Simon Vorontsov and the Ochakov Crisis of 1791

By his own admission, Simon Vorontsov (Woronzow or Woronzoff, 1744–1832) was ill-suited and unprepared for diplomatic service, yet for over twenty years (1784–1806) he served as Russia’s Minister to the Court of St. James’s. He is now widely considered to be one of Catherine II’s greatest and most innovative diplomats. Because of his determined and independent spirit, he averted a war between Britain and Russia during the Ochakov crisis of 1791 by adapting the methods of the so-called ‘new diplomacy’. Rather than seeking mediation and mutual understanding, he collaborated with the opposition and initiated a vigorous public opinion campaign in the press and through the publication of pamphlets and anonymous articles. He thereby supported Charles Fox, challenged William Pitt and, in the end, emerged victorious

Intravenous tPA for Acute Ischemic Stroke in Patients with COVID-19

BACKGROUND/PURPOSE: Coronavirus disease 2019 (COVID-19) is associated with increased risk of acute ischemic stroke (AIS), however, there is a paucity of data regarding outcomes after administration of intravenous tissue plasminogen activator (IV tPA) for stroke in patients with COVID-19. METHODS: We present a multicenter case series from 9 centers in the United States of patients with acute neurological deficits consistent with AIS and COVID-19 who were treated with IV tPA. RESULTS: We identified 13 patients (mean age 62 (±9.8) years, 9 (69.2%) male). All received IV tPA and 3 cases also underwent mechanical thrombectomy. All patients had systemic symptoms consistent with COVID-19 at the time of admission: fever (5 patients), cough (7 patients), and dyspnea (8 patients). The median admission NIH stroke scale (NIHSS) score was 14.5 (range 3-26) and most patients (61.5%) improved at follow up (median NIHSS score 7.5, range 0-25). No systemic or symptomatic intracranial hemorrhages were seen. Stroke mechanisms included cardioembolic (3 patients), large artery atherosclerosis (2 patients), small vessel disease (1 patient), embolic stroke of undetermined source (3 patients), and cryptogenic with incomplete investigation (1 patient). Three patients were determined to have transient ischemic attacks or aborted strokes. Two out of 12 (16.6%) patients had elevated fibrinogen levels on admission (mean 262.2 ± 87.5 mg/dl), and 7 out of 11 (63.6%) patients had an elevated D-dimer level (mean 4284.6 ±3368.9 ng/ml). CONCLUSIONS: IV tPA may be safe and efficacious in COVID-19, but larger studies are needed to validate these results

Playing for Their Share: A History of Creative Tradeswomen in Eighteenth Century Virginia

This dissertation reveals the commonality of public and active women who used creative trades to substantiate their lives in Virginia from 1716-1800. A creative tradeswoman, an existence identified by this scholarship, was an individual who used her musical, dancing, and singing abilities to incur wages. This study focuses on prominent creative tradeswomen such as Mrs. Sully and Mrs. Pick, a traveling musical duo; the singing actresses of the Hallam; Mary Stagg, assembly manager and contributor to the first theater in Williamsburg; Baroness Barbara deGraffenreit, who competed for Williamsburg\u27s premier dancing manager position; and Mrs. Ann Neill, an enterprising music teacher. Despite times of subordination, these women showcased unique forms of creative agency such as acquiring widespread idolization or organizing traveling musical duos. Creative tradeswomen challenged the conventional oppositions between trade and gentry women, education and creative ability, submission and dominance, amateur and professional culture, public and private spaces. The histories of creative tradeswomen demonstrate the fluidity between these binaries while also remapping cultural and social identities as informed by power, subjectivity, trade, music, and dance. As a result, this dissertation illustrates creative tradeswomen as situated within paradoxical systems of power and subordination. The archives at the Rockefeller Library, Virginia Historical Society, New York Historical Society, and the Library of Congress supported the research. This dissertation utilizes a feminist historiography methodology, incorporating a consideration of cultural and social conditions that bring forward creative women\u27s untold histories. Interdisciplinary in nature, this study makes points of contact between women\u27s history, cultural history, and gender studies. Creative tradeswomen expands the research on women\u27s labor while locating gender and class as major influencers informing a woman\u27s creative labor. This dissertation expands the normative categories used to shape historical women while demonstrating their contributions to the development of early American culture. This research appends women\u27s creative trade histories into the scholarly conversation and identifies their contributions as valuable components of American cultural history. The history of creative tradeswomen expands the foundational modes of early American scholarship while presenting a rarely included emphasis on women\u27s creative trades

Targeting amyloid-beta peptide via gene delivery of apolipoprotein epsilon 2 to the CNS

