This book taps the best American thinkers to answer the essential American question: How do we sustain our experiment in government of, by, and for the people? Authored by an extraordinary and politically diverse roster of public officials, scholars, and educators, these chapters describe our nation's civic education problem, assess its causes, offer an agenda for reform, and explain the high stakes at risk if we fail.

This paper is a reflection on the emergent directions of Australian culture and values in the context of the process of globalization. It views Australian society as a multi-cultural mosaic where aboriginal cultures coexist with the derived cultures of migrants from Europe, America and Asia. Adding that globalization has meant both greater confusion and conformity to intrusive American culture and practices, the author asks: Will we be able to find and clarify a changing set of shared values in this emergent (...) society? Although Australia still finds itself in the mould of the acquisitive Western society, a transition to the stronger communitarian value system of the East is a distinct possibility. Drawing inspiration from an experiential workshop in India, the author concludes with the hope that ultimately the survival and enrichment of an edifying Australian culture and set of human values will depend on and flow from the hearts, minds and human creativeness of Australians in a continually changing world. (shrink)

Future-bias is the preference, all else being equal, for negatively valenced events be located in the past rather than the future, and positively valenced ones to be located in the future rather than the past. Strong risk aversion is the preference to pay some cost to mitigate the badness of the worst outcome. People who are both strongly risk averse and future-biased can face a series of choices that will guarantee them more pain, for no compensating benefit: they will be (...) pain pumped. Thus, combining these preferences is rationally impermissible. Dougherty (2011) argues that this gives us reason to think that future-bias is rationally impermissible. This argument, and a similar one presented by Greene and Sullivan (2015), relies on the idea that if several preferences are not rationally combinable, then in the absence of some explanation of why they are not combinable, we should conclude that (at least) one of them is rationally impermissible. We take up this question by, inter alia, reflecting on the empirical results of a study we ran that probes people’s risk averse and future-biased preferences. We argue that the data, in conjunction with other considerations, suggests that we should not infer from the irrationality of the combination of these preferences to the irrationality of one of the preferences singly. We also argue that given the descriptive data about these preferences, there is no reason to think that, if one of them is rationally impermissible, then it is future-bias. (shrink)

Preston Greene (2020) argues that we should not conduct simulation investigations because of the risk that we might be terminated if our world is a simulation designed to research various counterfactuals about the world of the simulators. In response, we propose a sequence of arguments, most of which have the form of an "even if” response to anyone unmoved by our previous arguments. It runs thus: (i) if simulation is possible, then simulators are as likely to care about simulating simulations (...) as they are likely to care about simulating basement (i.e. non-simulated) worlds. But (ii) even if simulations are interested only in simulating basement worlds the discovery that we are in a simulation will have little or no impact on the evolution of ordinary events. But (iii) even if discovering that we are in a simulation impacts the evolution of ordinary events, the effects of seeming to do so could also happen in a basement world, and might be the subject of interesting counterfactuals in the basement world Finally, (iv) there is little reason to think that there is a catastrophic effect from successful simulation probes, and no argument from the precautionary principle can be used to leverage the negligible credence one ought have in this. Thus, if we do develop a simulation probe, then let’s do it. (shrink)

Deep brain stimulation of the subthalamic nucleus is a clinically effective tool for treating medically refractory Parkinson’s disease, but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials in the primary motor cortex, suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This (...) study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed – one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the “start” and the “end” EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude and latency, and the end, but not the start, EP magnitude has a significant relationship to ongoing high gamma power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs. (shrink)

Methods to facilitate co-production in mental health are important for engaging end users. As part of the Technology for Healthy Aging and Wellbeing initiative we organized two interactive co-production workshops, to bring together older adults, health and social care professionals, non-governmental organizations, and researchers. In the first workshop, we used two activities: Technology Interaction and Scavenger Hunt, to explore the potential for different stakeholders to discuss late life mental health and existing technology. In the second workshop, we used Vignettes, Scavenger (...) Hunt, and Invention Test to examine how older adults and other stakeholders might co-produce solutions to support mental wellbeing in later life using new and emerging technologies. In this paper, we share the interactive materials and activities and consider their value for co-production. Overall, the interactive methods were successful in engaging stakeholders with a broad range of technologies to support mental health and wellbeing and in co-producing ideas for how they could be leveraged and incorporated into older people’s lives and support services. We offer this example of using interactive methods to facilitate co-production to encourage greater involvement of older adults and other under-represented groups in co-producing mental health technologies and services. (shrink)

Monism is our name for a range of views according to which the connection between dispositions and their categorical bases is intimate and necessary, or on which there are no categorical bases at all. In contrast, Dualist views hold that the connection between dispositions and their categorical bases is distant and contingent. This paper is a defence of Monism against an influential conceivability argument in favour of Dualism. The argument suggests that the apparent possibility of causal behaviour coming apart from (...) categorical bases is best explained by Dualism. We argue that Monism can explain the apparent possibility as well, if we take metaphysically alien laws — namely, laws whose metaphysical nature is alien to the actual world — into account. (shrink)

A collection of personal narratives and essays, Living Professionalism is designed to help medical students and residents understand and internalize various aspects of professionalism. These essays are meant for personal reflection and above all, for thoughtful discussion with mentors, with peers, with others throughout the health care provider community who care about acting professionally.

