274 research outputs found

    A comparison of various approaches to the exponential random graph model:A reanalysis of 102 student networks in school classes

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    This paper describes an empirical comparison of four specifications of the exponential family of random graph models (ERGM), distinguished by model specification (dyadic independence, Markov, partial conditional dependence) and, for the Markov model, by estimation method (Maximum Pseudolikelihood, Maximum Likelihood). This was done by reanalyzing 102 student networks in 57 junior high school classes. At the level of all classes combined, earlier substantive conclusions were supported by all specifications. However, the different specifications led to different conclusions for individual classes. PL produced unreliable estimates (when ML is regarded as the standard) and had more convergence problems than ML. Furthermore, the estimates of covariate effects were affected considerably by controlling for network structure, although the precise specification of the structural part (Markov or partial conditional dependence) mattered less. (C) 2007 Elsevier BX All rights reserved

    No Longer Discrete:Modeling the Dynamics of Social Networks and Continuous Behavior

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    The dynamics of individual behavior are related to the dynamics of the social structures in which individuals are embedded. This implies that in order to study social mechanisms such as social selection or peer influence, we need to model the evolution of social networks and the attributes of network actors as interdependent processes. The stochastic actor-oriented model is a statistical approach to study network-attribute coevolution based on longitudinal data. In its standard specification, the coevolving actor attributes are assumed to be measured on an ordinal categorical scale. Continuous variables first need to be discretized to fit into such a modeling framework. This article presents an extension of the stochastic actor-oriented model that does away with this restriction by using a stochastic differential equation to model the evolution of a continuous attribute. We propose a measure for explained variance and give an interpretation of parameter sizes. The proposed method is illustrated by a study of the relationship between friendship, alcohol consumption, and self-esteem among adolescents

    The combined use of steroids and immune checkpoint inhibitors in brain metastasis patients:a systematic review and meta-analysis

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    BACKGROUND: Immune checkpoint inhibitors (ICI) have been a breakthrough for selected cancer patients, including those with brain metastases (BMs). Likewise, steroids have been an integral component of symptomatic management of BM patients. However, clinical evidence on the interaction between ICI and steroids in BM patients is conflicting and has not adequately been summarized thus far. Hence, the aim of this study was to perform a systematic literature review and meta-analysis on the association between steroid use and overall survival (OS) in BM patients receiving ICI. METHODS: A systematic literature search was performed. Pooled effect estimates were calculated using random-effects models across included studies. RESULTS: After screening 1145 abstracts, 15 observational studies were included. Fourteen studies reported sufficient data for meta-analysis, comprising 1102 BM patients of which 32.1% received steroids. In the steroid group, median OS ranged from 2.9 to 10.2 months. In the nonsteroid group, median OS ranged from 4.9 to 25.1 months. Pooled results demonstrated significantly worse OS (HR = 1.84, 95% CI 1.22-2.77) and systemic progression-free survival (PFS; HR = 2.00, 95% CI 1.37-2.91) in the steroid group. Stratified analysis showed a consistent effect across the melanoma subgroup; not in the lung cancer subgroup. No significant association was shown between steroid use and intracranial PFS (HR = 1.31, 95% CI 0.42-4.07). CONCLUSIONS: Administration of steroids was associated with significantly worse OS and PFS in BM patients receiving ICI. Further research on dose, timing, and duration of steroids is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI

    Adaptive Evolution of a Stress Response Protein

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    Some cancers are mediated by an interplay between tissue damage, pathogens and localised innate immune responses, but the mechanisms that underlie these linkages are only beginning to be unravelled.Here we identify a strong signature of adaptive evolution on the DNA sequence of the mammalian stress response gene SEP53, a member of the epidermal differentiation complex fused-gene family known for its role in suppressing cancers. The SEP53 gene appears to have been subject to adaptive evolution of a type that is commonly (though not exclusively) associated with coevolutionary arms races. A similar pattern of molecular evolution was not evident in the p53 cancer-suppressing gene.Our data thus raises the possibility that SEP53 is a component of the mucosal/epithelial innate immune response engaged in an ongoing interaction with a pathogen. Although the pathogenic stress mediating adaptive evolution of SEP53 is not known, there are a number of well-known candidates, in particular viruses with established links to carcinoma

    Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids

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    Treatment of common bile duct disorders such as biliary atresia or ischaemic strictures is limited to liver transplantation or hepatojejunostomy due to the lack of suitable tissue for surgical reconstruction. Here, we report a novel method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree and we explore the potential of bioengineered biliary tissue consisting of these extrahepatic cholangiocyte organoids (ECOs) and biodegradable scaffolds for transplantation and biliary reconstruction in vivo. ECOs closely correlate with primary cholangiocytes in terms of transcriptomic profile and functional properties (ALP, GGT). Following transplantation in immunocompromised mice ECOs self-organize into tubular structures expressing biliary markers (CK7). When seeded on biodegradable scaffolds, ECOs form tissue-like structures retaining biliary marker expression (CK7) and function (ALP, GGT). This bioengineered tissue can reconstruct the wall of the biliary tree (gallbladder) and rescue and extrahepatic biliary injury mouse model following transplantation. Furthermore, it can be fashioned into bioengineered ducts and replace the native common bile duct of immunocompromised mice, with no evidence of cholestasis or lumen occlusion up to one month after reconstruction. In conclusion, ECOs can successfully reconstruct the biliary tree following transplantation, providing proof-of-principle for organ regeneration using human primary cells expanded in vitro
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