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The thesis is intended primarily as an examination of the earlier Machiavels from their first appearance in The Spanish Tragedy and The Jew of Malta, through to 1604, which is probably the year in which Othello and The Malcontent were composed. It is also intended to prepare the ground for a more exhaustive study, which, in moving on to a scrutiny of the Jacobean Machiavels, might bring out certain contrasts between the early type and the later one. In Chapter One the question of whether the Machiavels have anything in common with Machiavelli or with the political exemplars of The Prince and The Discourses is raised. Despite the widespread belief that the Elizabethans possessed little firsthand knowledge of Machiavelli and that the Machiavel embodies the distortion of Machiavellian theory presented in Gentillet's Contre-Machiavel, an examination of the evidence suggests different conclusions. It appears that a number of editions of Machiavelli' works were available in the sixteenth century; Elizabethan prose commentary reveals, often a detailed knowledge of Machiavellian theory; beneath the sensational, legendary accretions there lies in both the prose and the drama an apparently informed and thoughtful critique of Machiavellianism in which the principal charges are those of atheism, amoral egoism, destructiveness and cunning. In Chapter Two the substance of these charges is scrutinised. Some examination of The Prince and The Discourses suggests that the Elizabethans were wholly justified in interpreting Machiavelli's works as they did. In the remaining four chapters the Machiavel is shown to be a peculiar type of villain, characterised by qualities which are essentially those inherent in Machiavelli's doctrines. By examining a wide range of characters and by drawing comparisons between the genuine Machiavellian and other figures, cast in different moulds, the central characteristics of the type are gradually defined. It is shown that although the Machiavel does not always reject God explicitly he is always the materialistic enemy of the God-centred world in which, commonly, the Elizabethan dramatist places him. Despite some apparent affection for others or sudden recantation, the Machiavel while he remains true to type, is an egoist, dedicated to the ruthless and amoral pursuit of personal power and gratification. He is a destroyer of life and of order in the mind, the family , the state and the universe. Finally, in his \politic\" cunning he employs reason in a limited but lethal fashion. Always in the earlier plays the Machiavel is eventually defeated by the forces of righteousness but at the same time he can be understood only when he is recognised as an embodiment of the real and massive threat to Christian civilisation which the Elizabethans discerned in the doctrines of Machiavelli."

Diamond-Blackfan anemia (DBA) is a rare bone marrow failure syndrome usually caused by heterozygous variants in ribosomal proteins (RP) and which leads to severe anemia. Genetic studies in DBA rely primarily on multigene panels that often result in variants of unknown significance. Our objective was to optimize polysome profiling to functionally validate new large subunit RP variants. We determined the optimal experimental conditions for B-cell polysome profiles then performed this analysis on 2 children with DBA and novel missense RPL5 (uL18) and RPL26 (uL24) variants of unknown significance. Both patients had reduced 60S and 80S fractions when compared with an unaffected parent consistent with a large ribosomal subunit defect. Polysome profiling using primary B-cells is an adjunctive tool that can assist in validation of large subunit RP variants of uncertain significance. Further studies are necessary to validate this method in patients with known DBA mutations, small RP subunit variants, and silent carriers.