text:
Investigational New Drugs
August 2019 , Volume 37, Issue 4, pp 658–665 | Cite as
A phase I study of the vascular endothelial growth factor inhibitor Vatalanib in combination with Pemetrexed disodium in patients with advanced solid tumors
Fen Wang
Julian Molina
Daniel Satele
Jun Yin
Vun-Sin Lim
Alex A. Adjei
PHASE I STUDIES
First Online: 31 October 2018
Introduction Vatalanib is an oral receptor tyrosine kinase inhibitor that blocks all known VEGF, PDGF, and c-Kit receptors. This phase I study evaluated the safety, tolerability, and biologic activity of the combination of vatalanib with pemetrexed disodium in patients with advanced solid tumors. Methods Patients were administered escalating twice daily doses of vatalanib in combination with pemetrexed disodium in 21-day cycles. A dose expansion cohort was enrolled to further define the maximum tolerated dose (MTD) and further evaluate efficacy. Results A total of 29 patients were enrolled in the study (dose escalation, 9; dose expansion, 20). Dose-limiting toxicities included grade 4 thrombocytopenia (6.9%) and febrile neutropenia, anorexia, constipation, and dehydration. Other common adverse events were fatigue (75%), nausea (66%), vomiting (48%), oral mucositis (31%) and diarrhea (28%). The majority of these toxicities were Grade 1–2. The MTD was reached at vatalanib 250 mg twice daily continuously combined with pemetrexed disodium 500 mg/m2 day 1. Overall, 2 patients (6.9%) had partial responses, 8 (27.6%) had stable disease for at least 4 cycles, 5 had progressive disease (17.2%) and 5 went off study before disease assessment. Conclusion The combination of vatalanib with pemetrexed disodium was feasible, but not well tolerated. The modest efficacy results are consistent with other results obtained from combinations of chemotherapy and a large number of VEGF tyrosine kinase inhibitors. This combination should not be developed further unless predictive biomarkers can be identified.
Vatalanib Pemetrexed Phase I VEGF inhibitor Solid tumors
This study was funded by the National Cancer Institute P30CA015083 grant.
Compliance with ethical standards
All authors have no conflict of interest to report.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285(21):1182–1186. https://doi.org/10.1056/NEJM197111182852108 CrossRefGoogle Scholar
Folkman J (1995) Seminars in medicine of the Beth Israel hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med 333(26):1757–1763. https://doi.org/10.1056/NEJM199512283332608 CrossRefGoogle Scholar
Hayes AJ, Li LY, Lippman ME (1999) Science, medicine, and the future. Antivascular therapy: a new approach to cancer treatment. BMJ 318(7187):853–856CrossRefGoogle Scholar
Keshet E, Ben-Sasson SA (1999) Anticancer drug targets: approaching angiogenesis. J Clin Invest 104(11):1497–1501. https://doi.org/10.1172/JCI8849 CrossRefGoogle Scholar
Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9(6):669–676. https://doi.org/10.1038/nm0603-669 CrossRefGoogle Scholar
Wood JM, Bold G, Buchdunger E, Cozens R, Ferrari S, Frei J, Hofmann F, Mestan J, Mett H, O'Reilly T, Persohn E, Rösel J, Schnell C, Stover D, Theuer A, Towbin H, Wenger F, Woods-Cook K, Menrad A, Siemeister G, Schirner M, Thierauch KH, Schneider MR, Drevs J, Martiny-Baron G, Totzke F (2000) PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res 60(8):2178–2189Google Scholar
Drevs J, Müller-Driver R, Wittig C, Fuxius S, Esser N, Hugenschmidt H, Konerding MA, Allegrini PR, Wood J, Hennig J, Unger C, Marmé D (2002) PTK787/ZK 222584, a specific vascular endothelial growth factor-receptor tyrosine kinase inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic enhanced magnetic resonance imaging. Cancer Res 62(14):4015–4022Google Scholar
Roboz GJ, Giles FJ, List AF, Cortes JE, Carlin R, Kowalski M, Bilic S, Masson E, Rosamilia M, Schuster MW, Laurent D, Feldman EJ (2006) Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor, for the treatment of acute myeloid leukemia and myelodysplastic syndrome. Leukemia 20(6):952–957. https://doi.org/10.1038/sj.leu.2404213 CrossRefGoogle Scholar
Langenberg MH, Witteveen PO, Lankheet NA, Roodhart JM, Rosing H, van den Heuvel IJ, Beijnen JH, Voest EE (2010) Phase 1 study of combination treatment with PTK 787/ZK 222584 and cetuximab for patients with advanced solid tumors: safety, pharmacokinetics, pharmacodynamics analysis. Neoplasia 12(2):206–213CrossRefGoogle Scholar
Hecht JR, Trarbach T, Hainsworth JD, Major P, Jäger E, Wolff RA, Lloyd-Salvant K, Bodoky G, Pendergrass K, Berg W, Chen BL, Jalava T, Meinhardt G, Laurent D, Lebwohl D, Kerr D (2011) Randomized, placebo-controlled, phase III study of first-line oxaliplatin-based chemotherapy plus PTK787/ZK 222584, an oral vascular endothelial growth factor receptor inhibitor, in patients with metastatic colorectal adenocarcinoma. J Clin Oncol 29(15):1997–2003. https://doi.org/10.1200/JCO.2010.29.4496 CrossRefGoogle Scholar
Van Cutsem E, Bajetta E, Valle J, Köhne CH, Hecht JR, Moore M, Germond C, Berg W, Chen BL, Jalava T, Lebwohl D, Meinhardt G, Laurent D, Lin E (2011) Randomized, placebo-controlled, phase III study of oxaliplatin, fluorouracil, and leucovorin with or without PTK787/ZK 222584 in patients with previously treated metastatic colorectal adenocarcinoma. J Clin Oncol 29(15):2004–2010. https://doi.org/10.1200/JCO.2010.29.5436 CrossRefGoogle Scholar
Thomas AL, Morgan B, Horsfield MA, Higginson A, Kay A, Lee L, Masson E, Puccio-Pick M, Laurent D, Steward WP (2005) Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. J Clin Oncol 23(18):4162–4171. https://doi.org/10.1200/JCO.2005.09.034 CrossRefGoogle Scholar
Hanauske AR, Chen V, Paoletti P, Niyikiza C (2001) Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Oncologist 6(4):363–373CrossRefGoogle Scholar
Adjei AA (2004) Pemetrexed (ALIMTA), a novel multitargeted antineoplastic agent. Clin Cancer Res 10(12 Pt 2):4276s–4280s. https://doi.org/10.1158/1078-0432.CCR-040010 CrossRefGoogle Scholar
Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P (2003) Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21(14):2636–2644. https://doi.org/10.1200/JCO.2003.11.136 CrossRefGoogle Scholar
Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D (2008) Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 26(21):3543–3551. https://doi.org/10.1200/JCO.2007.15.0375 CrossRefGoogle Scholar
Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, Wu YL, Bover I, Begbie S, Tzekova V, Cucevic B, Pereira JR, Yang SH, Madhavan J, Sugarman KP, Peterson P, John WJ, Krejcy K, Belani CP (2009) Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet 374(9699):1432–1440. https://doi.org/10.1016/S0140-6736(09)61497-5 CrossRefGoogle Scholar
Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C (2012) Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 13(3):247–255. https://doi.org/10.1016/S1470-2045(12)70063-3 CrossRefGoogle Scholar
Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C (2013) PARAMOUNT: final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 31(23):2895–2902. https://doi.org/10.1200/JCO.2012.47.1102 CrossRefGoogle Scholar
Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar MC, Paul S, Paoletti P, Einhorn L, Bunn PA (2004) Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 22(9):1589–1597. https://doi.org/10.1200/JCO.2004.08.163 CrossRefGoogle Scholar
Scagliotti G, Hanna N, Fossella F, Sugarman K, Blatter J, Peterson P, Simms L, Shepherd FA (2009) The differential efficacy of pemetrexed according to NSCLC histology: a review of two phase III studies. Oncologist 14(3):253–263. https://doi.org/10.1634/theoncologist.2008-0232 CrossRefGoogle Scholar
Stinchcombe TE, Borghaei H, Barker SS, Treat JA, Obasaju C (2016) Pemetrexed with platinum combination as a backbone for targeted therapy in non-small-cell lung Cancer. Clin Lung Cancer 17(1):1–9. https://doi.org/10.1016/j.cllc.2015.07.002 CrossRefGoogle Scholar
Masters GA, Temin S, Azzoli CG, Giaccone G, Baker S, Brahmer JR, Ellis PM, Gajra A, Rackear N, Schiller JH, Smith TJ, Strawn JR, Trent D, Johnson DH, Practice ASCOC (2015) Systemic therapy for stage IV non-small-cell lung Cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 33(30):3488–3515. https://doi.org/10.1200/JCO.2015.62.1342 CrossRefGoogle Scholar
Paz-Ares LG, Altug S, Vaury AT, Jaime JC, Russo F, Visseren-Grul C (2010) Treatment rationale and study design for a phase III, double-blind, placebo-controlled study of maintenance pemetrexed plus best supportive care versus best supportive care immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer. BMC Cancer 10:85. https://doi.org/10.1186/1471-2407-10-85 CrossRefGoogle Scholar
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol 5(6):649–655CrossRefGoogle Scholar
Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB, E3200 ECOGS (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the eastern cooperative oncology group study E3200. J Clin Oncol 25(12):1539–1544. https://doi.org/10.1200/JCO.2006.09.6305 CrossRefGoogle Scholar
Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Cassidy J (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26(12):2013–2019. https://doi.org/10.1200/JCO.2007.14.9930 CrossRefGoogle Scholar
Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C (2009) Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 27(8):1227–1234. https://doi.org/10.1200/JCO.2007.14.5466 CrossRefGoogle Scholar
Tebbutt NC, Wilson K, Gebski VJ, Cummins MM, Zannino D, van Hazel GA, Robinson B, Broad A, Ganju V, Ackland SP, Forgeson G, Cunningham D, Saunders MP, Stockler MR, Chua Y, Zalcberg JR, Simes RJ, Price TJ (2010) Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian gastrointestinal trials group randomized phase III MAX study. J Clin Oncol 28(19):3191–3198. https://doi.org/10.1200/JCO.2009.27.7723 CrossRefGoogle Scholar
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342. https://doi.org/10.1056/NEJMoa032691 CrossRefGoogle Scholar
Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550. https://doi.org/10.1056/NEJMoa061884 CrossRefGoogle Scholar
Tewari KS, Sill MW, Long HJ, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ (2014) Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 370(8):734–743. https://doi.org/10.1056/NEJMoa1309748 CrossRefGoogle Scholar
Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX, Group GO (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365(26):2473–2483. https://doi.org/10.1056/NEJMoa1104390 CrossRefGoogle Scholar
Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM, Investigators I (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365(26):2484–2496. https://doi.org/10.1056/NEJMoa1103799 CrossRefGoogle Scholar
Stark D, Nankivell M, Pujade-Lauraine E, Kristensen G, Elit L, Stockler M, Hilpert F, Cervantes A, Brown J, Lanceley A, Velikova G, Sabate E, Pfisterer J, Carey MS, Beale P, Qian W, Swart AM, Oza A, Perren T (2013) Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the international collaboration on ovarian neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol 14(3):236–243. https://doi.org/10.1016/S1470-2045(12)70567-3 CrossRefGoogle Scholar
Della Pepa C, Tonini G, Pisano C, Di Napoli M, Cecere SC, Tambaro R, Facchini G, Pignata S (2015) Ovarian cancer standard of care: are there real alternatives? Chin J Cancer 34(1):17–27. https://doi.org/10.5732/cjc.014.10274 CrossRefGoogle Scholar
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216CrossRefGoogle Scholar
Board R, Jayson GC (2005) Platelet-derived growth factor receptor (PDGFR): a target for anticancer therapeutics. Drug Resist Updat 8(1–2):75–83. https://doi.org/10.1016/j.drup.2005.03.004 CrossRefGoogle Scholar
Hicklin DJ, Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23(5):1011–1027. https://doi.org/10.1200/JCO.2005.06.081 CrossRefGoogle Scholar
Chiorean EG, Malireddy S, Younger AE, Jones DR, Waddell MJ, Sloop MI, Yu M, Hall SD, Schneider B, Sweeney CJ (2010) A phase I dose escalation and pharmacokinetic study of vatalanib (PTK787/ZK 222584) in combination with paclitaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol 66(3):441–448. https://doi.org/10.1007/s00280-009-1179-2 CrossRefGoogle Scholar
Sharma S, Freeman B, Turner J, Symanowski J, Manno P, Berg W, Vogelzang N (2009) A phase I trial of PTK787/ZK222584 in combination with pemetrexed and cisplatin in patients with advanced solid tumors. Investig New Drugs 27(1):63–65. https://doi.org/10.1007/s10637-008-9157-9 CrossRefGoogle Scholar
Hattori K, Heissig B, Wu Y, Dias S, Tejada R, Ferris B, Hicklin DJ, Zhu Z, Bohlen P, Witte L, Hendrikx J, Hackett NR, Crystal RG, Moore MA, Werb Z, Lyden D, Rafii S (2002) Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 8(8):841–849. https://doi.org/10.1038/nm740 CrossRefGoogle Scholar
Spigel DR, Hainsworth JD, Joseph MJ, Shipley DL, Hagan MK, Thompson DS, Burris HA, Greco FA (2018) Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell lung cancer and an eastern cooperative oncology group performance status of 2. Cancer 124(9):1982–1991. https://doi.org/10.1002/cncr.30986 CrossRefGoogle Scholar
Karayama M, Inui N, Fujisawa T, Enomoto N, Nakamura Y, Kuroishi S, Yokomura K, Koshimizu N, Sato M, Toyoshima M, Shirai T, Masuda M, Yamada T, Imokawa S, Suda T (2016) Maintenance therapy with pemetrexed and bevacizumab versus pemetrexed monotherapy after induction therapy with carboplatin, pemetrexed, and bevacizumab in patients with advanced non-squamous non small cell lung cancer. Eur J Cancer 58:30–37. https://doi.org/10.1016/j.ejca.2016.01.013 CrossRefGoogle Scholar
Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, von Pawel J, Gottfried M, Bondarenko I, Liao M, Gann CN, Barrueco J, Gaschler-Markefski B, Novello S, Group L-LS (2014) Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol 15(2):143–155. https://doi.org/10.1016/S1470-2045(13)70586-2 CrossRefGoogle Scholar
Hanna NH, Kaiser R, Sullivan RN, Aren OR, Ahn MJ, Tiangco B, Voccia I, Pawel JV, Kovcin V, Agulnik J, Gaschler-Markefski B, Barrueco J, Sikken P, Schloss C, Kim JH, group L-LS (2016) Nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with relapsed or refractory, advanced non-small cell lung cancer (LUME-lung 2): a randomized, double-blind, phase III trial. Lung Cancer 102:65–73. https://doi.org/10.1016/j.lungcan.2016.10.011 CrossRefGoogle Scholar
Herbst RS, Sun Y, Eberhardt WE, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE (2010) Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol 11(7):619–626. https://doi.org/10.1016/S1470-2045(10)70132-7 CrossRefGoogle Scholar
de Boer RH, Arrieta Ó, Yang CH, Gottfried M, Chan V, Raats J, de Marinis F, Abratt RP, Wolf J, Blackhall FH, Langmuir P, Milenkova T, Read J, Vansteenkiste JF (2011) Vandetanib plus pemetrexed for the second-line treatment of advanced non-small-cell lung cancer: a randomized, double-blind phase III trial. J Clin Oncol 29(8):1067–1074. https://doi.org/10.1200/JCO.2010.29.5717 CrossRefGoogle Scholar
Lee JS, Hirsh V, Park K, Qin S, Blajman CR, Perng RP, Chen YM, Emerson L, Langmuir P, Manegold C (2012) Vandetanib versus placebo in patients with advanced non-small-cell lung cancer after prior therapy with an epidermal growth factor receptor tyrosine kinase inhibitor: a randomized, double-blind phase III trial (ZEPHYR). J Clin Oncol 30(10):1114–1121. https://doi.org/10.1200/JCO.2011.36.1709 CrossRefGoogle Scholar
Laurie SA, Solomon BJ, Seymour L, Ellis PM, Goss GD, Shepherd FA, Boyer MJ, Arnold AM, Clingan P, Laberge F, Fenton D, Hirsh V, Zukin M, Stockler MR, Lee CW, Chen EX, Montenegro A, Ding K, Bradbury PA (2014) Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC clinical trials group study BR29. Eur J Cancer 50(4):706–712. https://doi.org/10.1016/j.ejca.2013.11.032 CrossRefGoogle Scholar
Goss GD, Arnold A, Shepherd FA, Dediu M, Ciuleanu TE, Fenton D, Zukin M, Walde D, Laberge F, Vincent MD, Ellis PM, Laurie SA, Ding K, Frymire E, Gauthier I, Leighl NB, Ho C, Noble J, Lee CW, Seymour L (2010) Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer: NCIC clinical trials group BR24 study. J Clin Oncol 28(1):49–55. https://doi.org/10.1200/JCO.2009.22.9427 CrossRefGoogle Scholar
Scagliotti G, Novello S, von Pawel J, Reck M, Pereira JR, Thomas M, Abrão Miziara JE, Balint B, De Marinis F, Keller A, Arén O, Csollak M, Albert I, Barrios CH, Grossi F, Krzakowski M, Cupit L, Cihon F, Dimatteo S, Hanna N (2010) Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol 28(11):1835–1842. https://doi.org/10.1200/JCO.2009.26.1321 CrossRefGoogle Scholar
Paz-Ares LG, Biesma B, Heigener D, von Pawel J, Eisen T, Bennouna J, Zhang L, Liao M, Sun Y, Gans S, Syrigos K, Le Marie E, Gottfried M, Vansteenkiste J, Alberola V, Strauss UP, Montegriffo E, Ong TJ, Santoro A, Group Nns-clcREUSNIS (2012) Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol 30(25):3084–3092. https://doi.org/10.1200/JCO.2011.39.7646 CrossRefGoogle Scholar
Scagliotti GV, Vynnychenko I, Park K, Ichinose Y, Kubota K, Blackhall F, Pirker R, Galiulin R, Ciuleanu TE, Sydorenko O, Dediu M, Papai-Szekely Z, Banaclocha NM, McCoy S, Yao B, Hei YJ, Galimi F, Spigel DR (2012) International, randomized, placebo-controlled, double-blind phase III study of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous non-small-cell lung cancer: MONET1. J Clin Oncol 30(23):2829–2836. https://doi.org/10.1200/JCO.2011.41.4987 CrossRefGoogle Scholar
Scagliotti GV, Felip E, Besse B, von Pawel J, Mellemgaard A, Reck M, Bosquee L, Chouaid C, Lianes-Barragán P, Paul EM, Ruiz-Soto R, Sigal E, Ottesen LH, Lechevalier T (2013) An open-label, multicenter, randomized, phase II study of pazopanib in combination with pemetrexed in first-line treatment of patients with advanced-stage non-small-cell lung cancer. J Thorac Oncol 8(12):1529–1537. https://doi.org/10.1097/JTO.0000000000000005 CrossRefGoogle Scholar
Aggarwal C, Somaiah N, Simon G (2012) Antiangiogenic agents in the management of non-small cell lung cancer: where do we stand now and where are we headed? Cancer Biol Ther 13(5):247–263. https://doi.org/10.4161/cbt.19594 CrossRefGoogle Scholar
Gasparini G, Longo R, Fanelli M, Teicher BA (2005) Combination of antiangiogenic therapy with other anticancer therapies: results, challenges, and open questions. J Clin Oncol 23(6):1295–1311. https://doi.org/10.1200/JCO.2005.10.022 CrossRefGoogle Scholar
© Springer Science+Business Media, LLC, part of Springer Nature 2018
1.Department of OncologyPeking University Shenzhen HospitalShenzhenChina
2.Department of OncologyMayo ClinicRochesterUnited States
3.Department of Health Sciences ResearchMayo ClinicRochesterUnited States
Wang, F., Molina, J., Satele, D. et al. Invest New Drugs (2019) 37: 658. https://doi.org/10.1007/s10637-018-0690-x
Received 27 September 2018
Accepted 25 October 2018
First Online 31 October 2018
DOI https://doi.org/10.1007/s10637-018-0690-x
Publisher Name Springer US

redpajama_set_name: RedPajamaCommonCrawl


Delegates to CWC's Iraq Petroleum 2012 conference in London last week received an update on the country's refining capacity and plans from H.E.. Dr Bayazeed Hassan Abdullah, MP, member of the Oil and Energy Committee of the Iraqi Parliament.
Six other small refineries (Kirkuk, Syniah-Baiji, Najaf, Samawa,Nasiriyah, Maysan), with a combined capacity of between 30k and 180k bpd.
However, these plants are running at an average of 65% of design capacity, or 565k bpd, and they produce too much heavy fuel oil; only Baiji, Doura and Basrah refineries produce gasoline. As a result, Iraq continues to import refined petroleum products.
Plans for modernizing and expanding these existing refineries to produce more and better quality fuels are already underway.


text:
Borat catches Donald Trump's lawyer Rudy Giuliani with his pants down. Literally
Sacha Baron Cohen's latest Borat film has scenes of an encounter that appears to leave former New York mayor and President Donald Trump's personal lawyer Rudy Giuliani in a highly compromising situation, caught quite literally with his hands down his pants.
India Today Web Desk
UPDATED: October 22, 2020 09:44 IST
Rudy Giuliani had admitted in July to being set up in a fake hotel room "interview" with an attractive and flirtatious young woman. However, at the time the exact details of the encounter were not known. (Reuters photo)
Comedian Sacha Baron Cohen is back with a sequel of his acerbic character Borat -- the Kazakh journalist who is not afraid to say things all of us are thinking.
This time around, however, Cohen's "Borat Subsequent Moviefilm" has exposed an unexpected character, former New York mayor and US President Donald Trump's personal lawyer Rudy Giuliani.
Filmed in secret this summer as the United States' coronavirus lockdown eased, the follow-up again sees British comedian Baron Cohen hoodwink members of the public and politicians via his bumbling and highly offensive reporter alter-ego.
The film's piece-de-resistance is an exceedingly awkward sit-down interview with Rudy Giuliani and Borat's in-film daughter Tutar that ends with Borat (disguised as the boom-mic holder) rushing in on the two of them in a charged moment alongside a hotel bed.
*Spoiler alert!*
The plot of the sequel revolves around Borat, who was last seen in a gulag in Kazakhstan for bringing dishonour to the nation, being given a chance to redeem himself. He must present a gift to Donald Trump.
After a series of hijinks, Borat decides to present his teenage daughter Tutar to someone in US President Donald Trump's inner circle.
Given his past encounters with Trump (Baron Cohen's character Ali G interviewed him; Borat previously defecated in front of a Trump building), it's judged best to instead seek out who Borat calls "America's most famous ladies man," Vice-President Mike Pence (he's famously not).
When Borat's first target Mike Pence doesn't take the bait, he moves on to 76-year-old Giuliani.
RUDY GIULIANI CAUGHT WITH HIS PANTS DOWN
Borat's daughter Tutar pretends to be a conservative reporter and meets Rudy Giuliani in a New York hotel suite for an "interview" about Trump's Covid response and the pandemic which basically devolves into Trump's lawyer brazenly flirting with the young woman.
The room is rigged with concealed cameras, which capture Giulani's misadventure in detail.
"I'll relax you, you want me to ask you a question?" Giuliani says as she giggles in response.
The two retire to the bedroom and begin drinking, even as Giuliani coughs and praises Donald Trump's Covid plan. In fact, he even agrees to eat a bat with her.
Rudy Giuliani (@RudyGiuliani), Trump's personal attorney, caught on film attempting to lure and/or possibly rape an actress (age 24) portraying a 15-year-old child and daughter of Borat (@BoratSagdiyev). #Borat2 #ByeRudy pic.twitter.com/yeqglbxhT9
— Anonymous (@YourAnonCentral) October 21, 2020
According to a report in the Guardian, Giuliani then removes Tutar's microphone and takes her to the bed. As she removes the microphone from his shirt, he starts patting her back.
The former New York mayor then proceeds to lie down and reaches into his pants suggestively in front of the supposedly 15-year-old character (played by a 24-year-old actress).
Before things can get more graphic, Borat (disguised as a boom mic operator) runs into the room and says, "She's 15. She's too old for you."
Giuliani quickly sits up and appears startled by the presence of Cohen, who wears a pink outfit that resembles lingerie.
The former mayor asks him: "Why are you dressed like this?"
Borat responds: "She's my daughter. Please, take me instead."
"I don't want you," Giuliani replies. He then makes his way out of the hotel suite.
BORAT CLIP CAUSES STORM, GIULIANI TRIES TO SAVE FACE
While the plot is officially under wraps, word of Baron Cohen's latest outrageous ambushes has begun to spread with many on Twitter confirming the scene.
I've seen the Giuliani moment in Borat 2. It's even wilder than it sounds. Beyond cringe.
— Maureen Dowd (@maureendowd) October 21, 2020
Holy shit, I DEFINITELY didn't have Rudy Giuliani busted trying to have sex with Borat's underage daughter on my batshit bingo card.
2020 is insane.
— BrooklynDad_Defiant! (@mmpadellan) October 21, 2020
Even Giuliani admitted in July to being set up in a fake hotel room "interview" with an attractive and flirtatious young woman.
Representatives did not respond to an AFP request for comment, but Giuliani earlier told the New York Post he had thought the meeting was a serious interview about the Trump administration's response to the Covid-19 pandemic.
"I only later realized it must have been Sacha Baron Cohen. I thought about all the people he previously fooled and I felt good about myself because he didn't get me," Giuliani told the publication, adding he was a "fan of some of his movies."
Giuliani, a close Trump ally has been in the news recently for illegally obtaining and leaking details of a laptop drive belonging to Democratic presidential nominee Joe Biden's son Hunter.
While the scandalous Borat clip may not influence Trump voters but it will certainly capture crucial air time for the Trump campaign just days before the US presidential elections.
(with inputs from AFP)
READ | Adult film star Stormy Daniels reveals details of sex with Trump
WATCH | Trump's leaked audio tape: I did try and f**k her, she was married
Posted byNishtha Gupta


