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1
Davidson, Ryan J. "Transatlantic Intersections: The Role of Ralph Waldo Emerson in the Dissemination of Blakean Thought into the Poetry of Walt Whitman." Hawliyat 17 (July 11, 2018): 33–50. http://dx.doi.org/10.31377/haw.v17i0.66.
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Whitman quoted no one in his poetry, at least not directly, as Matt Miller convincingly mgues in Collage of Myself However, Whitman was not above making use of the work of other writers in his poetry. It is through Whitman's early reading in conjunction with his collage approach to composition that he came to create Leaves of Grass as something which appears wholly original, but which resonates with so many echoes. It is often argued that Ralph Waldo Emerson is one of the most important influences on Whitman 's Leaves of Grass. The extent and significance of Emerson 's influence has been a subject of inquiry' since the advent of Whitman scholarship. This text will focus on Emerson's essays and lectures as the main influences on Whitman which can be read as providing a mediating influence between Blake and Whitman.
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Goryachok, K. L. "Dziga Vertov and Walt Whitman: Poetic Image in Documentary Films." Discourse 8, no. 1 (February 25, 2022): 51–63. http://dx.doi.org/10.32603/2412-8562-2022-8-1-51-63.
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Introduction. The article is devoted to the little-studied issue of the influence of the American poet Walt Whitman on the work of the Soviet film director Dziga Vertov. The creative world of films and literary experiences of the documentary filmmaker is largely inspired by the images of American poet.Methodology and sources. On the basis of Vertov`s scripts, poems and archival documents, author analyzes the phenomenon of the director`s dialogue with Whitman and his poetry. In a comparative analysis of the aesthetics of the two artists, revealed that the philosophical ideas and imaginative system of the American poet were objects of artistic reflection on Vertov`s documentary films.Results and discussion. The article analyzes the leitmotifs of the work of Dziga Vertov, which, according to the author, were born under the great influence of the poetry of Walt Whitman. The imagery and ideas of the American poet`s works emerged in the director`s texts in the early 1920s. In his first manifestos Vertov introduced the image of an “electric man”, which in many ways correlates with the analogous one in Whitman`s lyrics. The author also points out that the Old Testament Adam appears in the texts and verses of Vertov under the direct influence of the American. The article examines the model of state and society in the works of Vertov and Whitman. The author finds similarities between the two artists in relation to the individual, the desire for equality and emancipation, the search for a spiritual principle in collectivism. The images of Lenin and Lincoln are analyzed separately. The semantic parallels between them in the poetics of the Vertov and Whitman are revealed and shows their direct comparisons in the genre, imagery and approaches.Conclusion. Analysis and comparison of images and motives of the work of Dziga Vertov and Walt Whitman allows to reveal new facets of the artistic world of the Soviet film director. The author notes that the ideological basis of his paintings often hid genuine creative intensions to search for intertextuality, to reveal the poetic image in documentary film.
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Aspiz, Harold. "Reynolds, David S. Walt Whitman [review]." Walt Whitman Quarterly Review 22, no. 4 (April 1, 2005): 203–4. http://dx.doi.org/10.13008/2153-3695.1775.
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M. Lazić-Gavrilović, Aleksandra. "CRNJANSKI – FREILIGRATH – WHITMAN: CONNECTIONS AND INFLUENCES." Филолог – часопис за језик књижевност и културу 12, no. 24 (December 30, 2021): 342–57. http://dx.doi.org/10.21618/fil2124342l.
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This paper seeks to shed light on Ferdinand Freiligrath`s and Walt Whitman`s impact upon Miloš Crnjanski`s early political and poetological reflections. It is interesting that the Serbian poet and writer, who rarely and reluctantly spoke about his literary role models, mentions the German poet Ferdinand Freiligrath twice in his autobiographical work Ithaca and Comments, claiming he identified with him during his youth. Although obvious connections can be found in political ideas and revolutionary aspirations shared by the two poets, Freiligrath's significance seems to lie in the fact that he introduced Walt Whitman to the German literary audience and thus undoubtedly influenced the development of modern poetry.
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Tuma, J. "A New Proof of Whitman′s Embedding Theorem." Journal of Algebra 173, no. 2 (April 1995): 459–62. http://dx.doi.org/10.1006/jabr.1995.1097.
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Miller, Matt. "Walt Whitman and Abram S. Hewitt: A Previously Unknown Connection." Walt Whitman Quarterly Review 29, no. 2-3 (January 1, 2012): 96–99. http://dx.doi.org/10.13008/2153-3695.2013.
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Chandran, K. Narayana. "T. S. Eliot's Ghostly Compound: Coleridge and Whitman inLittle GiddingII." ANQ: A Quarterly Journal of Short Articles, Notes and Reviews 10, no. 1 (January 1997): 26–31. http://dx.doi.org/10.1080/08957699709600308.
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Dugan, Frank M., and Dean A. Glawe. "First Report of Powdery Mildew on Dipsacus sylvestris Caused by Sphaerotheca dipsacearum in North America." Plant Health Progress 7, no. 1 (January 2006): 54. http://dx.doi.org/10.1094/php-2006-0607-02-br.
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Common teasel (Dipsacus sylvestris) is a European species introduced into North America, and is now widely established and regarded as a noxious weed. In October 2005, a powdery mildew was observed on D. sylvestris in two locations in Pullman, Whitman Co., WA. Examination of diseased material confirmed that the causal agent was S. dipsacearum. This report provides the first documentation of S. dipsacearum on D. sylvestris in North America. Accepted for publication 20 April 2006. Published 7 June 2006.
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Bauerlein, Mark. "Reynolds, David S., ed., A Historical Guide to Walt Whitman [review]." Walt Whitman Quarterly Review 18, no. 3 (January 1, 2001): 147–49. http://dx.doi.org/10.13008/2153-3695.1648.
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Heryford, Ryan. "Book Review: Jane Bennett s influx efflux: writing up with Walt Whitman." Ecocene: Cappadocia Journal of Environmental Humanities, Cappadocia University 1, no. 1 (2) (December 29, 2020): 109–13. http://dx.doi.org/10.46863/ecocene.7.
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Badenhausen, Richard. "In Search of "Native Moments": T. S. Eliot (Re)Reads Walt Whitman." South Atlantic Review 57, no. 4 (November 1992): 77. http://dx.doi.org/10.2307/3199838.
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Burbick, Joan, and James Olney. "The Language(s) of Poetry: Walt Whitman, Emily Dickinson, Gerard Manley Hopkins." American Literature 66, no. 1 (March 1994): 167. http://dx.doi.org/10.2307/2927451.
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Shively, Charley. "Fone, Byrne R. S. Masculine Landscapes: Walt Whitman and the Homoerotic Text [review]." Walt Whitman Quarterly Review 10, no. 2 (October 1, 1992): 84–86. http://dx.doi.org/10.13008/2153-3695.1361.
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Pokrivčák, Anton. "Deconstruction, Walt Whitman, and the Purpose of Literary Education." International Journal on Language, Literature and Culture in Education 4, no. 2 (November 1, 2017): 68–75. http://dx.doi.org/10.1515/llce-2017-0010.
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AbstractThe article explores the purpose of literary theory, and, consequently, literary education at the beginning of the twenty-first century. It first discusses some of the ideas of Paul de Man for whom literary scholarship is challenged by the incompatibility between the nature of the object of literary theory and the methods used to analyse it. Then the author briefly traces some other ideas regarding the nature of literature and their reflection in establishing the purpose of literary education. A particular emphasis is paid to a re-evaluation of the universality of Walt Whitman´s message, as expressed in his “Song of Myself,” under the circumstances of contemporary ideological and cultural struggles.
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Folsom, Ed. "Reynolds, David S., ed., Walt Whitman, Leaves of Grass: The 150th Anniversary Edition [review]." Walt Whitman Quarterly Review 22, no. 4 (April 1, 2005): 205–6. http://dx.doi.org/10.13008/2153-3695.1776.
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Huttunen, Tomi. "Montage in Russian Imaginism: Poetry, theatre and theory." Sign Systems Studies 41, no. 2/3 (November 7, 2013): 219–29. http://dx.doi.org/10.12697/sss.2013.41.2-3.05.
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The article discusses the concept of montage as used by the Russian Imaginist poetic group: the montage principle in their poetry, theoretical writings and theatre articles. The leading Imaginist figures Vadim Shershenevich and Anatolij Mariengof were active both in theorizing and practising montage in their oeuvre at the beginning of the 1920s. Shershenevich’s application of the principle in poetry was called “image catalogue”, a radical poetic experiment in the spirit of both Walt Whitman and Sergei Eisenstein. Mariengof ’s main contribution to the montage poetics was his first fictional novel The Cynics (1928). The article also discusses the Imaginists’ writings on the essence of theatre as an autonomous art form – Shershenevich’s actitivy in the OGT (Experimental Heroic Theatre) and Mariengof ’s participation in the work of the MKT (Moscow Kamerny Theatre).
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REEVES, GARETH. "Songs of the Self: Berryman's Whitman." Romanticism 14, no. 1 (April 2008): 47–56. http://dx.doi.org/10.3366/e1354991x08000093.
