Since the realisation that the antigen‐binding regions of antibodies, the variable (V) regions, can be uncoupled from the rest of the molecule to create fragments that recognise and abrogate particular protein functions in cells, the use of antibody fragments inside cells has become an important tool in bioscience. Diverse libraries of antibody fragments plus in vivo screening can be used to isolate single chain variable fragments comprising VH and VL segments or single V‐region domains. Some of these are interfering antibody (...) fragments that compete with protein‐protein interactions, providing lead molecules for drug interactions that until now have been considered difficult or undruggable. It may be possible to deliver or express antibody fragments in target cells as macrodrugs per se. In future incarnations of intracellular antibodies, however, the structural information of the interaction interface of target and antibody fragment should facilitate development of binding site mimics as small drug‐like molecules. This is a new dawn for intracellular antibody fragments both as macrodrugs and as precursors of drugs to treat human diseases and should finally lead to the removal of the epithet of the ‘undruggable’ protein‐protein interactions. (shrink)

The organ donation and transplantation (ODT) system heavily relies on the willingness of individuals to donate their organs. While it is widely believed that public trust plays a crucial role in shaping donation rates, the empirical support for this assumption remains limited. In order to bridge this knowledge gap, this article takes a foundational approach by elucidating the concept of trust within the context of ODT. By examining the stakeholders involved, identifying influential factors, and mapping the intricate trust relationships among (...) trustors, trustees, and objects of trust, we aim to provide a comprehensive understanding of trust dynamics in ODT. We employ maps and graphs to illustrate the functioning of these trust relationships, enabling a visual representation of the complex interactions within the ODT system. Through this conceptual groundwork, we pave the way for future empirical research to investigate the link between trust and organ donation rates, informed by a clarified understanding of trust in ODT. This study can also provide valuable insights to inform interventions and policies aimed at enhancing organ donation rates. (shrink)

Music can reduce stress and anxiety, enhance positive mood, and facilitate social bonding. However, little is known about the role of music and related personal or cultural variables in maintaining wellbeing during times of stress and social isolation as imposed by the COVID-19 crisis. In an online questionnaire, administered in 11 countries, participants rated the relevance of wellbeing goals during the pandemic, and the effectiveness of different activities in obtaining these goals. Music was found to be the most effective activity (...) for three out of five wellbeing goals: enjoyment, venting negative emotions, and self-connection. For diversion, music was equally good as entertainment, while it was second best to create a sense of togetherness, after socialization. This result was evident across different countries and gender, with minor effects of age on specific goals, and a clear effect of the importance of music in people's lives. Cultural effects were generally small and surfaced mainly in the use of music to obtain a sense of togetherness. Interestingly, culture moderated the use of negatively valenced and nostalgic music for those higher in distress. (shrink)

Background: This research explores how public awareness and attitudes toward donation and transplantation policies may contribute to Spain's success in cadaveric organ donation. Materials and Methods: A representative sample of 813 people residing in Andalusia (Southern Spain) were surveyed by telephone or via Internet between October and December 2018. Results: Most participants trust Spain's donation and transplantation system (93%) and wish to donate their organs after death (76%). Among donors, a majority have expressed their consent (59%), and few nondonors have (...) expressed their refusal (14%). Only a minority are aware of the presumed consent system in force (28%) and feel sufficiently informed regarding the requirements needed to be an organ donor (16%). Participants mainly consider that relatives should represent the deceased's preferences and be consulted when the deceased's wishes are unknown, as is the case in Spain. Conclusion: Public trust in the transplant system may contribute to Spain's high performance in organ donation. High levels of societal support toward organ donation and transplantation do not correspond with similar levels of public awareness of donation and transplantation policies in Spain. (shrink)

BackgroundThe use of great apes (GA) in invasive biomedical research is one of the most debated topics in animal ethics. GA are, thus far, the only animal group that has frequently been banned from invasive research; yet some believe that these bans could inaugurate a broader trend towards greater restrictions on the use of primates and other animals in research. Despite ongoing academic and policy debate on this issue, there is no comprehensive overview of the reasons advanced for or against (...) restricting invasive research with GA. To address this gap, we conducted a systematic review of the reasons reported in the academic literature on this topic.MethodsSeven databases were searched for articles published in English. Two authors screened the titles, abstracts, and full texts of all articles. Two journals specialized in animal ethics, and the reference lists of included articles were subsequently also reviewed.ResultsWe included 60 articles, most of which were published between 2006 and 2016. Twenty-five articles argued for a total ban of GA research, 21 articles defended partial restrictions, and 14 articles argued against restrictions. Overall, we identified 110 reason types, 74 for, and 36 against, restricting GA research. Reasons were grouped into nine domains: moral standing, science, welfare, public and expert attitudes, retirement and conservation, respect and rights, financial costs, law and legal status, and longer-term consequences.ConclusionOur review generated five main findings. First, there is a trend in the academic debate in favor of restricting GA research that parallels worldwide policy changes in the same direction. Second, in several domains (e.g., moral standing, and respect and rights), the reasons were rather one-sided in favor of restrictions. Third, some prominent domains (e.g., science and welfare) featured considerable engagement between opposing positions. Fourth, there is low diversity and independence among authors, including frequent potential conflicts of interests in articles defending a strong position (i.e., favoring a total ban or arguing against restrictions). Fifth, scholarly discussion was not the norm, as reflected in a high proportion of non-peer-reviewed articles and authors affiliated to non-academic institutions. (shrink)

After centuries of philosophical explorations of the remote and the elevated, in our work we give credibility to the possibility that the time has come for philosophy to conquer back the ordinary. Nor only we assume this, but we would also conclude that the main task of philosophy is the recovery of the ordinary (world). A task that also helps to understand what philosophy is or should be or could be. We intend to explore philosophy traditional reluctance to the ordinary (...) and its tendency to look for answers far from it explaining the reasons it has for it. Secondly we would explore the ordinary world itself, trying to characterize it and what does inhabiting it mean. And finally we would look at some philosophical problems (mainly epistemological and moral problems, but not exclusively) from the perspective that gives a philosophy that finds itself comfortable in the ordinary world. (shrink)

A growing number of recreational races are being held in different locations, drawing many local and visiting runners. This study examined the relationships between quality, value, satisfaction, and loyalty among runners in a recreational race and examines potential differences in relationships between these constructs based on the runners’ experience. The participants were 985 runners with a mean age of 40.74±9.41years. Validated, reliable ad hoc instruments were used. A multi-group analysis was performed to ascertain the existence of relationships between the constructs (...) and differences in the relationships between the different study groups. The results show that quality is a direct antecedent of value and satisfaction. Value is directly related to satisfaction and indirectly related to loyalty. Satisfaction is related to the loyalty of participants in the race. Differences in the relationship between satisfaction and loyalty were dependent upon the runners’ experience. Loyalty to a race depends primarily on satisfaction and is modified by the runners’ experience. (shrink)

We give $A_p$ type conditions which are sufficient for two-weight, strong $$ inequalities for Calderón-Zygmund operators, commutators, and the Littlewood-Paley square function $g^*_\lambda $. Our results extend earlier work on weak $$ inequalities in [13].

Experimental balance is usually understood as the control for the value of the conditions, other than the one under study, which are liable to affect the result of a test. We discuss three different approaches to balance. ‘Millean balance’ requires identifying and equalizing ex ante the value of these conditions in order to conduct solid causal inferences. ‘Fisherian balance’ measures ex post the influence of uncontrolled conditions through the analysis of variance. In ‘efficiency balance’ the value of the antecedent conditions (...) is decided ex ante according to the efficiency they yield in the estimation of the treatment outcome. Against some old arguments by Worrall, we show that in both Fisherian and efficiency balance there are good reasons to randomize the allocation of treatments, in particular when there is no agreement among experimenters as to the antecedent conditions to be controlled for. (shrink)

