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Katz, Kimberly, and Oluwatoyin Oduntan. "Patricia Romero 1934–2015." Review of Middle East Studies 50, no. 2 (August 2016): 234–35. http://dx.doi.org/10.1017/rms.2016.144.
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Patricia Romero was born on 28 July 1934 and raised in Ohio. She earned her B.S. at Central State University in Education in 1964 while raising three boys. She chose Central State, a Historically Black University, both for its proximity and also, according to her middle son Arthur, for the “energy that was manifest in the burgeoning civil rights movement.” After graduating, she pursued her Master's degree at Miami University of Ohio in 1965, while raising her sons on her own and taking on a teaching role at Central State University. Ohio would round out Dr. Romero's education as she completed her Ph.D. in African History at The Ohio State University in 1971. She worked as a research assistant at the Association for the Study of African American Life and History, in Washington, D.C., to which she contributed a volume to its series, I Too Am America (1969), and as Editorial Director for United Publishing Company. She coauthored or edited four books during those years about Blacks in America, including: In Black America, 1968: The Year of the Awakening (ed.) and Negro Americans in the Civil War (coauthor). She enjoyed taking her sons around and visiting family members near sites of the nation's capital.
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DeVore, Melanie L., and Kathleen B. Pigg. "Donald Pinkava's journey from Asteraceae to Cactaceae: from the Ohio State University to Arizona State University." Journal of the Botanical Research Institute of Texas 16, no. 1 (July 15, 2022): 273–80. http://dx.doi.org/10.17348/jbrit.v16.i1.1232.
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Donald J. Pinkava is best known for his application of cytogenetics in unraveling the complex interspecific hybridization in the prickly pear genus Opuntia Mill. in the southwestern United States extending down into northern and central Mexico. Using cytogenetics, Pinkava delimited species boundaries within Opuntia for taxonomic treatments. His work on Opuntia in the Chihuahuan Desert led to later comprehensive contributions in the Flora of North America and the Flora of Arizona that include opuntias not only in the Southwest but in every US state. Pinkava's systematic knowledge, as reflected in his taxonomic treatments provided the basic scientific framework needed for ongoing conservation of Cactaceae in the Southwest to the present day. Interestingly, the starting point for all of Pinkava's contributions in Cactaceae began with his initial studies of Asteraceae as a student of T. Richard Fisher at The Ohio State University (OSU), an institution with longstanding research interests in the Asteraceae. It is there that he selected a genus, Berlandiera DC as his dissertation topic. Ironically, this genus has a range from the drier sites of the Eastern Coastal Plains, into the Ozark and Ouachita Mountains, with a disjunct distribution in the mountain floras of southeastern Arizona and Northern Mexico. Like Berlandiera, Pinkava’s own work reflects techniques and training in the eastern US, that migrated and was used as the basis for his groundbreaking studies of Cactaceae in the Southwest.
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Dixon, Robert S., Steven W. Ellingson, and Ronald J. Koch. "A Radio Frequency Interference Survey of Central Ohio." International Astronomical Union Colloquium 112 (1991): 181–87. http://dx.doi.org/10.1017/s025292110000395x.
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ABSTRACTA long-term radio frequency interference monitoring program is now in progress at the Ohio State University Radio Observatory. Current observations encompass the 1-2 GHz band, measuring the signal strength in each 150 KHz subband. Preliminary results show many strong and persistent signals, and wide bands in which no signals are detected. Daily and weekly variations appear to be correlated with periods of maximum human activity such as “rush hours”. It may be that aircraft reflections are causing many of the signals to be received, and that airline schedules correlate with “rush hours”. The program is being upgraded to automatically measure the direction of arrival of each signal, as an aid to further identify it. This directional information will also be used in designing rolled edges and side shields for the co-located OSU Radio Telescope, to further reduce its vulnerability to RFI.
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Reza Ghods, M., and Thomas W. Foster. "Conversation with a Revolutionary." Middle East Studies Association Bulletin 36, no. 1 (2002): 27–32. http://dx.doi.org/10.1017/s0026318400044047.
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Dr. Ebrahim Yazdi, who played a pivotal role in the Iranian revolution of 1979, and who is today a leading figure among Iran’s liberal political dissidents, visited the US in early November 2000 and spoke at several American universities, including Ohio State University. During his visit, we hosted a small reception for Dr. Yazdi at a home in central Ohio and had the opportunity of engaging him in an extended conversation about the events of the revolution, his personal relationship with the Ayatollah Khomeini, his views on the current political situation in Iran, and his thoughts on the future of Iran’s relationship with the US.
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Lindquist, Danille Christensen. ""Locating" the Nation: Football Game Day and American Dreams in Central Ohio." Journal of American Folklore 119, no. 474 (October 1, 2006): 444–88. http://dx.doi.org/10.2307/4137650.
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Abstract This article suggests how abstract ideas like "nation" are lived and situated by examining recurring features ofAmerican football as it is experienced by spectators in central Ohio. Football-an institutionalized drama formed by its inventors to address questions of national identity and social relations-is embedded within the generically complex event known as "game day" and is framed by ongoing social practices that stem from the sport’s competitive structure. As a multifaceted event grounded in both historical contexts and live performances, this spectator sport provides an ideal case for highlighting connections among form, ideology, and identity. This article argues that as a celebratory complex, Ohio State University football enacts aspects of national identity (including tropes of competitive opportunity, mechanized teamwork, and homeland defense) in terms of shared experiences and expressions grounded in local affiliations. In particular, the much-anticipated and ritually structured performances of the OSUMarching Band guide fans in endorsing "America" and its attendant ideologies while simultaneously emphasizing local difference.
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Borland, Katherine. "The Columbus-Copapayo Sister-City Collection: A Service Learning/Research Model." Practicing Anthropology 39, no. 2 (April 1, 2017): 39–43. http://dx.doi.org/10.17730/0888-4552.39.2.39.
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A central difficulty of the service learning paradigm is how to connect with and sustain a community identified project within the structural limitations of an academic course. The Columbus-Copapayo Sister-City Collection at the Ohio State University Folklore Archives resulted from an attempt to construct a research partnership independently of coursework to which service learning coursework could be appended. The model provides a flexible, open-ended means for pursuing academic-community collaborations.
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Rinehardt, Hannah, Evan Morgan, Mahmoud Kassem, Marilly Palettas, Abdul Miah, Iyad Alnahhas, Pilar Guillermo Prieto Eibl, et al. "Assessment of Leptomeningeal Carcinomatosis Diagnosis and Outcomes from 2005 to 2015 at Ohio State University." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e13554-e13554. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e13554.
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e13554 Background: Leptomeningeal carcinomatosis (LMC) is a complication of advanced malignancies wherein primary tumors metastasize to the leptomeninges surrounding brain and spinal cord. LMC complicates 4-15% of malignant solid tumors with incidence increasing as survival of patients with advanced cancer improves. Diagnostic methods include magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology. MRI findings may be nonspecific, and the gold standard of diagnosis is malignant cytology on CSF analysis. We assessed detection methods, incidence, and outcomes of LMC at The Ohio State University Comprehensive Cancer Center from 2005-2015. Methods: This was an IRB-approved single-institution retrospective study of 160 patients with confirmed diagnosis of LMC who were treated at the OSUCCC-James between Jan 1, 2005 and Dec 31, 2015. Patients with hematologic and central nervous system malignancies were excluded. Descriptive statistics were used to summarize demographic and clinical characteristics. Overall survival (OS) was defined as time from LMC diagnosis to death or last known follow-up, and was generated using Kaplan-Meier methods. Results: Median age of LMC diagnosis was 55.8 years (range: 48, 62.5). 69 (43%) patients had primary breast cancer, 41 (26%) had lung cancer, and 17 (11%) had melanoma. 73 patients (46%) presented with stage IV disease at initial diagnosis of the primary cancer, 41 (26%) with stage III disease, and 26 (16%) with stage II disease. Median time from diagnosis of primary cancer to diagnosis of LMC was 2 years (range: 0, 31.2). 158 (99%) patients had metastases at the time of LMC diagnosis, predominantly in bone (36%) or brain (36%). Median OS was 1.9 months (CI: 1.3, 2.5). 160 (100%) patients had an MRI of the brain or spine and 155 (97%) had MRI findings consistent with LMC. 75 (47%) patients underwent lumbar puncture, and 39 (52%) had CSF cytology positive for malignancy. Conclusions: Patients with LMC commonly presented with stage IV breast cancer, lung cancer, or melanoma with metastases to the brain or bone. Despite treatment, prognosis remains poor and confirmation of diagnosis can be challenging. Clinicians should have a low threshold for investigating LMC in high risk patients presenting with neurologic signs or symptoms.
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Blaiset, MA, CG Couto, KL Evans, and DD Smeak. "Complications of indwelling, silastic central venous access catheters in dogs and cats." Journal of the American Animal Hospital Association 31, no. 5 (September 1, 1995): 379–84. http://dx.doi.org/10.5326/15473317-31-5-379.
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The records of 35 dogs and two cats with Broviac-Cookea catheters implanted during a one-year period at The Ohio State University Veterinary Teaching Hospital (OSU-VTH) were reviewed for complications. In 36 patients, the catheters were used for daily anesthesia associated with cobalt radiotherapy, and in one dog the catheter was used for parenteral hyperalimentation. The catheters were in place for a mean of 16.7 days. Complications occurred in five patients and included infection or sepsis (n = 3), local abscess formation (n = 1), and local induration (n = 1); all the complications resolved with appropriate therapy. Broviac-Cooke catheters should be considered for use in dogs and cats requiring frequent blood sampling, repeated intravenous access, or in those for which routine venous access is difficult or impossible. The complication rate is minimal (13%) and is similar to that reported in studies of humans with indwelling, silastic catheters.
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Dabelko-Schoeny, Holly, Smitha Rao, Marisa Sheldon, and White Katie. "THE AGING NETWORK AND CLIMATE RESILIENCE." Innovation in Aging 7, Supplement_1 (December 1, 2023): 254. http://dx.doi.org/10.1093/geroni/igad104.0843.
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Abstract Originally established to support planning and services related to community-based supports, Area Agencies on Aging (AAA) are well-positioned to lead cutting edge innovations driven by local community needs and changing socio-environmental contexts. This presentation illustrates a partnership between the Central Ohio Area Agency on Aging (COAAA) and the Age-Friendly Innovation Center at The Ohio State University focused on advancing research-informed practice in response to the realities of aging in a warmer world. This project included three main phases. First, safety and emergency preparedness data were collected from individuals aged 50 and older living in central Ohio through a random sample survey (N=1417), revealing 25% of non-white residents (compared to 21% white) did not have or know they have 3-day emergency supplies, food, and medicine, and 84% of residents in urban areas did not have access to an alternative source of power in event of outages. Second, a community conversation identifying priorities and needs related to the rising number of extreme weather events was held with COAAA leadership, community organizations, and residents. Third, targeting locations of high density of older adults at highest risk, the last phase of this work focused on the development of a tool to reduce harm for older adults living in affordable housing in partnership with COAAA embedded Service Coordinators. This project illustrates how AAAs can partner with applied researchers to innovate and strengthen services within communities and build evidence to address emerging community needs across the aging network.
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Williams, Nicole, Hannah Rinehardt, Evan Morgan, Mahmoud Kassem, Marilly Palettas, Vinay Puduvalli, Pierre Giglo, et al. "LPTO-10. ASSESSMENT OF LEPTOMENINGEAL CARCINOMATOSIS DIAGNOSIS AND OUTCOMES FROM 2005 TO 2015 AT THE OHIO STATE UNIVERSITY." Neuro-Oncology Advances 1, Supplement_1 (August 2019): i8. http://dx.doi.org/10.1093/noajnl/vdz014.033.
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Abstract BACKGROUND: Leptomeningeal carcinomatosis (LMC) is a complication of solid tumor malignancies where tumors metastasize to the leptomeninges. LMC complicates 4–15% of malignancies with incidence increasing as survival of patients with advanced cancer improves. Diagnostic methods include magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology. We assessed detection methods, incidence, and outcomes of LMC at The Ohio State University Comprehensive Cancer Center from 2005–2015. METHODS: This was a single-institution retrospective study of 160 patients with confirmed diagnosis of LMC. Patients with hematologic and central nervous system malignancies were excluded. Descriptive statistics were used to summarize demographic and clinical characteristics. Overall survival (OS) was defined as time from LMC diagnosis to death or last known follow-up, and was generated using Kaplan-Meier methods. RESULTS: Median age of LMC diagnosis was 55.8 years (range: 48, 62.5). 69 (43%) patients had primary breast cancer, 41 (26%) had lung cancer, and 17 (11%) had melanoma. 73 patients (46%) presented with stage IV disease at initial diagnosis of the primary cancer, 41 (26%) with stage III disease, and 26 (16%) with stage II disease. Median time from diagnosis of primary cancer to diagnosis of LMC was 2 years (range: 0, 31.2). 158 (99%) patients had metastases at the time of LMC diagnosis, predominantly in bone (36%) or brain (36%). Median OS was 1.9 months (CI: 1.3, 2.5). 160 (100%) patients had an MRI of the brain or spine and 155 (97%) had MRI findings consistent with LMC. 75 (47%) patients underwent lumbar puncture, and 39 (52%) had CSF cytology positive for malignancy. CONCLUSIONS: Despite treatment, prognosis remains poor and confirmation of diagnosis can be challenging. This study highlights the need for novel therapeutics and improved diagnostic techniques for patients with LMC.
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Bechtel, Susan K., and David M. Stothers. "New Perspectives on the Settlement-Subsistence System of the Late Woodland Western Basin Tradition, ca. 500–1300 A.D." North American Archaeologist 14, no. 2 (October 1993): 95–121. http://dx.doi.org/10.2190/pfhd-606f-a06d-uc61.
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Based on joint efforts by the Williams County Historical Society and the Laboratories of Ethnoarchaeology at the University of Toledo, thirty-six new sites, including six Western Basin Tradition ceramic sites, have been documented in the tri-state region of northeastern Indiana, northwestern Ohio, and south-central Michigan. Also, data collected from throughout the Western Lake Erie region since 1984 has necessitated several revisions in the 1984 settlement-subsistence model proposed for the Late Woodland Western Basin Tradition populations, ca. 1000–1300 A.D. (Stothers, Graves, and Redmond, 1984). Key changes involve the relative sizes of functionally different site types that form component parts of a larger settlement system, a lack of formal village life, and a new perspective on seasonal patterns of population coalescence and dispersal.
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Braun, Ashlea, Joshua Hawley, and Jennifer Garner. "Maintaining School Foodservice Operations During COVID-19: The Case of Ohio." Current Developments in Nutrition 5, Supplement_2 (June 2021): 209. http://dx.doi.org/10.1093/cdn/nzab029_010.
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Abstract Objectives COVID-19-related school closures hindered the provision of meals to school-age youth nationwide, risking deficits in nutrition, health, and development. Foodservice staff faced substantial difficulties in their efforts to maintain foodservice operations. The state of Ohio, in which the prevalence of child food insecurity exceeds the national average (18.9% versus 15.2%), offers an illustrative case for exploration of these adaptations. The objective of this study was to characterize COVID-19-related foodservice adaptations, including impacts on both summer and school year meal provision. Methods An administrative representative from each Ohio school district was emailed in December 2020 and invited to complete an online survey. This cross-sectional analysis focuses on public school district experiences. Results Among responding districts (n = 298 of 611, 49%), the majority continued providing meals after the Spring 2020 shutdowns (73%) and functioned as an ‘open site’ (63%), offering food to students’ families and households without district affiliation. Most schools offered meals either once weekly (41%) or once per weekday (30%) and offered an average of 3.7 days-worth of meals at a time. Half (48%) of the districts employed a pre-order system. Districts used various distribution methods: 76% had central school or district-affiliated pick-up point(s); 38% delivered meals to community location(s); and 34% delivered directly to some households. Supply chain disruptions led the vast majority of schools to seek USDA meal pattern waivers. Only 39% of districts maintained food service operations during summer 2020. The majority of districts were hybrid (59%) or fully online (24%) for at least a portion of Fall 2020, yet only 12% reported offering meal delivery or pick-up. Districts reported many “successes” (e.g., feeding students safely) and “challenges” (e.g., extra costs, poor parental participation). Conclusions Public school districts in Ohio made numerous COVID-related foodservice adaptations in order to serve both their students and the community at large, though districts reported poor utilization of this service. Future research should evaluate whether reduced access to school meals impacted child food security and food security-related outcomes during this period. Funding Sources Office of Research at The Ohio State University
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Jezek, Kenneth C. "Surface elevation and velocity changes on the south-central Greenland ice sheet: 1980–2011." Journal of Glaciology 58, no. 212 (2012): 1201–11. http://dx.doi.org/10.3189/2012jog12j031.
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AbstractWe extend through 2011 an ice-sheet elevation and surface velocity record across three measurement networks established in south-central Greenland by The Ohio State University in 1980/81. Surface parameters are derived from repeat GPS in situ observations, elevations measured by airborne laser altimetry and by the Ice, Cloud and land Elevation Satellite (ICESat). Elevations at the western network steadily rose early in the record by 0.10 ± 0.02 m a-1, but an eastward-progressing thinning trend began in the mid-1990s followed by a ~1m elevation drop at all stations from 2005 to 2011. Measurements weakly suggest a surface velocity increase at the western cluster from 1980 to 2005. At the central network, elevations rose by 0.08 ± 0.02 m a-1 through 2005 and surface speed increased by 0.5–0.7 m a-1. Surface elevations at the central network remained nearly constant thereafter. Thickening occurred at the southern ice divide by 0.05 ± 0.02 m a-1, while east of the divide the ice sheet thinned with increasing rate from the divide, likely because of decreasing accumulation rate trends and drawdown into rapidly retreating coastal glaciers. Our most recent data show that thinning rates are slowing at several sites just east of the divide and that the elevation at the divide continues to increase.
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Lapotaire, Jane. "Pam Gems, Jane Lapotaire, and a Phenomenon Named Piaf." New Theatre Quarterly 33, no. 3 (July 10, 2017): 219–26. http://dx.doi.org/10.1017/s0266464x17000276.
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In this interview, award-winning actress Jane Lapotaire talks about the process of devel - op ing the central role in Pam Gems's Piaf, for which she won the Tony Award for Best Actress in 1981. She further describes how Gems gave her the chance to play a protagonist for the first time in her career in the British male-dominated theatre of the late 1970s. Gems established herself as a major feminist playwright in the British theatre in 1976 with the production of Dusa, Fish, Stas and Vi, although it was Piaf that brought her international attention and acclaim. Lapotaire discusses the significance of the female mission to create protagonist roles for women in the theatre who did not previously have the opportunity to drive a play's narrative. Esmaeil Najar is a translator, director, and theatre historian. He is currently writing his doctoral dissertation at the Ohio State University on Pam Gems's life and impact on British theatre.
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Petrina, Stephen. "Luella Cole, Sidney Pressey, and Educational Psychoanalysis, 1921–1931." History of Education Quarterly 44, no. 4 (2004): 524–53. http://dx.doi.org/10.1111/j.1748-5959.2004.tb00019.x.
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Trends in thePsychological Indexindicated a change in resources directed toward education between the early 1910s and late 1920s. By 1930, “educational” studies accounted for the highest percentage—about 25 percent—of 25, 472 articles in psychology, with studies in “abnormal” and “social” psychology accounting for respectively 21 percent and 19 percent. This trend, evident in theReader's Guide to Periodical Literatureas well, reflected an increasing popularity of psychotherapeutic knowledge and products in clinics, courts, hospitals, prisons, and schools. As a growth market, education offered resources and was viewed as the most promising institution in the United States for regulating normality. By the late 1910s, “educational psychology” was central to institutions of teacher training. Certainly, for psychologists, psychology was the “the source of fundamental assumptions” for guiding educational practice. Teachers' views were similar. In one survey in the mid 1920s, teachers recognized educational psychology as the most intrinsically valuable course in their university programs. In other words, within institutions like The Ohio State University (OSU), requirements in teacher training provided psychologists with a mechanism for demonstrating the uses of psychotherapeutic knowledge, products, and procedures. These trends beg a simple question: What was educational psychology?
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van Ittersum, Martine, Felicia Gottmann, and Tristan Mostert. "Writing Global History and Its Challenges—A Workshop with Jürgen Osterhammel and Geoffrey Parker." Itinerario 40, no. 3 (December 2016): 357–76. http://dx.doi.org/10.1017/s0165115316000607.
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On 4 June 2016, Jürgen Osterhammel of the University of Konstanz and Geoffrey Parker of Ohio State University gave an all-day workshop on global history for graduate students and junior and senior scholars of the Universities of Dundee and St. Andrews in Scotland. The workshop consisted of three discussion sessions, each with a different theme, namely the conceptualization(s), parameters, and possible future(s) of global history. The central question was to what extent this fast-changing field required adjustments of “normal” historiographical methodologies and epistemologies. The workshop participants agreed that global history focuses in particular on connections across large spaces or long timespans, or both. Yet reconstructing these webs of connections should not obscure global inequalities. In the case of empires, many of the exchanges across space and time have been ordered in a hierarchical fashion—metropoles profiting from peripheral spaces, for example—and imposed by certain groups of people on others, resulting in, for example, the enslavement or extermination of indigenous peoples. As historians, we should also ask ourselves what we do about peoples or areas that were or remain unconnected, local, and remote. Where does globalization end?
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Pokhrel, Srijana, Kaitlin A. Read, Devin M. Jones, Michael D. Powell, Robert T. Warren, and Kenneth J. Oestreich. "Eos regulates IL-7 signaling and central memory T cell differentiation." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 57.04. http://dx.doi.org/10.4049/jimmunol.208.supp.57.04.
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Abstract CD4+ central memory T cells (TCM) are key players in recall immune responses and thus are critical to long-term immunity. Despite their importance, much remains to be defined regarding the mechanisms that promote their differentiation and survival. Ikaros zinc finger (IkZF) transcription factors are known regulators of T and B cell differentiation programs. To date, the IkZF factor Eos has been mainly linked to regulatory T cell suppressive functions. Now, we have found that Eos is expressed at elevated levels in CD4+ TCM populations. Comparison between WT and Eos-deficient T cells in a murine model of influenza infection revealed a decrease in the percentage of CD4+ TCM cells in the absence of Eos, suggesting that Eos promotes TCM differentiation and/or survival. Using an established in vitro model of CD4+ TCM-like cell differentiation, we found that loss of Eos correlated with reduced expression of genes encoding key TCM transcription factors and cell surface markers. Further, Eos deficiency resulted in decreased STAT5 activation downstream of IL-7 signaling, a known positive regulator of TCM populations. In WT cells, IL-7 treatment increased Eos expression, suggesting a positive feed-forward relationship exists between Eos expression and IL-7/STAT5 signaling. Overall, our findings demonstrate that Eos is an important regulator of TCM populations. Understanding the mechanisms by which Eos regulates TCM function and survival may therefore be of interest in exploiting TCM protection against re-infection for therapeutic benefit. Supported by a grant from NIAID (NIH- R01 AI134972) and funds through The Ohio State University College of Medicine
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Dancey, William S. "The Archaic of Northeastern Ohio. Olaf H. Prufer and Dana A. Long. Kent State Research Papers in Archaeology No. 6, Mark F. Seeman, editor. Kent State University Press, Kent, Ohio, 1986. vi + 89 pp., figures, tables, references. $8.50 (paper). - The Locust Site (33 Mu 160): The 1983 Excavation of a Multicomponent Workshop in East Central Ohio. Mark F. Seeman. Kent State Research Papers in Archaeology No. 7. Kent State University Press, Kent, Ohio, 1985. vii + 111 pp., figures, tables, references. $8.50 (paper)." American Antiquity 53, no. 1 (January 1988): 215. http://dx.doi.org/10.2307/281199.
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KITLV, Redactie. "Book Reviews." Bijdragen tot de taal-, land- en volkenkunde / Journal of the Humanities and Social Sciences of Southeast Asia 157, no. 4 (2001): 903–59. http://dx.doi.org/10.1163/22134379-90003797.
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-Doris Jedamski, René Witte, De Indische radio-omroep; Overheidsbeleid en ontwikkeling, 1923-1942. Hilversum: Verloren, 1998, 202 pp. -Edwin Jurriëns, Philip Kitley, Television, nation, and culture in Indonesia. Athens, Ohio: Ohio University Center for International Studies, 2000, xviii + 411 pp. [Research in International Studies, Southeast Asia Series 104.] -Gerrit Knaap, Scott Merrillees, Batavia in nineteenth century photographs. Richmond, Surrey: Curzon, 2000, 282 pp. -C.C. MacKnight, David Bulbeck ,Land of iron; The historical archaelogy of Luwu and the Cenrana valley; Results of the Origin of Complex Society in South Sulawesi Project (OXIS). Hull and Canberra: Centre for South-East Asian Studies, University of Hull / School of Archaeology and Anthropology, Australian National University, 2000, vi + 141 pp., Ian Caldwell (eds) -Niels Mulder, Toh Goda, Political culture and ethnicity; An anthropological study in Southeast Asia. Quezon City: New Day, 1999, xviii + 182 pp. -Niels Mulder, Norman G. Owen, The Bikol blend; Bikolanos and their history. Quezon City: New Day, 1999, x + 291 pp. -Anton Ploeg, Donald Tuzin, Social complexity in the making; A case study among the Arapesh of New Guinea. London: Routledge, 2001, xii + 159 pp. -Henk Schulte-Nordholt, Maarten Kuitenbrouwer, Tussen oriëntalisme en wetenschap; Het Koninklijk Instituut voor Taal-, Land- en Volkenkunde in historisch verband 1851-2001. Leiden: KITLV Uitgeverij, 2001, ix + 362 pp. -Sri Margana, Peter Carey ,The archive of Yogyakarta, Volume II, Documents relating to economic and agrarian affairs. New York: Oxford University Press, 2000, 566 pp., Mason C. Hoadley (eds) -Eric Venbrux, Wilfried van Damme, Bijdragen over kunst en cultuur in Oceanië/Studies in Oceanic Art and Culture. Gent: Academia Press, 2000, 122 pp. -Edwin Wieringa, Raharjo Suwandi, A quest for justice; The millenary aspirations of a contemporary Javanese wali. Leiden: KITLV Press, 2000, x + 229 pp. [Verhandelingen van het Koninklijk Instituut voor Taal-, Land- en Volkenkunde 182.] -Willem G. Wolters, Benito J. Legarda Jr., After the galleons; Foreign trade, economic change and entrepreneurship in the nineteenth-century Philippines. Quezon City: Ateneo de Manila University Press, 1999, xiv + 401 pp. -Brenda Yeoh, Jürgen Rüland, The dynamics of metropolitan management in Southeast Asia. Singapore: Institute of Southeast Asian Studies, 1996, 230 pp. -David Henley, Albert Schrauwers, Colonial 'reformation' in the highlands of Central Sulawesi, Indonesia, 1892-1995. Toronto: University of Toronto Press, 2000, xiv + 279 pp. -David Henley, Lorraine V. Aragon, Fields of the Lord; Animism, Christian minorities, and state development in Indonesia. Honolulu: University of Hawai'i Press, 2000, xii + 383 pp. -Jennifer W. Nourse, Jennifer W. Nourse, Conceiving spirits; Birth rituals and contested identities among Laujé of Indonesia. Washington, D.C.: Smithsonian Institution Press, 1999, xii + 308 pp.
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Lee, Joan. "Reviewer Acknowledgements for Sustainable Agriculture Research, Vol. 7, No. 1." Sustainable Agriculture Research 7, no. 1 (January 30, 2018): 156. http://dx.doi.org/10.5539/sar.v7n1p156.
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Sustainable Agriculture Research wishes to acknowledge the following individuals for their assistance with peer review of manuscripts for this issue. Their help and contributions in maintaining the quality of the journal are greatly appreciated.Sustainable Agriculture Research is recruiting reviewers for the journal. If you are interested in becoming a reviewer, we welcome you to join us. Please find the application form and details at http://www.ccsenet.org/reviewer and e-mail the completed application form to sar@ccsenet.org. Reviewers for Volume 7, Number 1Aftab Alam, Vice President Agriculture (R&D), Edenworks Inc. New York, United StatesAhmed Ghannam, University of Strasbourg, FranceAmor Slama, Science Faculty of Bizerte, TunisiaBed Mani Dahal, Kathmandu University, NepalBenedict Jonathan Kayombo, Botswana College of Agriculture, BotswanaBeye Amadou Moustapha, Rice Research Center, Cote d'IvoireCarlos Enrrik Pedrosa, Alis - Bom Despacho - MG, BrazilClara Ines Pardo Martinez, University of La Salle, ColombiaCristina Bianca Pocol, University of Agricultural Sciences & Veterinary Medicine of Cluj Napoca, RomaniaEntessar Mohammad Al JBawi, General Commission for Scientific Agricultural Research, SyriaFrancesco Sunseri, Università Mediterranea di Reggio Calabria - Italy, ItalyGema Parra, Universidad de Jaén, SpainInder Pal Singh, Guru Angad Dev Veterinary and Animal Science University (GADVASU), IndiaJanakie Shiroma Saparamadu, The Open University of Sri Lanka, Sri LankaJiun-Yan Loh, UCSI University, MalaysiaKatarzyna Panasiewicz, Pozna? University of Life Sciences, Department of Agronomy, PolandManuel Teles Oliveira, University Tras os Montes Alto Douro (UTAD), PortugalMarcelo Augusto Gonçalves Bardi, Universidade Sao Francisco, BrazilMaren Langhof, Julius Kühn-Institut, GermanyMehmet Yagmur, Ahi Evran University, TurkeyMrutyunjay Swain, Sardar Patel University, IndiaMukantwali Christine, Rwanda Agriculture Board, RwandaMurtazain Raza, Subsidiary of Habib Bank AG Zurich, PakistanPelin Günç Ergönül, Celal Bayar University, TurkeyRaghuveer Sripathi, Advanta US, Inc., USARam Swaroop Jat, ICAR-Directorate of Medicinal and Aromatic Plants Research, IndiaRoberto José Zoppolo, Instituto Nacional de Investigación Agropecuaria (Uruguay), UruguaySilviu Beciu, University of Agronomic Sciences and Veterinary Medicine Bucharest, RomaniaStefano Marino, University of Molise, ItalySubbu Kumarappan, Ohio State ATI, United StatesSubhash Chand, Central Agricultural Research Institute CARI Port Blair, IndiaTenaw Workayehu, Hawassa Research Center, Southern Agricultural Research Institute (SARI), Ethiopia
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Wolner, Edward W. "Art: Architecture. Joint Conference Sponsored by the Wexner Center for the Visual Arts. The Ohio State University Department of Architecture and the ACSA East Central Region, Fall 1990." Journal of Architectural Education (1984-) 44, no. 4 (August 1991): 248. http://dx.doi.org/10.2307/1425151.
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Guerau-De-Arellano, Mireia, Shouvonik Sengupta, Stephanie Amici, Lindsay Webb, Kelly Weiss, and Kewal Asosingh. "Contribution of Protein Arginine Methyltransferase (PRMT)5 to House Dust Mite Asthma." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 119.6. http://dx.doi.org/10.4049/jimmunol.202.supp.119.6.
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Abstract Severe asthma affects 2.4 million Americans and 23.8 million people worldwide and accounts for the majority of total asthma hospital costs. Most severe asthma is mediated by Th17/neutrophilic responses, alone or combined with Th2 and/or Th1 responses. In contrast, Treg responses are deficient. Protein Arginine Methyl Transferase (PRMT) 5 catalyzes symmetric dimethylation (SDM) of arginine on histones and other proteins, thereby regulating gene expression. PRMT5 promotes murine Th1/Th17 responses in central nervous system autoimmunity. However, its impact on asthma has not been established. We evaluated the role of PRMT5 on mouse models of house dust mite (HDM) asthma. PRMT5 and its symmetric demethylation activity were increased in lung infiltrating cells during Th2/Th17-mediated HDM severe asthma, suggesting a role for PRMT5 in asthma pathogenesis. To determine the contribution of PRMT5 to HDM asthma pathogenesis, we used first-in-class PRMT5-specific inhibitors developed at The Ohio State University. PRMT5 inhibitor HLCL65 modulated Th1, Th2 and Th17 differentiation and suppressed airway hyperreactivity in Th2/Th17 models of house dust mite (HDM)-induced asthma. Overall, these results support a role for PRMT5 in severe asthma pathogenesis.
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Mahboubi, A. A., and R. Lal. "Long-term tillage effects on changes in structural properties of two soils in central Ohio1Contribution from The School of Natural Resources, The Ohio State University, Columbus, OH, USA.1." Soil and Tillage Research 45, no. 1-2 (May 1998): 107–18. http://dx.doi.org/10.1016/s0933-3630(96)00127-4.
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Corace, III, R. Gregory, P. Charles Goebel, David M. Hix, Tracy Casselman, and Nancy E. Seefelt. "Ecological forestry at National Wildlife Refuges: Experiences from Seney National Wildlife Refuge and Kirtland’s Warbler Wildlife Management Area, USA." Forestry Chronicle 85, no. 5 (October 1, 2009): 695–701. http://dx.doi.org/10.5558/tfc85695-5.
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Although land management over much of the history of the U.S. Fish and Wildlife Service’s National Wildlife Refuge System (NWRS) has emphasized single-species management, recent policy has encouraged land managers to focus on broader ecosystem restoration goals. One framework for forest ecosystem management that is becoming more popular in the NWRS and other federal and state resource agencies has been termed “ecological forestry”—an approach to forest ecosystem management where the focus is on incorporating an understanding of the outcomes of natural disturbances and stand development processes into designing silvicultural practices. This approach stresses understanding the effects of natural disturbances on biological legacies, structural and compositional heterogeneity, and the recovery periods between disturbance events (including how this recovery period influences stand complexity). Recently, resource managers and ecologists from Seney National Wildlife Refuge, The Ohio State University, and Central Michigan University have partnered to examine how these guiding principles can be integrated into NWRS forest ecosystem management. Specifically, we are partnering to develop management strategies to help: 1) restore the once extensive mixed-pine forest ecosystems of eastern Upper Michigan; 2) mitigate the effects of the beech-bark disease complex on American beech (Fagus grandifolia Ehrh.), a foundation species in northern hardwood forests of eastern North America; and 3) promote more natural forest patterns for wildlife species of young jack pine (Pinus banksiana Lamb.) forest ecosystems, including the federally endangered Kirtland’s warbler (Dendroica kirtlandii). These efforts are ongoing and will continue to be monitored over time. However, initial collaborations suggest that the NWRS provides an excellent crucible to study the application of ecological forestry principles and develop novel ways to manage forest ecosystems. Key words: ecological forestry, forest restoration, Kirtland’s warbler, National Wildlife Refuge, U.S. Fish and Wildlife Service
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Masias Castanon, Camila, Haiwa Wu, Michael McGookey, Lauren Jay, Haifeng Wu, Spero R. Cataland, and Shangbin Yang. "No Major Differences in Outcomes Between the Initial and Relapse Episodes in Patients with Thrombotic Thrombocytopenic Purpura: The Experience from the Ohio State University Registry." Blood 128, no. 22 (December 2, 2016): 2544. http://dx.doi.org/10.1182/blood.v128.22.2544.2544.
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Abstract Background: Thrombotic thrombocytopenic purpura (TTP) is characterized by consumptive thrombocytopenia and microangiopathic hemolytic anemia. At least a third of the patients with TTP will have one or more relapses throughout their life. There is very little data regarding the differences, if any, in clinical presentation and outcomes between the initial and subsequent TTP episodes. This information is relevant to understand if patients that present initially and those that present with a relapse can be seen as equal when being considered for clinical trials. Identifying the characteristics of patients that are prone to relapse will help guide the monitoring of patients after an acute episode of TTP to help to prevent relapse. Methods: Between March 2003 and June 2016 we collected clinical and laboratory data on all patients that presented to the Ohio State University with a diagnosis of acquired TTP (aTTP). The diagnostic criteria for aTTP included: thrombocytopenia, and a microangiopathic hemolytic anemia without an alternative explanation. The diagnosis was confirmed by the finding of severely deficient ADAMTS13 activity (<10%). Patients were consented to participate in our TTP registry and the information obtained included initial clinical presentation, platelets, LDH, kidney function, ADAMTS13 activity and inhibitor titer, number of plasma exchange (PEX) to achieve remission (defined as number of PEX needed to obtain a normal platelet count), and the outcome of the episode; clinical response (normal platelet count and LDH), exacerbation (recurrent TTP within 30 days of last PEX procedure), refractory (more than 30 PEX needed to obtain a clinical response), or death. Results: - All the patients enrolled were included in the study, except those with active cancer, leaving a total of 125 episodes from 57 patients. - 36 of the 57 patients had two or more TTP episodes (relapse rate 63.1%), with 21 of the 57 patients having 3 or more episodes. The time between episodes varied greatly, from 2 months to 8 years. - Of the 125 episodes, there were 42 initial and 83 relapses. - The initial group presented with central nervous system (CNS) symptoms more commonly than the relapse group. They also had significantly lower platelets and a higher LDH than the relapse group. - Regarding treatment, there was no significant difference in the number of PEX needed to achieve remission between the 2 groups. However, there was a significant number of patients in the initial group that needed more than 5 PEX to achieve remission, compared to the relapse group (p<0.0001) - There were no significant differences in the main clinical outcomes between the initial and relapse groups in rates of clinical response (p=0.267), exacerbation (p=0.483), refractory (p=0.075) or death (p=0.066) Conclusions: In their first episode of TTP, patients may present more ill than those patients having relapses (with more CNS symptoms, lower platelets and higher LDH), and may also require more PEX sessions to achieve remission. However, these findings do not change outcomes, and patients in their initial presentation and relapses can be seen as equal in terms of clinical response, exacerbation, refractory disease, and mortality rates. The high relapse rate seen in our registry may be due to the prolonged follow up (13 years) which is more than other series reported. Patients may have a relapse even after several years of being stable. Figure Figure. Table Table. Disclosures No relevant conflicts of interest to declare.
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Uy, Geoffrey L., Jun Yin, Heidi D. Klepin, Shira Dinner, Anthony J. Jaslowski, Stephen A. Strickland, Jane L. Liesveld, John C. Byrd, and Richard M. Stone. "Alliance A041701 - a Randomized Phase 2/3 Study of Conventional Chemotherapy +/- Uproleselan (GMI-1271) in Older Adults with Acute Myeloid Leukemia (AML) Receiving Intensive Induction Chemotherapy." Blood 134, Supplement_1 (November 13, 2019): 1366. http://dx.doi.org/10.1182/blood-2019-127142.
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Uproleselan (GMI-1271) is a novel antagonist of E-selectin, an adhesion molecule expressed on endothelial cells. E-selectin is expressed transiently in the normal vasculature during an inflammatory response and constitutively in the bone marrow (BM). Binding of E-selectin (E-sel) to sialyl Lex, the E-sel ligand (E-sel-L), on the leukemic cell surface activates cell survival pathways and promotes chemotherapy resistance in AML. In preclinical models, blockade of E-selectin with uproleselan disrupts the activation of cell survival pathways and enhanced the efficacy of chemotherapy across multiple AML tumor models. Furthermore, uproleselan protected against chemotherapy-induced mucositis by regulating macrophage trafficking to the site of injury in the gut lining. A previous phase I/II study of uproleselan added to chemotherapy in patients with untreated AML (older adults ≥60 yrs) and relapsed/refractory AML (≥ 18yrs) showed promising remission rates (CR/CRi) and survival outcomes, and reduced rates of mucositis. In the newly diagnosed older patients, high remission rates were achieved overall (CR/CRi 72%) and for the high risk subgroup with sAML (CR/CRi 69%). In this phase 2/3 study, we will test the addition of uproleselan to a standard daunorubicin/cytarabine regimen in older adults with previously untreated AML. The study will enroll patients age ≥ 60 yrs with untreated acute myeloid leukemia. Patients with acute promyelocytic leukemia, activating mutations in FLT3, or evidence of central nervous system involvement are excluded. Subjects are randomized to 7+3 induction (cytarabine + daunorubicin) +/- uproleselan. Subjects achieving a CR/CRi may receive up to 3 cycles of consolidation with intermediate dose cytarabine 2 gm/m2 IV d1-5 +/- uproleselan. The primary phase II objective is to compare the event-free survival (EFS). A sample size of 262 patients was selected for the phase II to detect an improvement in median EFS from 7 months to 11 months (HR= 0.64) with > 95% power, using a log rank test. The phase III primary objective will compare overall survival (OS). For the phase III, a sample size of 335 evaluable patients per arm (670 total inclusive of patients enrolled in phase II) will provide >90% power to detect an improvement in median OS from 12 months to 16 months (HR= 0.75), using a log-rank test. Correlative studies will measure E-selectin ligand on AML blasts and soluble E-selectin and will also measure minimal residual disease after remission induction by multiparameter flow cytometry. A comprehensive geriatric assessment will identify baseline measures associated with EFS and develop a risk model to predict OS among older adults receiving intensive AML therapy. The study is endorsed by SWOG and ECOG-ACRIN and opened to enrollment on 1/16/2019. Figure Disclosures Uy: Astellas: Consultancy; Pfizer: Consultancy; Curis: Consultancy; GlycoMimetics: Consultancy. Dinner:Agios: Consultancy; Pfizer: Consultancy; AstraZeneca: Consultancy. Strickland:Jazz: Consultancy; Sunesis Pharmaceuticals: Research Funding; Pfizer: Consultancy; Kite: Consultancy; Astellas Pharma: Consultancy; AbbVie: Consultancy. Liesveld:Onconova: Other: Data safety monitoring board; Abbvie: Membership on an entity's Board of Directors or advisory committees. Byrd:Acerta: Research Funding; Acerta: Research Funding; Genentech: Research Funding; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; BeiGene: Research Funding; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; Novartis: Other: Travel Expenses, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Genentech: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Acerta: Research Funding; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Ohio State University: Patents & Royalties: OSU-2S; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau. Stone:Argenx, Celgene, Takeda Oncology: Other: Data and Safety Monitoring Board/Committee: ; AbbVie, Actinium, Agios, Argenx, Arog, Astellas, AstraZeneca, Biolinerx, Celgene, Cornerstone Biopharma, Fujifilm, Jazz Pharmaceuticals, Amgen, Ono, Orsenix, Otsuka, Merck, Novartis, Pfizer, Sumitomo, Trovagene: Consultancy; Novartis, Agios, Arog: Research Funding. OffLabel Disclosure: Uproleselan in AML
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Tuazon, Jasmine, Bharath Sreekumar, Kaitlin Read, Michael Yaeger, Sanjay Varikuti, Kymberly M. Gowdy, and Kenneth J. Oestreich. "The Ikaros zinc finger transcription factor Eos as a candidate regulator of TH2 differentiation and function." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 166.21. http://dx.doi.org/10.4049/jimmunol.208.supp.166.21.
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Abstract Although CD4+ T helper 2 (TH2) cells normally defend against parasitic infection, they play a central role in the pathogenesis of allergic asthma. Therefore, understanding the molecular mechanisms governing TH2 differentiation and function is a top priority for improving asthma outcomes. One pathway of interest for controlling TH2-mediated disease is IL-2/STAT5 signaling, which is essential for TH2 polarization yet boasts a complex regulatory network that is incompletely understood. Here, we identify the Ikaros zinc finger (IkZF) transcription factor Eos as a candidate regulator of IL-2/STAT5 signaling underlying TH2 differentiation and function. To start, we show that Eos gene and protein expression is increased in TH2 cells relative to CD4+ T cell subsets that are negatively regulated by IL-2/STAT5 signaling, such as TH17 and TFH cells. Given these findings, we sought to define the functional effects of Eos in TH2 cells using in vitro and in vivo murine house dust mite asthma models. Intriguingly, Eos deficiency in vitro and in vivo results in reduced expression of key TH2 transcription factors (Gata3, Blimp-1), effector cytokines (IL-4, IL-13), and differentiation receptors (IL-2Rα, IL-2Rβ, IL-4Rα). Mechanistically, our data reveal that Eos interacts with and increases the activity of STAT5, suggesting that Eos enhances TH2 differentiation and effector function through direct STAT5 regulation. These findings in proinflammatory TH2 cells are of high significance, as Eos, to date, has largely been associated with the immunosuppressive functions of TREG cells. Taken together, our data reveal a novel mechanism by which Eos positively regulates IL-2/STAT5 signaling to promote TH2 differentiation and function. Work supported by grants from the NIH (R01AI134972) and The Ohio State University (Susan Huntington Dean’s Distinguished University Fellowship).
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Song, Rachel B., Carina A. Vitullo, Ronaldo C. da Costa, and Joshua B. Daniels. "Long-term survival in a dog with meningoencephalitis and epidural abscessation due to Actinomyces species." Journal of Veterinary Diagnostic Investigation 27, no. 4 (June 11, 2015): 552–57. http://dx.doi.org/10.1177/1040638715586439.
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A 2-year-old, female spayed Golden Retriever dog was presented to The Ohio State University Veterinary Medical Center for evaluation of ataxia, cervical pain, 1 episode of acute collapse, dull mentation, and inappetence. Physical examination revealed an elevated temperature of 39.7°C and severe cervical pain. Blood work revealed a mature neutrophilia. Cerebrospinal fluid (CSF) analysis revealed nondegenerative neutrophilic pleocytosis with no infectious agents. A presumptive diagnosis of steroid-responsive meningitis–arteritis was made, and corticosteroid therapy was started. The patient improved initially but experienced a vestibular episode characterized by falling and vertical nystagmus. A magnetic resonance imaging of the brain revealed an epidural abscess in the cervical vertebral canal and diffuse meningeal enhancement in the brain and cranial cervical spine. Abscess drainage revealed degenerate neutrophils and several filamentous, branching organisms. Culture of the initial CSF using an enrichment broth revealed growth of a Gram-positive organism 5 days after fluid collection. The isolate was identified by partial 16S ribosomal DNA sequencing as Actinomyces spp. The patient was successfully treated with long-term antibiotics. Our study reports the long-term survival after medical treatment of bacterial meningoencephalitis and epidural abscessation due to Actinomyces sp. infection in a dog. Bacterial meningoencephalitis should be included as a differential diagnosis in patients with cervical pain and fever, even when a nondegenerative neutrophilic pleocytosis is found on CSF analysis. Culture of the CSF with use of an enrichment broth should be considered in all cases of neutrophilic pleocytosis to rule out infections of the central nervous system.
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Mazzoccoli, Luciano, Stephen Iwanowycz, Soo Ngoi, Megan Hill, and Bei Liu. "Immune chaperone modulates dendritic cell functions in the tumor microenvironment." Journal of Immunology 210, no. 1_Supplement (May 1, 2023): 221.11. http://dx.doi.org/10.4049/jimmunol.210.supp.221.11.
