Drawing on ethical and legal frameworks in the Netherlands, the United States and France, we examine whether physicians are expected to inform patients about potentially relevant opportunities for expanded access to investigational drugs. While we found no definitive legal obligation, we argue that physicians have a moral obligation to discuss opportunities for expanded access with patients who have run out of treatment options to prevent inequality, to promote autonomy, and to achieve beneficence.

When seriously ill patients reach the end of the standard treatment trajectory for their condition, they may qualify for the use of unapproved, investigational drugs regulated via expanded access programs. In medical-ethical discourse, it is often argued that expanded access to investigational drugs raises ‘false hope’ among patients and is therefore undesirable. We set out to investigate what is meant by the false hope argument in this discourse. In this paper, we identify and analyze five versions of the false hope (...) argument which we call: (1) the limited chance at benefit argument, (2) the side effects outweighing benefits argument, (3) the opportunity costs argument, (4) the impossibility of making informed decisions argument, and (5) the difficulty of gaining access argument. We argue that the majority of these five versions do not provide normative ground for disqualifying patients’ hopes as false. Only when hope is rooted in a mistaken belief, for example, about the likelihood of benefits or chances on medical risks, or when hope is directed at something that cannot possibly be obtained, should it be considered false. If patients are adequately informed about their odds of obtaining medical benefit, however small, and about the risks associated with an investigational treatment, it is unjustified to consider patients’ hopes to be false, and hence, to deny them access to investigational drug based on that argument. (shrink)

Recent developments regarding the pharmacology of psychoactive substances are significant for treating depressions or opioid addictions. Current theories, hypotheses, and models of drug effects assume a cause–effect narrative, which is based on a stimulus/response mechanism. These narratives prioritize effects rather than conscious experiences. In this sense, drug experiences are quickly subsumed into common categories and codes of biological determinism. If subjective experiences are in the focus of the research, it quickly becomes a link to mystical, spiritual, or transcendental (...) narratives. These classifications lead to epistemological doublets (Gadamer). In this article, psychedelic experiences of drug users are analyzed in the frame of the pharmaco-analysis by Deleuze/Guattari. These framed psychedelic experiences are interpreted by means of a non-philosophical approach through philo-fictions (Laruelle), i.e., contradictory assumptions and hyperspeculations. In this respect, the aim of this article is to bring philo-fictions in relation to psychedelic experiences and to discuss them with models of information science, quantum mechanics, new materialism, and the philosophy of immanence. The result will be an open synthesis, with the assumption of further reflections on the agency, immanence, and the wholeness of matter. (shrink)

Sociologists of science have argued that due to the institutional reward system negative research results, such as failed experiments, may harm scientific careers. We know little, however, of how scientists themselves make sense of negative research findings. Drawing from the sociology of work, the author discusses how researchers involved in a double-blind, placebo, controlled randomized clinical trial for methamphetamine dependency informally and formally interpret the emerging research results. Because the drug tested in the trial was not an effective treatment, (...) the staff considered the trial a failure. In spite of the disappointing results, the staff involved in the daily work with research subjects still reframed the trial as meaningful because they were able to treat people for their drug dependency. The authors of the major publication also framed the results as worthwhile by linking their study to a previously published study in a post hoc analysis. The author concludes that negative research findings offer a collective opportunity to define what scientific work is about and that the effects of failed experiments depend on individual biography and institutional context. (shrink)

We reply to the Ioannidis's paper "Effectiveness of antidepressants; an evidence based myth constructed from a thousand controlled trials." We disagree that antidepressants have no greater efficacy than placebo. We present the efficacy from hundreds of trials in terms of the percentage of patients with a substantial clinical response (a 50% improvement or more symptomatic reduction). This meta-analysis finds that 42-70% of depressed patients improve with drug and 21%-39% improve with placebo. The response benefit of antidepressant treatment is 33%-11% (...) greater than placebo. Ioannidis argues that it would be vanishingly smaller because systematic biasing in these clinical trials would reduce the drug-placebo difference to zero. Ioannidis' argument that antidepressants have no benefit is eroded by his failures of logic because he does not present any evidence that there are a large number of studies where placebo is substantially more effective than drug. (To reduce to zero, one would also have to show that some of the unpublished studies find placebo better than drug and have substantial systematic or methodological bias). We also present the empirical evidence showing that these methodological concerns generally have the opposite effect of what Ioannidis argues, supporting our contention that the measured efficacy of antidepressants likely underestimates true efficacy.Our most important criticism is Ioannidis’ basic underlying argument about antidepressants that if the existing evidence is imperfect and methods can be criticized, then this proves that antidepressant are not efficacious. He presents no credible evidence that antidepressants have zero effect size. Valid arguments can point out difficulties with the data but do not prove that a given drug had no efficacy. Indeed better evidence might prove it was more efficacious that originally found.We find no empirical or ethical reason why psychiatrists should not try to help depressed patients with drugs and/or with psychotherapeutic/behavioral treatments given evidence of efficacy even though our treatment knowledge has limitations. The immense suffering of patients with major depression leads to ethical, moral, professional and legal obligations to treat patients with the best available tools at our disposal, while diligently and actively monitoring for adverse effects and actively revising treatment components as necessary. (shrink)

Die Entwicklung einer „personalisierten Medizin“ ist zurzeit in aller Munde. Insbesondere die personalisierte Arzneimitteltherapie gewinnt infolge der pharmakologischen und molekulargenetischen Entwicklungen immer mehr an Bedeutung. Dies macht es erforderlich, die Auswirkungen der personalisierten Arzneimitteltherapie auf die gesetzliche Krankenversicherung (GKV) und die Patientenversorgung zu untersuchen. In diesem Zusammenhang stellt sich die Frage nach einer „Orphanisierung“: Könnten Arzneimittel der personalisierten Medizin regelmäßig als Orphan Drugs, also als Arzneimittel für seltene Leiden, ausgewiesen werden, würde für sie nach dem Arzneimittelneuordnungsgesetz (AMNOG) grundsätzlich kein Nachweis (...) des Zusatznutzens im Rahmen der vom Gemeinsamen Bundesausschuss (GBA) vorzunehmenden frühen Nutzenbewertung erforderlich werden. Entscheidend für die Ausweisung des Arzneimittels als Orphan Drug ist unter anderem die Prävalenzrate der Patientengruppe, deren Erkrankung mit dem Arzneimittel behandelt werden soll. In diesem Zusammenhang kommt der Stratifizierung von Patientengruppen im Rahmen der personalisierten Arzneimitteltherapie eine besondere Bedeutung zu. Eine solche „Orphanisierung“ hätte für die GKV wegen der mangelnden Kenntnis von dem Zusatznutzen des Arzneimittels insbesondere preisrechtliche Konsequenzen; für die Patienten sind die Folgen durchaus differenzierter zu betrachten. (shrink)

