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4543 Glucocorticoid Receptors are essential effectors of TGFβ signaling in Triple Negative Breast Cancer
- Carlos Jesus Perez Kerkvliet, Amy R Dwyer, Caroline Diep, Robert Oakley, Christopher Liddle, Carol A Lange
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, pp. 7-8
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OBJECTIVES/GOALS: The glucocorticoid receptor (GR) is a ubiquitous steroid hormone receptor that is emerging as a mediator of breast cancer metastasis. We aim to better understand the biology associated with phospho-GR species in TNBC and their contribution to tumor progression. METHODS/STUDY POPULATION: To better understand how p-S134 GR may impact TNBC cell biology, we probed GR regulation by soluble factors that are rich within the tumor microenvironment (TME), such as TGFβ. TNBC cells harboring endogenous wild-type or S134A-GR species were created by CRISPR/Cas knock-in and subjected to in vitro assays of advanced cancer behavior. RNA-Seq was employed to identify pS134-GR target genes that are uniquely regulated by TGFβ in the absence of exogenously added GR ligands. Direct regulation of selected TGFβ-induced pS134-GR target genes was validated accordingly. Bioinformatics tools were used to probe publicly available TNBC patient data sets for expression of a pS134-GR 24-gene signature. RESULTS/ANTICIPATED RESULTS: In the absence of GR ligands, GR is transcriptionally activated via p38-MAPK-dependent phosphorylation of Ser134 upon exposure of TNBC cells to TME-derived agents (TGFβ, HGF). The ligand-independent pS134-GR transcriptome primarily encompasses gene sets associated with TNBC cell survival and migration/invasion. Accordingly, pS134-GR was essential for TGFβ-induced TNBC cell migration, anchorage-independent growth in soft-agar, and tumorsphere formation, an in vitro readout of breast cancer stemness properties. Finally, a 24-gene pSer134-GR-dependent signature induced by TGFβ1 predicts shortened survival in breast cancer. We expect to find similar results using an in-house tissue microarray. DISCUSSION/SIGNIFICANCE OF IMPACT: Phospho-S134-GR is a critical downstream mediator of p38 MAPK signaling and TNBC migration, survival, and stemness properties. Our studies define GR as a required effector of TGFβ1 signaling and nominate pS134-GR as a biomarker of elevated risk of breast cancer dissemination.
Iron Age landscape changes in the Benoué River Valley, Cameroon
- David K. Wright, Scott MacEachern, Stanley H. Ambrose, Jungyu Choi, Jeong-Heon Choi, Carol Lang, Hong Wang
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- Journal:
- Quaternary Research / Volume 92 / Issue 2 / September 2019
- Published online by Cambridge University Press:
- 28 June 2019, pp. 323-339
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The introduction of agriculture is known to have profoundly affected the ecological complexion of landscapes. In this study, a rapid transition from C3 to C4 vegetation is inferred from a shift to higher stable carbon (13C/12C) isotope ratios of soils and sediments in the Benoué River Valley and upland Fali Mountains in northern Cameroon. Landscape change is viewed from the perspective of two settlement mounds and adjacent floodplains, as well as a rock terrace agricultural field dating from 1100 cal yr BP to the recent past (<400 cal yr BP). Nitrogen (15N/14N) isotope ratios and soil micromorphology demonstrate variable uses of land adjacent to the mound sites. These results indicate that Early Iron Age settlement practices involved exploitation of C3 plants on soils with low δ15N values, indicating wetter soils. Conversely, from the Late Iron Age (>700 cal yr BP) until recent times, high soil and sediment δ13C and δ15N values reflect more C4 biomass and anthropogenic organic matter in open, dry environments. The results suggest that Iron Age settlement practices profoundly changed landscapes in this part of West Africa through land clearance and/or utilization of C4 plants.