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Abstract Dendritic cells (DCs) are central regulators of the adaptive immune response, thereupon necessary for T cell-mediated cancer immunity. To improve anti-tumor response, strategies to stimulate T cell response create new opportunities in DC cell biology, where DC maturation and antigen presentation are paramount. DC1 subtype is known for antigen-cross presentation to CD8 +T cells and the DC2 subtype to CD4 +T-cells. Previous studies showed that the immune chaperone GP96 plays a pivotal role in the processes of innate receptors. As a subject of interest from our lab, the GP96 client network offers potential targets to be explored for improving DC functions. We reported an increase in DC2 infiltration on the tumor side and a reduction of tumor growth in DC-specific GP96 deficient mice. Notwithstanding, the mechanism of GP96 in regulating DC functions is the subject of our study. By using in vitro approach, our study shows improvement in DC differentiation through gene expression assay, where DC subtypes display differential dependence on ER chaperone proteins. Also, the deletion of GP96 in DCs improves immunostimulatory activation and inhibits regulatory functions. Lastly, GP96 deficient DCs increased OVA antigen uptake and showed less T-cell exhaustion profile from in vivo tumor model. Directly DC activation or bypassing regulatory pathways can unleash T-cell response. Our study provides new insights into the role of GP96 in DCs in directing adaptive immune responses in the tumor microenvironment. This work was supported by the Pelotonia Institute of Immuno-Oncology (PIIO). The work was also supported in part by NIH/NCI (CA193939) and NIH/NIAID (AI125859) and supported by the Flow Cytometry Shared Resource at The Ohio State University Comprehensive Cancer Center and NIH/NCI P30 (CA138313).
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Scholnick, Robert J. "Florence Bernstein Freedman, William Douglas O'Connor: Walt Whitman's Chosen Knight, (Athens, Ohio: Ohio University Press: 1985, £35). Pp. xiv, 368. ISBN 0 8214 0767 8. - Dennis Berthold and Kenneth Price, Dear Brother Walt: The Letters of Thomas Jefferson Whitman (Kent, Ohio: The Kent State University Press, 1984, $27.50). Pp. xl, 202. ISBN 0 87338 297 8. - Agnieszka Saiska, Walt Whitman and Emily Dickinson: Poetry of the Central Consciousness (Philadelphia, Pennsylvania: University of Pennsylvania Press, 1985, £13.95). Pp. xii, 220. ISBN 0 8122 1203 7." Journal of American Studies 20, no. 3 (December 1986): 476–78. http://dx.doi.org/10.1017/s0021875800012901.
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Regnier, Emilie E. "Teaching Seed Bank Ecology in an Undergraduate Laboratory Exercise." Weed Technology 9, no. 1 (March 1995): 5–16. http://dx.doi.org/10.1017/s0890037x00022867.
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The study of weed life cycles, reproductive strategies, and the soil seed bank is emphasized in the undergraduate weed science course at Ohio State University as central to an understanding of the survival of weeds in the environment. A laboratory exercise was conducted every spring and fall academic quarter from 1991 to 1993 to demonstrate the effects of long-term cropping and soil disturbance histories on weed seed banks and aboveground weed communities. Five sites with diverse histories of culture were sampled; these included a field cultivated in vegetables under continuous conventional tillage for 59 yr, a field cultivated in field corn under continuous no-tillage for 11 yr, a 24 yr-old turfgrass research farm, a 70 yr-old forest, and a section of the forest border. Students conducted a survey of the weeds growing at the sites and separated and identified seeds from soil samples over a 3-wk period in weekly 2-h laboratory periods. Students wrote reports interpreting the data based on their knowledge of the site histories, weed life cycles, and weed seed production and longevity characteristics. The data were consistent over academic quarters as well as with published research, indicating that the survey and soil sampling techniques provided a reasonably accurate representation of the weed flora and soil seed populations. Weeds found growing at the sites were primarily summer annuals at the vegetable site, and a mix of summer and winter annuals, biennials, and perennials at the remaining sites. Annual weeds dominated the seed banks of all sites with common lambsquarters, pigweed spp., and common purslane being the most commonly found seeds. The presence of most seeds in the soil could be explained by a combination of species seed production and seed longevity characteristics and species abundance in the standing community. Interpretation of the data required students to integrate and apply lecture material and provided an excellent thinking exercise.
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Woyach, Jennifer, Amy S. Ruppert, Gabriela Perez, Allison M. Booth, Diane Feldman, Elie G. Dib, Aminah Jatoi, et al. "Alliance A041702: A Randomized Phase III Study of Ibrutinib Plus Obinutuzumab Versus Ibrutinib Plus Venetoclax and Obinutuzumab in Untreated Older Patients (≥ 70 Years of Age) with Chronic Lymphocytic Leukemia (CLL)." Blood 134, Supplement_1 (November 13, 2019): 1751. http://dx.doi.org/10.1182/blood-2019-127102.
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Background The phase 3 trial A041202 solidified the Bruton's Tyrosine Kinase (BTK) inhibitor ibrutinib as a standard of care for older patients with previously untreated CLL by showing superior progression-free survival (PFS) as compared with bendamustine plus rituximab. While ibrutinib is highly effective in previously untreated CLL, there do remain disadvantages to this therapy, specifically the low rate of complete response (CR) and therefore the need for continuous administration, which increases cost and toxicity. In older patients especially, toxicities with ibrutinib are common; 17% of patients had atrial fibrillation and 29% had grade 3 or higher hypertension on the A041202 study. Thus, strategies to decrease the exposure time to ibrutinib are of interest. Venetoclax is an inhibitor of BCL2 that has shown efficacy as a single agent and in combination with monoclonal antibodies, specifically the anti-CD20 monoclonal antibody obinutuzumab for patients with previously untreated CLL. One significant advantage to venetoclax is the ability to produce CRs and minimal residual disease negative (MRD-) responses. In this study, we compare ibrutinib plus obinutuzumab (IO) to ibrutinib plus venetoclax plus obinutuzumab (IVO) with a response-dependent discontinuation. While other studies have been designed with the goal of discontinuation of ibrutinib through combinations with venetoclax, no other study has been presented using a response-dependent discontinuation strategy. Study Design and Methods A041702 is a randomized phase 3 study led by the Alliance for Clinical Trials in Oncology that is currently enrolling through the NCI National Clinical Trials Network (NCTN). CLL patients age 70 years or older who are previously untreated and in need of therapy are eligible. Previous treatment of autoimmune complications with steroids or rituximab is allowed. Patients must have intermediate- or high-risk Rai stage, ECOG performance status 0-2, ANC ≥ 1000/mm3 unless due to marrow involvement, and platelets ≥ 30,000/mm3. CrCl must be ≥ 40 mL/min and AST/ALT ≤ 2.5x upper limit of normal. Patients with hepatitis B must have undetectable viral load, and patients must not have an intercurrent illness that is expected to limit survival to < 5 years. Warfarin and strong inhibitors or inducers of CYP3A4/5 are not permitted. Patients are initially preregistered to the study and submit a peripheral blood sample for central FISH analysis of del(17p). Patients who are registered are randomized 1:1 to Arm 1 (IO) or Arm 2 (IVO), and are stratified by Rai stage and presence of del(17p). IO consists of I daily starting cycle 1 day 1, and O dosed as standard starting cycle 1 day 1 and continuing to cycle 6 day 1. IVO consists of IO as in Arm 1, with V starting cycle 3 day 1 with standard 5-week ramp-up and continuing until cycle 14 day 28. At the end of 14 cycles, patients in both arms undergo response evaluation with central peripheral blood and bone marrow MRD testing. Patients on IO then continue I indefinitely. Patients on IVO who are in a bone marrow MRD- CR discontinue all therapy, and those who are not continue I indefinitely. The primary objective of the study is to compare PFS between IO and IVO using the strategy of response-dependent discontinuation. There is 90% power to detect a hazard ratio for PFS of 0.55 (corresponding to 5-year PFS rates of 70% and 82.187% for IO and IVO, respectively), at a one-sided significance level of 0.025 by a log-rank test. This design requires 128 events and 431 total evaluable patients assuming uniform accrual over the course of 3 years and minimum follow-up of 5 years. The study includes two interim analyses for superiority when 50% and 75% of the expected number of events have been observed and three interim analyses for futility when 25%, 50%, and 75% of the expected number of events have been observed. Conclusions A041702 is an ongoing phase 3 clinical trial using a novel response-dependent discontinuation method. Results of this study have the potential to change the standard of care for older patients with previously untreated CLL. The study is expected to accrue for 3 years beginning January 2019, and we welcome participation from sites throughout the NCTN. Support: U10CA180821, U10CA180882, UG1CA189823, U24CA196171; U10CA180820 (ECOG-ACRIN); https://acknowledgments.alliancefound.org; ClinicalTrials.gov Identifier: NCT03737981 Disclosures Woyach: Janssen: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Research Funding; Karyopharm: Research Funding; Loxo: Research Funding; Morphosys: Research Funding; Verastem: Research Funding. Lozanski:Beckman Coulter: Research Funding; Boehringer Ingelheim: Research Funding; Stemline Therapeutics Inc.: Research Funding; Genentec: Research Funding. Ding:Merck: Research Funding; DTRM Biopharma: Research Funding. Hill:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding; TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Stone:Argenx, Celgene, Takeda Oncology: Other: Data and Safety Monitoring Board/Committee: ; Novartis, Agios, Arog: Research Funding; AbbVie, Actinium, Agios, Argenx, Arog, Astellas, AstraZeneca, Biolinerx, Celgene, Cornerstone Biopharma, Fujifilm, Jazz Pharmaceuticals, Amgen, Ono, Orsenix, Otsuka, Merck, Novartis, Pfizer, Sumitomo, Trovagene: Consultancy. Byrd:Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Ohio State University: Patents & Royalties: OSU-2S; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Acerta: Research Funding; Novartis: Other: Travel Expenses, Speakers Bureau; BeiGene: Research Funding; Ohio State University: Patents & Royalties: OSU-2S; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Acerta: Research Funding; Genentech: Research Funding; BeiGene: Research Funding; Genentech: Research Funding; Acerta: Research Funding; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau.
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Eulitt, Patrick, Gretchen A. McNally, Pierluigi Porcu, Rebecca B. Klisovic, Sumithra Vasu, and Robert A. Baiocchi. "Blastic Plasmacytoid Dendritic Cell Neoplasm: A Single-Center Experience Documenting Frequent CNS Involvement." Blood 126, no. 23 (December 3, 2015): 5602. http://dx.doi.org/10.1182/blood.v126.23.5602.5602.
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Abstract Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare myeloid malignancy that often manifests with skin, lymph node, and bone marrow involvement. Patients diagnosed with BPDCN have a poor prognosis, with a median overall survival ranging from 12-14 months (Julia et al., 2014). Aoki et. al (2015) published a retrospective review reporting overall survival at 4 years for patients who underwent autologous and allogeneic hematopoietic stem cell transplant (HSCT) as 82% and 53%, respectively. Progressive disease, including central nervous system (CNS) involvement, excludes patients from receiving HSCT. Published case reports suggest that CNS presentation at diagnosis is rare, with estimates of only 10% of patients with CNS involvement at diagnosis (Feng et al., 2014; Starck et al., 2014). A retrospective case series of all patients treated for BPDCN at The Ohio State University from 1990 to present (n=11) was performed. Demographic data is summarized in table 1. Four of five patients undergoing CNS evaluation at diagnosis were found to have CNS involvement. All eleven patients underwent chemotherapy with the majority receiving induction chemotherapy (table 1). Three of the four patients with known CNS involvement at diagnosis expired within three months. The fourth patient survived with significant neurological complications secondary to intrathecal chemotherapy and was not a HSCT candidate. Two of eleven patients underwent HSCT. One died from relapsed disease in bone marrow, and one achieved long-term progression free survival. Two patients were lost to follow up, and were 7 and 16 months past diagnosis at last contact. CNS involvement with BPDCM at diagnosis may be more common than the literature suggests and should be investigated at diagnosis to allow these patients the best chance of long-term survival. Table 1. Patient characteristics and treatment summary Mean age at diagnosis 61.4 years Stage at diagnosis IV: 81.8% I: 18.2% BM involvement at diagnosis Yes: 81.8% No: 18.2% CNS involvement at diagnosis Yes: 36.4% No: 9.1% Unknown: 54.5% CNS involvement during clinical course Yes: 63.7% No: 18.2% Unknown: 18.2% Chemotherapy Hyper-CVAD: 45.5% CHOP: 18.2% EPOCH: 18.2% Clinical Trial: 18.2% SCT Yes: 18.2% No: 72.7% Unknown:9.1% Survival < 12 months: 45.5% 12-24 months: 27.3% >24 months: 18.2% Lost to follow up: 18.2% Median time to death in months 10.0* (range 1-26) *Time to death calculation excluded two patients lost to follow-up and two patients that are still living Disclosures Porcu: Cell Medica: Research Funding; Infinity: Research Funding; Seattle Genetics: Research Funding; Shape: Research Funding; Celgene: Research Funding.
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Couette, N., S. Gagne, and J. Paul. "AB1855 SUSAC SYNDROME: CASE SERIES FROM ADULT & PEDIATRIC TERTIARY ACADEMIC MEDICAL CENTERS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 2155–56. http://dx.doi.org/10.1136/annrheumdis-2023-eular.3980.
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BackgroundSusac Syndrome (SS) is a rare autoimmune endotheliopathy that affects the brain, retina, and inner ear, characterized by a clinical triad of encephalopathy, branch retinal artery occlusion (BRAO), and sensorineural hearing loss (SNHL)[1]. Brain MRI, fluorescein angiogram (FA), and audiometry help to establish a diagnosis[2]. The clinical presentation of SS is often variable leading to a delay in the diagnosis.ObjectivesThis study aims to compare clinical features and therapeutic strategies in adult and pediatric populations with Susac Syndrome.MethodsThis was a retrospective chart review of cases with a diagnosis of SS from December 2010 to December 2020 at The Ohio State University Wexner Medical Center (OSUWMC) and Nationwide Children’s Hospital in Columbus, Ohio, USA (tertiary care centers). We analyzed the following: age, gender, ethnicity, symptoms at the time of presentation, diagnostic studies, autoimmune serologies, brain MRI, FA, audiometry, treatment approaches, and outcomes.ResultsAll the patients (seven adult- patients and two pediatric-onset patients) identified as females, and the majority (78%) were Caucasian. The age at presentation ranged from 10 to 45 years old with a mean age of 38 years. The time to diagnosis ranged from 3 to 17 months with a mean of 7.8 months. The most common symptoms at onset included dizziness, hearing loss, and visual change. ESR was elevated in 50% with a range of 23 to 52 mm/hr (normal<30 mm/hr). CRP was elevated in 22% of patients with a range of 11 to 22 mg/dl (normal <10 mg/dL). Low to medium titer ANA was positive in 30%. FA detected unilateral or bilateral BRAO in seven patients (78%). Sensorineural hearing loss was confirmed on audiogram testing in 7 of 9 patients, and 44% of patients had bilateral hearing loss. 88% of our patient population had evidence of corpus callosal involvement (“snowball lesions”) in the brain MRI. CSF study was done in 5 patients - 4/5 had elevated CSF protein at 77 mg/dL (range 15-45 mg/dL) and the mean cell count was <3 (normal), without any oligoclonal bands. One patient had a brain biopsy.The most common initial treatment was high-dose steroids followed by a taper. Oral immunosuppressive therapy with mycophenolate mofetil (MMF) was initiated in 78% and was maintained in 56% of patients, who remained stable. Intravenous immunoglobulin (IVIG) was initially used in 56% of patients. Two patients transitioned from MMF to azathioprine due to pregnancy. Due to the severity of the disease, one patient transitioned from MMF to tacrolimus and Rituximab. 20% had a disease flare after the initial therapy requiring additional immunosuppression.ConclusionOur series highlights the rarity of SS. A neurologic exam, brain MRI, fluorescein angiogram, and audiogram should be performed in every case. A brain biopsy is not necessary for the diagnosis, unless for exclusion. BRAO was detected in 75% of our patients, highlighting the importance of an ophthalmology evaluation with FA, even in the absence of visual symptoms. In our series, only 20% presented with the full clinical triad of visual, auditory, and central nervous system symptoms, indicating that presentation of SS is often incomplete and diagnosis relies on a high index of suspicion[3]. Treatment depends on the severity of the presentation and involves the use of high-dose corticosteroids along with immunosuppression including mycophenolate, IVIG, tacrolimus, rituximab, and cyclophosphamide[4].References[1] Rennebohm R, Susac JO, Egan RA, Daroff RB. Susac’s Syndrome--update.Journal of the neurological sciences2010;299(1-2): 86-91.[2] Kleffner I, Dörr J, Ringelstein M, et al. Diagnostic criteria for Susac syndrome.Journal of neurology, neurosurgery, and psychiatry2016;87(12): 1287-95.[3] Dörr J, Krautwald S, Wildemann B, et al. Characteristics of Susac syndrome: a review of all reported cases.Nature reviews Neurology2013;9(6): 307-16.[4] Rennebohm RM, Asdaghi N, Srivastava S, Gertner E. Guidelines for treatment of Susac syndrome - An update.International journal of stroke: official journal of the International Stroke Society2020;15(5): 484-94.AcknowledgementsThe project described was supported by Award Number UL1TR002733 from the National Center for Advancing Translational Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.The authors have no conflict of interest to disclose.Disclosure of InterestsNone Declared.
