© The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved.Cell walls of grasses, including cereal crops and biofuel grasses, comprise the majority of plant biomass and intimately influence plant growth, development and physiology. However, the functions of many cell wall synthesis genes, and the relationships among and the functions of cell wall components remain obscure. To better understand the patterns of cell wall accumulation and identify genes that act in grass (...) cell wall biosynthesis, we characterized 30 samples from aerial organs of rice at 10 developmental time points, 3-100 d post-germination. Within these samples, we measured 15 cell wall chemical components, enzymatic digestibility and 18 cell wall polysaccharide epitopes/ligands. We also used quantitative reverse transcription-PCR to measure expression of 50 glycosyltransferases, 15 acyltransferases and eight phenylpropanoid genes, many of which had previously been identified as being highly expressed in rice. Most cell wall components vary significantly during development, and correlations among them support current understanding of cell walls. We identified 92 significant correlations between cell wall components and gene expression and establish nine strong hypotheses for genes that synthesize xylans, mixed linkage glucan and pectin components. This work provides an extensive analysis of cell wall composition throughout rice development, identifies genes likely to synthesize grass cell walls, and provides a framework for development of genetically improved grasses for use in lignocellulosic biofuel production and agriculture. (shrink)

The idea that technologies can change moral beliefs and practices is an old one. But how, exactly, does this happen? This paper builds on an emerging field of inquiry by developing a synoptic taxonomy of the mechanisms of techno-moral change. It argues that technology affects moral beliefs and practices in three main domains: decisional (how we make morally loaded decisions), relational (how we relate to others) and perceptual (how we perceive situations). It argues that across these three domains there are (...) six primary mechanisms of techno-moral change: (i) adding options; (ii) changing decision-making costs; (iii) enabling new relationships; (iv) changing the burdens and expectations within relationships; (v) changing the balance of power in relationships; and (vi) changing perception (information, mental models and metaphors). The paper also discusses the layered, interactive and second-order effects of these mechanisms. (shrink)

The Unprovability of Consistency is concerned with connections between two branches of logic: proof theory and modal logic. Modal logic is the study of the principles that govern the concepts of necessity and possibility; proof theory is, in part, the study of those that govern provability and consistency. In this book, George Boolos looks at the principles of provability from the standpoint of modal logic. In doing so, he provides two perspectives on a debate in modal logic that has persisted (...) for at least thirty years between the followers of C. I. Lewis and W. V. O. Quine. The author employs semantic methods developed by Saul Kripke in his analysis of modal logical systems. The book will be of interest to advanced undergraduate and graduate students in logic, mathematics and philosophy, as well as to specialists in those fields. (shrink)

It is unknown to what extent medical researchers generalize study findings beyond their samples when their sample size, sample diversity, or knowledge of conditions that support external validity do not warrant it. It is also unknown to what extent medical researchers describe their results with precise quantifications or unquantified generalizations, i.e., generics, that can obscure variations between individuals. We therefore systematically reviewed all prospective studies (n = 533) published in the top four highest ranking medical journals, Lancet, New England Journal (...) of Medicine (NEJM), Journal of the American Medical Association (JAMA), and the British Medical Journal (BMJ), from January 2022 to May 2023. We additionally reviewed all NEJM Journal Watch clinical research summaries (n = 143) published during the same time. Of all research articles reporting prospective studies, 52.5% included generalizations beyond specific national study populations, with the numbers of articles with generics varying significantly between journals (JAMA = 12%; Lancet = 77%) (p < 0.001, V = 0.48). There was no evidence that articles containing broader generalizations or generics were correlated with larger or more nationally diverse samples. Moreover, only 10.2% of articles with generalizations beyond specific national populations reported external validity strengthening factors that could potentially support such extrapolations. There was no evidence that original research articles and NEJM Journal Watch summaries intended for practitioners differed in their use of broad generalizations, including generics. Finally, from the journal with the highest citation impact, articles containing broader conclusions were correlated with more citations. Since there was no evidence that studies with generalizations beyond specific national study populations or with generics were associated with larger, more nationally diverse samples, or with reports of population similarity that may permit extensions of conclusions, our findings suggest that the generalizations in many articles were insufficiently supported. Caution against overly broad generalizations in medical research is warranted. (shrink)

This book provides papers of the conference of leading scientists and philosophers on the notion of progress of knowledge, which is constitutive of our modern selfunderstanding, from the perspective of their disciplines. Summary of contents: 1. GEorg Henrik von Wright, Progress: Fiction and Fact 2. WAlter Burkert, Impact and Limits of the Idea of Progress in Antiquity 3. AListair Crombie, Philosophical Commitments and Scientific Progress 4. SHigeru Nakayama, Chinese "Cyclic" View of History vs Japanese "Progress" 5. JEan Blondel, Political (...) Progress: Illusion or Reality 6. NIcholas Rescher, Progress and the Future 7. RUdolf Flotzinger, Progress and Development in Musical History 8. DAg Pravitz, Progress in Philosophy 9. JOhn D. BArrow, Time in the Universe 10. ANtonio Garcia-Bellido, Progress in Biological Evolution 11. GEreon Wolters, The Idea of Progress in Evolutionary Biology: Philosophical Considerations 12. PHilippe Lazar, The Idea of Progress in Human Health. (shrink)

-- v. 3. Truth, knowledge, and modality.

Volume 24 of _The Annual_ opens with a memorial tribute to the late Merton M. Gill, a major voice in American psychoanalysis for half a century. Remembrances of Gill by Robert Holt, Robert Wallerstein, Philip Holzman, and Irwin Hoffman are followed by thoughtful appreciations of Gill's final book, _Psychoanalysis in Transition: A Personal View_, by John Gedo, Jerome Oremland, Arnold Richards and Arthur Lynch, Joseph Schachter, and Bhaskar Sripada and Shara Kronmal. Section II offers four papers from a major conference (...) on "Mind/Brain" held in Osaka, Japan. In addition to publishing two clinical papers by the Chicago analyst John Gedo, _The Annual_ introduces readers to two prominent Japanese neuroscientists whose work is relevant to psychoanalysis. Hiroshi Utena links brain development to the individual's freedom to make optimal adaptive choices, whereas Makoto Iwata outlines the modular organization of vision in the brain and then illustrates each modular potential by examining the paintings of four artists: Mondrian, Duchamp, Seurat, and Rothko. Kenneth Newman's sensitive consideration of analyst self-discourse as the outcome of successful management of the countertransference and Frank Summers' astute assessment of the place of self psychology in the history of psychoanalytic ideas are followed by three engaging and instructive studies in applied analysis: Elaine Caruth and Milton Eber's examination of Woody Allen's _The Purple Rose of Cairo _as a metaphoric depiction of the blurring of boundaries in psychotherapy; Frank and Annette Lachmann's study of the creative process of Henrik Ibsen as a self-transformational response to narcissistic injury; and W. W. Meissner's exploration of the role of shame in Vincent van Gogh's life and art. The volume concludes with a provocative contribution to psychoanalytic history: J. Bos's social-constructivist rereading of the _Minutes of the Vienna Psycho-Analytic Society_ with an eye to illuminating why and how psychoanalysis changed during its early years. True to its distinguished lineage, volume 24 of _The Annual_ continues to broaden the conceptual, clinical, and historical vistas of its readers. Moreover, with its revealing reminiscences and substantive appraisals of Merton Gill, this volume becomes a fascinating marker in the very psychoanalytic history it helps recount. (shrink)

Cognitive science is experiencing a pragmatic turn away from the traditional representation-centered framework toward a view that focuses on understanding cognition as "enactive." This enactive view holds that cognition does not produce models of the world but rather subserves action as it is grounded in sensorimotor skills. In this volume, experts from cognitive science, neuroscience, psychology, robotics, and philosophy of mind assess the foundations and implications of a novel action-oriented view of cognition. Their contributions and supporting experimental evidence show that (...) an enactive approach to cognitive science enables strong conceptual advances, and the chapters explore key concepts for this new model of cognition. The contributors discuss the implications of an enactive approach for cognitive development; action-oriented models of cognitive processing; action-oriented understandings of consciousness and experience; and the accompanying paradigm shifts in the fields of philosophy, brain science, robotics, and psychology. ContributorsMoshe Bar, Lawrence W. Barsalov, Olaf Blanke, Jeannette Bohg, Martin V. Butz, Peter F. Dominey, Andreas K. Engel, Judith M. Ford, Karl J. Friston, Chris D. Frith, Shaun Gallagher, Antonia Hamilton, Tobias Heed, Cecilia Heyes, Elisabeth Hill, Matej Hoffmann, Jakob Hohwy, Bernhard Hommel, Atsushi Iriki, Pierre Jacob, Henrik Jörntell, Jürgen Jost, James Kilner, Günther Knoblich, Peter König, Danica Kragic, Miriam Kyselo, Alexander Maye, Marek McGann, Richard Menary, Thomas Metzinger, Ezequiel Morsella, Saskia Nagel, Kevin J. O'Regan, Pierre-Yves Oudeyer, Giovanni Pezzulo, Tony J. Prescott, Wolfgang Prinz, Friedemann Pulvermüller, Robert Rupert, Marti Sanchez-Fibla, Andrew Schwartz, Anil K. Seth, Vicky Southgate, Antonella Tramacere, John K. Tsotsos, Paul F. M. J. Verschure, Gabriella Vigliocco, Gottfried Vosgerau. (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)

Computational modeling should play a central role in philosophy. In this introduction to our topical collection, we propose a small topology of computational modeling in philosophy in general, and show how the various contributions to our topical collection fit into this overall picture. On this basis, we describe some of the ways in which computational models from other disciplines have found their way into philosophy, and how the principles one found here still underlie current trends in the field. Moreover, we (...) argue that philosophers contribute to computational modeling not only by building their own models, but also by thinking about the various applications of the method in philosophy and the sciences. In this context, we note that models in philosophy are usually simple, while models in the sciences are often more complex and empirically grounded. Bridging certain methodological gaps that arise from this discrepancy may prove to be challenging and fruitful for the further development of computational modeling in philosophy and beyond. (shrink)

Computational modeling should play a central role in philosophy. In this introduction to our topical collection, we propose a small topology of computational modeling in philosophy in general, and show how the various contributions to our topical collection ft into this overall picture. On this basis, we describe some of the ways in which computational models from other disciplines have found their way into philosophy, and how the principles one found here still underlie current trends in the feld. Moreover, we (...) argue that philosophers contribute to computational modeling not only by building their own models, but also by thinking about the various applications of the method in philosophy and the sciences. In this context, we note that models in philosophy are usually simple, while models in the sciences are often more complex and empirically grounded. Bridging certain methodological gaps that arise from this discrepancy may prove to be challenging and fruitful for the further development of computational modeling in philosophy and beyond. (shrink)

Theoria , the international Swedish philosophy journal, was founded in 1935. Its contributors in the first 75 years include the major Swedish philosophers from this period and in addition a long list of international philosophers, including A. J. Ayer, C. D. Broad, Ernst Cassirer, Hector Neri Castañeda, Arthur C. Danto, Donald Davidson, Nelson Goodman, R. M. Hare, Carl G. Hempel, Jaakko Hintikka, Saul Kripke, Henry E. Kyburg, Keith Lehrer, Isaac Levi, David Lewis, Gerald MacCallum, Richard Montague, Otto Neurath, Arthur N. (...) Prior, W. V. Quine, Nicholas Rescher, Ernest Sosa, Robert C. Stalnaker, P. F. Strawson, Patrick Suppes, Johan van Benthem, Georg Henrik von Wright and many others. Hempel's confirmation paradoxes, Ross's deontic paradox, Montague's universal grammar and Lindström's theorem are among the contributions to philosophy that were first published in Theoria. (shrink)

For eller imod Naturen? Naturen er traditionelt blevet opfattet som noget skidt, man kunne behandle, som man ville; som noget lavt, man har kunnet udnytte; endog som noget "syndigt", man skulle undertrykke! I denne bog vil Naturen blive skrevet med stort, og heri vil man møde en tradition, der som en understrøm, eller måske rettere overstrøm, har været til stede som alternativet til den herskende naturfjendske tænkemåde. Denne tradition har man forsøgt at undertrykke på alle måder! Man har gjort Platon (...) til discipel af Sokrates i stedet for Pythagoras, man har fortiet, at Cicero, Kepler, Leibniz, Goethe og Ørsted alle var inkarnerede platonikere -- ligesom også Henrik Pontoppidan var det: 'At lovprise det skønne, gode, retfærdige; at brændemærke skurkene, narrene, hyklerne -- det er og har været og vil vedblive at være en værdig opgave også for de skønne kunster' -- sådan skrev Pontoppidan selv, og hans. 'Lykke-Per' skriver (ligesom Platon!) en bog om en 'Fremtidsstat'. Den er baseret på "grøn energi", og i stedet for kirker har den templer for platoniske ideer som Sandheden og Retfærdigheden. (shrink)

This chapter discusses the works of Danish philosopher Soren Kierkegaard that were discovered after his death on November 11, 1855. These papers were compiled by his nephew Henrik Lund and were later given to his brother Bishop Peter Christian Kierkegaard. Four major editions of the papers were published, which include Af Soren Kierkegaards Efterladte Papirer, Soren Kierkegaards Samlede Værker, Soren Kierkegaards Papirer, and Soren Kierkegaards Skrifter. The chapter also considers some aspects of Kierkegaard's working process.

This paper presents some reflections about an approach in work psychology: the Activity Clinic. After a brief introduction to the conceptual background of the “Activity Clinic”, it covers three deeply interconnected themes. The first concerns the meaning attributed to the development of the affects present in the work situation under analysis; the second discusses the reasons for the conflicts that are ultimately due to these affects; the third considers how a method of co-analysis of the activity can lead towards transformation (...) of those conflicts. Our reflections refer to the process engendered by this methodological approach as one of “transferential activity”. The paper explains this process by empirically describing the “transport” of affects involved in the conflicts. The personal interpretation of the cause of problems gives way to the understanding that they are due to organizational dysfunction rather than to individual personalities. Measures can then be taken to break the deadlocks experienced both at the personal and collective level. (shrink)

We offer a precautionary account of why business managers should proactively rethink about what kinds of automation firms ought to implement, by exploring two challenges that automation will potentially pose. We engage the current debate concerning whether life without work opportunities will incur a meaning crisis, offering an argument in favor of the position that if technological unemployment occurs, the machine age may be a structurally limited condition for many without work opportunities to have or add meaning to their lives. (...) We term this the axiological challenge. This challenge, if it turns out to be persuasive, leads to a second challenge, to which managers should pay special attention: the teleological challenge, a topic especially relevant to the broad literature about corporate purpose and governance. We argue that both the shareholder profit-maximization model and its major alternative, stakeholder theory, are insufficient to address the meaning crisis. Unless rebutted, the two challenges compel business leaders to proactively rethink the purpose of business for future society. Otherwise, businesses will be contributors to a major ethical crisis and societal externality in the coming society. (shrink)

Analyses of so-called ‘post-truth’ discourse in populist politics have so far largely focussed on sorting it into cases of lying, bullshitting, bubble-like epistemic constraints, or alternative epistemic norms flouting objective truth. We review these proposals and point out problems with each. Some scholars, however, have recently drawn attention to how apparent assertions of facts in these contexts seem to be functionally entangled with expressing or affirming social identities. To get a clearer picture of what such an explanation might amount to, (...) we differentiate four different ways in which social identities might be connected to apparently assertive discourse: signalling, expressive affirmation, dissonance reduction, and identity grounding. Distinguishing and deciding among these will matter not only for providing an accurate analysis of post-truth discourse, but also for determining the exact grounds on which it merits criticism and for what might be done about it. (shrink)

The emergence of economic inequality has often been linked to individual differences in mental or physical capacities. By means of an agent-based simulation this paper shows that neither of these is a necessary condition. Rather, inequality can arise from iterated interactions of fully rational agents. This bears consequences for our understanding of both inequality and rationality. In a setting of iterated bargaining games, we claim that expected utility maximizing agents perform suboptimally in comparison with other strategies. The reason for this (...) lies in complex feedback effects between an agents’ action and the quality of beliefs used to calculate expected utility. Consequentially, we argue that the standard notion of rationality as maximizing expected utility is insufficient, even for certain standard cases of economic interaction. (shrink)

Im Erfolgsfall winken dem Wagemutigen Ruhm, ökonomischer Gewinn sowie wachsendes soziales und symbolisches Kapital. Dem Scheiternden bleibt zumindest der Nachruhm: Hat er nicht die Zukunft herausgefordert und sich nicht passiv in sein Schicksal ergeben? Eingegangene Risiken werden jedoch erst im nachträglichen Erzählen zum Wagnis. Was die einen als Wagnis preisen, mag von anderen als Fehler, Übermut, Hybris, ja Verbrechen gesehen werden.

