In “Missing the Forest for the Trees: Aduhelm, Accelerated Approvals & the Agency,” Dr. Matthew Herder argues that agency capture and politicized discretion drive delays in confirmatory trials of accelerated approval drugs amongst other concerns at US Food and Drug Administration (FDA). In highlighting this important problem and offering nuanced insight into agency workings based in part on interviews with twenty-three unnamed FDA officials and a three-drug case study, Dr. Herder suggests two innovative solutions. However, amidst broader debates balancing agency (...) expertise, data, and delegation, these proposed policy solutions would benefit from more corroborative evidence and consideration of institutional advantages within constitutional limits. (shrink)

The COVID-19 pandemic has resulted in more than 524 million cases and 6 million deaths worldwide. Various drug interventions targeting multiple stages of COVID-19 pathogenesis can significantly reduce infection-related mortality. The current within-host mathematical modeling study addresses the optimal drug regimen and efficacy of combination therapies in the treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Interferon and Lopinavir/ritonavir. It is concluded that these drugs, when administered singly or in combination, reduce the number of infected cells and viral load. (...) Four scenarios dealing with the administration of a single drug, two drugs, three drugs and all four are discussed. In all these scenarios, the optimal drug regimen is proposed based on two methods. In the first method, these medical interventions are modeled as control interventions and a corresponding objective function and optimal control problem are formulated. In this framework, the optimal drug regimen is derived. Later, using the comparative effectiveness method, the optimal drug regimen is derived based on the basic reproduction number and viral load. The average number of infected cells and viral load decreased the most when all four drugs were used together. On the other hand, the average number of susceptible cells decreased the most when Arbidol was administered alone. The basic reproduction number and viral load decreased the most when all four interventions were used together, confirming the previously obtained finding of the optimal control problem. The results of this study can help physicians make decisions about the treatment of the life-threatening COVID-19 infection. (shrink)

Compared to our understanding of positive prediction error signals occurring due to unexpected reward outcomes, less is known about the neural circuitry in humans that drives negative prediction errors during omission of expected rewards. While classical learning theories such as Rescorla–Wagner or temporal difference learning suggest that both types of prediction errors result from a simple subtraction, there has been recent evidence suggesting that different brain regions provide input to dopamine neurons which contributes to specific components of this prediction error (...) computation. Here, we focus on the brain regions responding to negative prediction error signals, which has been well-established in animal studies to involve a distinct pathway through the lateral habenula. We examine the activity of this pathway in humans, using a conditioned inhibition paradigm with high-resolution functional MRI. First, participants learned to associate a sensory stimulus with reward delivery. Then, reward delivery was omitted whenever this stimulus was presented simultaneously with a different sensory stimulus, the conditioned inhibitor. Both reward presentation and the reward-predictive cue activated midbrain dopamine regions, insula and orbitofrontal cortex. While we found significant activity at an uncorrected threshold for the CI in the habenula, consistent with our predictions, it did not survive correction for multiple comparisons and awaits further replication. Additionally, the pallidum and putamen regions of the basal ganglia showed modulations of activity for the inhibitor that did not survive the corrected threshold. (shrink)

This case is about a study of burn patients that included a request to the IRB for a waiver of consent for perianal specimen collection–a request which ultimately was not approved by a reviewing IR...

ABSTRACT:Psychedelics, including psilocybin, and other consciousness-altering compounds such as 3,4-methylenedioxymethamphetamine (MDMA), currently are being scientifically investigated for their potential therapeutic uses, with a primary focus on measurable outcomes: for example, alleviation of symptoms or increases in self-reported well-being. Accordingly, much recent discussion about the possible value of these substances has turned on estimates of the magnitude and duration of persisting positive effects in comparison to harms. However, many have described the value of a psychedelic experience with little or no reference (...) to such therapeutic benefits, instead seeming to find the experience valuable in its own right. How can we make sense of such testimony? Could a psychedelic experience be valuable even if there were no persisting beneficial effects? If so, how? Using the concept of psychological richness, combined with insights from the philosophy of aesthetics and the enhancement literature, this essay explores potential sources of value in the acute subjective experience, apart from the value derived from persisting beneficial effects. (shrink)

This article reflects on sustainability in the context of scientific conferences with emphasis on environmental, diversity, inclusivity, and intellectual aspects. We argue that it is imperative to embrace sustainability as a broad concept during conference organization. In‐person conferences have an obvious environmental impact but mitigating strategies can be implemented, such as incentivizing low‐emission travel, offering fellowships to support sustainable traveling, and promoting use of public transport or car‐pooling. Utilizing eco‐conscious venues, catering, and accommodations, along with minimizing resource wastage, further reduces (...) environmental impact. Additional considerations include facilitating hybrid format conferences that allow both in‐person and online attendance. Hybrid conferences enhance global participation whilst reducing resource consumption and environmental impact. Often‐overlooked benefits can arise from the simple recording of talks to enable asynchronous viewing for people unable to attend in person, in addition to providing a legacy of knowledge that, for example, could support the training of early career researchers (ECRs) or newcomers in the field. The longevity of a research field, intellectual sustainability, requires an inclusive conference atmosphere, offering optimal opportunities for ECRs, minority groups, and researchers from emerging countries. Diversity and inclusivity not only enrich conference experiences but also enhances creativity and innovation. (shrink)

There is increased interest in deviant behavior in the workplace. However, research is lacking on the moral economy of such behavior. Moral economy is particularly important in contexts where syncretic forces impinge on deviant behavior. Consequently, we use moral economy reasoning to examine the relationship between ethnic obligation and deviant behavior in the African context. In Study 1, data (_N_ = 27, 148) show an inverted U-shape effect of meta-agency and deviant behavior. In Study 2, difference-in-difference (DID) analysis of data (...) (_N_ = 25,387 in 2005 and _N _= 51,587 in 2013) shows significant DID effect of meta-agency. Primary data from Study 3 (_N_ = 229) shows a U-shaped effect of agency and deviant behavior. In Study 4 (_N_ = 333), a replication shows support for the U-shape effect in Study 3. The four studies thus show complex patterns that reflect U-shape and inverted U-shape relationships between ethnic obligation and deviant behavior as indicated by bribery, corruption, and unethicality. Robustness checks support the curvilinear relationships suggesting that the effects are not due to chance. We discuss implications for research and practice. (shrink)

As mariculture—the cultivation of aquatic organisms in marine environment—intensifies to meet the demands of sustainable blue growth and national policies, novel ethical challenges will arise. In the context of ethics, primary concerns over aquaculture and mariculture tend to stay within differing value-based perspectives focused on benefits to human and non-human subjects, specifically animal welfare and animal rights. Nonetheless, the burgeoning field of feminist blue humanities provides ethical considerations that extend beyond animal subjects (including humans), often because of its concerns with (...) new materialist, posthumanist, and other relations-based theories. This article examines feminist blue humanities and the contributions it may bring to understanding contemporary and future ethical challenges posed by mariculture and its intensification, especially the cultivation of low-trophic organisms. By offering an overview of feminist blue humanities, this article explores some of its particularities by drawing out three major ethical concerns facing contemporary mariculture, specifically material reconfigurations, radical alteration of the lives of low-trophic species through industrialization and increases in maricultural waste products. (shrink)

The consensus recommendations by Salter and colleagues (2023) regarding pediatric decision-making intentionally omitted adolescents due to the additional complexity their evolving autonomy presented. Using two case studies, one focused on truth-telling and disclosure and one focused on treatment refusal, this article examines medical decision-making with and for adolescents in the context of the six consensus recommendations. It concludes that the consensus recommendations could reasonably apply to older children.

The claim that Spinoza has a conception of animal mentality and consciousness that is superior to Descartes's is criticized. It is also argued that Spinoza fails to provide a coherent way of establishing what he considers to be our morally unconstrained “rights” with regard to brutes. Despite Spinoza's claim that brutes “feel,” i.e., are capable of sentience, his view that we are nonetheless entitled to treat animals in any way convenient to us is criticized. Questions are also raised as to (...) whether Spinoza is entitled to distinguish human from bestial nature on the basis of the possession of reason. (shrink)

