Oxygen heterogeneity in solid tumors is recognized as a limiting factor for therapeutic efficacy. This heterogeneity arises from the abnormal vascular structure of the tumor, but the precise mechanisms linking abnormal structure and compromised oxygen transport are only partially understood. In this paper, we investigate the role that red blood cell (RBC) transport plays in establishing oxygen heterogeneity in tumor tissue. We focus on heterogeneity driven by network effects, which are challenging to observe experimentally due to the reduced fields of view typically considered. Motivated by our findings of abnormal vascular patterns linked to deviations from current RBC transport theory, we calculated average vessel lengths L¯ and diameters d¯ from tumor allografts of three cancer cell lines and observed a substantial reduction in the ratio λ=L¯/d¯ compared to physiological conditions. Mathematical modeling reveals that small values of the ratio λ (i.e., λ<6) can bias hematocrit distribution in tumor vascular networks and drive heterogeneous oxygenation of tumor tissue. Finally, we show an increase in the value of λ in tumor vascular networks following treatment with the antiangiogenic cancer agent DC101. Based on our findings, we propose λ as an effective way of monitoring the efficacy of antiangiogenic agents and as a proxy measure of perfusion and oxygenation in tumor tissue undergoing antiangiogenic treatment.
The authors present an in-depth discussion of Lisfranc's fracture-dislocations, including classifications, mechanisms of injury, radiographic evaluation, and a literature review. Four cases are presented for review. Lisfranc's fracture-dislocation is a rare injury that can lead to prolonged disability if undiagnosed or if there is a delay in treatment.
Oxygen heterogeneity in solid tumours is recognised as a limiting factor for therapeutic efficacy. Vessel normalisation strategies, aimed at rescuing abnormal tumour vascular phenotypes and alleviating hypoxia, have the potential to improve tumour responses to treatments such as radiotherapy and chemotherapy. However, understanding how pathological blood vessel networks and oxygen transport are related remains limited. In this paper, we propose a novel source of oxygen heterogeneity in tumour tissue associated with the abnormal transport of red blood cells. We calculate average vessel lengthsL and diametersd from tumour allografts of three cancer cell lines and observe a substantial reduction in the ratio λ =L/d compared to physiological conditions. Mathematical modelling reveals that small values of the ratio λ (i.e. λ < 6) can bias haematocrit distribution in tumour vascular networks and drive heterogeneous oxygenation of tumour tissue. Finally, we show an increase in the value of λ in tumour vascular networks following treatment with the anti-angiogenic cancer agent DC101. Based on our findings, we propose a mechanism for oxygen normalisation associated with an increase in λ following treatment with anti-angiogenic drugs.
D isaster narratives recur in the high and popular culture of the nineteenth century, appearing in narrative fiction, poetry, drama, opera, fine-art history, and landscape painting, as well as in more spectacular popular forms. the events of such narratives turn on the annihilation of people and property; their structures are characterized by the interruption of narrative continuity; and their philosophy generally suggests the limitations of human powers and the inevitable frustration of schemes and hopes. we are familiar with disaster narratives as a component of our own international popular culture, with the disaster film a particularly recognizable genre that has shed its B-movie connotations to become a major strain of the bigbudget Hollywood blockbuster (a term with its own echoes of wholesale destruction). All such narratives share a relatively under-theorized aesthetic element: the pleasure of the reader or viewer in destruction-of people, of property, of hopes. while this pleasure may have something in common with the pity and terror evoked by Aristotelian tragedy, we might also speculate that enjoyment of such scenes is rooted in the subject's aggressive drives, whether or not one sees that aggression as the outward projection of an innate Freudian deathdrive. Yet while there are evident continuities, our familiarity with contemporary disaster narratives may mislead. in twentieth-and twentyfirst-century disaster texts the interest often resides in the post-disaster Abstract: this essay surveys the volcano spectacles, paintings, plays, and narratives that appear at the end of the eighteenth century, thrive in the nineteenth, and live on well into the twentieth. Moving amphibiously between popular and high culture, this polymodal "commodity experience" imagines historical change as catastrophe, and projects the modern into the past and the forces of modernity onto the natural world. its ability to absorb political content in part underwrites the success of the volcano story, and in such nineteenth-century versions as edward Lytton Bulwer's The Last Days of Pompeii (1834), the volcano is identified with the crowd and with revolution. But alongside the political allegory, a more basic audience delight in destruction itself seems part of the lingering power of the volcano.
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