Millions of people in the developing world lack access to curative drugs. Pogge identifies the cause of this problem as a lack of redistribution across borders. In contrast, this article shows that institutional shortcomings within developing countries are the main issue. These different explanations are the result of diverging analytic approaches to ethics: a cosmopolitan approach versus an ordonomic approach. This article compares both approaches with regard to how they conceptualize and propose to solve the problem of providing life-saving pharmaceuticals (...) to the poor in developing countries. (shrink)

Ontologies aim to represent what is general, by means of universal statements. In contrast, dispositional predications capture knowledge about what is likely to happen if a certain set of circumstances obtain, which is crucial in investigative research such as in drug discovery and systems biology, where entities which are constitutionally dissimilar can nevertheless have similar behavior in a biological context. While such dispositional properties are increasingly included in biomedical ontologies, the circumstances under which the dispositions are realized are seldom (...) explicitly modeled, and doing so is problematic due to the necessary restriction to binary relations in OWL ontologies. In this paper we address this shortcoming, focusing on the bioactivity of small molecules at varying levels of concentration within a living organism as our problem domain, although our approach is generalizable to other problems. We discuss the ontological nature and representation of dispositions and their realization; consider the nature of concentrations and their representation; and finally we detail an approach to linking dispositions to the conditions for their realization which regards conditions as triggers for the process in which the disposition is realized. (shrink)

Artificial Intelligence (AI) is increasingly adopted in society, creating numerous opportunities but at the same time posing ethical challenges. Many of these are familiar, such as issues of fairness, responsibility and privacy, but are presented in a new and challenging guise due to our limited ability to steer and predict the outputs of AI systems. This chapter first introduces these ethical challenges, stressing that overviews of values are a good starting point but frequently fail to suffice due to the context (...) sensitivity of ethical challenges. Frequently, additional (ethical) values emerge for specific applications, as e.g. challenges with fraud detection are very different from those around language technologies. Second, methods to tackle these challenges are discussed. Main ethical theories (virtue ethics, consequentialism, and deontology) are shown to provide a starting point, but often lack the details needed for actionable AI Ethics. Instead, mid-level philosophical theories coupled to design-approaches such as Design for Values, together with interdisciplinary working methods, offer the best way forwards. The chapter aims to show how these approaches can lead to an ethics of AI that is actionable and that can be proactively integrated in the design of AI systems. (shrink)

