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Azra Raza, Nicholas Iverson, Abdullah M AliThe MDS Center, Columbia University, New York, NY, USAAbstract: Myelodysplastic syndromes are malignant hematopoietic stem cell disorders that present with variable cytopenias and predominantly affect the elderly. Treatment options are limited, with allogeneic transplant being the only potentially curative strategy. Recent mutational profiling studies have led to cataloguing of driver and passenger mutations most commonly affecting the epigenetic regulators and genes involved in RNA splicing. Despite improved understanding of the disease biology, these emerging molecular insights have not led to identification of novel therapeutic strategies. Although several drugs approved in the last decade improve the cytopenias, the relief is temporary, most likely due to the sequential activation of clones. Future advances depend upon identification of signaling pathways in dominant clones and targeting these with agents that might be known but need to be matched to suit the needs of individual patients in a longitudinal, dynamic fashion. Myelodysplastic syndromes are ideally suited for the development of such personalized medicine.Keywords: cancer, epigenetics, iron, MDS, myelodysplasia, splicing

Journal of Mathematics and Science: Collaborative Explorations, 2005

Compared with other manifestations of climate variability that may not be perceived within a human lifetime, abrupt environmental disturbances arising from volcanism can be directly experienced. Despite abundant Pleistocene calderas in the East African Rift and Afar, and the significance of regional tephra horizons for archaeological and paleoenvironmental dating, the entanglements of volcanoes and their eruptions with human behaviour and paleoecology have received little attention. Here, we focus on the intertwined human and eruptive history at Nabro, a caldera-topped volcanic massif close to the Red Sea littoral of Eritrea. Nabro exemplifies the antagonism of opportunities and threats posed by a large silicic volcano, active at least since the Middle Pleistocene and as recently as 2011. Using argon isotopic measurements, we establish the first chronology of key eruptive stages of Nabro and neighbouring Mallahle revealing a history of explosive and effusive volcanism in the Middle and Late Pleistocene. Past eruptions were an important source of obsidian that was exchanged over long distances across land and sea during the Neolithic. We infer that the availability of high-quality obsidian, combined with Nabro’s favourable microclimate and proximity to the Red Sea coast, likely attracted humans to this volcanic landmark since the later Middle Pleistocene. Drawing on observations of the immediate impact of the 2011 eruption on landscape and local pastoralist communities, we consider the impacts of past volcanic cataclysms on human populations. In addition to the threat to life, explosive eruptions of Nabro circa 130 ka and 62 ka ago would have abruptly curtailed procurement of its obsidian resource. Our findings suggest further attention be paid to evaluating the significance of East African volcanic landscapes, eruptions and resources for understanding human behaviour in deep antiquity.

Correspondence: et al.