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2. A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC

Author

Lisberg, A, Cummings, A, Goldman, JW, Bornazyan, K, Reese, N, Wang, T, Coluzzi, P, Ledezma, B, Mendenhall, M, Hunt, J, Wolf, B, Jones, B, Madrigal, J, Horton, J, Spiegel, M, Carroll, J, Gukasyan, J, Williams, T, Sauer, L, Wells, C, Hardy, A, Linares, P, Lim, C, Ma, L, Adame, C, and Garon, Edward B

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Lung Cancer, Clinical Trials and Supportive Activities, Lung, Cancer, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adult, Aged, Antibodies, Monoclonal, Humanized, B7-H1 Antigen, Carcinoma, Non-Small-Cell Lung, ErbB Receptors, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Protein Kinase Inhibitors, NSCLC, programmed death 1, EGFR, tumor immunology, pembrolizumab, programmed death ligand 1, Cardiorespiratory Medicine and Haematology, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

BackgroundDespite the significant antitumor activity of pembrolizumab in NSCLC, clinical benefit has been less frequently observed in patients whose tumors harbor EGFR mutations compared to EGFR wild-type patients. Our single-center experience on the KEYNOTE-001 trial suggested that pembrolizumab-treated EGFR-mutant patients, who were tyrosine kinase inhibitor (TKI) naïve, had superior clinical outcomes to those previously treated with a TKI. As TKI naïve EGFR-mutants have generally been excluded from pembrolizumab studies, data to guide treatment decisions in this patient population is lacking, particularly in patients with programmed death ligand 1 (PD-L1) expression ≥50%.MethodsWe conducted a phase II trial (NCT02879994) of pembrolizumab in TKI naive patients with EGFR mutation-positive, advanced NSCLC and PD-L1-positive (≥1%, 22C3 antibody) tumors. Pembrolizumab was administered 200 mg every 3 weeks. The primary endpoint was objective response rate. Secondary endpoints included safety of pembrolizumab, additional pembrolizumab efficacy endpoints, and efficacy and safety of an EGFR TKI after pembrolizumab.ResultsEnrollment was ceased due to lack of efficacy after 11 of 25 planned patients were treated. Eighty-two percent of trial patients were treatment naïve, 64% had sensitizing EGFR mutations, and 73% had PD-L1 expression ≥50%. Only 1 patient had an objective response (9%), but repeat analysis of this patient's tumor definitively showed the original report of an EGFR mutation to be erroneous. Observed treatment-related adverse events were similar to prior experience with pembrolizumab, but two deaths within 6 months of enrollment, including one attributed to pneumonitis, were of concern.ConclusionsPembrolizumab's lack of efficacy in TKI naïve, PD-L1+, EGFR-mutant patients with advanced NSCLC, including those with PD-L1 expression ≥50%, suggests that it is not an appropriate therapeutic choice in this setting.

Published
2018

3. Comparing Gender Based Differences in Letters of Recommendation for Pulmonary Critical Care Fellowship Across Multiple Sites: A Cross-sectional Study

Author

Viglianti, E.M., primary, Spiegel, M., additional, Kilb, E.F., additional, Vranas, K.C., additional, Schweiger, L., additional, Sarma, N., additional, Lee, K.T., additional, Agarwal, G., additional, Choudhuri, I., additional, Schreidah, C., additional, Schroeder, J., additional, Vita, A.J., additional, Jain, S., additional, Akgun, K.M., additional, Heath, J.K., additional, and Byrd, K.M., additional

Published
2024
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5. Reconciling agriculture, carbon and biodiversity in a savannah transformation frontier

Author

Estes, LD, Searchinger, T, Spiegel, M, Tian, D, Sichinga, S, Mwale, M, Kehoe, L, Kuemmerle, T, Berven, A, Chaney, N, Sheffield, J, Wood, EF, and Caylor, KK

