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6. Integrating Palliative Care Into Physiatric Care: Perspective of the Association of Academic Physiatrists Physiatry Palliative Care Task Force

Author

Dorothy Weiss, Tolchin, Naomi M, Kaplan, Sean R, Smith, Kim D D, Barker, and Andrea L, Cheville

Subjects
Palliative Care, Humans, Physical and Rehabilitation Medicine, Physiatrists
Abstract

There are opportunities for physiatrists to apply a palliative care lens within clinical encounters across rehabilitation settings. The expanding population of patients with serious illness and injury cared for by physiatrists and the anticipated shortage of specialty palliative care clinicians make it important that physiatrists hone and apply basic palliative care skills as part of comprehensive physiatric care. In this article, four clinical vignettes highlight relevant palliative care communication skills and demonstrate the value of integrating these skills within physiatry encounters. Resources to support physiatrists in applying basic palliative skills are provided throughout.

Published
2022

10. P500: A REAL WORLD MULTI CENTRE STUDY OF CPX-351 REVEALS NO DIFFERENCE IN OVERALL SURVIVAL WHEN COMPARED WITH FLAG-IDA AND 3 + 7 IN HIGH RISK AML.

Author

Andrews, C., primary, AlNabhani, I., additional, Young, T., additional, Atenafu, E. G., additional, Assouline, S. E., additional, Brandwein, J. M., additional, Chan, S. M., additional, Chow, S., additional, Khalaf, D., additional, Gupta, V., additional, Kim, D. D. H., additional, Maze, D., additional, Minden, M. M., additional, Murphy, T., additional, Sanford, D., additional, Schimmer, A. D., additional, Schuh, A. C., additional, Sibai, J., additional, Yee, K., additional, and Sibai, H., additional

Published
2022
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11. P708: CANADIAN AND RUSSIAN EXPERIENCES OF ASCIMINIB IN CHRONIC MYELOID LEUKEMIA (CML) PATIENTS WHO FAILED MULTIPLE LINES OF TYROSINE KINASE INHIBITOR (TKI) THERAPY.

Author

Khadadah, F., primary, Turkina, A. G., additional, Lomaia, E., additional, Morozova, E. V., additional, Shukhov, O. A., additional, Petrova, A., additional, Chitanava, T., additional, Vlasova, J. J., additional, Kuzmina, E., additional, Nemchenko, I., additional, Chelysheva, E. Y., additional, Bykova, A., additional, Gurianova, M., additional, Xenocostas, A., additional, Busque, L., additional, Jamani, K., additional, Cerquozzi, S., additional, Kuruvilla, P., additional, Kaedbey, R., additional, Leber, B., additional, Assouline, S., additional, and Kim, D. D. H., additional

Published
2022
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12. S155: EFFICACY AND SAFETY RESULTS FROM ASCEMBL, A PHASE 3 STUDY OF ASCIMINIB VS BOSUTINIB IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE AFTER ≥2 PRIOR TYROSINE KINASE INHIBITORS: WK 96 UPDATE

Author

Rea, D., primary, Hochhaus, A., additional, Mauro, M. J., additional, Minami, Y., additional, Lomaia, E., additional, Voloshin, S., additional, Turkina, A., additional, Kim, D.-W., additional, Apperley, J. F., additional, Cortes, J. E., additional, Abdo, A., additional, Fogliatto, L. M., additional, Kim, D. D. H, additional, le Coutre, P., additional, Saussele, S., additional, Annunziata, M., additional, Hughes, T. P., additional, Chaudhri, N., additional, Chee, L., additional, García-Gutiérrez, V., additional, Sasaki, K., additional, Kapoor, S., additional, Allepuz, A., additional, Quenet, S., additional, Bédoucha, V., additional, and Boquimpani, C., additional

Published
2022
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18. zfit: scalable pythonic fitting

Author

Doglioni, C, Kim, D, Stewart, GA, Silvestris, L, Jackson, P, Kamleh, W, Doglioni, C ( C ), Kim, D ( D ), Stewart, G ( GA ), Silvestris, L ( L ), Jackson, P ( P ), Kamleh, W ( W ), Eschle, Jonas; https://orcid.org/0000-0002-7312-3699, Puig Navarro, Albert; https://orcid.org/0000-0001-8868-2947, Silva Coutinho, Rafael, Serra, Nicola, Doglioni, C, Kim, D, Stewart, GA, Silvestris, L, Jackson, P, Kamleh, W, Doglioni, C ( C ), Kim, D ( D ), Stewart, G ( GA ), Silvestris, L ( L ), Jackson, P ( P ), Kamleh, W ( W ), Eschle, Jonas; https://orcid.org/0000-0002-7312-3699, Puig Navarro, Albert; https://orcid.org/0000-0001-8868-2947, Silva Coutinho, Rafael, and Serra, Nicola

Abstract

Statistical modeling and fitting is a key element in most HEP analyses. This task is usually performed in the C++ based framework ROOT/RooFit. Recently the HEP community started shifting more to the Python language, which the tools above are only loose integrated into, and a lack of stable, native Python based toolkits became clear. We presented zfit, a project that aims at building a fitting ecosystem by providing a carefully designed, stable API and a workflow for libraries to communicate together with an implementation fully integrated into the Python ecosystem. It is built on top of one of the state-of-theart industry tools, TensorFlow, which is used the main computational backend. zfit provides data loading, extensive model building capabilities, loss creation, minimization and certain error estimation. Each part is also provided with convenient base classes built for customizability and extendability.

