Political Anglicanism in the Chesapeake, 1760-1800

While the Church of England in the mother country had developed the organizational structure that permitted it to respond successfully to its critics, the Anglican Church in Virginia and Maryland struggled with structural failures and problems pertinent to the American geography and ethnic composition. The absence of a resident bishop, the diverse ethnic origins of the colonials, as well as the existence of large numbers of slaves and Indians, together with the great extent of the parishes, rendered the task of colonial ministers extremely difficult. Despite the diligence of some clergymen, the Anglican Church in the Chesapeake failed to bring large numbers of converts into its fold and to gain, therefore, a firm footing on the American soil. As a result, it took the form of an institution which was more appealing to the elite than to those of a low social background. Among the former, there were numerous examples of piety and devotion which exhibit a true attachment to the ideals of Anglican civil theology. The great power that local elites acquired within the colonial church establishment of Virginia and Maryland prevented Anglican clergymen from developing an independent stance which would have allowed them to influence public opinion in the colonies in a staunchly conservative way. As a result, Anglican clergymen failed to stem the revolutionary tide that swept the region in mid-eighteenth century. There are elements, however, of Anglican political thought in the arguments voiced by the statesmen of the new nation in Virginia and in Maryland. Such ideas as the perception of society as an organic whole, the propriety of elite rule, the authority of governmental institutions to promote public virtue, the right to depose a monarch - when he acted in an unconstitutional way - and the importance of moderate and peaceful demeanour were cherished by Anglicans at both sides of the Atlantic

Genetic prediction of ICU hospitalization and mortality in COVID-19 patients using artificial neural networks

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype.- Pfizer Pharmaceuticals(undefined

Clonal expansion of B-cells in human systemic lupus erythematosus: Evidence from studies before and after therapeutic B-cell depletion

Anti-B-cell therapy may be beneficial for patients with SLE and active proliferative glomerulonephritis. Using genomic DNA, we examined how rituximab-induced transient B-cell depletion affected the composition of immunoglobulin heavy-chain (IG-V-H/D-H/J(H)) repertoire at the time-point of 33-35% B-cell reconstitution in these patients. Clusters of clonaly-related Ig-V-H/D-H/J(H) sequences were evident in all 7 patients with active SLE but in none of 4 healthy subjects studied for comparison. In addition to original somatic mutation(s) shared in the majority of clonaly-related sequences, ongoing mutation suggested expansion of single B-cell precursors and clonal evolution. Otherwise, lupus repertoire was similar to that of healthy subjects with the exception of increased somatic hypermutation. The regenerating repertoire was diverse and comparable to baseline, albeit with fewer somatic mutations but more clonal expansions. Since clonal expansion may lead to preferential survival/growth of potentially autoreactive B-cells further studies are warranted, especially as therapies aiming to reduce B-cell survival emerge. (C) 2009 Elsevier Inc. All rights reserved

Genetic prediction of ICU hospitalization and mortality in COVID-19 patients using artificial neural networks

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype