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3. The Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) on the New Horizons Mission

Author

McNutt, Jr., Ralph L., Livi, Stefano A., Gurnee, Reid S., Hill, Matthew E., Cooper, Kim A., Andrews, G. Bruce, Keath, Edwin P., Krimigis, Stamatios M., Mitchell, Donald G., Tossman, Barry, Bagenal, Fran, Boldt, John D., Bradley, Walter, Devereux, William S., Ho, George C., Jaskulek, Stephen E., LeFevere, Thomas W., Malcom, Horace, Marcus, Geoffrey A., Hayes, John R., Moore, G. Ty, Williams, Bruce D., Wilson IV, Paul, Brown, L. E., Kusterer, M., and Vandegriff, J.

Subjects
Astrophysics
Abstract

The Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) comprises the hardware and accompanying science investigation on the New Horizons spacecraft to measure pick-up ions from Pluto's outgassing atmosphere. To the extent that Pluto retains its characteristics similar to those of a "heavy comet" as detected in stellar occultations since the early 1980s, these measurements will characterize the neutral atmosphere of Pluto while providing a consistency check on the atmospheric escape rate at the encounter epoch with that deduced from the atmospheric structure at lower altitudes by the ALICE, REX, and SWAP experiments on New Horizons. In addition, PEPSSI will characterize any extended ionosphere and solar wind interaction while also characterizing the energetic particle environment of Pluto, Charon, and their associated system. First proposed for development for the Pluto Express mission in September 1993, what became the PEPSSI instrument went through a number of development stages to meet the requirements of such an instrument for a mission to Pluto while minimizing the required spacecraft resources. The PEPSSI instrument provides for measurements of ions (with compositional information) and electrons from 10s of keV to ~1 MeV in a 120 deg x 12 deg fan-shaped beam in six sectors for 1.5 kg and ~2.5 W., Comment: 107 pages, 38 figures, 29 tables; To appear in a special volume of Space Science Reviews on the New Horizons mission

Published
2007
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4. Validation of 13 Hot and Potentially Terrestrial TESS Planets

Author

Steven Giacalone, Courtney D. Dressing, Christina Hedges, Veselin B. Kostov, Karen A. Collins, Eric L. N. Jensen, Daniel A. Yahalomi, Allyson Bieryla, David R. Ciardi, Steve B. Howell, Jorge Lillo-Box, Khalid Barkaoui, Jennifer G. Winters, Elisabeth Matthews, John H. Livingston, Samuel N. Quinn, Boris S. Safonov, Charles Cadieux, E. Furlan, Ian J. M. Crossfield, Avi M. Mandell, Emily A. Gilbert, Ethan Kruse, Elisa V. Quintana, George R. Ricker, S. Seager, Joshua N. Winn, Jon M. Jenkins, Britt Duffy Adkins, David Baker, Thomas Barclay, David Barrado, Natalie M. Batalha, Alexander A. Belinski, Zouhair Benkhaldoun, Lars A. Buchhave, Luca Cacciapuoti, David Charbonneau, Ashley Chontos, Jessie L. Christiansen, Ryan Cloutier, Kevin I. Collins, Dennis M. Conti, Neil Cutting, Scott Dixon, René Doyon, Mohammed El Mufti, Emma Esparza-Borges, Zahra Essack, Akihiko Fukui, Tianjun Gan, Kaz Gary, Mourad Ghachoui, Michaël Gillon, Eric Girardin, Ana Glidden, Erica J. Gonzales, Pere Guerra, Elliott P. Horch, Krzysztof G. Hełminiak, Andrew W. Howard, Daniel Huber, Jonathan M. Irwin, Giovanni Isopi, Emmanuël Jehin, Taiki Kagetani, Stephen R. Kane, Kiyoe Kawauchi, John F. Kielkopf, Pablo Lewin, Lindy Luker, Michael B. Lund, Franco Mallia, Shude Mao, Bob Massey, Rachel A. Matson, Ismael Mireles, Mayuko Mori, Felipe Murgas, Norio Narita, Tanner O’Dwyer, Erik A. Petigura, Alex S. Polanski, Francisco J. Pozuelos, Enric Palle, Hannu Parviainen, Peter P. Plavchan, Howard M. Relles, Paul Robertson, Mark E. Rose, Pamela Rowden, Arpita Roy, Arjun B. Savel, Joshua E. Schlieder, Chloe Schnaible, Richard P. Schwarz, Ramatholo Sefako, Aleksandra Selezneva, Brett Skinner, Chris Stockdale, Ivan A. Strakhov, Thiam-Guan Tan, Guillermo Torres, René Tronsgaard, Joseph D. Twicken, David Vermilion, Ian A. Waite, Bradley Walter, Gavin Wang, Carl Ziegler, and Yujie Zou