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John Berryman's The Dream Songs and Walt Whitman's Song of Myself: the collocation sounds improbable, the former with their formal constrictions and regularities, their ironies and tensions, as well as their angularities, abruptnesses and disruptions, the latter free-form, open-ended, fluid, rhetorically fluent. Furthermore the collocation sounds unlikely in view of the fact that Berryman shared his generation's general, often knee-jerk, suspicion of Romanticism and ‘the romantic’ (the sliding back and forth in his prose between capital and lower-case ‘r’ signifying the kind of assumptions underlying the suspicion). The suspicion went with the territory, which was occupied by the forces of the New Criticism and the critical weaponry of T. S. Eliot, especially in the American academy (Berryman was an academic). (We have since learnt to question the New Criticism's anti-Romantic claims, and, even more, Eliot's championing of what was then called the ‘Classical’ over the ‘Romantic’ – but that is another story.)
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KOROSTELEVA-POLGLASE, ELENA A. "The European Neighbourhood Policy in Perspective: Context, Implementation and Impact - Edited by R.G. Whitman and S. Wolff." JCMS: Journal of Common Market Studies 49, no. 2 (February 2, 2011): 498. http://dx.doi.org/10.1111/j.1468-5965.2010.02142_14.x.
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DJIGUIMKOUDRE, Nathalie. "A Historical Development of Contrastive Analysis: A Relevant Review in Second and Foreign Language Teaching." International Journal of Education (IJE) 8, no. 4 (December 30, 2020): 81–96. http://dx.doi.org/10.5121/ije.2020.8408.
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Contrastive analysis (CA) was primarily used in the 1950’s as an effective means to address second or foreign language teaching and learning. In this context, it was used to compare pairs of languages, identify similarities and differences in order to predict learning difficulties, with the ultimate goal of addressing them (Fries, 1943; Lado, 1957). Yet, in the 1980’s and 1990’s the relevance of CA has been disputed. Many studies have pointed out the limit of CA with respect to its weak and strong versions (Oller and Ziahosseiny, 1970), (Wardhaugh, 1970) (Brown, 1989), (Hughes, 1980), (Yang, 1992), and (Whitman and Jackson, 1972). To answer the limits of CA with regards to its weak, strong, and moderate versions, many language teachers used CA with a new approach. Kupferberg and Olshtain (1996), James (1996), and Ruzhekova-Rogozherova (2007). Here, salient contrastive linguistic input (CLI) is presented to learners for an effective noticing. Yet, mere exposition of contrastive linguistic input to learners may not be enough for effective acquisition to occur. Hence, Djiguimkoudre (2020) proposed structured phonemic awareness activities to further strengthen such contrastive salient linguistic input when phonetics and phonology are involved. When grammar is involved, the processing instruction (PI) model of Lee and VanPatten (2003) is recommended since the types of activities that result in PI are believed to incite effective noticing for intake.
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Han, Chung-hye, Kyeong-min Kim, Keir Moulton, and Jeffrey Lidz. "Null Objects in Korean: Experimental Evidence for the Argument Ellipsis Analysis." Linguistic Inquiry 51, no. 2 (March 2020): 319–40. http://dx.doi.org/10.1162/ling_a_00342.
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Null object (NO) constructions in Korean and Japanese have received different accounts: as (a) argument ellipsis ( Oku 1998 , S. Kim 1999 , Saito 2007 , Sakamoto 2015 ), (b) VP-ellipsis after verb raising ( Otani and Whitman 1991 , Funakoshi 2016 ), or (c) instances of base-generated pro ( Park 1997 , Hoji 1998 , 2003 ). We report results from two experiments supporting the argument ellipsis analysis for Korean. Experiment 1 builds on K.-M. Kim and Han’s (2016) finding of interspeaker variation in whether the pronoun ku can be bound by a quantifier. Results showed that a speaker’s acceptance of quantifier-bound ku positively correlates with acceptance of sloppy readings in NO sentences. We argue that an ellipsis account, in which the NO site contains internal structure hosting the pronoun, accounts for this correlation. Experiment 2, testing the recovery of adverbials in NO sentences, showed that only the object (not the adverb) can be recovered in the NO site, excluding the possibility of VP-ellipsis. Taken together, our findings suggest that NOs result from argument ellipsis in Korean.
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Burke, Ian C., Joseph P. Yenish, Dennis Pittmann, and Robert S. Gallagher. "Resistance of a Prickly Lettuce (Lactuca serriola) Biotype to 2,4-D." Weed Technology 23, no. 4 (December 2009): 586–91. http://dx.doi.org/10.1614/wt-09-002.1.
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Dose-response experiments were conducted on a biotype of prickly lettuce collected from Whitman County, WA, to determine the level of resistance to 2,4-D. Initially, progeny of prickly lettuce that survived two applications of glyphosate and 2,4-D in mixture were collected to determine if antagonism of the 2,4-D or glyphosate was occurring. Prickly lettuce survival was determined to not be due to antagonism of 2,4-D or glyphosate when the two herbicides were applied in mixture. The doses required to reduce growth 50% (GR50) for resistant and susceptible field-collected prickly lettuce were 150 and 6 g ae/ha 2,4-D, respectively, indicating the resistant biotype was 25 times more resistant to 2,4-D than the susceptible biotype. The resistant biotype expressed injury but produced regrowth following application. A dose of 2,4-D at 220 g/ha was required to reduce regrowth frequency 50% (FR50) for resistant field-collected prickly lettuce. Regrowth was also observed with the susceptible biotype, although the FR50 was much lower (10 g/ha), resulting in an R/S ratio of 22 based on the respective FR50 values. A rate of 4,300 g/ha 2,4-D (10 times the maximum labeled rate in wheat) was required to reduce the regrowth frequency in the resistant biotype to zero.
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Viswanathan, Uma Maheswari, and Sangeetha K. "Voice of the East in Eliot and Oppenheimer." BL College Journal 5, no. 2 (December 2023): 85–91. http://dx.doi.org/10.62106/blc2023v5i2e8.
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This paper presents the influence of the mystic East in providing answers to some of the daunting ethical questions that haunted Westerners during the era of world wars. T S Eliot and Oppenheimer who admits the influence of Waste Land on him are taken for the study. Bhagavad Gita the emblematic Sanskrit text that appears in the epic Mahabharata, Vedas, and Upanishads has influenced poets and philosophers like Whitman, Emerson, Thoreau, Eliot, etc. as well as scientists like Oppenheimer, Heisenberg, Schrodinger, Tesla, etc. The references to Sanskrit texts cannot be taken as mere decorations or indulgence in exoticism; the messages are organically incorporated into their words, actions, and whole lives. In ‘The Waste Land’, the Upanishad is quoted explicitly while the theme of the Bhagavad Gita is used implicitly in the juxtaposition of life and death and treatment of sensual pleasures and means to control senses. Karmayoga or doing one’s duty in a detached manner gave strength to Oppenheimer who directed the project of building the Atomic Bomb which he knew would be used on the enemies. The message of Lord Krishna in Gita gave him the notion of duty/dharma and renunciation of the fruits of his action gave him the thrust to make a weapon of mass destruction.
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Wala, Michael. "Whitman, James Q.: Hitler’s American Model. The United States and the Making of Nazi Race Law, 224 S., Princeton UP, Princeton, NJ/Oxford 2017." Neue Politische Literatur 64, no. 2 (May 24, 2019): 416–18. http://dx.doi.org/10.1007/s42520-019-00092-6.
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Bouckovalis, George. "Discussion of “Drained Permanent Deformation of Sand Due to Cyclic Loading” by Ching S. Chang and Robert V. Whitman (October, 1988, Vol. 114, No. 10)." Journal of Geotechnical Engineering 116, no. 8 (August 1990): 1269–70. http://dx.doi.org/10.1061/(asce)0733-9410(1990)116:8(1269.2).
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Muhunthan, Balasingam, and Girish Agrawal. "Discussion of “Drained Permanent Deformation of Sand Due to Cyclic Loading” by Ching S. Chang and Robert V. Whitman (October, 1988, Vol. 114, No. 10)." Journal of Geotechnical Engineering 116, no. 8 (August 1990): 1270–73. http://dx.doi.org/10.1061/(asce)0733-9410(1990)116:8(1270.2).
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Chang, Ching S., and Robert V. Whitman. "Discussion of “Drained Permanent Deformation of Sand Due to Cyclic Loading” by Ching S. Chang and Robert V. Whitman (October, 1988, Vol. 114, No. 10)." Journal of Geotechnical Engineering 116, no. 8 (August 1990): 1273–74. http://dx.doi.org/10.1061/(asce)0733-9410(1990)116:8(1273.2).
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Bogardus, Ralph F. "The Twilight of Transcendentalism: Ralph Waldo Emerson, Edward Weston, and the End of Nineteenth-Century Literary Nature." Prospects 12 (October 1987): 347–64. http://dx.doi.org/10.1017/s0361233300005639.