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Life on Land, Zero Hunger, Agriculture, Biodiversity, Carbon, Conservation of Natural Resources, Forests, Grassland, Zambia, trade-offs, optimization, savannahs, agriculture, biodiversity, carbon, Medical and Health Sciences, Evolutionary Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Rapidly rising populations and likely increases in incomes in sub-Saharan Africa make tens of millions of hectares of cropland expansion nearly inevitable, even with large increases in crop yields. Much of that expansion is likely to occur in higher rainfall savannas, with substantial costs to biodiversity and carbon storage. Zambia presents an acute example of this challenge, with an expected tripling of population by 2050, good potential to expand maize and soya bean production, and large areas of relatively undisturbed miombo woodland and associated habitat types of high biodiversity value. Here, we present a new model designed to explore the potential for targeting agricultural expansion in ways that achieve quantitatively optimal trade-offs between competing economic and environmental objectives: total converted land area (the reciprocal of potential yield); carbon loss, biodiversity loss and transportation costs. To allow different interests to find potential compromises, users can apply varying weights to examine the effects of their subjective preferences on the spatial allocation of new cropland and its costs. We find that small compromises from the objective to convert the highest yielding areas permit large savings in transportation costs, and the carbon and biodiversity impacts resulting from savannah conversion. For example, transferring just 30% of weight from a yield-maximizing objective equally between carbon and biodiversity protection objectives would increase total cropland area by just 2.7%, but result in avoided costs of 27-47% for carbon, biodiversity and transportation. Compromise solutions tend to focus agricultural expansion along existing transportation corridors and in already disturbed areas. Used appropriately, this type of model could help countries find agricultural expansion alternatives and related infrastructure and land use policies that help achieve production targets while helping to conserve Africa's rapidly transforming savannahs.This article is part of the themed issue 'Tropical grassy biomes: linking ecology, human use and conservation'.

Published
2016

7. Bunyaviren

Author

Pöhlmann, S., Spiegel, M., Suerbaum, Sebastian, editor, Burchard, Gerd-Dieter, editor, Kaufmann, Stefan H.E., editor, and Schulz, Thomas F., editor

Published
2016
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11. List of contributors

Author

Abe, F., primary, Barnard, P., additional, Blum, R., additional, Chai, G., additional, deBarbadillo, J.J., additional, Di Gianfrancesco, A., additional, Forsberg, U., additional, Fukuda, M., additional, Hald, J., additional, Klöwer, J., additional, Kruger, K.L., additional, Liu, Z., additional, Lucacci, G., additional, Masuyama, F., additional, Roberts, S., additional, Schraven, P., additional, Shingledecker, J.P., additional, Sorrentino, S., additional, Spiegel, M., additional, Xie, X., additional, and Zeiler, G., additional

Published
2017
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21. Problems

Author

Rabinowitz, Stanley, Ling, Gao, Lyness, R. C., Propp, James, Holden, Herbert L., Fettis, Henry E., Klamkin, M. S., Spiegel, M. R., Lewan, Douglas, Facchini, Alberto, Shapiro, Daniel B., McCarty, Carl P., McCarty, Loretta, Reiter, Harold, Selfridge, J. L., Wall, Charles R., Dalton, Oren N., Galovich, Steve, and Foster, Lorraine L.

Published
1982
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25. Location of studies and evidence of effects of herbivory on Arctic vegetation: a systematic map

