An agent-based model of the response to angioplasty and bare-metal stent deployment in an atherosclerotic blood vessel

Purpose: While animal models are widely used to investigate the development of restenosis in blood vessels following an intervention, computational models offer another means for investigating this phenomenon. A computational model of the response of a treated vessel would allow investigators to assess the effects of altering certain vessel- and stent-related variables. The authors aimed to develop a novel computational model of restenosis development following an angioplasty and bare-metal stent implantation in an atherosclerotic vessel using agent-based modeling techniques. The presented model is intended to demonstrate the body's response to the intervention and to explore how different vessel geometries or stent arrangements may affect restenosis development. Methods: The model was created on a two-dimensional grid space. It utilizes the post-procedural vessel lumen diameter and stent information as its input parameters. The simulation starting point of the model is an atherosclerotic vessel after an angioplasty and stent implantation procedure. The model subsequently generates the final lumen diameter, percent change in lumen cross-sectional area, time to lumen diameter stabilization, and local concentrations of inflammatory cytokines upon simulation completion. Simulation results were directly compared with the results from serial imaging studies and cytokine levels studies in atherosclerotic patients from the relevant literature. Results: The final lumen diameter results were all within one standard deviation of the mean lumen diameters reported in the comparison studies. The overlapping-stent simulations yielded results that matched published trends. The cytokine levels remained within the range of physiological levels throughout the simulations. Conclusion: We developed a novel computational model that successfully simulated the development of restenosis in a blood vessel following an angioplasty and bare-metal stent deployment based on the characteristics of the vessel crosssection and stent. A further development of this model could ultimately be used as a predictive tool to depict patient outcomes and inform treatment options. © 2014 Curtin, Zhou

Secreted Frizzled-related protein-1 is a negative regulator of androgen receptor activity in prostate cancer

Secreted Frizzled-related protein-1 (sFRP1) associates with Wnt proteins and its loss can lead to activation of Wnt/β-catenin signalling. It is frequently downregulated in cancer, including prostate cancer, but its function in prostate cancer is unclear because it can increase proliferation of prostate epithelial cells. We investigated the function of sFRP1 in androgen-dependent prostate cancer and found that sFRP1 inhibited androgen receptor (AR) transcriptional activity. In addition, sFRP1 inhibited the proliferation of androgen-dependent LNCaP cells but not of an androgen-independent subline LNCaP-r, suggesting a role in androgen-dependent growth. The inhibition of AR by sFRP1 was unaffected by co-expression of Wnt3a, stabilised β-catenin or β-catenin shRNA, suggesting it does not involve Wnt/β-catenin signalling. Wnt5a also inhibited AR and expression of Wnt5a and sFRP1 together did not further inhibit AR, suggesting that Wnt5a and sFRP1 activate the same signal(s) to inhibit AR. However, sFRP1 inhibition of AR was unaffected by inhibitors of kinases involved in Wnt/Ca2+ and Wnt/planar cell polarity non-canonical Wnt signalling. Interestingly, the cysteine-rich domain of sFRP1 interacted with Frizzled receptors expressed in prostate cancer cells, suggesting that sFRP1/Frizzled complexes activate a signal that leads to repression of AR. Taken together, these observations highlight the function of β-catenin-independent Wnt signalling in the control of AR activity and provide one explanation for sFRP1 downregulation in prostate cancer

Towards a Critical Sociology of Dominant Ideologies: An Unexpected Reunion between Pierre Bourdieu and Luc Boltanski

This article aims to demonstrate the enduring relevance of Pierre Bourdieu and Luc Boltanski’s ‘La production de l’idéologie dominante’ [‘The production of the dominant ideology’], which was originally published in Actes de la recherche en sciences sociales in 1976. More than three decades later, in 2008, a re-edited version of this study was printed in book format as La production de l’idéologie dominante, which was accompanied by a detailed commentary, written by Luc Boltanski and entitled Rendre la réalité inacceptable. À propos de « La production de l’idéologie dominante » [Making Reality Unacceptable. Comments on ‘The production of the dominant ideology’]. In addition to containing revealing personal anecdotes and providing important sociological insights, this commentary offers an insider account of the genesis of one of the most seminal pieces Boltanski co-wrote with his intellectual father, Bourdieu. In the Anglophone literature on contemporary French sociology, however, the theoretical contributions made both in the original study and in Boltanski’s commentary have received little – if any – serious attention. This article aims to fill this gap in the literature, arguing that these two texts can be regarded not only as forceful reminders of the fact that the ‘dominant ideology thesis’ is far from obsolete but also as essential for understanding both the personal and the intellectual underpinnings of the tension-laden relationship between Bourdieu and Boltanski. Furthermore, this article offers a critical overview of the extent to which the unexpected, and partly posthumous, reunion between ‘the master’ (Bourdieu) and his ‘dissident disciple’ (Boltanski) equips us with powerful conceptual tools, which, whilst illustrating the continuing centrality of ‘ideology critique’, permit us to shed new light on key concerns in contemporary sociology and social theory. Finally, the article seeks to push the debate forward by reflecting upon several issues that are not given sufficient attention by Bourdieu and Boltanski in their otherwise original and insightful enquiry into the complexities characterizing the daily production of ideology

Hermeneutics of Modern Death: Science, Philosophy and the Brain Death Controversy in Orthodox Judaism

Brain death criteria is acknowledged by 80 countries worldwide as the death of a human being. Such acknowledgement has not gone without critical perspectives being voiced. Philosopher Hans Jonas (1903–1993), for example, who criticizes the brain death criteria as the modern version of the old mind-body dualism, names it today’s brain-body dualism. He argues in favor of a more holistic perspective on the human dying process, thus resembling in his opposition modern Jewish Ultra-Orthodox’ strict reservations against brain death. Contrary to the Western philosophic way of argumentation, Orthodox Jews and their religious authorities looked into the matter following other interests: In Orthodox Judaism, the question whether brain death is per definitionem halachic death (death according to religious law) created a controversy in its own right. This article intends to discuss two main arguments: First, the Orthodox brain death controversy shows in a nutshell how production and governance of knowledge, secular (also medical) and religious knowledge alike, depends on processes of legitimization within a specific interpretive community. The issues of brain death and organ donation, generally rejected by the Ultra-Orthodox but accepted by their “modern” co-religionists, show that trust in the medical determination of death as well as trust in the uncertainty of the dying process are both legitimate options within the same religious normative framework. Thus, the acceptance or rejection of the brain death concept in different Jewish religious cultures may have (among other factors) to be considered together with the question of “knowledge sovereignty” when it comes to death and dying. Second, the question of which knowledge generating system should best be trusted is indirectly mirrored by Jonas’ idea of a new mind-body dualism that alludes to a general dichotomy between (medical) science and religion