Herodotus gives a lengthy description of the important council of the Greek allies which took place at Samos after Mycale in 479, but Thucydides fails to mention it. This is likely not because of succinctness in his treatment of the period. Throughout the Pentecontaetia, Thucydides presents the events which led to the Peloponnesian War in a somewhat indirect and passive way in order to attribute its causality to historical forces of deeper import. His desire to accentuate the role of Athenian (...) growth and Spartan fear of that growth in making the war inevitable commended the omission of events which by their nature might focus attention instead on the deliberate policy choices of the protagonists. Thucydides’ decision to omit other key events during the Pentecontaetia may stem from the same motivation. (shrink)

The paper deals with the conception of logical empiricism developed by Eino Kaila. Eino Kaila, being a thinker close to the Vienna Circle, departs from some of the central ideas of logical positivism. He identifies a limited number of problems in metaphysics that are meaningful and need to be solved, but he declares the rest of metaphysics to be a logical fallacy. For Eino Kaila, it is not the principle of verification (as a criterion of meaning) but the principle of (...) testability that plays the most important role. In addition, he revises the principle of translatability, insisting that it is impossible to translate a single sentence into the language of experience, but it is possible to translate the whole theory to which the sentence belongs. This is related to his structuralist position in the philosophy of science and his understanding of scientific theories as ‘rationalisations’ as opposed to simple inductive generalisations. The paper compares Eino Kaila’s views expressed during the period of his active interaction with the Vienna Circle be regarded as a predecessor of later critics of logical positivism (in particular, W.V.O. Quine). (shrink)

A hypothetical scenario is presented in which a female patient is admitted to a private hospital to undergo a mastectomy and breast reconstruction. The surgeons and anaesthetists conducting the different procedures charge three times the medical aid rates. When the patient asks what the co-payments are likely to be, she is informed by the doctors’ accounts section that they can only provide this information after each procedure. The patient’s medical scheme also advises her that it cannot determine the likely co-payments (...) unless she completes the assessment form sent to her. The form requires her to include the costs reflected against the relevant ICD10 codes. The patient cannot complete the form because the doctors’ accounts sections have not informed her about the proposed procedures and the likely costs of each. This article builds on a previous article discussing doctors’ overarching responsibility to disclose medical treatment costs in advance. The present article outlines the legal requirements in the South African Constitution, the National Health Act and the Health Professions Act, and refers to the Promotion of Access to Information Act and Consumer Protection Act. Similar to the earlier article, this article addresses the ethical requirements of the Health Professions Council of South Africa and the internationally recognised biomedical ethical principles. Furthermore, it also refers to the National Patients Charter, the government’s policy document on health care services. (shrink)

Thinking About Thinking: Mind and Meaning in the Era of Techno-Nihilism addresses our existential crisis by reminding us of the conditions for meaning that have been obscured by the modern technological mentality. Madden weaves together disparate insights from Wittgenstein, Hegel, Aristotle, Heidegger, Merleau-Ponty, Nietzsche, Sophocles, and others in an attempt to account for our mindedness in terms of its inextricable connection to a world capable of inspiring our care. The mind is not a discrete entity locked behind the skull or (...) withdrawn into a ghostly realm, but a participation in an inheritance (biological and cultural) held in common with other participants, and taking responsibility for that world is crucial for the meaning. The ever-increasing technological mediation of our lives undermines this worldliness. We are subsequently "losing our minds," and as our mindedness fades, so goes our sense of dignity and value. Madden makes this case deploying insights from phenomenology, analytic philosophy, Aristotelianism, neuroscience, and cognitive science, and along the way confronts the mind-body problem, freedom, artificial intelligence, transhumanism, and nihilism. More importantly, he invites the reader into an accessible dialogue concerning issues of grave importance to the meaning of our lives. (shrink)

Supports Ernest Barker's interpretation that Aristotle offers a ‘vindication of the right of private property.’ Although Aristotle emphasizes the common interests of the citizens, he also provides a place for private property in all of his constitutions, including the best constitution. The chapter argues that Aristotle gives a basic account of property ownership that is similar to modern concepts of property rights. He offers justifications of private property, states conditions under which property may be justly acquired, defends private property against (...) Plato's communism, and argues that property is indispensable for the exercise of citizenship. (shrink)