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that (...) has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. (shrink)

In this paper we describe a few interrelated issues for validating theories that posit levels of consciousness. First, validating levels of consciousness requires consensus about the ordering of conscious states, which cannot be easily achieved. This problem is particularly severe if we believe conscious states can be irreducibly smeared over time. Second, the relationship between conscious states is probably sometimes intransitive, which means levels of consciousness will not be amenable to a single continuous measure. Finally, even if a multidimensional approach (...) to levels of consciousness is adopted, we argue that there are further problems for its validation. (shrink)

In order to improve our understanding of the components that reflect functionally important processes during reward anticipation and consumption, we used principle components analyses (PCA) to separate and quantify averaged ERP data obtained from each stage of a modified monetary incentive delay (MID) task. Although a small number of recent ERP studies have reported that reward and loss cues potentiate ERPs during anticipation, action preparation, and consummatory stages of reward processing, these findings are inconsistent due to temporal and spatial overlap (...) between the relevant electrophysiological components. Our results show three components following cue presentation are sensitive to incentive cues (N1, P3a, P3b). In contrast to previous research, reward‐related enhancement occurred only in the P3b, with earlier components more sensitive to break‐even and loss cues. During feedback anticipation, we observed a lateralized centroparietal negativity that was sensitive to response hand but not cue type. We also show that use of PCA on ERPs reflecting reward consumption successfully separates the reward positivity from the independently modulated feedback‐P3. Last, we observe for the first time a new reward consumption component: a late negativity distributed over the left frontal pole. This component appears to be sensitive to response hand, especially in the context of monetary gain. These results illustrate that the time course and sensitivities of electrophysiological activity that follows incentive cues do not follow a simple heuristic in which reward incentive cues produce enhanced activity at all stages and substages. (shrink)

Malignant tumours are often characterised by significant rearrangement of the genome. This may be visible in the form of a deranged karyotype with both loss and gain of DNA sequences extending from chromosomal regions to whole chromosomes. In several tumour types, however, gross genomic derangements are minimal, and tumour cells contain one or more additional (supernumerary) chromosomes that may be unrecognisable in terms of a single origin. In this review we term such chromosomes cancer‐associated neochromosomes (CaNCs). In the absence of (...) other identified genomic abnormalities, and because the CaNC is a common feature of the cancer type, it is hypothesised that the genetic alterations required for cell transformation are contained within its structure. In this review, we discuss the potential impact of modern genomic technologies on our understanding of the nature and causes of CaNC formation, which is central to several cancer types, exemplified here by well‐differentiated liposarcoma. (shrink)

What does it mean to consider the world of AI through a Christian lens? Rapid developments in AI continue to reshape society, raising new ethical questions and challenging our understanding of the human person. Encountering Artificial Intelligence draws on Pope Francis’ discussion of a culture of encounter and broader themes in Catholic social thought in order to examine how current AI applications affect human relationships in various social spheres and offers concrete recommendations for better implementation. The document also explores questions (...) regarding personhood, consciousness, and the kinds of relationships humans might have with even the most advanced AI. Through these discussions, this book investigates the theoretical and practical challenges to interpersonal encounter raised by the age of AI. (AI Research Group for the Centre for Digital Culture of the Dicastery of Culture and Education of the Holy See). (shrink)

1 Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2 During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for (...) generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3 The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4 The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5 Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible. (shrink)

I argue that when we use email, text messaging, or social media websites such as Facebook to interact, rather than communicating face-to-face, we do not experience the best kind of empathy, which is most conducive to experiencing benevolence for others. My arguments rely on drawing interdisciplinary connections between sources: early modern accounts of sympathy, dance theory, philosophy of technology, and neuroscience/psychology. I reflect on theories from these disciplines which, taken together, suggest that to empathize optimally, we must see or hear (...) each other’s bodily gestures, vocal intonations, and facial expressions. (shrink)

I read Henry David Thoreau as an environmental virtue theorist. In this paper, I use Thoreau’s work as a tool to explore the relation between the virtue of greatness of soul and environmental virtues. Reflecting on connections between Thoreau’s texts and historical discussions of greatness of soul, or magnanimity, I offer a novel conception of magnanimity. I argue that (1) to become magnanimous, most individuals need to acquire the environmental virtue of simplicity; and (2) magnanimous individuals must possess the (...) environmental virtue of benevolence in order to achieve their goals. (shrink)