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That there is a striking correspondence between the thinking of such A nineteenth-century transcendentalists as Ralph Waldo Emerson and Henry David Thoreau and that of the twentieth-century American master of photography Edward Weston should come as no great surprise, for it is widely recognized that transcendentalism has been an essential ingredient in the lives and work of numerous major American artists. During the nineteenth century, this influence was most fully expressed by poets like Walt Whitman and Emily Dickinson, by the painter Thomas Eakins, and by the architect Louis Sullivan. At the turn of the century, the composer Charles Ives and painters Robert Henri and his “Ashcan” colleagues John Sloan, George Luks, William Glackens, and Everett Shinn continued to draw sustenance from the ideas and example of the transcendentalists. And during the early twentieth century, the brilliant architect Frank Lloyd Wright, the gifted painter Georgia O'Keeffe, and major poets Ezra Pound, T. S. Eliot, Robert Frost, Wallace Stevens, and William Carlos Williams made clear through their work the looming presence of the transcendentalist tradition. Thus, well before the 1920s, when Edward Weston began making his most innovative photographs, transcendentalism consciously and unconsciously pervaded American intellectual and artistic life: It was something to absorb or reject-or both. “Matthew and Waldo, guardians of the faith, the army of unalterable law,” was how Eliot put it. Weston was not exempt from this law.
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Young, Davis. "Origin of the American Quantitative Igneous Rock Classification: Part 1." Earth Sciences History 27, no. 2 (November 3, 2008): 188–219. http://dx.doi.org/10.17704/eshi.27.2.am78846828316676.
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In 1902, four American petrologists, C. Whitman Cross, Joseph P. Iddings, Louis V. Pirsson, and Henry S. Washington co-authored a lengthy paper in which they proposed an extremely complex, quantitative classification of igneous rocks. Taking advantage of developments in microscopic petrography, the theory of magmatic differentiation, and knowledge of the chemical composition of igneous rocks, the ‘CIPW’ classification marked a radical break with all previous igneous rock classification schemes such as those of Rosenbusch and Zirkel.The present paper is the first in a series that explores the genesis and conceptual development of the American quantitative classification. In 1893 Iddings posed a simple question to three young American petrologist friends, Cross, Pirsson, and George H. Williams, about the legitimacy of the use of the terms ‘porphyry’ and ‘porphyrite’. Henry Washington was to join the group later, but Williams was one of the original four. From this question there emerged an expanded discussion, conducted primarily via correspondence and mutual criticism of lengthy essays written by each of the four, dealing with larger questions of principles of classification and nomenclature. Any future classification, they agreed, should be based on igneous rock chemical composition and must reject geological age and geological occurrence as factors. Despite calls within the group for construction of a totally new igneous rock classification, the process evolved cautiously to a decision to publish a statement of general principles of igneous rock classification together with suggestions for changes in nomenclature for the benefit of petrologists. Eventually the project foundered because of health problems for Williams and the press of other obligations and interests on all four. In 1894, the project ground to a halt with the untimely death of Williams from typhoid fever.
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Niestlé, Axel. "Norman Polmar and Edward Whitman, Hunters and Killers, vol. 2: Anti-Submarine Warfare from 1943, Annapolis, MD: Naval Institute Press 2016, XV, 256 S., $ 49.95 [ISBN 978-1-61251-897-8]." Militaergeschichtliche Zeitschrift 76, no. 2 (September 26, 2017): 651–54. http://dx.doi.org/10.1515/mgzs-2017-0124.
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Niestlé, Axel. "Norman Polmar and Edward Whitman, Hunters and Killers, vol. 1: Anti-Submarine Warfare from 1776 to 1943, Annapolis, MD: Naval Institute Press 2015, XII, 209 S., $ 44.95 [ISBN 978-1-59114-689-6]." Militaergeschichtliche Zeitschrift 76, no. 1 (May 4, 2017): 206–9. http://dx.doi.org/10.1515/mgzs-2017-0013.
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Brown, Jane K. "Kai Sina, Kollektivpoetik. Zu einer Literatur der offenen Gesellschaft in der Moderne. Mit Studien zu Goethe, Emerson, Whitman und Thomas Mann. (Quellen und Forschungen zur Literaturgeschichte 98 [332]) De Gruyter, Berlin – Boston 2019. 290 S., € 89,95." Arbitrium 39, no. 1 (April 1, 2021): 95–98. http://dx.doi.org/10.1515/arb-2020-0052.
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Young, Davis. "Origin of the American Quantitative Igneous Rock Classification: Part 4." Earth Sciences History 30, no. 1 (December 1, 2011): 1–38. http://dx.doi.org/10.17704/eshi.30.1.65q0ng14n572846u.
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After several failed attempts to construct a new chemico-mineralogical igneous rock classification on the basis of three or more factors, C. Whitman Cross, Joseph P. Iddings, Louis V. Pirsson, and Henry S. Washington decided to establish a practical and logically consistent scheme on the basis of only two factors, namely, two primary groups consisting of hypothetical minerals with ideal chemical compositions, the amounts of which were to be calculated from the chemical compositions of igneous rocks. One primary group consisted mainly of alkali alumina silicates and quartz (salic minerals), whereas the other consisted mainly of calcic ferromagnesian minerals (femic). A list of the amounts of these calculated standard minerals within an igneous rock was termed the norm, and the list of the proportions of actual minerals in a rock was termed its mode.In the Fall of 1901 the quartet decided to publish a preliminary paper that presented the major themes of their two-factor classification scheme. Iddings was charged with writing a draft of the scheme, and Washington was assigned the task of producing an essay on nomenclature to be published later. The team continually refined the definitions of specific subdivisions of the scheme proposed by Iddings as well as the corresponding nomenclature proposed by Washington. They also refined the norm calculation algorithm and developed methods for calculating the norm from the mode of rocks containing aluminous ferromagnesian minerals such as hornblende and biotite.After a few months of evaluating and revising a succession of drafts, the team eventually determined to publish their work of classification and nomenclature all at once by combining the refined drafts into one large comprehensive manuscript in three parts: Part I on classification, Part II on nomenclature, and Part III on methods of calculation. Iddings coordinated and edited the various criticisms and drafts contributed by team members into one large manuscript and shepherded the project to final publication in late October 1902 in Journal of Geology. The massive 139-page article entitled ‘A quantitative chemico-mineralogical classification and nomenclature of igneous rocks’ was preceded in earlier issues of the same journal by a two-part series authored by Cross on the historical development of systematic petrography. In early 1903, both of Cross's papers and the CIPW article were combined and published as a book, Quantitative Classification of Igneous Rocks.
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Glaude, Eddie S. "The Magician’s Serpent." James Baldwin Review 5, no. 1 (September 2019): 9–22. http://dx.doi.org/10.7227/jbr.5.2.
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In this essay, Eddie S. Glaude, Jr. addresses the historical and contemporary failures of American democracy. Using the metaphor of “the magician’s serpent,” Glaude brings Walt Whitman’s views on democracy into the full light of America’s failure to resolve the problem of race. Glaude places Whitman’s Democratic Vistas (1871) in conversation with James Baldwin’s No Name in the Street (1972) in order to construct a different sort of reading practice that can both engage with Whitman’s views on democracy and reckon with what George Hutchinson calls Whitman’s “white imperialist self and ideology” as an indication of the limits of a certain radical democratic imagining.
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Zuck, Meghan, Myriam Bouchlaka, Huyen Dinh, Kevin Green, Francisco Zapata, Ramya Chandrasekaran, Tatyana Pisarenko, et al. "Abstract 6376: Discovery and preclinical characterization of dual antagonist antibodies targeting both LILRB1 and LILRB2 that enhance innate and adaptive anti-cancer immune responses." Cancer Research 83, no. 7_Supplement (April 4, 2023): 6376. http://dx.doi.org/10.1158/1538-7445.am2023-6376.
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Abstract Background: One cause for the failure of checkpoint inhibitors is the immunosuppressive nature of the tumor microenvironment. LILRB1 (ILT2) and LILRB2 (ILT4) are ITIM-containing inhibitory receptors that recognize HLA Class 1 and nonclassical ligands (e.g., HLA-A, HLA-G, etc.). LILRB1 is expressed on myeloid cells and subsets of B, NK, and T cells, while LILRB2 expression is mostly restricted to myeloid cells. Interaction of LILRB1 and LILRB2 receptors with HLA ligands promotes an inhibitory milieu that prevents T cells from attacking cancer cells. The distinct pattern of expression and function of these lymphoid and myeloid checkpoints suggests complementary targeting approaches for cancer immunotherapy. Dual blockade of LILRB1 and LILRB2 receptors by a single antibody that restores both innate and adaptive immune responses is a promising strategy to enhance efficacy of checkpoint inhibitors. Methods: Dual LILRB1 and LILRB2 targeting antibodies were cloned from B cells derived from rabbits immunized with human LILRB2 recombinant protein, and subsequently humanized. Antibodies were evaluated for binding to human LILRB1 and LILRB2 proteins. Dual targeting antibodies were evaluated in a panel of functional and phenotypic assays. Selected antibodies were further tested for efficacy in a humanized NSG-SGM3 tumor model. Results: Dual antibodies were selected based on binding to recombinant human LILRB1 and LILRB2 protein, as well as blocking of HLA-G binding. These antibodies demonstrated binding to cells expressing LILRB1 and LILRB2, with no appreciable binding to other family members. Lead antibodies demonstrated activity in functional cell-based assays modeling LILRB1- or LILRB2-mediated immunosuppression. Dual antibodies also enhanced IFN-γ production by LPS-stimulated human PBMC. Selected clones restored T-cell function from M2c macrophage-mediated suppression in coculture with CD8+ T cell, and enhanced the tumoricidal activity of NK cells. Importantly, the lead antibody demonstrated in vivo efficacy with significant tumor growth inhibition and tumor regression in an SK-MEL-5 tumor model in humanized NSG-SGM3 mice. Conclusions: We have identified dual antagonist antibodies targeting both LILRB1 and LILRB2 antibodies that restore both innate and adaptive immune responses. Additionally, dual antibodies restored CD8+ T cell activation from macrophage-mediated suppression and enhanced NK cell cytotoxic activity. These data provide a strong rationale for further development of dual antibodies as an anti-cancer immunotherapy. Citation Format: Meghan Zuck, Myriam Bouchlaka, Huyen Dinh, Kevin Green, Francisco Zapata, Ramya Chandrasekaran, Tatyana Pisarenko, Lauren Loh, Gajendra S. Naika, Meilyn Sylvestre, Jacob Heit, Raymond Fox, Darbie Whitman, Tom Graddis, Kamal D. Puri, Peter Probst. Discovery and preclinical characterization of dual antagonist antibodies targeting both LILRB1 and LILRB2 that enhance innate and adaptive anti-cancer immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6376.
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ASKARI, F. "A lag in intracellular degradation of mutant alpha1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ alpha1-antitrypsin deficiency Wu Y, Whitman I, Molmenti E, Moore K, Hippenmeyer P, Perlmutter DH. Proc Natl Acad Sci U S A 1994; 91: 9014?9018." Hepatology 21, no. 6 (June 1995): 1745–47. http://dx.doi.org/10.1016/0270-9139(95)90484-0.
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Grayson, Ellen Hickey. "Walt Whitman's America: A Cultural Biography. David S. Reynolds." Archives of American Art Journal 34, no. 3 (January 1994): 29–32. http://dx.doi.org/10.1086/aaa.34.3.1557724.
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Patel, Miral M., Beatriz E. Adrada, Benjamin Lopez, Rosalind P. Candelaria, Jia Sun, Medine Boge, Rania M. Mohamed, et al. "Abstract P3-02-03: Quantitative molecular breast imaging for early prediction of neoadjuvant systemic therapy response in locally advanced breast cancer patients." Cancer Research 82, no. 4_Supplement (February 15, 2022): P3–02–03—P3–02–03. http://dx.doi.org/10.1158/1538-7445.sabcs21-p3-02-03.
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Abstract BACKGROUND: Increasing use of neoadjuvant systemic therapy (NAT) for early and locally advanced breast cancer led to critical need for development of tools capable of early treatment response assessment after NAT. Tc-99m sestamibi Molecular breast Imaging (MBI) as a functional imaging modality has a promise to detect changes in the tumor prior to anatomical changes detected by mammogram or ultrasound. PURPOSE: To evaluate the ability of quantitative MBI parameters to predict pathologic complete response (pCR) after completion of NAT in breast cancer patients. MATERIALS AND METHODS: Patients with invasive breast cancer (T1-T4, N0-N3, M0) planned for NAT followed by surgery were enrolled in a prospective IRB approved trial. MBI was performed at baseline and after two cycles of NAT. Patient demographic and tumor biology information (Ki-67, HER2, ER/PR) was collected. MBI images were quantified using a novel approach with corrections for scatter and attenuation and regions of interest (ROI) were drawn over tumors to compute three quantitative MBI uptake metrics for correlation with pathologic response: MBI-specific standardized uptake value (SUV), tumor to background ratio (TBR), and tumor volume. Pathologic complete response was determined based on final histopathology report at the time of surgery as absence of the invasive disease in the breast and axillary lymph nodes. MBI metrics at baseline, after 2 cycles of NAT and interval change were correlated with pCR and tumor biology using the Wilcoxon Rank Sum test, Kruskal-Wallis test or Fisher’s exact test. Statistical analysis was carried out using R (version 3.6.3, R Development Core Team). RESULTS: A total of 70 patients with median age 47.5 years (range 30-77) were included in the analysis. Breast cancer subtypes were: HER2 negative (ER/PR+) 35.7% (25/70), HER2 positive (ER/PR +/-) 35.7% (25/70), and triple negative (HER2-, ER/PR-) 28.6% (20/70). Change in SUV after 2 cycles of NAT was higher in patients with pCR compared to those who did not achieve pCR (mean decrease in SUV of 15.57 and 4.83 respectively, p<0.001). Additionally, change in TBR in patients with pCR was also higher compared to patients who did not achieve pCR (mean decreases of 1.14 and 0.56, respectively, p<0.001). No correlation was found between baseline SUV, baseline TBR, change in volume, and pCR. CONCLUSION: MBI-specific SUV and TBR changes after two cycles of NAT correlate and may predict pCR in patients with locally advanced breast cancer. Quantitative MBI parameters are novel promising imaging tools that may help to detect early clinical benefit and optimize management in patients receiving NAT. Citation Format: Miral M Patel, Beatriz E Adrada, Benjamin Lopez, Rosalind P Candelaria, Jia Sun, Medine Boge, Rania M Mohamed, Nabil Elshafeey, Gary Whitman, MD, Huong T Le-Petross, Lumarie Santiago, Marion E Scoggins, Deanna Lane, Tanya Moseley, Galit Zylberman, Jerica Saddler, Jessica WT Leung, Wei T Yang, Vincente Valero, S Cheenu Kappadath, Gaiane M Rauch. Quantitative molecular breast imaging for early prediction of neoadjuvant systemic therapy response in locally advanced breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-03.
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Pratiwi, Hardiyanti, Ikta Yarliani, Murniyanti Ismail, Rizki Noor Haida, and Noer Asmayanti. "Assessing the Toxic Levels in Parenting Behavior and Coping Strategies Implemented During the COVID-19 Pandemic." JPUD - Jurnal Pendidikan Usia Dini 14, no. 2 (November 30, 2020): 231–46. http://dx.doi.org/10.21009/jpud.142.03.
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The COVID-19 pandemics have caused a lot of stressors for parents. Apart from doing daily activities, parents also have to take care of their children and accompany them to study. The number of stressors can lead to toxic behavior in parenting. This study aims to measure the level of toxicity in parenting behavior and coping strategies adopted by parents. This study uses quantitative descriptive methods to measure toxic levels in parenting behavior during the COVID-19 pandemic. A total of 568 parents from Banjarmasin and Yogyakarta participated in this study. The survey results show that several factors can trigger parenting stress during the COVID-19 pandemic, namely worsening economic conditions, delinquent children, excessive anxiety, accumulated daily hassles, growing family demands, and disputes with spouses. However, some of these stressors do not lead to toxic parenting. The results showed that 97.79% of respondents from Banjarmasin and 95.29% from Yogyakarta showed a low toxic level. The remaining 2.21% of respondents in Banjarmasin and 4.71% of respondents in Yogyakarta indicated a moderate toxic level. Coping strategies are crucial for neutralizing stress. There are several strategies applied, namely trying to consider a problem is God's test, and there is a positive side to every problem; trying to address the source of stress and solving it; Withdrawing and finding individual time; looking for social support from the family and others; crying and releasing it by doing favorite things and capitulate and get back the problem. This Research is expected to be a reference for parents in choosing coping strategies to manage the stress they feel in parenting during the pandemic.
Keywords: Toxic parenting; stress trigger, coping strategy; COVID-19
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Zhou, Zijian, Nabil A. Elshafeey, David E. Rauch, Beatriz E. Adrada, Rosalind P. Candelaria, Mary S. Guirguis, Wei Yang, et al. "Abstract P1-08-03: Deep learning for early prediction of neoadjuvant chemotherapy response in triple negative breast cancers." Cancer Research 82, no. 4_Supplement (February 15, 2022): P1–08–03—P1–08–03. http://dx.doi.org/10.1158/1538-7445.sabcs21-p1-08-03.