Although past commentators saw Aristotle as recognizing the rights of individuals, recent interpreters have objected that no single Greek word corresponds to the modern word ‘rights’. In reply, it is shown with evidence from Aristotle and other writers that the ancient Greek discourse of law and politics included distinct locutions corresponding to the different senses of ‘rights’ distinguished by the jurist W. N. Hohfeld: to dikaion corresponds to Hohfeld's claim right, exousia to a liberty or privilege, kurios to authority or (...) power, and adeia and ateleia to immunity. A right for Aristotle is essentially a just claim that a person has against other members of the same community, and a natural right is a just claim based in nature. Recent arguments that rights have theoretical implications inimical to Aristotle's principles are also found to be unpersuasive, because they rely on tendentious assumptions that would rule out many modern theories of rights as well. The chapter also indicates how a respect for the rights of others might be justified on the basis of Aristotelian practical wisdom. (shrink)

Aristotle states that ‘there is only one constitution which is everywhere according to nature the best.’ This constitution is unqualifiedly just and ‘according to nature’ because it promotes the common advantage. The interpretation of ‘common advantage’ is problematic: does it consist in the advantage of the citizens considered as distinct individuals or the advantage of the polis considered as a whole? Only on the former, individualistic interpretation would the best constitution be deeply committed to individual rights, and it is argued (...) that a moderate version of individualism is the correct interpretation of Aristotle's best constitution. The chapter goes on to consider difficulties in Aristotle's account of the best constitution, including his views on education and the question of which is better: virtuous kingship or the rule of law. (shrink)

Recognizing that the best or ideal constitution is generally unattainable, Aristotle employs a principle of proximity: although the highest end is best, if it is unattainable, legislation should aim at the result that is closest to the end and thus the best attainable outcome. In politics, this is called the ‘second sailing’, and Aristotle discusses such a constitution under the headings of polity, mixed constitution, and middle constitution. Although this constitution is correct and just, the standard is lowered in the (...) face of necessity. Still, the second‐best constitution serves as a norm for evaluating the various deviant constitutions that are forms of democracy and oligarchy. The second‐best constitution emulates the ideal constitution and it satisfies the maxim of unanimity, which in its strongest form requires that if a constitution is to be preserved, all the citizens should wish that it exist and continue unchanged. (shrink)

The contemporaneous ecological concern constitutes a tread line issue; the distance from superficial activist actions, although, as well as the credible philosophical - phenomenological - background that support the request for the stem cause, distinguishes and outstands Abram ‘s reflection. His poetic and prophetically discourse calls upon the need for a extremely disavowal reorganisation of the position of Man and his task within the cosmos.

A common theme conspicuously emerges from the few translated and published narratives of Vietnamese who participated in resistance against French colonialism in the 1950s. These narratives tend to identify moments of being an audience member to theater as having significant roles in these individuals’ political awakening and desire to sacrifice themselves for anticolonial struggle. Drawing on these narratives, this essay shows how some audience members engage in an empowering kind of political theorizing that elicits cross-cultural revelation, is progressive, generates feelings (...) of solidarity, and inspires them to engage in political action. In showing how being an audience member can lead to revolutionary action, these cases exceed the expectations of theorists of revolutionary theater such as Bertolt Brecht and Augusto Boal. They also offer a direct refutation of Jean-Jacques Rousseau’s famous claim that being an audience member at a theatrical performance is politically and morally enervating. (shrink)

One of the strongest motivations for being an anti‐realist with regard to mathematics is the difficulty in formulating a plausible realist epistemology, given that there seems to be a lack of ties between the mathematical apparatus and observation. In this chapter, I discuss a few puzzles that the mathematical realist has to solve in order to formulate an acceptable epistemology, and I hint at the direction in which one might hope to find the solution to these puzzles. One of the (...) puzzles, that was first clearly formulated by Paul Benacerraf, is that since mathematical objects are supposed to be causally inert entities existing outside of space and time, it is hard to see how we can ever get in contact with them, i.e. how we can ever gain knowledge of them or refer to them. A second puzzle concerns the incompleteness of mathematical entities that has it, that we have no conceivable evidence and so no answers to questions of whether the objects that one mathematical theory discusses are identical to those that another theory treats. Realists can reject the presuppositions of both these puzzles. The first presupposes that there must be some sort of direct or indirect interaction between us and the objects of our knowledge. The second assumes that there is always a fact of the matter as to whether the objects of one theory are the same or distinct, as those of another. In later chapters, I will try to undermine both of these presuppositions. (shrink)