ABSTRACT I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments. INTRODUCTION In contrast to the classic model of randomized-control trials, often with a large number of (...) subjects enrolled, precision medicine attempts to optimize therapeutic outcomes by focusing on the individual.[i] A recent publication highlights the strengths and weakness of both traditional evidence-based medicine and precision medicine.[ii] Plus, it outlines a tension in the shift from evidence-based medicine’s inductive reasoning style (the collection of data to postulate general theories) to precision medicine’s abductive reasoning style (the generation of an idea from the limited data available).[iii] The paper’s main example is the application of precision medicine for the treatment of cancer.[iv] I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. As the name suggests, brain-computer interfaces are a significant advancement in neurotechnology that directly connects someone’s brain to external or implanted devices.[v] Among the various kinds of brain-computer interfaces, adaptive deep brain stimulation devices require numerous personalized adjustments to their settings during the implantation and computation stages in order to provide adequate relief to patients with treatment-resistant disorders. What makes these devices unique is how adaptive deep brain stimulation integrates a sensory component to initiate the stimulation. While not commonly at the level of sophistication as self-supervising or generative large language models,[vi] they currently allow for a semi-autonomous form of neuromodulation. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments.[vii] ANALYSIS I. The State of Precision Medicine in Oncology and the Epistemological Shift While a thorough overview of precision medicine for the treatment of cancer is beyond the scope of this article, its practice can be roughly summarized as identifying clinically significant characteristics a patient possesses (e.g., genetic traits) to land on a specialized treatment option that, theoretically, should benefit the patient the most.[viii] However, in such a practice of stratification patients fall into smaller and smaller populations and the quality of evidence that can be applied to anyone outside these decreases in turn.[ix] As inductive logic helps to articulate, the greater the number of patients that respond to a particular therapy the higher the probability of its efficacy. By straying from this logical framework, precision medicine opens the treatment of cancer to more uncertainty about the validity of these approaches to the resulting disease subcategories.[x] Thus, while contemporary medical practices explicitly describe some treatments as “personalized”, they ought not be viewed as inherently better founded than other therapies.[xi] A relevant contemporary case of precision medicine out of Norway focuses on the care of a patient with cancer between the ventricles of the heart and esophagus, which had failed to respond to the standard regimen of therapies over four years.[xii] In a last-ditch effort, the patient elected to pay out-of-pocket for an experimental immunotherapy (nivolumab) at a private hospital. He experienced marked improvements and a reduction in the size of the tumor. Understandably, the patient tried to pursue further rounds of nivolumab at a public hospital. However, the hospital initially declined to pay for it given the “lack of evidence from randomised clinical trials for this drug relating to this [patient’s] condition.”[xiii] In rebuttal to this claim, the patient countered that he was actually similar to a subpopulation of patients who responded in “open‐label, single arm, phase 2 studies on another immune therapy drug” (pembrolizumab).[xiv] Given this interpretation of the prior studies and the patient’s response, further rounds of nivolumab were approved. Had the patient not had improvements in the tumor’s size following a round of nivolumab, then pembrolizumab’s prior empirical evidence in isolation would have been insufficient, inductively speaking, to justify his continued use of nivolumab.[xv] The case demonstrates a shift in reasoning from the traditional induction to abduction. The phenomenon of ‘cancer improvement’ is considered causally linked to nivolumab and its underlying physiological mechanisms.[xvi] However, “the weakness of abductions is that there may always be some other better, unknown explanation for an effect. The patient may for example belong to a special subgroup that spontaneously improves, or the change may be a placebo effect. This does not mean, however, that abductive inferences cannot be strong or reasonable, in the sense that they can make a conclusion probable.”[xvii] To demonstrate the limitations of relying on the abductive standard in isolation, commentators have pointed out that side effects in precision medicine are hard to rule out as being related to the initial intervention itself unless trends from a group of patients are taken into consideration.[xviii] As artificial intelligence (AI) assists the development of precision medicine for oncology, this uncertainty ought to be taken into consideration. The implementation of AI has been crucial to the development of precision medicine by providing a way to combine large patient datasets or a single patient with a large number of unique variables with machine learning to recommend matches based on statistics and probability of success upon which practitioners can base medical recommendations.[xix] The AI is usually not establishing a causal relationship[xx] – it is predicting. So, as AI bleeds into medical devices, like brain-computer interfaces, the same cautions about using abductive reasoning alone should be carried over. II. Responsive Neurostimulation, AI, and Personalized Medicine Like precision medicine in cancer treatment, computer-brain interface technology similarly focuses on the individual patient through personalized settings. In order to properly expose the intersection of AI, precision medicine, abductive reasoning, and implantable neurotechnologies, the descriptions of adaptive deep brain stimulation systems need to deepen.[xxi] As a broad summary of adaptive deep brain stimulation, to provide a patient with the therapeutic stimulation, a neural signal, typically referred to as a local field potential,[xxii] must first be detected and then interpreted by the device. The main adaptive deep brain stimulation device with premarket approval, the NeuroPace Responsive Neurostimulation system, is used to treat epilepsy by detecting and storing “programmer-defined phenomena.”[xxiii] Providers can optimize the detection settings of the device to align with the patient’s unique electrographic seizures as well as personalize the reacting stimulation’s parameters.[xxiv] The provider adjusts the technology based on trial and error. One day machine learning algorithms will be able to regularly aid this process in myriad ways, such as by identifying the specific stimulation settings a patient may respond to ahead of time based on their electrophysiological signatures.[xxv] Either way, with AI or programmers, adaptive neurostimulation technologies are individualized and therefore operate in line with precision medicine rather than standard treatments based on large clinical trials. Contemporary neurostimulation devices are not usually sophisticated enough to be prominent in AI discussions where the topics of neural networks, deep learning, generative models, and self-attention dominate the conversation. However, implantable high-density electrocorticography arrays (a much more sensitive version than adaptive deep brain stimulation systems use) have been used in combination with neural networks to help patients with neurologic deficits from a prior stroke “speak” through a virtual avatar.[xxvi] In some experimental situations, algorithms are optimizing stimulation parameters with increasing levels of independence.[xxvii] An example of neurostimulation that is analogous to the use of nivolumab in Norway surrounds a patient in the United States who was experiencing both treatment-resistant OCD and temporal lobe epilepsy.[xxviii]Given the refractory nature of her epilepsy, implantation of an adaptive deep brain stimulation system was indicated. As a form of experimental therapy, her treatment-resistant OCD was also indicated for the off-label use of an adaptive deep brain stimulation set-up. Another deep brain stimulation lead, other than the one implanted for epilepsy, was placed in the patient’s right nucleus accumbens and ventral pallidum region given the correlation these nuclei had with OCD symptoms in prior research. Following this, the patient underwent “1) ambulatory, patient-initiated magnet-swipe storage of data during moments of obsessive thoughts; (2) lab-based, naturalistic provocation of OCD-related distress (naturalistic provocation task); and (3) lab-based, VR [virtual reality] provocation of OCD-related distress (VR provocation task).”[xxix] Such signals were used to identify when to deliver the therapeutic stimulation in order to counter the OCD symptoms. Thankfully, following the procedure and calibration the patient exhibited marked improvements in their OCD symptoms and recently shared her results publicly.[xxx] In both cases, there is a similar level of abductive justification for the efficacy of the delivered therapy. In the case study in which the patient was treated with adaptive deep brain stimulation, they at least had their neural activity tested in various settings to determine the optimum parameters for treatment to avoid them being based on guesswork. Additionally, the adaptive deep brain stimulation lead was already placed before the calibration trials were conducted, meaning that the patient had already taken on the bulk of the procedural risk before the efficacy could be determined. Such an efficacy test could have been replicated in the first patient’s cancer treatment, had it been biopsied and tested against the remaining immunotherapies in vitro. Yet, in the case of cancer with few options, one previous dose of a drug that appeared to work on the patient may justify further doses. However, as the Norwegian case presents, corroboration with known responses to a similar drug (from a clinical trial) could be helpful to validate the treatment strategy. (It should be noted that both patients were resigned to these last resort options regardless of the efficacy of treatment.) There are some elements of inductive logic seen with adaptive deep brain stimulation research in general. For example, abductively the focus could be that patient X’s stimulation parameters are different from patient Y’s and patient Z’s. In contrast, when grouped as subjects who obtained personalized stimulation, patients X, Y, and Z demonstrate an inductive aspect to this approach’s safety and/or efficacy. The OCD case holds plenty of abductive characteristics in line with precision medicine’s approach to treating cancer and as more individuals try the method, there will be additional data. With the gradual integration of AI into brain-computer interfaces in the name of efficacy, this reliance on abduction will continue, if not grow, over time. Moving forward, if a responsive deep brain stimulation treatment is novel and individualized (like the dose of nivolumab) and there is some other suggestion of efficacy (like clinical similarities to other patients in the literature), then it may justify insurance coverage for the investigative intervention, absent other unrelated reasons to deny it. III. Ethical Implications and Next Steps While AI’s use in oncology and neurology is not yet as prominent as its use in other fields (e.g., radiology), it appears to be on the horizon for both.