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Abstract Introduction: Neoadjuvant chemotherapy (NACT) is becoming standard of care for presurgical treatment of triple negative breast cancer (TNBC) patients. Achievement of pathological complete response (pCR) after NACT is associated with improved outcomes. There is currently an unmet need in development of imaging and clinical tools for prediction of pCR to NACT in TNBC. We investigated use of deep learning convolution neural networks (CNNs) for early prediction of pCR in a TNBC cohort on the basis of MRI acquired before the initiation and at the midpoint, after completion of four cycles of NACT (C4). Materials and Methods: Baseline and C4 MRIs of 112 TNBC patients were collected from an ongoing prospective clinical trial (NCT02276443). Four patients were excluded because they underwent different treatment for the second regimen. Among the 108 patients, 52 patients (48%) had pCR confirmed at surgery. Positive enhancement integral (PEI) derived from the early phases of DCE MRI, and apparent diffusion coefficients (ADC) derived from DWI MRI (b = 100 and 800 s/mm2), were used for our investigation. The images were aligned and the tumor regions were cropped from all images. All tumor patches were normalized between [0, 1], and were padded to form matrices of the same size of 192×192×64 for PEI, or the size of 192×192×16 for ADC. The CNN was constructed using stacked 3D convolution and MaxPooling layers. It consisted of up to four channels for the inputs (baseline and C4 PEI and ADC). Features extracted from each channel were concatenated and regressed for pCR prediction via three densely connected layers. Binary cross-entropy was used as the loss function for CNN training, and the loss was optimized using an Adam optimizer with the initial learning rate of 0.0001. Because of the currently limited sample size, four-fold cross-validation was used for CNN training and evaluation. The patients were divided into four groups, each group had 27 patients and the pCR:non-pCR ratio was controlled as 13:14. For each fold, one group was reserved as the independent testing group, and the other three groups were combined for network training and internal validation. Receiver operating characteristic (ROC) curve was plotted for each fold of testing, and area under the curve (AUC) was calculated. Final performance of the CNN was determined by averaging the AUCs of the four testing folds. Additionally, to test the prediction efficacy of each input, we trained the CNN under the same settings but used PEI or ADC only as input, and the results were compared. Results: The CNN trained with PEI only achieved an average AUC of 0.65 ± 0.09. The second CNN trained with ADC only achieved an average AUC of 0.72 ± 0.07. The third CNN trained with both PEI and ADC achieved an average AUC of 0.73 ± 0.06. Conclusion and Discussion: Using baseline and mid-treatment MRIs, deep learning CNN showed promising performance to predict pCR in the early course of NACT. The prediction AUC for the independent testing groups was largely improved by using ADC to train the network, indicating that ADC can have more critical information than PEI in assisting pCR prediction during the early course of NACT. Future work includes curation of a larger patient data for network training and evaluation to improve the prediction performance and further validate generalization of the network. We will also explore more advanced network structures, through which the prediction performance can be improved. Four-fold cross-validation AUCs of the network using different data as inputs.PEIADCPEI+ADCFold 10.570.640.66Fold 20.760.800.77Fold 30.660.700.68Fold 40.590.740.79Average0.65 ± 0.090.72 ± 0.070.73 ± 0.06 Citation Format: Zijian Zhou, Nabil A Elshafeey, David E Rauch, Beatriz E Adrada, Rosalind P Candelaria, Mary S Guirguis, Wei Yang, Medine Boge, Rania M Mohamed, Gary J Whitman, Deanna L Lane, Huong C Le-Petross, Jessica WT Leung, Lumarie Santiago, Marion E Scoggins, David A Spak, Miral M Patel, Frances Perez, Debu Tripathy, Vicente Valero, Clinton Yam, Stacy Moulder, Jason B White, Jong Bum Son, Mark D Pagel, Jingfei Ma. Deep learning for early prediction of neoadjuvant chemotherapy response in triple negative breast cancers [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-03.
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Halbert, Brian, David Einstein, David McDermott, Emanuelle Andrianopoulos, Mamta Gupta, Virginia Seery, Kenneth Onimus, et al. "176 Successful generation of tumor-infiltrating lymphocyte (TIL) product from renal cell carcinoma (RCC) tumors for adoptive cell therapy." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (November 2021): A188. http://dx.doi.org/10.1136/jitc-2021-sitc2021.176.
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BackgroundPatients with RCC may achieve remission with immune-checkpoint inhibitors (ICI); however, most patients will progress. Adoptive cell therapy with autologous TIL allows for expansion of T-cells from tumor tissue leading to a polyclonal T-cell product with a diverse T-cell receptor repertoire capable of recognizing an array of tumor antigens. TIL therapy with centrally manufactured lifileucel demonstrated a 36% overall response rate in patients with ICI-refractory melanoma.1 We present our preclinical experience of TIL production in RCC.MethodsThis study was approved by the DF/HCC Institutional Review Board. Fresh tumor samples (≥1.5-cm) were harvested from consented patients undergoing resection for RCC. TIL were manufactured using pre-rapid expansion (1/10th scale) and rapid expansion (1/100th scale) protocol for 22 days. Characterization (total viable cells [TVC],% viability, identity, and potency) was performed on the final TIL product. TIL purity, differentiation, memory, activation, and exhaustion status were characterized using multi-color flow cytometry.ResultsBaseline characteristics of 11 recruited patients are shown in table 1. Clear cell was the most common histology (73%). Two patients had previously treated metastatic disease with samples harvested from the lung and adrenal gland; one patient had prior cryoablation with adjacent local recurrence. The remainder were treatment-naïve primary nephrectomy samples. Eight products (73%) showed acceptable TIL product attributes (table 2). Median (range) TVC, viability, and identity (CD45+CD3+%) for the final TIL product were 74×109 (18×109–133×109), 95% (86%–97%), and 98% (94%–99%), respectively. Median (range) percentage of CD4+ cells was 69% (21%–97%) and CD8+ cells was 27% (2%–72%). The non–T-cell population, including B cells, monocytes, and NK cells, was <7%. The final TIL product was functional, and responded to polyclonal bead stimulation; the median (range) IFNg and granzyme B were 8834 (3319–12,957) pg/mL and 34,329 (15,565–65,521) pg/mL, respectively. Acceptable TIL product was generated from both metastatic lesions and primary tumor samples. Of the 3 tumor samples that did not demonstrate acceptable TIL product attributes, one (ID 1) was from a patient treated with a CXCR4 inhibitor <1 month before resection, another (ID 4) was from a patient previously treated with ocrelizumab (CD20-directed cytolytic antibody) for multiple sclerosis, and the final (ID 8) was harvested from the cryoablated tumor nodule rather than the adjacent recurrent tumor.Abstract 176 Table 1Baseline demographics and tumor characteristicsAbstract 176 Table 2Summary of product attributes. 1, No CD3+ subset. 2, Product not available to testConclusionsThese feasibility data suggest that TIL can be successfully expanded ex vivo from RCC samples (including pre-treated and metastatic tumors) and support potential clinical investigation of TIL in patients with RCC.ReferencesSarnaik AA, Hamid O, Khushalani NI, Lewis KD, Medina T, Kluger HM, Thomas SS, Domingo-Musibay E, Pavlick AC, Whitman ED, Martin-Algarra S, Corrie P, Curti BD, Oláh J, Lutzky J, Weber JS, Larkin JMG, Shi W, Takamura T, Jagasia M, Qin H, Wu X, Chartier C, Graf Finckenstein F, Fardis M, Kirkwood JM, Chesney JA. Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. J Clin Oncol 2021 May 12:JCO2100612. doi: 10.1200/JCO.21.00612. Epub ahead of print. PMID: 33979178.Ethics ApprovalThis study was approved by the DF/HCC Institutional Review Board protocol # 06-105.
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Guirguis, Mary S., Beatriz E. Adrada, Rosalind P. Candelaria, Jia Sun, Gary J. Whitman, Wei T. Yang, Medine Boge, et al. "Abstract P3-03-06: Prediction of response to neoadjuvant systemic therapy in triple negative breast cancer using baseline tumor MRI characteristics and imaging patterns of response." Cancer Research 82, no. 4_Supplement (February 15, 2022): P3–03–06—P3–03–06. http://dx.doi.org/10.1158/1538-7445.sabcs21-p3-03-06.
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Abstract Background: Triple negative breast cancer (TNBC) has a poor prognosis. In particular, TNBC patients who have significant residual disease at the time of surgery following completion of neoadjuvant systemic therapy (NST) have an especially poor prognosis. In an effort to identify patients who are unlikely to achieve pathologic complete response (pCR), we investigated if pre-treatment breast MRI morphological characteristics and imaging response patterns during NST can predict pCR in TNBC patients. Materials and Methods: As part of a prospective IRB-approved clinical trial (ARTEMIS, NCT02276443), 199 patients with biopsy-proven stage I-III TNBC received NST and were classified as pCR or non-pCR based on histopathology at surgery. Patients underwent breast MRI at baseline (BL), after 2 cycles (C2), and 4 cycles (C4) of Adriamycin-based chemotherapy (AC). Subsequently, patients received either taxane-based NST or targeted therapy guided by mid-treatment imaging response. MRI studies were reviewed by two fellowship-trained breast radiologists who were blinded to the pathology results. ACR MRI BIRADS lexicon (5th Ed) was used to describe BL tumor morphology. Imaging response pattern at C2 and C4 MRI was classified as follows: type 0 (complete), type 1 (concentric shrinkage), type 2 (crumble), type 3 (diffuse enhancement), type 4 (stable), or type 5 (progression). Morphological baseline features and response patterns were summarized and compared to the pCR status on surgical pathology using Fisher’s exact test. P values less than 0.05 were considered statistically significant. Results: Median age was 53 years, range 24-79. Of 199 patients, 95 (48%) had pCR and 104 (52%) had non-pCR. At BL MRI, an irregularly-shaped mass and homogenous or clumped non-mass enhancement were associated with pCR (p=0.026 and p=0.013, respectively). Multifocality, peritumoral edema, and intratumoral necrosis were independent of pCR. Following NST, the most common MRI response pattern was type 1, seen with equal frequency in pCR and non-pCR at C2 (58% and 42%, respectively) and C4 (47% and 53%, respectively). The following response pattern associations were found: type 0 was associated with pCR at both C2 and C4 timepoints (p<0.001), while types 4 and 5 were associated with non-pCR at C2, (p<0.001). The four patterns: types 2, 3, 4, 5, were associated with non-pCR at C4 (p<0.001). Conclusion: Baseline MRI tumor morphological characteristics and MRI imaging response patterns during NST may be valuable markers for pCR prediction in TNBC. Qualitative breast MRI assessment may act as an accessible tool to identify TNBC patients who are unlikely to achieve pCR and may benefit from targeted therapies. Citation Format: Mary S Guirguis, Beatriz E Adrada, Rosalind P Candelaria, Jia Sun, Gary J Whitman, Wei T Yang, Medine Boge, Rania M Mohamed, Nabil A Elshafeey, Deanna L Lane, Huong Le-Petross, Jessica WT Leung, Lumarie Santiago, Marion E Scoggins, David A Spak, Miral Patel, Frances Perez, Peng Wei, Debu Tripathy, Jason White, Elizabeth Ravenberg, Lei Huo, Jennifer Litton, Banu Arun, Vincente Valero, Alastair Thompson, Stacy Moulder, Clinton Yam, Gaiane M Rauch. Prediction of response to neoadjuvant systemic therapy in triple negative breast cancer using baseline tumor MRI characteristics and imaging patterns of response [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-03-06.