Author

Soininen, E. M. (E. M.), Barrio, I. C. (I. C.), Bjørkås, R. (R.), Björnsdottir, K. (K.), Ehrich, D. (D.), Hopping, K. A. (K. A.), Kaarlejärvi, E. (E.), Kolstad, A. L. (A. L.), Abdulmanova, S. (S.), Björk, R. G. (R. G.), Bueno, C. G. (C. G.), Eischeid, I. (I), Finger-Higgens, R. (R.), Forbey, J. S. (J. S.), Gignac, C. (C.), Gilg, O. (O.), den Herder, M. (M.), Holm, H. S. (H. S.), Hwang, B. C. (B. C.), Jepsen, J. U. (J. U.), Kamenova, S. (S.), Kater, I. (I), Koltz, A. M. (A. M.), Kristensen, J. A. (J. A.), Little, C. J. (C. J.), Macek, P. (P.), Mathisen, K. M. (K. M.), Metcalfe, D. B. (D. B.), Mosbacher, J. B. (J. B.), Mörsdorf, M. (M.), Park, T. (T.), Propster, J. R. (J. R.), Roberts, A. J. (A. J.), Serrano, E. (E.), Spiegel, M. P. (M. P.), Tamayo, M. (M.), Tuomi, M. W. (M. W.), Verma, M. (M.), Vuorinen, K. E. (K. E. M.), Väisänen, M. (M.), Van der Wal, R. (R.), Wilcots, M. E. (M. E.), Yoccoz, N. G. (N. G.), Speed, J. D. (J. D. M.), Soininen, E. M. (E. M.), Barrio, I. C. (I. C.), Bjørkås, R. (R.), Björnsdottir, K. (K.), Ehrich, D. (D.), Hopping, K. A. (K. A.), Kaarlejärvi, E. (E.), Kolstad, A. L. (A. L.), Abdulmanova, S. (S.), Björk, R. G. (R. G.), Bueno, C. G. (C. G.), Eischeid, I. (I), Finger-Higgens, R. (R.), Forbey, J. S. (J. S.), Gignac, C. (C.), Gilg, O. (O.), den Herder, M. (M.), Holm, H. S. (H. S.), Hwang, B. C. (B. C.), Jepsen, J. U. (J. U.), Kamenova, S. (S.), Kater, I. (I), Koltz, A. M. (A. M.), Kristensen, J. A. (J. A.), Little, C. J. (C. J.), Macek, P. (P.), Mathisen, K. M. (K. M.), Metcalfe, D. B. (D. B.), Mosbacher, J. B. (J. B.), Mörsdorf, M. (M.), Park, T. (T.), Propster, J. R. (J. R.), Roberts, A. J. (A. J.), Serrano, E. (E.), Spiegel, M. P. (M. P.), Tamayo, M. (M.), Tuomi, M. W. (M. W.), Verma, M. (M.), Vuorinen, K. E. (K. E. M.), Väisänen, M. (M.), Van der Wal, R. (R.), Wilcots, M. E. (M. E.), Yoccoz, N. G. (N. G.), and Speed, J. D. (J. D. M.)

Abstract

Background: Herbivores modify the structure and function of tundra ecosystems. Understanding their impacts is necessary to assess the responses of these ecosystems to ongoing environmental changes. However, the effects of herbivores on plants and ecosystem structure and function vary across the Arctic. Strong spatial variation in herbivore effects implies that the results of individual studies on herbivory depend on local conditions, i.e., their ecological context. An important first step in assessing whether generalizable conclusions can be produced is to identify the existing studies and assess how well they cover the underlying environmental conditions across the Arctic. This systematic map aims to identify the ecological contexts in which herbivore impacts on vegetation have been studied in the Arctic. Specifically, the primary question of the systematic map was: ”What evidence exists on the effects of herbivores on Arctic vegetation?”. Methods: We used a published systematic map protocol to identify studies addressing the effects of herbivores on Arctic vegetation. We conducted searches for relevant literature in online databases, search engines and specialist websites. Literature was screened to identify eligible studies, defined as reporting primary data on herbivore impacts on Arctic plants and plant communities. We extracted information on variables that describe the ecological context of the studies, from the studies themselves and from geospatial data. We synthesized the findings narratively and created a Shiny App where the coded data are searchable and variables can be visually explored. Review findings We identified 309 relevant articles with 662 studies (representing different ecological contexts or datasets within the same article). These studies addressed vertebrate herbivory seven times more often than invertebrate herbivory. Geographically, the largest cluster of studies was in Northern Fennoscandia. Warmer and wetter parts of the Arctic

Published
2021

27. Evaluating planetary digital terrain models—The HRSC DTM test

Author

Heipke, C., Oberst, J., Albertz, J., Attwenger, M., Dorninger, P., Dorrer, E., Ewe, M., Gehrke, S., Gwinner, K., Hirschmüller, H., Kim, J.R., Kirk, R.L., Mayer, H., Muller, J.-P., Rengarajan, R., Rentsch, M., Schmidt, R., Scholten, F., Shan, J., Spiegel, M., Wählisch, M., and Neukum, G.