Geoarchaeological evidence for the construction, irrigation, cultivation, and resilience of 15th--18th century AD terraced landscape at Engaruka, Tanzania
- Carol Lang, Daryl Stump
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- Journal:
- Quaternary Research / Volume 88 / Issue 3 / November 2017
- Published online by Cambridge University Press:
- 18 August 2017, pp. 382-399
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Agricultural landscapes are human-manipulated landscapes, most obviously in areas modified by terracing and/or irrigation. Examples from temperate, arid, and desert environments worldwide have attracted the attention of many disciplines, from archaeologists, palaeoecologists, and geomorphologists researching landscape histories to economists, agronomists, ecologists, and development planners studying sustainable resource management. This article combines these interdisciplinary interests by exploring the role archaeology can play in assessing sustainability. Our case study is Engaruka, Tanzania, archaeologically famous as the largest abandoned irrigated and terraced landscape in East Africa. The site has been cited as an example of economic and/or ecological collapse, and it has long been assumed to have been irrigated out of necessity because agriculture was presumed to be nearly impossible without irrigation in what is now a semiarid environment. Geoarchaeological research refutes this assumption, however, demonstrating that parts of the site flooded with sufficient regularity to allow the construction of more than 1000 ha of alluvial sediment traps, in places greater than 2 m deep. Soil micromorphology and geochemistry also record changes in irrigation, with some fields inundated to create paddylike soils. Geoarchaeological techniques can be applied to both extant and abandoned agricultural systems, thereby contributing to an understanding of their history, function, and sustainability.
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- By Frank Andrasik, Melissa R. Andrews, Ana Inés Ansaldo, Evangelos G. Antzoulatos, Lianhua Bai, Ellen Barrett, Linamara Battistella, Nicolas Bayle, Michael S. Beattie, Peter J. Beek, Serafin Beer, Heinrich Binder, Claire Bindschaedler, Sarah Blanton, Tasia Bobish, Michael L. Boninger, Joseph F. Bonner, Chadwick B. Boulay, Vanessa S. Boyce, Anna-Katharine Brem, Jacqueline C. Bresnahan, Floor E. Buma, Mary Bartlett Bunge, John H. Byrne, Jeffrey R. Capadona, Stefano F. Cappa, Diana D. Cardenas, Leeanne M. Carey, S. Thomas Carmichael, Glauco A. P. Caurin, Pablo Celnik, Kimberly M. Christian, Stephanie Clarke, Leonardo G. Cohen, Adriana B. Conforto, Rory A. Cooper, Rosemarie Cooper, Steven C. Cramer, Armin Curt, Mark D’Esposito, Matthew B. Dalva, Gavriel David, Brandon Delia, Wenbin Deng, Volker Dietz, Bruce H. Dobkin, Marco Domeniconi, Edith Durand, Tracey Vause Earland, Georg Ebersbach, Jonathan J. Evans, James W. Fawcett, Uri Feintuch, Toby A. Ferguson, Marie T. Filbin, Diasinou Fioravante, Itzhak Fischer, Agnes Floel, Herta Flor, Karim Fouad, Richard S. J. Frackowiak, Peter H. Gorman, Thomas W. Gould, Jean-Michel Gracies, Amparo Gutierrez, Kurt Haas, C.D. Hall, Hans-Peter Hartung, Zhigang He, Jordan Hecker, Susan J. Herdman, Seth Herman, Leigh R. Hochberg, Ahmet Höke, Fay B. Horak, Jared C. Horvath, Richard L. Huganir, Friedhelm C. Hummel, Beata Jarosiewicz, Frances E. Jensen, Michael Jöbges, Larry M. Jordan, Jon H. Kaas, Andres M. Kanner, Noomi Katz, Matthew