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Current scholarship on Anne Askew has tended to disparage the editorial tactics of John Bale, her first editor, as intrusive and distorting. In contrast, the reprinting of her text by John Foxe, in his “Book of Martyrs, “ has been commended for its lack of editorial intervention. Yet afresh consideration of Foxes work with Askew's narrative suggests that Foxe's shaping force in the text was as strong as Bale's, if more subtle. Furthermore, attempts to locate Askew's authorial agency within one text or the other impose modern ideas about authorship on a period in which such ideas were still being formed.
Novel approaches to improving disaster response have begun to include the use of big data and information and communication technology (ICT). However, there remains a dearth of literature on the use of these technologies in disasters. We have conducted an integrative literature review on the role of ICT and big data in disasters. Included in the review were 113 studies that met our predetermined inclusion criteria. Most studies used qualitative methods (39.8%, n=45) over mixed methods (31%, n=35) or quantitative methods (29.2%, n=33). Nearly 80% (n=88) covered only the response phase of disasters and only 15% (n=17) of the studies addressed disasters in low- and middle-income countries. The 4 most frequently mentioned tools were geographic information systems, social media, patient information, and disaster modeling. We suggest testing ICT and big data tools more widely, especially outside of high-income countries, as well as in nonresponse phases of disasters (eg, disaster recovery), to increase an understanding of the utility of ICT and big data in disasters. Future studies should also include descriptions of the intended users of the tools, as well as implementation challenges, to assist other disaster response professionals in adapting or creating similar tools. (Disaster Med Public Health Preparedness. 2019;13:353–367)
Amid the great Protestant martyrologies of the mid-sixteenth century, Heinrich Pantaleon's Martyrvm historia (1563) has been comparatively overlooked. This article argues that Pantaleon's martyrology acted as a capstone to the narrative framework of Protestant suffering and resistance. Pantaleon's command of vernacular languages gave him access to a wider range of material than other martyrologists, material which his Latin text made accessible to learned readers across Europe. This article also examines the collaboration between Pantaleon and John Foxe, which directly inspired Pantaleon's martyrology and enabled Foxe to give a cohesive, trans-European account of Protestant martyrs in his Acts and monuments.
Cognitive behavioural therapy (CBT) for major depression is an effective treatment, but outcomes for complex cases, with co-occurring biological, psychological and social factors, are variable. Complexity factors can cause treatment to become diffuse, disorganized and over-complicated. At Step 3, disorder-specific protocols should be provided with therapy kept as simple as possible and delivered responsively, e.g. barriers to treatment should be tackled, ensure the client is well-prepared and seek to form a strong therapeutic alliance. At Step 4, if disorder-specific protocols have been ineffective, the priority is to formulate how complexity factors are interacting with the client's depression. An individualized formulation is used to carefully target these interactions. The treatment is still evidence-based and simple at the point of delivery, but there is greater emphasis on case-level interactions that are unique to each individual. Case examples are used to illustrate both approaches.
Although the reign of Mary i (1553–8) was a tumultuous and eventful one, for over four hundred years there was little debate about it or about the queen's efforts to restore Catholicism to England. The reign was almost universally perceived as poor, nasty, brutish and short-lived and the restoration of Catholicism was believed to have been doomed to failure, both because the burning of heretics offended English sensibilities and because Protestantism was already so deeply embedded in England that it could not be uprooted. Yet towards the end of the twentieth century, the tectonic plates of historical research began to shift and the resulting tremors altered the historiographical landscape of Mary's reign, and indeed of the English Reformation.
This paper presents the first major data release and survey description for the ANU WiFeS SuperNovA Programme. ANU WiFeS SuperNovA Programme is an ongoing supernova spectroscopy campaign utilising the Wide Field Spectrograph on the Australian National University 2.3-m telescope. The first and primary data release of this programme (AWSNAP-DR1) releases 357 spectra of 175 unique objects collected over 82 equivalent full nights of observing from 2012 July to 2015 August. These spectra have been made publicly available via the WISEREP supernova spectroscopy repository.
