We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure coreplatform@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
OBJECTIVES/GOALS: While mutant TP53 is an attractive therapeutic target in TNBC, attempts to target the mutant p53 protein directly have failed. Thus, we aim to identify pathways critical for the survival of TP53 mutant cells that can be targeted in TNBC. We have identified Kif11 as one such target and aim to further investigate its function in TP53 mutant TNBC. METHODS/STUDY POPULATION: We conducted a dual in silico/in vivo screen that identified Kif11 inhibition as preferentially inhibiting the growth of TP53 mutant TNBC. We obtained data on TP53 mutational status, KIF11 mRNA expression levels, and clinical characteristics from TCGA, METABRIC, and CCLE datasets. We treated breast cancer cell lines with the KIF11 inhibitor SB-743921. Cell counts were obtained through staining with DAPI or Hoechst and imaging on the ImageXPress PICO. We detected cell death by DRAQ7 staining and flow cytometry analysis following Annexin V-PI staining. To investigate mitotic spindle organization, we performed immunofluorescent staining with an anti-tubulin antibody and DAPI co-staining. Cell cycle analysis was performed through flow cytometry. RESULTS/ANTICIPATED RESULTS: KIF11 is highly expressed in TP53 mutant and TNBC clinical samples. High KIF11 expression is associated with poorer clinical outcomes. Kif11 inhibition suppresses growth of both TP53 mutant and wild-type breast cancer cells, but preferentially induces the death of TP53 mutant cells as detected by DRAQ7 and Annexin V/PI staining. Kif11 inhibition induces a G2-M block and growth inhibition in TP53 wild-type cells. On the other hand, following treatment with the Kif11 inhibitor SB-743921, TP53 mutant cells undergo mitotic spindle dysfunction leading to the formation of multinucleated cells and cell death. DISCUSSION/SIGNIFICANCE: These results demonstrate that Kif11 is a promising therapeutic target in aggressive, TP53 mutant TNBCs. Kif11 inhibitors, including SB-743921, have been tested in human trials, and are well tolerated, but it is unclear which patients would most benefit. Our studies show that Kif11 inhibitors may be most useful in patients with TP53 mutant TNBCs.
This chapter introduces several health-related social problems. The first is that there are health disparities by socioeconomic status and racial group. These disparities are long standing and persistent, despite overall improvements in health. Three models are used to explain health disparities: health behaviors, health care, and the physical and social environment. Next, we discuss the dauntingly complicated US health care system. We focus on two problematic aspects: the high costs of health care and lack of access to health care. We examine this both before and after the 2010 enactment of the Patient Protection and Affordable Care Act and find it will not significantly improve costs in the short run. It may not reduce health disparities given that the Medicaid expansion piece is voluntary. We conclude that there is much work to be done to create a fair and equitable health care system.
Cooling devices (CDs) worn under personal protective equipment (PPE) can alleviate some of the heat stress faced by health care workers responding to the Ebola outbreak in West Africa.
Methods
Six healthy, young individuals were tested while wearing 4 different CDs or no cooling (control) under PPE in an environmental chamber (32°C/92% relative humidity) while walking (3 METs, 2.5 mph, 0% grade) on a treadmill for 60 minutes. Exercise was preceded by a 15-minute stabilization period and a 15-minute donning period.
Results
The control condition resulted in a significantly higher rectal temperature (Tre) at the end of the exercise than did all CD conditions (CD1, P=0.004; CD2, P=0.01; CD3, P=0.000; CD4, P=0.000) with CD1 and CD2 resulting in a higher Tre than CD3 and CD4 (P<0.05). The control condition resulted in a higher heart rate (HR) at the end of exercise than did the CD3 (P=0.01) and CD4 (P=0.009) conditions, whereas the HR of the CD1 and CD2 conditions was higher than that of the CD3 and CD4 conditions (P<0.05). Weight loss in the control condition was higher than in the CD3 (P=0.003) and CD4 (P=0.01) conditions. Significant differences in subjective measurements of thermal stress were found across conditions and time.
Conclusions
Use of CDs can be advantageous in decreasing the negative physiological and subjective responses to the heat stress encountered by health care workers wearing PPE in hot and humid environments. (Disaster Med Public Health Preparedness. 2017;11:573–579)
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
The title ‘Poetry in Motion’ suits the travel across language, culture, and time that constitutes literary translation. Across what bridge, by what mode, can a text arrive at the further shore – ‘[a] esotra parte, en la ribera’ – transformed to a new language and occupying a foreign literary context, yet with intangible spirit intact? Does it best travel naked or robed, empty-handed or with baggage? In particular, how do we bring across Baroque lyric: rhymed, metered, allusive, with incisively doubled meaning or gorgeously encrusted figuration. Should highly ornate originals be simplified in translation, in order to make them understandable? The paradoxically swift stillness and profuse simplicity expressed in classical Epicurean thought, and its relationship to the more familiar Stoicism, suggest a model not only for reading but rendering these poems into another language.
