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Around two-thirds of patients with auditory hallucinations experience derogatory and threatening voices (DTVs). Understandably, when these voices are believed then common consequences can be depression, anxiety and suicidal ideation. There is a need for treatment targeted at promoting distance from such voice content. The first step in this treatment development is to understand why patients listen to and believe voices that are appraised as malevolent.
To learn from patients their reasons for listening to and believing DTVs.
Theoretical sampling was used to recruit 15 participants with non-affective psychosis from NHS services who heard daily DTVs. Data were obtained by semi-structured interviews and analysed using grounded theory.
Six higher-order categories for why patients listen and/or believe voices were theorised. These were: (i) to understand the voices (e.g. what is their motive?); (ii) to be alert to the threat (e.g. prepared for what might happen); (iii) a normal instinct to rely on sensory information; (iv) the voices can be of people they know; (v) the DTVs use strategies (e.g. repetition) to capture attention; and (vi) patients feel so worn down it is hard to resist the voice experience (e.g. too mentally defeated to dismiss comments). In total, 21 reasons were identified, with all participants endorsing multiple reasons.
The study generated a wide range of reasons why patients listen to and believe DTVs. Awareness of these reasons can help clinicians understand the patient experience and also identify targets in psychological intervention.
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.
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.
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.
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.
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.
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.
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’.
With the recent shift in literary studies towards what is often described as a “global Renaissance,” it is hardly surprising that figures of merchants and travelers both in early modern travelogues and plays have come under greater scrutiny as sites for understanding the formation of a fluid English identity, transnational commerce, emergent colonialism, and nation building. What still remains largely unexplored, however, particularly in the context of the East Indies trade, is the impact of this emergent globalization on the bodies of the European women who were closely related to the merchants or factors. While scholarship on plays such as Fletcher's The Island Princess or Dryden's Amboyna emphasizes the roles of both European men and their beloved native women, the white woman still remains a shadowy presence at the fringes of our current academic interest in the early modern spice trade.
This essay seeks to address this gap by turning to the public stage, particularly to a play that explores how the emergent trade with the East Indies appeared to affect the physical and moral complexion of one such European woman. In the trial scene of John Webster's play The Devil's Law-Case (1623), Jolenta, the sister of Romelio, an East Indies merchant enters with “her face colour'd like that of a Moore,” accompanied by two Surgeons, “one of them like a Jew.” Although the assembled people quickly recognize her they still comment on her changed complexion. Ariosto the advocate exclaims, “Shee’s a blacke one indeed” (5.5.40) while Ercole, one of her suitors, wails “to what purpose / Are you thus ecclipst?” (5.5.57–58). Of course, Jolenta’s transformation is temporary and apparently superficial; yet her blackening appears to gesture towards deeper concerns regarding the impact of the East Indies trade, particularly on a woman who has never left her home or sailed the high seas to profit from pepper, cinnamon, cardamom and mace.
Gods apprentice is a jorneyman: he must allwayes learne the mystery of his profession, & walking forward aime hard to the marke for the price of his high calling. as the teacher in Gods schoole must give Line upon Line, precept upon precept: so to the scholler likewise nulla dies sine linea, no day must pass without a new lesson, as Cato said, so Gods child must grow old every day learning many things. And so in practise also. he must adde to his faith vertue, | & to plowing, sowing. Like Charles the fifth, plus ultra must be his motto: he must go from strength to strength untill he appeare be=fore the Lord in Sion. And that because, he is leaving his abode in this world but an im=perfect pilgrime. he is not what, he is not where he should be … [There are those who] ‘looke behind them, that turne their face in the day of battell, & quite give over Gods husbandry’, [those] ‘that forget their first love who though they forsake not the plough yet are they idle companions that do the worke of the Lord negligently … [For them] it had beene better never to have knowne the way of righ=teousness then that they should bee like a dog to his vomit & a sow to wallowing in the mire.
Analyses of Antony and Cleopatra have long noted the dialectical opposition between Rome and Egypt, an opposition that sets up a concomitant correspondence between geography and gender. Although recent scholarship has destabilized the categories, Rome has traditionally represented the masculine—solid, controlled, bounded—while Egypt is feminine—fluid, unchecked, limitless, and thus constantly generating. Egypt in the play evokes an elemental fecundity that is spontaneous and natural at the same time that it is corrupting and degenerate, “dungy,” in Antony's words. Further, the connection between Cleopatra and Egypt is inextricable in the play; she exists in metonymic relation to her country, the word “Egypt” used no less than seven times to refer to her directly. Picking up on Janet Adelman's argument that the play constructs Cleopatra as “one with her feminized kingdom as though it were her body,” this essay examines the complex idea of Egyptian earthiness in connection with Cleopatra and her fertile/infertile body by reading it in conjunction with various theories of reproduction—what the Renaissance called generation. Specifically, I seek to show how the trope of spontaneous generation allows Shakespeare to expand his interrogation of procreation in the play, blurring gender boundaries as he does so.
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.
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:
Renaissance Papers collects the best scholarly essays submitted each year to the Southeastern Renaissance Conference. The 2012 volume opens with two essays on sexuality in Elizabethan narrative poetry: on homoeroticism in Spenser's Faerie Queene and on Shakespeare's "swerve" into Lucretian imagery in Venus and Adonis. The volume then turns to Renaissance drama and its links to the wider culture: the commodification of spirit in Marlowe's Doctor Faustus, Shakespeare's evocation of the Acts of the Apostles in The Comedy of Errors, "summoning" in Hamlet and King Lear, discourses of procreation and generation in Antony and Cleopatra/, trade and gender in John Webster's Devil's Law-Case, and an examination of street scenes in Romeo and Juliet in relation to Paul's Cross Churchyard, the hub of the London bookselling market in the early modern period. The volume closes with essays on seventeenth-century literature and literary culture: on the "puritan logic" of the elder Andrew Marvell in his famous son's poem "To His Coy Mistress," on the "sociable lexicography" of a Royalist polymath attempting to reconcile with the English Commonwealth, and on the underestimated roles of Urania in Milton's Paradise Lost. Contributors: David Ainsworth, Thomas W. Dabbs, Sonya Freeman Loftis, Russell Hugh McConnell, Robert L. Reid, Amrita Sen, Susan C. Staub, Emily Stockard, Nathan Stogdill, Christina A. Taormina, Emma Annette Wilson. Andrew Shifflett and Edward Gieskes are Associate Professors of English at the University of South Carolina, Columbia.