Published
2020

28. Laying the foundation for genomically-based risk assessment in chronic myeloid leukemia

Author

Branford, S, Kim, D, Apperley, J, Eide, C, Mustjoki, S, Ong, S, Nteliopoulos, G, Ernst, T, Chuah, C, Gambacorti-Passerini, C, Mauro, M, Druker, B, Mahon, F, Cortes, J, Radich, J, Hochhaus, A, Hughes, T, Branford S., Kim D. D. H., Apperley J. F., Eide C. A., Mustjoki S., Ong S. T., Nteliopoulos G., Ernst T., Chuah C., Gambacorti-Passerini C., Mauro M. J., Druker B. J., Kim D. -W., Mahon F. -X., Cortes J., Radich J. P., Hochhaus A., Hughes T. P., Branford, S, Kim, D, Apperley, J, Eide, C, Mustjoki, S, Ong, S, Nteliopoulos, G, Ernst, T, Chuah, C, Gambacorti-Passerini, C, Mauro, M, Druker, B, Mahon, F, Cortes, J, Radich, J, Hochhaus, A, Hughes, T, Branford S., Kim D. D. H., Apperley J. F., Eide C. A., Mustjoki S., Ong S. T., Nteliopoulos G., Ernst T., Chuah C., Gambacorti-Passerini C., Mauro M. J., Druker B. J., Kim D. -W., Mahon F. -X., Cortes J., Radich J. P., Hochhaus A., and Hughes T. P.

Abstract

Outcomes for patients with chronic myeloid leukemia (CML) have substantially improved due to advances in drug development and rational treatment intervention strategies. Despite these significant advances there are still unanswered questions on patient management regarding how to more reliably predict treatment failure at the time of diagnosis and how to select frontline tyrosine kinase inhibitor (TKI) therapy for optimal outcome. The BCR-ABL1 transcript level at diagnosis has no established prognostic impact and cannot guide frontline TKI selection. BCR-ABL1 mutations are detected in ~50% of TKI resistant patients but are rarely responsible for primary resistance. Other resistance mechanisms are largely uncharacterized and there are no other routine molecular testing strategies to facilitate the evaluation and further stratification of TKI resistance. Advances in next-generation sequencing technology has aided the management of a growing number of other malignancies, enabling the incorporation of somatic mutation profiles in diagnosis, classification, and prognostication. A largely unexplored area in CML research is whether expanded genomic analysis at diagnosis, resistance, and disease transformation can enhance patient management decisions, as has occurred for other cancers. The aim of this article is to review publications that reported mutated cancer-associated genes in CML patients at various disease phases. We discuss the frequency and type of such variants at initial diagnosis and at the time of treatment failure and transformation. Current limitations in the evaluation of mutants and recommendations for future reporting are outlined. The collective evaluation of mutational studies over more than a decade suggests a limited set of cancer-associated genes are indeed recurrently mutated in CML and some at a relatively high frequency. Genomic studies have the potential to lay the foundation for improved diagnostic risk classification according to clinical and g

Published
2019

29. A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation

Author

Magenau, J, primary, Westervelt, P, additional, Khaled, S, additional, McGuirk, J, additional, Hari, P, additional, Eapen, M, additional, Becker, P S, additional, Parkin, B, additional, Braun, T, additional, Logan, B, additional, Wang, H, additional, Jagasia, M, additional, Rowley, S D, additional, Kim, D D H, additional, Schechter, T, additional, Frey, N, additional, Scott, B, additional, Churay, T, additional, Lieland, S, additional, Forman, S, additional, and Mineishi, S, additional

Published
2016
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31. Adverse prognostic effect of homozygous TET2 mutation on the relapse risk of acute myeloid leukemia in patients of normal karyotype

Author

Ahn, J.-S., primary, Kim, H.-J., additional, Kim, Y.-K., additional, Jung, S.-H., additional, Yang, D.-H., additional, Lee, J.-J., additional, Lee, I.-K., additional, Kim, N. Y., additional, Minden, M. D., additional, Jung, C. W., additional, Jang, J.-H., additional, Kim, H. J., additional, Moon, J. H., additional, Sohn, S. K., additional, Won, J.-H., additional, Kim, S.-H., additional, Kim, N., additional, Yoshida, K., additional, Ogawa, S., additional, and Kim, D. D. H., additional

Published
2015
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33. Deficiency of decay-accelerating factor and complement receptor 1-related gene/protein y on murine platelets leads to complement-dependent clearance by the macrophage phagocytic receptor CRIg

Author

Kim, D D, Miwa, T, Kimura, Y, Schwendener, R, van Lookeren Campagne, M, Song, W C, Kim, D D, Miwa, T, Kimura, Y, Schwendener, R, van Lookeren Campagne, M, and Song, W C

Abstract

Complement activation on human platelets is known to cause platelet degranulation and activation. To evaluate how normal platelets escape complement attack in vivo, we studied the fate of murine platelets deficient in 2 membrane complement regulatory proteins using an adoptive transfer model. We show here that deficiency of either decay-accelerating factor (DAF) or complement receptor 1-related gene/protein y (Crry) on murine platelets was inconsequential, whereas DAF and Crry double deficiency led to rapid clearance of platelets from circulation in a complement- and macrophage-dependent manner. This finding contrasted with the observation on erythrocytes, where Crry deficiency alone resulted in complement susceptibility. Quantitative flow cytometry showed DAF and Crry were expressed at similar levels on platelets, whereas Crry expression was 3 times higher than DAF on erythrocytes. Antibody blocking or gene ablation of the newly identified complement receptor CRIg, but not complement receptor 3 (CR3), rescued DAF/Crry-deficient platelets from complement-dependent elimination. Surprisingly, deficiency of CRIg, CR3, and other known complement receptors failed to prevent Crry-deficient erythrocytes from complement-mediated clearance. These results show a critical but redundant role of DAF and Crry in platelet survival and suggest that complement-opsonized platelets and erythrocytes engage different complement receptors on tissue macrophages in vivo.

Published
2008

35. New measurements of [Formula Presented] decays to charmonium final states

Author

Briere, R.A. (R. A.), Chen, G.P. (G. P.), Ferguson, T. (T.), Tatishvili, G. (G.), Vogel, H. (H.), Watkins, M.E. (M. E.), Adam, N.E. (N. E.), Alexander, J.P. (J. P.), Berkelman, K. (K.), Cassel, D.G. (D. G.), Duboscq, J.E. (J. E.), Ecklund, K.M. (K. M.), Ehrlich, R. (R.), Fields, L. (L.), Galik, R.S. (R. S.), Gibbons, L. (L.), Gittelman, B. (B.), Gray, R. (R.), Gray, S.W. (S. W.), Hartill, D.L. (D. L.), Heltsley, B.K. (B. K.), Hertz, D. (D.), Hsu, L. (L.), Jones, C.D. (C. D.), Kandaswamy, J. (J.), Kreinick, D.L. (D. L.), Kuznetsov, V.E. (V. E.), Mahlke-Krüger, H. (H.), Meyer, T.O. (T. O.), Onyisi, P.U.E. (P. U.E.), Patterson, J.R. (J. R.), Peterson, D. (D.), Pivarski, J. (J.), Riley, D. (D.), Rosner, J.L. (J. L.), Ryd, A. (A.), Sadoff, A.J. (A. J.), Schwarthoff, H. (H.), Shepherd, M.R. (M. R.), Sun, W.M. (W. M.), Thayer, J.G. (J. G.), Urner, D. (D.), Wilksen, T. (T.), Weinberger, M. (M.), Athar, S.B. (S. B.), Avery, P. (P.), Breva-Newell, L. (L.), Patel, R. (R.), Potlia, V. (V.), Stoeck, H. (H.), Yelton, J. (J.), Rubin, P. (P.), Eisenstein, B.I. (B. I.), Gollin, G.D. (G. D.), Karliner, I. (I.), Kim, D. (D.), Lowrey, N. (N.), Naik, P. (P.), Sedlack, C. (C.), Selen, M. (M.), Thaler, J.J. (J. J.), Williams, J. (J.), Wiss, J. (J.), Edwards, K.W. (K. W.), Besson, D. (D.), Gao, K.Y. (K. Y.), Gong, D.T. (D. T.), Kubota, Y. (Y.), Li, S.Z. (S. Z.), Poling, R. (R.), Scott, A.W. (A. W.), Smith, A. (A.), Stepaniak, C.J. (C. J.), Urheim, J. (J.), Metreveli, Z. (Z.), Seth, K.K. (K. K.), Tomaradze, A. (A.), Zweber, P. (P.), Ernst, J. (J.), Arms, K. (K.), Gan, K.K. (K. K.), Severini, H. (H.), Skubic, P. (P.), Asner, D.M. (D. M.), Dytman, S.A. (S. A.), Mehrabyan, S. (S.), Mueller, J.A. (J. A.), Savinov, V. (V.), Li, Z. (Z.), Lopez, A. (A.), Mendez, H. (H.), Ramirez, J. (J.), Huang, G.S. (G. S.), Miller, D.H. (D. H.), Pavlunin, V. (V.), Sanghi, B. (B.), Shibata, E.I. (E. I.), Shipsey, I.P.J. (I. P.J.), Adams, G.S. (G. S.), Chasse, M. (M.), Cummings, J.P. (J. P.), Danko, I. (I.), Napolitano, J. (J.), Cronin-Hennessy, D. (D.), Park, C.S. (C. S.), Park, W. (W.), Thayer, J.B. (J. B.), Thorndike, E.H. (E. H.), Coan, T.E. (T. E.), Gao, Y.S. (Y. S.), Liu, F. (F.), Stroynowski, R. (R.), Artuso, M. (M.), Boulahouache, C. (C.), Blusk, S. (S.), Butt, J. (J.), Dambasuren, E. (E.), Dorjkhaidav, O. (O.), Menaa, N. (N.), Mountain, R. (R.), Muramatsu, H. (H.), Nandakumar, R. (R.), Redjimi, R. (R.), Sia, R. (R.), Skwarnicki, T. (T.), Stone, S. (S.), Wang, J.C. (J. C.), Zhang, K. (K.), Mahmood, A.H. (A. H.), Csorna, S.E. (S. E.), Bonvicini, G. (G.), Cinabro, D. (D.), Dubrovin, M. (M.), Bornheim, A. (A.), Lipeles, E. (E.), Pappas, S.P. (S. P.), Weinstein, A.J. (A. J.), Briere, R.A. (R. A.), Chen, G.P. (G. P.), Ferguson, T. (T.), Tatishvili, G. (G.), Vogel, H. (H.), Watkins, M.E. (M. E.), Adam, N.E. (N. E.), Alexander, J.P. (J. P.), Berkelman, K. (K.), Cassel, D.G. (D. G.), Duboscq, J.E. (J. E.), Ecklund, K.M. (K. M.), Ehrlich, R. (R.), Fields, L. (L.), Galik, R.S. (R. S.), Gibbons, L. (L.), Gittelman, B. (B.), Gray, R. (R.), Gray, S.W. (S. W.), Hartill, D.L. (D. L.), Heltsley, B.K. (B. K.), Hertz, D. (D.), Hsu, L. (L.), Jones, C.D. (C. D.), Kandaswamy, J. (J.), Kreinick, D.L. (D. L.), Kuznetsov, V.E. (V. E.), Mahlke-Krüger, H. (H.), Meyer, T.O. (T. O.), Onyisi, P.U.E. (P. U.E.), Patterson, J.R. (J. R.), Peterson, D. (D.), Pivarski, J. (J.), Riley, D. (D.), Rosner, J.L. (J. L.), Ryd, A. (A.), Sadoff, A.J. (A. J.), Schwarthoff, H. (H.), Shepherd, M.R. (M. R.), Sun, W.M. (W. M.), Thayer, J.G. (J. G.), Urner, D. (D.), Wilksen, T. (T.), Weinberger, M. (M.), Athar, S.B. (S. B.), Avery, P. (P.), Breva-Newell, L. (L.), Patel, R. (R.), Potlia, V. (V.), Stoeck, H. (H.), Yelton, J. (J.), Rubin, P. (P.), Eisenstein, B.I. (B. I.), Gollin, G.D. (G. D.), Karliner, I. (I.), Kim, D. (D.), Lowrey, N. (N.), Naik, P. (P.), Sedlack, C. (C.), Selen, M. (M.), Thaler, J.J. (J. J.), Williams, J. (J.), Wiss, J. (J.), Edwards, K.W. (K. W.), Besson, D. (D.), Gao, K.Y. (K. Y.), Gong, D.T. (D. T.), Kubota, Y. (Y.), Li, S.Z. (S. Z.), Poling, R. (R.), Scott, A.W. (A. W.), Smith, A. (A.), Stepaniak, C.J. (C. J.), Urheim, J. (J.), Metreveli, Z. (Z.), Seth, K.K. (K. K.), Tomaradze, A. (A.), Zweber, P. (P.), Ernst, J. (J.), Arms, K. (K.), Gan, K.K. (K. K.), Severini, H. (H.), Skubic, P. (P.), Asner, D.M. (D. M.), Dytman, S.A. (S. A.), Mehrabyan, S. (S.), Mueller, J.A. (J. A.), Savinov, V. (V.), Li, Z. (Z.), Lopez, A. (A.), Mendez, H. (H.), Ramirez, J. (J.), Huang, G.S. (G. S.), Miller, D.H. (D. H.), Pavlunin, V. (V.), Sanghi, B. (B.), Shibata, E.I. (E. I.), Shipsey, I.P.J. (I. P.J.), Adams, G.S. (G. S.), Chasse, M. (M.), Cummings, J.P. (J. P.), Danko, I. (I.), Napolitano, J. (J.), Cronin-Hennessy, D. (D.), Park, C.S. (C. S.), Park, W. (W.), Thayer, J.B. (J. B.), Thorndike, E.H. (E. H.), Coan, T.E. (T. E.), Gao, Y.S. (Y. S.), Liu, F. (F.), Stroynowski, R. (R.), Artuso, M. (M.), Boulahouache, C. (C.), Blusk, S. (S.), Butt, J. (J.), Dambasuren, E. (E.), Dorjkhaidav, O. (O.), Menaa, N. (N.), Mountain, R. (R.), Muramatsu, H. (H.), Nandakumar, R. (R.), Redjimi, R. (R.), Sia, R. (R.), Skwarnicki, T. (T.), Stone, S. (S.), Wang, J.C. (J. C.), Zhang, K. (K.), Mahmood, A.H. (A. H.), Csorna, S.E. (S. E.), Bonvicini, G. (G.), Cinabro, D. (D.), Dubrovin, M. (M.), Bornheim, A. (A.), Lipeles, E. (E.), Pappas, S.P. (S. P.), and Weinstein, A.J. (A. J.)

Abstract

Using data collected by the CLEO III detector at CESR, we report on measurements of [Formula Presented] decays to charmonium final states. The data sample used for this analysis consists of [Formula Presented] [Formula Presented] decays, representing about 35 times more data than previous CLEO [Formula Presented] data samples. We present substantially improved measurements of the branching fraction [Formula Presented] using [Formula Presented] and [Formula Presented] decays. The branching fractions for these two modes are averaged, thereby obtaining: [Formula Presented]. A greatly improved measurement of the [Formula Presented] momentum distribution is presented and indicates a spectrum which is much softer than predicted by the color-octet model and somewhat softer than the color-singlet model. First measurements of the [Formula Presented] polarization and production angle are also presented. In addition, we report on the first observation of [Formula Presented] and evidence for [Formula Presented]. Their branching fractions are measured relative to [Formula Presented] and are found to be [Formula Presented], [Formula Presented], and [Formula Presented] at 90% confidence level. The resulting feed-down contributions to [Formula Presented] are [Formula Presented] for [Formula Presented], [Formula Presented] for [Formula Presented], [Formula Presented] for [Formula Presented], and [Formula Presented] at 90% confidence level for [Formula Presented]. These measurements (apart from [Formula Presented]) are about a factor of 2 larger than expected based on the color-octet model.

Published
2004
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39. Congenital bowing of the ulna and aggressive fibromatosis

Author

Eady, J. L., Lundquist, J. E., Grant, R. E., Nagel, A., and Kim, D. D.

Subjects
musculoskeletal diseases, Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, animal structures, Adolescent, Bone Neoplasms, Ulna, Fibroma, musculoskeletal system, body regions, Radiography, Humans, Female, Research Article
Abstract

The association of skeletal anomalies and aggressive fibromatosis has been documented. Isolated bowing of the ulna is rare, yet its occurrence, particularly in conjunction with congenital dislocation of the radial head, has been documented. This article presents two cases of ulnar bowing in which the patients subsequently developed aggressive fibromatosis. We feel that aggressive fibromatosis may be a latent manifestation of congenital bowing of the ulna. The course of the disease appears to be of an aggressive nature, and patients who present with bowing of the ulna should be followed for the potential development of this disease.

Published
1991

40. Measurement of the mass splittings between the [Formula Presented] states

Author

Edwards, K.W. (K. W.), Bellerive, A. (Alain), Janicek, R. (R.), MacFarlane, D.B. (D. B.), Patel, P.M. (P. M.), Sadoff, A.J. (A. J.), Ammar, R. (R.), Baringer, P. (P.), Bean, A. (A.), Besson, D. (D.), Coppage, D. (D.), Darling, C. (C.), Davis, R. (R.), Kotov, S. (S.), Kravchenko, I. (I.), Kwak, N. (N.), Zhou, L. (L.), Anderson, S. (S.), Kubota, Y. (Y.), Lee, S.J. (S. J.), O’Neill, J.J. (J. J.), Poling, R. (R.), Riehle, T. (T.), Smith, A. (A.), Alam, M.S. (M. S.), Athar, S.B. (S. B.), Ling, Z. (Z.), Mahmood, A.H. (A. H.), Timm, S. (S.), Wappler, F. (F.), Anastassov, A. (A.), Duboscq, J.E. (J. E.), Fujino, D. (D.), Gan, K.K. (K. K.), Hart, T. (T.), Honscheid, K. (K.), Kagan, H. (H.), Kass, R. (R.), Lee, J. (J.), Schwarthoff, H. (H.), Spencer, M.B. (M. B.), Sung, M. (M.), Undrus, A. (A.), Wolf, A. (A.), Zoeller, M.M. (M. M.), Richichi, S.J. (S. J.), Severini, H. (H.), Skubic, P. (P.), Bishai, M. (M.), Fast, J. (J.), Hinson, J.W. (J. W.), Menon, N. (N.), Miller, D.H. (D. H.), Shibata, E.I. (E. I.), Shipsey, I.P.J. (I. P.J.), Yurko, M. (M.), Glenn, S. (S.), Kwon, Y. (Y.), Lyon, A.L. (A. L.), Roberts, S. (S.), Thorndike, E.H. (E. H.), Jessop, C.P. (C. P.), Lingel, K. (K.), Marsiske, H. (H.), Perl, M.L. (M. L.), Savinov, V. (V.), Ugolini, D. (D.), Zhou, X. (X.), Coan, T.E. (T. E.), Fadeyev, V. (V.), Korolkov, I. (I.), Maravin, Y. (Y.), Narsky, I. (I.), Shelkov, V. (V.), Staeck, J. (J.), Stroynowski, R. (R.), Volobouev, I. (I.), Ye, J. (J.), Artuso, M. (M.), Azfar, F. (F.), Efimov, A. (A.), Goldberg, M. (M.), He, D. (D.), Kopp, S. (S.), Moneti, G.C. (G. C.), Mountain, R. (R.), Schuh, S. (S.), Skwarnicki, T. (T.), Stone, S. (S.), Viehhauser, G. (G.), Wang, J.C. (J. C.), Xing, X. (X.), Bartelt, J. (J.), Csorna, S.E. (S. E.), Jain, V. (V.), McLean, K.W. (K. W.), Marka, S. (S.), Godang, R. (R.), Kinoshita, K. (K.), Lai, I.C. (I. C.), Pomianowski, P. (P.), Schrenk, S. (S.), Bonvicini, G. (G.), Cinabro, D. (D.), Greene, R. (R.), Perera, L.P. (L. P.), Zhou, G.J. (G. J.), Chadha, M. (M.), Chan, S. (S.), Eigen, G. (G.), Miller, J.S. (J. S.), Schmidtler, M. (M.), Urheim, J. (J.), Weinstein, A.J. (A. J.), Würthwein, F. (F.), Bliss, D.W. (D. W.), Jaffe, D.E. (D. E.), Masek, G. (G.), Paar, H.P. (H. P.), Prell, S. (S.), Sharma, V. (V.), Asner, D.M. (D. M.), Gronberg, J. (J.), Hill, T.S. (T. S.), Lange, D.J. (D. J.), Morrison, R.J. (R. J.), Nelson, H.N. (H. N.), Nelson, T.K. (T. K.), Roberts, D. (D.), Behrens, B.H. (B. H.), Ford, W.T. (W. T.), Gritsan, A. (A.), Roy, J. (J.), Smith, J.G. (J. G.), Alexander, J.P. (J. P.), Baker, R. (R.), Bebek, C. (C.), Berger, B.E. (B. E.), Berkelman, K. (K.), Bloom, K. (K.), Boisvert, V. (V.), Cassel, D.G. (D. G.), Crowcroft, D.S. (D. S.), Dickson, M. (M.), von Dombrowski, S. (S.), Drell, P.S. (P. S.), Ecklund, K.M. (K. M.), Ehrlich, R. (R.), Foland, A.D. (A. D.), Gaidarev, P. (P.), Galik, R.S. (R. S.), Gibbons, L. (L.), Gittelman, B. (B.), Gray, S.W. (S. W.), Hartill, D.L. (D. L.), Heltsley, B.K. (B. K.), Hopman, P.I. (P. I.), Kandaswamy, J. (J.), Kreinick, D.L. (D. L.), Lee, T. (T.), Liu, Y. (Y.), Mistry, N.B. (N. B.), Ng, C.R. (C. R.), Nordberg, E. (E.), Ogg, M. (M.), Patterson, J.R. (J. R.), Peterson, D. (D.), Riley, D. (D.), Soffer, A. (A.), Valant-Spaight, B. (B.), Ward, C. (C.), Athanas, M. (M.), Avery, P. (P.), Jones, C.D. (C. D.), Lohner, M. (M.), Patton, S. (S.), Prescott, C. (C.), Yelton, J. (J.), Zheng, J. (J.), Brandenburg, G. (G.), Briere, R.A. (R. A.), Ershov, A. (A.), Gao, Y.S. (Y. S.), Kim, D. (D. Y.-J.), Wilson, R. (R.), Yamamoto, H. (H.), Browder, T.E. (T. E.), Li, Y. (Y.), Rodriguez, J.L. (J. L.), Bergfeld, T. (T.), Eisenstein, B.I. (B. I.), Ernst, J. (J.), Gladding, G.E. (G. E.), Gollin, G.D. (G. D.), Hans, R.M. (R. M.), Johnson, E. (E.), Karliner, I. (I.), Marsh, M.A. (M. A.), Palmer, M. (M.), Selen, M. (M.), Thaler, J.J. (J. J.), Edwards, K.W. (K. W.), Bellerive, A. (Alain), Janicek, R. (R.), MacFarlane, D.B. (D. B.), Patel, P.M. (P. M.), Sadoff, A.J. (A. J.), Ammar, R. (R.), Baringer, P. (P.), Bean, A. (A.), Besson, D. (D.), Coppage, D. (D.), Darling, C. (C.), Davis, R. (R.), Kotov, S. (S.), Kravchenko, I. (I.), Kwak, N. (N.), Zhou, L. (L.), Anderson, S. (S.), Kubota, Y. (Y.), Lee, S.J. (S. J.), O’Neill, J.J. (J. J.), Poling, R. (R.), Riehle, T. (T.), Smith, A. (A.), Alam, M.S. (M. S.), Athar, S.B. (S. B.), Ling, Z. (Z.), Mahmood, A.H. (A. H.), Timm, S. (S.), Wappler, F. (F.), Anastassov, A. (A.), Duboscq, J.E. (J. E.), Fujino, D. (D.), Gan, K.K. (K. K.), Hart, T. (T.), Honscheid, K. (K.), Kagan, H. (H.), Kass, R. (R.), Lee, J. (J.), Schwarthoff, H. (H.), Spencer, M.B. (M. B.), Sung, M. (M.), Undrus, A. (A.), Wolf, A. (A.), Zoeller, M.M. (M. M.), Richichi, S.J. (S. J.), Severini, H. (H.), Skubic, P. (P.), Bishai, M. (M.), Fast, J. (J.), Hinson, J.W. (J. W.), Menon, N. (N.), Miller, D.H. (D. H.), Shibata, E.I. (E. I.), Shipsey, I.P.J. (I. P.J.), Yurko, M. (M.), Glenn, S. (S.), Kwon, Y. (Y.), Lyon, A.L. (A. L.), Roberts, S. (S.), Thorndike, E.H. (E. 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(F.), Bliss, D.W. (D. W.), Jaffe, D.E. (D. E.), Masek, G. (G.), Paar, H.P. (H. P.), Prell, S. (S.), Sharma, V. (V.), Asner, D.M. (D. M.), Gronberg, J. (J.), Hill, T.S. (T. S.), Lange, D.J. (D. J.), Morrison, R.J. (R. J.), Nelson, H.N. (H. N.), Nelson, T.K. (T. K.), Roberts, D. (D.), Behrens, B.H. (B. H.), Ford, W.T. (W. T.), Gritsan, A. (A.), Roy, J. (J.), Smith, J.G. (J. G.), Alexander, J.P. (J. P.), Baker, R. (R.), Bebek, C. (C.), Berger, B.E. (B. E.), Berkelman, K. (K.), Bloom, K. (K.), Boisvert, V. (V.), Cassel, D.G. (D. G.), Crowcroft, D.S. (D. S.), Dickson, M. (M.), von Dombrowski, S. (S.), Drell, P.S. (P. S.), Ecklund, K.M. (K. M.), Ehrlich, R. (R.), Foland, A.D. (A. D.), Gaidarev, P. (P.), Galik, R.S. (R. S.), Gibbons, L. (L.), Gittelman, B. (B.), Gray, S.W. (S. W.), Hartill, D.L. (D. L.), Heltsley, B.K. (B. K.), Hopman, P.I. (P. I.), Kandaswamy, J. (J.), Kreinick, D.L. (D. L.), Lee, T. (T.), Liu, Y. (Y.), Mistry, N.B. (N. B.), Ng, C.R. (C. R.), Nordberg, E. (E.), Ogg, M. (M.), Patterson, J.R. (J. R.), Peterson, D. (D.), Riley, D. (D.), Soffer, A. (A.), Valant-Spaight, B. (B.), Ward, C. (C.), Athanas, M. (M.), Avery, P. (P.), Jones, C.D. (C. D.), Lohner, M. (M.), Patton, S. (S.), Prescott, C. (C.), Yelton, J. (J.), Zheng, J. (J.), Brandenburg, G. (G.), Briere, R.A. (R. A.), Ershov, A. (A.), Gao, Y.S. (Y. S.), Kim, D. (D. Y.-J.), Wilson, R. (R.), Yamamoto, H. (H.), Browder, T.E. (T. E.), Li, Y. (Y.), Rodriguez, J.L. (J. L.), Bergfeld, T. (T.), Eisenstein, B.I. (B. I.), Ernst, J. (J.), Gladding, G.E. (G. E.), Gollin, G.D. (G. D.), Hans, R.M. (R. M.), Johnson, E. (E.), Karliner, I. (I.), Marsh, M.A. (M. A.), Palmer, M. (M.), Selen, M. (M.), and Thaler, J.J. (J. J.)

