Conceptions of Analysis in Early Analytic Philosophy

Over the last few years, within analytic philosophy as a whole, there has developed a wider concern with methodological questions, partly as a result of the increasing interest in the foundations - both historical and philosophical - of analytic philosophy, and partly due to the resurgence of metaphysics in reaction to the positivism that dominated major strands in the early analytic movement. In this paper I elucidate the key conceptions of analysis that arose during the formative years of analytic philosophy, focusing, in particular, on the debate over the nature of analysis in the early 1930s, within what was called at the time the 'Cambridge School of Analysis', and the development of Carnap's conception(s) of logical analysis during his critical phase when he was a central figure in the Vienna Circle. In the final section, with this in mind, I revisit the origins of analytic philosophy in the work of Frege, and show how the distinctions I draw can be used in diagnosing some of the tensions that are present in Frege's thought and which have given rise to controversy in the interpretation of Frege

XIV-Swimming Happily in Chinese Logic

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Open-mindedness and Ajar-mindedness in History of Philosophy

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The Early Life Of Russell’s Notion Of A Propositional Function

In this paper I describe the birth of Russell’s notion of a propositional function on 3 May 1902 (precise time of day unknown) and its immediate context and implications. In particular, I consider its significance in relation to the development of his views on analysis

Getting to Know Knowing-as as Knowing

In ‘Swimming Happily in Chinese Logic’ (2021) I suggested that the root conception of knowing for the ancient Chinese Mohists was knowing-as, a conception that fits well with perspectivism in the Zhuangzi, a key Daoist text. Drawing on Wittgenstein’s discussion of both seeing-as and samples, and developing the analogy between seeing-as and knowing-as, I explore various forms of knowing with particular reference to the Mozi, in attempting to make sense of ancient Chinese epistemology and thereby shed light on the whole phenomenon of knowing.Peer Reviewe

Wittgenstein's Ways

Aristotle first investigated different modes, or ways of being. Unfortunately, in the modern literature the discussion of this concept has been largely neglected. Only recently, the interest towards the concept of ways increased. Usually, it is explored in connection with the existence of universals and particulars. The approach we are going to follow in this chapter is different. It discusses Wittgenstein’s conception of higher ontological levels as ways of arranging elements of lower ontological levels. In the Tractatus, Wittgenstein developed his ontology of ways (Art und Weise) in six steps: (i) Constructing states of affairs out of objects; (ii) Constructing propositions out of states of affairs; (iii) Constructing propositional signs; (iv) Constructing thoughts with the help of propositional signs; (v) Constructing truth / falsity; (vi) Constructing works of art. In Philosophical Investigations he added further five ways of producing new ontological levels: (vii) the meaning of a proposition is the way in which it is verified; (viii) the child gets command on language/calculus in the way it replicates demonstrations of the teacher; (ix) the products of mind are ways of doing something; (x) an action is a way of carrying out the instructions for acting

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

Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate and high-risk early stage triple negative breast cancer

Background: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK-TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected (ctDNA+). Patients and methods: c-TRAK-TN, a multi-centre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or, stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three monthly blood sampling to 12 months (18 months if samples were missed due to COVID), and ctDNA+ patients were randomised 2:1; intervention:observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16/09/2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were i) ctDNA detection rate ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). Results: 208 patients registered between 30/01/18 - 06/12/19, 185 had tumour sequenced, 171 (92·4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27·3% (44/161,95%CI:20·6-34·9). Seven patients relapsed without prior ctDNA detection. 45 patients entered the therapeutic component (intervention n=31; observation n=14; 1 observation patient was re-allocated to intervention following protocol amendment). Of patients allocated intervention, 72% (23/32) had metastases on staging at time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. Conclusion: c-TRAK-TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes