increasing amount of attention from academics in a range of disciplines, and from concerned members of the public. This volume addresses the emergence of ‘new atheism’ and the developing ‘spiritual but not religious’ phenomenon. Avoiding simplistic accounts of atheism, and of religious belief, it provides readers with insight into a wide range of nuances within theism and a-theism, as well as spiritual practice and faith. (...) The chapters by an international panel of contributors focus on topics such as: a typology or cartography of atheisms and agnosticism; contrasting types of atheism within Christianity and Buddhism; questions about cognitive and doxastic stances in atheisms; theist rejections of and atheist embracing of ‘God’; atheist aesthetics. Reaching beyond the Christian tradition, the book will be of particular interest to scholars of the philosophy of religion, as well as religious studies and theology more generally. (shrink)

Don Isaac Abravanel was one of the main leaders of medieval Spanish Jewry. This work presents a systematic exposition of Abravanel's defence of Judaism, analyzing and evaluating his views on the basic issues of medieval philosophy and theology.

In this article, we explicate evidence-based nursing (EBN), critically appraise its framework and respond to nurses’ concern that EBN sidelines the caring elements of nursing practice. We use resources from care ethics, especially Vrinda Dalmiya’s work that considers care as crucial for both epistemology and ethics, to show how EBN is compatible with, and indeed can be enhanced by, the caring aspects of nursing practice. We demonstrate that caring can act as a bridge between ‘external’ evidence and the other pillars (...) of the EBN framework: clinical expertise; patient preferences and values. Drawing on an influential EBN handbook, section 1 presents the aims and features of EBN, including the normative principle that EBN should take place within a ‘context of caring’. We aim to understand this context and whether it can be neatly detached from the EBN framework, as the handbook seems to suggest. In section 2, we highlight the grounds for resistance to EBN from the nursing community, before mounting the argument that nursing practices can be understood fruitfully through feminist care ethics and/or virtue ethics lenses. In section 3, we deepen that analysis using Dalmiya’s concepts of care-knowing and care as a hybrid ethico-epistemic virtue, which are ideally suited to the complex practices of nursing. In section 4, we bring this rich understanding of care into conversation with EBN, showing that its framework cannot be adequately theorised without paying proper attention to care. Caring can be neither an innocuous background assumption of nor an afterthought to the EBN framework. (shrink)

In this work, the evolution of demographic and health patterns in a Basque rural population from Spain is analysed, as they relate to progress in demographic and epidemiological transition. For this purpose, parochial record data on 13,298 births and 9215 deaths, registered during the 19th and 20th centuries (180090) resulting from cardiovascular diseases and malignant neoplasms (post-transition causes). This last point is in contrast with observations from the first four decades of the 20th century, when infectious diseases and respiratory ailments (...) were determining factors in mortality among this population. The data provided by the study of the variation over time in demographic and health patterns indicate that reducing the risk of mortality is one of the most important preconditions for fertility decline. (shrink)

Bailey (2021) offers a clever argument for the compatibility of determinism and moral responsibility based on the nature of intrinsic intentions. The argument is mistaken on two counts. First, it is invalid. Second, even setting that first point aside, the argument proves too much: we would be blameworthy in paradigm cases of non-blameworthiness. I conclude that we cannot reason from intentions to responsibility solely from the “inside out”—our possessing a blameworthy intention cannot tell us whether this intention is also blameworthy (...) in deterministic worlds. (shrink)