The cyclic GMP‐AMP synthase–stimulator of interferon genes (cGAS‐STING) pathway is central for the initiation of anti‐tumoural immune responses. Enormous effort has been made to optimise the design and administration of STING agonists to stimulate tumour immunogenicity. However, in certain contexts the cGAS‐STING axis fuels tumourigenesis. Here, we review recent findings on the regulation of cGAS expression and activity. We particularly focus our attention on the DNA‐dependent protein kinase (DNA‐PK) complex, that recently emerged as an activator of inflammatory responses in tumour (...) cells. We propose that stratification analyses on cGAS and DNA‐PK expression/activation status should be carried out to predict treatment efficacy. We herein also provide insights into non‐canonical functions borne by cGAS and cGAMP, highlighting how they may influence tumourigenesis. All these parameters should be taken into consideration concertedly to choose strategies aiming to effectively boost tumour immunogenicity. (shrink)

John Lemos argues persuasively that libertarian free will is required for moral desert, that we may have free will, and that even if we have doubts, we should retain the assumption of desert, given its importance to essential values, such as justice, dignity, love, and pride. While sharing his optimism about the possibility of free will, I challenge two claims: The claim that we can confidently attribute responsibility for actions to agents across the board on the basis that each agent (...) has some opportunity to shape their own characters, and the claim that if we cannot appeal to desert, we would have reason to lower evidentiary standards, as a way of keeping the most vulnerable safe from crime. (shrink)

Supervenient libertarianism maintains that indeterminism may exist at a supervening agency level, consistent with determinism at a subvening physical level. It seems as if this approach has the potential to break the longstanding deadlock in the free will debate, since it concedes to the traditional incompatibilist that agents can only do otherwise if they can do so in their actual circumstances, holding the past and the laws constant, while nonetheless arguing that this ability is compatible with physical determinism. However, we (...) argue that supervenient libertarianism faces some serious problems, and that it fails to break us free from this deadlock within the free will debate. (shrink)

With robots being introduced into caregiving, particularly for older persons, various ethical concerns are raised. Among them is the fear of replacing human caregiving. While ethical concepts like well-being, autonomy, and capabilities are often used to discuss these concerns, this paper brings forth the concept of social dignity to further develop guidelines concerning the use of robots in caregiving. By social dignity, we mean that a person’s perceived dignity changes in response to certain interactions and experiences with other persons. In (...) this paper, we will first present the concept of social dignity, and then identify a niche where robots can be used in caregiving in an ethical manner. Specifically, we will argue that, because some activities of daily living are performed in solitude to maintain dignity, a care recipient will usually prefer robotic assistance instead of human assistance for these activities. Secondly, we will describe how other philosophical concepts, which have been commonly used to judge robotic assistance in caregiving for the elderly so far, such as well-being, autonomy, and capabilities, are less useful in determining whether robotic assistance in caregiving is ethically problematic or not. To conclude, we will argue that social dignity offers an advantage to the other concepts, as it allows to ask the most pressing questions in caregiving. (shrink)

ABSTRACT Despite Institutional Review Board concerns about psychological harm arising from research participation, evidence from trauma-questionnaire research suggests that participation is typically well-tolerated by participants. Yet, it is unclear how participant experiences of in-lab trauma simulations align with IRB ethical guidelines. Thus, we compared reactions to a trauma film paradigm with reactions to a positive film task or cognitive tasks. Overall, relative to other conditions, the trauma film was well-tolerated by participants: they generally reported low-to-moderate negative emotions, moderate benefits, and (...) that participation was not worse than everyday stressors. Our results have implications for the research community in designing trauma-based research. (shrink)

Susser and Cabrera (2024) assess the role of bespoke neuro-privacy regulations including the creation of a novel right to mental privacy. They argue that focusing on what distinguishes mental priva...

Pereboom has formulated a Frankfurt-style counterexample in which an agent is alleged to be responsible despite the fact that there are only non-robust alternatives present (Pereboom, Moral responsibility and alternative possibilities: essays on the importance of alternative possibilities, 2003; Phil Explor 12(2):109–118, 2009). I support Widerker’s objection to Pereboom’s Tax Evasion 2 example (Widerker, J Phil 103(4):163–187, 2006) (which rests on the worry that the agent in this example is derivatively culpable as opposed to directly responsible) against Pereboom’s recent counterarguments (...) to this objection (Pereboom 2009). Building on work by Moya (J Phil 104:475–486, 2007; Critica 43(128):3–26, 2011) and Widerker (Widerker 2006), I argue that there is good reason to measure the robustness of alternatives in terms of comparative, rather than non-comparative likelihood of exemption, where the important factor for blame is whether the agent is “doing her reasonable best” to avoid blameworthy behaviour. I maintain that an agent only ever appears responsible when alternatives are robust in this sense. In Pereboom’s examples, both Tax Evasion 2, and his more recent version, Tax Evasion 3 (Pereboom 2009), I maintain the robustness of the alternatives, so understood, is unclear. We can clear up any ambiguity by sharpening the examples, and the result is that the agent appears responsible when the alternatives are made clearly robust, and does not appear responsible when alternatives appear clearly non-robust. The comparative nature of our judgements about blame, I maintain helps to explain the continuing appeal of the “leeway-incompatibilist” viewpoint. (shrink)

Background The worldwide increase in older persons demands technological solutions to combat the shortage of caregiving and to enable aging in place. Smart home health technologies (SHHTs) are promoted and implemented as a possible solution from an economic and practical perspective. However, ethical considerations are equally important and need to be investigated. Methods We conducted a systematic review according to the PRISMA guidelines to investigate if and how ethical questions are discussed in the field of SHHTs in caregiving for older (...) persons. Results 156 peer-reviewed articles published in English, German and French were retrieved and analyzed across 10 electronic databases. Using narrative analysis, 7 ethical categories were mapped: privacy, autonomy, responsibility, human vs. artificial interactions, trust, ageism and stigma, and other concerns. Conclusion The findings of our systematic review show the (lack of) ethical consideration when it comes to the development and implementation of SHHTs for older persons. Our analysis is useful to promote careful ethical consideration when carrying out technology development, research and deployment to care for older persons. Registration We registered our systematic review in the PROSPERO network under CRD42021248543. (shrink)

Fake news is a scourge within modern society, brought about by foreign powers amplifying messages throughout the recently constructed echo chambers of social media and exacerbated by the lack of co...

The artistic work of photographer Gudio Baselgia focuses on landscapes formed by nature s forces and, more recently, on the sky with the stellar and solar movements and phenomena as we see them from earth. Celestial mechanics have fascinated mankind in all known cultures, the Babylonians and ancient Egyptians as well as the Greek and Celts, the Maya, or the ancient Indians and Chinese. Until the present day we look at the sky and keep being amazed, and try to read (...) what it tells us. Many artists throughout history have been captivated by the spectacle we observe above us day and night. The modern term astrodynamics describes all movements of celestial bodies, in particular the solar system including the moon and other satellites, asteroids and comets, but also movements of stars within a stellar system or galaxy, or of galaxies towards each other. They are well understood today and depicted in coordinate systems and elaborate visualizations. Guido Baselgia s artistic project on astrodynamics and celestial phenomena has no scientific or didactic ambition. His analogue camera is used as a recorder inscribing the movement of stars on the light-sensitive surface of photographic paper. Thus Baselgia s images make traceable the trajectory of celestial bodies invisible to the human eye and show us astounding occurrences of light and shadow. Baselgia has been captivated in particular also by the phenomenon of the umbra, planet earth s shadow thrown into space. It becomes visible occasionally on a clear evening at sunset when a slight mist lies at the horizon: looking in opposite direction to the sun, a dark and sharply marked band of shadow can be seen rising while sun sets behind the observer. But also by recording sunrise and sunset at the polar circle or the tropic, Baselgia visualizes the geometry of celestial mechanics and the concurrence of forces, as well as the miracle of light as such that leaves us awestruck today as much as it did our ancestors. The new book "Guido Baselgia Light Fall" presents 80 outstanding black-and-white images from the artist s Light Fall project taken in Norway, the Tierra del Fuego archipelago in Argentina, in Ecuador, and the Swiss Alps. The brilliant tritone plates are complemented with essays by the German scholar Andrea Gnam and Swiss photography critic Nadine Olonetzky. ". (shrink)

Objective The establishment of patient-centered measures capable of empirically determining meaningful cognitive change after surgery can significantly improve the medical care of epilepsy patients. Thus, this study aimed to develop reliable change indices (RCIs) and standardized regression-based (SRB) change norms for a comprehensive neuropsychological test battery in the German language. Methods Forty-seven consecutive patients with temporal lobe epilepsy underwent neuropsychological assessments, both before and 12 months after surgery. Practice-effect-adjusted RCIs and SRB change norms for each test score were computed. To (...) assess their usefulness, the presented methods were applied to a clinical sample, and binary logistic regression analyses were conducted to model the odds of achieving improvement in quality of life (QOL) after surgery. Results The determined RCIs at 90% confidence intervals and the SRB equations for each test score included in the test battery are provided. Cohen’s kappa analyses revealed a moderate mean agreement between the two measures, varying from slight to almost perfect agreement across test scores. Using these measures, a negative association between improvement in QOL and decline in verbal memory functions after surgery was detected (adjusted odds ratio = 0.09, p = 0.006). Significance To the best of our knowledge, this study is the first to develop RCIs and SRB change norms necessary for the objective determination of neuropsychological change in a comprehensive test battery in the German language, facilitating the individual monitoring of improvement and decline in each patients’ cognitive functioning and psychosocial situations after epilepsy surgery. The application of the described measures revealed a strong negative association between improvement in QOL and decline in verbal memory functions after surgery. (shrink)

In January 2022 the new Dutch Civic Integration programme was launched together with promises of improvements it would bring in facilitating the ‘integration’ of newcomers to the Netherlands. This study presents a critical discourse analysis of texts intended for municipalities to take on their new coordinating role in this programme. The analysis aims to understand the discourse in the texts, which actors are mobilized by them, and the role these texts and these actors play in processes of governmental racialization. The (...) analysis demonstrates shifting complex assemblages are brought into cascades of governance in which all actors are disciplined to accept the problem of integration as a problem of cultural difference and distance, and then furthermore disciplined to adopt new practices deemed necessary to identify and even ‘objectively’ measure the inherent traits contributing to this problematic. Lastly, the analysis displays that all actors are disciplined to accept the solution of ‘spontaneous compliance’; a series of practices and knowledges, which move the civic integration programme beyond an aim of responsibilization, into a programme of internalization, wherein newcomers are expected to own and address their problematic ‘nature’, making ‘modern’ values their own. (shrink)

Fox and Spector use multiple instances of the exhaustivity operator EXH to derive the correct meaning of utterances that include pitch-focus marked disjunction in downward-entailing environments. They argue that the \ operator evaluates alternatives to be used by EXH. Though the method is sound and gets the right result, we argue that the way in which EXH would need to interact with other instances of EXH, as well as other focus-sensitive elements, is at odds with how EXH is used to (...) explain other phenomena. Specifically, the analysis in Fox and Spector predicts intervention effects for cases where EXH interacts with other focus-sensitive elements. This is problematic for many cases in which EXH is used to derive the desired inferences. We propose a different way of focus association for EXH that would work for the approach introduced in Fox and Spector as well as elsewhere. In addition, our account does not require a covert element to be focused. (shrink)

Graphical models are a powerful tool for causal model specification. Besides allowing for a hierarchical representation of variable interactions, they do not require any a priori specification of the functional dependence between variables. The construction of such graphs hence often relies on the mere testing of whether or not model variables are marginally or conditionally independent. The identification of causal relationships then solely requires some general assumptions on the relation between stochastic and causal independence, such as the Causal Markov Condition (...) and the Faithfulness Condition (Spirtes et al. 2000; Pearl 2000). However, a procedure would require further assumptions to hold. Namely those the independence tests themselves are based on. In continuous settings, Spirtes et al. (2000) suggest causal inference based on a very restrictive formulation of independence, that is, vanishing partial correlations. Such a measure does, however, limit the applicability of causal inference to linear systems. This constitutes a serious drawback especially for the social sciences where an a priori specification of the functional form proves difficult or at odds with linearity. In short: graphical models theoretically reduce specification uncertainty regarding functional dependence, but their implementation in practice deprives them of this virtue. In this paper we investigate how causal structures in continuous settings can be identified when both functional forms and probability distributions of the variables remain unspecified. We focus on tests exploiting the fact that if X and Y are conditionally independent given a set of variables Z, the two conditional densities f (X|Y, Z) and f (X|Z) must coincide. We start by estimating the conditional densities f(X|Y, Z) and f(X|Z) via nonparametric techniques (kernel methods). We proceed by testing if some metric expressing the distance between these very conditional densities is sufficiently close to zero. Out of several metrics available in the literature to express such distance we choose two, the Euclidean, and the Hellinger distance. We investigate in a Monte Carlo study how different tests involving either measure are able to detect statistical independence, conditioned on a small set of variables. One limitation may result from nonparametric density estimation being subject to the curse of dimensionality. As the number of variables increases, the estimated empirical density converges at a slower rate to its population value. To compensate this drawback we use a local bootstrap procedure which consists of resampling the data for each test. While local bootstrap strongly increases the computational time of the test, it succeeds in counterbalancing the curse of dimensionality. (shrink)

It may be possible, one day, to use gene therapy to treat diseases whose genetic defects have been discerned. Because many genes responsible for inherited eye disorders within the retina have been identified, diseases of the eye are prime candidates for this form of therapy. The eye also has the advantage of being highly accessible with altered immunological properties, important considerations for easy delivery of virus and avoidance of systemic immune responses. Currently, adenovirus, adeno‐associated virus and lentivirus have been used (...) to successfully transfer genetic material to retinal pigment epithelium and photoreceptor cells. By harnessing therapeutic genes to these viruses, researchers have been able to demonstrate rescue in rodent models of retinitis pigmentosa, providing evidence that this form of therapy can be effective in delaying photoreceptor cell death. Future challenges include confirming therapeutic effects in animal models with eyes more anatomically similar to those of humans and demonstrating long‐term rescue with minimal toxicity. BioEssays 23:662–668, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

This paper examines cancer through the lens of abjection. While cancer can be understood as an abject lifeform, we explore what we name the abject ontologies created through both cancer detection technologies/practices and cancer treatment, specifically the drug combination Adriamycin and Cytoxan. We ask: what are the abject ontologies produced through living with and living on from cancer diagnosis and treatment? Our concern is to map how cancer undoes our supposedly stable categories inherited from modernist logic, challenges our very ideas (...) of what it means to be human, and demands an ethical reorientation of public cancer discourse. (shrink)

I examine Manuel Vargas's revisionist justification for continuing with our responsibility-characteristic practices in the absence of basic desert. I query his claim that this justification need not depend on how we settle questions about the content of morality, arguing that it requires us to reject the Kantian principle that prohibits treating anyone merely as a means. I maintain that any convincing argument against this principle would have to be driven by concerns that arise within the sphere of moral theory itself, (...) whereas Vargas's argument draws solely on concerns about the expensive metaphysics involved in a libertarian conception of freedom. I argue that this amounts not just to changing the concept of free will by stipulation, but also (more problematically) to changing our moral principles by stipulation. (shrink)

A “contrastive explanation” explains not only why some event A occurred, but why A occurred as opposed to some alternative event B. Some philosophers argue that agents could only be morally responsible for their choices if those choices have contrastive explanations, since they would otherwise be “luck infested”. Assuming that contrastive explanations cannot be offered for causally undetermined events, this requirement entails that no one could be held responsible for a causally undetermined choice. Such arguments challenge incompatibilism, since they entail (...) that causal determinism is a prerequisite for moral responsibility. However, I argue that for a significant class of choices, even if we stipulate that they are determined, we will be unable to provide a relevant contrastive explanation. Hence causal determinism is no remedy for luck infestation, and compatibilists do not fare much better than incompatibilists in the face of this requirement. This should serve to weaken its philosophical appeal. (shrink)

