Apocalyptic Mentalities in Late-Medieval England

Apocalypticism, defined by expectation of an imminent End, assumes many forms and proves influential in the second half of the Fourteenth Century in England. Throughout my study, I demonstrate that a rich apocalyptic environment emerges in works of the period, including those of Chaucer, Gower, Langland, and the Pearl-poet. In this period, apocalypticism has provided explanations for plague, narratives that make evil more vivid, and arguments for urgent action. It gives contemporary phenomena special meaning. My study is organized around conspicuous centers of meaning that work reciprocally with the apocalyptic, simultaneously defining the End and defined by it. First, I center on death, which as a theological last thing in itself necessarily shares a sense of anxiety with the apocalypse. In connection with both death and apocalypse, fear and hope are often invoked. And as forms of death are tied to the apocalyptic, this means that data from the late-medieval world are used to tell a vivid story with implications for the future of daily life. My second chapter deals with how the meaning of the apocalyptic is interrelated with ecclesiastical authority. In an apocalyptic context, authority delineates not only power but also the important matters of good and evil. In this period in which notions of power and evil are intensely debated, apocalypticism proves adaptable to different circumstances and different perspectives while still remaining grounded in predictive ancient prophecy. Third, I maintain that the period\u27s still-developing practices of confession (which claim to regulate all human activity) are given a special urgency by the sense of impending doom. Then I close my study with an examination of how writing embodies a curious tension with the apocalyptic in mind: writing is confined to time, but it also must serve as a witness to eternal matters. The apocalypse, while it argues for ephemerality of earthly things, requires a qualified permanence of texts that spread its explanations and stories. Overall, I maintain that the richness and variety of apocalyptic meaning in this period is best understood through the apocalyptic\u27s interaction with key cultural terms, including mortality, authority, confession, and textual permanence

Free sialic acid storage disorder: Progress and promise

Lysosomal free sialic acid storage disorder (FSASD) is an extremely rare, autosomal recessive, neurodegenerative, multisystemic disorder caused by defects in the lysosomal sialic acid membrane exporter SLC17A5 (sialin). SLC17A5 defects cause free sialic acid and some other acidic hexoses to accumulate in lysosomes, resulting in enlarged lysosomes in some cell types and 10-100-fold increased urinary excretion of free sialic acid. Clinical features of FSASD include coarse facial features, organomegaly, and progressive neurodegenerative symptoms with cognitive impairment, cerebellar ataxia and muscular hypotonia. Central hypomyelination with cerebellar atrophy and thinning of the corpus callosum are also prominent disease features. Around 200 FSASD cases are reported worldwide, with the clinical spectrum ranging from a severe infantile onset form, often lethal in early childhood, to a mild, less severe form with subjects living into adulthood, also called Salla disease. The pathobiology of FSASD remains poorly understood and FSASD is likely underdiagnosed. Known patients have experienced a diagnostic delay due to the rarity of the disorder, absence of routine urine sialic acid testing, and non-specific clinical symptoms, including developmental delay, ataxia and infantile hypomyelination. There is no approved therapy for FSASD. We initiated a multidisciplinary collaborative effort involving worldwide academic clinical and scientific FSASD experts, the National Institutes of Health (USA), and the FSASD patient advocacy group (Salla Treatment and Research [S.T.A.R.] Foundation) to overcome the scientific, clinical and financial challenges facing the development of new treatments for FSASD. We aim to collect data that incentivize industry to further develop, obtain approval for, and commercialize FSASD treatments. This review summarizes current aspects of FSASD diagnosis, prevalence, etiology, and disease models, as well as challenges on the path to therapeutic approaches for FSASD