Applicability of routine targeted next-generation sequencing to estimate Tumor Mutational Burden (TMB) in patients treated with immune checkpoint inhibitor therapy.

It remains unclear whether targeted next-generation sequencing (tNGS) conveys a reliable estimate of tumor mutational burden (TMB). We sequenced 79 archival samples of immune checkpoint inhibitors (ICPIs) recipients (57% lung cancer, 43% melanoma) using Ion Ampliseq Cancer Hotspot Panel. Employing multiple cutoff values, we verified that TMB by tNGS did not correlate with response or survival following ICPI. We found enrichment of ATM mutations in ICPI-refractory tumors (P=0.01) to correlate with worse survival (4.2 vs. 10 mo, P=0.03). Limited-coverage tNGS delivers an imprecise estimate of patients' TMB but may aid identification of candidate somatic variants of predictive/prognostic significance

New liberalism, new language? The use of collectivist concepts in the budget speeches of 1893–95 and 1906–14

The article considers the Budget Speeches of Asquith and Lloyd George during the period of the Liberal social reforms of 1906–14. It examines how these Budget speeches conceptualised the debate surrounding these reforms and discusses the extent to which this conceptualisation can be seen as reflecting the discursive character of a New Liberalism. The focus is on key collectivist concepts—“the state”, “the community”, “the people” and “the nation”. These were concepts which were very far from being the preserve of the Liberals but it is argued they were unpacked and used in ways that constituted a different conceptual terrain from that which had characterised previous Liberal budget speeches. The article considers the frequency of their usage but, more importantly, their collocation and rhetorical context and argues that these do indeed suggest that in important respects these budgets displayed a rhetorical character reflective of the ideology of New Liberalism