44 results on '"M. Weingart"'
Search Results
2. Endothelial-Derived Highly-Sulfated Chondroitin Sulfate Deposition in the Hippocampus as a Driver of Sepsis-Induced Delirium
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Paco S. Herson, James E. Orfila, Kaori Oshima, Fuming Zhang, Eric P. Schmidt, M. Weingart, Joseph A. Hippensteel, Nuala J. Meyer, Robert J. Linhardt, and Brian J. Anderson
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medicine.medical_specialty ,Chemistry ,Hippocampus ,medicine.disease ,Sepsis ,chemistry.chemical_compound ,Sulfation ,Endocrinology ,Internal medicine ,medicine ,Delirium ,Chondroitin sulfate ,medicine.symptom ,Deposition (chemistry) - Published
- 2021
3. Efficacy and Safety of Lumateperone for Treatment of Schizophrenia. A Randomized Clinical Trial (translation into Russian)
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C. U. Correll, R. E. Davis, M. Weingart, A.V. Moskvitin, and M.P. Marachev
- Abstract
Importance: Individuals living with schizophrenia are affected by cardiometabolic, endocrine, and motor adverse effects of current antipsychotic medications. Lumateperone is a serotonin, dopamine, and glutamate modulator with the potential to treat schizophrenia with few adverse effects. Objective: To examine the efficacy and safety of lumateperone for the short-term treatment of schizophrenia. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, phase 3 clinical trial was conducted from November 13, 2014, to July 20, 2015, with data analyses performed from August 13 to September 15, 2015. Patients with schizophrenia who were aged 18 to 60 years and were experiencing an acute exacerbation of psychosis were enrolled from 12 clinical sites in the United States. Interventions: Patients were randomized 1:1:1 (150 patients in each arm) to receive lumateperone tosylate, 60 mg; lumateperone tosylate, 40 mg (equivalent to 42 or 28 mg, respectively, of the active moiety lumateperone); or placebo once daily for 4 weeks. Main Outcomes and Measures: The prespecified primary efficacy end point was mean change from baseline to day 28 in the Positive and Negative Syndrome Scale (PANSS) total score vs placebo. The key secondary efficacy measure was the Clinical Global Impression–Severity of Illness (CGI-S) score. The PANSS subscale scores, social function, safety, and tolerability were also assessed. Results: The study comprised 450 patients (mean [SD] age, 42.4 [10.2] years; 346 [77.1%] male; mean [SD] baseline PANSS score, 89.8 [10.3]; mean [SD] baseline CGI-S score, 4.8 [0.6]). In the prespecified modified intent-to-treat efficacy analysis (n = 435), 42 mg of lumateperone met the primary and key secondary efficacy objectives, demonstrating a statistically significant improvement vs placebo from baseline to day 28 on the PANSS total score (least-squares mean difference [LSMD], −4.2; 95% CI, −7.8 to −0.6; P = .02; effect size [ES], −0.3) and the CGI-S (LSMD, −0.3; 95% CI, −0.5 to −0.1; P = .003; ES, −0.4). For 28 mg of lumateperone, the LSMD from baseline to day 28 was −2.6 (95% CI, −6.2 to 1.1; P = .16; ES, −0.2) on the PANSS total score and −0.2 (95% CI, −0.5 to 0.0; P = .02; ES, −0.3) on the CGI-S. Both lumateperone doses were well tolerated without clinically significant treatment-emergent motor adverse effects or changes in cardiometabolic or endocrine factors vs placebo. Conclusions and Relevance: Lumateperone demonstrated efficacy for improving the symptoms of schizophrenia and had a favorable safety profile. Trial Registration: ClinicalTrials.gov identifier: NCT02282761
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- 2020
- Full Text
- View/download PDF
4. High Prevalence of Non-Tuberculous Mycobacterial Lung Disease in Patients with Sjogren's Syndrome
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M. Weingart, S. Choi, E.D. Chan, T. Truong, Q. Li, and Y. Kwon
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Non tuberculous mycobacterial ,medicine.medical_specialty ,High prevalence ,business.industry ,Lung disease ,Internal medicine ,medicine ,In patient ,Sjogren s ,business ,Gastroenterology - Published
- 2020
5. In vitro comparison of two encapsulated pancreatin preparations
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M. Weingart, S. Hartmann, and M. Orera-Peña
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Chromatography ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,Medicine ,business ,In vitro - Published
- 2020
6. P.671 Efficacy and safety of lumateperone tosylate 42mg in the treatment of schizophrenia: A pooled analysis of phase 2 and 3 studies
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J.M. Kane, K.E. Vanover, S. Durgam, M. Weingart, R. Davis, A. Satlin, and C. Tamminga
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Pharmacology ,Psychiatry and Mental health ,Neurology ,Pharmacology (medical) ,Neurology (clinical) ,Biological Psychiatry - Published
- 2019
7. P.673 Results from a 12-month open-label safety study of lumateperone (ITI-007) in patients with stable symptoms of schizophrenia
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C.U. Correll, K.E. Vanover, S. Durgam, M. Weingart, R. Davis, and A. Satlin
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Pharmacology ,Psychiatry and Mental health ,Neurology ,Pharmacology (medical) ,Neurology (clinical) ,Biological Psychiatry - Published
- 2019
8. Lumateperone (ITI-007): a novel investigational agent with broad therapeutic potential across multiple neuropsychiatric disorders
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Christoph U. Correll, S. Mates, J. Saillard, M. Weingart, C. O’Gorman, S. Glass, Robert E. Davis, and K.E. Vanover
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Pharmacology ,business.industry ,030226 pharmacology & pharmacy ,03 medical and health sciences ,Psychiatry and Mental health ,0302 clinical medicine ,Neurology ,Lumateperone ,Medicine ,Pharmacology (medical) ,Neurology (clinical) ,business ,Neuroscience ,030217 neurology & neurosurgery ,Biological Psychiatry - Published
- 2017
9. HIGH GRADE GLIOMAS AND DIPG
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C. F. Classen, D. William, M. Linnebacher, A. Farhod, W. Kedr, B. Elsabe, S. Fadel, S. Van Gool, S. De Vleeschouwer, C. Koks, A. Garg, M. Ehrhardt, M. Riva, P. Agostinis, N. Graf, T.-W. Yao, Y. Yoshida, J. Zhang, T. Ozawa, D. James, T. Nicolaides, R. Kebudi, F. B. Cakir, O. Gorgun, F. Y. Agaoglu, E. Darendeliler, A. Al-Kofide, E. Al-Shail, Y. Khafaga, H. Al-Hindi, M. Dababo, A. U. Haq, M. Anas, M. G. Barria, K. Siddiqui, M. Hassounah, M. Ayas, S. V. van Zanten, M. Jansen, D. van Vuurden, M. Huisman, D. Vugts, O. Hoekstra, G. van Dongen, G. Kaspers, J. Cockle, E. Ilett, K. Scott, A. Bruning-Richardson, S. Picton, S. Short, A. Melcher, M. Benesch, M. Warmuth-Metz, A. O. von Bueren, M. Hoffmann, T. Pietsch, R.-D. Kortmann, M. Eyrich, S. Rutkowski, M. C. Fruhwald, J. Faber, C. Kramm, M. Porkholm, L. Valanne, T. Lonnqvist, S. Holm, B. Lannering, P. Riikonen, D. Wojcik, A. Sehested, N. Clausen, A. Harila-Saari, E. Schomerus, H. K. Thorarinsdottir, P. Lahteenmaki, M. Arola, H. Thomassen, U. M. Saarinen-Pihkala, S.-M. Kivivuori, P. Buczkowicz, C. Hoeman, P. Rakopoulos, S. Pajovic, A. Morrison, E. Bouffet, U. Bartels, O. Becher, C. Hawkins, T. W. A. Gould, C. V. Rahman, S. J. Smith, D. A. Barrett, K. M. Shakesheff, R. G. Grundy, R. Rahman, N. Barua, D. Cronin, S. Gill, S. Lowisl, A. Hochart, C.-A. Maurage, N. Rocourt, M. Vinchon, O. Kerdraon, F. Escande, J. Grill, V. K. Pick, P. Leblond, G. Burzynski, T. Janicki, S. Burzynski, A. Marszalek, N. Ramani, W. Zaky, G. Kannan, A. Morani, D. Sandberg, L. Ketonen, O. Maher, F. Corrales-Medina, H. Meador, S. Khatua, M. Brassesco, L. Delsin, G. Roberto, C. Silva, L. Ana, E. Rego, C. Scrideli, K. Umezawa, L. Tone, S. J. Kim, C.-Y. Kim, I.-A. Kim, J. H. Han, B.-S. Choi, H. S. Ahn, H. S. Choi, F. Haque, R. Layfield, R. Grundy, L. Gandola, E. Pecori, V. Biassoni, E. Schiavello, C. Chiruzzi, F. Spreafico, P. Modena, F. Bach, E. Pignoli, M. Massimino, M. Drogosiewicz, B. Dembowska-Baginska, E. Jurkiewicz, I. Filipek, M. Perek-Polnik, E. Swieszkowska, D. Perek, S. Bender, D. T. Jones, H.-J. Warnatz, B. Hutter, T. Zichner, J. Gronych, A. Korshunov, R. Eils, J. O. Korbel, M.-L. Yaspo, P. Lichter, S. M. Pfister, S. Yadavilli, O. J. Becher, M. Kambhampati, R. J. Packer, J. Nazarian, F. C. Lechon, L. Fowkes, K. Khabra, L. M. Martin-Retortillo, L. V. Marshall, S. Vaidya, D.-M. Koh, M. O. Leach, A. D. Pearson, S. Zacharoulis, D. Schrey, G. Barone, E. Panditharatna, M. Stampar, A. Siu, H. Gordish-Dressman, J. Devaney, E. I. Hwang, A. H. Chung, R. K. Mittapalli, W. F. Elmquist, D. Castel, M.-A. Debily, C. Philippe, N. Truffaux, K. Taylor, R. Calmon, N. Boddaert, L. Le Dret, P. Saulnier, L. Lacroix, A. Mackay, C. Jones, S. Puget, C. Sainte-Rose, T. Blauwblomme, P. Varlet, N. Entz-Werle, C. Maugard, G. Bougeard, A. Nguyen, M. P. Chenard, A. Schneider, M. P. Gaub, M. Tsoli, A. Vanniasinghe, P. Luk, P. Dilda, M. Haber, P. Hogg, D. Ziegler, S. Simon, M. Monje, K. Gurova, A. Gudkov, M. Zapotocky, M. Churackova, B. Malinova, J. Zamecnik, M. Kyncl, M. Tichy, A. Puchmajerova, J. Stary, D. Sumerauer, J. Boult, M. Vinci, L. Perryman, G. Box, A. Jury, S. Popov, W. Ingram, S. Eccles, S. Robinson, S. Emir, H. A. Demir, C. Bayram, F. Cetindag, G. B. Kabacam, A. Fettah, J. Li, Y. Jamin, C. Cummings, J. Bamber, R. Sinkus, M. Nandhabalan, L. Bjerke, A. Burford, A. von Bueren, M. Baudis, P. Clarke, I. Collins, P. Workman, N. Olaciregui, J. Mora, A. Carcaboso, A. Bullock, M. Alonso, C. de Torres, O. Cruz, E. Pencreach, F. M. Moussalieh, D. Guenot, I. Namer, I. Pollack, R. Jakacki, L. Butterfield, R. Hamilton, A. Panigrahy, D. Potter, A. Connelly, S. Dibridge, T. Whiteside, H. Okada, S. Ahsan, E. Raabe, M. Haffner, K. Warren, M. Quezado, L. Ballester, C. Eberhart, F. Rodriguez, C. Ramachandran, S. Nair, K.-W. Quirrin, Z. Khatib, E. Escalon, S. Melnick, M. Hofmann, I. Schmid, T. Simon, E. Maass, A. Russo, G. Fleischhack, M. Becker, H. Hauch, A. Sander, C. Grasso, N. Berlow, L. Liu, L. Davis, E. Huang, P. Woo, Y. Tang, A. Ponnuswami, S. Chen, Y. Huang, M. Hutt-Cabezas, L. Dret, P. Meltzer, H. Mao, J. Abraham, M. Fouladi, M. N. Svalina, N. Wang, E. Hulleman, X.-N. Li, C. Keller, P. T. Spellman, R. Pal, M. H. A. Jansen, A. C. P. Sewing, T. Lagerweij, D. J. Vuchts, D. G. van Vuurden, V. Caretti, P. Wesseling, G. J. L. Kaspers, K. Cohen, M. Pearl, M. Kogiso, L. Zhang, L. Qi, H. Lindsay, F. Lin, S. Berg, J. Muscal, N. Amayiri, U. Tabori, B. Campbel, D. Bakry, M. Aronson, C. Durno, S. Gallinger, D. Malkin, I. Qaddumi, A. Musharbash, M. Swaidan, M. Al-Hussaini, S. Shandilya, C. McCully, R. Murphy, S. Akshintala, D. Cole, R. P. Macallister, R. Cruz, B. Widemann, R. Salloum, A. Smith, M. Glaunert, A. Ramkissoon, S. Peterson, S. Baker, L. Chow, J. Sandgren, S. Pfeifer, S. Popova, I. Alafuzoff, T. D. de Stahl, S. Pietschmann, M. J. Kerber, I. Zwiener, G. Henke, K. Muller, N. Y.-F. Sieow, R. H. M. Hoe, A. M. Tan, M. Y. Chan, S. Y. Soh, K. Burrell, Y. Chornenkyy, M. Remke, B. Golbourn, M. Barzczyk, M. Taylor, J. Rutka, P. Dirks, G. Zadeh, S. Agnihotri, R. Hashizume, Y. Ihara, N. Andor, X. Chen, R. Lerner, X. Huang, M. Tom, D. Solomon, S. Mueller, C. Petritsch, Z. Zhang, N. Gupta, T. Waldman, A. Dujua, J. Co, F. Hernandez, D. Doromal, M. Hegde, A. Wakefield, V. Brawley, Z. Grada, T. Byrd, K. Chow, S. Krebs, H. Heslop, S. Gottschalk, E. Yvon, N. Ahmed, G. Cornilleau, J. Paulsson, F. Andreiuolo, L. Guerrini-Rousseau, B. Geoerger, G. Vassal, A. Ostman, D. W. Parsons, L. R. Trevino, F. Gao, X. Shen, O. Hampton, M. Kosigo, P. A. Baxter, J. M. Su, M. Chintagumpala, R. Dauser, A. Adesina, S. E. Plon, D. A. Wheeler, C. C. Lau, G. Gielen, A. z. Muehlen, R. Kwiecien, J. Wolff, R. R. Lulla, J. Laskowski, S. Goldman, V. Gopalakrishnan, J. Fangusaro, M. Kieran, A. Fontebasso, S. Papillon-Cavanagh, J. Schwartzentruber, H. Nikbakht, N. Gerges, P.-O. Fiset, D. Bechet, D. Faury, N. De Jay, L. Ramkissoon, A. Corcoran, D. Jones, D. Sturm, P. Johann, T. Tomita, M. Nagib, A. Bendel, L. Goumnerova, D. C. Bowers, J. R. Leonard, J. B. Rubin, T. Alden, A. DiPatri, S. Browd, S. Leary, G. Jallo, M. D. Prados, A. Banerjee, A.-S. Carret, B. Ellezam, L. Crevier, A. Klekner, L. Bognar, P. Hauser, M. Garami, J. Myseros, Z. Dong, P. M. Siegel, W. Gump, K. Ayyanar, J. Ragheb, M. Krieger, E. Kiehna, N. Robison, D. Harter, S. Gardner, M. Handler, N. Foreman, B. Brahma, T. MacDonald, H. Malkin, S. Chi, P. Manley, P. Bandopadhayay, L. Greenspan, A. Ligon, S. Albrecht, K. L. Ligon, J. Majewski, N. Jabado, F. Cordero, K. Halvorson, I. Taylor, M. Hutt, M. Weingart, A. Price, M. Kantar, S. Onen, S. Kamer, T. Turhan, O. Kitis, Y. Ertan, N. Cetingul, Y. Anacak, T. Akalin, Y. Ersahin, G. Mason, C. Ho, F. Crozier, G. Vezina, R. Packer, E. Hwang, S. Gilheeney, N. Millard, K. DeBraganca, Y. Khakoo, K. Kramer, S. Wolden, M. Donzelli, C. Fischer, M. Petriccione, I. Dunkel, S. Afzal, A. Fleming, V. Larouche, S. Zelcer, D. L. Johnston, M. Kostova, C. Mpofu, J.-C. Decarie, D. Strother, L. Lafay-Cousin, D. Eisenstat, C. Fryer, J. Hukin, M. Hsu, J. Lasky, T. Moore, L. Liau, T. Davidson, R. Prins, T. Hassal, J. Baugh, J. Kirkendall, R. Doughman, J. Leach, B. Jones, L. Miles, D. Hargrave, T. Jacques, S. Savage, D. Saunders, R. Wallace, B. Flutter, D. Morgenestern, E. Blanco, K. Howe, M. Lowdell, E. Samuel, A. Michalski, J. Anderson, Y. Arakawa, K. Umeda, K.-i. Watanabe, T. Mizowaki, M. Hiraoka, H. Hiramatsu, S. Adachi, T. Kunieda, Y. Takagi, S. Miyamoto, S. Venneti, M. Santi, M. M. Felicella, L. M. Sullivan, I. Dolgalev, D. Martinez, A. Perry, P. W. Lewis, D. C. Allis, C. B. Thompson, and A. R. Judkins
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,03 medical and health sciences ,Abstracts ,0302 clinical medicine ,Text mining ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Published
- 2014
10. Characterization of nucleosome sediments for protein interaction studies by solid-state NMR spectroscopy
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U. B. le Paige, S. Xiang, M. M. R. M. Hendrix, Y. Zhang, G. E. Folkers, M. Weingarth, A. M. J. J. Bonvin, T. G. Kutateladze, I. K. Voets, M. Baldus, and H. van Ingen
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Electricity and magnetism ,QC501-766 - Abstract
Regulation of DNA-templated processes such as gene transcription and DNA repair depend on the interaction of a wide range of proteins with the nucleosome, the fundamental building block of chromatin. Both solution and solid-state NMR spectroscopy have become an attractive approach to study the dynamics and interactions of nucleosomes, despite their high molecular weight of ∼200 kDa. For solid-state NMR (ssNMR) studies, dilute solutions of nucleosomes are converted to a dense phase by sedimentation or precipitation. Since nucleosomes are known to self-associate, these dense phases may induce extensive interactions between nucleosomes, which could interfere with protein-binding studies. Here, we characterized the packing of nucleosomes in the dense phase created by sedimentation using NMR and small-angle X-ray scattering (SAXS) experiments. We found that nucleosome sediments are gels with variable degrees of solidity, have nucleosome concentration close to that found in crystals, and are stable for weeks under high-speed magic angle spinning (MAS). Furthermore, SAXS data recorded on recovered sediments indicate that there is no pronounced long-range ordering of nucleosomes in the sediment. Finally, we show that the sedimentation approach can also be used to study low-affinity protein interactions with the nucleosome. Together, our results give new insights into the sample characteristics of nucleosome sediments for ssNMR studies and illustrate the broad applicability of sedimentation-based NMR studies.
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- 2021
- Full Text
- View/download PDF
11. Dynamical Lattice QCD with Ginsparg-Wilson-Type Fermions
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T. Burch, D. Chakrabarti, C. Ehmann, C. Gattringer, M. Göckeler, C. Hagen, P. Hasenfratz, D. Hierl, C. B. Lang, M. Limmer, V. Maillart, T. Maurer, D. Mohler, F. Niedermayer, A. Schäfer, S. Solbrig, C. Weiermann, and M. Weingart
- Published
- 2008
12. 2+1 Flavor QCD simulated in the epsilon-regime in different topological sectors
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Andreas Schäfer, Vidushi Maillart, C. Weiermann, M. Weingart, Ferenc Niedermayer, Peter Hasenfratz, and Dieter Hierl
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Quantum chromodynamics ,Physics ,Nuclear and High Energy Physics ,Chiral perturbation theory ,High Energy Physics - Lattice (hep-lat) ,FOS: Physical sciences ,Lattice QCD ,Dirac operator ,Topology ,symbols.namesake ,High Energy Physics - Lattice ,Lattice constant ,symbols ,Order (group theory) ,Random matrix ,Eigenvalues and eigenvectors - Abstract
We generated configurations with the parametrized fixed-point Dirac operator D_{FP} on a (1.6 fm)^4 box at a lattice spacing a=0.13 fm. We compare the distributions of the three lowest k=1,2,3 eigenvalues in the nu= 0,1,2 topological sectors with that of the Random Matrix Theory predictions. The ratios of expectation values of the lowest eigenvalues and the cumulative eigenvalue distributions are studied for all combinations of k and nu. After including the finite size correction from one-loop chiral perturbation theory we obtained for the chiral condensate in the MSbar scheme Sigma(2GeV)^{1/3}=0.239(11) GeV, where the error is statistical only., Comment: 19 pages, 13 figures, added Sigma in MSbar
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- 2007
- Full Text
- View/download PDF
13. Preliminary results: Effect of whole-body cooling in patients with myasthenia gravis
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Alfred B. Gurney, Suzanne M. Schneider, Heidi M Weingart, M. Virginia Wilmerding, and Christine M. Mermier
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Adult ,Male ,medicine.medical_specialty ,Vital capacity ,Weakness ,Physical Therapy, Sports Therapy and Rehabilitation ,Isometric exercise ,Pulmonary function testing ,Upper Extremity ,Grip strength ,FEV1/FVC ratio ,Hypothermia, Induced ,Isometric Contraction ,Myasthenia Gravis ,medicine ,Humans ,Orthopedics and Sports Medicine ,Muscle, Skeletal ,Human body temperature ,Core (anatomy) ,business.industry ,Middle Aged ,Surgery ,Respiratory Function Tests ,Anesthesia ,Female ,medicine.symptom ,business - Abstract
Introduction: Local muscle cooling has been shown to reduce symptoms in some neuromuscular diseases. Purpose: To determine whether lowering body temperature using a cooling vest would result in improvement in muscle strength, subjective perceptions of weakness and fatigue, and pulmonary function in patients with generalized myasthenia gravis (MG). Methods: Patients (five female, one male) with generalized MG, aged 29-58 yr, were studied when mean body temperature was lowered (34.9 +/- 0.62[degrees]C) using a cooling vest (CT) and at normal body temperature (35.8 +/- 0.58[degrees]C) (NT). Isokinetic and isometric muscle strength and isokinetic endurance were measured using upper body muscle groups. The myasthenic muscle score (MMS) was performed to assess muscle impairment specific to MG patients. Pulmonary function measurements included forced vital capacity (FVC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP). The fatigue impact scale (FIS) was used to track subjective perceptions of fatigue. Core body and skin temperatures were measured throughout each NT and CT trial. Results: Mean body temperature (0.65core + 0.35skin) was reduced significantly following 30-45 min of cooling (NT = 35.76 +/- 0.58, CT= 34.96 +/- 0.62[degrees]C). The MMS and MIP increased significantly (NT = 91.9 vs CT = 96.3; and NT = 69.3 vs CT = 79.5 cm/H2O) with cooling. Although all other variables were not statistically different between temperature conditions, individual results for grip strength of the right hand, fatigue ratio for wrist extensors and shoulder internal and external rotators, FVC, and MEP showed improvement for the majority of the subjects. Conclusion: Cooling in patients with MG shows promise to decrease symptoms of weakness and fatigue, thus allowing increased muscle strength and endurance in some patients.
- Published
- 2006
14. Nearest neighbor analysis in one dimension
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S. Selvin and M. Weingart
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Best bin first ,Cover tree ,Computer science ,Nearest-neighbor chain algorithm ,Nearest neighbor search ,Nearest neighbour algorithm ,Ball tree ,Statistics ,Fixed-radius near neighbors ,Algorithm ,k-nearest neighbors algorithm - Abstract
Since its initial presentation by Clark and Evans, nearest neighbor analysis for spatial randomness has gained considerable popularity in fields as diverse as geography, ecology, archaeology, cell biology, forestry, meteorology, and epidemiology. Epidemiologists are often interested in determining whether disease cases are clustered, dispersed, or randomly distributed, since different patterns of disease incidence over time or space can provide dues to the etiology of the disease. An environmental hazard or a transmissable agent can produce a cluster of disease events, i.e. a set of events occurring unusually dose to each other in time, space, or both time and space. In spite of its wide applicability, few attempts have been made to adapt the nearest neighbor method to the analysis of points distributed along a line. This report outlines the theoretical derivation of the moments of the mean nearest neighbor distance in the one dimension case and the correction of its expected value in order to overcome the boundary problem. It presents the derivation of the moments of order statistics, for specific sample sizes and for the general case. These results are then used for the derivation of the moments of nearest neighbor distances, and for the derivation of the moments of the mean nearest neighbor distance. Then the boundary problem and an examination of five alternative ways to compensate for it in the calculation of the expected value of the mean nearest neighbor distance are discussed. Finally, the results from a large scale computer simulation which compares the various correction methods are presented.
- Published
- 1995
15. Global aspects of sunlight as a major energy source
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Jerome M. Weingart
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Engineering ,business.industry ,Natural resource economics ,Mechanical Engineering ,Environmental engineering ,Building and Construction ,Technology assessment ,Energy technology ,Pollution ,Industrial and Manufacturing Engineering ,Energy conservation ,Water resources ,General Energy ,Energy development ,Global network ,Electricity ,Electrical and Electronic Engineering ,business ,Energy source ,Civil and Structural Engineering - Abstract
To achieve and sustain a decent livable world for all is a central goal for human society. While an abundant supply of energy is not in itself a determinant of such a world, it is nevertheless essential. A careful inquiry suggests that sunlight could eventually be the primary and even exclusive source of heat, electricity and synthetic fuels for the entire world, continuously and eternally on a scale (upwards of 100 TW) generally regarded possible only with fusion or with fission via the fast breeder. This could be achieved through a global network of solar conversion facilities coupled with appropriate energy transport and storage systems, and appears to be possible within acceptable constraints on energy payback time, materials and water resources, capital investment, and available suitable land.
- Published
- 1979
16. Emerging Energy Technologies in an Island Environment: Hawaii
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John W. Shupe and Jerome M. Weingart
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business.industry ,Natural resource economics ,Fossil fuel ,Energy planning ,Indigenous ,Energy policy ,Renewable energy ,chemistry.chemical_compound ,Geography ,chemistry ,Environmental protection ,General Earth and Planetary Sciences ,Petroleum ,Energy supply ,business ,Energy source ,General Environmental Science - Abstract
Island communities have energy-supply problems that differ appreciably from those of major land masses. There is usually an absence of local fossil fuel reserves, such as oil, natural gas and coal, as well as a limited infrastructure for delivering energy. This lack of flexibility requires island communities to satisfy their energy demands with indigenous resources, plus whatever energy supply is imported by sea. In recent years, the energy needs of many island communities have been met almost entirely by seaborne petroleum. As imported oil has become increasingly more expensive and less secure, greater effort has been directed by some island communities toward the development of their local energy resources. A case study illustrates the progress made to date in one island area - Hawaii - in minimizing its near-total dependence on seaborne petroleum. However, there should be some spin-off of this experience to regional energy planning, not only to other island communities, but also to regions within developing countries that share many of these characteristics. 34 references, 6 figures, 6 tables.
- Published
- 1980
17. Radiolysis of aqueous oxygen-free solutions of tryptophan at various pH values
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M. Weingart, V. Vlasáková, and J. Kopoldová
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Aqueous solution ,Health, Toxicology and Mutagenesis ,Inorganic chemistry ,Public Health, Environmental and Occupational Health ,Tryptophan ,Deamination ,chemistry.chemical_element ,Pollution ,Oxygen ,High-performance liquid chromatography ,Analytical Chemistry ,Ammonia ,chemistry.chemical_compound ,Nuclear Energy and Engineering ,chemistry ,Radiolysis ,Radiology, Nuclear Medicine and imaging ,Irradiation ,Spectroscopy - Abstract
Gamma radiolysis of 10−2M aqueous oxygen-free tryptophan solutions irradiated at various pH values and in a N2O atmosphere was investigated. The values of the radiation losses of tryptophan and the yields of NH3 were determined. Using HPLC with an electrochemical detector the formation of hydroxylated radiation products of tryptophan was followed and the effect of pH on the radiolysis course discussed.
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- 1985
18. A Community Project
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Estelle M. Weingart
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Community project ,Management of Technology and Innovation ,Political science ,Developmental and Educational Psychology ,Environmental planning ,Education - Published
- 1929
19. [Automatized endothelium morphometry]
- Author
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C, Hartmann, M, Weingart, P, Dünner, and J P, Giraud
- Subjects
Cornea ,Microscopy ,Computers ,Humans ,Endothelium - Published
- 1982
20. Cost Data Management System (CDMS). User's guide. CDMS Version 1. 1
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J M Weingart
- Subjects
World Wide Web ,Database ,Computer science ,Management system ,computer.software_genre ,computer ,Cost database - Published
- 1984
21. Program for satellites: launch and learn
- Author
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M, Weingart
- Subjects
Hospital Administration ,Texas - Published
- 1965
22. Feed transition in larval rearing of bocudo, Steindachneridion scripta (Pisces, Pimelodidae), using Artemia spp. nauplii and artificial diet Transição alimentar na larvicultura do bocudo, Steindachneridion scripta (Pisces, Pimelodidae), com o uso de náuplios de Artemia spp. e dieta artificial
- Author
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W.B. Adamante, M. Weingartner, and A.P.O. Nuñer
- Subjects
bocudo ,Steindachneridion scripta ,transição alimentar ,alimentação de larvas ,feed transition ,larval feeding ,Animal culture ,SF1-1100 - Abstract
Feed transition of Steindachneridion scripta larvae was investigated using seven treatments in which the reference diet, Artemia spp. nauplii, was totally substituted for a 56% crude protein artificial diet in two-day intervals. Initially, all treatments were fed with Artemia spp. nauplii and, subsequently, during the transition period, feed was equally composed by Artemia sp. nauplii and artificial diet. Everyday, one of the treatments began the feed transition, which was implemented between the second and the eighth days of culturing. Two treatments were used as control: one exclusively fed Artemia spp. nauplii and another only with artificial diet. Total weight, total length, and survival rate were not influenced by the day in which feed transition was implemented (P>0.05), and their mean values (± SD) were 31.1±25.0mg, 13.3±1.5mm and 58.8±12.0%, respectively. This suggests that Steindachneridion scripta larvae adapted well the transition to artificial diet.A transição alimentar de larvas de Steindachneridion scripta foi investigada utilizando-se sete tratamentos, nos quais a dieta básica, composta por náuplios de Artemia spp., foi integralmente substituída, em intervalo de dois dias, por uma dieta artificial contendo 56% de proteína bruta. Inicialmente, todos os tratamentos receberam náuplios de Artemia spp. No período de transição alimentar, metade da alimentação foi formada por náuplios de Artemia spp. e metade por dieta artificial. A cada dia, um dos tratamentos entrou na fase de transição, que foi implementada entre o segundo e o oitavo dia de cultivo. Utilizaram-se dois tratamentos como controle; em um as larvas foram alimentadas, exclusivamente, com náuplios de Artemia spp. e em outro, somente, com dieta artificial. Peso total, comprimento total e sobrevivência não foram influenciados pelo dia de implantação da transição alimentar (P>0,05) e, apresentaram valores médios iguais a (± desvio padrão) 31,1±25,0mg, 13,3±1,5mm e 58,8±12,0%, respectivamente, sugerindo que as larvas Steindachneridion scripta aceitaram bem a transição alimentar para a dieta artificial.
- Published
- 2007
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23. New High-Precision Photoelectric Universal Polarimeter and Birefringence Compensator*
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S. J. Williamson, R. D. Andrews, and J. M. Weingart
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Physics ,Birefringence ,Linear polarization ,business.industry ,General Engineering ,Polarimeter ,Photoelectric effect ,Polarization (waves) ,Azimuth ,symbols.namesake ,Light intensity ,Optics ,Faraday effect ,symbols ,business - Abstract
A null-type photoelectric universal polarimeter (or ellipsometer) utilizing Faraday cells and a quarter-wave plate is described and its precision evaluated. For elliptically polarized light of small circularity (i.e., almost linearly polarized), the azimuth could be determined with a precision of 10 sec and the circularity to within 20 sec of arc. For light of large circularity (on the order of 35 deg), the corresponding precisions were 7 min (0.12 deg) for azimuth and 14 min (0.24 deg) for circularity. Errors due to a nonexact quarter-wave plate and nonperfect alignment of the compensator with respect to the elliptically polarized light are discussed. The use of this instrument as a high-precision Senarmont compensator for the measurement of birefringence is also described.
- Published
- 1964
24. Überlegungen zu Innovation und Entwicklung
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M. Gutmann and M. Weingarten
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Technology ,Social Sciences - Published
- 1998
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25. Bioimpedance as a tool for evaluating the body composition of suruvi (Steindachneridion scriptum)
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E. Zaniboni-Filho, S. Hermes-Silva, M. Weingartner, J. E. Jimenez, M. R. Borba, and D. M. Fracalossi
- Subjects
BIA ,bioimpedance analysis ,non-destructive method ,native species ,Science ,Biology (General) ,QH301-705.5 ,Zoology ,QL1-991 ,Botany ,QK1-989 - Abstract
Abstract Bioelectrical impedance analysis (BIA) is regarded as an important tool for evaluating the body composition of different animals in a rapid, non-destructive, and low-cost manner. A South American fish species, Steindachneridion scriptum, known as suruvi, was selected for study in this investigation. A protocol to produce fish with different body composition was used to allow BIA to adequately predict the body composition of suruvi. The fish were fed twice each day with two different diets; a low lipid diet (8.90%), and a high lipid diet (18.68%). These dietary differences allowed suruvi specimens with different body compositions to be produced. The BIA readings were determined using a Quantum X Bioelectrical Body Composition Analyzer. Two readings (dorsal and ventral) were obtained for each fish. After BIA readings were obtained, the proximate composition of the fish bodies for each individual was determined. All of the study data were used to establish correlation equations between proximate analyses and BIA values. Strong correlations were found for S. scriptum. The highest correlations were obtained for the following pairs of quantities, using BIA data from dorsal readings: moisture and resistance in series (R2 = 0.87); protein and resistance in series (R2 = 0.87); and ash and reactance in parallel (R2 = 0.82). We conclude that BIA is an effective method in determining the body composition of S. scriptum without sacrificing the fish. However, to expand the use of this new technology it is important to define strict BIA protocols to guarantee accurate estimates.
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26. White and green rust chimneys accumulate RNA in a ferruginous chemical garden.
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Helmbrecht V, Weingart M, Klein F, Braun D, and Orsi WD
- Abstract
Mechanisms of nucleic acid accumulation were likely critical to life's emergence in the ferruginous oceans of the early Earth. How exactly prebiotic geological settings accumulated nucleic acids from dilute aqueous solutions, is poorly understood. As a possible solution to this concentration problem, we simulated the conditions of prebiotic low-temperature alkaline hydrothermal vents in co-precipitation experiments to investigate the potential of ferruginous chemical gardens to accumulate nucleic acids via sorption. The injection of an alkaline solution into an artificial ferruginous solution under anoxic conditions (O
2 < 0.01% of present atmospheric levels) and at ambient temperatures, caused the precipitation of amakinite ("white rust"), which quickly converted to chloride-containing fougerite ("green rust"). RNA was only extractable from the ferruginous solution in the presence of a phosphate buffer, suggesting RNA in solution was bound to Fe2+ ions. During chimney formation, this iron-bound RNA rapidly accumulated in the white and green rust chimney structure from the surrounding ferruginous solution at the fastest rates in the initial white rust phase and correspondingly slower rates in the following green rust phase. This represents a new mechanism for nucleic acid accumulation in the ferruginous oceans of the early Earth, in addition to wet-dry cycles and may have helped to concentrate RNA in a dilute prebiotic ocean., (© 2023 The Authors. Geobiology published by John Wiley & Sons Ltd.)- Published
- 2023
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27. Alkaline vents recreated in two dimensions to study pH gradients, precipitation morphology, and molecule accumulation.
- Author
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Weingart M, Chen S, Donat C, Helmbrecht V, Orsi WD, Braun D, and Alim K
- Abstract
Alkaline vents (AVs) are hypothesized to have been a setting for the emergence of life, by creating strong gradients across inorganic membranes within chimney structures. In the past, three-dimensional chimney structures were formed under laboratory conditions; however, no in situ visualization or testing of the gradients was possible. We develop a quasi-two-dimensional microfluidic model of AVs that allows spatiotemporal visualization of mineral precipitation in low-volume experiments. Upon injection of an alkaline fluid into an acidic, iron-rich solution, we observe a diverse set of precipitation morphologies, mainly controlled by flow rate and ion concentration. Using microscope imaging and pH-dependent dyes, we show that finger-like precipitates can facilitate formation and maintenance of microscale pH gradients and accumulation of dispersed particles in confined geometries. Our findings establish a model to investigate the potential of gradients across a semipermeable boundary for early compartmentalization, accumulation, and chemical reactions at the origins of life.
- Published
- 2023
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28. The Effect of Frailty on Walking Recovery After Hip Fracture: A Secondary Analysis of the Community Ambulation Project.
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Mangione KK, Craik RL, Kenny A, Memaj A, Miller MF, Chen M, Weingart M, Orwig D, and Magaziner J
- Subjects
- Aged, Frail Elderly, Geriatric Assessment, Humans, Independent Living, Walking, Frailty epidemiology, Hip Fractures epidemiology
- Abstract
Background: The impact of frailty on walking recovery after hip fracture has not been reported. We describe the prevalence of frailty approximately 3 months after hip fracture, and identify the impact of baseline frailty on ambulation recovery., Methods: Data from the Community Ambulation Project, that examined the effects of 2 multicomponent home exercise programs on 6-minute walk test in participants post hip fracture, were used to reconstruct the 5-item frailty phenotype. We detailed the prevalence of frailty by subgroup and assessed the comparability between frailty groups for the categorical variable of achieving 300 m in 6-minute walk test (community ambulation threshold), and the continuous variable of total distance in 6-minute walk test before and after 16 weeks of intervention., Results: Of the 210 participants, 9% were nonfrail, 59% were prefrail, and 32% were frail. The odds of a nonfrail participant achieving the 300-m threshold were 14.4 (95% CI: 2.4-87.6) times the odds of a frail participant, while a prefrail participant's odds were 6.1 (95% CI: 1.3-28.4) times after controlling for treatment group and baseline walking distance. The nonfrail participants had an increase of 92.1 m from baseline to 16 weeks, the prefrail had a 50.8 m increase, and the frail group had the smallest increase of 36.6 m (p < .001 for all)., Conclusions: Prefrailty and frailty were highly prevalent in this sample of community-dwelling survivors of a recent hip fracture. Gains in walking distance and attaining a level of community ambulation were affected significantly by the level of baseline frailty., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2021
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29. Correction to: Comparative multidimensional molecular analyses of pediatric diffuse intrinsic pontine glioma reveals distinct molecular subtypes.
- Author
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Saratsis AM, Kambhampati M, Snyder K, Yadavilli S, Devaney JM, Harmon B, Hall J, Raabe EH, An P, Weingart M, Rood BR, Magge SN, MacDonald TJ, Packer RJ, and Nazarian J
- Abstract
The original version of this article unfortunately contained a mistake.
- Published
- 2020
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30. LIN28B promotes neuroblastoma metastasis and regulates PDZ binding kinase.
- Author
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Chen D, Cox J, Annam J, Weingart M, Essien G, Rathi KS, Rokita JL, Khurana P, Cuya SM, Bosse KR, Pilgrim A, Li D, Shields C, Laur O, Maris JM, and Schnepp RW
- Abstract
Neuroblastoma is an aggressive pediatric malignancy of the neural crest with suboptimal cure rates and a striking predilection for widespread metastases, underscoring the need to identify novel therapeutic vulnerabilities. We recently identified the RNA binding protein LIN28B as a driver in high-risk neuroblastoma and demonstrated it promotes oncogenic cell proliferation by coordinating a RAN-Aurora kinase A network. Here, we demonstrate that LIN28B influences another key hallmark of cancer, metastatic dissemination. Using a murine xenograft model of neuroblastoma dissemination, we show that LIN28B promotes metastasis. We demonstrate that this is in part due to the effects of LIN28B on self-renewal and migration, providing an understanding of how LIN28B shapes the metastatic phenotype. Our studies reveal that the let-7 family, which LIN28B inhibits, decreases self-renewal and migration. Next, we identify PDZ Binding Kinase (PBK) as a novel LIN28B target. PBK is a serine/threonine kinase that promotes the proliferation and self-renewal of neural stem cells and serves as an oncogenic driver in multiple aggressive malignancies. We demonstrate that PBK is both a novel direct target of let-7i and that MYCN regulates PBK expression, thus elucidating two oncogenic drivers that converge on PBK. Functionally, PBK promotes self-renewal and migration, phenocopying LIN28B. Taken together, our findings define a role for LIN28B in neuroblastoma metastasis and define the targetable kinase PBK as a potential novel vulnerability in metastatic neuroblastoma., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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31. Efficacy and Safety of Lumateperone for Treatment of Schizophrenia: A Randomized Clinical Trial.
- Author
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Correll CU, Davis RE, Weingart M, Saillard J, O'Gorman C, Kane JM, Lieberman JA, Tamminga CA, Mates S, and Vanover KE
- Subjects
- Adult, Antipsychotic Agents adverse effects, Double-Blind Method, Female, Heterocyclic Compounds, 4 or More Rings adverse effects, Humans, Male, Antipsychotic Agents therapeutic use, Heterocyclic Compounds, 4 or More Rings therapeutic use, Schizophrenia drug therapy
- Abstract
Importance: Individuals living with schizophrenia are affected by cardiometabolic, endocrine, and motor adverse effects of current antipsychotic medications. Lumateperone is a serotonin, dopamine, and glutamate modulator with the potential to treat schizophrenia with few adverse effects., Objective: To examine the efficacy and safety of lumateperone for the short-term treatment of schizophrenia., Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, phase 3 clinical trial was conducted from November 13, 2014, to July 20, 2015, with data analyses performed from August 13 to September 15, 2015. Patients with schizophrenia who were aged 18 to 60 years and were experiencing an acute exacerbation of psychosis were enrolled from 12 clinical sites in the United States., Interventions: Patients were randomized 1:1:1 (150 patients in each arm) to receive lumateperone tosylate, 60 mg; lumateperone tosylate, 40 mg (equivalent to 42 or 28 mg, respectively, of the active moiety lumateperone); or placebo once daily for 4 weeks., Main Outcomes and Measures: The prespecified primary efficacy end point was mean change from baseline to day 28 in the Positive and Negative Syndrome Scale (PANSS) total score vs placebo. The key secondary efficacy measure was the Clinical Global Impression-Severity of Illness (CGI-S) score. The PANSS subscale scores, social function, safety, and tolerability were also assessed., Results: The study comprised 450 patients (mean [SD] age, 42.4 [10.2] years; 346 [77.1%] male; mean [SD] baseline PANSS score, 89.8 [10.3]; mean [SD] baseline CGI-S score, 4.8 [0.6]). In the prespecified modified intent-to-treat efficacy analysis (n = 435), 42 mg of lumateperone met the primary and key secondary efficacy objectives, demonstrating a statistically significant improvement vs placebo from baseline to day 28 on the PANSS total score (least-squares mean difference [LSMD], -4.2; 95% CI, -7.8 to -0.6; P = .02; effect size [ES], -0.3) and the CGI-S (LSMD, -0.3; 95% CI, -0.5 to -0.1; P = .003; ES, -0.4). For 28 mg of lumateperone, the LSMD from baseline to day 28 was -2.6 (95% CI, -6.2 to 1.1; P = .16; ES, -0.2) on the PANSS total score and -0.2 (95% CI, -0.5 to 0.0; P = .02; ES, -0.3) on the CGI-S. Both lumateperone doses were well tolerated without clinically significant treatment-emergent motor adverse effects or changes in cardiometabolic or endocrine factors vs placebo., Conclusions and Relevance: Lumateperone demonstrated efficacy for improving the symptoms of schizophrenia and had a favorable safety profile., Trial Registration: ClinicalTrials.gov identifier: NCT02282761.
- Published
- 2020
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32. Dopamine D 2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia.
- Author
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Vanover KE, Davis RE, Zhou Y, Ye W, Brašić JR, Gapasin L, Saillard J, Weingart M, Litman RE, Mates S, and Wong DF
- Subjects
- Adult, Carbon Radioisotopes, Dopamine D2 Receptor Antagonists pharmacokinetics, Female, Humans, Male, Middle Aged, Neostriatum diagnostic imaging, Positron-Emission Tomography, Raclopride pharmacokinetics, Schizophrenia diagnostic imaging, Antipsychotic Agents pharmacokinetics, Butyrophenones pharmacokinetics, Neostriatum drug effects, Receptors, Dopamine D2 drug effects, Schizophrenia drug therapy
- Abstract
Dopamine D
2 receptor occupancy (D2 RO) is a key feature of all currently approved antipsychotic medications. However, antipsychotic efficacy associated with high D2 RO is often limited by side effects such as motor disturbances and hyperprolactinemia. Lumateperone (ITI-007) is a first-in-class selective and simultaneous modulator of serotonin, dopamine and glutamate in development for the treatment of schizophrenia and other disorders. The primary objective of the present study was to determine D2 RO at plasma steady state of 60 mg ITI-007, a dose that previously demonstrated antipsychotic efficacy in a controlled trial, administered orally open-label once daily in the morning for two weeks in patients with schizophrenia (N = 10) and after at least a two-week washout period from standard of care antipsychotics. D2 RO was determined using positron emission tomography with11 C-raclopride as the radiotracer. Mean peak dorsal striatal D2 RO was 39% at 60 mg ITI-007 occurring 1 h post-dose. Lumateperone was well-tolerated with a favorable safety profile in this study. There were no clinically significant changes in vital signs, ECGs, or clinical chemistry laboratory values, including prolactin levels. There were no adverse event reports of akathisia or other extrapyramidal motor side effects; mean scores on motor function scales indicated no motor disturbances with lumateperone treatment. This level of occupancy is lower than most other antipsychotic drugs at their efficacious doses and likely contributes to the favorable safety and tolerability profile of lumateperone with reduced risk for movement disorders and hyperprolactinemia. If approved, lumateperone may provide a new and safe treatment option for individuals living with schizophrenia.- Published
- 2019
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33. Deep Surgical Site Infections after Open Radical Cystectomy and Urinary Diversion Significantly Increase Hospitalisation Time and Total Treatment Costs.
- Author
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Wolters M, Oelke M, Lutze B, Weingart M, Kuczyk MA, Chaberny IF, and Graf K
- Subjects
- Case-Control Studies, Critical Care economics, Female, Health Care Costs, Humans, Length of Stay, Male, Prospective Studies, Surgical Wound Infection diagnosis, Tertiary Care Centers, Treatment Outcome, Urinary Bladder, Urinary Bladder Neoplasms surgery, Cystectomy adverse effects, Cystectomy economics, Hospitalization economics, Surgical Wound Infection etiology, Urinary Bladder Neoplasms economics, Urinary Diversion
- Abstract
Introduction: Deep surgical site infections (DSSI) usually require secondary treatments. The aim of this study was to compare the total length of hospitalisation (LOH), intensive care unit (ICU) duration, and total treatment costs in patients with DSSI versus without DSSI after open radical cystectomy (ORC) and urinary diversion., Material and Methods: Prospective case-control study in a tertiary care hospital in patients after ORC with urinary diversion during April 2008 to July 2012. DSSI was defined based on Centers for Disease Control and Prevention criteria. Matched-pair analysis for patients with versus without DSSI was done in 1:2 ratios. Patients with superficial surgical site infections (SSI) were excluded from analysis., Results: In total, 189 operations were performed. Thirty-eight patients (20.1%) developed SSI of which 28 patients (14.8%) had DSSI. Out of 28 patients, 27 (96.4%) were with DSSI and required surgical re-intervention. Due to insufficient matching criteria, 11 patients with DSSI were excluded from analyses. Consequently, 17 patients with DSSI were matched with 34 patients without DSSI. Significant differences were seen for median overall LOH (30 vs. 18 days, p < 0.001), median ICU duration (p = 0.024), and median overall treatment costs (€17,030 vs. €11,402, p = 0.011)., Conclusions: DSSI significantly increases LOH (67%) and treatment costs (49%), adding up to a financial loss for the hospital of approximately €5,500 in patients with DSSI., (© 2016 S. Karger AG, Basel.)
- Published
- 2017
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34. The transcriptional modulator HMGA2 promotes stemness and tumorigenicity in glioblastoma.
- Author
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Kaur H, Ali SZ, Huey L, Hütt-Cabezas M, Taylor I, Mao XG, Weingart M, Chu Q, Rodriguez FJ, Eberhart CG, and Raabe EH
- Subjects
- AC133 Antigen metabolism, Apoptosis, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Glioblastoma genetics, Glioblastoma pathology, HMGA2 Protein genetics, Humans, Neoplasm Invasiveness, Neoplastic Stem Cells pathology, Phenotype, RNA Interference, Signal Transduction, Spheroids, Cellular, Time Factors, Transfection, Tumor Burden, Up-Regulation, Xenograft Model Antitumor Assays, Cell Movement, Cell Proliferation, Glioblastoma metabolism, HMGA2 Protein metabolism, Neoplastic Stem Cells metabolism
- Abstract
Glioblastoma (GBM) contains a population of stem-like cells that promote tumor invasion and resistance to therapy. Identifying and targeting stem cell factors in GBM may lead to the development of more effective therapies. High Mobility Group AT-hook 2 (HMGA2) is a transcriptional modulator that mediates motility and self-renewal in normal and cancer stem cells. We identified increased expression of HMGA2 in the majority of primary human GBM tumors and cell lines compared to normal brain. Additionally, HMGA2 expression was increased in CD133+ GBM neurosphere cells compared to CD133- cells. Targeting HMGA2 with lentiviral short hairpin RNA (shRNA) led to decreased GBM stemness, invasion, and tumorigenicity. Ectopic expression of HMGA2 in GBM cell lines promoted stemness, invasion, and tumorigenicity. Our data suggests that targeting HMGA2 in GBM may be therapeutically beneficial., Competing Interests: None., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2016
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35. Comparative multidimensional molecular analyses of pediatric diffuse intrinsic pontine glioma reveals distinct molecular subtypes.
- Author
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Saratsis AM, Kambhampati M, Snyder K, Yadavilli S, Devaney JM, Harmon B, Hall J, Raabe EH, An P, Weingart M, Rood BR, Magge SN, MacDonald TJ, Packer RJ, and Nazarian J
- Subjects
- Adolescent, Adult, Blotting, Western, Brain Neoplasms genetics, Brain Neoplasms metabolism, Brain Stem Neoplasms genetics, Child, Child, Preschool, Cohort Studies, DNA Methylation, Female, Gene Expression Profiling, Glioma genetics, Histones genetics, Histones metabolism, Humans, Immunohistochemistry, Male, Proteomics, RNA, Messenger metabolism, Young Adult, Brain metabolism, Brain Stem Neoplasms metabolism, Glioma metabolism
- Abstract
Diffuse intrinsic pontine glioma (DIPG) is a highly morbid form of pediatric brainstem glioma. Here, we present the first comprehensive protein, mRNA, and methylation profiles of fresh-frozen DIPG specimens (n = 14), normal brain tissue (n = 10), and other pediatric brain tumors (n = 17). Protein profiling identified 2,305 unique proteins indicating distinct DIPG protein expression patterns compared to other pediatric brain tumors. Western blot and immunohistochemistry validated upregulation of Clusterin (CLU), Elongation Factor 2 (EF2), and Talin-1 (TLN1) in DIPGs studied. Comparisons to mRNA expression profiles generated from tumor and adjacent normal brain tissue indicated two DIPG subgroups, characterized by upregulation of Myc (N-Myc) or Hedgehog (Hh) signaling. We validated upregulation of PTCH, a membrane receptor in the Hh signaling pathway, in a subgroup of DIPG specimens. DNA methylation analysis indicated global hypomethylation of DIPG compared to adjacent normal tissue specimens, with differential methylation of 24 genes involved in Hh and Myc pathways, correlating with protein and mRNA expression patterns. Sequencing analysis showed c.83A>T mutations in the H3F3A or HIST1H3B gene in 77 % of our DIPG cohort. Supervised analysis revealed a unique methylation pattern in mutated specimens compared to the wild-type DIPG samples. This study presents the first comprehensive multidimensional protein, mRNA, and methylation profiling of pediatric brain tumor specimens, detecting the presence of two subgroups within our DIPG cohort. This multidimensional analysis of DIPG provides increased analytical power to more fully explore molecular signatures of DIPGs, with implications for evaluating potential molecular subtypes and biomarker discovery for assessing response to therapy.
- Published
- 2014
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36. LIN28A facilitates the transformation of human neural stem cells and promotes glioblastoma tumorigenesis through a pro-invasive genetic program.
- Author
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Mao XG, Hütt-Cabezas M, Orr BA, Weingart M, Taylor I, Rajan AK, Odia Y, Kahlert U, Maciaczyk J, Nikkhah G, Eberhart CG, and Raabe EH
- Subjects
- Animals, Brain Neoplasms metabolism, Brain Neoplasms pathology, Carcinogenesis genetics, Cell Transformation, Neoplastic pathology, DNA-Binding Proteins metabolism, Down-Regulation, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Glioblastoma metabolism, Glioblastoma pathology, HEK293 Cells, Humans, Mice, Mice, Nude, MicroRNAs genetics, Neoplastic Stem Cells metabolism, Neural Stem Cells metabolism, RNA-Binding Proteins, Snail Family Transcription Factors, Transcription Factors genetics, Transcription Factors metabolism, Xenograft Model Antitumor Assays, Brain Neoplasms genetics, Cell Transformation, Neoplastic genetics, DNA-Binding Proteins genetics, Glioblastoma genetics, Neoplastic Stem Cells pathology, Neural Stem Cells pathology
- Abstract
The cellular reprogramming factor LIN28A promotes tumorigenicity in cancers arising outside the central nervous system, but its role in brain tumors is unknown. We detected LIN28A protein in a subset of human gliomas observed higher expression in glioblastoma (GBM) than in lower grade tumors. Knockdown of LIN28A using lentiviral shRNA in GBM cell lines inhibited their invasion, growth and clonogenicity. Expression of LIN28A in GBM cell lines increased the number and size of orthotopic xenograft tumors. LIN28A expression also enhanced the invasiveness of GBM cells in vitro and in vivo. Increasing LIN28A was associated with down-regulation of tumor suppressing microRNAs let-7b and let-7g and up-regulation of the chromatin modifying protein HMGA2. The increase in tumor cell aggressiveness in vivo and in vitro was accompanied by an upregulation of pro-invasive gene expression, including SNAI1. To further investigate the oncogenic potential of LIN28A, we infected hNSC with lentiviruses encoding LIN28A together with dominant negative R248W-TP53, constitutively active KRAS and hTERT. Resulting subclones proliferated at an increased rate and formed invasive GBM-like tumors in orthotopic xenografts in immunodeficient mice. Similar to LIN28A-transduced GBM neurosphere lines, hNSC-derived tumor cells showed increased expression of HMGA2. Taken together, these data suggest a role for LIN28A in high grade gliomas and illustrate an HMGA2-associated, pro-invasive program that can be activated in GBM by LIN28A-mediated suppression of let-7 microRNAs.
- Published
- 2013
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37. A meta-analysis of occupational trichloroethylene exposure and liver cancer.
- Author
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Alexander DD, Kelsh MA, Mink PJ, Mandel JH, Basu R, and Weingart M
- Subjects
- Case-Control Studies, Cohort Studies, Humans, Trichloroethylene pharmacology, Liver Neoplasms chemically induced, Occupational Exposure adverse effects, Trichloroethylene poisoning
- Abstract
Objective: Findings from epidemiologic studies of trichloroethylene (TCE) exposure and liver cancer have been inconsistent. To quantitatively evaluate this association and to examine sources of heterogeneity, we conducted a meta-analysis of occupational studies of TCE exposure and liver/biliary tract cancer., Methods: We identified 14 occupational cohort studies of TCE exposed workers and one case-control study that met our inclusion criteria. Nine studies specifically identified TCE as a workplace exposure, and were classified as Group I cohort studies. Subcohorts of workers, identified within eight of these studies as more likely exposed to TCE than the total cohort, were analyzed separately., Results: The combined liver/biliary cancer summary relative risk estimate (SRRE) for all studies was 1.08 (95% CI 0.91-1.29; heterogeneity (H)-P-value=0.12). For the total study populations in the Group I cohorts, the SRRE was 1.14 (95% CI 0.93-1.39; H-P-value=0.05) and for the subcohorts, the SRRE was 1.30 (95% CI 1.09-1.55). Within this subcohort analysis, the association for the European studies of workers from various industries (SRRE=1.38; based on four studies) was higher than the association for the US studies of aerospace and aircraft workers (SRRE=0.97, based on four studies)., Conclusion: Although positive associations were observed for some analyses, results were inconsistent across occupational groups (aerospace/aircraft vs. other industries combined), study location, and incidence versus mortality endpoints. In addition, exposure-response trends were not observed consistently across studies. Interpretation is also limited by the potential impact of uncontrolled confounding by other occupational or lifestyle exposures such as smoking or alcohol consumption. Given these limitations, the currently available epidemiologic data are not sufficient to support a causal relation between occupational TCE exposure and liver/biliary cancer.
- Published
- 2007
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38. Occupational trichloroethylene exposure and non-Hodgkin's lymphoma: a meta-analysis and review.
- Author
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Mandel JH, Kelsh MA, Mink PJ, Alexander DD, Kalmes RM, Weingart M, Yost L, and Goodman M
- Subjects
- Case-Control Studies, Cohort Studies, Industry, Lymphoma, Non-Hodgkin chemically induced, Odds Ratio, Risk Assessment, Lymphoma, Non-Hodgkin epidemiology, Occupational Diseases epidemiology, Occupational Exposure adverse effects, Solvents toxicity, Trichloroethylene toxicity
- Abstract
Methods: Meta-analysis and review of 14 occupational cohort and four case-control studies of workers exposed to trichloroethylene (TCE) to investigate the relation between TCE exposure and the risk of non-Hodgkin's lymphoma (NHL). Studies were selected and categorised based on a priori criteria, and results from random effects meta-analyses are presented., Results: The summary relative risk estimates (SRRE) for the group of cohort studies that had more detailed information on TCE exposure was 1.29 (95% CI 1.00 to 1.66) for the total cohort and 1.59 (95% CI 1.21 to 2.08) for the seven studies that identified a specific TCE exposed sub-cohort. SRREs for three studies with cumulative exposure information were 1.8 (95% CI 0.62 to 5.26) for the lowest exposure category and 1.41 (95% CI 0.61 to 3.23) for the highest category. Comparison of SRREs by levels of TCE exposure did not indicate exposure-response trends. The remaining cohort studies that identified TCE exposure but lacked detailed exposure information had an SRRE of 0.843 (95% CI 0.72 to 0.98). Case-control studies had an SRRE of 1.39 (95% CI 0.62 to 3.10). Statistically significant findings for the Group 1 studies were driven by the results from the subgroup of multiple industry cohort studies (conducted in Europe) (SRRE = 1.86; 95% CI 1.27 to 2.71). The SRRE for single industry cohort studies was not significantly elevated (SRRE = 1.25; 95% CI 0.87 to 1.79)., Conclusions: Interpretation of overall findings is hampered by variability in results across the Group 1 studies, limited exposure assessments, lack of evidence of exposure response trends, lack of supportive information from toxicological and mechanistic data, and absence of consistent findings in epidemiologic studies of exposure and NHL. Although a modest positive association was found in the TCE sub-cohort analysis, a finding attributable to studies that included workers from multiple industries, there is insufficient evidence to suggest a causal link between TCE exposure and NHL.
- Published
- 2006
- Full Text
- View/download PDF
39. Investigation of mediastinitis due to coagulase-negative staphylococci after cardiothoracic surgery.
- Author
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Van Kerkhove MD, Parsonnet J, Weingart M, and Tompkins LS
- Subjects
- Aged, Case-Control Studies, Coagulase adverse effects, Female, Heart Diseases surgery, Humans, Male, Mediastinitis etiology, Middle Aged, Postoperative Complications, Risk Factors, Skin microbiology, Coagulase isolation & purification, Disease Outbreaks, Mediastinitis microbiology
- Abstract
Six cases of coagulase-negative staphylococcal mediastinitis were identified in the latter half of 1999. A new preoperative cleansing solution was suspected by hospital staff to be a factor in the outbreak. We evaluated this possible risk factor along with other known and suspected surgical site infection risk factors in this case-control study.
- Published
- 2006
- Full Text
- View/download PDF
40. Fungal types and concentrations from settled dust in normal residences.
- Author
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Hicks JB, Lu ET, De Guzman R, and Weingart M
- Subjects
- Environmental Monitoring, Floors and Floorcoverings, Housing, Reproducibility of Results, Air Pollution, Indoor analysis, Dust, Fungi isolation & purification
- Abstract
Analysis of settled dust collected from carpeting and furnishings is occasionally used by investigators to determine whether an environment contains unusual fungi. Little information is available concerning the types and concentrations of culturable fungi present on textile surfaces in normal residential settings not affected by unusual mold reservoirs, such as from fungal growth sites within the built environment. This study presents the results of the collection and analysis of surface dust from 26 residential environments that were prescreened by interview, physical inspection, and air sampling to limit the surface dust collection to structures in which there was no history of water intrusion, flooding, plumbing leaks, signs of mold growth, or evidence of unusual airborne fungal spore types or concentrations. In those structures found to have no history or indications of water events or unusual fungi, surface dust was vacuumed from prescribed horizontal areas on carpet and textile-covered furnishings. These samples were then subjected to fungal culture, from which viable colonies were enumerated and identified. Based on the study results, it does not appear reasonable that the frequently quoted total fungi concentration exceeding 10(5) CFU/g is definitive evidence that a residential surface is contaminated with unusual amounts of culturable fungi. Collocated samples collected from eight side-by-side carpets sections revealed poor reproducibility. While settled dust sampling may be appropriate for determining the fungal status of a localized area, or as a gross screening tool, using settled dust results alone to establish the presence of unusual fungal types or concentrations within a structure appears to be inappropriate, and using settled dust results with other investigative methods, such as visual observations and air sampling, requires cautious interpretation.
- Published
- 2005
- Full Text
- View/download PDF
41. Commercially managed healthcare: an experience.
- Author
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Weingart M
- Subjects
- Humans, Managed Care Programs standards, Mental Health Services standards, Quality Assurance, Health Care, Interinstitutional Relations, Managed Care Programs organization & administration, Mental Health Services organization & administration
- Published
- 1991
- Full Text
- View/download PDF
42. [Automatized endothelium morphometry].
- Author
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Hartmann C, Weingart M, Dünner P, and Giraud JP
- Subjects
- Computers, Endothelium cytology, Humans, Cornea cytology, Microscopy methods
- Published
- 1982
43. Operational parameters of voltammetric high-performance liquid chromatographic detectors with copper electrodes and application to a determination of some fodder biofactors.
- Author
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Stulík K, Pacáková V, Weingart M, and Podolák M
- Subjects
- Ammonia analysis, Chromatography, High Pressure Liquid, Copper, Electrodes, Amino Acids analysis, Animal Feed analysis
- Abstract
Two versions of an amperometric detector with a copper working electrode have been constructed and tested for high-performance liquid chromatography (HPLC). The performance of the detectors was studied using selected amino acids. The dependence of the detector response on the mobile phase flow-rate was studied in the range common in both macro- and microcolumn HPLC (5 microliter/min to 1.0 ml/min). It has been found that the detection sensitivity generally increases with decreasing flow-rate, i.e., the detector response is governed by the rate of the complexation reaction between the cupric ions and the solutes. This fact makes amperometric detection with a copper electrode especially useful for microcolumn separations. For all 20 amino acids studied, calibration curve parameters and detection limits have been determined; the latter vary from 0.4 to 18 ng in the injected volume. The amino acids can also be sensitively detected in a medium of 0.1-1.0 M ammonia, which is promising for the use of strong anion exchangers in amino acid separations. Choline can also be detected at a copper electrode, with a detection limit of 40 ng. An HPLC method with amperometric detection at a copper electrode has been developed for the determination of lysine, methionine and choline in fodder biofactors.
- Published
- 1986
- Full Text
- View/download PDF
44. Program for satellites: launch and learn.
- Author
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Weingart M
- Subjects
- Texas, Hospital Administration
- Published
- 1965
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