text:
Supreme Court Unanimously Rejects Texas Bid to Overturn Election
James Joyner · Saturday, December 12, 2020 · 29 comments
President Donald Trump appointed two-thirds of the justices on the United States Supreme Court. They all summarily rejected the outrageous bid by the indicted Texas attorney general—signed off by 17 other Republican states and Trump himself—to subvert the election. The press reaction is unusually blunt.
Adam Liptak, New York Times ("Supreme Court Rejects Texas Suit Seeking to Subvert Election"):
The Supreme Court on Friday rejected a lawsuit by Texas that had asked the court to throw out the election results in four battleground states that President Trump lost in November, ending any prospect that a brazen attempt to use the courts to reverse his defeat at the polls would succeed.
The court, in a brief unsigned order, said Texas lacked standing to pursue the case, saying it "has not demonstrated a judicially cognizable interest in the manner in which another state conducts its elections."
Texas' lawsuit, filed directly in the Supreme Court, challenged election procedures in four states: Georgia, Michigan, Pennsylvania and Wisconsin. It asked the court to bar those states from casting their electoral votes for Mr. Biden and to shift the selection of electors to the states' legislatures. That would have required the justices to throw out millions of votes.
Mr. Trump's campaign did not immediately issue a statement. In an appearance on the conservative network Newsmax soon after the decision was announced, Rudolph W. Giuliani, Mr. Trump's personal lawyer, said that the campaign's legal effort would continue, insisting that his team had originally planned for "four or five separate cases."
"We're not finished, believe me," he said with a laugh at the end of the interview.
The president, who at a White House Hanukkah party earlier in the week eagerly mentioned the pending court case in his remarks, was scheduled to attend another holiday party around the time the ruling came down. But around 8:30 p.m., guests were informed that Mr. Trump would not be coming down from the residence to speak.
Mr. Trump weighed in later on Twitter. "The Supreme Court really let us down," he said. "No Wisdom, No Courage!"
Robert Barnes, Washington Post ("Supreme Court dismisses bid led by Texas attorney general to overturn the presidential election results, blocking Trump's legal path to a reversal of his loss"):
The Supreme Court on Friday dismissed a long-shot bid by President Trump and the state of Texas to overturn the results in four states won by Democrat Joe Biden, blocking the president's legal path to reverse his reelection loss.
Justices Samuel A. Alito Jr. and Clarence Thomas said they did not think the court had the authority to simply reject a state's filing, a position they have taken in past cases. But they said they would not have granted Texas the remedy it sought, which was to disallow the electors from those four states.
Legal experts from the beginning had derided Texas's unprecedented action as implausible, and the court's rejection was fast and emphatic — the order came just hours after briefing was completed. The justices seemed to have bypassed a lengthy explanation in favor of a unified outcome.
Taking into account an earlier request from Republicans in Pennsylvania, it means that in two cases to reach the court — where conservatives hold a 6-to-3 majority — no justice has expressed support for the drastic idea of throwing out election results.
Nina Totenberg, NPR ("Supreme Court Shuts Door On Texas Suit Seeking To Overturn Election"):
The U.S. Supreme Court on Friday night rejected an eleventh hour challenge to Joe Biden's election as president.
The court's action came in a one-page order, which said the complaint was denied "for lack of standing."
The Guardian ("Supreme court rejects Trump-backed Texas lawsuit aiming to overturn election results") and CNN ("Supreme Court rejects Texas' and Trump's bid to overturn election") apparently got the memo as well.
SCOTUSblog's Tom Goldstein, writing before the announcement, was hoping for more:
The easy thing for the Supreme Court to do is simply deny Texas permission to file the complaint (and deny the motions to intervene as moot) and be done with it. No fuss, no muss.
But the court should do more. It is perfectly ordinary and appropriate for the justices to write an opinion explaining the various reasons why they are rejecting Texas' request. Indeed, the minority of justices who think that the court is required to accept original actions like Texas' may well write short opinions of their own or note that they think the case was properly filed. So there is nothing overreaching if a majority of the court explains why the case is meritless.
The justices' decision whether to do that needs to account for this extraordinary, dangerous moment for our democracy. President Donald Trump, other supportive Republicans, and aligned commentators have firmly convinced many tens of millions of people that the 2020 presidential election was stolen. If that view continues to take hold, it threatens not only our national politics for the next four years but the public's basic faith in elections of all types that are the foundations of our society.
A simple five-page per curiam opinion genuinely could end up in the pantheon of all-time most significant rulings in American history. Every once in a long while, the court needs to invest some of its accumulated capital in issuing judgments that are not only legally right but also respond to imminent, tangible threats to the nation. That is particularly appropriate when, as here, the court finds itself being used as a tool to actively undermine faith in our democratic institutions — including by the members of the court's bar on whom the justices depend to act much more responsibly.
In a time that is so very deeply polarized, I cannot think of a person, group or institution other than the Supreme Court that could do better for the country right now. Supporters of the president who have been gaslighted into believing that there has been a multi-state conspiracy to steal the election recognize that the court is not a liberal institution. If the court will tell the truth, the country will listen.
Volokh Conspiracy's Jonathan Adler argues that the opinion is actually much more of a smackdown than the reporting would have us believe:
This result was not a surprise. As I indicated in my prior posts on AG Paxton's initial filing, the intervening briefs, amici, state defendants' responses, and Paxton's feeble replies, this case never had merit. As the Court concluded, Texas could not satisfy the requirements of Article III standing to challenge the election procedures utilized by other states to select presidential electors. What is more, even the two justices who believed the Court was obligated to hear the case-arguably the Court's two most conservative justices-did not believe Texas was entitled to the extraordinary relief it sought, relief which would have been necessary for AG Paxton's last-ditch effort to have any result on the electoral college. AG Paxton's office submitted transparently weak arguments, and the Court summarily dispatched them.
It is important to underscore that the Supreme Court's decision is, for all practical purposes, unanimous. Justices Alito and Thomas have long held the view that when a state seeks to invoke the Court's original and exclusive jurisdiction, the Court is obligated to hear the case. (See, e.g., their dissent from the Court's refusal to hear Arizona v. California.) This is a serious argument, which Ilya Somin discussed here and which I suspect may be correct. So while the vote on Texas' Motion for Leave was technically 7-2 on this basis, the Court was 9-0 in rejecting AG Paxton's attempt to get any sort of actual relief, such as an injunction preventing states from appointing presidential electors. Not a single justice was willing to express any sympathy for any aspect of Texas's legal claims.
As for the rest of Justice Alito's statement, what "other issue" might he be referring to? I suspect this is a reference to the Pennsylvania litigation that is still pending, about which Justice Alito previously issued a statement.
On the rest of the Court's order, it is significant that the Court did not merely note the lack of standing, but also specified that Texas had not "demonstrated a judicially cognizable interest in the manner in which another State conducts its elections." In other words, one state cannot invoke the jurisdiction of the federal courts to challenge another states election processes, even when it concerns the selection of presidential electors. This should discourage other states from trying such things in the future, whether to raise Electors Clause claims, Equal Protection claims, or anything else.
As I have already noted, this should not have been a surprise to anyone who was paying attention. The briefs submitted by AG Paxton's office were weak on the facts and weak on the law. In some respects, as I noted in prior posts, they were downright embarrassing. The briefs filed in support of Paxton's claims were, on the whole, not much better. Those attorneys who were willing to file briefs that actually embraced the substance of Paxton's claims should be particularly embarrassed. If Paxton's own Solicitor General would not sign on to these briefs, why would the SG of Missouri or Utah?
The #Kraken may have been released. Tonight's Supreme Court order should also have put it out of its misery.
Emphases all mine.
The Trump legal team is now something like 0-55 in the courts. Despite outrageous statements from Republican officials from the President to the House Minority Leader to numerous Senators, Governors, and lower state office-holders, the wishes of the voters in every state were ultimately upheld.
One hopes that there is a reckoning for those who so brazenly tried to steal this election. Alas, judging from my Facebook feed, the "stop the steal" nonsense had the desired effect of poisoning the well. People I know to be intelligent and otherwise decent and patriotic folks honestly think—or are at least willing to publicly proclaim in what they think are semi-private conversations among friends and comrades—that the Democrats somehow stole the election and that we're living in a banana republic.
Indeed, Adler's colleague Ilya Somin fears the Supremes didn't do enough to dispel that notion.
I do worry that the Court's decision to reject the case on procedural grounds will give more fuel to Trumpist claims that the plaintiffs were actually right on the merits, and that Texas would have won if only the justices had been willing to take up its claims. Texas' position had numerous substantive flaws, as well. But committed partisans are likely to ignore that or be unaware of it.
More generally, I fear that tonight's ruling won't stem the dangerous tide of conspiracy-mongering about the election by Trump and many of his allies, and it won't prevent a good many of his supporters from continuing to believe such claims. That said, the Supreme Court cannot be expected to solve all the flaws of our screwed-up political discourse. The justices' job is much narrower than that. And tonight they did it well.
Indeed, they did. A unanimous verdict here is likely as powerful a message as we could have expected.
FILED UNDER: Campaign 2020, Democracy, Law and the Courts, Supreme Court, US Politics, Arizona, battleground states, California, Clarence Thomas, CNN, Donald Trump, elections, electoral college, electoral votes, equal protection, Facebook, Georgia, Ilya Somin, Joe Biden, Jonathan Adler, Michigan, Missouri, New York, New York Times, Nina Totenberg, NPR, Pennsylvania, polarization, SCOTUSBlog, Texas, The Guardian, Twitter, Utah, Washington Post, Wisconsin
About James Joyner
James Joyner is Professor and Department Head of Security Studies at Marine Corps University's Command and Staff College and a nonresident senior fellow at the Scowcroft Center for Strategy and Security at the Atlantic Council. He's a former Army officer and Desert Storm vet. Views expressed here are his own. Follow James on Twitter @DrJJoyner.
CSK says:
Saturday, 12 December 2020 at 08:00
It's quite ironic that Trump wanted Amy Coney Barrett appointed to the SC before November 3 so that he'd have a majority to decide this case in his favor.
It also indicates that he knew he was going to lose not just the popular but the electoral votes as well.
Despite outrageous statements from Republican officials from the President to the House Minority Leader to numerous Senators, Governors, and lower state office-holders, the wishes of the voters in every state were ultimately upheld. […]
People I know to be intelligent and otherwise decent and patriotic folks honestly think—or are at least willing to publicly proclaim in what they think are semi-private conversations among friends and comrades—that the Democrats somehow stole the election and that we're living in a banana republic.
There is no way this is going to end well.
I also think this is a perfect illustration of the (perhaps) irreparable damage norm busting can do.
There were people who initially said when Trump claimed the election was stolen "Give him a few days to process his loss. This is just blowing off steam, the guard rails will hold."
And here we are now.
I'm not saying a stronger response by political commentators would have prevented this, but their refusal to properly identify what was happening and the accompanying lack of urgency certainly didn't help.
Same thing with the Russia-sponsored hacks in 2016. People were given an opportunity to look away and pretend that maybe things weren't as bad as they almost certainly were, i.e. that the POTUS was elected thanks to the willingly accepted assistance provided by a geopolitical adversary. Ultimately, ignoring this fact didn't exactly help to preserve the political health of the nation.
Best-case scenario right now is that "Every election that Democrats win, is stolen," becomes the next "Abortion is murder" – something that people profess to sincerely believe but not act in accordance with.
So hopefully, no armed insurrection.
Even so, in practice this will mean a significant rollback of voting rights in the red areas of the country. But how long will the economically productive blue states/counties (i.e. the actual majority) be willing to accept this situation?
This decision marks a major victory for states' rights.
rn2md says:
A small correction, Trump appointment one third of the court.
Mikey says:
In an appearance on the conservative network Newsmax soon after the decision was announced, Rudolph W. Giuliani, Mr. Trump's personal lawyer, said that the campaign's legal effort would continue, insisting that his team had originally planned for "four or five separate cases."
You'll be done at noon on January 20, you seditious goon.
I do worry that the Court's decision to reject the case on procedural grounds will give more fuel to Trumpist claims that the plaintiffs were actually right on the merits, and that Texas would have won if only the justices had been willing to take up its claims.
That's pretty much the standard line on the idiot side of this issue right now, alongside quotes of Patrick Henry ("Give me liberty or give me death!"). It's insane.
So now along with damaging Americans' faith in our electoral system, Trump has done the same for the courts.
OzarkHillbilly says:
'Tis but a scratch.
Paine says:
Someone should get Trump a "I nominated three justices to the Supreme Court and all I got was this lousy t-shirt" shirt.
gVOR08 says:
The courts are proving to be the last guardrail preserving democracy and reason. Which is why the Koch Bros et al set out years ago on a decades long program of corrupting the judiciary through The Federalist Society.
This video sums up the GOPs efforts to overturn the election better than any column or blogpost ever could.
Monala says:
Trump tweeted this morning, "We have just begun to fight!"
OTOH, the auto entry on my phone has already forgotten about him. It offered me Truck and Trumpet as options.
@Monala:
He knows he lost. He's just playing to the Trumpkins at this point.
de stijl says:
21st century American dolchstosslegende.
Trump is Trump. We all knew he was going to sting us on his way out. It's who he is.
What is troubling and very concerning is the amount of our elected officials who explicitly or implicitly encouraged his behavior.
And the number who will bray "We wuz robbed" for the next few decades.
The djinni is definitely out of the bottle.
The end was easily forseeable. I did not see that acceptance and encouragement of Trump's idiotic lies would become a R litmus test.
This is burning the building down cuz you got evicted behavior. And a shockingly large chunk of the neighbors bought the gasoline to help him.
Someone convince me this isn't active sedition.
Slugger says:
This effort by Trump has been very successful. He sat back, sent a few tweets, played golf, didn't bother with the ASEA trade conference, didn't bother with his government's Covid committee meetings, and raised more tha $207 million. Literally money for nothing. He is not letting go of this. Giving a sucker an even break is not in a casino owner's DNA.
@Slugger:
How does one manage to bankrupt a casino in Atlantic City in the 80s?
Seriously, 85% of adult Americans if gifted a casino in AC could run it fairly well.
It takes hard work and active mismanagement to bankrupt a casino properly located. Rubes give you money knowing they are going to get fleeced. You make 2 to 5% off every bet.
Any idiot could make that work.
@de stijl:
Don't forget that he also went bust trying to peddle vodka.
Any idiot can make money promoting gambling and selling booze. Trump couldn't.
Michael Reynolds says:
@CSK:
I don't think ACB was about stealing the election because I don't think Trump thought he'd lose. IMO, ACB is about blocking prosecution of Trump for his crimes. She may still pay off on that front.
@Michael Reynolds:
According to Maggie Haberman Trump himself alluded to the idea of having ACB in place before the election, just so she could fix things if they went south on him.
Teve says:
@CSK: The vodka business is the easiest thing in the world. It's a little known fact, but virtually no vodka bottler produces their own alcohol. There are three industrial giants like Archer Daniels Midland that produce vast quantities of grain alcohol. Vodka bottlers buy the alcohol, dilute it and filter it, put it in a bottle with a label and ship it. High school kids could successfully run that business.
@Teve:
Well, Trump slapped a $100 price tag on his Trump Gold (or whatever the hell it was called), which made it approximately five times the cost of any of the premium vodkas at the time. Vodka is vodka. Only an idiot would pay $100 for it.
From the mouth of R. Giuliani, Esq., today:
"We plan to move immediately, seamlessly, to Plan B, which is to bring lawsuits now in each one of the states. They're just a version of the one that was in the Supreme Court."
According to Giuliani, Trump made this decision last night.
@de stijl: My personal theory on bankrupting a casino comes from my study of The Producers.. Bankruptcy doesn't mean that the owner of an enterprise loses money; the people who relied on the owner lose money. I think that the casino was intended to go bankrupt with the laws governing business providing a shield for the principals. This making money while driving a business into the ground is not rare. The casino business in New Jersey may even involve guys with bent noses.
Michael Cain says:
Texas is going to sue in the district courts? The Trump campaign is going to sue on behalf of Texas and its voters? At some point one or more of the courts are going to toss Rudy in jail on contempt charges for repeated frivolous lawsuits.
@Michael Cain:
Yeah; I know. It doesn't make much sense to me, either. But I suppose all they can come up with at this point is to keep repeating themselves. We all know the definition of insanity. No need for me to repeat it.
@CSK: There are different grades of grain alcohol you can buy, known in the industry as head, heart, and tail. The cheaper stuff has more chemical impurities. But yeah Trump was selling cheap vodka for $100 a bottle. People who only want cheap vodka can get it for 8 dollars a bottle, and people who are willing to pay more aren't going to do so for cheap filthy vodka. You can't re-label an AMC Gremlin and sell it for Maserati prices.
Bent nose guys in AC in 1982? Who coulda knew?
Gustopher says:
My worry is that by failing to take the case, and by deciding that states have no interest at all in the elections of other states, that the Supreme Court has created a protection for antidemocratic behavior at the state level in future elections.
What if Georgia had decided to toss out the election results and install their own electors? What would the remedy have been?
With 20 Republican State AGs signing onto this, and 130+ Republican Congress Critters, they have stated that they are willing to do this, and I think we should take them at their word. This is a constitutional crisis, and the gravest threat to our country since at least the civil war (even there, the two countries would both be democracies, limited as they were at the time, so this may be worse other than, you know, slavery), and the Supreme Court said they have no jurisdiction.
That does not seem good.
Also, I was looking forward to Ted Cruz arguing gibberish in front of the Supreme Court…
@Gustopher:
What would make it funny was the way and manner Trump treated Cruz in 2015.
Trump got really rude and personal with Cruz.
A whipped dog licking his master's fingers is sad.
Why would Cruz entertain such an endeavor? It makes him look weak.
Sadly, the time has passed. I would have paid good money to see that.
Pylon says:
Rudy might want to check the decision of the Trump appointed judge in the district court in WI to day.
Mike Schilling says:
Monday, 14 December 2020 at 11:22
resident Donald Trump appointed two-thirds of the justices on the United States Supreme Court.
One third.
Supreme Court Upholds 'Faithless Elector' Laws
Are Electors Free to Choose?
Texas Attorney General Tells Clerks They Can Ignore The Constitution If They Want To
Appeals Court Rules States Cannot Punish 'Faithless Electors'
What To Expect Today From The Electoral College


text:
Home Parenting Issues & Tips Sexting: The New 'First Base'
From the February 2015 magazine
Sexting: The New 'First Base'
Alexander Grabski
Are you sure your teen isn't sending sexy photos or texts? Not so fast.
"Sexting" – the sending and receiving of explicit messages – is so common among digital-native kids that it's the new "first base" of adolescent sexual behavior, says a recent study by the American Academy of Pediatrics.
That's right: A not-safe-for-school selfie is akin to what kissing once was. Unlike making out, it's a lot harder to get rid of the evidence. But that isn't stopping kids.
Teens sext "as a normal part of adolescent sexual experimentation and development," says Robert Weiss, a California therapist who specializes in technology and relationships.
While standard, the repercussions can be steep. Anxious about broaching the issue? Weiss offers this advice.
How can I tell? "Unless a parent has access to a child's smartphone," Weiss levels, "there is no way to know for sure." You can certainly attempt to set restrictions or monitor your child's tech activity. But Weiss says a better option is to simply have a conversation.
Acknowledge your child may be sexting, going on to say, "I'd really like to talk to you about it so I can know what's going on, and also to make sure you understand the potential consequences of this behavior."
Confronting. Weiss says the worst thing a parent can do is overreact: "Oh my god, you're sending filthy pictures using your smartphone and I'm taking it away this instant!" Instead, try an "open-minded, non-judgmental way, recognizing that their child may have very different views of the meaning and effects of sexting." Be calm. Allow your child a chance to be honest. Then, emphasizing you don't want to stifle him or her, spell out your rules and reasons.
In more serious situations, if you opt to add monitoring software, talk to your kid about this. "Include your children in the 'settings' process, giving them input about what material should be blocked and/or reported."
Start talking about sexting and porn early, Weiss adds – even before adolescence. It's something kids may encounter in daily web use. "(That) makes it less awkward later on."
Consequences. There are two types of sexting, Weiss says. "The first is when people send existing sexualized imagery that does not depict themselves," he says. "The second is when people take sexy selfies and pass them along." The second is usually more concerning. Once gone, the sender loses control of it. "The recipient can delete it, keep it for personal use, forward it to friends, post it online, etc."
This has redefined the meaning of a bad breakup. Sexted imagery can be used as a weapon – pictures get shared with others at school or even splashed on social media. There can be very real legal consequences.
"The making and dissemination of child pornography is a felony. This means that a minor who sexts an image of himself or herself has committed a serious crime," Weiss says. "Receiving such an image is also a serious crime." Explaining this may not curb the behavior entirely. It can, however, encourage teens to make better decisions.
Previous articleRobot Valentine Mailbox Crafts for Kids
Next articleRaising Children Who Volunteer
Helping Kids Adjust to Daylight Saving Time Change
10 Tips to Address Diversity with Your Kids
Talking With Kids About Race


text:
Original Cartoons since 1998.
An interview with director Robert Alvarez.
Photograph of Robert Alvarez @ Cartoon Network by Steve Hulett, 2010
Listen to Robert's two part interview here and here.
Director & artist Robert Alvarez is one of the great ones, and incredibly important to me (and Frederator). So I was very pleased to listen to the oral history interview posted this week by feature film writer Steve Hulett of Hollywood's Animation Guild.
As you can hear in the interview, Robert's wanted to be in the cartoon biz since he was in the 8th grade, he succeeded in getting into the industry very early, and he's been a thriving, creative stalwart for over 40 years. His imdb page has its first credit as 1969's animated Winky Dink and You, and he's worked on the full range of projects from The Smurfs to Samurai Jack (where he got his first Emmy®) right through to Regular Show. You really can't keep a good man down. Every new generation of talent is eager to make their own mark on the business and looks skeptically on the people who came before them, as if they're somehow not good enough for their masterpieces. After initial doubts, Robert has won over every new group of creators that have invigorated cartoons for the almost 20 years I've known him. He's done it with his skills, certainly, but it might be his patience, excitement, and generosity that have most triumphed.
When I arrived at Hanna-Barbera in 1992, Robert was one of the veterans who's respect I seriously desired. He was the real deal, a talented, serious professional who was also a complete animation fanboy. If only I could convince him that my plans for the studio weren't frivolous or mercenary. We had a minor tussle early on, when he thought I might be treating the characters recklessly and I think he was convinced my love for them was genuine. But, it was after he started working with Pat Ventura on his first short for us that we really bonded. I was extremely proud that Robert went on to create Pizza Boy and Tumbleweed Tex for What A Cartoon! (He's nice enough to mention moi in the second part of the interview, talking about the changes we brought to Hanna-Barbera.)
I want to put in a word for the Animation Guild and its Business Representative Steve Hulett too. There's probably no institution more dedicated to keeping show business animation alive than the Guild (no, not Disney or Pixar), and Steve's right at the front of the line. I was once a Doubting Thomas having grown up throughout my life in management (my parents owned their own business, and I've been running companies for quite a few years) and having had a few particularly unpleasant run-ins with a past Guild president. But, now I send every single new Hollywood animation arrival straight over to Steve. I know he's there to make everyone's entry into the industry as smooth and productive as possible, and that the Guild runs classes and events designed to broaden everyone's skills and networking possibilities. They're a bunch of solid citizens over there, and I encourage everyone with an interest to check out their site and blog as often as possible. We're all indebted.
And I love these oral histories, four of which are posted on the blog now. Keep 'em coming Steve, we're all waiting.
Animators, Interview, What A Cartoon!, World Premiere Toons, cartoon shorts
Available on Amazon.
Book> The Big Payback: The History of the Business of Hip Hop by Dan Charnas
Blog History of Frederator shorts
Cartoon heroes
cartoon music
cartoon shorts
Channel Frederator RAW
Dan Meth
Drinking + Drawing
Fairly Oddparents
Fredbot
Frederator Books
Frederator Films backstory
Frederator Postcards
Frederator posters
Frederators
Meth Minute 39
MTV: Music Television
Muse Records
Next New Networks
Other Fred Seiberts
Produced by FS
Studio Visitors
title cards
What A Cartoon!
World Premiere Toons
Wubbzy
The Frederator RSS
Search Frederator
Fred's Tumblr Scraps
Fred's Tumblr Galleries
More at Fred's Tumblr Scraps
Fred Seibert's Blog built with WordPress MU


text:
"I saw a girl riding the other day struggling and her tires had maybe 20 percent of the air that they should have had in them," Underwood says. "That right off the bat would make it 50 percent easier at least, if not 100 percent easier. Little things can make a big difference."
As riders old and new hop on their bikes across the Southern Tier this spring, Underwood and other bike shop owners from the area share some tips on bike maintenance, accessories and questions you should ask when buying a bicycle for yourself or your child.
Bicycling is the most popular outdoor activity among youth in the United States, and it is the third-most-popular outdoor activity among adults. Twenty-four percent of youth and 12 percent of adults rode a bike in 2012 according to research by the Outdoor Foundation.
Making sure your bicycle is properly maintained is crucial before taking your first ride of the year. Many things can go wrong as bicycles sit in a garage or shed for months during long winters, including corrosion affecting tires, chains or breaks and tires losing air pressure.
Most bike shops offer several tuneup packages ranging from standard to advanced, which includes modifications and wheel truing (a specialized tool for straightening wheels). Standard tuneups include a safety inspection on all aspects of the bike, minor adjustments, cleaning cables and lubing chains.
The most frequent error cyclists make when they resume riding is not checking the air pressure.
"Most people notice when it's out of air totally, but they don't notice it when it's low," says Gary Weidberg, owner of The Bike Rack in Ithaca. "If you hit a pothole when it's low you'll likely bend your rim, for sure put it out of true. That's a biggie."
Kevin Babcock, owner of Babcock Bicycles in Endicott, compared it to tire pressure in a car.
"We see so many flats caused by lack of inflation, but not only that the bike rides really terrible," Babcock says. "Having low tire pressure in your car means low gas mileage and if you pump the tires up the gas mileage goes right up. And since you're the engine on a bike, you want to get good gas mileage."
When it comes to buying a bicycle, Weidberg says most customers are unsure of what they want. There are several questions shop employees ask to get an idea of what type of riding that person would like to do.
• Do you have a bike presently? If so, which type? An employee can use this information to understand someone's riding patterns and their history.
• What kind of riding do you want to do? The main options include on the road, off road or something in between.
• Who are you riding with? If you are planning on riding with a partner or group, be sure to have the same type of bicycle or you may not be able to ride the same terrain.
• Where do you plan on going? Someone who will use a bike mainly for commuting to work may want a different bike than someone who does not.
• What do you want to do in five years? If you plan to be at a different point in five years maybe you want to buy a higher-quality bike, and you can make upgrades and repairs as you go.
"For adults, the bike should be purchased for 90 percent of the riding," Underwood says. "Some people will say, 'I will mainly commute to work, but once in a while I might do something else.' If you're going to be commuting mostly, get a suitable bike and maybe we can get you toward that 'once in a while' just by making small changes in the bike."
The three bicycles most adults use are road bikes, mountain bikes and hybrids.
Road bicycles are built for traveling at speed on paved roads. They are lightweight with a multi-gear sprocket system and narrow tires.
Mountain bikes are heavy-duty bicycles used for riding off road on trails and other unpaved environments. They have lower gear ratios, more powerful breaks and include a suspension.
Hybrids are general-purpose bicycles that can be used on multiple terrains. Not quite as durable as a mountain bike and not as lightweight as a road bike, they are a popular choice for beginners.
BMX bikes and fattie bikes, which use 3.8-inch-wide wheels for use in winter conditions, are other less popular bike options for adults.
In addition to the different styles of bikes, more alterations can be made to improve comfort.
"We can take a person and let them sit upright, have them in a race position, maybe slightly leaning forward, whatever someone is looking for," Babcock says. "From mild to wild."
Buying from a bike shop will be more expensive than purchasing a bicycle at a big-box retailer, but quality is worth the higher pricetag for most riders. Repairs on bikes from retail stores often exceed the cost of the bike.
Bicycles for children and adults can start from less than $100 at big-box stores to as much as $3,000 for specialized bicycles. Some of the most popular models sell for about $400-$600 at many bike shops.
When parents buy a bicycle for their child, 50 percent of the time the child is not present. Weidberg says the most important number parents should know is the child's inseam measurement (if that's not known, height is the next best measurement). Purchasing a bike is easier when the child is there, so bike shop workers can ask questions and let the child try out several options.
Options for children start at tricycles and training-wheel bikes for young kids. Smaller models of mountain bikes, road bikes and hybrids are also available. BMX bikes are the most popular for kids and teenagers. Whatever style bike you choose, making sure it fits properly is key.
"We don't want to see them outgrow it fast because parents don't want to buy a new bike every year," Babcock says. "Get them on a bike that they're just beginning to get into, then they're going to grow into it and the parents can get the most amount of use on it."
Weidberg says the parent makes the final decision but it's his duty to speak up if he doesn't think a bike is safe. A boy should clear the top bar by at least an inch, but Weidberg said as long as they clear it the bike should be safe.
"The popular question is: 'Will it last until he's 18?' Weidberg says.
A helmet is by far the most important accessory for cyclists and children under the age of 14 are required by law to wear one. Most bike shops suggest all riders wear a helmet, and a 1993 study by Public Health Reports says wearing a helmet is proven to influence others to wear a helmet.
Other accessories may not be able to save your life, but they can save you headaches. It doesn't matter if you're riding on the Rail Trail in Vestal, down the South Hill into the Ithaca valley or on the Lackawanna Rail Trail in Elmira, a flat tire can leave you angry and stranded. A bike pump can attach to the frame of a bike and a small pouch under your seat can hold a spare tube, patch kit and small tool.
The number of Americans who commute to work and school primarily by bicycle has increased almost 50 percent since 2000, which means more bicycles on the road. Bright-colored bicycle clothing and flashing lights can help give motorists the ability to spot you from farther away.
Gloves can serve a few purposes, including cleaning off tires and protecting your palms from cinder and dirt when you fall. A cyclometer is also useful tool that can display heart rate, speed, mileage and other data.
The options are endless when it comes to customization, but riders should not let customization get in the way of safety. When buying a bike or making upgrades on your current bicycle, make sure to visit a qualified bike shop with a good reputation.
"Make sure you are getting quality work, or else you will be throwing money away," Babcock says. "Saving a few dollars can be meaningless if the work is subpar."
Are you OUT THERE? Share your ideas and the stories of your active life — from fishing to skiing to rock climbing to hiking to other recreation — with us. Send to outthere@gannett.com.
On Twitter: @SteinTime44
CONQUERING THE HILLS
The Southern Tier is known for its rolling hills, which can be daunting for bicyclists. Growing up on top of a long steep hill, Kevin Babcock says the battle is more mental than physical.
"We'd go ride as kids and we'd climb up every hill everywhere around here but when I got home I could never make it up that last hill," the owner of Babcock Bicycles in Endicott says. "One day I finally realized it's mind over matter so I made myself go over it. The first time was the hardest but after that it's easy.
"I tend not to look to the top of the hill because then I know how farther the suffering is, because you do suffer a little bit."
Babcock says the more you ride hills the easier they become. He also says technology on bicycles has made it easier too.
"I tell people now, and it's so true, if you can walk it without stopping, you should be able to sit in the seat and ride up it on most of these bikes," Babcock said. "You don't really have to work at it, it's just a matter of keeping the pedals moving and not getting depressed."
BC Bicycles
Address: 215 Vestal Parkway E., Vestal, NY 13850
Babcock Bicycles
Address: 108-110 W. Main St., Endicott, NY 13760
Cayuga Ski and Cyclery
Address: 624 W. State St., Ithaca, NY 14850
Chenango Point Cycles
Address: 125 Park Ave., Binghamton, NY 13901
Corning Bike Works
Address: 96 E. Market St., Corning, NY 14830
Kingsbury's Cyclery
Address: 228 W. Water St., Elmira, NY 14901
The Bike Rack
Address: 409 College Ave., Ithaca, NY 14850
Swan Cycles Inc.
Address: 226 Mount Pleasant Rd., Ithaca, NY 14850
Big Horn Velo
Based out of: Elmira
Website: www.bighornvelo.org/
Membership: $20
Finger Lakes Cycling Club
Based out of: Ithaca
Website: flcycling.org/
Membership: $12 per individual/$15 per family.
Southern Tier Bicycle Club
Based out of: Binghamton
Website: www.southerntierbicycleclub.org/
Membership: $5 per individual/$10 per family. Full-time students can join for free.
Tioga Velo Club
Website: www.tiogavelo.com/
Membership: $15-$30 for indivuduals/$35 for families
BIKE BREAKDOWN
A breakdown of the three most popular types of bicycles for adults:
•Built for traveling at speed on paved roads, these bikes were lovingly known as "10 speeds" for a lot of people growing up. They are lightweight with a multi-gear sprocket system and narrow tires.
•Heavy-duty bicycles used for off-road riding on trails and other unpaved environments. They have lower gear ratios, more powerful breaks and include a suspension. Other mountain bike variations include fatbikes, which use 3.8-inch wide tires to travel through snow and ice.
•General-purpose bicycles that can be used on multiple terrains. Not quite as durable as a mountain bike and not as lightweight as a road bike, they are a popular choice for beginners. It is also a popular bike for daily commuters.