We analyse the ANU WiFeS SuperNovA Programme sample of Type Ia supernova spectra, including measurements of narrow sodium absorption features afforded by the high spectral resolution of the Wide Field Spectrograph instrument. In some cases, we were able to use the integral-field nature of the Wide Field Spectrograph instrument to measure the rotation velocity of the SN host galaxy near the SN location in order to obtain precision sodium absorption velocities. We also present an extensive time series of SN 2012dn, including a near-nebular spectrum which both confirms its ‘super-Chandrasekhar’ status and enables measurement of the sub-solar host metallicity at the SN site.
On New Year’s Day, 1578, Sir John Langley, a wealthy alderman of the City of London, lay dying. Present at his deathbed were three of the most eminent preachers in the capital: Robert Crowley, who held four London livings, Alexander Nowell, the dean of St Paul’s cathedral and John Foxe, the martyrologist. As Langley’s life ebbed away, Foxe went up to the dying man and ‘used both godly councell unto him and some devote prayers’. Since Langley could no longer speak, Foxe urged him to signify his belief in Christ by holding up his hands:
Ymmediatly so he did and then … Mr Fox was verie gladd, and told him that he had done ynoughe to show him self both a Crystian and to depend only uppon the merittes of Chrystes passione.
On 20 January 1574, at about 7.00 p.m., Alexander Nyndge, one of the sons of William Nyndge, a gentleman of Herringwell, Suffolk, suddenly went into violent paroxysms. Edward Nyndge, Alexander’s brother, intervened. Edward was a Cambridge graduate and a former fellow of Gonville and Caius, and his University education had apparently prepared him for just such an emergency. He immediately declared that Alexander was possessed by an evil spirit and summoned the villagers to come and pray for his brother’s recovery. As the praying continued, Alexander’s convulsions grew worse; a half dozen men had to hold him in his chair. Meanwhile the onlookers were praying extemporaneously. Suddenly someone invoked both God and the Virgin Mary. Edward pounced on this remark and admonished the crowd that such prayers offended God. The evil spirit, in a voice ‘much like Alexanders voice’, chimed in, endorsing the propriety of the prayer. But ‘Edward made answere and said thou lyest, for ther is no other name under Heaven, wherby we may challenge Salvacion, but thonly name of Ihesus Christe’. This point settled, Edward proceeded to organize his brother’s exorcism.
Readers of the second edition of John Foxe’s Acts and Monuments, or any of the subsequent editions of that massive history of the persecutions inflicted on the Church, popularly known as ‘Foxe’s Book of Martyrs’, would have found a coherent, lucid description, filled with circumstantial and often dramatic details, of the ordeals of James Bainham. According to this account, James Bainham, a member of the Middle Temple and the son of a Gloucestershire knight, was accused of heresy in 1531, arrested, and transported to Lord Chancellor More’s house in Chelsea. There he was tied to a tree in More’s garden and whipped; subsequently he was taken to the Tower and racked in More’s presence. Eventually, after repeated interrogations and under the threat of burning, Bainham abjured and did penance at Paul’s Cross. Yet Bainham’s conscience tormented him and, a little over a month after his release, he prayed for God’s forgiveness before an evangelical congregation, meeting secretly in a warehouse in Bow Lane. A week later, Bainham stood up on his pew in St Austin’s church, clutching a vernacular New Testament and William Tyndale’s Obedience of a Christian Man to his chest and tearfully declared that he had denied God. He prayed for the congregation’s forgiveness and exhorted them to die rather than to submit as he had done. If this defiance was not sufficiently public, Bainham sent letters proclaiming his doctrinal convictions to the Bishop of London and others. Rearrested and re-examined, he was inevitably condemned to death as a relapsed heretic.
In this overview we will examine drug target identification, a key early step in the drug discovery and development process and a significant and interesting challenge. Today, target identification is akin to solving a very difficult puzzle using all of the information that we can generate or have available to identify those points of intervention within a highly interconnected dynamic system that will improve a disease state. I see our current approaches as surrogates for a true understanding of the molecular basis of disease, which when achieved should clearly reveal points for therapeutic intervention. Before we attempt to discuss methods used for target identification, we will begin by exploring what a target is and what hurdles a potential target must overcome to be successfully “drugged.” We will examine how the targets from currently approved drugs have been elucidated. A brief historical perspective on target identification will focus on how advances in our understanding of biology have driven our progress. Finally, we will review current directions in selecting drug targets and in understanding disease in an integrated and multi-scale manner.