Published
2007
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33. Acute Cerebrovascular Disease in the Young: The Stroke in Young Fabry Patients Study

Author

Rolfs, Arndt, Fazekas, Franz, Grittner, Ulrike, Dichgans, Martin, Martus, Peter, Holzhausen, Martin, Böttcher, Tobias, Heuschmann, Peter U., Tatlisumak, Turgut, Tanislav, Christian, Jungehulsing, Gerhard J., Giese, Anne-Katrin, Putaala, Jukaa, Huber, Roman, Bodechtel, Ulf, Lichy, Christoph, Enzinger, Christian, Schmidt, Reinhold, Hennerici, Michael G., Kaps, Manfred, Kessler, Christof, Lackner, Karl, Paschke, Eduard, Meyer, Wolfgang, Mascher, Hermann, Riess, Olaf, Kolodny, Edwin, Norrving, Bo, Rolfs, A, Ginsberg, M, Hennerici, MG, Kessler, C, Kolodny, E, Martus, P, Norrving, B, Ringelstein, EB, Rothwell, PM, Venables, G, Bornstein, N, deDeyn, P, Dichgans, M, Fazekas, F, Markus, H, Rie, O, Biedermann, C, Böttcher, T, Brüderlein, K, Burmeister, J, Federow, I, König, F, Makowei, G, Niemann, D, Rolfs, A, Rösner, S, Zielke, S, Grittner, U, Martus, P, Holzhausen, M, Fazekas, F, Enzinger, C, Schmidt, R, Ropele, S, Windisch, M, Sterner, E, Bodamer, O, Fellgiebel, A, Hillen, U, Jonas, L, Kampmann, C, Kropp, P, Lackner, K, Laue, M, Mascher, H, Meyer, W, Paschke, E, Weidemann, F, Berrouschot, J, Stoll, A, Rokicha, A, Sternitzky, C, Thomä, M, DeDeyn, PP, Sheorajpanday, R, De Brabander, I, Yperzeele, L, Brouns, R, Oschmann, P, Pott, M, Schultes, K, Schultze, C, Hirsekorn, J, Jungehulsing, GJ, Villringer, A, Schmidt, W, Liman, T, Nowe, T, Ebinger, M, Wille, A, Loui, H, Objartel, A, übelacker, A, Mette, R, Jegzentis, K, Nabavi, DG, Crome, O, Bahr, D, Ebke, M, Platte, B, Kleinen, C, Mermolja Gunther, K, Heide, W, Pape, O, Hanssen, JR, Stangenberg, D, Klingelhofer, J, Schmidt, B, Schwarz, S, Schwarze, J, Frandlih, L, Iwanow, J, Steinbach, I, Krieger, D, Boysen, G, Leth Jeppesen, L, Petersen, A, Reichmann, H, Becker, U, Dzialkowski, I, Hentschel, H, Lautenschlager, C, Hanso, H, Gahn, G, Ziemssen, T, Fleischer, K, Sehr, B, McCabe, DJH, Tobin, O, Kinsella, J, Murphy, RP, Jander, S, Hartung, HP, Siebler, M, Bottcher, C, Kohne, A, Platzen, J, Brosig, TC, Rothhammer, V, Henseler, C, Neumann-Haefelin, T, Singer, OC, Ermis, U, dos Santos, IMRM, Schuhmann, C, van