[xxxi] AI can be found in both the functioning of the neurotechnologies as well as the implementation of precision medicine. The increasing use of AI may serve to further individualize both oncologic and neurological therapies. Given these implications and the handful of publications cited in this article, it is important to have a nuanced evaluation of how these treatments, which heavily rely on abductive justification, ought to be managed. The just use an abductive approach may be difficult as AI infused precision medicine is further pursued. At baseline, such technology relies on a level of advanced technology literacy among the general public and could exclude populations who lack access to basic technological infrastructure or know-how from participation.[xxxii] Even among nations with adequate infrastructure, as more patients seek out implantable neurotechnologies, which require robust healthcare resources, the market will favor patient populations that can afford this complex care.[xxxiii] If patients already have the means to pay for an initial dose/use of a precision medicine product out of pocket, should insurance providers be required to cover subsequent treatments?[xxxiv] That is, if a first dose of a cancer drug or a deep brain stimulator over its initial battery life is successful, patients may feel justified in having the costs of further treatments covered. The Norwegian patient’s experience implies there is a precedent for the idea that some public insurance companies ought to cover successful cancer therapies, however, insurance companies may not all see themselves as obligated to cover neurotechnologies that rely on personalized settings or that are based on precision/abductive research more than on clinical trials. CONCLUSION The fact that the cases outlined above rely on abductive style of reasoning implies that there may not be as strong a justification for coverage by insurance, as they are both experimental and individualized, when compared to the more traditional large clinical trials in which groups have the same or a standardized protocol (settings/doses). If a study is examining the efficacy of a treatment with a large cohort of patients or with different experimental groups/phases, insurance companies may conclude that the resulting symptom improvements are more likely to be coming from the devices themselves. A preference for inductive justification may take priority when ruling in favor of funding someone’s continued use of an implantable neurostimulator. There are further nuances to this discussion surrounding the classifications of these interventions as research versus clinical care that warrant future exploration, since such a distinction is more of a scale[xxxv] than binary and could have significant impacts on the “right-to-try” approach to experimental therapies in the United States.[xxxvi] Namely, given the inherent limitations of conducting large cohort trials for deep brain stimulation interventions on patients with neuropsychiatric disorders, surgically innovative frameworks that blend abductive and inductive methodologies, like with sham stimulation phases, have traditionally been used.[xxxvii] Similarly, for adaptive brain-computer interface systems, if there are no large clinical trials and instead only publications that demonstrate that something similar worked for someone else, then, in addition to the evidence that the first treatment/dose worked for the patient in question, the balance of reasoning would be valid and arguably justify insurance coverage. As precision approaches to neurotechnology become more common, frameworks for evaluating efficacy will be crucial both for insurance coverage and for clinical decision making. ACKNOWLEDGEMENT This article was originally written as an assignment for Dr. Francis Shen’s “Bioethics & AI” course at Harvard’s Center for Bioethics. I would like to thank Dr. Shen for his comments as well as my colleagues in the Lázaro-Muñoz Lab for their feedback. - [i] Jonathan Kimmelman and Ian Tannock, “The Paradox of Precision Medicine,” Nature Reviews. Clinical Oncology 15, no. 6 (June 2018): 341–42, https://doi.org/10.1038/s41571-018-0016-0. [ii] Henrik Vogt and Bjørn Hofmann, “How Precision Medicine Changes Medical Epistemology: A Formative Case from Norway,” Journal of Evaluation in Clinical Practice 28, no. 6 (December 2022): 1205–12, https://doi.org/10.1111/jep.13649. [iii] David Barrett and Ahtisham Younas, “Induction, Deduction and Abduction,” Evidence-Based Nursing 27, no. 1 (January 1, 2024): 6–7, https://doi.org/10.1136/ebnurs-2023-103873. [iv] Vogt and Hofmann, “How Precision Medicine Changes Medical Epistemology,” 1208. [v] Wireko Andrew Awuah et al., “Bridging Minds and Machines: The Recent Advances of Brain-Computer Interfaces in Neurological and Neurosurgical Applications,” World Neurosurgery, May 22, 2024, S1878-8750(24)00867-2, https://doi.org/10.1016/j.wneu.2024.05.104. [vi] Mark Riedl, “A Very Gentle Introduction to Large Language Models without the Hype,” Medium (blog), May 25, 2023, https://mark-riedl.medium.com/a-very-gentle-introduction-to-large-language-models-without-the-hype-5 f67941fa59e. [vii] David E. Burdette and Barbara E. Swartz, “Chapter 4 - Responsive Neurostimulation,” in Neurostimulation for Epilepsy, ed. Vikram R. Rao (Academic Press, 2023), 97–132, https://doi.org/10.1016/B978-0-323-91702-5.00002-5. [viii] Kimmelman and Tannock, 2018. [ix] Kimmelman and Tannock, 2018. [x] Simon Lohse, “Mapping Uncertainty in Precision Medicine: A Systematic Scoping Review,” Journal of Evaluation in Clinical Practice 29, no. 3 (April 2023): 554–64, https://doi.org/10.1111/jep.13789. [xi] Kimmelman and Tannock, “The Paradox of Precision Medicine.” [xii] Vogt and Hofmann, 1206. [xiii] Vogt and Hofmann, 1206. [xiv] Vogt and Hofmann, 1206. [xv] Vogt and Hofmann, 1207. [xvi] Vogt and Hofmann, 1207. [xvii] Vogt and Hofmann, 1207. [xviii] Vogt and Hofmann, 1210. [xix] Mehar Sahu et al., “Chapter Three - Artificial Intelligence and Machine Learning in Precision Medicine: A Paradigm Shift in Big Data Analysis,” in Progress in Molecular Biology and Translational Science, ed. David B. Teplow, vol. 190, 1 vols., Precision Medicine (Academic Press, 2022), 57–100, https://doi.org/10.1016/bs.pmbts.2022.03.002. [xx] Stefan Feuerriegel et al., “Causal Machine Learning for Predicting Treatment Outcomes,” Nature Medicine 30, no. 4 (April 2024): 958–68, https://doi.org/10.1038/s41591-024-02902-1. [xxi] Sunderland Baker et al., “Ethical Considerations in Closed Loop Deep Brain Stimulation,” Deep Brain Stimulation 3 (October 1, 2023): 8–15, https://doi.org/10.1016/j.jdbs.2023.11.001. [xxii] David Haslacher et al., “AI for Brain-Computer Interfaces,” 2024, 7, https://doi.org/10.1016/bs.dnb.2024.02.003. [xxiii] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 103–4; “Premarket Approval (PMA),” https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100026. [xxiv] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 104. [xxv] Burdette and Swartz, 126. [xxvi] Sean L. Metzger et al., “A High-Performance Neuroprosthesis for Speech Decoding and Avatar Control,” Nature 620, no. 7976 (August 2023): 1037–46, https://doi.org/10.1038/s41586-023-06443-4. [xxvii] Hao Fang and Yuxiao Yang, “Predictive Neuromodulation of Cingulo-Frontal Neural Dynamics in Major Depressive Disorder Using a Brain-Computer Interface System: A Simulation Study,” Frontiers in Computational Neuroscience 17 (March 6, 2023), https://doi.org/10.3389/fncom.2023.1119685; Mahsa Malekmohammadi et al., “Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson’s Disease,” Movement Disorders 31, no. 3 (2016): 426–28, https://doi.org/10.1002/mds.26482. [xxviii] Young-Hoon Nho et al., “Responsive Deep Brain Stimulation Guided by Ventral Striatal Electrophysiology of Obsession Durably Ameliorates Compulsion,” Neuron 0, no. 0 (October 20, 2023), https://doi.org/10.1016/j.neuron.2023.09.034. [xxix] Nho et al. [xxx] Nho et al.; Erik Robinson, “Brain Implant at OHSU Successfully Controls Both Seizures and OCD,” OHSU News, accessed March 3, 2024, https://news.ohsu.edu/2023/10/25/brain-implant-at-ohsu-successfully-controls-both-seizures-and-ocd. [xxxi] Awuah et al., “Bridging Minds and Machines”; Haslacher et al., “AI for Brain-Computer Interfaces.” [xxxii] Awuah et al., “Bridging Minds and Machines.” [xxxiii] Sara Green, Barbara Prainsack, and Maya Sabatello, “The Roots of (in)Equity in Precision Medicine: Gaps in the Discourse,” Personalized Medicine 21, no. 1 (January 2024): 5–9, https://doi.org/10.2217/pme-2023-0097. [xxxiv] Green, Prainsack, and Sabatello, 7. [xxxv] Robyn Bluhm and Kirstin Borgerson, “An Epistemic Argument for Research-Practice Integration in Medicine,” The Journal of Medicine and Philosophy: A Forum for Bioethics and Philosophy of Medicine 43, no. 4 (July 9, 2018): 469–84, https://doi.org/10.1093/jmp/jhy009. [xxxvi] Vijay Mahant, “‘Right-to-Try’ Experimental Drugs: An Overview,” Journal of Translational Medicine 18 (June 23, 2020): 253, https://doi.org/10.1186/s12967-020-02427-4. [xxxvii] Michael S. Okun et al., “Deep Brain Stimulation in the Internal Capsule and Nucleus Accumbens Region: Responses Observed during Active and Sham Programming,” Journal of Neurology, Neurosurgery & Psychiatry 78, no. 3 (March 1, 2007): 310–14, https://doi.org/10.1136/jnnp.2006.095315. (shrink)