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Borate, Uma, Amy S. Ruppert, Fei Yang, Dan Jones, Sean Caruthers, Weiqiang Zhao, Jo-Anne Vergilio, et al. "Newly Diagnosed AML Patient Samples Demonstrate High Degree of Concordance in Identification of Pathogenic Mutations By Next Generation Sequencing (NGS) Performed at Enrolling Institutions Compared to Central Laboratory Results in the Beat AML Master Trial." Blood 134, Supplement_1 (November 13, 2019): 2145. http://dx.doi.org/10.1182/blood-2019-131253.
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Background: NGS of myeloid mutations is an integral part of AML clinical decision-making. There is currently no information regarding concordance between NGS panels in AML using samples from the same patient across various platforms in different diagnostic laboratories. To study this important question, we analyzed NGS of myeloid mutations in diagnostic samples from The Beat AML Master Trial (BAMT) for newly diagnosed older AML patients, and compared variant calls made between institutional laboratories enrolling the study subject with those made by Foundation Medicine (FM), the central laboratory used for treatment assignment in this precision medicine trial. Methods: We identified newly diagnosed AML patient samples (peripheral blood (PB) and/or bone marrow (BM)) from 2 lead institutions in the BAMT(Ohio State, OSU and Oregon Health and Sciences University, OHSU) that were analyzed by both the institutional and by FM from Nov 15, 2016 to Apr 15, 2019. Samples sent to both laboratories >3 days apart were excluded. Samples were analyzed at the institutional laboratories using their respective NGS mutational panels and by FM using the FoundationOne®Heme(FMH) NGS panel which utilizes capture based sequencing. The OSU NGS assay utilizes sequencing on Illumina MiSeq. The OHSU NGS assay employs semiconductor-based sequencing (Ion Torrent PGM platform). The variant allele frequency (VAF) sensitivity for detection for all 3 laboratories range from 1-2%. We evaluated the ability to identify mutations in 8 genes : FLT3, IDH1/ 2, NPM1, TET2, DNMT3A, WT1 and TP53 used in treatment assignment in theBAMT. A detection cutoff of 2% was used to define the presence or absence of a mutation. Overall, agreement was defined as the number of times the local and central laboratories made the same call divided by the total number of patients. Sensitivity was defined as the number of present calls made locally divided by the number of present calls made centrally, and specificity as the number of absent calls made locally divided by the number of absent calls made centrally. The overall kappa statistic, controlling for institution, provided another measure of agreement between local and central calls, where a value of 1 indicates perfect agreement. Results: 194 patient samples were identified using methods above and analyzed locally at the screening institution (125 at OSU, 69 at OHSU) and centrally at FM. Type of tissue analyzed for variants between local site and FM were 59 PB, 129 BM, and 6 with BM/PB mismatch. Overall agreement in presence/absence calls between local and central results for each of the 8 genes was over 95% (Table 1). There was perfect agreement for NPM1. The sensitivity was above 94% for all genes except TP53 (88.6%) and WT1 (63.6%). Failure to detect a mutation locally was primarily due to reporting of all TP53 variants, including variants of unknown significance (VUS) (5) by FM as agreed upon in the study protocol, detection at low levels below local site sensitivity cutoff (1), detection of variants in a portion of gene not covered at the local site(1)and possible artifact (1). For the WT1 gene, discordance in 5 samples included VUS (3) reported by FM ,a variant detected in a portion of the gene not covered at the local site(1).and difference in leukemic tissue analyzed with mutation not detected by the central laboratory on a PB sample, and present at the institutional lab on a BM sample; affecting the overall agreement and specificity but not sensitivity. Specificity was at least 98% for each of the 8 genes. Finally, most discrepancies in reported mutations in FLT3 (n=2), IDH1 (n=1), IDH2 (n=2), DNMT3A (n=4) and TET2 (n=5) were due to reporting of VUS in one laboratory and not by another. Conclusion: Detection of pathogenic myeloid mutations using orthogonal assays showed a high degree of concordance for genes used in therapeutic assignment on the BAMT.The small number of discordant results, in TP53 and WT1, were attributed to the reporting of VUS. This study illustrates the importance of quality control and standardization as NGS continues to be widely utilized in AML for clinical decision making, with a variety of platforms across multiple laboratories. Our next steps involve evaluating the differences in VAFs reported between local and central laboratories when a given mutation is identified, as well as the potential reasons for observed differences and clinical implications of known pathogenic mutations vs putative VUS. Disclosures Borate: Daiichi Sankyo: Consultancy; AbbVie: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Pfizer: Consultancy. Vergilio:Foundation Medicine: Employment; Roche Holding AG: Equity Ownership. Stein:Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo, Inc.: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas Pharma US, Inc: Membership on an entity's Board of Directors or advisory committees; Bioline: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees. Patel:France Foundation: Honoraria; Dava Oncology: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Baer:Astellas: Research Funding; Abbvie: Research Funding; AI Therapeutics: Research Funding; Forma: Research Funding; Incyte: Research Funding; Kite: Research Funding; Takeda: Research Funding. Stock:Daiichi: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria; UpToDate: Honoraria; Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Schiller:Amgen: Other, Research Funding; Astellas: Research Funding; Biomed Valley Discoveries: Research Funding; Bristol Myer Squibb: Research Funding; Celgene: Research Funding, Speakers Bureau; Constellation Pharmaceutical: Research Funding; Daiichi Sankyo: Research Funding; Eli Lilly and Company: Research Funding; FujiFilm: Research Funding; Genzyme: Research Funding; Gilead: Research Funding; Incyte: Research Funding; J&J: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Karyopharm: Research Funding; Novartis: Research Funding; Onconova: Research Funding; Pfizer Pharmaceuticals: Equity Ownership, Research Funding; Sangamo Therapeutics: Research Funding; Agios: Research Funding, Speakers Bureau. Blum:AmerisourceBergen: Consultancy; Boehringer Ingelheim: Research Funding; Celgene: Research Funding; Astellas,: Research Funding; Xencor: Research Funding; Forma: Research Funding. Kovacsovics:Pfizer: Research Funding; Jazz: Consultancy; Novartis: Research Funding; Abbvie: Research Funding; Amgen: Consultancy, Research Funding. Foran:Agios: Honoraria, Research Funding. Druker:Pfizer: Research Funding; OHSU (licensing fees): Patents & Royalties: #2573, Constructs and cell lines harboring various mutations in TNK2 and PTPN11, licensing fees ; Cepheid: Consultancy, Honoraria; Aileron Therapeutics: #2573, Constructs and cell lines harboring various mutations in TNK2 and PTPN11, licensing fees , Membership on an entity's Board of Directors or advisory committees; ALLCRON: Membership on an entity's Board of Directors or advisory committees; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Aptose Biosciences: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Beta Cat: Membership on an entity's Board of Directors or advisory committees, Other: Stock options; GRAIL: Equity Ownership, Other: former member of Scientific Advisory Board; Patient True Talk: Consultancy; The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees, Other: Stock options; Beat AML LLC: Other: Service on joint steering committee; CureOne: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Gilead Sciences: Other: former member of Scientific Advisory Board; ICON: Other: Scientific Founder of Molecular MD, which was acquired by ICON in Feb. 2019; Monojul: Other: former consultant; Novartis: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Patents & Royalties: Patent 6958335, Treatment of Gastrointestinal Stromal Tumors, exclusively licensed to Novartis, Research Funding; Bristol-Myers Squibb: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Research Funding; Pfizer: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Research Funding; Merck & Co: Patents & Royalties: Dana-Farber Cancer Institute license #2063, Monoclonal antiphosphotyrosine antibody 4G10, exclusive commercial license to Merck & Co; Dana-Farber Cancer Institute (antibody royalty): Patents & Royalties: #2524, antibody royalty; Burroughs Wellcome Fund: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Patents & Royalties, Research Funding. Byrd:Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Acerta: Research Funding; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; Ohio State University: Patents & Royalties: OSU-2S. Levine:C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Isoplexis: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees; Qiagen: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Prelude Therapeutics: Research Funding; Novartis: Consultancy; Gilead: Consultancy; Lilly: Honoraria; Imago Biosciences: Membership on an entity's Board of Directors or advisory committees. Mims:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Astellas Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.
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Sharma, Ruchika, Gary Woods, Susan E. Creary, Kan Hor, Cody Young, Christina Gallagher, Emily McLain, et al. "Impact of Erythrocytapheresis on Endogenous Anticoagulants in Sickle Cell Disease." Blood 126, no. 23 (December 3, 2015): 4590. http://dx.doi.org/10.1182/blood.v126.23.4590.4590.
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Abstract Introduction The rate of venous thrombo-embolism (VTE) in patients with sickle cell disease (SCD) is estimated to be 4 - 8%; the incidence of catheter-associated VTE in this cohort is 0.16-0.99 per 1000 catheter days. Possible mechanisms for VTE in patients with SCD include hyperviscosity, ischemia reperfusion injury and chronic vascular inflammation. Additionally, patients with SCD exhibit decreased plasma levels of natural anticoagulants such as proteins C and S compared to healthy adults. A retrospective review at our institution found that the incidence of central venous line (CVL)-associated VTE in children with SCD was 0.12/1000 catheter days. On multivariate analysis, CVLs were identified as the only independent risk factor for VTE. Among patients with CVL, we found an association between bilateral CVLs and VTE (Odds Ratio [95% CI] = 10.3 [1.1-92.2]). Children with SCD frequently require CVLs for intravenous access or chronic erythrocytapharesis to reduce SCD-related complications. It is unknown, however, if erythrocytapharesis may also disrupt their natural anticoagulants levels and further increase their risk for subsequent VTE. We hypothesized that erythrocytapheresis may contribute to the pro-coagulant phenotype by altering patients' natural anticoagulants levels. Methods As part of a quality improvement initiative we measured antithrombin (AT), protein C antigen and activity, protein S antigen (total and free) and activity prior to being placed on the apheresis circuit and after completion of exchange in patients with SCD (0-21 years of age) undergoing chronic erythrocytapheresis who had a CVL (between January 1, 2009 and January 31, 2015). D-Dimer levels were obtained pre exchange only. Protein C and S levels were measured using ELISA based assays; protein C and S activities were measured using a clotting based assay and AT was measured using a chromogenic assay. The resulting levels, pre and post-erythrocytapheresis were analyzed using a paired nonparametric Wilcoxon rank test. Results Eleven patients were eligible for this study (8 females, 3 males). Median age at the time of erythrocytapheresis was 14 years (±3.65 SD) years. Indications for erythrocytapheresis included primary/ secondary stroke prevention or recurrent acute chest syndrome. All patients had bilateral CVLs in place. Four of the included patients had a history of VTE; 2 patients were on anticoagulation with low molecular weight heparin at the time of the study. The mean value for total protein S antigen (65u/dL; normal >72u/dL), free protein S antigen (53u/dL; normal >70u/dL), and protein S activity (51IU/mL; normal 65-138IU/ml) were all abnormal pre- erythrocytapheresis and decreased significantly following erythrocytapheresis (52u/dL, 44u/dL, and 44IU/mL respectively). Mean protein C antigen (71u/dL; normal >55u/dL), protein C activity (71%; normal 55-111%), and AT activity (104%; normal 77-132%) were within the normal range pre-erythrocytapheresis and decreased significantly post-erythrocytapheresis. We demonstrated significantly lower levels of protein C antigen (p=0.01), protein C activity (p=0.01), total protein S antigen (p=0.005), free protein S antigen (p=0.036), protein S activity (p=.04), and AT activity (p=.004) following erythrocytapheresis (Figure). D-Dimer levels were elevated in 6/11 patients (54.5%). Conclusions Pre- and post-erythrocytapheresis levels of natural endogenous anticoagulants investigated in a cohort of patients with SCD undergoing chronic erythrocytapheresis demonstrated that levels of all investigated proteins were significantly lower in patients following erythrocytapheresis. D-dimer levels were elevated in the majority of patients pre exchange but the importance of this finding is unclear. Given the relatively short half-life of the natural anticoagulants (2-3 hours for protein C and 36-60 hours for AT and protein S), it is unclear if this acute decrease of natural anticoagulants is clinically relevant. Further investigation is needed to determine if this acute decrease may contribute to an increased VTE risk in children with SCD undergoing apheresis. Figure 1. Figure 1. Disclosures Woods: Biogen: Other: Educational Grant. Dunn:Novo Nordisk: Consultancy, Other: Educational Grant; CSL Behring: Consultancy, Other: Data Safety Monitoring Board; Bayer: Consultancy, Other: educational grant; Biogen: Consultancy, Other: Educational grant, Research Funding; Baxalta: Consultancy, Other: educational grant, Research Funding; Ohio State University: Employment; Pfizer: Other: Grant Review Board.
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Klimaszewski, Haley L., Christoph Weigel, Selamawit Addissie, Sarah Schlotter, Tounkara Fode, James P. Dugan, Bradley M. Haverkos, et al. "Targeting EBV Encoded Viral Kinases with GCV, AZT, Rituximab and Dexamethasone (GARD) Results in Durable Responses in Patients with CNS Lymphoproliferative Disease." Blood 142, Supplement 1 (November 28, 2023): 4476. http://dx.doi.org/10.1182/blood-2023-189618.