Pregnancy is thought to be a metabolically very expensive endeavor, yet investigations have produced inconsistent results concerning the responsiveness of human birth weight to maternal nutritional stress or nutritional intervention. These findings have led some researchers to conclude that fetal growth is strongly buffered against fluctuations in maternal energy balance, making the fetus in effect a “nearly perfect parasite.” This buffering would appear to be a reasonable adaptive response given the high risk of morbidity and mortality associated with low birth (...) weight. However, a life-history approach leads to the prediction that maternal investment strategies in pregnancy should be geared toward maximizing lifetime reproductive success rather than simply the success of the current pregnancy, and by extension that maternal investment strategies should vary with reproductive value. The physiology of human pregnancy in fact appears to include a number of mechanisms that protect maternal energy resources from diversion to the fetus and preserve them for future reproductive events. These mechanisms include adjustment of blood flow to the uterus and perhaps minor adjustments in gestation length, although evidence for the latter is scant. Suggestions are made for ways of investigating these maternal options. (shrink)

In this paper, we show that native speakers spontaneously divide the complex meaning of a new word into a presuppositional component and an assertive component. These results argue for the existence of a productive triggering algorithm for presuppositions, one that is not based on alternative lexical items nor on contextual salience. On a methodological level, the proposed learning paradigm can be used to test further theories concerned with the interaction of lexical properties and conceptual biases.

The current assumptions of knowledge acquisition brought about the crisis in the reproducibility of experiments. A complementary perspective should account for the specific causality characteristic of life by integrating past, present, and future. A “second Cartesian revolution,” informed by and in awareness of anticipatory processes, should result in scientific methods that transcend the theology of determinism and reductionism. In our days, science, itself an expression of anticipatory activity, makes possible alternative understandings of reality and its dynamics. For this purpose, the (...) study advances G-complexity for defining and comparing decidable and undecidable knowledge. AI and related computational expressions of knowledge could benefit from the awareness of what distinguishes the dynamics of life from any other expressions of change. (shrink)

Name der Zeitschrift: Neue Zeitschrift für Systematische Theologie und Religionsphilosophie Jahrgang: 58 Heft: 3 Seiten: 285-308.

This article re-examines the profession of the late antique mechanikos, who is identified as a practising architect with a sound liberal arts education as well as practical training. Despite the practical orientation of his profession, the mechanikos was of high social standing. This was possible because the practical utility of a vocation was increasingly acknowledged favourably in late antiquity and is reflected in early Byzantine portrayals of patrons, who allegedly invested hard labour in prestigious building campaigns and posed as the (...) supreme architects. (shrink)

Controversies in food and agriculture abound, with many portrayed as conflicts between polarized viewpoints. Framing such controversies as dichotomies, however, can at times obscure what might be a plurality of views and potential common ground on the subject. We used Q methodology to explore stakeholders’ views about pesticide safety, agricultural worker exposure, and human health concerns in the tree fruit industry of central Washington State. Using a purposive sample of English and Spanish-speaking agricultural workers, industry representatives, state agencies, educators, and (...) advocates, participants sorted 45 statements on pesticide use and perceived human safety risks in the tree fruit industry in 2011. We used PQMethod 2.33 statistical software program to identify viewpoints, based on differences between how participants sorted the statements. The results revealed three distinct viewpoints among 38 sorters that explained 52 percent of the variance. The viewpoints included the: skeptics who expressed concern over the environmental and human health impacts of pesticide use; acceptors who acknowledged inherent risks for using pesticides but saw the risks as known, small and manageable; and incrementalists who prioritized opportunities to introduce human capital and technological improvements to increase agricultural worker safety. We then brought representatives with these different viewpoints together to analyze the results of the Q study, and to brainstorm mutually acceptable improvements to health and safety in tree fruit orchards. In describing and analyzing this case study, we argue that Q methodology can serve as one potentially effective tool for collaborative work, in this case facilitating a process of orchard safety improvements despite perceived stakeholder polarization. (shrink)

The informed consent process presents challenges for psychological trauma research (e.g. Institutional Review Board [IRB] apprehension). While previous research documents researcher and IRB-member perspectives on these challenges, participant views remain absent. Thus, using a mixed-methods approach, we investigated participant views on consent guidelines in two convenience samples: crowdsourced (N = 268) and undergraduate (N = 265) participants. We also examined whether trauma-exposure influenced participant views. Overall, participants were satisfied with current guidelines, providing minor feedback and ethical reminders for researchers. Moreover, (...) participant views for consent were similar irrespective of trauma-exposure. Our study has implications for IRBs and psychological researchers. (shrink)

