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Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
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- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
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Notes
- Scott Paul Gordon, Lehigh University, Pennsylvania
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- The Power of the Passive Self in English Literature, 1640–1770
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- Scott Paul Gordon, Lehigh University, Pennsylvania
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2 - “The belief of the people”: Thomas Hobbes and the battle over the heroic
- Scott Paul Gordon, Lehigh University, Pennsylvania
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Summary
Writers such as Hooker, Perkins, Cotton, Crisp or Cromwell treat universal self-interest as a given of the fallen world. Man's will, corrupted by the fall, cannot choose worthily without divine help. “It is impossible that Man, mere fallen Man,” Mandeville's Fable of the Bees (1714–29) claims, “should act with any other View but to please himself.” Denying that, unprompted, individuals could choose virtuous actions, these writers deploy what I have called the passivity trope to imagine a subjectivity which allows individuals to believe that their every action is not self-interested. Of course the assumption of universal self-interest pervades discourses other than those founded on the doctrine of original sin. Thomas Hobbes's articulation of this position so shocked his contemporaries that they installed him, permanently, as its most prominent advocate. “Of the voluntary acts of every man,” his Leviathan (1651) contends, “the Object is some Good to himselfe.” Confronted with ideologies that require individuals to reject selfish and choose disinterested behaviors, Hobbes insists that “till it please God to give men an extraordinary, and supernaturall grace” (L, 211), we will always choose what we imagine will benefit ourselves. Each individual, Hobbes contends, is little more than a “Tennis-Ball,” controlled rather than controlling, ceaselessly batted about by desires and interests. The generous, disinterested behaviors (demanded by the discourse of the heroic, which, I argue below, Hobbes aims to demolish) are well beyond this passive object's capacities.
3 - “For want of some heedfull Eye”: Mr. Spectator and the power of spectacle
- Scott Paul Gordon, Lehigh University, Pennsylvania
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The interpellation of all selves as interested selves, the aim not only of Hobbes's texts but of the social sciences themselves, ensures that all public behavior will be seen as rhetorical. Leviathan's sovereign functions as a permanent observer for whom subjects must tailor their conduct, lapses of which will be punished more swiftly and visibly than by God himself. As we have seen, Hobbes expects that after the sovereign's installation, when subjects act with the sovereign in mind, their behaviors will be legible. “He that keepe's a watchfull or vigilant eie upon that mans Interest whom he is to treate withall,” wrote Samuel Butler, “shall hardly be deceivd with fair Pretenses.” Hobbes promises that the sovereign's capacity to produce legible subjects, each recognizing and acting upon an interested self, will in turn produce social peace. Another view of a culture comprised of atomized, interested selves, however, is evident in the Spectator (1711–12), which also depicts all behavior as rhetorical, designed to satisfy or persuade imagined audiences, and which also shares the desire to produce legible subjects. The Spectator's aim, announced in its fourth paper, to “make both Sexes appear in their Conduct what they are in their Hearts” imagines the possibility of non-rhetorical subjects whose exterior signs will perfectly represent their internal feelings or motives. But the Spectator reveals that the strategies it borrows from Leviathan to achieve this aim – strategies that solicit each subject's interested self – merely provoke the suspicion that beneath public conformity lurk dangerous designs.
Contents
- Scott Paul Gordon, Lehigh University, Pennsylvania
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The Power of the Passive Self in English Literature, 1640–1770
- Scott Paul Gordon
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- 28 March 2002
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Challenging recent work that contends that seventeenth-century English discourses privilege the notion of a self-enclosed, self-sufficient individual, The Power of the Passive Self in English Literature recovers a counter-tradition that imagines selves as more passively prompted than actively choosing. This tradition - which Scott Paul Gordon locates in seventeenth-century religious discourse, in early eighteenth-century moral philosophy, in mid eighteenth-century acting theory, and in the emergent novel - resists autonomy and defers agency from the individual to an external 'prompter'. Gordon argues that the trope of passivity aims to guarantee a disinterested self in a culture that was increasingly convinced that every deliberate action involves calculating one's own interest. Gordon traces the origins of such ideas from their roots in the non-conformist religious tradition to their flowering in one of the central texts of eighteenth-century literature, Samuel Richardson's Clarissa.
1 - “Acted by Another”: agency and action in early modern England
- Scott Paul Gordon, Lehigh University, Pennsylvania
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- The Power of the Passive Self in English Literature, 1640–1770
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- 22 September 2009
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- 28 March 2002, pp 21-53
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Summary
Discussions of agency and autonomy, terms too infrequently distinguished, often share a common assumption: to be the agent of another, rather than a self-determining subject, is an undesirable, anxiety-ridden, and disempowered position. One locus classicus for this assumption is the “Epilogue” to Renaissance Self-Fashioning (1980), which describes an odd plane trip in which Stephen Greenblatt, asked to mouth the words “I want to die,” suddenly realizes his reluctance to “perform lines that were not my own, that violated my sense of my own desires.” This incident reminds Greenblatt of the early modern texts he has been studying: expecting to find that Renaissance “middle-class and aristocratic males” felt that “they possessed … shaping power over their lives,” he discovered instead that in these texts “the human subject itself began to seem remarkably unfree.” This incident led Greenblatt to recognize “this power and the freedom that it implied as an important element in my own sense of myself.” Indeed, in his concluding sentence, Greenblatt confesses his “overwhelming need to sustain the illusion that I am the principal maker of my own identity.” Greenblatt's discomfort at being written by another mirrors the assumption in recent discourse that every loss of self-possession brings a corresponding anxiety or alienation. To be fashioned produces anxiety.
For the writers discussed in this study, however, autonomy or self-sufficiency is the undesirable (and perhaps heretical) position.
Epilogue: “A sign of so noble a passion”: the politics of disinterested selves
- Scott Paul Gordon, Lehigh University, Pennsylvania
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- The Power of the Passive Self in English Literature, 1640–1770
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- 22 September 2009
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- 28 March 2002, pp 212-214
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Summary
Are there objects in mid-century England more complex than tears? Literary texts often display the capacity to fake tears, using this practice (as we have seen) to mark sinister characters. Virtuous characters in Tom Jones (1749) do shed “tender Tears,” but Blifil fakes them (wiping away non-existent tears, not producing false ones) and Mrs. Honour produces them at will: “[S]he found Sophia standing motionless, with the Tears trickling from her Eyes. Upon which [Mrs. Honour] immediately ordered a proper quantity of Tears into her own Eyes.” Nor is this practice evident only in novels. Refusing to be moved by speeches delivered “with weeping eyes,” Cromwell's enemies insist that “he hath teares at will, & can dispense with any Oath or Protestation without troubling his conscience.” A hundred years later the capacity to manipulate tears no longer signals such serious faults (oath-breaking, lack of conscience), but it remains a troubling phenomenon. When in 1779 Hester Thrale coaxed Sophy Streatfield to prove that “she had Tears at command,” Frances Burney watched Streatfield make “Tears come into her Eyes, & [roll] down her fine Cheeks” and then “ran away”: “When I saw real Tears, I was shocked.” Four months later Thrale demands a repeat performance (“Lord, she shall Cry again if you like it”) and Burney records that “two Crystal Tears came into the soft eyes of the S. S., – and rolled gently down her Cheeks! – such a sight I never saw before, nor could I have believed.… indeed, she was smiling all the Time.”
Introduction. “Spring and Motive of our Actions”: disinterest and self-interest
- Scott Paul Gordon, Lehigh University, Pennsylvania
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- The Power of the Passive Self in English Literature, 1640–1770
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- 22 September 2009
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- 28 March 2002, pp 1-20
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Summary
DREAMS OF DISINTEREST
This is a book about the difficulty of belief, a story about late seventeenth-and early eighteenth-century writing that illuminates late twentieth-century writing as well. First and foremost, it traces the struggle of seventeenth- and eighteenth-century writers to reestablish the reality of disinterestedness – of behavior done for others, rather than for self – and to combat those who had argued that all public behavior is self-interested. The powerful critiques of Thomas Hobbes and Bernard Mandeville, reinforced by and reinforcing economic and political changes in Restoration and eighteenth-century England, aim to leave in their wake no space for even the possibility of behavior done for another; they position sincerity, disinterestedness, and virtue not as rare but as non-existent, as empty terms that correspond to no actual behaviors. As George Blewitt complained in 1725, “It is not only that most things are not Virtue, which the World take for such, but the Thing itself, we are told, is ridiculous in Theory, and mischievous in Practice.” Perhaps more than their logical “proofs,” these writers' rhetorical skill – their ability to construe everything through what Paul Ricoeur and Hans-Georg Gadamer call a “hermeneutics of suspicion” – seems to dismantle any criteria that might insulate behaviors from the accusation that they hide self-interest. Faced with this challenge, Restoration and eighteenth-century writers devise complicated strategies to re-convince themselves that disinterestedness is indeed possible.
But this story is not only about a distant time, for the difficulty of believing in disinterestedness persists.
6 - “I wrote my Heart”: Richardson's Clarissa and the tactics of sentiment
- Scott Paul Gordon, Lehigh University, Pennsylvania
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- The Power of the Passive Self in English Literature, 1640–1770
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- 22 September 2009
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- 28 March 2002, pp 182-211
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Few eighteenth-century bodies display the results of the difficulty with which eighteenth-century readers and writers credit disinterested behavior more than Clarissa's. Readers in and of Richardson's Clarissa (1747–48) have portrayed her body as fundamentally rhetorical, its visible signs (blushes and tears) and its literary productions (letters) designed to persuade audiences. After Pamela (1740) had in the spring and summer of 1741 provoked the same phenomena, Richardson complained that “anti-Pamelist” texts had his “whole Purpose inverted” – depicting both his heroine and Richardson himself as cunning manipulators rewarded not for virtue but for calculated deception. If these critics position Pamela's letters less as transparent transcriptions of her heart (“I wrote my Heart,” she claims) than as instruments of persuasion, her “Behavior” less as “artless and innocent” than as that “of an hypocritical, crafty Girl … who understands the Art of bringing a Man to her Lure,” they warn as well that Richardson's “Art” exactly mirrors Pamela's. Richardson “very artfully work'd up” his story to titillate male and female readers – “How artfully has the Author introduced an Image that no Youth can read without Emotion!” – and, like Pamela, “Cloaks” his texts in virtue only to further his interests, to seduce readers and snare a healthy reward. The storm over Pamela showed the ease with which any text can be absorbed into a discourse of universal self interest, “depreciated and debased” in Richardson's phrase, by those whom I call “Mandevillian (mis)readers.”
5 - “Not perform'd at all”: managing Garrick's body in eighteenth-century England
- Scott Paul Gordon, Lehigh University, Pennsylvania
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- Book:
- The Power of the Passive Self in English Literature, 1640–1770
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- 22 September 2009
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- 28 March 2002, pp 153-181
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The previous chapter argued that British moral philosophy, confronted by arguments for universal egoism, deploys the passivity trope to imagine a disinterested self “acted by another,” much like the protestant self. Although grounded in a “Nature” that could restrict its availability, this disinterested self is an enticing enough cultural fiction to encourage many to feel they possess the same natural capacities as their supposed betters. These subjects who seize the capacity to feel may simultaneously disable themselves from recognizing their own “interests” as anything but partial or deviant, but the passivity trope enables these subjects to trust that their actions are disinterested and non-rhetorical. Eighteenth-century acting theory deploys the passivity trope as well to construct the objects it analyzes – actors' bodies – as trustworthy spectacles. Compensating for the unsettling possibility that all individuals can persuasively manipulate all public signs, even apparently “natural” bodily signs, theatrical discourse appropriates the passivity trope in a series of contests surrounding the stage practice of David Garrick, the eighteenth-century stage's premier actor. By means of the passivity trope, acting discourse explains away Garrick's remarkable capacity to transform himself, seemingly at will, into anything at all. This discourse secures his legibility, insisting that exterior sign corresponds to interior feeling, by stripping from Garrick control over his own appearance. This discourse, I argue, not only subjects Garrick to his nerves but also implies that each member of his audience is similarly subjected.
Frontmatter
- Scott Paul Gordon, Lehigh University, Pennsylvania
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- The Power of the Passive Self in English Literature, 1640–1770
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- 22 September 2009
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- 28 March 2002, pp i-viii
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Index
- Scott Paul Gordon, Lehigh University, Pennsylvania
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- The Power of the Passive Self in English Literature, 1640–1770
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- 22 September 2009
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- 28 March 2002, pp 273-279
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4 - “For its own sake”: virtue and agency in early eighteenth-century England
- Scott Paul Gordon, Lehigh University, Pennsylvania
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- The Power of the Passive Self in English Literature, 1640–1770
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- 22 September 2009
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- 28 March 2002, pp 119-152
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In 1705 Samuel Clarke delivered his second set of Boyle Lectures. Robert Boyle's will funded a series of lectures, delivered by a preaching minister or learned divine in a parish church of London, to “prov[e] the Christian religion against notorious Infidels, viz. Atheists, Theists, Pagans, Jews, Mahometans.” Clarke's lectures, which when published announced on their title-page their targets as “Mr Hobbs, Spinoza and their Followers,” challenge Hobbes's claim that, as John Eachard puts it in 1672, “there is nothing either in actions or speeches, in Arts or Sciences, in wit or judgment … that is good and valuable, but it is all upon the accompt of power.” Clarke reassures listeners that “Virtue and Goodness are truly amiable, and to be chosen for their own sakes and intrinsick worth; though a man had no prospect of gaining any particular Advantage to himself, by the Practice of them.” Even pagans defined “Virtue,” Clarke notes, as “that, which, though no Profit or Advantage whatsoever, was to be expected to a Man's self from the Practice of it, yet must without all Controversy be acknowledged to be truly desirable for its own sake alone.” In maintaining that choice can be made without considerations of “Advantage,” Clarke preserves the possibility of disinterested virtue, the deliberate choice to benefit another, which Christianity figures in its founding moment of Christ “freely” sacrificing himself for humankind.
Acknowledgments
- Scott Paul Gordon, Lehigh University, Pennsylvania
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- Book:
- The Power of the Passive Self in English Literature, 1640–1770
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- 22 September 2009
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- 28 March 2002, pp x-xii
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