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1. Subclonal Somatic Copy-Number Alterations Emerge and Dominate in Recurrent Osteosarcoma

Author

Kinnaman, M, Zaccaria, S, Makohon-Moore, A, Arnold, B, Levine, M, Gundem, G, Arango Ossa, J, Glodzik, D, Rodriguez-Sanchez, M, Bouvier, N, Li, S, Stockfisch, E, Dunigan, M, Cobbs, C, Bhanot, U, You, D, Mullen, K, Melchor, J, Ortiz, M, O'Donohue, T, Slotkin, E, Wexler, L, Dela Cruz, F, Hameed, M, Glade Bender, J, Tap, W, Meyers, P, Papaemmanuil, E, Kung, A, Iacobuzio-Donahue, C, Kinnaman M. D., Zaccaria S., Makohon-Moore A., Arnold B., Levine M. F., Gundem G., Arango Ossa J. E., Glodzik D., Rodriguez-Sanchez M. I., Bouvier N., Li S., Stockfisch E., Dunigan M., Cobbs C., Bhanot U. K., You D., Mullen K., Melchor J. P., Ortiz M. V., O'Donohue T. J., Slotkin E. K., Wexler L. H., Dela Cruz F. S., Hameed M. R., Glade Bender J. L., Tap W. D., Meyers P. A., Papaemmanuil E., Kung A. L., Iacobuzio-Donahue C. A., Kinnaman, M, Zaccaria, S, Makohon-Moore, A, Arnold, B, Levine, M, Gundem, G, Arango Ossa, J, Glodzik, D, Rodriguez-Sanchez, M, Bouvier, N, Li, S, Stockfisch, E, Dunigan, M, Cobbs, C, Bhanot, U, You, D, Mullen, K, Melchor, J, Ortiz, M, O'Donohue, T, Slotkin, E, Wexler, L, Dela Cruz, F, Hameed, M, Glade Bender, J, Tap, W, Meyers, P, Papaemmanuil, E, Kung, A, Iacobuzio-Donahue, C, Kinnaman M. D., Zaccaria S., Makohon-Moore A., Arnold B., Levine M. F., Gundem G., Arango Ossa J. E., Glodzik D., Rodriguez-Sanchez M. I., Bouvier N., Li S., Stockfisch E., Dunigan M., Cobbs C., Bhanot U. K., You D., Mullen K., Melchor J. P., Ortiz M. V., O'Donohue T. J., Slotkin E. K., Wexler L. H., Dela Cruz F. S., Hameed M. R., Glade Bender J. L., Tap W. D., Meyers P. A., Papaemmanuil E., Kung A. L., and Iacobuzio-Donahue C. A.

Abstract

Multiple large-scale genomic profiling efforts have been undertaken in osteosarcoma to define the genomic drivers of tumorigenesis, therapeutic response, and disease recurrence. The spatial and temporal intratumor heterogeneity could also play a role in promoting tumor growth and treatment resistance. We conducted longitudinal whole-genome sequencing of 37 tumor samples from 8 patients with relapsed or refractory osteosarcoma. Each patient had at least one sample from a primary site and a metastatic or relapse site. Subclonal copy-number alterations were identified in all patients except one. In 5 patients, subclones from the primary tumor emerged and dominated at subsequent relapses. MYC gain/amplification was enriched in the treatment-resistant clones in 6 of 7 patients with multiple clones. Amplifications in other potential driver genes, such as CCNE1, RAD21, VEGFA, and IGF1R, were also observed in the resistant copy-number clones. A chromosomal duplication timing analysis revealed that complex genomic rearrangements typically occurred prior to diagnosis, supporting a macroevolutionary model of evolution, where a large number of genomic aberrations are acquired over a short period of time followed by clonal selection, as opposed to ongoing evolution. A mutational signature analysis of recurrent tumors revealed that homologous repair deficiency (HRD)-related SBS3 increases at each time point in patients with recurrent disease, suggesting that HRD continues to be an active mutagenic process after diagnosis. Overall, by examining the clonal relationships between temporally and spatially separated samples from patients with relapsed/refractory osteosarcoma, this study sheds light on the intratumor heterogeneity and potential drivers of treatment resistance in this disease. Significance: The chemoresistant population in recurrent osteosarcoma is subclonal at diagnosis, emerges at the time of primary resection due to selective pressure from neoadjuvant chemotherapy, an

Published
2023

3. New Collaborative Research on Suicide Prevention, Practice, and Policy With American Indian and Alaska Native Communities Holds Promise for All Peoples

Author

Barlow, A., primary, Haroz, E. E., additional, O’Keefe, V. M., additional, Brockie, T., additional, Manson, S. M., additional, Allen, J., additional, Wexler, L., additional, Buchwald, D., additional, Rasmus, S., additional, Goklish, N., additional, Ivanich, J., additional, Stifter, M., additional, and Cwik, M., additional

Published
2023
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4. 52P Long-term outcomes in children, adolescents, and young adults with localized Ewing sarcoma treated with standard vs dose-intensified ifosfamide

Author

Kinnaman, M.D., primary, Goodboy, C., additional, Avutu, V., additional, Glade Bender, J., additional, Dickson, M., additional, Dela Cruz, F., additional, O'Donohue, T., additional, Tap, W.D., additional, Wexler, L., additional, Slotkin, E., additional, Kolb, E.A., additional, Kushner, B., additional, and Meyers, P., additional

Published
2023
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5. Patient-derived xenografts effectively capture responses to oncology therapy in a heterogeneous cohort of patients with solid tumors

Author

Izumchenko, E., Paz, K., Ciznadija, D., Sloma, I., Katz, A., Vasquez-Dunddel, D., Ben-Zvi, I., Stebbing, J., McGuire, W., Harris, W., Maki, R., Gaya, A., Bedi, A., Zacharoulis, S., Ravi, R., Wexler, L. H., Hoque, M. O., Rodriguez-Galindo, C., Pass, H., Peled, N., Davies, A., Morris, R., Hidalgo, M., and Sidransky, D.

Published
2017
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9. Effect of theophylline on sleep-disordered breathing in heart failure

Author

Javaheri, S., Parker, T.J., Wexler, L., Liming, J.D., Lindower, P., and Roselle, G.A.

Subjects
Sleep apnea syndromes -- Drug therapy, Theophylline -- Evaluation
Abstract

Theophylline may be effective in restoring normal breathing patterns in patients with heart failure. These patients often stop breathing periodically during sleep, a condition called apnea. Fifteen men with heart failure and sleep apnea took theophylline twice a day or placebo for five days and then switched treatments. Theophylline reduced the number of apnea episodes and also the percent of time the men experienced low blood oxygen levels.

Published
1996

14. Arctic Indigenous Youth Resilience and Vulnerability: Comparative Analysis of Adolescent Experiences and Resilience Strategies across Five Circumpolar Communities

Author

Ulturgasheva, O., Rasmus, S., Wexler, L., Nystad, K., M, Kral

Subjects
Arctic, indigenous, resilience, vulnerability, youth
Abstract

Arctic peoples today find themselves on the front line of rapid environmental change brought about by globalizing forces, shifting climates, and destabilizing physical condi- tions. The weather is not the only thing undergoing rapid change here. Social climates are intrinsically connected to physical climates, and changes within each have profound effects on the daily life, health, and well-being of circumpolar indigenous peoples. This paper describes a collaborative effort between university researchers and community members from five indigenous communities in the circumpolar north aimed at compar- ing the experiences of indigenous Arctic youth in order to come up with a shared model of indigenous youth resilience. The discussion introduces a sliding scale model that emerged from the comparative data analysis. It illustrates how a “sliding scale” of resilience captures the inherent dynamism of youth strategies for “doing well” and what forces represent positive and negative influences that slide towards either personal and communal resilience or vulnerability. The model of the sliding scale is designed to reflect the contingency and interdependence of resilience and vulnerability and their fluctuations between lowest and highest points based on timing, local situ- ation, larger context, and meaning.

Published
2014

17. Rhabdomyosarcoma: Current Challenges and Their Implications for Developing Therapies

Author

Hettmer, S., primary, Li, Z., additional, Billin, A. N., additional, Barr, F. G., additional, Cornelison, D. D. W., additional, Ehrlich, A. R., additional, Guttridge, D. C., additional, Hayes-Jordan, A., additional, Helman, L. J., additional, Houghton, P. J., additional, Khan, J., additional, Langenau, D. M., additional, Linardic, C. M., additional, Pal, R., additional, Partridge, T. A., additional, Pavlath, G. K., additional, Rota, R., additional, Schafer, B. W., additional, Shipley, J., additional, Stillman, B., additional, Wexler, L. H., additional, Wagers, A. J., additional, and Keller, C., additional

Published
2014
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18. Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary

Author

Gorlick, R., Anderson, P., Andrulis, I., Arndt, C., Beardsley, G. P., Bernstein, M., Bridge, J., Cheung, N. -K, Dome, J. S., Ebb, D., Gardner, T., Gebhardt, M., Grier, H., Hansen, M., John Healey, Helman, L., Hock, J., Houghton, J., Houghton, P., Huvos, A., Khanna, C., Kieran, M., Kleinerman, E., Ladanyi, M., Lau, C., Malkin, D., Marina, N., Meltzer, P., Meyers, P., Schofield, D., Schwartz, C., Smith, M. A., Toretsky, J., Tsokos, M., Wexler, L., Wigginton, J., Withrow, S., Schoenfeldt, M., and Anderson, B.