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Introduction: Epstein-Barr virus positive (EBV+) central nervous system lymphoproliferative diseases (CNS-LPD) are aggressive clinical conditions with poor prognosis. EBV+ CNS-LPD often occurs in the setting of immune suppression and comorbidities (solid organ transplant, autoimmunity). Treatment with high-dose methotrexate has increased survival but is not a viable option for all patients, highlighting the need for alternative treatments. Previous research has reported EBV+ CNS-LPD exhibits unique genetic and immunobiological signatures, however, few studies have reported on the epigenetic landscape. We have previously reported use of ganciclovir (GCV), zidovudine (AZT), rituximab and dexamethasone (GARD) regimen induced complete and durable responses in a cohort of 13 patients with primary CNS post-transplant lymphoproliferative disease (PCNS-PTLD). Here we present 24 patients (10 from prior cohort and 14 new) with EBV+ CNS-LPD treated with GARD. We extend follow-up time for the previous cohort and add molecular context to clinical observations. We performed DNA methylation and expression analysis of EBV viral kinases in available tumor samples and revealed unique viral epigenetic states leading to expression of antiviral drug targets in an array of EBV+ CNS-LPD. Methods: We conducted an IRB-approved, retrospective review of patients with EBV+ CNS-LPD treated with GARD at The Ohio State University Wexner Medical Center between 1998-2022. Patient information was extracted from the electronic medical record. Treatment consisted of two-week induction of twice daily IV GCV/AZT (5mg/kg and 1,500 mg) IV dexamethasone (10-40mg), and weekly rituximab (375mg/m 2). After induction, dexamethasone was tapered, and GCV/AZT was switched to maintenance oral dosing of 450mg valganciclovir twice daily and 300mg of AZT twice daily. Rituximab was administered on days 1, 8, 15, and 22. Two-year overall survival (OS), five-year OS, and overall response rate were assessed. Available CNS-LPD biopsy samples were obtained, and expression of EBV lytic genes BZLF1, BXLF1 (thymidine kinase), and BGLF4 (protein kinase) were measured via qRT-PCR. Mass spectrometry based EpiTYPER assay was used to report the percentage of DNA CpG methylation in the gene promoters for viral BZLF1, BXLF1, BGLF4 and LMP1 genes . Biopsies from 17 patients with systemic PTLD with no CNS involvement were used for comparison. Results: 24 patients with EBV+ CNS-LPD were identified. 21 (87.5%) patients were diagnosed with a primary CNS-LPD (PCNS-LPD). Of the PCNS-LPD, 14 patients were PCNS-PTLD, 4 were receiving immunosuppression for autoimmune conditions, 1 patient had type 2 diabetes and two had no known history of immunosuppression. The remaining three patients had systemic PTLD with secondary CNS involvement. Diffuse large B-cell lymphoma was the most common histology (11; 45.8%) followed by grade 3 lymphomatoid granulomatosis (5; 20.8%), B-cell LPD (5;20.8%), polymorphic PTLD (2;8.3%) and one large cell lymphoma of ambiguous lineage. All patients were HIV negative. EBER was positive in all biopsies and EBV PCR of cerebrospinal fluid was positive in patients without biopsy. Sixteen patients (66.7%) achieved a completed response, with an overall response rate of 83%. Two-year OS was 62.5% (95% CI, 45.8-85.2%) and five-year OS was 52.8% (95% CI, 35.7%-77.9%). Five CNS-LPD brain biopsies were available for analysis. qRT-PCR of biopsy specimens showed expression of LMP1, BXLF1, and BGLF4, but not BZLF1. Expression of BGLF4 was significantly higher (p=1.35e-5) in CNS-LPD when compared to systemic EBV+ PTLD. EpiTYPER data showed significantly decreased promoter methylation for viral kinases BXLF1 and BGLF4 (p=0.0281 p=0.0089). Conclusions: We have shown that GARD regimen shows efficacy in the treatment of EBV+ CNS-LPD, with 62.5% two-year OS and 52.8% five-year OS. Our results provide the molecular basis for expression of lytic viral kinases BXLF1 and BGLF4 in CNS-LPD by showing that both genes exhibit decreased promotor methylation. This expression of viral kinases in CNS-LPD supports the mechanistic rationale of this antiviral approach and could be further investigated as a predictive biomarker. Overall, this research highlights unique epigenetic features of EBV in CNS-LPD that support the use of antiviral, specifically the GARD regimen, in EBV+ CNS-LPD.
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Al Malki, Monzr M., Miguel-Angel Perales, Dipenkumar Modi, Sumithira Vasu, Megan Nelson, Donna Bui, Sojung Kim, et al. "Preliminary Results of the First-in-Human Study of Nexi-001, a Multi-Antigen Specific CD8+ T Cell Product, in Acute Myeloid Leukemia (AML) Patients with Relapsed Disease after Allogeneic Hematopoietic Cell Transplantation (Allo-HSCT) Demonstrate Early Signs of Safety, Tolerability and Robust Immune Responses." Blood 136, Supplement 1 (November 5, 2020): 31–33. http://dx.doi.org/10.1182/blood-2020-139342.
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Relapse after allo-HSCT is the leading cause of death in patients with AML. While donor lymphocyte infusions (DLI) achieve modest graft-versus-leukemia (GVL) effects in a small group of responders, responses are often accompanied by significant morbidity and mortality from graft-versus host disease (GVHD). Therefore, there is a significant need for cellular approaches that enhance the benefit of GVL while decoupling toxicities associated with GVHD. Herein, we report initial results from a first-in-human study of a non-genetically engineered adoptive cellular therapy product, NEXI-001, which contains populations of anti-leukemia antigen-specific CD8+ T cells. NEXI-001is generated using a novel technology platform referred to as Artificial Immune Modulation (AIM). Specifically, nano-artificial Antigen Presenting Cells are used in combination with a proprietary cellular expansion system to isolate and expand populations of CD8+ T cells that recognize five specific HLA 02.01-restricted peptides from the WT1, PRAME, and Cyclin A1 antigens, each of which is commonly over-expressed on AML blasts and leukemic stem cells. The ability to direct T cells against multiple leukemic antigens may reduce potential for tumor escape via target down-regulation. The AIM manufacturing process is optimized to consistently produce cellular products that contain T cell subtypes which combine anti-tumor potency with long-term persistence. Each NEXI-001 product is comprised of >95% memory T cells, and include stem-like central memory (Tscm), central memory (Tcm) and effector memory (Tem) cells - those T cell subtypes with potential to provide long lasting GVL effects. Importantly, each product also contains very low proportions of naïve T cells with allo-reactive potential (Tn), which may further reduce the risk of GVHD. (Table 1) Patients underwent bridging therapy to control leukemic burden while NEXI-001 T cells were manufactured for 14 days. After a 14-day wash out period, lymphodepleting therapy (fludarabine 30mg/m2, Cytoxan 300mg/m2 D-5 to D-3) was given followed by two rest days before NEXI-001 cell infusion. Dose levels for Phase 1 patients enrolled include safety D-1 (50 million T cells, n=1); followed by two additional dose-escalating safety cohorts {100 million T cells (n=3); and 200 million T cells, (n=3)}, and expansion cohort (n=16). A total of 7 AML patients (median age 43) with HLA-02:01 who had relapsed after allo-HSCT have been enrolled to-date. The same HLA-matched donor PBMCs are used for NEXI-001 manufacturing. Median time from previous SCT to relapse was 10 months, median bone marrow blast at relapse was 9%. and all patients were determined as poor risk category. To-date, there have been no infusion reactions, CRS or ICANS events observed for any patient treated. Significantly, there is no evidence of GVHD in any patient (n=3). Analysis of primary end point demonstrates a safe and well tolerated profile. Analyses of secondary end points support early signs of clinical response. We observed early and significant in vivo T cell proliferation as early as Day 5 (Figure 1). This may suggest that NEXI- T cells are actively engaging leukemic targets. Multimer staining confirmed the presence of NEXI-001 T cells in peripheral blood (Figure 2). Uniquely, the CD8+ T cells in peripheral blood maintain the phenotype subsets of the infused product over all time points measured (Figure 3). Despite complete lymphodepletion, CD4 reconstitution is robust, earlier than expected and consistent with increased levels of IL2. Evidence of cytotoxic activity, likely mediated by CD8+ T cells, was evident with increased serum levels of IFNg, TNFa, Granzymes A and B, and sFas. Additionally, we observed recruitment and trafficking of CD4 T cells to the bone marrow which may contribute to the initiation of a more robust cell-mediated immune response. Maintaining populations of T-stem cell and T-central memory subtypes may provide marrow-resident effector T cells with a source of continued replenishment over time, providing potential for a durable anti-tumor response. In conclusion, early results suggest that infusion of NEXI-001 product, is safe, well tolerated and capable of generating an early and robust cell-mediated immune response in patients with relapsed AML post allo-HSCT. As a novel cellular therapy, NEXI-001 may have potential to enhance the benefit of GVL while decoupling the toxicities associated with GVHD. Disclosures Al Malki: Neximmune: Consultancy; Jazz Pharmacuticals, Inc: Consultancy; Rigel Pharma: Consultancy. Perales:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Research Funding; Miltenyi Biotec: Research Funding; Medigene: Membership on an entity's Board of Directors or advisory committees, Other; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria; Servier: Membership on an entity's Board of Directors or advisory committees, Other; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Incyte Corporation: Honoraria, Research Funding; MolMed: Membership on an entity's Board of Directors or advisory committees; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; NexImmune: Membership on an entity's Board of Directors or advisory committees; Cidara Therapeutics: Other; Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees. Modi:MorphoSys: Membership on an entity's Board of Directors or advisory committees. Vasu:Janssen: Membership on an entity's Board of Directors or advisory committees; Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University; Omeros: Membership on an entity's Board of Directors or advisory committees. Kim:Neximmune: Current Employment. Wang:Neximmune: Current Employment. Lu:Neximmune: Current Employment. Oelke:Neximmune: Current Employment. Myint:Neximmune: Current Employment, Current equity holder in private company; BMS: Current equity holder in publicly-traded company; Celgene: Ended employment in the past 24 months. Varela:Neximmune: Consultancy, Current equity holder in private company.
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Alinari, Lapo, Alejandro Gru, Carl Quinion, Ying Huang, Jeffrey A. Jones, Steven M. Devine, Kami J. Maddocks, Beth Christian, Robert A. Baiocchi, and Kristie A. Blum. "Poor Prognostic Effect of CD5 Positivity for Patients with Diffuse Large B-Cell Lymphoma: Results from a Retrospective Single Institution Analysis." Blood 124, no. 21 (December 6, 2014): 1700. http://dx.doi.org/10.1182/blood.v124.21.1700.1700.
Full textAbstract:
Abstract Background. CD5+ diffuse large B-cell lymphomas (DLBCLs) are an uncommon subgroup of DLBCLs representing 5-10% of de novo DLBCLs. Compared with CD5- DLBCLs, de novo CD5+ DLBCLs are associated with a more aggressive clinical course with higher international prognostic index (IPI), more frequent extranodal disease burden including central nervous system (CNS) involvement, and a significantly poorer overall prognosis with conventional anthracycline-based chemotherapy with or without rituximab (Miyazaki K et al. Ann Oncol 2011). Historically, most of these cases belong to the activated B cell (ABC)-type of DLBCLs (Jain P et al., Am J Hematol 2013). The vast majority of the published reports on CD5+ DLBCL are from Asia with limited data on outcomes in US or European patients (pts) in the modern era utilizing rituximab based therapy with no standard guidelines available for the management of this high risk disease. Methods. We reviewed pts with newly diagnosed de novo CD5+ DLBCL treated at the Ohio State University (OSU) from August 2000 to July 2014. Pts did not have an antecedent history of CLL or MCL and diagnosis was confirmed by centralized hematopathology review at OSU. We examined pts' characteristics, treatment response, and survival. Response to treatment was determined by PET/CT. Progression-free survival (PFS) was calculated as the time from diagnosis to the time of progression and/or death, and overall survival (OS) was calculated as time from diagnosis to the time of death. PFS and OS were summarized using Kaplan-Meier methods. Results. Of the 16 CD5+ DLBCL, 11 (70%) were male, and the median age at diagnosis was 58 (range 44-67). Eight pts had CD5+ DLBCL ABC-type, 4 had germinal center (GCB)-type and 4 were non-classifiable by Hans criteria. At diagnosis, 11 pts were stage III/IV; 6 pts had bone marrow involvement, 2 had CNS involvement; and 2 pts had bulky disease (≥10cm). IPI was ≥ 3 in 4 pts (unable to calculate in 6 pts due to unknown LDH) and 2 pts had B symptoms. The median Ki67 was 75% (range 50-95%), EBER was negative in all pts; 3 of 13 evaluable pts were positive for MYC gene rearrangement, and 0 pts had an IGH/BCL2 translocation. Therapies at diagnosis included R-CHOP (12 pts), R-EPOCH (2 pts), R-CHOP with 3 g/m2 of methotrexate (1 pt), and hyperfractionated cytoxan (1 patient). In addition, 2 pts received IT methotrexate prophylaxis and 5 pts received involved field radiation therapy to residual disease sites post frontline chemotherapy. None of the pts underwent autologous stem cell transplant (SCT) in first remission. Thirteen pts (81%) achieved a complete remission (CR) with frontline treatment. Three patients had primary refractory disease, 2 rapidly progressed and died within 1 month from diagnosis. Of the 13 pts in CR, 4 (31%) remain in remission with a median follow up of 28 months (range 10-61). Nine pts in CR relapsed (69%), including 6 pts who proceeded to salvage therapy and autologous SCT, 1 pt who received both autologous and allogeneic SCT, 1 pt who underwent allogeneic SCT, and 1 pt who received multiple lines of salvage chemotherapy with no transplant and eventually died. Five of the 6 pts (84%) that underwent autologous SCT relapsed and both pts that underwent allogeneic SCT relapsed. Ten pts (63%) received ≥ 3 lines of chemotherapy. Of the 16 pts, 5 (31%) have died from disease progression. At a median follow up of 32 months (range 9.4 to 99.4), the 2 year PFS and OS for all pts were 38% and 72%, respectively (Figure 1). The median time to progression (TTP) from frontline therapy was 14 months (95% CI 7-28 months). The median TTP from second line therapy in 10 pts was 17 months (95% CI 7-33 months). Conclusions. To the best of our knowledge,this is the first series of CD5+ DLBCL from Western countries in the PET/rituximab era reported to date. With the recognized limitation of a small sample size and retrospective analysis, our current study confirms that CD5+ DLBCL pts have a poor prognosis which appears to be inferior to CD5- DLBCL despite a multimodality approach. Interestingly, autologous as well as allogeneic SCT at relapse do not seem to improve outcome, raising the question if there is even a role for transplant in these pts outside the context of a clinical trial. Similar to the initial reports about the poor prognosis of MYC translocation and DLBCL (Savage KJ et al. Blood 2009), we suggest that CD5 positivity is a particularly poor prognostic marker and should be used for risk stratification in DLBCL clinical trials. Disclosures Jones: Pharmacyclics: Consultancy, Research Funding. Blum:Janssen, Pharmacyclics: Research Funding.
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Landsburg, Daniel J., Mitchell E. Hughes, Alexa Koike, David A. Bond, Kami J. Maddocks, Ling Guo, Allison M. Winter, et al. "Outcomes of Patients with Relapsed/Refractory Double Expressor B Cell Lymphoma As Defined By Multicenter Pathology Review Treated with Ibrutinib Monotherapy." Blood 132, Supplement 1 (November 29, 2018): 455. http://dx.doi.org/10.1182/blood-2018-99-117514.
Full textAbstract:
Abstract Introduction: Preclinical data have suggested that B-cell receptor-associated genes are upregulated in diffuse large B cell lymphoma (DLBCL) with increased expression of MYC protein, as well as MYC and BCL2 protein, also known as "double expressor" lymphoma (DEL) (Am J Surg Pathol. 2017 Apr;41(4):541-549 and PLoS One. 2017 Feb 17;12(2):e0172364). Patients (pts) with DEL respond poorly to cytotoxic chemotherapy; thus novel treatment approaches are needed for this disease. Here, we report outcomes of pts with relapsed/refractory (R/R) DLBCL and high grade B cell lymphoma (HGBL) treated with ibrutinib (ibr) monotherapy. Methods: Pts analyzed were those with R/R DLBCL or HGBL treated with ibr monotherapy at University of Pennsylvania, Ohio State University or Cleveland Clinic with immunohistochemical (IHC) stains for MYC and BCL2 from the tissue specimen obtained most recently prior to initiation of ibr available for hematopatholoigst (HP) review, and determined to have IHC scores of ≥40% for MYC and ≥50% for BCL2, meeting criteria for definition of DEL. Exclusion criteria were HIV positivity, post-transplant lymphoproliferative disorder, prior chronic lymphocytic leukemia and inadequate data. All available IHC stains for MYC and BCL2 were scored as positive or negative as per the aforementioned cutoffs by a HP at the treating center (HP1) as well as a second HP at one of the other centers (HP2) through review of digital slide images. In cases of disagreement, the score assigned in the clinical pathology report (CPR) was used as a tiebreaker. Progression free survival (PFS) was defined as the interval between time of initiation of ibr and documented disease progression, change in therapy (tx) if no disease response or last follow-up in remission, and overall survival (OS) between time of initiation of ibr and death or last follow-up while alive. Data were censored on 7/1/18. Results: Twenty-five cases with IHC stains for MYC and BCL2 were reviewed, with 19 meeting criteria for DEL which were included in the analysis. Clinicopathologic characteristics at time of ibr initiation were median age 69 years, 32% female, 63% stage III-IV, 74% elevated LDH, 11% bone marrow (BM) involvement, 11% B symptoms present, 21% extranodal (EN) disease at >1 site, 32% ECOG performance status (PS) >1, 58% with International Prognostic Index score (IPI)≥3, 26% HGBL, median Ki67 80% and 21% germinal center (GCB) cell of origin (COO) by Hans algorithm. Of pts with available fluorescence in situ hybridization (FISH) data, 50% (7/14), 25% (3/12) and 14% (1/7) demonstrated MYC, BCL2 and BCL6 rearrangements, respectively, and 3 pts were known to be double hit lymphoma. First-line tx was R-EPOCH in 26% and R-CHOP in 74%. Autologous stem cell transplantation was received by 42% prior to treatment with ibr. The proportion of pts receiving ibr as 2nd, 3rd, 4th and ≥5th line of tx was 21%, 37%, 21% and 21%, respectively. The time from initiation of the prior line of tx to initiation of ibr was <6 months (mo), 6-12 mo and >12 mo in 79%, 16% and 5%, respectively. Overall response to ibr was 47% (37% complete response and 10% partial response) and 5% with stable disease. All responses were seen in pts with non-GCB COO. The median PFS was 4.7 mo, median OS 5.5 mo and median duration of response 4.2 mo. For all cases reviewed (n=25), MYC IHC was scored by HP1 and HP2 and available in the CPR in 100%, 84% and 88%, respectively, and BCL2 IHC in 100%, 84% and 100%, respectively. Rates of concordance and kappa (κ) coefficient were as follows: HP1 and HP2 for MYC 85.7% (κ=0.49), BCL2 95.2% (κ=0.64) and DEL 84.0% (κ=0.61); HP1 and CPR for MYC 86.3% (κ=0.70), BCL2 96.0% (κ=0.78) and DEL 81.8% (κ=0.62); HP2 and CPR for MYC 66.7% (κ=0.18), BCL2 90.5% (κ=0.45) and DEL 68.2% (κ=0.34). In 4 cases with disagreement between HP1 and HP2 regarding DEL status, the CPR agreed with HP1, and 4 cases were identified as DEL by both HP1 and HP2 but not by CPR. Conclusion: An objective response to ibr was experienced by nearly half of pts with R/R DEL as defined by multicenter HP review in this series. Our data suggest a potential benefit to the use of ibr monotherapy as bridging tx to curative-intent cellular tx, as well as support the incorporation of ibr into clinical trials for the R/R DEL pt population. A relatively high rate of concordance between HP1 and CPR in identifying cases of DEL suggests that local review of MYC and BCL2 IHC may be a reasonable alternative for determining DEL status when central review is infeasible. Disclosures Landsburg: Curis, INC: Consultancy, Research Funding; Takeda: Research Funding. Maddocks:Novartis: Research Funding; Pharmacyclics/Janssen: Honoraria; BMS: Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding; AstraZeneca: Honoraria; Teva: Honoraria. Hill:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dwivedy Nasta:Incyte: Research Funding; Merck: Other: DSMC; Pharmacyclics: Research Funding; Aileron: Research Funding; Roche: Research Funding; Takeda/Millenium: Research Funding; Rafael/WF: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Debiopharm: Research Funding. Svoboda:Regeneron: Research Funding; TG Therapeutics: Research Funding; Seattle Genetics: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Merck: Research Funding; Pharmacyclics: Consultancy, Research Funding; KITE: Consultancy; Kyowa: Consultancy. Schuster:Physician's Education Source, LLC: Honoraria; Dava Oncology: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; OncLive: Honoraria; Genentech: Honoraria, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Nordic Nanovector: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.
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Segura, Peter Paul. "Oliverio O. Segura, MD (1933-2021) Through A Son’s Eyes – A Tribute to Dad." Philippine Journal of Otolaryngology Head and Neck Surgery 36, no. 1 (May 30, 2021): 73. http://dx.doi.org/10.32412/pjohns.v36i1.1679.
Full textAbstract:
I was born and raised in the old mining town of Barrio DAS (Don Andres Soriano), Lutopan, Toledo City where Atlas Consolidated Mining and Development Corp. (ACMDC) is situated. Dad started his practice in the company’s hospital as an EENT specialist in the early 60’s and was the ‘go to’ EENT Doc not only of nearby towns or cities (including Cebu City) but also the surrounding provinces in the early 70’s. In my elementary years, he was Assistant Director of ACMDC Hospital (we lived just behind in company housing, only a 3-minute walk). I grew interested in what my dad did, sometimes staying in his clinic an hour or so after school, amazed at how efficiently he handled his patients who always felt so satisfied seeing him. At the end of the day, there was always ‘buyot’ (basket) of vegetables, live chickens, freshwater crabs, crayfish, catfish or tilapia. I wondered if he went marketing earlier, but knew he was too busy for that (and mom did that) until I noticed endless lines of patients outside and remembered when he would say: “Being a doctor here - you’ll never go hungry!” I later realized they were PFs (professional fees) of his patients. As a company doctor, Dad received a fixed salary, free housing, utilities, gasoline, schooling for kids and a company car. It was the perfect life! The company even sponsored his further training in Johns-Hopkins, Baltimore, USA.
A family man, he loved us so much and was a bit of a joker too, especially at mealtimes. Dad’s daily routine was from 8 am – 5 pm and changed into his tennis, pelota, or badminton outfit. He was the athlete, winning trophies and medals in local sports matches.
Dad wanted me to go to the University of the Philippines (UP) High School in the city. I thought a change of environment would be interesting, but I would miss my friends. Anyway, I complied and there I started to understand that my dad was not just an EENT practicing in the Mines but was teaching in Cebu Institute of Medicine and Cebu Doctors College of Medicine (CDCM) and was a consultant in most of the hospitals in Cebu City. And still he went back up to the mountains, back to Lutopan, our mining town where our home was. The old ACMDC hospital was replaced with a new state-of-the-art hospital now named ACMDC Medical Center, complete with Burn Unit, Trauma center and an observation deck in the OR for teaching interns from CDCM. Dad enjoyed teaching them. Most of them are consultants today who are so fond of my dad that they always send their regards when they see me.
My dad loved making model airplanes, vehicles, etc. and I realized I had that skill when I was 8 years old and I made my first airplane model. He used to build them out of Balsa wood which is so skillful. I can’t be half the man he was but I realized this hobby enhanced his surgical skills. My dad was so diplomatic and just said to get an engineering course before you become a pilot (most of dads brothers are engineers). I actually gave engineering a go, but after 1 ½ years I realized I was not cut out for it. I actually loved Biology and anything dealing with life and with all the exposure to my dad’s clinic and hospital activities … med school it was!
At this point, my dad was already President of the ORL Central Visayas Chapter and was head of ENT Products and Hearing Center. As a graduate of the UP College of Medicine who finished Otorhinolaryngology residency with an additional year in Ophthalmology as one of the last EENTs to finish in UP PGH in the late 50’s, he hinted that if I finished my medical schooling in CDCM that I consider Otorhinolaryngology as a residency program and that UP-PGH would be a good training center. I ended up inheriting the ORL practice of my dad mostly, who taught me some of Ophthalmology outpatient procedures. Dad showed me clinical and surgical techniques in ENT management especially how to deal with patients beyond being a doctor! You don’t learn this in books but from experience. I learned a lot from my dad. Just so lucky I guess! He actually designed and made his own ENT Treatment Unit, which I’m still using to this day (with some modifications of my own). And he created a certain electrically powered ‘eye magnet’ with the help of my cousin (who’s an engineer now in Chicago) which can attract metallic foreign bodies from within the eyeball to the surface so they can easily be picked out – it really works!
Dad loved to travel in his younger years especially abroad for conventions or just simply leisure or vacations, most of the time with my mom. But as he was getting older, travels became uncomfortable. His last travel with me was in 2012 for the AAO-HNS Convention in Washington DC. It was a great time as we then proceeded to a US Navy Airshow in nearby Virginia after the convention, meeting up with my brother who is retired from the USN. Then we took the train to New York and stayed with my sister who is a PICU nurse in NY Presbyterian. Then off to Missouri and Ohio visiting the National Museum of the US Air Force, the largest military aircraft museum in the world.
For years, Dad had been battling with heredofamilial-hypercholesterolemia problem which took its toll on his liver and made him weak and tired but still he practiced and continued teaching and sharing his knowledge until he retired at the age of 80. By then, my wife and I would take him and my mom out on weekends, he loved to be driven around and eat in different places. I really witnessed and have seen how he suffered from his illness in his final years. But he never showed it or complained, never even wanted to use a cane! He didn’t want to be a burden to anyone. What most affected me was that my dad passed and I wasn’t even there. I had helped call for a physician to rush to the house and had oxygen cylinders to be brought for him as his end stage liver cirrhosis was causing cardio-pulmonary complications (non-COVID). Amidst all this I was the one admitted for 14 days because of COVID-19 pneumonia. My dad passed away peacefully at home as I was being discharged from the hospital. He was 88. I never reached him just to say good bye and cried when I reached home still dyspneic recovering from the viral pneumonia. I realized from my loved ones who told me that dad didn’t want me to stress out taking care of him, as I’ve been doing ever since, but instead to rest and recuperate myself. I cried again with that thought. In my view, he was not only a great Physician and Surgeon but also the greatest Dad. He lived a full life and touched so many lives with his treatments, charity services and teaching new physicians. It’s seeing, remembering and carrying on what he showed and taught us that really makes us miss him. I really love and miss my dad and with a smile on my face, I see he’s also happy to be with his brothers and sisters who passed on ahead. And that he’s rested. He is a man content, I remember he always said this, ‘ As long as I have a roof over my head and a bed to rest my back, I’m okay!”
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Burd, Amy, Ross L. Levine, Amy S. Ruppert, Alice S. Mims, Uma Borate, Eytan M. Stein, Prapti A. Patel, et al. "Precision Medicine Treatment in Older AML: Results of Beat AML Master Trial." Blood 134, Supplement_1 (November 13, 2019): 175. http://dx.doi.org/10.1182/blood-2019-130201.
Full textAbstract:
*equal contribution of AB, RLL, BD and JCB Background: Acute myeloid leukemia (AML) is common with increasing age, and older adults with AML rarely achieve long-term remission with chemotherapy. Gene discovery studies in older adults with AML have shown that this malignancy is characterized by a multitude of somatic genomic alterations beginning with initiating somatic events followed by acquisition of collaborative transforming mutations. Despite these important biologic insights, current therapeutic approaches to AML remain limited, particularly in adults ≥ 60 years of age. The Beat AML trial was designed to assess the feasibility of using genetic profiling to assign patients (pts) to molecularly defined, subtype-specific therapies within 7 days of the initial diagnosis in a multi-center clinical trial setting, and to delineate the role of molecularly informed first-line treatment of AML with mechanism based novel therapies. Methods: Treatment-naïve patients with AML were enrolled in this prospective trial which offered accelerated cytogenetic and comprehensive mutational testing within 7 days followed by treatment assignment using these molecular data. Pt eligibility included age ≥ 60 years with non-APML AML, no known CNS leukemia, no prior hypomethylating agent (HMA) therapy and no clinical need for emergent therapy. Eligible pts were profiled by local cytogenetics analysis and using a central next generation sequencing (NGS) assay (Foundation Medicine, Inc.) with all molecular data required for treatment assignment (TA) obtained < 7 days. TA was made centrally using a pre-determined algorithm considering somatic cytogenetic and molecular alterations in the dominant clone, available targeted therapeutics for specific AML subsets, and the likelihood of cure with intensive chemotherapy. Results: From November 2016 to January 2019, 487 pts with a suspected diagnosis of AML had enrolled at 14 clinical sites; 395 were eligible for the study (77% of the patients not eligible for the study had an alternative diagnosis). The median age of eligible patients was 72 years (range: 60 to 92) with 38% being≥ 75 years and 16% with treatment-related AML. From the 395 eligible patients, 374 (94.7%) were centrally assigned to the different cytogenetic/genomic groups within 7 days. The most common groups were TP53 mutated (19%) and marker negative (18%) molecular groups. The Beat AML trial is dynamic by design, thereby allowing different arms to open over time; all trial arms are designed to evaluate for substantial clinical efficacy in small, molecularly defined patient subsets. As shown in Figure 1, 224 patients (57%) had a TA and consented to a BEAT AML sub-study. Of the remaining 171 patients, 103 received standard therapy defined as induction therapy (7+3) or hypomethylation agent (25 before TA and 78 after TA), 28 received an alternative investigational agent (5 before TA and 23 after TA), 38 received palliative care, and 2 had an unknown treatment status and are grouped with the palliative care patients in subsequent analyses; 9 patients died before TA (2 who received standard therapy and 7 in the palliative care group). Demographic, clinical, performance and molecular characteristics were not largely different between pts who elected targeted therapy as part of the BEAT AML trial versus those who elected standard therapy. As shown in Figure 2, the overall survival was significantly longer for patients enrolled in a targeted therapy arm as part of the BEAT AML trial compared to those who elected standard therapy. (p<0.0001). The 30-day estimated death rate was 3.7% (95% CI: 1.9-7.2) for patients electing treatment on a BEAT AML sub-study, 20.4% (95% CI: 13.0-31.2) for those receiving standard therapy, 0% for those receiving an investigational therapy, and 72.6% (95% CI: 57.8-85.7) for the palliative care group. Conclusion: Our data support the feasibility of a rapid precision medicine approach in older patients with previously untreated AML. Patients with AML who elected treatment assigned based upon cytogenetic and molecular alterations in the dominant clone using a novel precision medicine approach had significantly improved overall survival versus those who elected standard of care treatment. Disclosures Levine: Gilead: Consultancy; Prelude Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Isoplexis: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Research Funding; Qiagen: Membership on an entity's Board of Directors or advisory committees; Loxo: Membership on an entity's Board of Directors or advisory committees; Imago Biosciences: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Lilly: Honoraria. Mims:Abbvie: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Astellas Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Borate:Novartis: Consultancy; Takeda: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; AbbVie: Consultancy. Stein:Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas Pharma US, Inc: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo, Inc.: Membership on an entity's Board of Directors or advisory committees; Bioline: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Patel:France Foundation: Honoraria; Dava Oncology: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Baer:Takeda: Research Funding; Incyte: Research Funding; Kite: Research Funding; Forma: Research Funding; AI Therapeutics: Research Funding; Abbvie: Research Funding; Astellas: Research Funding. Stock:Daiichi: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria; UpToDate: Honoraria; Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Deininger:Pfizer: Consultancy, Honoraria, Research Funding; Ascentage Pharma: Consultancy, Honoraria; TRM: Consultancy; Sangoma: Consultancy; Fusion Pharma: Consultancy; Adelphi: Consultancy; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Humana: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Sangamo: Consultancy; Blueprint: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Blum:Boehringer Ingelheim: Research Funding; Celgene: Research Funding; Astellas,: Research Funding; Xencor: Research Funding; Forma: Research Funding; AmerisourceBergen: Consultancy. Schiller:Amgen: Other, Research Funding; Agios: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Constellation Pharmaceutical: Research Funding; Daiichi Sankyo: Research Funding; Eli Lilly and Company: Research Funding; FujiFilm: Research Funding; Genzyme: Research Funding; Gilead: Research Funding; Incyte: Research Funding; J&J: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Karyopharm: Research Funding; Novartis: Research Funding; Onconova: Research Funding; Pfizer Pharmaceuticals: Equity Ownership, Research Funding; Sangamo Therapeutics: Research Funding; Bristol Myer Squibb: Research Funding; Astellas: Research Funding; Biomed Valley Discoveries: Research Funding. Olin:Daiichi Sankyo: Research Funding; Astellas: Research Funding; Genentech: Consultancy, Research Funding; Pfizer: Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria; Revolution Medicine: Consultancy; AstraZeneca: Research Funding; Clovis: Research Funding; Ignyta: Research Funding; MedImmune: Research Funding; Mirati Therapeutics: Research Funding; Novartis: Research Funding; Spectrum: Research Funding. Foran:Agios: Honoraria, Research Funding. Lin:Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria. Traer:AbbVie: Consultancy; Agios: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Notable Labs: Equity Ownership. Odenike:AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Astra Zeneca: Research Funding; Astex Pharmaceuticals: Research Funding; NS Pharma: Research Funding; Gilead Sciences: Research Funding; Janssen Oncology: Research Funding; Oncotherapy: Research Funding; Agios: Research Funding; CTI/Baxalta: Research Funding. Arellano:Gilead: Consultancy. Vergilio:Roche Holding AG: Equity Ownership; Foundation Medicine: Employment. Brennan:Foundation Medicine: Employment. Vietz:Foundation Medicine: Employment. Druker:ALLCRON: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Aileron Therapeutics: #2573, Constructs and cell lines harboring various mutations in TNK2 and PTPN11, licensing fees , Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Patents & Royalties, Research Funding; Burroughs Wellcome Fund: Membership on an entity's Board of Directors or advisory committees; Cepheid: Consultancy, Honoraria; The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; GRAIL: Equity Ownership, Other: former member of Scientific Advisory Board; Patient True Talk: Consultancy; Dana-Farber Cancer Institute (antibody royalty): Patents & Royalties: #2524, antibody royalty; Pfizer: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Research Funding; Merck & Co: Patents & Royalties: Dana-Farber Cancer Institute license #2063, Monoclonal antiphosphotyrosine antibody 4G10, exclusive commercial license to Merck & Co; OHSU (licensing fees): Patents & Royalties: #2573, Constructs and cell lines harboring various mutations in TNK2 and PTPN11, licensing fees ; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Aptose Biosciences: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Beta Cat: Membership on an entity's Board of Directors or advisory committees, Other: Stock options; Blueprint Medicines: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees, Other: Stock options; Beat AML LLC: Other: Service on joint steering committee; CureOne: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Gilead Sciences: Other: former member of Scientific Advisory Board; ICON: Other: Scientific Founder of Molecular MD, which was acquired by ICON in Feb. 2019; Monojul: Other: former consultant; Novartis: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Patents & Royalties: Patent 6958335, Treatment of Gastrointestinal Stromal Tumors, exclusively licensed to Novartis, Research Funding; Bristol-Myers Squibb: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Research Funding. Byrd:Novartis: Other: Travel Expenses, Speakers Bureau; BeiGene: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Acerta: Research Funding; Ohio State University: Patents & Royalties: OSU-2S; Genentech: Research Funding; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau.
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Kellogg, Wendy, and Kathryn Wertheim Hexter. "The role of the university in city planning: Cleveland's Lakefront Redevelopment Plan." Ekistics and The New Habitat 71, no. 427-429 (December 1, 2004). http://dx.doi.org/10.53910/26531313-e200471427-429187.
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Wendy A. Kellogg is an Associate Professor of Urban Planning and Environmental Studies. She earned her Ph. D (City and Regional Planning) at Cornell University in 1993. Her major fields of research interest are citizen participation, urban and regional sustainability, neighborhood redevelopment, and Great Lakes water quality and land use issues. She has published analyses of Great Lakes water quality planning programs and citizen participation in neighborhood-based environmental planning. Her research projects have included an environmental history and inventory of a neighborhood in central Cleveland, Ohio, the role of local decision makers in coastal and watershed protection, and the role of training programs in shaping local decision-maker behavior toward coastal management. Dr Kellogg was an Ohio Campus Compact Learn and Serve Fellow in 1998 and a USEPA-funded Fellow at the CSU Program on Risk Analysis in 2000-2001. She currently is a research associate of the Great Lakes Environmental Finance Center at Cleveland State University. Dr Kellogg teaches courses in urban planning, environmental planning, environmental policy, and urban theory.
Kathryn Wertheim Hexter, Director of the Levin College ForumProgram since 2000, joined the Maxine Goodman Levin College asa public policy analyst on housing and energy issues in 1989. The Forum brings together the university and the community to address critical public policy issues that impact Northeast Ohio, the state and the nation. She also manages the Thomas F. Campbell, Ph. D Exhibition Gallery that houses exhibits that complement special forum programs. A planner and public policy analyst, Ms Hexter has over 25 years of experience managing and directing projects and evaluating programs in the areas of housing policy, neighborhood development, low-income energy assistance, city and regional planning and civic engagement.
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Mason, Thomas, Nayanika Challa, Jae Baek, Arthur Pollauf, Emily Veach, Luis Regalado, and Jacy Leon. "PODEMOS: A Student-Led International Medical Brigade." Journal of Student-Run Clinics 7, no. 1 (July 28, 2021). http://dx.doi.org/10.59586/jsrc.v7i1.184.
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PODEMOS, Spanish for “We Canâ€, is an interdisciplinary healthcare organization based in Columbus, Ohio, that is designed to meet the healthcare needs of communities around the city of El Progreso, Honduras. Honduras is a developing country in Central America that scores low in most indicators of healthcare quality and access. Most notably, there is a tremendous need for expanded access in rural communities. Established in 2008 by students from the Ohio State University College of Medicine, PODEMOS conducts biannual medical brigades that run primary care clinics in three rural communities around El Progreso through the volunteer service of United States (US)-based medical, pharmacy, and dental professionals. Additionally, the organization works with local leaders to provide healthcare services for patients with chronic conditions, fill gaps in US-based provider coverage, and recruit patients. PODEMOS bases its care on two models, the acute care model for common adult complaints and all children under the age of 18, and the chronic care model for a subset of adult patients who need more complex care for chronic conditions such as diabetes mellitus and hypertension. Providers then have access to select laboratory and pharmacy services for their patient’s needs. PODEMOS has had a large impact on local communities since its inception, as evidenced by the numerous acute patient visits in its 11 years of existence and the 136 patients currently enrolled in chronic care program. Nevertheless, the organization continues to face challenges in areas such as interprofessional collaboration, security, and maintaining patient turnout. This piece is a descriptive report on PODEMOS, a student-run international medical organization based out of the Ohio State University Wexner Medical Center, that seeks to inform other student-run organizations about the organization’s structure and operation.
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"Book Reviews." Journal of Economic Literature 51, no. 2 (June 1, 2013): 564–70. http://dx.doi.org/10.1257/jel.51.2.544.r12.
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Belton M. Fleisher of Ohio State University, Central University of Finance and Economics, and IZA reviews, “Demystifying the Chinese Economy “ by Justin Yifu Lin. The Econlit abstract of this book begins: “Originally published in Chinese in 2009. Updated English-language edition explores China's economic development and transition over the past few centuries and considers the reforms necessary for China to complete the transition to a well-functioning market economy. Discusses opportunities and challenges in China's economic development; why the Scientific and Industrial Revolutions bypassed China; the great humiliation and the Socialist Revolution; the comparative advantage-defying, catching-up strategy and the traditional economic system; enterprise viability and factor endowments; the comparative-advantage-following development strategy; rural reform and the three rural issues; urban reform and the remaining issues; reforming the state-owned enterprises; the financial reforms; deflationary expansion and building a new socialist countryside; improving the market system and promoting fairness and efficiency for harmonious development; and reflections on neoclassical theories. Lin is Senior Vice President and Chief Economist of the World Bank.”
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"H. Gordon Skilling. Samizdat and an Independent Society in Central and Eastern Europe. Columbus: Ohio State University Press. 1989. Pp. xi, 293. $30.00." American Historical Review, October 1991. http://dx.doi.org/10.1086/ahr/96.4.1240.
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Eze, Gbalam Peter, and Ekokeme, Tamaroukro Timipere. "Insurance Sector Development and Foreign Direct Investment in Nigeria." Asian Journal of Economics, Business and Accounting, February 17, 2020, 17–27. http://dx.doi.org/10.9734/ajeba/2020/v14i130183.
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Aims: The study examined the impact of insurance sector development on foreign direct investment in Nigeria.
Study Design: The ex-post facto research design was employed to observe the study components in retrospect. Secondary data spanning 1996 to 2017 was sourced and collated from the World Development Indicators, Central Bank of Nigeria statistical bulletin and National Insurance Commission annual balance sheets.
Place and Duration of Study: Department of Banking and Finance, Niger Delta University, Wilberforce Island, Bayelsa State, Nigeria. The study was carried out between November 2019 to January 2020.
Methodology: The ex-post facto research design was employed to observe the study components in retrospect. Secondary data spanning 1996 to 2017 was sourced and collated from the World Development Indicators, Central Bank of Nigeria statistical bulletin and National Insurance Commission annual balance sheets. The time series data was estimated using the least square technique.
Results: The results indicates that; the total asset size of the insurance sector exerts a negative and statistically insignificant impact on foreign direct investment inflow to Nigeria, total insurance business investment exerts a positive and statistically insignificant impact on foreign direct investment inflow to Nigeria and finally, total insurance premium exerts a negative and statistically significant impact on foreign direct investment inflow to Nigeria.
Conclusion: The study concludes that insurance sector development does not attract foreign investment inflow to Nigeria. The study recommends that the insurance sector should be revamped in order to absorb risk and uncertainty and be a vehicle for risk transfer and minimization. A policy of restructuring would help instil public confidence, boost insurance policy sales, increase insurance premium and invariably increase the availability of investible funds to boost economic activity. The study suggests that these would help attract foreign direct investment to meet domestic funding needs of Nigeria.
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Castellon Larios, Karina, Katherine Rybka, Diana Greene-Chandos, Sergio Bergese, and Michel Torbey. "Abstract W P240: The Effect of Telestroke Network on Tissue Plasminogen Activator Utilization and Door to Needle Time on Rural Hospitals." Stroke 45, suppl_1 (February 2014). http://dx.doi.org/10.1161/str.45.suppl_1.wp240.
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Introduction: Stroke is the 4 th leading cause of death in the United States. Only 2-3% of ischemic stroke patients are receiving Tissue plasminogen activator (t-PA) despite an increase in time window to 4.5 hours. With less than 85% of the US population living within 30 minutes of primary stroke centers, it is important to review the effectiveness of telestroke network in delivering t-PA. The Ohio State University Wexner Medical Center (OSUWMC) Telestroke network was established in May 2011. Currently the network expands across 24 spokes located in rural central Ohio. Most of these centers have not given t-PA prior to joining the network. Objective: Evaluate the effectiveness of the OSUWMC telestroke in delivering t-PA for acute ischemic stroke in a rural setting and compare the stroke quality metrics to Ohio Coverdell registered Hospitals. Methods: We conducted a retrospective data review from the OSUWMC Telestroke Network database from May 22, 2011 to November 30, 2012. This included demographics, diagnostic impression, NIHSS score, average symptom onset to ED arrival, average door to CT time, average consult duration. t-PA administration and transfer status to OSUMWC were also collected. Summary statistics were generated using Microsoft Excel (version 2010, Microsoft Corporation) and SAS (version 9.3, SAS Institute). Results: In this study, a total of 422 Telestroke consultations were completed. 180 patients were diagnosed with ischemic stroke (57.5%). Average NIHSS score was 5 ±6, average symptom onset to ED arrival time was 4 hours 26 minutes (n=378), and the average door to CT time was 26 minutes (n=204). Forty-four percent (n=80) were approved to receive IV t-PA; 60% within one hour of ED arrival. From this number of patients thirty percent received t-PA within one hour compared to 38% in Ohio Coverdell hospitals. Conclusion: The implementation of telestroke network can deliver care that is equivalent to primary stroke centers. This approach may be an effective tool for rapid evaluation of patients in remote hospitals that require neurologic specialists.
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Schwabe, Joachim, Torsten Mayer-Gürr, Christian Hirt, and Tobias Bauer. "A new spherical harmonic approach to residual terrain modeling: a case study in the central European Alps." Journal of Geodesy 98, no. 7 (July 2024). http://dx.doi.org/10.1007/s00190-024-01843-4.
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AbstractFor decades, the residual terrain model (RTM) concept (Forsberg and Tscherning in J Geophys Res Solid Earth 86(B9):7843–7854, https://doi.org/10.1029/JB086iB09p07843, 1981) has been widely used in regional quasigeoid modeling. In the commonly used remove-compute-restore (RCR) framework, RTM provides a topographic reduction commensurate with the spectral resolution of global geopotential models. This is usually achieved by utilizing a long-wavelength (smooth) topography model known as reference topography. For computation points in valleys this neccessitates a harmonic correction (HC) which has been treated in several publications, but mainly with focus on gravity. The HC for the height anomaly only recently attracted more attention, and so far its relevance has yet to be shown also empirically in a regional case study. In this paper, the residual spherical-harmonic topographic potential (RSHTP) approach is introduced as a new technique and compared with the classic RTM. Both techniques are applied to a test region in the central European Alps including validation of the quasigeoid solutions against ground-truthing data. Hence, the practical feasibility and benefits for quasigeoid computations with the RCR technique are demonstrated. Most notably, the RSHTP avoids explicit HC in the first place, and spectral consistency of the residual topographic potential with global geopotential models is inherently achieved. Although one could conclude that thereby the problem of the HC is finally solved, there remain practical reasons for the classic RTM reduction with HC. In this regard, both intra-method comparison and ground-truthing with GNSS/leveling data confirms that the classic RTM (Forsberg and Tscherning 1981; Forsberg in A study of terrain reductions, density anomalies and geophysical inversion methods in gravity field modeling. Report 355, Department of Geodetic Sciences and Surveying, Ohio State University, Columbus, Ohio, USA, https://earthsciences.osu.edu/sites/earthsciences.osu.edu/files/report-355.pdf, 1984) provides reasonable results also for a high-resolution (degree 2160) RTM, yet neglecting the HC for the height anomaly leads to a systematic bias in deep valleys of up to 10–20 cm.
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"Evaluation of a New Clinical Test of Fusion Status: A Pilot Study." Vision Development & Rehabilitation, June 28, 2019, 113–18. http://dx.doi.org/10.31707/vdr2019.5.2.p113.
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Background Suppression is associated with binocular vision conditions such as amblyopia and strabismus. Commercial methods of testing fusion often only measure central fusion or suppression at near. The purpose of this pilot study was to assess a new iPad picture fusion test that assesses foveal and central fusion at near. Methods Participants aged 5 years and older presenting for eye examination at The Ohio State University College of Optometry were enrolled. Results from visual acuity, dry and wet refraction/retinoscopy, stereopsis and cover testing were recorded from the patient chart. The iPad picture fusion test, Worth four-dot, Worth type test with foveal letter targets, and Polarized four-dot were performed by one examiner in a randomized order at 40 cm. Testing was repeated with the anaglyphic filters reversed. Crosstabulation and McNemar chi-square analysis were used to compare the results between fusion testing devices. Results Of the fifty participants (mean age = 17.5), twelve reported suppression and one reported diplopia. Testability was excellent for all tests (98% to 100%). There were no significant differences between tests in reported results (P ≥ 0.22 for all comparisons). No difference in reported fusion or suppression status was observed with change in orientation of the anaglyphic filters. Six participants reported foveal suppression alone at near which was not identified with Worth four-dot at near. Conclusion The iPad picture fusion test provided excellent testability and agreement with commonly used tests of fusion and allowed testing of both central and foveal fusion at near. Nearly half (46%) of participants with suppression reported foveal suppression, supporting the importance of testing for foveal suppression.