This paper offers a composite portrait of the concept of magnanimity in nineteenth-century America, focusing on Ralph Waldo Emerson, Margaret Fuller, and Henry David Thoreau. A composite portrait, as a method in the history of philosophy, is designed to bring out characteristic features of a group's philosophizing in order to illuminate characteristic features that may still resonate in today's philosophy. Compared to more standard methods in the historiography of philosophy, the construction of a composite portrait de-privileges the views of (...) individual authors. These philosophers saw the virtue of magnanimity as a remedy for a number of modern ills. American philosophers suggest that the best sort of magnanimity is acquired by adopting the correct relation to the natural world, including new forms of inquiry, or by adopting a life of voluntary poverty. Magnanimous individuals are critics of capitalism and offer themselves as exemplars of a better, experimental life. (shrink)

I contend that Adam Smith and David Hume offer re-interpretations of Aristotle’s notion of greatness of soul, focusing on the kind of magnanimity Aristotle attributes to Socrates. Someone with Socratic magnanimity is worthy of honor, responds moderately to fortune, and is virtuous—just and benevolent. Recent theorists err in claiming that magnanimity is less important to Hume’s account of human excellence than benevolence. In fact, benevolence is a necessary ingredient for the best sort of greatness. Smith’s “Letter to Strahan” attributes (...) this greatness to Hume. It encourages us to admire Hume as an exemplar of human excellence, to seek Hume’s virtues for ourselves, and to approve of the “love of literary fame” which Hume calls his “ruling passion.”. (shrink)

We report on the deliberations of an interdisciplinary group of experts in science, law, and philosophy who convened to discuss novel ethical and policy challenges in stem cell research. In this report we discuss the ethical and policy implications of safety concerns in the transition from basic laboratory research to clinical applications of cell-based therapies derived from stem cells. Although many features of this transition from lab to clinic are common to other therapies, three aspects of stem cell biology pose (...) unique challenges. First, tension regarding the use of human embryos may complicate the scientific development of safe and effective cell lines. Second, because human stem cells were not developed in the laboratory until 1998, few safety questions relating to human applications have been addressed in animal research. Third, preclinical and clinical testing of biologic agents, particularly those as inherently complex as mammalian cells, present formidable challenges, such as the need to develop suitable standardized assays and the difficulty of selecting appropriate patient populations for early phase trials. We recommend that scientists, policy makers, and the public discuss these issues responsibly, and further, that a national advisory committee to oversee human trials of cell therapies be established. **NB we did not reccommend a NAC, we think it might be appropriate**. (shrink)

We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate (...) assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)

If stem cell-based therapies are developed, we will likely confront a difficult problem of justice: for biological reasons alone, the new therapies might benefit only a limited range of patients. In fact, they might benefit primarily white Americans, thereby exacerbating long-standing differences in health and health care.

Background The European Union aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury, aiming to inform and stimulate initiatives to improve efficiency. Methods We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury. (...) Documents included detailed information on IRB procedures and the duration from IRB submission until approval. They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe. Results From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally or locally and primary IRB approval was obtained after one, two or three review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days and appeared to be shorter after submission to local IRBs compared to central IRBs. Conclusion We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries. (shrink)

Cerebral organoid models in-of-themselves are considered as an alternative to research animal models. But their developmental and biological limitations currently inhibit the probability that organoids can fully replace animal models. Furthermore, these organoid limitations have, somewhat ironically, brought researchers back to the animal model via xenotransplantation, thus creating hybrids and chimeras. In addition to attempting to study and overcome cerebral organoid limitations, transplanting cerebral organoids into animal models brings an opportunity to observe behavioral changes in the animal itself. Traditional animal (...) ethics frameworks, such as the well-known three Rs (reduce, refine, and replace), have previously addressed chimeras and xenotransplantation of tissue. But these frameworks have yet to completely assess the neural-chimeric possibilities. And while the three Rs framework was a historical landmark in animal ethics, there are identifiable gaps in the framework that require attention. The authors propose to utilize an expanded three Rs framework initially developed by David DeGrazia and Tom L. Beauchamp, known as the Six Principles (6Ps). This framework aims to expand upon the three Rs, fill in the gaps, and be a practical means for assessing animal ethical issues like that of neural-chimeras and cerebral organoid xenotransplantation. The scope of this 6Ps application will focus on two separate but recent studies, which were published in 2019 and 2020. First, they consider a study wherein cerebral organoids were grown from donors with Down syndrome and from neurotypical donors. After these organoids were grown and studied, they were then surgically implanted into mouse models to observe the physiological effects and any behavioral change in the chimera. Second, they consider a separate study wherein neurotypical human embryonic stem cell-derived cerebral organoids were grown and transplanted into mouse and macaque models. The aim was to observe if such a transplantation method would contribute to therapies for brain injury or stroke. The authors place both studies under the lens of the 6Ps framework, assess the relevant contexts of each case, and provide relevant normative conclusions. In this way, they demonstrate how the 6Ps could be applied in future cases of neural-chimeras and cerebral organoid xenotransplantation. (shrink)