S. Kayser, Annmarie Kelleher, Gerd Kempermann, Timothy E. Kennedy, Jürg Kesselring, Fary Khan, Rachel Kizony, Jeffery D. Kocsis, Boudewijn J. Kollen, Hubertus Köller, John W. Krakauer, Hermano I. Krebs, Gert Kwakkel, Bradley Lang, Catherine E. Lang, Helmar C. Lehmann, Angelo C. Lepore, Glenn S. Le Prell, Mindy F. Levin, Joel M. Levine, David A. Low, Marilyn MacKay-Lyons, Jeffrey D. Macklis, Margaret Mak, Francine Malouin, William C. Mann, Paul D. Marasco, Christopher J. Mathias, Laura McClure, Jan Mehrholz, Lorne M. Mendell, Robert H. Miller, Carol Milligan, Beth Mineo, Simon W. Moore, Jennifer Morgan, Charbel E-H. Moussa, Martin Munz, Randolph J. Nudo, Joseph J. Pancrazio, Theresa Pape, Alvaro Pascual-Leone, Kristin M. Pearson-Fuhrhop, P. Hunter Peckham, Tamara L. Pelleshi, Catherine Verrier Piersol, Thomas Platz, Marcus Pohl, Dejan B. Popović, Andrew M. Poulos, Maulik Purohit, Hui-Xin Qi, Debbie Rand, Mahendra S. Rao, Josef P. Rauschecker, Aimee Reiss, Carol L. Richards, Keith M. Robinson, Melvyn Roerdink, John C. Rosenbek, Serge Rossignol, Edward S. Ruthazer, Arash Sahraie, Krishnankutty Sathian, Marc H. Schieber, Brian J. Schmidt, Michael E. Selzer, Mijail D. Serruya, Himanshu Sharma, Michael Shifman, Jerry Silver, Thomas Sinkjær, George M. Smith, Young-Jin Son, Tim Spencer, John D. Steeves, Oswald Steward, Sheela Stuart, Austin J. Sumner, Chin Lik Tan, Robert W. Teasell, Gareth Thomas, Aiko K. Thompson, Richard F. Thompson, Wesley J. Thompson, Erika Timar, Ceri T. Trevethan, Christopher Trimby, Gary R. Turner, Mark H. Tuszynski, Erna A. van Niekerk, Ricardo Viana, Difei Wang, Anthony B. Ward, Nick S. Ward, Stephen G. Waxman, Patrice L. Weiss, Jörg Wissel, Steven L. Wolf, Jonathan R. Wolpaw, Sharon Wood-Dauphinee, Ross D. Zafonte, Binhai Zheng, Richard D. Zorowitz
- Edited by Michael Selzer, Stephanie Clarke, Leonardo Cohen, Gert Kwakkel, Robert Miller, Case Western Reserve University, Ohio
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- Book:
- Textbook of Neural Repair and Rehabilitation
- Published online:
- 05 May 2014
- Print publication:
- 24 April 2014, pp ix-xvi
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Contributor affiliations
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- By Frank Andrasik, Melissa R. Andrews, Ana Inés Ansaldo, Evangelos G. Antzoulatos, Lianhua Bai, Ellen Barrett, Linamara Battistella, Nicolas Bayle, Michael S. Beattie, Peter J. Beek, Serafin Beer, Heinrich Binder, Claire Bindschaedler, Sarah Blanton, Tasia Bobish, Michael L. Boninger, Joseph F. Bonner, Chadwick B. Boulay, Vanessa S. Boyce, Anna-Katharine Brem, Jacqueline C. Bresnahan, Floor E. Buma, Mary Bartlett Bunge, John H. Byrne, Jeffrey R. Capadona, Stefano F. Cappa, Diana D. Cardenas, Leeanne M. Carey, S. Thomas Carmichael, Glauco A. P. Caurin, Pablo Celnik, Kimberly M. Christian, Stephanie Clarke, Leonardo G. Cohen, Adriana B. Conforto, Rory A. Cooper, Rosemarie Cooper, Steven C. Cramer, Armin Curt, Mark D’Esposito, Matthew B. Dalva, Gavriel David, Brandon Delia, Wenbin Deng, Volker Dietz, Bruce H. Dobkin, Marco Domeniconi, Edith Durand, Tracey Vause Earland, Georg Ebersbach, Jonathan J. Evans, James W. Fawcett, Uri Feintuch, Toby A. Ferguson, Marie T. Filbin, Diasinou Fioravante, Itzhak Fischer, Agnes Floel, Herta Flor, Karim Fouad, Richard S. J. Frackowiak, Peter H. Gorman, Thomas W. Gould, Jean-Michel Gracies, Amparo Gutierrez, Kurt Haas, C.D. Hall, Hans-Peter Hartung, Zhigang He, Jordan Hecker, Susan J. Herdman, Seth