Explainable artificial intelligence (XAI) aims to help people understand black box algorithms, particularly of their outputs. But what are these explanations and when is one explanation better than another? The manipulationist definition of explanation from the philosophy of science offers good answers to these questions, holding that an explanation consists of a generalization that shows what happens in counterfactual cases. Furthermore, when it comes to explanatory depth this account holds that a generalization that has more abstract variables, is broader in (...) scope and/or more accurate is better. By applying these definitions and contrasting them with alternative definitions in the XAI literature I hope to help clarify what a good explanation is for AI. (shrink)

According to Hempel’s influential theory of explanation, explaining why some a is G consists in showing that the truth that a is G follows from a law-like generalization to the effect that all Fs are G together with the initial condition that a is F. While Hempel’s overall account is now widely considered to be deeply flawed, the idea that some generalizations play the explanatory role that the account predicts is still often endorsed by contemporary philosophers of science. This idea, (...) however, conflicts with widely shared views in metaphysics according to which the generalization that all Fs are G is partially explained by the fact that a is G. I discuss two solutions to this conflict that have been proposed recently, argue that they are unsatisfactory, and offer an alternative. (shrink)

How ought you to evaluate your options if you’re uncertain about which axiology is true? One prominent response is Expected Moral Value Maximisation, the view that under axiological uncertainty, an option is better than another if and only if it has the greater expected moral value across axiologies. EMVM raises two fundamental questions. First, there’s a question about what it should even mean. In particular, it presupposes that we can compare moral value across axiologies. So to even understand EMVM, we (...) need to explain what it is for such comparisons to hold. Second, assuming that we understand it, there’s a question about whether EMVM is true. Since there are many plausible rivals, we need an argument to defend it. In this paper, I’ll introduce a representation theorem for axiological uncertainty to answer these two questions. Roughly, the theorem shows that if all our axiologies satisfy the von Neumann–Morgenstern axioms, and if the facts about which options are better than which in light of your uncertainty also satisfy these axioms as well as a Pareto condition, then these facts have a relevantly unique expected utility representation. If I’m right, this theorem at once affords us a compelling way to understand EMVM—and specifically intertheoretic comparisons—and a systematic argument for its truth. (shrink)

Not all truths are on a par. The realm of truths is structured: some propositions are only true because others are. The relation that endows the realm of truths with this structure is often called grounding. Grounding has achieved much attention in 21st century metaphysics, but the topic is arguably as old as philosophy itself. -/- This becomes apparent when investigating the works of the 19th-century philosopher Bernard Bolzano, who developed what is perhaps the first comprehensive theory of grounding, drawing (...) on a rich tradition that goes back to Aristotle’s Posterior Analytics. Roski’s book provides, for the first time, a comprehensive study of Bolzano’s theory of grounding in its entirety, paying more attention than previous studies to the interaction between grounding and the consequence-relation of deducibility. -/- . (shrink)

Intuitively, we lack the standing to blame others in light of moral norms that we ourselves don't take seriously: if Adam is unrepentantly aggressive, say, he lacks the standing to blame Celia for her aggressiveness. But why does blame have this feature? Existing proposals try to explain this by reference to specific principles of normative ethics – e.g. to rule‐consequentialist considerations, to the wrongness of hypocritical blame, or principles of rights‐forfeiture based on this wrongness. In this paper, I suggest a (...) fundamentally different approach. Employing Timothy Williamson's idea of ‘constitutive rules’ of speech acts, I argue that this feature of blame is simply constitutive of any essentially moral form of disapproval. So if Adam had the standing to disapprove of Celia's aggressiveness in some form, necessarily, this disapproval couldn't be blame. If I'm right, this proposal thus not only answers our main question, but also sheds an interesting novel light on the very nature of blame. If we didn't have a form of disapproval with that feature, we wouldn't have our practice of holding each other to moral norms. (shrink)

This paper discusses counterexamples to the thesis that the probabilities of conditionals are conditional probabilities. It is argued that the discrepancy is systematic and predictable, and that conditional probabilities are crucially involved in the apparently deviant interpretations. Furthermore, the examples suggest that such conditionals have a less prominent reading on which their probability is in fact the conditional probability, and that the two readings are related by a simple step of abductive inference. Central to the proposal is a distinction between (...) causal and purely stochastic dependence between variables. (shrink)

How ought you to evaluate your options if you're uncertain about what's fundamentally valuable? A prominent response is Expected Value Maximisation (EVM)—the view that under axiological uncertainty, an option is better than another if and only if it has the greater expected value across axiologies. But the expected value of an option depends on quantitative probability and value facts, and in particular on value comparisons across axiologies. We need to explain what it is for such facts to hold. Also, EVM (...) is by no means self-evident. We need an argument to defend that it’s true. This book introduces an axiomatic approach to answer these worries. It provides an explication of what EVM means by use of representation theorems: intertheoretic comparisons can be understood in terms of facts about which options are better than which, and mutatis mutandis for intratheoretic comparisons and axiological probabilities. And it provides a systematic argument to the effect that EVM is true: the theory can be vindicated through simple axioms. The result is a formally cogent and philosophically compelling extension of standard decision theory, and original take on the problem of axiological or normative uncertainty. (shrink)

According to the standard account of forgiveness, you forgive your wrongdoer by overcoming your resentment towards them. But how exactly must you do so? And when is such overcoming fitting? The aim of this paper is to introduce a novel version of the standard account to answer these questions. Its core idea is that the reactive attitudes are a fitting response not just to someone’s blameworthiness, but to their blameworthiness being significant for you, or worthy of your caring, in virtue (...) of your relationship to it. Someone’s blameworthiness is significant for you to the extent you’re bound up with what grounds it––e.g. with the wrongdoer’s being a participant in human relationships, with their attitudes, or with the victim’s being a source of demands. So you may fittingly not care about someone’s blameworthiness if it’s sufficiently insignificant for you in this manner––e.g. if their wrong happened far off in place and time. And forgiveness revolves around this. You forgive your wrongdoer if and only if, partly out of goodwill towards them, you cease to care about their blameworthiness––a bit as if their wrong had happened far off. If I’m right, this agent-relativity-based account can resolve the apparent ‘paradoxy of forgiveness’, satisfies a number of desiderata, and is plausible on an intuitive level. (shrink)