Alzheimer's disease (AD) is a devastating neurodegenerative disorder for which no disease modifying treatment exists. Inheritance of the apolipoprotein E (APOE) ε4 allele strongly increases the risk of developing the sporadic form of AD, whereas the ε2 allele is protective. Though the precise role of the different APOE alleles remains unclear, in vitro and in vivo studies have demonstrated that each isoform differentially modulates the deposition, clearance, and degradation of amyloid-beta (Aβ) peptides that form the extracellular plaques of AD. Strategies directed toward increasing the levels of APOE2 could be useful in reducing plaques and alleviating disease progression. Additionally, advances in gene transfer using adeno-associated vectors (AAV) enable efficient and safe expression of therapeutic genes like APOE2. This dissertation, describes experiments that (1) test if intracerebroventricular gene delivery of APOE isoform can modulate amyloid pathology in transgenic animals that accumulate beta-amyloid, (2) evaluate the efficacy of a novel approach by intravenous infusion of AAV, and (3) characterize oligomeric Aβ (oAβ) in rhesus monkeys as a potential translational target. Experiment 1 explored how each APOE isoform impacts the progression of AD pathology using intracerebroventricular injection of AAV4. This demonstrated isoform-dependent effects on Aβ-related neuropathology using multi-photon imaging, in vivo microdialysis, post-mortem immunohistochemistry, and array tomography. Experiment 2 demonstrated the efficacy of intravenous delivery of AAV9 and increased efficiency of self-complementary AAV9 vectors compared to single-stranded AAV9. Furthermore, expression of transgene was restricted to CNS astrocytes by utilizing a restrictive promoter. Finally, the presence of oAβ in rhesus macaque monkeys and its possible association with age-related cognitive decline was explored using fresh samples of monkey cortex. Soluble oAβ was detected in multiple cortical areas but was not significantly associated with age. Nevertheless, a significant positive correlation was observed between oAβ in frontal pole cortex and impairment on a behavioral test of executive function. Taken together, these data suggest that gene transfer of APOEε2 may be useful for modulation APOE expression and beta-amyloid accumulations for the treatment of AD. Furthermore, the rhesus monkey may serve as a model system for future preclinical studies

Playing for Their Share: A History of Creative Tradeswomen in Eighteenth Century Virginia

This dissertation reveals the commonality of public and active women who used creative trades to substantiate their lives in Virginia from 1716-1800. A creative tradeswoman, an existence identified by this scholarship, was an individual who used her musical, dancing, and singing abilities to incur wages. This study focuses on prominent creative tradeswomen such as Mrs. Sully and Mrs. Pick, a traveling musical duo; the singing actresses of the Hallam; Mary Stagg, assembly manager and contributor to the first theater in Williamsburg; Baroness Barbara deGraffenreit, who competed for Williamsburg\u27s premier dancing manager position; and Mrs. Ann Neill, an enterprising music teacher. Despite times of subordination, these women showcased unique forms of creative agency such as acquiring widespread idolization or organizing traveling musical duos. Creative tradeswomen challenged the conventional oppositions between trade and gentry women, education and creative ability, submission and dominance, amateur and professional culture, public and private spaces. The histories of creative tradeswomen demonstrate the fluidity between these binaries while also remapping cultural and social identities as informed by power, subjectivity, trade, music, and dance. As a result, this dissertation illustrates creative tradeswomen as situated within paradoxical systems of power and subordination. The archives at the Rockefeller Library, Virginia Historical Society, New York Historical Society, and the Library of Congress supported the research. This dissertation utilizes a feminist historiography methodology, incorporating a consideration of cultural and social conditions that bring forward creative women\u27s untold histories. Interdisciplinary in nature, this study makes points of contact between women\u27s history, cultural history, and gender studies. Creative tradeswomen expands the research on women\u27s labor while locating gender and class as major influencers informing a woman\u27s creative labor. This dissertation expands the normative categories used to shape historical women while demonstrating their contributions to the development of early American culture. This research appends women\u27s creative trade histories into the scholarly conversation and identifies their contributions as valuable components of American cultural history. The history of creative tradeswomen expands the foundational modes of early American scholarship while presenting a rarely included emphasis on women\u27s creative trades

Case of Heidenhain Variant Creutzfeldt-Jakob Disease Presenting with Homonymous Quadrantanopia and Corresponding Nuclear Imaging Findings

Sporadic Creutzfeldt-Jakob disease (sCJD) belongs to a class of prion diseases in which prion protein forms abnormal and pathological folds. In the Heidenhain variant of Creutzfeldt-Jakob disease (HvCJD), patients present with early, prominent visual complaints prior to the onset of more typical features of sCJD. MRI brain is commonly normal, making early diagnosis of this variant particularly challenging. We present a case of a patient with impaired depth perception and homonymous inferior quadrantanopia with normal MRI, in contrast to marked focal FDG-PET and SPECT abnormalities providing clinical-anatomical correlate