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)

This book takes a bold new look at ways of exploring the nature, origins, and potentials of consciousness within the context of science and religion.

The thesis that there can be vague objects is the thesis that there can be identity statements which are indeterminate in truth-value (i.e., neither true nor false) as a result of vagueness (as opposed, e.g., to reference-failure), "the singular terms of which do not have their references fixed by vague descriptive means". (if this is "not" what is meant by the thesis that there can be vague objects, it is not clear what "is" meant by it.) the possibility of vague (...) objects should not be taken, in itself, to imply the more radical thesis that the identity relation can be one of "degree". one can hold that the concept of degrees of identity is absurd (how can one thing be more or less identical to another?) "and" that indeterminacy in identity is possible; hence, any incoherence in the idea of degrees of identity does not thereby undermine the idea of indeterminate identity. (shrink)

Objectives: To compare attitudes of medical and law students toward informing a cancer patient about diagnosis and prognosis and to examine whether differences are related to different convictions about benefit or harm of information.Setting and design: Anonymous questionnaires were distributed to convenience samples of students at the University of Geneva containing four vignettes describing a cancer patient who wishes, or alternatively, who does not wish to be told the truth.Participants: One hundred and twenty seven medical students and 168 law students.Main (...) outcome measures: Five point Likert scale of responses to the vignettes ranging from “certainly inform” to “certainly not inform” the patient.Results: All medical students and 96% of law students favoured information about the diagnosis of cancer if the patient requests it. Seventy four per cent of medical students and 82% of law students favoured informing a cancer patient about his or her prognosis . Thirty five per cent of law students and 11.7% of medical students favoured telling about the diagnosis and 25.6% of law students and 7% of medical students favoured telling about the prognosis even if the patient had clearly expressed his wish not to be informed. Law students indicated significantly more often than medical students reasons to do with the patient’s good, legal obligations, and the physician’s obligation to tell the truth, and significantly less often than medical students that their attitude had been determined predominantly by respect for the autonomous choice of the patient.Conclusion: Differences in attitudes according to the type of case and the type of studies were related to convictions about the benefit or harm to the patient caused by being given information. The self reported reasons of future physicians and future lawyers are helpful when considering means to achieve a better acceptance of patients’ right to know and not to know. (shrink)

This paper explores John Rawls’s strangely neglected notion, the political conception as educator, which captures how the public political culture can educate citizens. The aim is to elucidate both the idea itself and above all its function in Rawls’s Political Liberalism. After first surveying its main content and some historical parallels, the main body of the paper explores why Rawls places so much trust in the educative effect of institutions and, apparently, so little in schools. Along the way we shall (...) discuss the relation between political liberalism and republicanism, the border disagreement between political conception and comprehensive doctrine, Mackie’s distinction between wide and narrow morality and the importance of trust in Rawls’s view of society. (shrink)

Open peer commentary on the article “Radical Constructivist Structural Design Education for Large Cohorts of Chinese Learners” by Christiane M. Herr. Upshot: In this comment, I take Herr’s proposition for a constructivist-informed pedagogy for structural design education to extract initial ideas for a framework for a constructivist pedagogy, a framework focused on the decision-making of a constructivist teacher. I enhance this initial framework with initial findings of a study I conducted with a constructivist mathematics teacher.

Brock Macdonald1, Evi Vakiani2, Rhonda K Yantiss3, Jun Lee4, Robert S Brown Jr5, Samuel H Sigal61Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA, 2Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, 3Department of Pathology and Laboratory Medicine, New York Weill Cornell Medical College, New York, NY, 4Division of Nephrology, Department of Medicine, Weill Cornell Medical College, New York, NY, 5Division of Gastroenterology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, (...) NY, 6Division of Gastroenterology and Hepatology, Department of Medicine, New York University, New York, NY, USA: The use of sirolimus as an alternative to calcineurin inhibitors for posttransplant immunosuppression is associated with a variety of inflammatory conditions. In this report, we describe the case of a 34-year-old man who developed abnormal liver tests 6 years after live-donor kidney transplantation and 5 years after initiation of sirolimus-based immunosuppression. Elevated aminotransferase levels persisted after withdrawal of potentially hepatotoxic medications, and serologic evaluation for viral hepatitis, autoimmune disease, and genetic disorders was unrevealing. Liver biopsy revealed prominent hepatocellular injury associated with a mixed inflammatory infiltrate and liver tests normalized within 2 weeks of discontinuation of sirolimus. In this report, we review previous reports of sirolimus hepatotoxicity and propose a unifying hypothesis for the various inflammatory conditions that have been attributed to sirolimus.Keywords: sirolimus, immunosuppression, transplant, inflammatory conditions, hepatotoxicity. (shrink)

This essay explains the inescapability of moral demands. I deny that the individual has genuine reason to comply with these demands only if she has desires that would be served by doing so. Rather, the learning of moral reasons helps to shape and channel self- and other-interested motivations so as to facilitate and promote social cooperation. This shaping happens through the “embedding” of reasons in the intentional objects of motivational propensities. The dominance of the instrumental conception of reason, according to (...) which reasons must be based in desires of the individual, has made it harder to recognize that reasons shape desires. I attempt to undermine this dominance by arguing that the concept of a self that extends over time is constructed to meet the demands of social cooperation. Prudential reasons to act on behalf of the persisting self's desires are often taken to constitute the paradigm of reasons based on desires of the individual. But such reasons, along with the very concept of the persisting self, are constructed to promote human cooperation and to shape the individual's desires. (shrink)

The baker's transformation is one of the earliest and simplest examples of a bijective mixing transformation. By determining its cycle structure, we show that this transformation is not embeddable in any flow, i.e., one-parameter semigroup, on the nonnegative rationals and,a fortiori, not emdeddable in any flow on the reals.

SummaryThis paper firms up previous arguments for referential transparency in intensional constructions by providing conclusive proofs of this, both formal and informal. Centrally the paper uses epsilon terms to symbolise referring expressions, and so it obtains the rigid designators needed to allow the same object to be referred to in all worlds and minds. The details of several contrary ideas are examined to reinforce the claim that they are incorrect. But also certain world‐dependent or mind‐dependent objects are identified, using epsilon (...) terms, to give an understanding of what might have caused the historical belief in referential opacity. (shrink)

Fregean logic has difficulty with certain arguments in which there is cross-reference between premises and conclusion. In this paper I describe a method of handling arguments of the troublesome kind: It involves replacing standard quantifiers with explicit existential statements, and turns standard logic into a free one. A validation procedure is provided for the logic.

Abortion is an especially salient issue for considering the general problematic of religiously based conversation in the public square. It remains deeply divisive, fully thirty-four years after Roe v. Wade. Such divisiveness cannot be interpreted as merely an expression of profound differences between “secular” and “religious” voices, because differences also emerge among Christian denominations, reflecting different sources of moral authority, different accounts of moral discernment, and different judgments about the appropriate relations between law and morality in the context of pluralism. (...) As this paper explores, however, despite those differences, a generally identifiable “Christian” position concerning the moral status of abortion can be distinguished from secular philosophical judgments on the issue, which is important for Christian engagement with public policy debate. (shrink)