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Mohamed, Rania M., Bikash Panthi, Beatriz Adrada, Rosalind Candelaria, Mary S. Guirguis, Wei Yang, Medine Boge, et al. "Abstract P6-01-06: Multi-Parametric MRI-Based Radiomics Models from Tumor and Peritumoral Regions as Potential Predictors of Treatment Response to Neoadjuvant Systemic Therapy in Triple Negative Breast Cancer Patients." Cancer Research 83, no. 5_Supplement (March 1, 2023): P6–01–06—P6–01–06. http://dx.doi.org/10.1158/1538-7445.sabcs22-p6-01-06.
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Abstract PURPOSE Triple negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer. Pathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) predicts better survival. Early prediction of the treatment response can potentially triage non-responding patients to alternative protocol treatments, spare them of the unneeded toxicity, and improve pCR. We evaluated the ability of radiomic textural analysis of intratumoral and peritumoral regions on the dynamic contrast enhanced (DCE) and diffusion-weighted imaging (DWI) MRI images obtained early during NAST to predict pCR. MATERIALS AND METHODS This IRB-approved prospective study (NCT02276443) included 182 patients with biopsy proven stage I-III TNBC who had multiparametric MRIs at baseline (BL), post 2 cycles (C2), and post 4 cycles (C4) of NAST before surgery. Tumors and peritumoral regions of 5 mm and 10 mm in thickness were segmented on the 2.5 minutes DCE subtraction images and on the b=800 DWI images. Ten histogram-based first order texture features including mean, minimum, maximum, standard deviation, kurtosis, skewness, 1st, 5th, 95th, and 99th percentile, and 300 radiomic Grey Level Co-occurrence matrix (GLCM) features along with their absolute and relative differences between the 3 imaging time points were extracted from the tumors and from the peritumoral regions with an in-house Matlab toolbox. Treatment response at surgery (pCR vs non-pCR) was documented. The samples were divided into training and testing datasets by a 2:1 ratio. Area under the receiver operating characteristics curve (AUC ROC) was calculated for univariate analysis in predicting pCR. Logistic regression with elastic net regularization was performed for texture feature selection. Parameter optimization was performed by using 5-fold cross-validation based on mean cross-validated AUC in the training set. RESULTS Of 182 TNBC patients, 88 (48%) had pCR and 94 (52%) did not achieve pCR. Eight multivariate models combining radiomic features from both DCE and DWI tumoral and peritumoral regions had AUC > 0.8 (0.807-0.831) with p-value < 0.001 in both training and testing sets. The highest AUC=0.831 was obtained from a model consisting of 15 radiomic features: tumor DWI (5 GLCM features) at C2, peritumoral region on DCE (skewness) at C2, tumor DCE (1st, 5th percentile) at C4, tumor DWI (3 GLCM features) at C4, peritumoral region DWI (1 GLCM feature) at C4, and the relative difference between C4/C2 on DCE (5th, 95th percentile and mean). CONCLUSION Multi-parametric MRI-based radiomics models from the tumor and the peritumoral regions showed high accuracy as potential early predictors of NAST response in TNBC patients. Citation Format: Rania M. Mohamed, Bikash Panthi, Beatriz Adrada, Rosalind Candelaria, Mary S. Guirguis, Wei Yang, Medine Boge, Miral Patel, Nabil Elshafeey, Sanaz Pashapoor, Zijian Zhou, Jong Bum Son, Ken-Pin Hwang, H. T. Carisa Le-Petross, Jessica Leung, Marion E. Scoggins, Gary J. Whitman, Zhan Xu, Deanna L. Lane, Tanya Moseley, Frances Perez, Jason White, Elizabeth Ravenberg, Alyson Clayborn, Mark Pagel, Huiqin Chen, Jia Sun, Peng Wei, Alastair M. Thompson, Stacy Moulder, Anil Korkut, Lei Huo, Kelly K. Hunt, Jennifer K. Litton, Vicente Valero, Debu Tripathy, Clinton Yam, Jingfei Ma, Gaiane Rauch. Multi-Parametric MRI-Based Radiomics Models from Tumor and Peritumoral Regions as Potential Predictors of Treatment Response to Neoadjuvant Systemic Therapy in Triple Negative Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-06.
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Mohamed, Rania M., Bikash Panthi, Beatriz Adrada, Rosalind Candelaria, Mary S. Guirguis, Wei Yang, Medine Boge, et al. "Abstract P6-01-35: A Pre-operative Dynamic Contrast Enhanced MRI-Based Radiomics Models as Predictors of Treatment Response after Neoadjuvant Systemic Therapy in Triple Negative Breast Cancer Patients." Cancer Research 83, no. 5_Supplement (March 1, 2023): P6–01–35—P6–01–35. http://dx.doi.org/10.1158/1538-7445.sabcs22-p6-01-35.
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Abstract Background and Purpose Triple negative breast cancer (TNBC) is a biologically aggressive tumor and a refractory subtype of breast cancer due to the lack of therapeutic targets, such as estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. In this study, we investigated the accuracy of radiomic models based on the dynamic contrast enhanced (DCE) MRI images obtained after the completion of NAST as discriminators of treatment response in TNBC patients. Materials and Methods This IRB-approved prospective study (ARTEMIS trial, NCT02276443) included 181 patients with biopsy proven stage I-III TNBC who Had MRIs after completion of NAST and before surgery. Patients were classified as pathologic complete response (pCR) and non-pCR at the surgery. Tumors were segmented on the 2.5 minutes DCE subtraction images. Regions with necrosis or clip artifacts were excluded from the contour. If tumors were not visible, the tumor bed was contoured. Whole-tumor histogram-based first order texture features (p=10) including mean, minimum, maximum, Standard deviation, kurtosis, skewness, 1st, 5th, 95th, and 99th percentiles, and radiomic (p=300) Grey Level Co-occurrence matrix (GLCM) features were extracted with an in-house Matlab toolbox. The samples were split into training and testing data sets by a 2:1 ratio. For univariate analysis area under the receiver operating characteristics curve (AUC ROC) was performed for pCR status prediction. For texture feature selection logistic regression with elastic net regularization was performed. Parameter optimization was performed by using 5-fold cross-validation based on mean cross-validated AUC in the training set. A P-value less than 0.05 was considered statistically significant. Results Of the total 181 patients, 88 (49%) had pCR and 93 (51%) had non-pCR. Univariate analysis identified 7 statistically significant first order imaging features (Minimum, Maximum, Mean, 1st Percentile, 5th Percentile, 95th Percentile, and 99th Percentile) with AUC >= 0.7 (p< 0.001), in both training and testing data sets. Percentile 5 showed highest AUC = 0.78 (p< 0.001). Two multivariate models were statistically significant at cross-validation with AUC>=0.7. The first model combined 2 first order data (Percentile 1 and Percentile 5) with AUC = 0.73 (p< 0.001). The second model combined 8 first order features (Percentile 1, 5, 95, 99, Mean, Minimum, Maximum, and Skewness) and 24 GLCM features with AUC = 0.7 (p=0.003). Conclusion DCE-MRI radiomic features from tumor and tumor bed regions in TNBC may be helpful imaging biomarkers for predicting treatment response after NAST. Citation Format: Rania M. Mohamed, Bikash Panthi, Beatriz Adrada, Rosalind Candelaria, Mary S. Guirguis, Wei Yang, Medine Boge, Miral Patel, Nabil Elshafeey, Sanaz Pashapoor, Zijian Zhou, Jong Bum Son, Ken-Pin Hwang, H. T. Carisa Le-Petross, Jessica Leung, Marion E. Scoggins, Gary J. Whitman, Zhan Xu, Deanna L. Lane, Tanya Moseley, Frances Perez, Jason White, Huiqin Chen, Jia Sun, Peng Wei, Jennifer K. Litton, Vicente Valero, Clinton Yam, Mark Pagel, Jingfei Ma, Gaiane Rauch. A Pre-operative Dynamic Contrast Enhanced MRI-Based Radiomics Models as Predictors of Treatment Response after Neoadjuvant Systemic Therapy in Triple Negative Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-35.