de Loo, S, Kaps, M, Allendorfer, J, Tanislav, C, Brandtner, M, Muir, K, Dani, K, MacDougall, N, Smith, W, Rowe, A, Welch, A, Fazekas, F, Schrotter, G, Krenn, U, Horner, S, Pendl, B, Pluta-Fuerst, A, Trummer, U, Kessler, C, Chatzopoulos, M, v Sarnowski, Bettina, Schminke, Ulf, Link, T, Khaw, A, Nieber, E, Zierz, S, Muller, T, Wegener, N, Wartenberg, K, Gaul, C, Richter, D, Rosenkranz, M, Krützelmann, AC, Hoppe, J, Choe, CU, Narr, S, Magnus, TU, Thomalla, G, Leypoldt, F, Otto, D, Lichy, C, Hacke, W, Barrows, RJ, Tatlisumak, T, Putaala, J, Curtze, S, Metso, M, Willeit, J, Furtner, M, Spiegel, M, Knoflach, MH, Prantl, B, Witte, OW, Brämer, D, Günther, A, Prell, T, Herzau, C, Aurich, K, Deuschl, G, Wodarg, F, Zimmermann, P, Eschenfelder, CC, Levsen, M, Weber, JR, Marecek, SM, Schneider, D, Michalski, D, Kloppig, W, Küppers-Tiedt, L, Schneider, M, Schulz, A, Matzen, P, Weise, C, Hobohm, C, Meier, H, Langos, R, Urban, D, Gerhardt, I, Thijs, V, Lemmens, R, Marcelis, E, Hulsbosch, C, Aichner, F, Haring, HP, Bach, E, Machado Candido, J, e Silva, AA, Lourenco, M, de Sousa, AIM, Derex, L, Cho, TH, Díez-Tejedor, E, Fuentes, B, Martínez-Sanchez, P, Pérez-Guevara, MI, Hamer, H, Metz, A, Hallenberger, K, Müller, P, Baron, P, Bersano, A, Gattinoni, M, Vella, N, Mallia, M, Jauss, M, Adam, L, Heidler, F, Gube, C, Kiszka, M, Dichgans, M, Karpinska, A, Mewald, Y, Straub, V, Dörr, A, Zollver, A, Ringelstein, EB, Schilling, M, Borchert, A, Preuth, N, Duning, T, Kuhlenbäumer, G, Schulte, D, Rothwell, PM, Marquardt, L, Schlachetzki, F, Boy, S, Mädl, J, Ertl, GM, Fehm, NPR, Stadler, C, Benecke, R, Dudesek, A, Kolbaske, S, Lardurner, G, Sulzer, C, Zerbs, A, Lilek, S, Walleczek, AM, Sinadinowska, D, Janelidze, M, Beridze, M, Lobjanidze, N, Dzagnidze, A, Melms, A, Horber, K, Fink, I, Liske, B, Ludolph, AC, Huber, R, Knauer, K, Hendrich, C, Raubold, S, Czlonkowska, A, Baranowska, A, Blazejewska-Hyzorek, B, Lang, W, Kristoferitsch, W, Ferrari, J, Ulrich, E, Flamm-Horak, A, Lischka-Lindner, A, Schreiber, W, Demarin, V, Tranjec, Z, Bosner-Puretic, M, Jurašić, MJ, Basic Kes, V, Budisic, M, and Kopacevic, L

Published
2013
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40. Contributor Contact Details

Author

Schütze, M., primary, Quadakkers, W.J., additional, Brady, Michael P., additional, Tortorelli, Petel F., additional, More, Karrel L., additional, Andrew Payzant, E., additional, Armstrong, Betl L., additional, Lin, Hua-Tay, additional, Lance, Michael J., additional, Huang, Feng, additional, Weaver, Marl L., additional, Zhang, Jianqiang, additional, Cole, Danie.M.I., additional, Young, Davil J., additional, Simms, N.J., additional, Norton, J.F., additional, McColvin, G., additional, Strehl, Gernot, additional, Borchardt, G., additional, Beaven, P., additional, Lesage, B., additional, Trindade, V.B., additional, Krupp, U., additional, Wagenhuber, Ph.E.-G., additional, Yang, S., additional, Christ, H.-J., additional, Nishiyama, Y., additional, Moriguchi, K., additional, Otsuka, N., additional, Kudo, T., additional, Kochubey, V., additional, Naumenko, D., additional, Al-Badairy, H., additional, Tatlock, G., additional, Le-Coze, J., additional, Nicholls, J.R., additional, Bennett, M.J., additional, Hattendorf, H., additional, Britton, D., additional, Smith, A.J., additional, Fordham, R., additional, Bachorczyk, R., additional, Goossens, D., additional, Tatlock, G.J., additional, Bachorczyk-Nagy, R., additional, Rohr, V., additional, Schütze, M., additional, Fortuna, E., additional, Tsipas, D.N., additional, Milewska, A., additional, Pérez, F.J., additional, Nieto Hierro, L., additional, Ennis, P.J., additional, Huttunen-Saarivirta, E., additional, Kalidakis, S., additional, Stott, F.H., additional, Berreth, K., additional, Maile, K., additional, Lyutovich, A., additional, Braun, R., additional, Fröhlich, M., additional, Leyens, C., additional, Bonnet, G., additional, Brossard, J.M., additional, Balmain, J., additional, Malessa, M., additional, Osgerby, S., additional, Pettersson, R., additional, Coleman, S.Y., additional, Niewolak, L., additional, Rose, T., additional, Hojda, R., additional, Beck, T., additional, Hähner, Peter, additional, Kühn, H.-J., additional, Rae, C., additional, Affeldt, E.E., additional, Andersson, H., additional, Köster, A., additional, Marchionni, M., additional, Echsler, H., additional, Singheiser, L., additional, Teneva-Kosseva, G., additional, Köhne, H., additional, Ackermann, H., additional, Spähn, M., additional, Richter, S., additional, Mayer, J., additional, Henderson, P.J., additional, Andersson, C., additional, Högberg, H.Kassman J., additional, Szakálos, P., additional, Deuis, R.L., additional, Brown, A.M., additional, Petrone, S., additional, Cabet, C., additional, Terlain, A., additional, Lett, P., additional, Guétaz, L., additional, Gentzbittel, J.-M., additional, Orosz, R., additional, Blomberg, T., additional, Heikinheimo, L., additional, Baxter, D., additional, Hack, K., additional, Spiegel, M., additional, Hämäläinen, M., additional, Arponen, M., additional, Ruh, A., additional, Jantzen, T., additional, Schmidt, P., additional, Buschmann, U., additional, Wiechert, W., additional, Nijdam, T.J., additional, van der Pers, N.M., additional, and Sloof, W.G., additional

Published
2008
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45. Contributor contact details

Author

Grabke, H.J., primary, Schütze, M., additional, Grabke, H.J., additional, Chun, C.M., additional, Ramanarayanan, T.A., additional, Pippel, E., additional, Woltersdorf, J., additional, Müller-Lorenz, E.M., additional, Zinke, M., additional, Schneider, A., additional, Spiegel, M., additional, Sainz-Rozas, C.Rosado, additional, Martinz, H.P., additional, Di Gabriele, F., additional, Bernstein, J.R., additional, Al-Qhatani, M.M., additional, Liu, Z., additional, Jordan, M.P., additional, Stott, F.H., additional, Richardson, J.A., additional, Zhang, J., additional, Inden, G., additional, Szakálos, P.K.M., additional, Bonnet, F., additional, Ropital, F., additional, Berthier, Y., additional, Marcus, P., additional, Jakobi, D., additional, Gommans, R., additional, Christ, H.J., additional, Chang, S.Y., additional, Krupp, U., additional, Strauss, S., additional, and Vogel, D., additional

Published
2007
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