Subjects
Osteosarcoma, Neovascularization, Pathologic, Humans, Angiogenesis Inhibitors, Bone Neoplasms, Child
Abstract

Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The North American pediatric cooperative groups have performed a series of clinical treatment trials in this disease over the past several decades, and biology studies of tumor tissue have been an important study component. A meeting was held in Bethesda, Maryland on November 29-30, 2001, sponsored by the NIH Office of Rare Diseases, the Children's Oncology Group, and the National Cancer Institute-Cancer Therapy Evaluation Program with the general objectives: (a) to review the current state of knowledge regarding OS biology; (b) to identify, prioritize, and support the development of biology studies of potential clinical relevance in OS; and (c) to discuss the available tissue resources and the appropriate methods for analysis of OS samples for the conduct of biology studies. This report summarizes the information presented and discussed by the meeting participants.

Published
2003

19. Use of multidetector computed tomography for the assessment of acute chest pain: A consensus statement of the North American Society of Cardiac Imaging and the European Society of Cardiac Radiology

Author

Stillman, A.E. (Arthur), Oudkerk, M. (Matthijs), Ackerman, M. (Margaret), Becker, C.R. (Christoph), Buszman, P.E. (Pawel), Feyter, P.J. (Pim) de, Hoffmann, U. (Udo), Keadey, M.T. (Matthew), Marano, R. (Riccardo), Lipton, M.J. (Martin), Raff, G.L. (Gilbert), Reddy, G.P. (Gautham), Rees, M.R. (Michael), Rubin, G.D. (Geoffrey), Schoepf, U.J. (Joseph), Tarulli, G. (Giuseppe), Beek, E.J.R. (Edwin) van, Wexler, L. (Lewis), White, C.S. (Charles), Stillman, A.E. (Arthur), Oudkerk, M. (Matthijs), Ackerman, M. (Margaret), Becker, C.R. (Christoph), Buszman, P.E. (Pawel), Feyter, P.J. (Pim) de, Hoffmann, U. (Udo), Keadey, M.T. (Matthew), Marano, R. (Riccardo), Lipton, M.J. (Martin), Raff, G.L. (Gilbert), Reddy, G.P. (Gautham), Rees, M.R. (Michael), Rubin, G.D. (Geoffrey), Schoepf, U.J. (Joseph), Tarulli, G. (Giuseppe), Beek, E.J.R. (Edwin) van, Wexler, L. (Lewis), and White, C.S. (Charles)

Published
2007
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20. Use of multidetector computed tomography for the assessment of acute chest pain: a consensus statement of the North American Society of Cardiac Imaging and the European Society of Cardiac Radiology

Author

Stillman, AE, Oudkerk, M, Ackerman, M, Becker, CR, Buszman, PE, Feijter, Pim, Hoffmann, U, Keadey, MT, Marano, R, Lipton, MJ, Raff, GL, Reddy, GP, Rees, MR, Rubin, GD, Schoepf, UJ, Tarulli, G, van Beek, EJR, Wexler, L, White, CS, Stillman, AE, Oudkerk, M, Ackerman, M, Becker, CR, Buszman, PE, Feijter, Pim, Hoffmann, U, Keadey, MT, Marano, R, Lipton, MJ, Raff, GL, Reddy, GP, Rees, MR, Rubin, GD, Schoepf, UJ, Tarulli, G, van Beek, EJR, Wexler, L, and White, CS

Published
2007

21. Improving Population Assumptions in Greenhouse Emissions Models

Author

Wexler, L.

Abstract

It is no surprise that population plays an important role in long-term models of greenhouse gas emissions and global climate change. Population represents both a primary scale factor for the size of the human economy and the fundamental unit at which societal welfare is measured. This paper surveys the population assumptions in several important models of global warming in the 1990s, including energy models, integrated emissions models, and economic policy models. Choice of population inputs, the role of population variables in model equations, sensitivity analyses, and consideration of population policy are all described. The paper finds room for improvement in the following areas: choice and provision of population projections, consistent treatment of age structure and urbanization, specification of relationship between per capita income and population, and the consideration of population policy in economic policy models. It is suggested that improvement in these areas would be greatly aided by interdisciplinary cooperation, especially between demographers, economists, and energy modelers.