Abstract

We present new measurements of photon energies and branching fractions for the radiative transitions [Formula Presented] The masses of the [Formula Presented] states are determined from the measured radiative photon energies. The ratio of mass splittings between the [Formula Presented] substates, [Formula Presented] with [Formula Presented] the [Formula Presented] mass, provides information on the nature of the [Formula Presented] confining potential. We find [Formula Presented] This value is somewhat lower than the previous world average, but more consistent with the theoretical expectation that [Formula Presented] i.e., that this mass splitting ratio is smaller for the [Formula Presented] states than for the [Formula Presented] states.

Published
1999
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45. Stable bioavailability of cyclosporin A, regardless of food intake, from soft gelatin capsules containing a new self-nanoemulsifying formulation.

Author

Yang, S. G., Kim, D. D., Chung, S. J., and Shim, C. K.

Subjects
CYCLOSPORINE, BIOAVAILABILITY, TRIGLYCERIDES, DIGLYCERIDES, THERAPEUTIC equivalency in drugs, EMULSIONS (Pharmacy), DOSAGE forms of drugs
Abstract

Aim: We recently succeeded in preparing soft gelatin capsules containing a new self-nanoemulsifying formulation consisting of cyclosporin A (CsA), triacetin, polyoxyl 40 hydrogenated castor oil, polysorbate 20, medium chain triglycerides and medium chain mono- and diglycerides. The soft capsules containing the new formulation exhibited a significantly improved physical stability in terms of the appearance of the gelatin capsule shells and the composition of the fill mass during long-term storage, compared to commercially available soft capsules containing CsA, in which ethanol was employed as a cosolvent of CsA. In the present study, the influence of a fat-rich meal on the bioavailability of CsA from the soft capsule containing the new formulation (test drug) was evaluated and the results compared to those obtained with a representative soft capsule of CsA. Volunteers and methods: A randomized, open-label, 3-way crossover study was performed in the test capsules and reference soft capsules, in a fasted state or after a fat-rich breakfast. 18 healthy male volunteers received a single dose of the reference formulation (Neoral, Novartis AG, Basel, Switzerland) or test formulation (2 capsules each, 200 mg as CsA) with 240 ml of water with a 1-week washout period between the treatments, after a fat-rich (670 kcal, 45 g fat) breakfast (for the test drug, Treatment A; for the reference drug, Treatment B) or a 12-h fasting (for the test drug, Treatment C). Serial blood samples, collected over a 24-h period after the administration, were assayed for blood CsA concentrations using a specific monoclonal radioimmunoassay. Results: The differences in bioavailability parameters (i.e., AUC0–24h, AUC0-∞ and Cmax) between the Treatments were within the range of 80–125% of the reference treatment. An analysis of variance (ANOVA) revealed no significant differences (p > 0.05) between subjects, formulations or periods. The 90% confidence intervals (CI) indicated that the differences between the treatments (Treatments A and B, Treatments A and C) were also within the criteria. Conclusion: These results indicate that the bioavailability of CsA from the test drug is equivalent to reference in the fed state, and is likely to be less influenced by a fat-rich meal. Therefore, the new formulation of CsA using triacetin appears to have an advantage over the commercial soft capsules of CsA using a volatile cosolvent such as ethanol. [ABSTRACT FROM AUTHOR]

Published
2006
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47. Asciminib in Newly Diagnosed Chronic Myeloid Leukemia.

Author

Hochhaus, A., Wang, J., Kim, D.-W., Kim, D. D. H., Mayer, J., Goh, Y.-T., le Coutre, P., Takahashi, N., Kim, I., Etienne, G., Andorsky, D., Issa, G. C., Larson, R. A., Bombaci, F., Kapoor, S., McCulloch, T., Malek, K., Yau, L., Ifrah, S., and Hoch, M.

Subjects
*CHRONIC myeloid leukemia, *PROTEIN-tyrosine kinase inhibitors, *CLINICAL trials, *IMATINIB, *PATIENT safety
Abstract

BACKGROUND Patients with newly diagnosed chronic myeloid leukemia (CML) need long-term therapy with high efficacy and safety. Asciminib, a BCR::ABL1 inhibitor specifically targeting the ABL myristoyl pocket, may offer better efficacy and safety and fewer side effects than currently available frontline ATP-competitive tyrosine kinase inhibitors (TKIs). METHODS In a phase 3 trial, patients with newly diagnosed CML were randomly assigned in a 1:1 ratio to receive either asciminib (80 mg once daily) or an investigator-selected TKI, with randomization stratified by European Treatment and Outcome Study long-term survival score category (low, intermediate, or high risk) and by TKI selected by investigators before randomization (including imatinib and second-generation TKIs). The primary end points were major molecular response (defined as BCR::ABL1 transcript levels =0.1% on the International Scale [IS]) at week 48, for comparisons between asciminib and investigator-selected TKIs and between asciminib and investigator-selected TKIs in the prerandomization-selected imatinib stratum. RESULTS A total of 201 patients were assigned to receive asciminib and 204 to receive investigator-selected TKIs. The median follow-up was 16.3 months in the asciminib group and 15.7 months in the investigator-selected TKI group. A major molecular response at week 48 occurred in 67.7% of patients in the asciminib group, as compared with 49.0% in the investigator-selected TKI group (difference, 18.9 percentage points; 95% confidence interval [CI], 9.6 to 28.2; adjusted two-sided P<0.001]), and in 69.3% of patients in the asciminib group as compared with 40.2% in the imatinib group within the imatinib stratum (difference, 29.6 percentage points; 95% CI, 16.9 to 42.2; adjusted two-sided P<0.001). The percentage of patients with a major molecular response at week 48 was 66.0% with asciminib and 57.8% with TKIs in the second-generation TKI stratum (difference, 8.2 percentage points; 95% CI, -5.1 to 21.5). Adverse events of grade 3 or higher and events leading to discontinuation of the trial regimen were less frequent with asciminib (38.0% and 4.5%, respectively) than with imatinib (44.4% and 11.1%) and second-generation TKIs (54.9% and 9.8%). CONCLUSIONS: In this trial comparing asciminib with investigator-selected TKIs and imatinib, asciminib showed superior efficacy and a favorable safety profile in patients with newly diagnosed chronic-phase CML. Direct comparison between asciminib and second-generation TKIs was not a primary objective. [ABSTRACT FROM AUTHOR]

Published
2024
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