Drug development is a long and intricate process but one that is quite predictable. The development of a drug usually begins with the selection of a molecular target for modulation by a small molecule or biological compound with the goal of safely improving a disease phenotype. The target concept can be logically extended to include plant biology and perhaps synthetic biology. Crop improvement by increasing yield, quality (i.e., amino acid composition), and insect or drought resistance require identification of points for molecular intervention to bring about the desired phenotype. Similarly, synthetic biology projects require the manipulation of existing biological systems or ultimately creation of modified biological systems, and require a very high level understanding of the genetic and molecular processes involved in producing the desired outcome without destabilizing the system. Our review here will focus on target identification for the purpose of drug discovery and development to address unmet medical need.
Drug discovery research is performed at many levels: in the pharmaceutical industry, in biotechnology companies, government laboratories, research foundations, increasingly in computation-based companies, and even larger generic drug companies. In terms of dollars and number of drugs approved, the pharmaceutical industry has been the largest sector in drug discovery to date.
The need for computational methods to characterize a new therapeutic compound's potential secondary pharmacology early in the drug development process is becoming increasingly important. The United States Food and Drug Administration (FDA) acceptance rate of new chemical entities (NCE) used in the treatment of human diseases has been unchanged over the past 60 years despite dramatically increasing investment in the past two decades (Munos, 2009). Multiple factors have contributed to this decrease in NCE approvals per unit investment including increased FDA standards, therapeutic approaches addressing more complex diseases, as well as issues with patient pharmacogenomic diversity.
As more small molecules are designed using combinatorial libraries and computational/structural biology methods, new and disparate forms of chemical matter are being produced for NCE consideration. These novel compounds do not have a history of associated side-effect profiles that established chemical matter have (e.g., penicillin analog). A retrospective analysis shows that nearly 30% of all new NCE failures in the year 2000 were attributed to problems with clinical toxicology, far more than any other single reason (DataMonitor, pharmaceutical report). From 2008 to 2010 there were 108 reported Phase II failures; of those reporting reasons for failure, 19% were reported due to clinical or preclinical safety issues (Arrowsmith, 2011a). At later stages in the development pipeline, combined successes in Phase III and submission have fallen to approximately 50%, with 83 failures between 2007 and 2010. Twenty-one percent of the failures across all therapeutic areas are due to safety issues (Arrowsmith, 2011b). Accordingly, while some progress has been made, it is critical that compound safety issues be addressed as early in the discovery pipeline as possible to reduce costly late-stage attrition.
The basic premise of drug toxicology is simple, but is complicated by the sheer size and complexity of the human proteome (Waring et al., 2015). Compounds, or their metabolites, that interact with the desired target protein can also bind to and alter the activity of other “off-target” proteins. Many times, these proteins can have their activity altered without significantly affecting normal human physiology. However, a protein's altered activity can lead to a change in a metabolic or signaling pathway critical to normal physiological function and hence to toxicological effects. Thus, identification of these “off-target” proteins and understanding the role they play in the human body is important.
This essay considers the life, death, and afterlife of William Cowbridge a religious eccentric executed for heresy in 1538. It explores the significance of his religious beliefs, which became the source of a heated controversy between the Protestant martyrologist John Foxe and the Catholic polemicist Nicholas Harpsfield. The case casts light on a range of issues, including the dynamic between Protestant and Catholic controversialists, the use of the label of ‘madness’ in argument, and the value of archival documentation alongside the use of oral sources in Reformation-era polemic. It also yields insight into Thomas Cromwell’s authority over the English Church during the late 1530s, and highlights his position among Henrician evangelicals as a source of influence and aid. Finally, it offers a critique about interpretations of early modern belief and the designation of the label ‘Lollard’.
In the sticky, sweet, and sweaty world in which Shakespeare situates his Venus and Adonis, something has gone awry. According to Venus, “Nature” is “at strife” with herself for having made Adonis. By “Nature” Venus is, of course, referring to herself. Compared to the Venus of book 10 of Ovid's Metamorphoses—a goddess who makes men and women fall in love, who brings stone to life, and whose magical doves transport her anywhere she wishes to go—Shakespeare's Venus is, by comparison, a much more natural being. A creature of the senses, most especially smell, Shakespeare's Venus does not so much manipulate the natural world as bond with it. She experiences heightened, animal-like sensibilities that allow her to commune with Adonis's horse and to imagine herself as the earthbound and hunted Wat the Hare.
