Hyperinflammation triggered by SARS-CoV-2 is a major cause of disease severity, with activated macrophages implicated in this response. OP-101, a hydroxyl-polyamidoamine dendrimer– N -acetylcysteine conjugate that specifically targets activated macrophages, improves outcomes in preclinical models of systemic inflammation and neuroinflammation. In this multicenter, randomized, double-blind, placebo-controlled, adaptive phase 2a trial, we evaluated safety and preliminary efficacy of OP-101 in patients with severe COVID-19. Twenty-four patients classified as having severe COVID-19 with a baseline World Health Organization seven-point ordinal scale of ≥5 were randomized to receive a single intravenous dose of placebo ( n = 7 patients) or OP-101 at 2 ( n = 6), 4 ( n = 6), or 8 mg/kg ( n = 5 patients). All study participants received standard of care, including corticosteroids. OP-101 at 4 mg/kg was better than placebo at decreasing inflammatory markers; OP-101 at 4 and 8 mg/kg was better than placebo at reducing neurological injury markers, (neurofilament light chain and glial fibrillary acidic protein). Risk for the composite outcome of mechanical ventilation or death at 30 and 60 days after treatment was 71% (95% CI: 29%, 96%) for placebo and 18% (95% CI: 4%, 43%; P = 0.021) for the pooled OP-101 treatment arms. At 60 days, 3 of 7 patients given placebo and 14 of 17 OP-101–treated patients were surviving. No drug-related adverse events were reported. These data show that OP-101 was well tolerated and may have potential to treat systemic inflammation and neuronal injury, reducing morbidity and mortality in hospitalized patients with severe COVID-19.

This article interprets Foucault's life-long involvement with transgressive experiences as an art of not being oneself, an effort to escape identity and become other. By bringing together Foucault's own theoretical practices with those drawn from Deleuze and Blanchot, and linking these with biographical material (modes of existence), I show how Foucault's `encounters' with passion and pleasure in film, philosophy, S/M, drugs, the Greeks and suicide amount to an `art of living', an intensification of the power to affect oneself and others in processes of `subjectivation', creating new possibilities of life. This is what Foucault more precisely called an `ethics' - an immanent ethics in which one becomes worthy of what happens to oneself by becoming a work of art.

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In this paper I combine aspects of process philosophy and elements from philosophies of difference in order to give some indication of how we might begin to construct a metaphysics of contemporary science. I will focus on the work of Whitehead and Deleuze as representatives of each respective tradition and try to show how their work can be fruitfully articulated together in the context of complexity theory.Whitehead and Deleuze formulate a new kind of transcendental philosophy that enables us to think the self-actualizing structure of the real. The key here is to develop a realist ontology that redefines the universal as individuals, particular things, or actual entities produced by processes of individuation. These processes are driven either by intensive differences (Deleuze) or creative processes of concrescence and transition (Whitehead), which, at certain critical or poised thresholds, change in kind and become self-organizing. Without any need for transcendent or external productive principles (traditional views of self, cause, God, etc.) the real is the product of nothing but the internal difference of its own self-realizing occurrence, bootstrapping itself or creatively advancing into ever new and more complex combinations.The process-product model underpins a fundamental vision of the nature of reality. Here Whitehead and Deleuze give us something like a nested ontology, similar to the kinds of Chinese boxes that so fascinated Leibniz, and revealing what Whitehead would call the connectedness of all occasions in nature whereby individuals or occasions enter into relations with each other from which other entities spontaneously emerge. This metaphysical image correlates at a deep level with transformations in science -especially the sciences of wholeness and so called complex systems. My basic objective will be to construct this metaphysical image from the work of Deleuze and Whitehead and then show how this image is developed in the work of complexity theorists

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