This paper proposes a five-part empirical typology of interconnections of race and class. We describe the mechanisms whereby (1) race is a form of class relation; (2) race relations and class relations reciprocally affect each other; (3) race acts as a sorting mechanism into class locations; (4) race acts as a mediating linkage to class locations; and (5) race interacts with class in determining other outcomes. Rather than insisting on one or another mechanism as the overarching framework for conceptualising the (...) interconnections between race and class, we propose a theoretical integration of all five within a functionalist model. The model reconciles the empirical effects of race variables with a class-functionalist explanation of race. Our typology of interconnections is useful for situating concrete empirical phenomena, and our theoretical integration of those interconnections offers a coherent explanatory system that captures the recursive causality of race and class. (shrink)

Despite the salient experience of encoding threatening events, these memories are prone to distortions and often non-veridical from encoding to recall. Further, threat has been shown to preferentially disrupt the binding of event details and enhance goal-relevant information. While extensive work has characterised distinctive features of emotional memory, research has not fully explored the influence threat has on temporal memory, a process putatively supported by the binding of event details into a temporal context. Two primary competing hypotheses have been proposed; (...) that threat can impair or enhance temporal memory. We analysed two datasets to assess temporal memory for an in-person haunted house experience. In study 1, we examined the temporal structure of memory by characterising memory contiguity in free recall as a function of individual levels of heart rate as a proxy of threat. In study 2, we replicated marginal findings of threat-related increases in memory contiguity found in study 1. We extended these findings by showing threat-related increases in recency discriminations, an explicit test of temporal memory. Together, these findings demonstrate that threat enhances temporal memory regarding free recall structure and during explicit memory judgments. (shrink)

In recent years, the most widespread doctrine about the conflicts between fundamental (usually constitutional) legal rights could be summarized in the following three main theses: (1) The elements in conflict are legal principles, as opposed to legal rules; (2) Those conflicts are not consequences of the existence of inconsistencies or antinomies between the norms involved, but rather depend on the empirical circumstances of the case. In other words, the norms are logically consistent and the conflicts are not determinable a priori (...) or in abstracto , but only in concreto ; and (3) The classical criteria for solving conflicts between norms, such as lex superior , lex posterior and lex specialis , are not suitable to solve conflicts among fundamental legal rights. Indeed, they require a specific method known as ‘weighing and balancing’. Although all three theses could be (and indeed have been) regarded as problematic, in this paper I address mainly the second one. I try to show that there is room for a tertium genus between antinomies (deontic inconsistencies) and conflicts caused by strict empirical circumstances that I call ‘contextual antinomies’. There are situations in which the norms involved are not inconsistent but the conflict arises for logical reasons. My thesis is that many conflicts between fundamental legal rights fall in this category. I offer, in an appendix, a proposal of formalization of this kind of conflict and the elements involved in it. (shrink)

Localization Wireless Sensor Networks (WSN) represent a research topic with increasing interest due to their numerous applications. However, the viability of these systems is compromised by the attained localization uncertainties once implemented, since the network performance is highly dependent on the sensors location. The Node Location Problem (NLP) aims to obtain the optimal distribution of sensors for a particular environment, a problem already categorized as NP-Hard. Furthermore, localization WSN usually perform a sensor selection for determining which nodes are to be (...) utilized for maximizing the achieved accuracy. This problem, defined as the Sensor Selection Problem (SSP), has also been categorized as NP-Hard. While different metaheuristics have been proposed for attaining a near optimal solution in both problems, no approach has considered the two problems simultaneously, thus resulting in suboptimal solutions since the SSP is biased by the actual node distribution once deployed. In this paper, a combined approach of both problems simultaneously is proposed, thus considering the SSP within the NLP. Furthermore, a novel metaheuristic combining the Black Widow Optimization (BWO) algorithm and the Variable Neighbourhood Descent Chains (VND-Chains) local search, denominated as BWO-VND-Chains, is particularly devised for the first time in the author’s best knowledge for the NLP, resulting in a more efficient and robust optimization technique. Finally, a comparison of different metaheuristic algorithms is proposed over an actual urban scenario, considering different sensor selection criteria in order to attain the best methodology and selection technique. Results show that the newly devised algorithm with the SSP criteria optimization achieves mean localization uncertainties up to 19.66 % lower than traditional methodologies. (shrink)

Experimental balance is usually understood as the control for the value of the conditions, other than the one under study, which are liable to affect the result of a test. We will discuss three different approaches to balance. ‘Millean balance’ requires to identify and equalize ex ante the value of these conditions in order to conduct solid causal inferences. ‘Fisherian balance’ measures ex post the influence of uncontrolled conditions through the analysis of variance. In ‘efficiency balance’ the value of the (...) antecedent conditions is decided ex ante according to the efficiency they yield in the estimation of the treatment outcome. Against some old arguments by John Worrall, we will show that in both Fisherian and efficiency balance there are good reasons to randomize the allocation of treatments, in particular when there is no agreement among experimenters as to the antecedent conditions to be controlled for. (shrink)

This study aimed to explore the role of two models of well-being in the prediction of psychological distress during the COVID-19 pandemic, namely PERMA and mature happiness. According to PERMA, well-being is mainly composed of five elements: positive emotions, engagement, relationships, meaning in life, and achievement. Instead, mature happiness is understood as a positive mental state characterized by inner harmony, calmness, acceptance, contentment, and satisfaction with life. Rooted in existential positive psychology, this harmony-based happiness represents the result of living in (...) balance between positive and negative aspects of one's life. We hypothesized that mature happiness would be a more prominent protective factor during the present pandemic than the PERMA composite. A total of 12,203 participants from 30 countries responded to an online survey including the Depression Anxiety Stress Scale (DASS-21), the PERMA-Profiler, and the Mature Happiness Scale-Revised (MHS-R). Confirmatory factor analyses indicated that PERMA and mature happiness were highly correlated, but nonetheless, they represented two separate factors. After controlling for demographic factors and country-level variables, both PERMA Well-being and MHS-R were negative predictors of psychological distress. Mature happiness was a better predictor of stress, anxiety, and general distress, while PERMA showed a higher prediction of depression. Mature happiness moderated the relation between the perceived noxious effects of the pandemic and all markers of distress (depression, anxiety, stress, and total DASS-21). Instead, PERMA acted as a moderator in the case of depression and stress. These findings indicate that inner harmony, according to the mature happiness theory, is an essential facet of well-being to be taken into consideration. The results of this study can also orient policies aimed to alleviate the negative effects of the pandemic on mental health through the promotion of well-being. (shrink)

The ethics of deceased organ procurement (OP) is supposedly based on individual consent to donate, either explicit (opt-in) or presumed (opt-out). However, in many cases, individuals fail to express any preference regarding donation after death. When this happens, the decision to remove or not to remove their organs depends on the policy’s default option or on family preferences. Several studies show that in most countries the family plays a significant and often decisive role in the process of decision-making for OP. (...) Depending on the country, the family may be allowed to take different kinds of actions in different situations, and this may be granted either by law or by clinical practice only. This adds much complexity to the usual classification of consent policies in two categories: opt-in and opt-out. Here we propose a novel and comprehensive taxonomy of the models of consent for OP according to three variables: (1) the deceased’s wishes, if any, (2) family wishes, if any, and (3) default policies. By analysing these models of consent, we show that they rely on at least three different concepts of autonomy: individual autonomy, relational autonomy, and family autonomy. In light of this analysis, we discuss the ethical debates surrounding two policy approaches: presumed consent and family veto. (shrink)