But why would Shakespeare strip Ovid's goddess of her supernatural powers and drive her so literally down to earth? The answer, I would suggest, is that Venus and Adonis traces its ancestry not only to Ovid's Metamorphoses but also to Lucretius's De Rerum Natura. Consider the powerful invocation to Venus with which Lucretius begins his great philosophical poem on “the nature of things”: “Venus, power of life, it is you who beneath the sky's sliding stars inspirit the ship-bearing sea, inspirit the productive land.
The more we learn about the physical environments and associated print culture of Paul's Cross Churchyard and the St. Paul's precinct of the City of London, the more we can understand how Shakespeare's plays were popularly received. It may seem that Shakespeare avoids direct reference to contemporary London—at least in comparison to Jonson, Middleton, and Marston, who satirize actual persons in their city comedies—but his references are more stealthy and intricate than theirs, and they are quite important in what they can tell us about the connections between drama and urban contexts during the Elizabethan period. Here I will focus on some colloquial banter between Romeo and Mercutio in Romeo and Juliet. Of course this banter, which first saw print in quarto versions of the plays in 1597 and 1599, belongs to the streets of London, not distant to Verona. More specifically, it points to the attitudes of the young gallants who contemporary records tell us were common in the St. Paul's precinct during the 1590s.
Two competing but also mutually beneficial cultural forces met within Paul's Cross Churchyard. The first involved dramatic preaching events and public proclamations, which promoted and were promoted by religious print sold by the booksellers. In many cases these booksellers surrounded the pulpit, and the fronts of their shops physically echoed the sounds of sermons coming from the pulpit. The second force was the new market for pleasure reading that flourished in surprisingly close proximity to religious expression.
In act 4 of The Comedy of Errors, Adriana, in response to her husband's wildly erratic behaviour, recruits one Doctor Pinch to cure his apparent madness. Antipholus of Ephesus is of course not really mad at all, but understandably frustrated and confused with the events of the day, which have seen him locked out of his own house and accused of failing to pay for valuables that he actually never received, thanks to a series of misunderstandings involving his identical twin, Antipholus of Syracuse. When Antipholus of Ephesus refuses to cooperate with his wife's well-intentioned intervention, Doctor Pinch attempts an exorcism to drive away the demons which he supposes to possess him:
I charge thee, Satan, housed within this man,
To yield possession to my holy prayers
And to thy state of darkness hie thee straight:
I conjure thee by all the saints in heaven!
Of course, Pinch's attempted exorcism fails, because there is no Satan to exorcise, and Antipholus becomes so angry that Adriana has him forcibly bound and taken away in Pinch's custody. In a later scene a messenger reports that Antipholus and his servant Dromio have gnawed through their bonds and escaped and then captured and tormented the hapless Doctor Pinch, burning off his beard “with brands of fire,” putting it out again with “Great pails of puddled mire,” and then preaching patience to him while cutting him with scissors and concludes that “unless you send some present help, / Between them they will kill the conjurer” (5.1.172, 74–76, 177–78).
In John Shawcross's book The Development of Milton's Thought: Law, Religion, and Government, he quotes that famous phrase from Milton, “fit audience, though few.” I was brought up short while reading because this quotation does not include an ellipsis. Can even Shawcross nod? I was reassured when I realized that he had not cited book and line numbers for the quotation; he was simply quoting an oft-used phrase rather than Paradise Lost itself. I thus felt better about John, but continued to be troubled by the broader implications of “fit audience … though few,” with or without the ellipsis. Here I shall argue that the ellipsis eliminates a central element, in the line and the poetic sentence and in terms of Milton's own concerns about the fate of his text. And what scholars so often omit by typifying Milton's audience using this phrase is the place of the ineffable Spirit of God in the communion or community of believers.
I shall dispense with the simple part first: how often is the ellipsis used, and what does it skate over? The phrase appears in the invocation to Book 7 of Paradise Lost: