Primary Tumor Size in Renal Cell Cancer in Relation to the Occurrence of Synchronous Metastatic Disease

Objectives: To investigate the controversially discussed relationship between tumor size and the occurrence of primary synchronous metastatic disease in renal cell cancer (RCC). Patients and Methods: A consecutive RCC cohort of 2,058 patients (150 primary metastatic) who underwent surgery between 1995 and 2010 was investigated. Rates of synchronous metastases were calculated for stratified groups of tumor size. Uni- and multivariate logistic regression models were calculated for the correlation of tumor size with primary metastatic disease. Results: The rate of metastatic disease increased with increasing tumor size. Tumor size was significantly correlated with synchronous metastatic disease (p < 0.001, c-index 0.772), but for RCCs ≤ 4 cm in size no significant correlation was found. Regarding tumors ≤ 5 cm in size, the correlation became significant (p = 0.028, c-index 0.621). A multivariate logistic regression model for the prediction of synchronous metastatic disease including tumor size, age and comorbidity yielded a significant c-index of 0.82 and was used to construct a nomogram. Conclusion: Our data confirm the correlation between tumor size and the rate of synchronous metastatic disease. Small renal tumors <4 cm in size have a low risk of synchronous metastatic disease. The risk becomes significantly associated with tumor size for tumors ≤ 5 cm

Embracing Chance: Post-Modern Meditations on Punishment

Since the modern era, the discourse of punishment has cycled through three sets of questions. The first, born of the Enlightenment itself, asked: On what ground does the sovereign have the right to punish? Nietzsche most forcefully, but others as well, argued that the question itself begged its own answer. The right to punish, they suggested, is what defines sovereignty, and as such, can never serve to limit sovereign power. With the birth of the social sciences, this skepticism gave rise to a second set of questions: What then is the true function of punishment? What is it that we do when we punish? From Durkheim to the Frankfurt School to Michel Foucault, 20th century moderns explored social organization, economic production, political legitimacy, and the construction of the self – turning punishment practices upside down, dissecting not only their repressive functions but more importantly their role in constructing society and the contemporary subject. A series of further critiques – of meta-narratives, of functionalism, of scientific objectivity – softened this second line of inquiry and helped shape a third set of questions: What does punishment tell us about ourselves and our culture? What is the cultural meaning of our punishment practices? These three sets of questions set the contours of our modern discourse on crime and punishment. What happens now – now that we have seen what lies around the cultural bend and realize that the same critiques apply with equal force to any interpretation of social meaning that we could possibly read into our contemporary punishment practices? Should we continue to labor on this third and final set of questions, return to an earlier set, or, as all our predecessors did, craft a new line of inquiry? What question shall we – children of the 21st century – pose of our punishment practices and institutions? In this essay, I argue that we should abandon the misguided project of modernity, recognize once and for all the limits of reason, and turn instead to randomization and chance. In all the modern texts, there always came this moment when the empirical facts ran out or the deductions of principle reached their limit – or both – and yet the reasoning continued. There was always this moment, ironically, when the moderns took a leap of faith. And it was always there, at that precise moment, that we learned the most: that we could read from the text and decipher a vision of just punishment that was never entirely rational, never purely empirical, and never fully determined by the theoretical premises of the author. In each and every case, the modern text let slip a leap of faith – an ethical choice about how to resolve a gap, an ambiguity, an indeterminacy in an argument of principle or fact. Rather than continue to take these leaps of faith, I urge us to recognize the critical limits of reason and, whenever we reach them, to rely instead on randomization. Where our facts run out, where our principles no longer guide us, we should leave the decision-making to the coin toss, the roll of the dice, the lottery draw – in sum, to chance. This essay begins to explore what that would mean in the field of crime and punishment

Guidelines for the use of flow cytometry and cell sorting in immunological studies

International audienceThe classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. Whereas CD127(-) ELPs comprised precursors of T cells, marginal zone B cells, and natural killer (NK) and innate lymphoid cells (ILCs), CD127(+) ELPs supported production of all NK cell, ILC, and B cell populations but lacked T potential. On the basis of these results, we propose a "two-family" model of human lymphoid development that differs from the prevailing model of hematopoiesis