Herman, Leigh R. Hochberg, Ahmet Höke, Fay B. Horak, Jared C. Horvath, Richard L. Huganir, Friedhelm C. Hummel, Beata Jarosiewicz, Frances E. Jensen, Michael Jöbges, Larry M. Jordan, Jon H. Kaas, Andres M. Kanner, Noomi Katz, Matthew S. Kayser, Annmarie Kelleher, Gerd Kempermann, Timothy E. Kennedy, Jürg Kesselring, Fary Khan, Rachel Kizony, Jeffery D. Kocsis, Boudewijn J. Kollen, Hubertus Köller, John W. Krakauer, Hermano I. Krebs, Gert Kwakkel, Bradley Lang, Catherine E. Lang, Helmar C. Lehmann, Angelo C. Lepore, Glenn S. Le Prell, Mindy F. Levin, Joel M. Levine, David A. Low, Marilyn MacKay-Lyons, Jeffrey D. Macklis, Margaret Mak, Francine Malouin, William C. Mann, Paul D. Marasco, Christopher J. Mathias, Laura McClure, Jan Mehrholz, Lorne M. Mendell, Robert H. Miller, Carol Milligan, Beth Mineo, Simon W. Moore, Jennifer Morgan, Charbel E-H. Moussa, Martin Munz, Randolph J. Nudo, Joseph J. Pancrazio, Theresa Pape, Alvaro Pascual-Leone, Kristin M. Pearson-Fuhrhop, P. Hunter Peckham, Tamara L. Pelleshi, Catherine Verrier Piersol, Thomas Platz, Marcus Pohl, Dejan B. Popović, Andrew M. Poulos, Maulik Purohit, Hui-Xin Qi, Debbie Rand, Mahendra S. Rao, Josef P. Rauschecker, Aimee Reiss, Carol L. Richards, Keith M. Robinson, Melvyn Roerdink, John C. Rosenbek, Serge Rossignol, Edward S. Ruthazer, Arash Sahraie, Krishnankutty Sathian, Marc H. Schieber, Brian J. Schmidt, Michael E. Selzer, Mijail D. Serruya, Himanshu Sharma, Michael Shifman, Jerry Silver, Thomas Sinkjær, George M. Smith, Young-Jin Son, Tim Spencer, John D. Steeves, Oswald Steward, Sheela Stuart, Austin J. Sumner, Chin Lik Tan, Robert W. Teasell, Gareth Thomas, Aiko K. Thompson, Richard F. Thompson, Wesley J. Thompson, Erika Timar, Ceri T. Trevethan, Christopher Trimby, Gary R. Turner, Mark H. Tuszynski, Erna A. van Niekerk, Ricardo Viana, Difei Wang, Anthony B. Ward, Nick S. Ward, Stephen G. Waxman, Patrice L. Weiss, Jörg Wissel, Steven L. Wolf, Jonathan R. Wolpaw, Sharon Wood-Dauphinee, Ross D. Zafonte, Binhai Zheng, Richard D. Zorowitz
- Edited by Michael E. Selzer, Stephanie Clarke, Leonardo G. Cohen, Gert Kwakkel, Robert H. Miller, Case Western Reserve University, Ohio
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- Book:
- Textbook of Neural Repair and Rehabilitation
- Published online:
- 05 June 2014
- Print publication:
- 24 April 2014, pp ix-xvi
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Results of a Canadian study examining the prevalence and potential for developing compassion fatigue and burnout in radiation therapists
- Carol Gillies, Bonnie Bristow, Francois Gallant, Kari Osmar, Irene Lange-Mechlen, William Tyler Tran
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- Journal:
- Journal of Radiotherapy in Practice / Volume 13 / Issue 4 / December 2014
- Published online by Cambridge University Press:
- 23 April 2014, pp. 383-392
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Objective
Caring is a fundamental tenet of healthcare. Caring ‘too much’ can result in compassion fatigue syndrome and is often linked to burnout and low morale. The objective of this study was to examine compassion fatigue, secondary traumatic stress (STS) and burnout by investigating the relationship between levels of compassion (compassion satisfaction) and STS and burnout. The study also aimed to identify radiation therapist (RTTs) groups who may be at risk for developing (STS) and burnout. Finally, we investigated the level of social support that RTTs receive.
MethodsRTTs practicing across Canada were invited to participate in an electronic questionnaire. The questionnaire consisted of: demographic information including health-related issues and occupational variables; the Professional Quality of Life Compassion Satisfaction and Fatigue Questionnaire (ProQOL-V) to assess the potential for compassion satisfaction and vulnerability for STS and burnout; and the Multidimensional Scale of Perceived Social Support (MSPSS) to examine the level and sources of social support. A two-way ANOVA was performed to test the statistical significance between varying groups within the study population. A linear regression analysis using potential co-factors was used to test correlations between compassion fatigue, compassion satisfaction and burnout and variables in age, education, years of experience and levels of caring to patients.
ResultsA total of 477 survey responses were received representing a 36% response rate. Results of the regression analyses generally indicate inverse correlations between the risks associated with compassion satisfaction, burnout and STS compared with the independent study variables of age, education, years of experience and levels of caring to patients. It was observed that responses were not linear within subgroups (age groups, education classifications, years of study).
ConclusionRTTs practicing in Canada have a substantial social support network and demonstrate high levels of compassion satisfaction in their daily practice. The results of the study indicate that compassion levels are inversely correlated with burnout and compassion fatigue, although some groups may be at higher risk than others. A possible risk catalyst for compassion fatigue and burnout is associated with underdeveloped managerial workplace support programmes.
Chapter 9 - Responding to parents with complex needs who are involved with statutory child protection services
- Edited by Fiona Arney, University of South Australia, Dorothy Scott, University of South Australia
- Foreword by Fiona Stanley, University of South Australia
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- Book:
- Working with Vulnerable Families
- Published online:
- 05 June 2012
- Print publication:
- 17 May 2010, pp 187-208
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Summary
Learning goals
This chapter will enable you to:
Understand some of the characteristics of families who become involved with statutory child protection services
Understand some of the barriers to working collaboratively to assist families with complex problems who are involved with statutory child protection services
Recognise how intersectoral collaboration can support families with complex problems who are involved with statutory child protection services
Gain knowledge of how a program designed to work with families experiencing mental health problems and child protection concerns can overcome the barriers to collaborative work with families with complex needs.
Introduction
Inter-agency or inter-professional conflict is worse in bad cases, what happens is you see the other person as having the solution, you can't fix it, so you imagine they can fix it, so you blame them for not fixing it and then get angry… I could see that all over the place.
– Staff member interviewed for the evaluation of the Mental Health Liaison ProjectMental health is one issue…child is another issue…issues bounce back and clash each other… [The child protection service] needs to take mental illness seriously, serious things could happen, [the child protection service] need to be more active in connecting people to services, get people's mental health stable because the concern is for the children. [The child protection service] need to take more steps to help families [in this situation]. […]