The connection between the probabilities of conditionals and the corresponding conditional probabilities has long been explored in the philosophical literature, but its implementation faces both technical obstacles and objections on empirical grounds. In this paper I ?rst outline the motivation for the probabilistic turn and Lewis’ triviality results, which stand in the way of what would seem to be its most straightforward implementation. I then focus on Richard Jeffrey’s ’random-variable’ approach, which circumvents these problems by giving up the notion that (...) conditionals denote propositions in the usual sense. Even so, however, the random-variable approach makes counterintuitive predictions in simple cases of embedded conditionals. I propose to address this problem by enriching the model with an explicit representation of causal dependencies. The addition of such causal information not only remedies the shortcomings of Jeffrey’s conditional, but also opens up the possibility of a uni?ed probabilistic account of indicative and counterfactual conditionals. (shrink)

Conditionals with conditional constituents pose challenges for _the Thesis_, the idea that the probability of a conditional is the corresponding conditional probability. This note is concerned with two proposals for overcoming those challenges, both inspired by early work of van Fraassen: the _Bernoulli Semantics_ associated with Stalnaker and Jeffrey, and augmented with a mechanism for obtaining “local probabilities” by Kaufmann; and a proposal by Bacon which I dub _Ordinal Semantics_. Despite differences in mathematical details and emphasis of presentation, both proposals (...) lend themselves for use as a basis for a modal-theoretic interpretation of embedded conditionals. The goal of this note is to compare the two frameworks by implementing a model for the interpretation of conditionals in each, based on the same underlying probability model for non-conditional sentences. I show that in the Ordinal model, certain sentences are assigned probabilities that do not accord with intuitions. This problem is familiar from the literature on Bernoulli models and can be addressed by introducing Kaufmann-style local probabilities into Ordinal models. I then show that Bernoulli Semantics has other limitations, in that it assigns probabilities in violation of the Thesis to certain very complex formulas. The upshot is that a fusion of the theories may be our best shot at getting the predictions right. (shrink)

Bostrom rejects Nietzsche as an ancestor of the transhumanist movement, as he claims that there were merely some “surface-level similarities with the Nietzschean vision” (Bostrom 2005a, 4). In contrast to Bostrom, I think that significant similarities between the posthuman and the overhuman can be found on a fundamental level. In addition, it seems to me that Nietzsche explained the relevance of the overhuman by referring to a dimension which seems to be lacking in transhumanism. In order to explain my position, (...) I will progress as follows. First, I will compare the concept of the posthuman to that of Nietzsche’s overhuman, focusing more on their similarities than their differences. Second, I will contextualise the overhuman in Nietzsche’s general vision, so that I can point out which dimension seems to me to be lacking in transhumanist thought. (shrink)

How do we get out knowledge of the natural numbers? Various philosophical accounts exist, but there has been comparatively little attention to psychological data on how the learning process actually takes place. I work through the psychological literature on number acquisition with the aim of characterising the acquisition stages in formal terms. In doing so, I argue that we need a combination of current neologicist accounts and accounts such as that of Parsons. In particular, I argue that we learn the (...) initial segment of the natural numbers on the basis of the Fregean definitions, but do not learn the natural number structure as a whole on the basis of Hume's principle. Therefore, we need to account for some of the consistency of our number concepts with the Dedekind-Peano axioms in other terms. (shrink)

In their paper Nothing but the Truth Andreas Pietz and Umberto Rivieccio present Exactly True Logic, an interesting variation upon the four-valued logic for first-degree entailment FDE that was given by Belnap and Dunn in the 1970s. Pietz & Rivieccio provide this logic with a Hilbert-style axiomatisation and write that finding a nice sequent calculus for the logic will presumably not be easy. But a sequent calculus can be given and in this paper we will show that a calculus for (...) the Belnap-Dunn logic we have defined earlier can in fact be reused for the purpose of characterising ETL, provided a small alteration is made—initial assignments of signs to the sentences of a sequent to be proved must be different from those used for characterising FDE. While Pietz & Rivieccio define ETL on the language of classical propositional logic we also study its consequence relation on an extension of this language that is functionally complete for the underlying four truth values. On this extension the calculus gets a multiple-tree character—two proof trees may be needed to establish one proof. (shrink)

By using the notions of exact truth and exact falsity, one can give 16 distinct definitions of classical consequence. This paper studies the class of relations that results from these definitions in settings that are paracomplete, paraconsistent or both and that are governed by the Strong Kleene schema. Besides familiar logics such as Strong Kleene logic, the Logic of Paradox and First Degree Entailment, the resulting class of all Strong Kleene generalizations of classical logic also contains a host of unfamiliar (...) logics. We first study the members of our class semantically, after which we present a uniform sequent calculus that is sound and complete with respect to all of them. Two further sequent calculi and \ calculus) will be considered, which serve the same purpose and which are obtained by applying general methods to construct sequent calculi for many-valued logics. Rules and proofs in the SK calculus are much simpler and shorter than those of the \ and the \ calculus, which is one of the reasons to prefer the SK calculus over the latter two. Besides favourably comparing the SK calculus to both the \ and the \ calculus, we also hint at its philosophical significance. (shrink)

Philosophers investigating the interpretation and use of conditional sentences have long been intrigued by the intuitive correspondence between the probability of a conditional `if A, then C' and the conditional probability of C, given A. Attempts to account for this intuition within a general probabilistic theory of belief, meaning and use have been plagued by a danger of trivialization, which has proven to be remarkably recalcitrant and absorbed much of the creative effort in the area. But there is a strategy (...) for avoiding triviality that has been known for almost as long as the triviality results themselves. What is lacking is a straightforward integration of this approach in a larger framework of belief representation and dynamics. This paper discusses some of the issues involved and proposes an account of belief update by conditionalization. (shrink)

The search for ethical guidance in the development of artificial intelligence (AI) systems, especially in healthcare and decision support, remains a crucial effort. So far, principles usually serve as the main reference points to achieve ethically correct implementations. Based on reviewing classical criticism of principle-based ethics and taking into account the severity and potentially life-changing relevance of decisions assisted by AI-driven systems, we argue for strengthening a complementary perspective that focuses on the life-world as ensembles of practices which shape people’s (...) lives. This perspective focuses on the notion of ethical judgment sensitive to life forms, arguing that principles alone do not guarantee ethicality in a moral world that is rather a joint construction of reality than a matter of mere control. We conclude that it is essential to support and supplement the implementation of moral principles in the development of AI systems for decision-making in healthcare by recognizing the normative relevance of life forms and practices in ethical judgment. (shrink)

The topic of this thesis is axiological uncertainty – the question of how you should evaluate your options if you are uncertain about which axiology is true. As an answer, I defend Expected Value Maximisation (EVM), the view that one option is better than another if and only if it has the greater expected value across axiologies. More precisely, I explore the axiomatic foundations of this view. I employ results from state-dependent utility theory, extend them in various ways and interpret (...) them accordingly, and thus provide axiomatisations of EVM as a theory of axiological uncertainty. (shrink)

This paper explores links between different ethical motivations and kinds of corporate social responsibility activities to distinguish between different types of business cases with regard to sustainability. The design of CSR and corporate sustainability can be based on different ethical foundations and motivations. This paper draws on the framework of Roberts which distinguishes four different ethical management versions of CSR. The first two ethical motivations are driven either by a reactionary concern for the short-term financial interests of the business, or (...) reputational, driven by a narcissistic concern to protect the firm’s image. The third responsible motivation works from the inside-out and seeks to embed social and environmental concerns within the firm’s performance management systems, and the fourth, a collaborative motivation, works to bring the outside in and seeks to go beyond the boundaries of the firm to create a dialogue with those who are vulnerable to the unintended consequences of corporate conduct. Management activities based on these different ethical motivations to CSR and sustainability result in different operational activities for corporations working towards sustainability and thus have very different effects on how the company’s economic performance is influenced. Assuming that corporate managers are concerned about creating business cases for their companies to survive and prosper in the long term, this paper raises the question of how different ethical motivations for designing CSR and corporate sustainability relate to the creation of different business cases. The paper concludes by distinguishing four different kinds of business cases with regard to sustainability: reactionary and reputational business cases of sustainability, and responsible and collaborative business cases for sustainability. (shrink)

Many people think that if you're uncertain about which moral theory is correct, you ought to maximize the expected choice-worthiness of your actions. This idea presupposes that the strengths of our moral reasons are comparable across theories – for instance, that our reasons to create new people, according to total utilitarianism, can be stronger than our reasons to benefit an existing person, according to a person-affecting view. But how can we make sense of such comparisons? In this article, I introduce (...) a constructivist account of intertheoretic comparisons. On this account, such comparisons don't hold independently of facts about morally uncertain agents. They're simply the result of an ideal deliberation in terms of certain epistemic norms about what you ought to do in light of your uncertainty. If I'm right, this account is metaphysically more parsimonious than some existing proposals, and yet has plausible and strong implications. (shrink)

In this paper I offer an anti-Humean critique to Williamson and Russo’s approach to medical mechanisms. I focus on one of the specific claims made by Williamson and Russo, namely the claim that micro-structural ‘mechanisms’ provide evidence for the stability across populations of causal relationships ascertained at the (macro-) level of (test) populations. This claim is grounded in the epistemic account of causality developed by Williamson, an account which—while not relying exclusively on mechanistic evidence for justifying causal judgements—appeals nevertheless to (...) mechanisms, and rejects their anti-Humean interpretation in terms of capacities, powers, potencies, etc. By using (and expanding on) Cartwright’s basic critique against Humean mechanisms, I suggest that, in order to move beyond the level of plausibility, Williamson and Russo’s position is in need of a clarification as to the occurent reading of the components, functioning and interferences of mechanisms. Relatedly, as concerns Williamson’s epistemic account of causation, I argue that this account is in need of a more straightforward answer as to what truth-makers its causal claims should have. (shrink)

ABSTRACT How do non-experts single out numbers for reference? Linnebo has argued that they do so using a criterion of identity based on the ordinal properties of numerals. Neo-logicists, on the other hand, claim that cardinal properties are the basis of individuation, when they invoke Hume’s Principle. I discuss empirical data from cognitive science and linguistics to answer how non-experts individuate numbers better in practice. I use those findings to develop an alternative account that mixes ordinal and cardinal properties to (...) provide a detailed answer to the question: how do we in fact semantically individuate numbers? (shrink)

Prospect Theory (PT) is widely regarded as the most promising descriptive model for decision making under uncertainty. Various tests have corroborated the validity of the characteristic fourfold pattern of risk attitudes implied by the combination of probability weighting and value transformation. But is it also safe to assume stable PT preferences at the individual level? This is not only an empirical but also a conceptual question. Measuring the stability of preferences in a multi-parameter decision model such as PT is far (...) more complex than evaluating single-parameter models such as Expected Utility Theory under the assumption of constant relative risk aversion. There exist considerable interdependencies among parameters such that allegedly diverging parameter combinations could in fact produce very similar preference structures. In this paper, we provide a theoretic framework for measuring the (temporal) stability of PT parameters. To illustrate our methodology, we further apply our approach to 86 subjects for whom we elicit PT parameters twice, with a time lag of 1 month. While documenting remarkable stability of parameter estimates at the aggregate level, we find that a third of the subjects show significant instability across sessions. (shrink)

Can concepts be acquired by testing hypotheses about these concepts? Fodor famously argued that this is not possible. Testing the correct hypothesis would require already possessing the concept. I argue that this does not generally hold for mathematical concepts. I discuss specific, empirically motivated, hypotheses for number concepts that can be tested without needing to possess the relevant number concepts. I also argue that one can test hypotheses about the identity conditions of other mathematical concepts, and then fix the application (...) conditions based on those hypotheses—under the assumption that the neo‐logicist view on abstraction principles is correct. (shrink)

In this paper, I focus on life-threatening medical conditions and argue that from the point of view of natural properties, induction(s), and participation in laws, at least some of the ill organisms dealt with in somatic medicine form natural kinds in the same sense in which the kinds in the exact sciences are thought of as natural. By way of comparing two ‘divisions of nature’, viz., a ‘classical’ exact science kind (gold) and a kind of disease (Graves disease), I show (...) that there is no justifiable ‘ontological gap’ between disease kinds and exact sciences kinds. We have instead a difference of degree. (shrink)

We investigate the issue of aggregativity in fair division problems from the perspective of cooperative game theory and Broomean theories of fairness. Paseau and Saunders proved that no non-trivial theory of fairness can be aggregative and conclude that theories of fairness are therefore problematic, or at least incomplete. We observe that there are theories of fairness, particularly those that are based on cooperative game theory, that do not face the problem of non-aggregativity. We use this observation to argue that the (...) universal claim that no non-trivial theory of fairness can guarantee aggregativity is false. Paseau and Saunders’s mistaken assertion can be understood as arising from a neglect of the games approach to fair division. Our treatment has two further pay-offs: for one, we give an accessible introduction to the games approach to fair division, whose significance has hitherto not been appreciated by philosophers working on fairness. For another, our discussion explores the issue of aggregativity in fair division problems in a comprehensive fashion. (shrink)

In a recent article, Emanuel Rutten has presented a novel argument for the existence of God, defined as a personal being that is the first cause of reality. An interesting feature of the argument, which caused quite a stir, is that it does not fall within any of the traditional categories of arguments for God’s existence. Rutten calls his argument a modal-epistemic one, which reflects the fact that the first premise of his argument states that all possible truths are knowable. (...) The main purpose of this article is a simple one: to point out that Rutten’s modal-epistemic argument is flawed. (shrink)

In a recent article, Emanuel Rutten defends his Modal-Epistemic Argument (MEA) for the existence of God against various objections that I raised against it. In this article, I observe that Rutten’s defence fails for various reasons. Most notably though, the defence is self-undermining: the very claims that Rutten argues for in his defence yield novel counterexamples to the first premise of the MEA.