Published
1996

22. Decomposing Models of Demographic Impact on the Environment

Author

Wexler, L.

Abstract

Demographic Impact (DI) models are multiplicative identities used to decompose environmental impacts into components due to population, economic and technological change. While such decompositions have played an important role in the population-environment literature, inconsistent and ambiguous methods have made their results difficult to interpret and nearly impossible to compare. This paper demonstrates and clarifies the differences between these methods using the example of anthropogenic greenhouse gas (GHG) emissions. This paper locates two distinct approaches to DI model decomposition: The annual growth rate decomposition and the multiplicative decomposition. Stable indices are provided for each approach. Finally, the Divisia Index -- a common price index used by economists -- is suggested as an appropriate method to aggregate DI model results.

Published
1996

26. The greenhouse externality to childbearing: A sensitivity analysis

Author

O'Neill, B.C., Wexler, L., O'Neill, B.C., and Wexler, L.

Abstract

Externalities to childbearing measure costs or benefits associated with the birth of a child that fall on society but are not considered in the parents' fertility decisions. Externalities are a key part of the theoretical justification for policies that affect fertility behavior. Environmental externalities potentially constitute a significant part of the net externality to childbearing, but few estimates of their magnitude have been made. Here we estimate the 'greenhouse externality' to childbearing resulting from the increased CO2 abatement costs necessitated by an additional birth assuming atmospheric CO2 levels are eventually stabilized, and examine the sensitivity of the results to a number of factors. We find that the greenhouse externality, calculated over the period 1995-2100, is generally negative and in most cases ranges from several hundred to several thousand dollars per birth. These estimates are most sensitive to the discount rate and the institutional arrangements, such as the allowance of emissions trading, according to which reductions are made. They are less sensitive to, although still significantly affected by, the stabilization level, the timing of reductions, future population growth, and the abatement cost function. Estimates of impacts on MDCs and LDCs considered separately demonstrate that the externality can be truly global, in that effects of births in one region can spill over onto the other. In general, negative externalities rival or, in some cases, greatly exceed estimates of the costs of averting births. Investments in fertility-related population policies such as voluntary family planning services and female education are considered desirable in their own right; these results indicate that they can also be considered likely candidates for cost-effective `no-regrets' climate change policy.

Published
2000

32. Radiation therapy for Ewing’s sarcoma

Author

La, T. H., primary, Meyers, P. A., additional, Wexler, L. H., additional, Healey, J. H., additional, La Quaglia, M. P., additional, Boland, P. J., additional, and Wolden, S. L., additional

Published
2005
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46. Training standards for physicians performing peripheral angioplasty and other percutaneous peripheral vascular interventions. A statement for health professionals from the Special Writing Group of the Councils on Cardiovascular Radiology, Cardio-Thoracic and Vascular Surgery, and Clinical Cardiology, the American Heart Association.

Author

Levin, D C, primary, Becker, G J, additional, Dorros, G, additional, Goldstone, J, additional, King, S B, additional, Seeger, J M, additional, Spies, J B, additional, Spittell, J A, additional, and Wexler, L, additional

Published
1992
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49. Who's your patty? Consumer acceptance and sensory properties of burger patties made with different types of meat or plant-based products.

Author

Rohall S, Ballintine J, Vowels J, Wexler L, and Goto K

Abstract

Having more healthful options at campus eateries is a viable way to meet consumer demand, as well as to promote health on campus. Our study tested three healthier alternatives (low-fat beef, turkey, and soy/rice burgers) against the conventional full-fat hamburger patty (control). We examined consumer acceptance of the four burger patties with 48 untrained student panelists. A 9-point scale hedonic test was used to measure consumer acceptance. Quantitative descriptive analysis (QDA) was also conducted with six trained panelists to evaluate the intensity of sensory properties. Analysis of variance was used to detect significant differences among the treatments. Consumer acceptance mean scores for full-fat beef, lean beef, turkey, and soy/rice patties were 5.98, 6.68, 5.50 and 5.56, respectively, with no preference of the control patty over turkey or soy/rice, but a significant preference of the lean beef over turkey and soy/rice. QDA results showed flavor, spiciness, and elasticity significantly varied across the treatments. Panelists rated lean beef as significantly more elastic than all other patties. It is uncertain whether those sensory attributes contributed to consumer acceptance. In conclusion, our research indicates that college consumers may accept these healthier substitutes for traditional full-fat beef patties. Consumer acceptance of healthier patty substitutes should be further investigated in primary and secondary schools as well. With proper marketing, healthier alternatives to the conventional, full-fat hamburger patty could become competitive choices. [ABSTRACT FROM AUTHOR]

Published
2009

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