In this contribution we analyze how the actions of rational agents feed back on their beliefs. We present two agent-based computer simulations studying complex social interactions in which agents that follow utility maximizing strategies thereby deteriorate their own long-term quality of beliefs. We take these results as a starting point to discuss the complex relationship between rational action couched in terms of maximizing utility and the emergence of informational inequalities.

In this book, Henrik Lagerlund offers students, researchers, and advanced general readers the first complete history of what is perhaps the most famous of all philosophical problems: skepticism. As the first of its kind, the book traces the influence of philosophical skepticism from its roots in the Hellenistic schools of Phyrronism and the Middle Academy up to its impact inside and outside of philosophy today. Along the way, it covers skepticism during the Latin, Arabic, and Greek Middle Ages and (...) during the Renaissance before moving on to cover Descartes's methodological skepticism and Pierre Bayle's super-skepticism in the seventeenth century. In the eighteenth century, it deals with Humean skepticism and the anti-skepticism of Reid and Kant, taking care to also include reflections on the connections between idealism and skepticism. The book covers similar themes in a chapter on G.E. Moore and Ludwig Wittgenstein, and then ends its historical overview with a chapter on skepticism in contemporary philosophy. In the final chapter, Lagerlund captures some of skepticism's impact outside of philosophy, highlighting its relation to issues like the replication crisis in science and knowledge resistance. (shrink)

Recent metaphysics has seen a surge of interest in grounding—a relation of non-causal determination underlying a distinctive kind of explanation common in philosophy. In this article, I investigate the connection between grounding and another phenomenon of great interest to metaphysics: ontological dependence. There are interesting parallels between the two phenomena: for example, both are commonly invoked through the use of “dependence” terminology, and there is a great deal of overlap in the motivations typically appealed to when introducing them. I approach (...) the question of the relationship between grounding and ontological dependence through an investigation of their modal connections. I argue, firstly, that on the common assumption that grounding is factive, it can be shown that no known variety of rigid ontological dependence is either necessary or sufficient for grounding. I also offer some suggestions in support of the claim that this generalizes to every possible form of rigid ontological dependence. I then broaden the discussion by considering a non-factive conception of grounding, as well as by looking at forms of generic ontological dependence. I argue that there is at least one form of rigid ontological dependence that is sufficient for non-factive grounding, and that a form of generic dependence may be necessary both for factive and non-factive grounding. However, justifying even these fairly weak modal connections between grounding and ontological dependence turns out to require some quite specific and substantive assumptions about the two phenomena that have only rarely been discussed. (shrink)

This volume distinguishes between two main traditions in the philosophy of science - the aristotelian, with its stress on explanation in terms of purpose and intentionality, and the galilean, which takes causal explanation as primary. It then traces the complex history of these competing traditions as they are manifested in such movements as positivism, idealism, Marxism and contemporary linguistic analysis. Hempels's theory of scientific explanation, the claims of cybernetics the rise of an analytic philosophy of action and the revival of (...) hermenuetics are all discussed. The volume also deals with causal explanation, intentionality and teleological explanation, and explanation in history and the social sciences. The author concludes that explanation of human actions cannot be reduced to simple causality, and discusses the implications of this conclusion for the disciplines of history and sociology. (shrink)

Many democratic theorists hold that when a decision is collectively made in the right kind of way, in accordance with the right procedure, it is permissible to enforce it. They deny that there are further requirements on the type of reasons that can permissibly be used to justify laws and policies. In this paper, I argue that democratic theorists are mistaken about this. So-called public reason requirements follow from commitments that most of them already hold. Drawing on the democratic ideal (...) of civic equality, I show that it can successfully explain why political decision-making must have the right sort of procedure-independent justification. However, contra standard accounts of public reason, I argue that laws and policies need to be justified with convergence accessible, not shared, reasons. Public reasons are those that are accessible in light of evaluative standards shared by all, or in light of every citizen’s private evaluative standards. Since this will make the set of public reasons wider, it makes the theory more palatable to sceptics while retaining the framework’s justificatory potential. (shrink)

The emerging concept of systems medicine (or ‘P4 medicine’—predictive, preventive, personalized and participatory) is at the vanguard of the post-genomic movement towards ‘precision medicine’. It is the medical application of systems biology, the biological study of wholes. Of particular interest, P4 systems medicine is currently promised as a revolutionary new biomedical approach that is holistic rather than reductionist. This article analyzes its concept of holism, both with regard to methods and conceptualization of health and disease. Rather than representing a medical (...) holism associated with basic humanistic ideas, we find a technoscientific holism resulting from altered technological and theoretical circumstances in biology. We argue that this holism, which is aimed at disease prevention and health optimization, points towards an expanded form of medicalization, which we call ‘holistic medicalization’: Each person’s whole life process is defined in biomedical, technoscientific terms as quantifiable and controllable and underlain a regime of medical control that is holistic in that it is all-encompassing. It is directed at all levels of functioning, from the molecular to the social, continual throughout life and aimed at managing the whole continuum from cure of disease to optimization of health. We argue that this medicalization is a very concrete materialization of a broader trend in medicine and society, which we call ‘the medicalization of health and life itself’. We explicate this holistic medicalization, discuss potential harms and conclude by calling for preventive measures aimed at avoiding eventual harmful effects of overmedicalization in systems medicine (quaternary prevention). (shrink)

Ecosystems, the human brain, ant colonies, and economic networks are all complex systems displaying collective behaviour, or emergence, beyond the sum of their parts. Complexity science is the systematic investigation of these emergent phenomena, and stretches across disciplines, from physics and mathematics, to biological and social sciences. This introductory textbook provides detailed coverage of this rapidly growing field, accommodating readers from a variety of backgrounds, and with varying levels of mathematical skill. Part I presents the underlying principles of complexity science, (...) to ensure students have a solid understanding of the conceptual framework. The second part introduces the key mathematical tools central to complexity science, gradually developing the mathematical formalism, with more advanced material provided in boxes. A broad range of end of chapter problems and extended projects offer opportunities for homework assignments and student research projects, with solutions available to instructors online. Key terms are highlighted in bold and listed in a glossary for easy reference, while annotated reading lists offer the option for extended reading and research. (shrink)

Walter applies the methodology of neurophilosophy to one of philosophy's centralchallenges, the notion of free will. Neurophilosophical conclusions are based on, and consistentwith, scientific knowledge about the brain and its functioning.

It is well known that Niels Bohr insisted on the necessity of classical concepts in the account of quantum phenomena. But there is little consensus concerning his reasons, and what he exactly meant by this. In this paper, I re-examine Bohr’s interpretation of quantum mechanics, and argue that the necessity of the classical can be seen as part of his response to the measurement problem. More generally, I attempt to clarify Bohr’s view on the classical/quantum divide, arguing that the relation (...) between the two theories is that of mutual dependence. An important element in this clarification consists in distinguishing Bohr’s idea of the wave function as symbolic from both a purely epistemic and an ontological interpretation. Together with new evidence concerning Bohr’s conception of the wave function collapse, this sets his interpretation apart from both standard versions of the Copenhagen interpretation, and from some of the reconstructions of his view found in the literature. I conclude with a few remarks on how Bohr’s ideas make much sense also when modern developments in quantum gravity and early universe cosmology are taken into account. (shrink)

This article reviews concepts of, as well as neurocognitive and genetic studies on, empathy. Whereas cognitive empathy can be equated with affective theory of mind, that is, with mentalizing the emotions of others, affective empathy is about sharing emotions with others. The neural circuits underlying different forms of empathy do overlap but also involve rather specific brain areas for cognitive (ventromedial prefrontal cortex) and affective (anterior insula, midcingulate cortex, and possibly inferior frontal gyrus) empathy. Furthermore, behavioral and imaging genetic studies (...) provide evidence for a genetic basis for empathy, indicating a possible role for oxytocin and dopamine as well as for a genetic risk variant for schizophrenia near the gene ZNF804A. (shrink)

A set of moral problems known as The Trolley Dilemmas was presented to 3000 randomly selected inhabitants of the USA, Russia and China. It is shown that Chinese are significantly less prone to support utility-maximizing alternatives, as compared to the US and Russian respondents. A number of possible explanations, as well as methodological issues pertaining to the field of surveying moral judgment and moral disagreement, are discussed.

Self-organized criticality (SOC) is based upon the idea that complex behavior can develop spontaneously in certain multi-body systems whose dynamics vary abruptly. This book is a clear and concise introduction to the field of self-organized criticality, and contains an overview of the main research results. The author begins with an examination of what is meant by SOC, and the systems in which it can occur. He then presents and analyzes computer models to describe a number of systems, and he explains (...) the different mathematical formalisms developed to understand SOC. The final chapter assesses the impact of this field of study, and highlights some key areas of new research. The author assumes no previous knowledge of the field, and the book contains several exercises. It will be ideal as a textbook for graduate students taking physics, engineering, or mathematical biology courses in nonlinear science or complexity. (shrink)

This article explores the concept of metaphysically opaque grounding, a largely neglected form of metaphysical grounding that challenges the commonly held assumptions that grounding is an especially intimate and powerful connection between facts and that it is necessarily connected with the essences of things. I provide a definition of opaque grounding, identify some interesting philosophical views that are committed to it, and explore some consequences for the general theory of grounding. Finally, I briefly address some natural initial doubts about opaque (...) grounding and find them unwarranted. The upshot is that the notion deserves more attention than it has previously received. (shrink)

This book presents the first study of the development of the theory of modal syllogistic in the Middle Ages.

Pragmatism gained considerable attention in bioethical discussions in the early 21st century. However, some dimensions and contributions of pragmatism to bioethics remain underexplored in both research and practice. It is argued that pragmatism can make a distinctive contribution to bioethics through its concept, developed by Charles S. Peirce and John Dewey, that ethical issues can be resolved through experimental inquiry. Dewey’s proposal that policies can be confirmed or disconfirmed through experimentation is developed by comparing it to the confirmation of scientific (...) hypotheses, with a focus on the objection that the consequences of following a moral view or policy do not provide guidance on choosing among competing ethical perspectives. As confirmation of scientific hypotheses typically relies on evidence gathered from observation, the possibility of ethically relevant observation is then explored based on Peirce’s views on feelings as emotional interpretants. Finally, the connection between Dewey’s experimental ethics and democracy is outlined and compared to unfettered ethical progressivism. (shrink)

Recent philosophical inquiry into the relations thought to metaphysically structure the world has largely focused on the notion of metaphysical grounding, whereas previously analytic metaphysicians tended to talk in terms of ontological dependence. This raises the question of how metaphysical grounding and ontological dependence relate to one another. In this article, I sketch a picture of grounding as a form of metaphysically substantive sufficient condition and ontological dependence as a form of metaphysically substantive necessary condition, anchored in widely accepted principles (...) for how these relations work. As a case study, I apply this picture to Jack Casey's recent attempt to reduce ontological dependence to a special case of grounding. I argue that Casey's account fails and I show how the picture of grounding and ontological dependence presented here helps us diagnose where the account goes wrong, as well as how it makes sense of the phenomena Casey's account struggles with without having to resort to any ad hoc maneuvers. Thinking of grounding as a form of metaphysically substantive sufficient condition and ontological dependence as a form of metaphysically substantive necessary condition is thus shown to help sharpen our understanding of these phenomena and provide minimal constraints on any purported reductive account of one of the phenomena in terms of the other. (shrink)

Joint attention is an early-emerging and uniquely human capacity that lies at the foundation of many other capacities of humans, such as language and the understanding of other minds. In this article, I summarize what developmentalists and philosophers have come to find out about joint attention, and I end by stating that two problems or questions of joint attention require additional research: 1) the relation between joint attention and the skills for dyadic sharing or affect exchange in young infants, and (...) 2) the evolution of joint attention. (shrink)