Moral development has become an integral part in military training and the importance of moral judgment and behavior in military operations can hardly be overestimated. Many armed forces have integrated military ethics and moral decision-making interventions in their training programs. However, little is known about the effectiveness of these interventions. This study examined the effectiveness of a 1-week training program in moral decision making in the Swiss Armed Forces. The program was based on a strategy-based interactional moral dilemma approach. Results (...) of this quasi-experimental intervention study showed significant improvements in content-related (moral and instrumental awareness, quality of moral information processing, development of compensatory actions) as well as process-related (situational analysis, development and evaluation of alternative solutions, justification of decision) aspects in moral decision making. Results of a follow-up test indicated positive long-term effects with regard to moral and instrumental awareness and process-related aspects. Findings are discussed, and consequences for leadership development programs and further research are explored. (shrink)

Theater rehearsals are (usually) confronted with the problem of having to transform a written text into an audio-visual, situated and temporal performance. Our contribution focuses on the emergence and stabilization of a gestural form as a solution for embodying a certain aesthetic concept which is derived from the script. This process involves instructions and negotiations, making the process of stabilization publicly and thus intersubjectively accessible. As scenes are repeatedly rehearsed, rehearsals are perspicuous settings for tracking interactional histories. Based on videotaped (...) professional theatre interactions in Germany, we focus on consecutive instances of rehearsing the same scene and trace the interactional history of a particular gesture. This gesture is used by the director to instruct the actors to play a particular aspect of a scene adopting a certain aesthetic concept. Stabilization requires the emergence of shared knowledge. We will show the practices by which shared knowledge is established over time during the rehearsal process and, in turn, how the accumulation of knowledge contributes to a change in the interactional practices themselves. Specifically, we show how a gesture emerges in the process of developing and embodying an aesthetic concept, and how this gesture eventually becomes a sign that refers to and evokes accumulated knowledge. At the same time, we show how this accumulated knowledge changes the instructional activities in the rehearsal process. Our study contributes to the overall understanding of knowledge accumulation in interaction in general and in theater rehearsals in particular. At the same time, it is devoted to the central importance of gestures in theater, which are both a means and a product of theatrical staging. (shrink)

Is it appropriate to blame people unequally if the only difference between them was a matter of luck? Suppose Alice would drive recklessly if she could, Belen drove recklessly but didn’t harm anyone, and Cleo drove recklessly and killed a child. Luck-advocates emphasize that in real life we do blame such agents very unequally. Luck-skeptics counter that people aren’t responsible for factors beyond their control, or beyond their quality of will. I’ll defend a somewhat reconciliatory view. I’ll concede to the (...) skeptics that these agents are equally culpable. Nonetheless, I’ll suggest with the luck-advocates that it’s fitting to blame them unequally. That’s because their culpability is unequally significant for us: Cleo’s culpability concerns us more than Belen’s, and Belen’s more than Alice’s—just like the fault of a close aggressor concerns us more than that of an aggressor far off in place and time. And it’s fitting for us to respond with more blame to faults that concern us more. Indeed, blaming people simply in proportion to their culpability manifests a form of fetishism, or problematic mere-matter-of-principle concern. So while many skeptical tenets may hold, in substance the luck-advocates are right. (shrink)

Statements about the behavior of biochemical entities (e.g., about the interaction between two proteins) abound in the literature on molecular biology and are increasingly becoming the targets of information extraction and text mining techniques. We show that an accurate analysis of the semantics of such statements reveals a number of ambiguities that have to be taken into account in the practice of biomedical ontology engineering: Such statements can not only be understood as event reporting statements, but also as ascriptions of (...) dispositions or tendencies that may or may not refer to collectives of interacting molecules or even to collectives of interaction events. (shrink)

"Provides translations of Bolzano's most important work on grounding, including previously untranslated material"--.

As conservation biology has developed as a distinct discipline from ecology, conservation guidelines based on ecological theory have been largely cast aside in favor of theory-independent decision procedures for designing conservation reserves. I argue that this transition has failed to advance the field toward its aim of preserving biodiversity. The abandonment of island biogeography theory in favor of complementarity-based algorithms is a case in point. In what follows, I consider the four central objections raised against island biogeographic conservation guidelines, arguing (...) that they fail to undermine the credibility of this framework as a conservation tool. At best, these objections call for a more careful application of this framework to conservation problems, not its wholesale abandonment. At the same time, complementarily-based algorithms are biased in favor of networks of small reserves containing non-overlapping species. These conditions threaten to promote inbreeding depression, genetic drift and other factors that increase a population’s risk of extinction. Therefore, recent developments in the field of conservation biology have arguably not contributed to its ultimate aim of preserving the maximum amount of biodiversity in the long run. (shrink)

“Existential risks” are risks that threaten the destruction of humanity’s long-term potential: risks of nuclear wars, pandemics, supervolcano eruptions, and so on. On standard utilitarianism, it seems, the reduction of such risks should be a key global priority today. Many effective altruists agree with this verdict. But how should the importance of these risks be assessed on a Christian moral theory? In this paper, I begin to answer this question – taking Thomas Aquinas as a reference, and the risks of (...) anthropogenic extinction as an example. I’ll suggest that on a Thomist framework, driving ourselves extinct would constitute a complete failure to fulfil our God-given nature, a radical form of hubris, and a loss of cosmological significance. So the reduction of such risks seems vital for Thomists, or Christians more broadly. Indeed, I end with the thought that these considerations are not parochially Christian, or indeed specifically religious: everyone with a similar view of mankind – as immensely valuable yet fallen and fragile – should agree that existential risks are a pressing moral concern. (shrink)

A computational model of inference during story comprehension is presented, in which story situations are represented distributively as points in a high‐dimensional “situation‐state space.” This state space organizes itself on the basis of a constructed microworld description. From the same description, causal/temporal world knowledge is extracted. The distributed representation of story situations is more flexible than Golden and Rumelhart's [Discourse Proc 16 (1993) 203] localist representation.A story taking place in the microworld corresponds to a trajectory through situation‐state space. During the (...) inference process, world knowledge is applied to the story trajectory. This results in an adjusted trajectory, reflecting the inference of propositions that are likely to be the case. Although inferences do not result from a search for coherence, they do cause story coherence to increase. The results of simulations correspond to empirical data concerning inference, reading time, and depth of processing.An extension of the model for simulating story retention shows how coherence is preserved during retention without controlling the retention process. Simulation results correspond to empirical data concerning story recall and intrusion. (shrink)