Bayesian Networks for Max-linear Models

We study Bayesian networks based on max-linear structural equations as introduced in Gissibl and Kl\"uppelberg [16] and provide a summary of their independence properties. In particular we emphasize that distributions for such networks are generally not faithful to the independence model determined by their associated directed acyclic graph. In addition, we consider some of the basic issues of estimation and discuss generalized maximum likelihood estimation of the coefficients, using the concept of a generalized likelihood ratio for non-dominated families as introduced by Kiefer and Wolfowitz [21]. Finally we argue that the structure of a minimal network asymptotically can be identified completely from observational data.Comment: 18 page

Influence of intestinal microbial metabolites on the abscopal effect after radiation therapy combined with immune checkpoint inhibitors

Background: Most clinical studies failed to elicit a strong antitumor immune response and subsequent systemic tumor regression after radiation therapy (RT), even in combination with the immune checkpoint inhibitors (ICI) anti-CTLA4 or anti-PD1. Mechanistically, type I interferon (IFN-I) activation is essential for the development of such abscopal effects (AE); however, mechanisms driving or limiting IFN–I activation are ill defined. Groundbreaking discoveries have shown that antibiotics (ABx) can affect oncological outcomes and that microbiota-derived metabolites can modulate systemic antitumor immunity. Recent studies have demonstrated that the bacterial metabolites desaminotyrosine (DAT) and indole-3-carboxaldehyde (ICA) can enhance IFN-I activation in models of inflammatory diseases. Materials and Methods: The subcutaneous bilateral MC38 tumor model is a widely used experimental tool to study the AE in mice. We applied it to explore the influence of broad-spectrum ABx, DAT and ICA on the AE after radioimmunotherapy (RIT). We performed 1x8 Gy of the primary tumor ± anti-CTLA4 or anti-PD1, and ± daily oral application of ABx or metabolites. Result: Combinatory ABx had neither a significant effect on tumor growth of the irradiated tumor nor on tumor progression of the abscopal tumor after RIT with anti-CTLA4. Furthermore, DAT and ICA did not significantly impact on the AE after RIT with anti-CTLA4 or anti-PD1. Surprisingly, ICA even appears to reduce outcomes after RIT with anti-CTLA4. Conclusion: We did not find a significant impact of combinatory ABx on the AE. Experimental application of the IFN-I-inducing metabolites DAT or ICA did not boost the AE after combined RIT. Additional studies are important to further investigate whether the intestinal microbiota or specific microbiota-derived metabolites modulate the AE

Imagined races : from environmental determinism to geographical authenticity in twentieth‐century Argentina

This article explores how Argentine intellectuals incorporated the natural environment into their accounts of the racial, cultural and political features of the nation. In the late nineteenth century environmental determinism, based on the assumption of a cause–effect relationship between geographical and racial factors, entered Argentina through three main routes: Lamarckism, Darwinism and Spencerianism. By the mid twentieth century, however, anti‐positivist philosophies had been fully incorporated into a body of work that analysed Argentina's socio‐historical foundations. This article examines the shift that occurred during the first half of the twentieth century in how those seeking to define race incorporated the environment into their arguments. The raza was commonly taken to be synonymous with nation. Selected works by sociologist and legal scholar Carlos Octavio Bunge (1875‐1918) and by writer and ensayista Bernardo Canal Feijóo (1897‐1982) will be analysed as influential yet overlooked examples of how ‘the problem of Argentine culture’ could not be separated from the question of nature understood in terms of both physical and human geography. The goal will be to reveal, firstly, the extent to which the notion of the interior as geographical and anthropological desert deeply informed the political vision of the early national period in relation to race and nation and, secondly, how later interpretations of the nation recast American nature as a foundational element of cultural authenticity based on a sentiment of geographical belonging