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Panthi, Bikash, Rania M. Mohamed, Beatriz Adrada, Rosalind Candelaria, Mary S. Guirguis, Wei Yang, Medine Boge, et al. "Abstract P6-01-34: Longitudinal DCE-MRI Radiomic Models for Early Prediction of Response to Neoadjuvant Systemic Therapy (NAST) in Triple Negative Breast Cancer (TNBC) Patients." Cancer Research 83, no. 5_Supplement (March 1, 2023): P6–01–34—P6–01–34. http://dx.doi.org/10.1158/1538-7445.sabcs22-p6-01-34.
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Abstract Background and Purpose Early prediction of neoadjuvant systemic therapy (NAST) response in triple negative breast cancer (TNBC) patients could potentially aid in the selection of alternative therapies and avoid unnecessary toxicity in patients unlikely to achieve pathologic complete response (pCR) with NAST. In this study, we investigated the radiomic features of the peritumoral and the tumoral regions from dynamic contrast enhanced (DCE) MRI acquired at different time points of NAST for early treatment response prediction in TNBC. Methods and Materials This study included 182 biopsy-confirmed stage I-III TNBC patients enrolled in an IRB approved prospective clinical trial (NCT02276433). All patients underwent DCE-MRI on a GE 3T MRI scanner at baseline (BL), after two (C2) and four (C4) cycles of doxorubicin/cyclophosphamide based chemotherapy and before surgery. The peritumoral and the tumoral regions were segmented manually by two fellowship-trained radiologists using early phase (2.5 min) DCE-MRI subtraction images. Ten first order radiomic features, 300 grey-level-co-occurrence matrix (GLCM) features along with their absolute and relative differences (C4/BL, C2/BL, C4/C2) between the 3 imaging time points were extracted from the peritumoral and the tumoral regions. Patients were randomly divided into training and testing sets in a 2:1 ratio. For univariate analysis, area under the receiver operating characteristics curve (AUC ROC) was measured to determine the features most predictive of pCR/non-pCR. Wilcoxon Rank Sum test was used to test the statistical significance of predictive performance. In multivariate analysis, radiomic models were established using logistic regression with elastic net regularization followed by 5-fold cross validation for performance assessment. Results Eighty-eight (48%) patients had pCR (59 training, 29 testing) and 94 (52%) patients had non-pCR (63 training, 31 testing). Twenty-five radiomic features (4 from peritumoral C4, 5 from tumoral C4, 4 from peritumoral C4/BL, 6 from tumoral C4/BL, 2 from peritumoral C4/C2 and 4 from tumoral C4/C2) were statistically significant with AUC ≥ 0.75 in both the training and the testing sets at the univariate analysis. The significant features at C4 had AUCs of 0.75-0.79 for the training set and 0.76-0.81 for the testing set. Changes measured between C4 and BL or C2 showed AUC of 0.76-0.84 in the training and 0.75-0.81 in the testing datasets. Eleven multivariate regression models comprised of radiomic features at BL, C2, C4 and their changes (C4/BL, C4/C2 and C2/BL) showed an AUC of 0.80-0.84 for cross validation and an AUC of 0.80-0.82 for independent testing. Conclusions Radiomic models using longitudinal DCE MRI parameters of peritumoral and tumoral regions during NAST have the potential to predict pCR in TNBC patients undergoing NAST. Citation Format: Bikash Panthi, Rania M. Mohamed, Beatriz Adrada, Rosalind Candelaria, Mary S. Guirguis, Wei Yang, Medine Boge, Miral Patel, Nabil Elshafeey, Sanaz Pashapoor, Zijian Zhou, Jong Bum Son, Ken-Pin Hwang, H. T. Carisa Le-Petross, Jessica Leung, Marion E. Scoggins, Gary J. Whitman, Zhan Xu, Deanna L. Lane, Tanya Moseley, Frances Perez, Jason White, Elizabeth Ravenberg, Alyson Clayborn, Mark Pagel, Huiqin Chen, Jia Sun, Peng Wei, Alastair M. Thompson, Stacy Moulder, Anil Korkut, Lei Huo, Kelly K. Hunt, Jennifer K. Litton, Vicente Valero, Debu Tripathy, Clinton Yam, Jingfei Ma, Gaiane Rauch. Longitudinal DCE-MRI Radiomic Models for Early Prediction of Response to Neoadjuvant Systemic Therapy (NAST) in Triple Negative Breast Cancer (TNBC) Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-34.
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Braga-Miranda, Lourdislene Costa, Marcos Miranda, and Eunice A. Bianchi Galati. "Phlebotomine fauna in a rural area of the Brazilian Pantanal." Revista de Saúde Pública 40, no. 2 (April 2006): 324–26. http://dx.doi.org/10.1590/s0034-89102006000200021.
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The aim of the study was to identify among the phlebotomine fauna potential leishmaniasis vectors. The study was carried out in Corumbá county, State of Mato Grosso do Sul, Mid-West Brazil (18º59'S, 56º39'W). Sand fly captures were undertaken fortnightly with automatic light traps at 11 sites in forested environments and anthropic areas from April 2001 to July 2003. A total of only 41 specimens were captured. Thirty-one percent of the specimens were captured in forests and 68.3% in anthropic areas. The predominance of non-anthropophilic groups and the low density of N. whitmani, a known cutaneous leishmaniasis vector, does not seem to indicate any actual risk of the transmission of this disease in the study area.
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Marx, Angela N., Megumi Kai, Min Fu, Hope E. Murphy, Jie S. Willey, Huiming Sun, Angela Alexander, et al. "Abstract P4-06-09: A phase 1b study of neratinib with THP in metastatic and locally advanced breast cancer, and phase II study of THP followed by AC in HER2 + primary inflammatory breast cancer (IBC), and neratinib with taxol followed by AC in HR+/HER2- IBC." Cancer Research 83, no. 5_Supplement (March 1, 2023): P4–06–09—P4–06–09. http://dx.doi.org/10.1158/1538-7445.sabcs22-p4-06-09.
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Abstract Background: The pathologic complete response (pCR) rate in inflammatory breast cancer (IBC) patients is worse than in non-IBC patients; new drug combinations are warranted to improve pCR rates across all IBC molecular subtypes. Based on our preclinical data, we added neratinib to standard neoadjuvant chemotherapy in both HER2+ (synergy) and HER2-/hormone receptor (HR)+ (high frequency of ERBB2 mut) untreated IBC, as a single-center, non-randomized phase I/II trial. Patients and Method: This study enrolled three cohorts: Cohort I phase Ib (C1P1B), Cohort I Phase II (C1P2) and Cohort II (C2). In C1P1B to determine the recommended phase 2 dose (RP2D), we enrolled patients with HER2+ metastatic or locally advanced breast cancer. Patients received paclitaxel/trastuzumab/pertuzumab (THP) + neratinib x 4 cycles (up to 8 cycles per physician’s discretion). For C1P2 and C2, we enrolled Stage III – IV primary IBC patients. In C1P2, patients with HER2+ IBC received neratinib (RP2D) combined with THP x 4 cycles followed by doxorubicin/cyclophosphamide (AC) x 4 cycles. Per stage I design, 11 patients were enrolled with plan to enroll 20 more patients in Stage II if at least 6 had a pCR. In C2, patients with HER2-/HR+ IBC received neratinib 200 mg/day combined with paclitaxel x 4 cycles followed by AC x 4 cycles. Stage I design planned for enrollment of 16 patients with enrollment of 15 more patients on stage II, if at least 2 Stage I patients had pCR. In all three cohorts, patients initiated prophylactic anti-diarrheal medication (loperamide & budesonide) with the first dose of neratinib. Results: From 2018 to 2022, thirty-four patients were enrolled and treated (n=4 C1P1B, n=14 C1P2, n=16 C2). In C1P1B, observed DLTs (dose limiting toxicities) were Grade (Gr) 2 Diarrhea, n=2 (50%); Gr3 diarrhea, n=2 (50%); 2 patients had a serious adverse event (SAE); 3 patients (55%) had Gr2 nausea. The RP2D was established at 80 mg/day (dose level 0). For patients in C1P2, the most frequently occurring adverse events (AEs) included Gr2 Alopecia, n=14 (100%); Gr2&3 Diarrhea, n=14 (100%); Gr2/3 Nausea, n=12 (86%); Gr2/3 Anemia, n=7 (50%); Gr2/3 Fatigue, n=8 (57%); Gr2/3 Hypokalemia, n=6 (57%); and Gr2/3 Neutrophil count decreased, n= 7 (50%). 6 patients had an SAE. Of the first 11 patients, 5 (46%) had pCR, 1 (9%) RCB-1, 1 (9%) RCB-II and 1 (9%) RCB-III. Three patients stopped study treatment for toxicity (27%), were non-evaluable and replaced. Of these, one had RCB-III (33.3%), one progression of disease (PD) (33.3%), and one came off study for toxicity (33.3%). Rather than replacing additional non-evaluable patients, the study was closed to new patient accrual. In C2, the most frequently occurring AEs were Gr2 diarrhea, n=7(44%); Gr3 diarrhea, n=8 (50%); Gr2 alopecia, n=14 (88%); Gr2/3 Anemia, n=10 (63%); Gr2/3 Nausea, n=7 (44%); Gr2/3 Neutropenia, n= 7 (44%). 3 patients had an SAE. Of 16 patients in this cohort, 1 had pCR (6%), 5 RCB-II (31%), 4 RCB-III (25%), 3 came off study for toxicity (19%) and 3 had PD (19%). C2 also closed to new patient accrual given the high toxicity profile. Conclusion: The addition of neratinib did not improve the pCR rate in HER2+ or HER2-/HR+ subtypes of IBC, and increased toxicities were observed. The trial closed to new patient entry March 2022. However, some patients achieved significant response. Biomarker analysis is ongoing. Evaluable participants will continue long-term follow-up per protocol. Acknowledgments: This study is supported by PUMA Biotechnology. Citation Format: Angela N. Marx, Megumi Kai, Min Fu, Hope E. Murphy, Jie S. Willey, Huiming Sun, Angela Alexander, Roland L. Bassett, Gary J. Whitman, H. T. Carisa Le-Petross, Miral Patel, Banu K. Arun, Sausan Abouharb, Parijatham S. Thomas, Carlos H. Barcenas, Nuhad K. Ibrahim, Vicente Valero, Naoto T. Ueno, Rachel M. Layman, Bora Lim, Wendy Woodward, Anthony Lucci. A phase 1b study of neratinib with THP in metastatic and locally advanced breast cancer, and phase II study of THP followed by AC in HER2 + primary inflammatory breast cancer (IBC), and neratinib with taxol followed by AC in HR+/HER2- IBC [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-09.
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Guirguis, Mary S., Beatriz Adrada, Miral Patel, Frances Perez, Rosalind Candelaria, Wei Yang, Jia Sun, et al. "Abstract P1-05-15: DCE-MRI for early prediction of excellent response versus chemoresistance in triple negative breast cancer." Cancer Research 83, no. 5_Supplement (March 1, 2023): P1–05–15—P1–05–15. http://dx.doi.org/10.1158/1538-7445.sabcs22-p1-05-15.
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Abstract PURPOSE Triple-negative breast cancer (TNBC) is a heterogeneous disease with variable response to neoadjuvant therapy (NAT). Pathologic complete response (pCR) has become a prognostic marker for overall and disease-free survival. The aim of this study was to determine if dynamic contrast-enhanced (DCE)-MRI after 2 and/or 4 cycles of NAT can identify patients with a high likelihood of achieving pCR, triaging them to standard of care (SOC), or, when appropriate, to de-escalation trials. Conversely, we aimed to identify chemoresistant tumors that are unlikely to achieve pCR and may benefit from escalated targeted trials. METHOD AND MATERIALS 309 patients with stage I-III TNBC underwent DCE-MRI (temporal resolution: 9-12 sec) at baseline (BL), 2 cycles (C2), and 4 cycles (C4) of SOC doxorubicin/cyclophosphamide (AC) NAT as part of a prospective IRB-approved study (NCT02276443). Tumor volumes of the index lesion were calculated using 3 axis measurements during the early phase of the DCE-MRI (60s). Percent tumor volume reduction (TVR) between BL, C2, and C4 was calculated. Patients were randomly assigned to a training or a validation cohort in a 1:1 ratio. pCR was assessed at surgery after completion of SOC NAT. Correlation between pCR and TVR was evaluated using ROC analysis. RESULTS Of 309 TNBC patients, 136 (44%) achieved pCR. Following 2 cycles of NAT, TVR >80% was predictive of pCR (chemosensitivity), while TVR ≤ 55% was predictive of non-pCR (chemoresistance) with PPV 80%, NPV 89%, AUC 0.811 (0.73~0.893, p< 0.0001) in the training cohort, and PPV 82%, NPV 85%, AUC 0.815 (CI:0.736~0.894, p< 0.0001) in the validation cohort. Following 4 cycles of NAT, TVR >90% was predictive of pCR, while TVR ≤80% was predictive of non-pCR with PPV 80%, NPV 84%, AUC 0.827 (0.756~0.898, p< 0.0001) in the training cohort and with PPV 73%, NPV 82%, AUC 0.785 (CI:0.709~0.862, p< 0.001) in the validation cohort. Using this model, the pCR status was correctly classified in 50% of TNBC patients using C2 DCE-MRI in the training cohort, and 54% in the validation cohort. Only 8% were misclassified in the training cohort, and 10% in the validation cohort. Using C4 DCE-MRI, the pCR status of 61% and 57% of TNBC was correctly classified in the validation and the testing cohorts, respectively. 12% were misclassified in the validation cohort, and 21% in the testing cohort. CONCLUSION DCE-MRI after 2 and 4 cycles of AC-based NAT correctly predicted the pCR status of 54% and 57% of TNBC patients, respectively, as either excellent responders or nonresponders with high AUC 0.811 and 0.827. This may allow patients to be triaged to SOC NAT with option of de-escalation or early targeted therapies for non-responders. Citation Format: Mary S. Guirguis, Beatriz Adrada, Miral Patel, Frances Perez, Rosalind Candelaria, Wei Yang, Jia Sun, Rania M. Mohamed, Medine Boge, H. T. Carisa Le-Petross, Jessica Leung, Gary J. Whitman, Deanna L. Lane, Marion E. Scoggins, Tanya Moseley, Benjamin Musall, Jason White, Sanaz Pashapoor, Peng Wei, Jong Bum Son, Ken-Pin Hwang, Bikash Panthi, Mark Pagel, Lei Huo, Kelly K. Hunt, Elizabeth Ravenberg, Alastair M. Thompson, Jennifer K. Litton, Vicente Valero, Debu Tripathy, Stacy Moulder, Clinton Yam, Jingfei Ma, Gaiane Rauch. DCE-MRI for early prediction of excellent response versus chemoresistance in triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-15.
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Gates, Rosemary L., Mallarme, and Laforgue. "T. S. Eliot's Prosody and the Free Verse Tradition: Restricting Whitman's "Free Growth of Metrical Laws"." Poetics Today 11, no. 3 (1990): 547. http://dx.doi.org/10.2307/1772826.
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BUTTERFIELD, R. W. (HERBIE). "David S. Reynolds, Walt Whitman's America: A Cultural Biography (New York: Alfred A. Knopf, 1995, $35.00). Pp. 671. ISBN 0 394 58023 0." Journal of American Studies 31, no. 1 (April 1997): 115–52. http://dx.doi.org/10.1017/s0021875896325486.
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Walsh, J. F., D. H. Molyneux, and M. H. Birley. "Deforestation: effects on vector-borne disease." Parasitology 106, S1 (January 1993): S55—S75. http://dx.doi.org/10.1017/s0031182000086121.
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SUMMARYThis review addresses' changes in the ecology of vectors and epidemiology of vector-borne diseases which result from deforestation. Selected examples are considered from viral and parasitic infections (arboviruses, malaria, the leishmaniases, nlariases, Chagas Disease and schistosomiasis) where disease patterns have been directly or indirectly influenced by loss of natural tropical forests. A wide range of activities have resulted in deforestation. These include colonisation and settlement, transmigrant programmes, logging, agricultural activities to provide for cash crops, mining, hydropower development and fuelwood collection. Each activity influences the prevalence, incidence and distribution of vector-borne disease. Three main regions are considered – South America, West & Central Africa and South-East Asia. In each, documented changes in vector ecology and behaviour and disease pattern have occurred. Such changes result from human activity at the forest interface and within the forest. They include both deforestation and reafforestation programmes. Deforestation, or activities associated with it, have produced new habitats for Anopheles darlingi mosquitoes and have caused malaria epidemics in South America. The different species complexes in South-East Asia (A. dirus, A. minimus, A. balabacensis) have been affected in different ways by forest clearance with different impacts on malaria incidence. The ability of zoophilic vectors to adapt to human blood as an alternative source of food and to become associated with human dwellings (peridomestic behaviour) have influenced the distribution of the leishmaniases in South America. Certain species of sandflies (Lutzomyia intermedia, Lu. longipalpis, Lu. whitmani), which were originally zoophilic and sylvatic, have adapted to feeding on humans in peridomestic and even periurban situations. The changes in behaviour of reservoir hosts and the ability of pathogens to adapt to new reservoir hosts in the newly-created habitats also influence the patterns of disease. In anthroponotic infections, such as Plasmodium, Onchocerca and Wuchereria, changes in disease patterns and vector ecology may be more difficult to detect. Detailed knowledge of vector species and species complexes is needed in relation to changing climate associated with deforestation. The distributions of the Anopheles gambiae and Simulium damnosum species complexes in West Africa are examples. There have been detailed longitudinal studies of Anopheles gambiae populations in different ecological zones of West Africa. Studies on Simulium damnosum cytoforms (using chromosome identification methods) in the Onchocerciasis Control Programme were necessary to detect changes in distribution of species in relation to changed habitats. These examples underline the need for studies on the taxonomy of medically-important insects in parallel with long-term observations on changing habitats. In some circumstances, destruction of the forest has reduced or even removed disease transmission (e.g. S. neavei-transmitted Onchocerca in Kenya). Whilst the process of deforestation can be expected to continue, hopefully at a decreased rate, it is expected that unpredictable and sometimes rapid changes in disease patterns will pose problems for the public health services.