In this essay I splice two themes. First, an infrequently mentioned philosophical engagement with ‘Neo-’ or Christianized Epicureanism shapes Baroque Hispanic poetry and poetics along with more widely explored Neo-Stoic and Platonic influences. Second, Epicurean and Stoic models can illuminate approaches to the translation of early modern lyric into English today. Why mix these topics in limited space when each deserves full development? My brief answer: Epicureanism engages imagery that resonates with the intricacies of Baroque poetry, although in seldom acknowledged ways, and this philosophy can usefully inform a practice in translating that poetry. Indeed, the charged current between Stoic and Epicurean influences in the Baroque energizes my own approach to translating these works.
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
The fourteen essays of this volume engage in distinct ways with the matter of motion in early modern Spanish poetics, without limiting the dialectic of stasis and movement to any single sphere or manifestation. Interrogation of the interdependence of tradition and innovation, poetry, power and politics, shifting signifiers, the intersection of topography and deviant temporalities, the movement between the secular and the sacred, tensions between centres and peripheries, issues of manuscript circulation and reception, poetic calls and echoes across continents and centuries, and between creative writing and reading subjects, all demonstrate that Helgerson's central notion of conspicuous movement is relevant beyond early sixteenth-century secular poetics, By opening it up we approximate a better understanding of poetry's flexible spatio-temporal co-ordinates in a period of extraordinary historical circumstances and conterminous radical cultural transformation. Los catorce ensayos de este volumen conectan de una manera perceptible con el tema del movimiento en la poesía española del siglo de oro, sin limitar la dialéctica de la estasis y movimiento a una sola esfera o manifestación única. Entre los multiples enfoques cabe destacar: el cuestionamiento de la interdependencia de la tradición e inovación, de la poesía, del poder y la política, de los significantes que se transforman, de los espacios que conectan y cruzan con los tiempos 'desviados'; análisis de las tensiones entre lo sagrado y lo secular, del conflicto centro-periferia y del complejo sistema de producción, circulación y recepción de los manuscritos; el diálogo con el eco poético a través de los siglos y de los continentes y la construcción creativa del sujeto escritor y/o lector. Al abrir la noción central de Helgerson del "movimiento conspicuo" más allá de la poesía nueva secular, este libro propone un entendimiento más completo de las coordinadas espacio-temporales de la poesía en un periodo de circunstancias históricas extrao. Jean Andrews is Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham. Isabel Torres is Professor of Spanish Golden Age Literature at Queen's University, Belfast. Contributors: Jean Andrews, Dana Bultman, Noelia Cirnigliaro, Marsha Collins, Trevor J. Dadson, Aurora Egido, Verónica Grossi, Anne Holloway, Mark J. Mascia, Terence O'Reilly, Carmen Peraita, Amanda Powell, Colin Thompson, Isabel Torres.
Like their counterparts elsewhere in early modern Europe, Spanish and Portuguese women poets redirected Petrarchan conventions in order to critique gender inequities and to discard the mute, passive role assigned to women on and off the page. Three seventeenth-century poets who boldly redirect courtly love in poems addressed to women are Marcia Belisarda, Catalina Clara Ramírez de Guzmán, and Sor Violante del Cielo/do Ceu. Just as strictly delineated vestimentary codes allowed some venturing women to don male disguise for broader horizons or access to a wage economy, so the structures and conventions of Petrarchan verse allowed for startling gender play by women lyricists.
Belisarda, Ramírez, and Sor Violante (like the better-known María de Zayas y Sotomayor and Sor Juana Inés de la Cruz) on the surface adopt Petrarchan and courtly love traditions, while at the same time they incisively rewrite those conventions. Critical views hewing to binary considerations of genre, and implicitly to “either-or” definitions of sexuality, seek to identify these poems as utterances couched in the discourse either of friendship or of passionate love. Our times seem notably uneasy when confronted with these amorous poems of women to other women. Nevertheless, the lexical, figural, and discursive conventions of the poems themselves raise the topic of lesbianism, or whatever eroticized love between women may without anachronism be termed. Terms suggested by critics and historians, drawn variously from period texts and present-day usage, include “same-sex love and desire between women” (Canadé Sautman and Sheingorn), the “silent sin” (Alain Saint-Saëns), “sapphism” (Susan Lanser), female homoeroticism, “lesbianlike” textual presence (Judith Bennett), or queer desire.
Is “lesbianism” (by any terminology) anachronistic for the seventeenth century, as has been suggested of Sor Violante's poems and those of her better-known coeval, Sor Juana Inés de la Cruz? Social constructionist views tended in the 1980s and 90s to locate the formation of homo- (or hetero-) sexual “identities” in the eighteenth or nineteenth century, and thus to deny or elide the investigation of same-sex desire and eroticism in earlier periods. This haste to rule out “sex before sexuality” (Canadé Sautman and Sheingorn 6) works to shut down inquiry into the erotic power of women's poetry to women and into the self-replicating critical paradigms (including those of some feminist criticism) that reinforce patriarchal and “heteronormative” views.