text:
Security updates for OnePlus 8 will continue to be implemented every two months
The decision to fully enter the "upper" market segment implies constant and constant attention. At these levels, it is the details that matter, and it is for this reason that the decision of the Chinese company not to change the frequency of monthly updates to the latest makes us think. OnePlus 8,
The new series, officially released in the middle of the week (click here to find out more), was marked by a notable price increase. Just think about it OnePlus 8 Pro in Italy break through the wall of the gods 1000 euros (although the initial price of the "top" option is $ 999). Despite this, even with a more expensive model, the manufacturer will not change its policy regarding security updates for software.
As it has been for several years, Oneplus let go Android patches every two monthsand not monthly. A decision that is now beginning to be criticized, but will not change with OnePlus 8: unofficial confirmation received 9to5Google who contacted the company directly to get clarification on this. On the other hand, the total support time is on average longer than that of other competitors.
OnePlus 8 Pro arrives with on board Android Security Patch for the month of March: therefore, the next update will be available only in May.
A copywriter for over ten years, passionate about sports, history, technology and new media. He loves to travel, for many years he decided to live in Spain, without denying his origin in Campania.
Enthusiastic about Apple and how the "apple" has changed our perception of technology, it still manages to fully appreciate Android and its many aspects.
Bayern to fine one player for training at McLaren
Ukraine also purchased 176 fans


Frequently asked questions about your Flexport account: how to use the app, pay invoices, assign user roles, send messages, and access powerful reporting tools.
How Do I Add and Review My Product Information?
How Can I Subscribe to a Specific Set of Shipments?
How Do I Access My Payment Methods?
How Can I Bulk-Upload Locations to My Network?
How Can I Add My Supplier's Contact Information?
Why Isn't My Dashboard Map Displaying?
How Can I Adjust My Language Settings?
Which Browsers Can I Use to Access the Flexport App?
Frequently asked questions about data, reporting, and analytics are listed here.
If you're in the process of setting up your Flexport account, you may find these articles helpful.
How Can I Share Status Updates Outside of the Flexport App?
How Are Messages Sent and Received Within the Flexport App?
How Can I Follow a Specific Shipment?
How Can I Add a Bank Account for ACH?
How Can I Pay Multiple Invoices at Once?


text:
Paul Marstrand (født 26. april 1895 på Frederiksberg, død 24. april 1965 i Birkerød) var en dansk arkitekt, bror til Vilhelm og Knud Marstrand.

Uddannelse
Han var søn af jernstøber, maskinfabrikant og direktør Poul Marstrand og Thyra Valgerda Burmeister. I 1913 var Paul Marstrand på tre måneders ophold i Nordamerika. Fra 1913 til sin uventede og voldsomme død under revolutionen var broderen Knud Marstrand - kun afbrudt af perioden 1914-15 - bosat i Rusland, hvor han fra 1915 havde en tegnestue. Også hans ni år yngre bror Paul fik sin uddannelse i Rusland i 1914-17 og var i øvrigt autodidakt. Han var gesandtskabsdelegeret i Petrograd for de østrig-ungarske og tyrkiske krigsfangeinteresser 1917-18.

Virke
Paul Marstrand rejste videre til Fransk Marokko, hvor han 1920-26 og atter 1930-35 drev egen tegnestue og var den første eksportstipendiat for Danmark i Marokko fra 1931. Hans bygninger her følger den lokale byggeskik. Han var i Grækenland 1927-30, hvor han var formand for Folkeforbundets græsk-tyrkiske nævn i Saloniki til vurdering af ejendomme 1928-30.

I 1942 var Marstrand permanent hjemme i Danmark, hvor han især fik en række opgaver med lejligheds- og parcelhusbyggeri for Lejerbo, som søgte at afhjælpe den store boligmangel. Hans huse følger den stilfærdige danske funktionelle tradition fra Kay Fisker.

Marstrand var redaktør af fagbladet Bygmesteren 1943-45, medlem af Danske arkitekters genopbygningskommission 1945-47, medlem af bestyrelsen for Byggesocietetet 1945 samt kommitteret i Dansk Arkitektforening 1946. Desuden medlem af komitéen for Nordisk Byggedag, af Boligministeriets udvalg vedr. generalbeskrivelser m.m. og vurderingsmand i Københavns Kreditforening. Han bar en række udenlandske ordener.

Marstrand blev gift 3. februar 1921 i Casablanca med Dorothea "Dorrit" Hedegaard (21. juni 1898 i Sørup Sogn ved Svendborg - 4. september 1984 på Frederiksberg), datter af læge Carl Peter Hedegaard og Marie Roedsted.

Han er begravet på Vestre Kirkegård.

Værker
I Marokko:
 Herregårdene Domaine Richards (1923); Domaine de la Borde (1924) og Domaine soc. d'exploitation marocaine (1926)
 Det danske Konsulat, Casablanca (1926)
 Katolsk klosterskole, Marrakech (1932)
 Fransk reformert kirke med annekser, Rabat (1933-35, udstillet 1931)
 Embedsbolig for den engelske generalkonsul, Rabat (1933)
 Pavillon til den fransk reformerte kirke, Casablanca (o. 1935)

I Danmark:
 Sengeløse Centralskole, Sengeløse (1942)
 Præstegård genopført efter en brand, Sengeløse (1942-43)
 Vintappervænget, Lyngby Hovedgade 95A-N, Kongens Lyngby (1945-46)
 11 enfamiliehuse, Peder Mathiassensvej 1-21, Birkerød (1947-48)
 14 parcelhuse, Vibevej 1-13, 2-14, Haslev (1948-49)
 10 parcelhuse, Tranevej 1-9, 4-12, Haslev (1948-49)
 3 parcelhuse, Stengårdsvej 8, 10, 23, Haslev (1948-49)
 Parkbebyggelsen Bistruplund 1-33, 2-10, Vasevej 68A-70B, Birkerød (1949-50)
 Funktionærboliger til Sydøstsjællands Elektricitets A/S, Nordgården, Ringstedvej 58, Haslev (1949-50)
 Solbjerget 2-64, 3-63, Solbjergsvinget 2-6, Grøndalsvej 82-100, Birkerød (1950-53)
 Blokbebyggelsen Prøvesteenen, Strandvejen 62-96, Frederiksværk (1951-53)
 Bistrupskolen, Birkerød (1954-55, sammen med Tage Pullich)
 Desuden adskillige enfamiliehuse i Rødovre og i Kregme

Kilder

 Kraks Blå Bog 1957

Personer i Kraks Blå Bog (afdøde)
Paul
Personer fra Frederiksberg
Arkitekter fra Danmark
Danskere i 1900-tallet
Redaktører fra Danmark
Modernistiske arkitekter

redpajama_set_name: RedPajamaWikipedia


text:
Will You Benefit from Biden's Student Loan Relief?
• Relief Amounts
• Income Limitations
• Dependents of Another
• Pell Grant Recipients
• Repayment Pause
• Monthly Payment Reduction
• Cancellation of Debt Income
On August 24, President Biden announced a three-part plan to deal with student loan debt which includes, among other things, $20,000 in loan relief to borrowers with loans held by the Department of Education whose individual income is less than $125,000 ($250,000 for married couples) and who received a Pell Grant. Borrowers who meet those income standards but did not receive a Pell Grant in college can receive up to $10,000 in loan relief. Current students with loans are eligible for this debt relief.
TARGETED STUDENT LOAN DEBT RELIEF
Pell Grant Recipients
Amount To Be Forgiven
Up to $20,000
Income Limit
Married Filing Jointly $250,000
Others $125,000
Note: This is not a phaseout, $1 over the income limit ends the qualification.
Dependents of Another - Borrowers who are dependent students will be eligible for relief based on parental income, rather than their own income.
Who Will Benefit? – Since the forgiveness is targeted to lower income families, per a White House Fact Sheet, nearly every Pell Grant recipient comes from a family that made less than $60,000 a year. Based on that at least 93% of Pell Grant recipients have income less than $60,000 and would qualify for the $20,000 forgiveness.
DISTRIBUTION OF PELL GRANT RECIPIENTS BY INCOME
$30,001 through $59,999
$60,000 or more
Apparently the White House used rounded numbers thus the total is not 100%
The Department of Education estimates that, among borrowers who are no longer in college, nearly 90% of relief dollars will go to those earning less than $75,000 a year.
Repayment Pause – Repayments were previously paused as part of the COVID relief. That pause has been extended one last time until December 31, 2022. Borrowers should plan to resume payments in January 2023.
Monthly Payments Cuts - The program would also cut monthly payments in half for under-graduate loans. The Department of Education is proposing a new income-driven repayment plan that protects more low-income borrowers from making any payments and caps monthly payments for undergraduate loans at 5% of a borrower's discretionary income—half of the rate that borrowers must pay now under most existing plans. This means that the average annual student loan payment will be lowered by more than $1,000 for both current and future bor-rowers.
It is estimated that nearly 8 million borrowers will be eligible to receive automatic relief because income data is already available to the U.S. Department of Education. If not, a borrower will be able to provide that information when the department makes a simple application available in the coming weeks. Watch for additional details.
Normally, per the tax code, when debt is forgiven the amount relived is treated as taxable income. That issue is not addressed in the Fact Sheet from the White House.
If you have questions, please give this office a call.


text:
Marcum is committed to fostering a culture that is both diverse and inclusive
Marcum is committed to fostering a culture that is both diverse and inclusive — one that encourages and enables all associates and partners to be successful.
At Marcum diversity, equity, and inclusion aren't just buzzwords. We are laser-focused on achieving representation of diverse talents at all levels across our workforce. We are also committed to fostering an environment where associates feel a strong sense of belonging. This is achieved through our numerous Associate Resource Groups (ARGs). Our ARGs are pillars of our community that not only help to celebrate diversity but also promote leadership, professional development, and mentorship opportunities.
Marcum DEI Events
In addition to our ARGs, Marcum also sponsors regular Firm-wide DEI events to continue to educate and build awareness on critical topics.
A national Diversity, Equity and Inclusion (DEI) Steering Committee comprised of Firm leaders oversees a rich program of activities and initiatives implemented at the local level in the Firm's offices across the country. Local activities and implementation of national initiatives are managed by regional DEI boards.
Over the Years, We've Helped Launch Many Successful Careers!
Providence Business News interviewed DEI Director Pauline Vesleno and Chief HR Officer Molly Crane for a profile on Marcum's diversity programs, celebrating the Firm's honor as a DEI leader.
Marcum LLP Honored for Diversity, Equity & Inclusion
Yahoo! and other news outlets covered Marcum's partnership with BurgerFi and Anthony's to provide relief for those affected by Hurricane Ian.
HR Senior Manager Erica Marcantonio was interviewed by the Hartford Business Journal for a story on companies' changing office space needs in the age of remote work.
Marcum Promotes 37 to Partner
CPA Practice Advisor reported on the largest class of partner promotions in Marcum's history.
The New York State Brewers Association published a think-piece by Senior Manager David Oksenhorn, about diversity, equity and inclusion in the craft beer industry.
Accounting Today announced the formation of Marcum's Diversity Scholarship Fund for college students from underrepresented groups.
Marcum was the first national accounting firm to establish a practice dedicated to serving the highly specialized needs of the LGBTQ community and others not fitting traditional definitions. Marcum's Modern Family & LGBT Services group is nationally recognized as the thought leader in the specialty area of tax compliance and consulting services for high net worth modern families, same-sex couples, and LGBT individuals.
Leadership & Collaboration
Collaboration & Networking
Marcum women are active in numerous industry organizations and professional events devoted to advancing a diverse workforce, both inside and outside of the accounting profession. Marcum women have leadership roles in the following, among others:
AICPA Women's Global Leadership Summit
Blue River Partners Blue Impact
CalCPA Education Foundation Women's Leadership Forum
Federation of Protestant Welfare Agencies Female Wave of Change
Financial Executive Women (FEW)
Forum of Executive Women
George Washington University Women in Business Conference
Healthcare Financial Management Association Women in Leadership
HIA-LI Women Leading the Way
Illinois CPA Society Women's Committee
Moxxie Network
NYSSCPA Nassau Chapter Women's Focus Group
Wealth Dimensions
Women's White Collar Defense Association (WWCDA)
Marcum supports a variety organizations focused on promoting and celebrating diversity. Some of the organizations we support include:
Association of Latino Professionals in Finance and Accounting (ALPFA)
Capital Pride Alliance
Career Opportunities in the Accounting Profession (COAP)
CEO Action for Diversity & Inclusion
Georgetown University Center for Public & Nonprofit Leadership Racial Equity Working Group
National Association of Black Accountants (NABA)
Vital Voices
Marcum Women's Forum
The Marcum Women's Forum, geared towards impactful women leaders from across the business and nonprofit spectrum, features panel discussions and keynote speakers focused on women's health and women having a voice. The forum is presented in Marcum markets across the U.S. by the Marcum Women's Initiative.
Speakers have included these world-class women leaders:
Barbara Bradley Baekgaard, co-founder of Vera Bradley Designs Inc.
Erin Brokovich, environmental activist
Chelsea Clinton, global health advocate
Hillary Rodham Clinton, former U.S. Secretary of State
Laura Fredricks, JD, founder & CEO of THE ASK
Carey Lohrenz, U.S. Navy's first female F14 fighter pilot and author of Fearless Leadership: High-Performance Lessons from the Flight Deck
Kakenya Ntaiya, founder and director of Kakenya's Dream
Diane Rehm, former host of the Diane Rehm Show, National Public Radio
Jeanne Rizzo, former CEO of Breast Cancer Prevention Partners
Melanne Verveer, director of Georgetown University's Institute for Women, Peace and Security
Stay connected with Marcum.
Follow us on social media to keep in touch.
Marcum Women's Initiative
The Marcum Women's Initiative is dedicated to the success of women at Marcum at all levels.
The program was established to invigorate a compelling work environment and enhanced career opportunities for women at the Firm, through national and local programs and activities that motivate, support, advance, retain, and reward women associates and partners along their career paths.
The initiative's objectives are to:
Foster an inclusive environment where women can thrive.
Increase networking opportunities for women.
Connect Marcum women to women in the marketplace.
Develop mentoring relationships.
Further the development and advancement of women.
Provide a forum for women to share experiences and support each other in personal and professional pursuits.
Encourage and support women throughout their development at the Firm.
I have clients from all over the world, and it is key for them to be with a firm that not only represents them but also understands their culture and concerns.
Fiorella "Fio" Belardi Senior Manager, International Tax - Miami, FL
Joined Marcum in 2016
I've always been passionate about start-ups, technology and biotech. Over my 14 years with the Firm, I've been able to grow my practice to focus primarily in these areas, growing as a professional and a leader in the process. I am so grateful for these opportunities.
Marilea Campomizzi Director, Assurance Services - Cleveland, OH
Working for a firm that allows me to integrate and blend work and life is key to ensuring I maintain my sanity. I couldn't be more grateful for the Firm's flexibility and support.
Jennifer Carro Director of Client Experience - National
Upon interviewing with Marcum, I felt that this was it. I met with eight people and did not feel that it was a job interview, but rather a conversation. Marcum allows me the flexibility to be both a professional and a mother.
Katerina Gewarges Supervisor, Tax & Business Services - Fort Lauderdale, FL
Within my first three months at Marcum, I have been able to expand my knowledge of accounting and professional development beyond what I anticipated.
Nicholas Martin Manager, Assurance Services - Miami, FL
I have been working at Marcum for over three years. I'm so happy I joined a firm who truly invests in their employees. Marcum has an exceptional training program and is very dedicated to developing their team.
Heather Santonino Partner, Tax & Business Services - Melville, NY


Christman > Company > Leadership > Douglas J. Peters, P.E.
Doug oversees all operations for Christman Constructors, Inc., Christman's self-perform affiliate. In this role, he provides leadership for all of the projects performed, as well as safety leadership in which Christman Constructors, Inc. is generally acknowledged as one of the industry's leaders. Doug joined Christman in 2001 as a project manager, and was promoted to Director of Concrete Operations in 2007 and to Vice President in 2009. Prior to joining Christman, Doug spent four years with the Army Corps of Engineers and was a commissioned officer. After serving with the U.S. Army, he worked for a national concrete construction services firm. Doug is a member of the American Society of Concrete Contractors Safety and Risk Management Council and is an Associate Member of the American Concrete Institute (ACI) Committee 207-Mass Concrete and ACI Committee 347-Formwork. He is a registered Professional Engineer in Michigan and Virginia. He is also a member of the Christman Constructors board of directors.


text:
DCW Chief Dragged By Car In AIIMS, FIR Registered
By Sujal Sharma
DCW Chief Swati Maliwal
The National Commission for Women (NCW) On Thursday took the perception of the media reports with respect to the Delhi Commission for Women (DCW) Chief Swati Maliwal being attacked and later hauled by a vehicle for 10-15 meters.
Director Rekha Sharma has kept in touch with the Magistrate of Police, Delhi to mediate regarding this situation and to guarantee that a severe move is made against the blamed individual and ensured that the report should be notified to the Commission in 2 days. DCW chief was purportedly attacked and later dragged when her hand hindered out in his vehicle's window at around 3:11 am opposite AIIMS gate no 2.
As per the police, the denounced has been arrested and the vehicle engaged in the occurrence has been seized regarding this situation.
"The Commission has taken cognizance of the matter. Chairperson Ms. Rekha Sharma has written to the Commissioner of Police, Delhi to personally intervene in the matter and to ensure that strict action is taken against the accused person. A detailed action taken report must be apprised to the Commission within 2 days," the NCW said in a statement
Earlier, the Delhi Police said that it has captured one individual regarding an occurrence in which DCW chief Maliwal claimed that she was "attacked" and "hauled by a vehicle" for a few meters opposite AIIMS in the national capital in the early hours of the day.
The charge has been identified as 47-year-old Harish Chandra.
His vehicle was additionally seized by the Delhi Police.
DCP South Chandan Chowdhary expressed that as per Maliwal she was with her group outside the All India Institute Of Medical Sciences (AIIMS) around here at around 2.45 am the point at which the captured charge distinguished as Harish Chandra, a resident of Sangam Vihar region, was drunk.
The DCW chief in her statement to police claimed that the one who was driving a white-shaded vehicle halted his vehicle close to where she was standing and "made revolting motions" at her.
He then, at that point, coaxed her to sit inside his vehicle, asserted Maliwal.
At the point when she condemned him, the man supposedly disappeared but returned a brief time and again rehashed his activities, police said.
She was remaining with her group at Gate number 2 of the AIIMS which comes under the Kotla Police headquarters region.
As indicated by Maliwal's objection, when she was remaining on the trail, a white-shaded vehicle moved toward her whose driver offered her a lift and began demanding that she sit inside the vehicle.
"When she refused again and went near the driver's side window to reprimand him the man rolled up the car's glass window and her hand got stuck and she got dragged for about 10-15 meters," the DCP Chowdhary said.
The police official said that a PCR call was gotten at around 3.12 am and a police group including ACP Hauz Khas arrived at the spot at around 3.20 am the blame was captured.
"The police took a written complaint from Maliwal and sent her and the accused for medical examination," the DCP added.
Further examination concerning the matter is in progress. Maliwal's cases come days following a 20-year-person recognized as Anjali died after supposedly being hauled in the Kanjhawala area of Delhi for a few kilometers.
hauled
kanjahwala
NCW
Sujal Sharma
Here's what real estate developers have to say about Union Budget