Epistemic loops and measurement realism

Recent philosophy of measurement has emphasized the existence of both diachronic and synchronic “loops,” or feedback processes, in the epistemic achievements of measurement. A widespread response has been to conclude that measurement outcomes do not convey interest-independent facts about the world, and that only a coherentist epistemology of measurement is viable. In contrast, I argue that a form of measurement realism is consistent with these results. The insight is that antecedent structure in measuring spaces constrains our empirical procedures such that successful measurement conveys a limited, but veridical knowledge of “fixed points,” or stable, interest- independent features of the world

Apophatic science:How computational modeling can explain consciousness

This study introduces a novel methodology for consciousness science. Consciousness as we understand it pretheoretically is inherently subjective, yet the data available to science are irreducibly intersubjective. This poses a unique challenge for attempts to investigate consciousness empirically. We meet this challenge by combining two insights. First, we emphasize the role that computational models play in integrating results relevant to consciousness from across the cognitive sciences. This move echoes Alan Newell’s call that the language and concepts of computer science serve as a lingua franca for integrative cognitive science. Second, our central contribution is a new method for validating computational models that treats them as providing negative data on consciousness: data about what consciousness is not. This method is designed to support a quantitative science of consciousness while avoiding metaphysical commitments. We discuss how this methodology applies to current and future research and address questions that others have raised

Mechanism Hierarchy Realism and Function Perspectivalism

Mechanistic explanation involves the attribution of functions to both mechanisms and their component parts, and function attribution plays a central role in the individuation of mechanisms. Our aim in this paper is to investigate the impact of a perspectival view of function attribution for the broader mechanist project, and specifically for realism about mechanistic hierarchies. We argue that, contrary to the claims of function perspectivalists such as Craver, one cannot endorse both function perspectivalism and mechanistic hierarchy realism: if functions are perspectival, then so are the levels of a mechanistic hierarchy. We illustrate this argument with an example from recent neuroscience, where the mechanism responsible for the phenomenon of ephaptic coupling cross-cuts (in a hierarchical sense) the more familiar mechanism for synaptic firing. Finally, we consider what kind of structure there is left to be realist about for the function perspectivalist

Mechanism Hierarchy Realism and Function Perspectivalism

Mechanistic explanation involves the attribution of functions to both mechanisms and their component parts, and function attribution plays a central role in the individuation of mechanisms. Our aim in this paper is to investigate the impact of a perspectival view of function attribution for the broader mechanist project, and specifically for realism about mechanistic hierarchies. We argue that, contrary to the claims of function perspectivalists such as Craver, one cannot endorse both function perspectivalism and mechanistic hierarchy realism: if functions are perspectival, then so are the levels of a mechanistic hierarchy. We illustrate this argument with an example from recent neuroscience, where the mechanism responsible for the phenomenon of ephaptic coupling cross-cuts (in a hierarchical sense) the more familiar mechanism for synaptic firing. Finally, we consider what kind of structure there is left to be realist about for the function perspectivalist

Escape from Zanzibar: The Epistemic Value of Precision in Measurement

A “Zanzibar” is an island of measurement values that internally cohere, but are detached from independent contact with reality. In the history of physics, one manifestation of Zanzibars is through “bandwagon effects,” the tendency of contemporaneous measurements to agree. Bandwagons appear to be an example where the otherwise virtuous drive towards coherence has negative epistemic consequences. I argue that precision is an epistemic virtue that mitigates against bandwagon effects and illustrate the evidential power of precision for breaking bandwagons with a case study from the history of measurements of c. I conclude by demonstrating how precision-first reasoning motivates the practice of blind data analysis at the bleeding edge of high precision measurement, where measurement outcomes can point the way to new physics

Genomic profile of advanced breast cancer in circulating tumour DNA.

The genomics of advanced breast cancer (ABC) has been described through tumour tissue biopsy sequencing, although these approaches are limited by geographical and temporal heterogeneity. Here we use plasma circulating tumour DNA sequencing to interrogate the genomic profile of ABC in 800 patients in the plasmaMATCH trial. We demonstrate diverse subclonal resistance mutations, including enrichment of HER2 mutations in HER2 positive disease, co-occurring ESR1 and MAP kinase pathway mutations in HR + HER2- disease that associate with poor overall survival (p = 0.0092), and multiple PIK3CA mutations in HR + disease that associate with short progression free survival on fulvestrant (p = 0.0036). The fraction of cancer with a mutation, the clonal dominance of a mutation, varied between genes, and within hotspot mutations of ESR1 and PIK3CA. In ER-positive breast cancer subclonal mutations were enriched in an APOBEC mutational signature, with second hit PIK3CA mutations acquired subclonally and at sites characteristic of APOBEC mutagenesis. This study utilises circulating tumour DNA analysis in a large clinical trial to demonstrate the subclonal diversification of pre-treated advanced breast cancer, identifying distinct mutational processes in advanced ER-positive breast cancer, and novel therapeutic opportunities