This study focuses on the profile of principals who seem to be able to shape the school culture to best encourage teaching and learning. Data from a representative sample of primary schools (N = 46) were collected through questionnaires for principals and for teachers (N = 700) and semi?structured interviews with the principals. Functioning, well?being and personal characteristics of the principal, structural and cultural characteristics of school, and organisational context are examined. Compared to their opposites, principals in schools with cultures (...) stimulating professional development, combine (1) type A, achievement?oriented behaviour, (2) transformational leadership, (3) a preference for tasks related to education matters and people management and (4) effective time management allowing them to devote most of their time to their preferred role and task component. (shrink)

The notion of computation has changed the world more than any previous expressions of knowledge. However, as know-how in its particular algorithmic embodiment, computation is closed to meaning. Therefore, computer-based data processing can only mimic life’s creative aspects, without being creative itself. AI’s current record of accomplishments shows that it automates tasks associated with intelligence, without being intelligent itself. Mistaking the abstract for the concrete has led to the religion of “everything is an output of computation”—even the humankind that conceived (...) the computer. The hypostatized role of computers explains the increased dependence on them. The convergence machine called deep learning is only the most recent form through which the deterministic theology of the machine claims more than what it actually is: extremely effective data processing. A proper understanding of complexity, as well as the need to distinguish between the reactive nature of the artificial and the anticipatory nature of the living are suggested as practical responses to the challenges posed by machine theology. (shrink)

Aus einer philosophisch-phanomenologischen und literaturwissenschaftlichen Perspektive heraus gewinnt Nadine Benz nahere Erkenntnisse uber das temporale Phanomen des Wartens. Zunachst wird die historische Entwicklung der Zeitvorstellung aus philosophisch-phanomenologischer Sicht thematisiert, spezifisch im Hinblick auf die Fragen nach Messbarkeit, Vermitteltheit und nach objektiven und subjektiven Komponenten von Zeiterfahrung in ihrer Aporetik. Im Anschluss wird vom Konzept der Lebenswelt zur Literatur ubergeleitet: Die vorliegende Studie bindet die Aporien der Zeit zunachst theoretisch in eine Narratologie von Zeiterfahrung ein, die vor allem den Faktor (...) des Fiktiven produktiv berucksichtigt. Schliesslich werden die gewonnenen Erkenntnisse und Instrumente fur eine Analyse von Erzahltexten des 20. und 21. Jahrhunderts fruchtbar gemacht. Hier erlangen die literarischen Konfigurationen von Wartezeit als Semantiken des Wartens fur die Subjekte der fiktiven Zeiterfahrung einen konstitutiven Status. (shrink)

How do the practices of philosophy and film converge in ethical and political theory? Untimely Affects is an ethical and aesthetic interweaving of Deleuzian philosophy and close film analysis to discern how thought persists productively after the horrors of World War II. In the first extensive analysis of Chris Marker and Alain Resnais' films, Nadine Boljkovac draws on concepts and images that interrogate 'what we are now living through', in the words of Klossowski's Nietzsche. Mindful of the seen and (...) unseen 'that quicken the heart', this book of film-philosophy discerns new and deeply ethical life-affirming possibilities through its weave of cine-philosophy. As such, this book speaks directly to essences of cinema, thought and life through creative untimeliness and the idea of the 'ever new'. (shrink)

In this paper I present the philosophical backdrop to Russell's 1923 "Vagueness" paper. I argue that his view of vagueness in 1923 is the result of a rise in the importance of symbolism in his thinking coupled with a new interest in psychology. I show how these new interests are related to concerns he had with his theory of judgment as well as his logicist project. I attend to the two major complaints against his view of vagueness: that all language (...) is vague and his purported conflation of vagueness with generality. I lastly show how Russell's view is distinct from modern approaches to vagueness in so far as he is not concerned with truth-value gaps but instead sees vagueness as applying primarily to what is cognitive and as a transitory position between ignorance and knowledge. (shrink)