Background: Several countries have recently changed their model of consent for organ donation from opt-in to opt-out. We undertook a systematic review to determine public knowledge and attitudes towards these models in Europe. Methods: Six databases were explored between 1 January 2008 and 15 December 2017. We selected empirical studies addressing either knowledge or attitudes towards the systems of consent for deceased organ donation by lay people in Europe, including students. Study selection, data extraction, and quality assessment were conducted by (...) two or more reviewers independently. Findings: Awareness of the consent model was lower in opt-out countries than in opt-in countries. A majority of the public agrees with opt-in, regardless of the law in their own country. There are ambivalent attitudes regarding the opt-out system. The public tend to prefer opt-in and mandatory choice over opt-out when several options are offered. Interpretation: The assumption that people in opt-out countries are aware of the legal requirements to be excluded from the pool of potential donors is not supported by the results of this review. This is a concern, since ignorance hinders people's autonomy regarding organ donation decision-making. Higher awareness of consent model in opt-in countries may reflect greater efforts to inform the public through campaigns to motivate donation. Legal moves towards opt-out are at odds with people's expressed preferences. Main limitations of this review are the lack of data from some countries, study population heterogeneity, and methodological shortcomings. (shrink)

Gaston Bachelard's thought remains a continual source of inspiration for a phenomenological psychology that takes human habitation as a fundamental given and as an abiding mystery of the human condition. the following essay explores the ideas Bachelard developed in the course of his study of poetry. It examines in particular his vision of imagination as a unique passage way by means of which we reach an inhabitable, intersubjective and fully human world. Within that perspective, our lives are constantly renewed by (...) the appearance of a revealing image or a telling metaphor. Each time that we are awakened by this appeal we commemorate the birth and rebirth of a human world. (shrink)

Altruism and solidarity are concepts that are closely related to organ donation for transplantation. On the one hand, they are typically used for encouraging people to donate. On the other hand, they also underpin the regulations in force in each country to different extents. They are often used indistinctly and equivocally, despite the different ethical implications of each concept. This paper aims to clarify to what extent we can speak of altruism and solidarity in the predominant models of organ donation. (...) It also raises the ethical question of whether these categories are adequate as a basis for such models, bearing in mind that organs are a scarce resource and that a shortage of them may mean that fewer lives are saved or improved. (shrink)

Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. The classical explanation for this process had been built around the notion of positional information. Accordingly the programmed appearance of sources of Morphogens at localized positions within a field of cells directs their differentiation. Recently, the development of organs and tissues from unpatterned and initially identical (...) stem cells (adult and embryonic) has challenged the need for positional information and even the integrity of the embryo, for pattern formation. Here we review the emerging area of organoid biology from the perspective of Developmental Biology. We argue that the events underlying the development of these systems are not purely linked to “self‐organization,” as often suggested, but rather to a process of genetically encoded self‐assembly where genetic programs encode and control the emergence of biological structures. (shrink)

Este texto analiza la teoría del naturalismo ético de Finnis y su relevancia en la fundamentación de la ley y el derecho, con el fin de señalar cómo las ideas de este autor proporcionan una alternativa al iuspositivismo. En su obra Ley natural y derechos naturales, Finnis propone una ética de la racionalidad práctica que demuestra la posibilidad de hacer juicios objetivos sobre lo bueno y razonar sobre el bien. En este sentido, la racionalidad práctica adquiere un papel fundamental en (...) la justificación de la ley y el derecho, dado que implica decidir sobre acciones coherentes con principios morales objetivos. Con el fin de facilitar el diálogo y la comprensión de la teoría de Finnis, esta es discutida en relación con las perspectivas de Tughendhat y Habermas. (shrink)

Transplantation continues to push the frontiers of medicine into domains that summon forth troublesome ethical questions. Looming on the frontier today is human facial transplantation. We develop criteria that, we maintain, must be satisfied in order to ethically undertake this as-yet-untried transplant procedure. We draw on the criteria advanced by Dr. Francis Moore in the late 1980s for introducing innovative procedures in transplant surgery. In addition to these we also insist that human face transplantation must meet all the ethical requirements (...) usually applied to health care research. We summarize the achievements of transplant surgery to date, focusing in particular on the safety and efficacy of immunosuppressive medications. We also emphasize the importance of risk/benefit assessments that take into account the physical, aesthetic, psychological, and social dimensions of facial disfiguration, reconstruction, and transplantation. Finally, we maintain that the time has come to move facial transplantation research into the clinical phase. (shrink)