SUMMARY Prognostically relevant RNA expression states exist in pancreatic ductal adenocarcinoma (PDAC), but our understanding of their drivers, stability, and relationship to therapeutic response is limited. To examine these attributes systematically, we profiled metastatic biopsies and matched organoid models at single-cell resolution. In vivo , we identify a new intermediate PDAC transcriptional cell state and uncover distinct site- and state-specific tumor microenvironments (TMEs). Benchmarking models against this reference map, we reveal strong culture-specific biases in cancer cell transcriptional state representation driven by altered TME signals. We restore expression state heterogeneity by adding back in vivo -relevant factors and show plasticity in culture models. Further, we prove that non-genetic modulation of cell state can strongly influence drug responses, uncovering state-specific vulnerabilities. This work provides a broadly applicable framework for aligning cell states across in vivo and ex vivo settings, identifying drivers of transcriptional plasticity and manipulating cell state to target associated vulnerabilities.

Liberal democracy is often viewed by its supporters as a system of government that responds to the informed and rational preferences of the public organized as voters. And liberal democracy is often viewed by its critics as a system that fails to respond to the informed and rational preferences of its citizens. In this book Larry Bartels and Chris Achen draw on decades of research to argue that a “realistic” conception of democracy cannot be centered on the idea of a “rational voter,” and that the ills of contemporary democracies, and especially democracy in the U.S., must be sought in the dynamics that link voters, political parties and public policy in ways that reproduce inequality. “We believe,” write the authors, “that abandoning the folk theory of democracy is a prerequisite to both greater intellectual clarity and real political change. Too many democratic reformers have squandered their energy on misguided or quixotic ideas.”

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In every democratic polity there exist individuals and groups who hold some but not all of the essential elements of citizenship. Scholars who study citizenship routinely grasp for shared concepts and language that identify forms of membership held by migrants, children, the disabled, and other groups of individuals who, for various reasons, are neither full citizens nor non-citizens. This book introduces the concept of semi-citizenship as a means to dramatically advance debates about individuals who hold some but not all elements of full democratic citizenship. By analytically classifying the rights of citizenship and their various combinations, scholars can typologize semi-citizens and produce comparisons of different kinds of semi-citizenships and of semi-citizenships in different states. The book uses theoretical analysis, historical examples, and contemporary cases of semi-citizenship to illustrate how normative and governmental doctrines of citizenship converge and conflict, making semi-citizenship an enduring and inevitable part of democratic politics.

BackgroundThe "right to health," including access to basic healthcare, has been recognized as a universal human right through a number of international agreements. Attempts to protect this ideal, however, have relied on states as the guarantor of rights and have subsequently ignored stateless individuals, or those lacking legal nationality in any nation-state. While a legal nationality alone is not sufficient to guarantee that a right to healthcare is accessible, an absence of any legal nationality is almost certainly an obstacle in most cases. There are millions of so-called stateless individuals around the globe who are, in effect, denied medical citizenship in their countries of residence. A central motivating factor for this essay is the fact that statelessness as a concept is largely absent from the medical literature. The goal for this discussion, therefore, is primarily to illustrate the need for further monitoring of health access issues by the medical community, and for a great deal more research into the effects of statelessness upon access to healthcare. This is important both as a theoretical issue, in light of the recognition by many of healthcare as a universal right, as well as an empirical fact that requires further exploration and amelioration.DiscussionMost discussions of the human right to health assume that every human being has legal nationality, but in reality there are at least 11 to 12 million stateless individuals worldwide who are often unable to access basic healthcare. The examples of the Roma in Europe, the hill tribes of Thailand, and many Palestinians in Israel highlight the negative health impacts associated with statelessness.SummaryStateless individuals often face an inability to access the most basic healthcare, much less the "highest attainable standard of health" outlined by international agreements. Rather than presuming nationality, statelessness must be recognized by the medical community. Additionally, it is imperative that stateless populations be recognized, the health of these populations be tracked, and more research conducted to further elaborate upon the connection between statelessness and access to healthcare services, and hence a universal right to health.