Published
2022
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5. Using Agricultural Waste to Create More Environmentally Friendly and Affordable Products and Help Poor Coconut Farmers

Author

Bradley Walter L. and Conroy Sean

Subjects
coconut shell filler, coir non-woven, polypropylene, composites, Environmental sciences, GE1-350
Abstract

Each year, 64 000 000 000 coconuts are harvested around the world. The coconut water, coconut milk and/are coconut oil are produced from the coconut, leaving behind the coconut shells and the coconut husks, which are not well utilized. Exciting new ways to utilized coconut shell powder as function filler in engineering plastic such as polypropylene or polyethylene and to utilize coir fiber from the husk with polypropylene in non-woven fabric composites. These application demonstrate that the resulting environmental friendly composite materials have enhanced mechanical properties at a reduced cost.

Published
2019
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6. The Effect of Coconut Shell Powder as Functional Filler in Polypropylene during Compounding and Subsequent Molding

Author

Kirby Matt, Lewis Benjamin, Peterson Benjamin, Anggono Juliana, and Bradley Walter

Subjects
functional filler, impact strength, natural filler reinforcement, polymeric composites, rheological behavior, Environmental sciences, GE1-350
Abstract

Fine powder produced from coconut shells (CSP) has been found to be excellent functional filler in polypropylene, significantly increasing flexural and tensile moduli, slightly increasing tensile strength, and good retention of Izod impact strength at weight percentages less than 20 %. The research presented in this paper explores the temperature processing window for coconut shell powder filled polypropylene and the change in the rheological behavior of the polypropylene due to the addition of CSP as functional filler in this processing temperature window. The reason for the simultaneous increase in flexural modulus, tensile strength, and good retention of Izod impact behavior is also investigated

Published
2019
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7. ALS risk factors: Industrial airborne chemical releases

Author

Andrew, Angeline, primary, Zhou, Jie, additional, Gui, Jiang, additional, Shi, Xun, additional, Li, Meifang, additional, Harrison, Antoinette, additional, Guetti, Bart, additional, Nathan, Ramaa, additional, Butt, Tanya, additional, Peipert, Daniel, additional, Tischbein, Maeve, additional, Pioro, Erik P., additional, Stommel, Elijah, additional, and Bradley, Walter, additional

Published
2022
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12. Patient-reported tolerability of veliparib combined with cisplatin and etoposide for treatment of extensive stage small cell lung cancer: Neurotoxicity and adherence data from the ECOG ACRIN cancer research group E2511 phase II randomized trial

Author

David Cella, Suresh S. Ramalingam, Lynne I. Wagner, Josephine Feliciano, Charu Aggarwal, James L. Wade, Gordan Srkalovic, Nisha Mohindra, Laurie E. McLouth, Fengmin Zhao, Suzanne E. Dahlberg, Bradley Walter Lash, Ticiana A. Leal, Joseph W. Leach, and Taofeek K. Owonikoko

Subjects
0301 basic medicine, Male, Cancer Research, Lung Neoplasms, law.invention, Carboplatin, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Antineoplastic Combined Chemotherapy Protocols, Etoposide, chemotherapy‐induced peripheral neuropathy, veliparib, Original Research, Aged, 80 and over, Peripheral Nervous System Diseases, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Oncology, Tolerability, 030220 oncology & carcinogenesis, Female, medicine.drug, Randomization, Veliparib, Gynecologic oncology, Placebo, lcsh:RC254-282, Medication Adherence, 03 medical and health sciences, medicine, Humans, Radiology, Nuclear Medicine and imaging, Patient Reported Outcome Measures, tolerability, Aged, business.industry, Neurotoxicity, Clinical Cancer Research, small cell, medicine.disease, Small Cell Lung Carcinoma, 030104 developmental biology, chemistry, Cancer research, Benzimidazoles, business, patient‐reported outcomes
Abstract

Objectives The ECOG‐ACRIN Cancer Research Group trial E2511 recently demonstrated a potential benefit for the addition of veliparib to cisplatin‐etoposide (CE) in patients with extensive stage small cell lung cancer (ES‐SCLC) in a phase II randomized controlled trial. Secondary trial endpoints included comparison of the incidence and severity of neurotoxicity, hypothesized to be lower in the veliparib arm, and tolerability of the addition of veliparib to CE. Physician‐rated and patient‐reported neurotoxicity was also compared. Materials and Methods Patients randomized to veliparib plus CE (n = 64) or placebo plus CE (n = 64) completed the 11‐item Functional Assessment of Cancer Therapy Gynecologic Oncology Group Neurotoxicity (questionnaire pre‐treatment, end of cycle 4 [ie 3 months after randomization] and 3 months post‐treatment [ie 6‐months]). Adherence analysis was based on treatment forms. Results and Conclusion No significant differences in mean or magnitude of change in neurotoxicity scores were observed between treatment arms at any time point. However, patients in the placebo arm reported worsening neurotoxicity from baseline to 3‐months (M difference = −1.5, P = .045), compared to stable neurotoxicity in the veliparib arm (M difference = −0.2, P = .778). Weakness was the most common treatment‐emergent (>50%) and moderate to severe (>16%) symptom reported, but did not differ between treatment arms. The proportion of adherence to oral therapy in the overall sample was 75%. Three percent of patients reported clinically significant neurotoxicity that was not captured by physician assessment. Neurotoxicity scores were not different between treatment arms. The addition of veliparib to CE appeared tolerable, though weakness should be monitored. ClinicalTrials.gov Identifier NCT01642251., We examined patient‐reported tolerability of the addition of a PARP inhibitor, veliparib, to cisplatin‐etoposide for treatment of extensive stage small cell lung cancer in randomized controlled trial E2511. The addition of veliparib to cisplatin‐etoposide was tolerable according to a patient‐reported outcome and adherence. Future studies should assess whether veliparib may have a protective effect against chemotherapy‐induced peripheral neuropathy.

Published
2020

13. Long-term survival analysis of masitinib in amyotrophic lateral sclerosis

Author

Mora, Jesus S., primary, Bradley, Walter G., additional, Chaverri, Delia, additional, Hernández-Barral, María, additional, Mascias, Javier, additional, Gamez, Josep, additional, Gargiulo-Monachelli, Gisella M., additional, Moussy, Alain, additional, Mansfield, Colin D., additional, Hermine, Olivier, additional, and Ludolph, Albert C., additional

Published
2021
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15. Randomized Phase II Trial of Cisplatin and Etoposide in Combination With Veliparib or Placebo for Extensive-Stage Small-Cell Lung Cancer: ECOG-ACRIN 2511 Study

Author

James L. Wade, Taofeek K. Owonikoko, Ticiana Leal, Suzanne E. Dahlberg, Bradley Walter Lash, Gabriel Sica, Charu Aggarwal, Suresh S. Ramalingam, Gordan Srkalovic, Lynne I. Wagner, and Joseph W. Leach

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Veliparib, medicine.medical_treatment, Placebo, Placebos, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Double-Blind Method, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Progression-free survival, Lung cancer, Survival rate, Etoposide, Aged, Cisplatin, Chemotherapy, business.industry, ORIGINAL REPORTS, Middle Aged, medicine.disease, Small Cell Lung Carcinoma, Progression-Free Survival, Survival Rate, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Benzimidazoles, Female, business, medicine.drug
Abstract

Purpose Veliparib, a poly (ADP ribose) polymerase inhibitor, potentiated standard chemotherapy against small-cell lung cancer (SCLC) in preclinical studies. We evaluated the combination of veliparib with cisplatin and etoposide (CE; CE+V) doublet in untreated, extensive-stage SCLC (ES-SCLC). Materials and Methods Patients with ES-SCLC, stratified by sex and serum lactate dehydrogenase levels, were randomly assigned to receive four 3-week cycles of CE (75 mg/m2 intravenously on day 1 and 100 mg/m2 on days 1 through 3) along with veliparib (100 mg orally twice per day on days 1 through 7) or placebo (CE+P). The primary end point was progression-free survival (PFS). Using an overall one-sided 0.10-level log-rank test, the study had 88% power to demonstrate a 37.5% reduction in the PFS hazard rate. Results A total of 128 eligible patients received treatment on protocol. The median age was 66 years, 52% of patients were men, and Eastern Cooperative Oncology Group performance status was 0 for 29% of patients and 1 for 71%. The respective median PFS for the CE+V arm versus the CE+P arm was 6.1 versus 5.5 months (unstratified hazard ratio [HR], 0.75 [one-sided P = .06]; stratified HR, 0.63 [one-sided P = .01]), favoring CE+V. The median overall survival was 10.3 versus 8.9 months (stratified HR, 0.83; 80% CI, 0.64 to 1.07; one-sided P = .17) for the CE+V and CE+P arms, respectively. The overall response rate was 71.9% versus 65.6% (two-sided P = .57) for CE+V and CE+P, respectively. There was a significant treatment-by-strata interaction in PFS: Male patients with high lactate dehydrogenase levels derived significant benefit (PFS HR, 0.34; 80% CI, 0.22 to 0.51) but there was no evidence of benefit among patients in other strata (PFS HR, 0.81; 80% CI, 0.60 to 1.09). The following grade ≥ 3 hematology toxicities were more frequent in the CE+V arm than the CE+P arm: CD4 lymphopenia (8% v 0%; P = .06) and neutropenia (49% v 32%; P = .08), but treatment delivery was comparable. Conclusion The addition of veliparib to frontline chemotherapy showed signal of efficacy in patients with ES-SCLC and the study met its prespecified end point.

Published
2018

17. Nusinersen versus sham control in later-onset spinal muscular atrophy

Author

Vogt, Sibylle, Krueger, Marcus, Pechmann, Astrid, Rippberger, Bianca, Eckenweiler, Matthias, Schara, Ulrike, Koelbel, Heike, Andres, Barbara, Rupprich, Katrin, Gangfuss, Andrea, Jachertz, Philipp, Della Marina, Adela, Sponemann, Nina, Pane, Markia, Palermo, Concetta, Piastra, Marco, Fanelli, Lavinia, de Sanctis, Roberto, Genovese, Orazio, Antonaci, Laura, Pera, Maria Carmela, Lamendola, Priscilla, Messina, Sonia, Vita, Gianluca, Di Bella, Vincenzo, Sframeli, Maria, Rosa, Matteo, Barcellona, Costanza, Distefano, Maria Grazia, Cavallaro, Filippo, Versaci, Antonio, de Luca, Francesco, Vita, Giuseppe, Nacimento Osorio, Andres, Tizzano, Eduardo, Ortez Gonzalez, Carlos Ignacio, Ortigoza Escobar, Juan Dario, Colomer Oferil, Juame, Medina Cantillo, Julita, Febrer Rotger, Anna, Vigo Morancho, Meritxell, Eldblom, Johanneh, Darin, Niklas, Kroksmark, Anna Karin, Lindstedt, Asa, Michael, Eva, Kimber, Eva, Wahlgren, Lisa, Chan, Sophelia Hoi-Shan, Chim, Stella, Chiu, Joseph, Ho, Alvin Chi Chung, Ip, Jing Kun Janice, Lam, Wendy Wai Man, Ng, Maggie Chui-San, Wan, Connie, Wong, Virginia Chun Nei, Yue, Yvonne, Arakawa, Reiko, Yamauchi, Akemi, Nagata, Satoru, Ito, Yasushi, Nakatsukasa, Hidetsugu, Takeshita, Akiko, Hirasawa, Kyoko, Ikai, Tetsuo, Eto, Kaoru, Otamni, Yui, Takeshima, Yasuhiro, Fukuda, Noroki, Tanaka, Yasuhiro, Shimomura, Hideki, Lee, Tomoko, Shibano, Takayuki, Mercuri, E., Tachikawa, Tomohiro, Darras, B. T., Chae, Jong-Hee, Chiriboga, C. A., Lim, Byung Chan, Day, J. W., Shin, Hyung-Ik, Campbell, C., Kim, Soo Yeon, Connolly, A. M., Choi, Sun Ah, Iannaccone, S. T., Son, Woo Sung, Kirschner, J., Jo, Hyemi, Kuntz, N. L., Chun, Seong Min, Saito, K., Kim, Hyuna, Shieh, P. B., Tulinius, M., Mazzone, E. S., Montes, J., Bishop, K. M., Yang, Q., Foster, R., Gheuens, S., Bennett, C. F., Farwell, W., Schneider, E., de Vivo, D. C., Finkel, R. S., Bradley, Walter G., Kaufmann, Petra, Dickson, Patricia I., Reingold, Stephen C., Davis, Charles S., Arredondo, Kristen, Castro, Diana, Cowie, Margaret, Farrow-Gillespie, Alan, Hebert, Andrew, Kauk, Melissa, Miller, Nancy, Nelson, Leslie, Spain, Thomas, Cappell, Joshua, Constantinescu, Andrei, Cruz, Rosangel, Dastgir, Jahannaz, de Vivo, Darryl, Dunaway, Sally, Engelstad, Kristin, Khandji, Alexander G., Kramer, Samantha, Marra, Jonathan, Popolizio, Molly, Salazar, Rachel, Weimer, Louis H., Aziz-Zaman, Sonya, Lamarca, Nicole, Ghosh, Partha, Al-Ghamdi, Fouad, Liew, Wendy, Graham, Robert, Berde, Charles, Sethna, Navil, Koka, Anjali, Wang, Luke, Laine, Regina, Souris, Michelle, Ordonez, Grace, Harrington, Timothy, Szelag, Heather, Pasternak, Amy, Mirek, Elizabeth, Quigley, Janet, Finkel, Richard, Berry, Debbie, Civitello, Matthew, Endsley, Julie Duke, Eden, Candace, Leon, Wendy, O'Reardon, Kathleen, Sigurdardottir, Laufey, Johnson, Craig, Turner, Jenna, Vega, Melisa, Weber-Guzman, Fabiola, Zinn, Matthias, Rocha, Ana Carolina Tesi, Watson, Karolina, d'Souza, Genevieve, Ramamurthi, R. J., Gee, Richard, Kitsuwa-Lowe, Janis, Hagerman, Katharine, Crasta, Sheela, Welsh, Lesly, Paulose, Shirley, Mcfall, Danielle, Perez, Jennifer, Patnaik, Swetapadma, Sanjanwala, Bharati, Sakamuri, Sarada, Proud, Crystal, Purse, Bona Park, Duong, Trinh Tina, Sampson, Jacinda, Tennekoon, Gihan, Brandsema, John, Glanzman, Allan, Flickinger, Jean, Toms, Michele, Adang, Laura, Stanford, Delores, Mayer, Oscar, Zigmont, Joshua, Chadehumbe, Madeline, Kichula, Elizabeth, Finanger, Erika, Russman, Barry, Roberts, Colin, Frank, Andrea, Benjamin, Danielle, Zilke, Kirsten, Golumbek, Paul T., Zaidman, Craig M., Anand, Pallavi, Gadeken, Rebecca, Siener, Catherine, Kuntz, Nancy, Epstein, Leon, Krueger, Jena, Goldman, Stewart, Krosschell, Kristin, Blomgren, Colleen, Choi, Hyoung Won, Kurz, Jonathan, Parsons, Julie, Janas, Joanne, Yang, Michele, Ballard, Alison, Carry, Terri, Shea, Stephanie, Bielsky, Alan, Booker, Kaylee, Camuto, Alicia, Lord-Halvorson, Sierra, Gibbons, Melissa, Zimmerman, Carl, Allen, Victoria, Fuhr, Peter, Johnson, Hannah, Tran, Vi, Vanderveen, Gina, Shieh, Perry, Fowler, Eileen, Parziale, Nicholas, Rao, Lekha, Skura, Christy, Kelley, Carolyn, Shu, Francy, Oskoui, Maryam, Zielinski, David, Poulin, Chantal, Ingelmo, Pablo Mauricio, Desilets, Sarah Turgeon, Dinunzio, Pamela, Rivera, Gonzalo, Srour, Myriam, Arpin, Stephanie, Goobie, Sharan, Gibson, Paul, Scholtes, Cheryl, Mcdonald, Wendy, Zapata, Eugenio, Nguyen, Cam-Tu Emilie, Servais, Laurent, Gargaun, Elena, Le Moing, Anne-Gaelle, Gidaro, Teresa, Vialle, Raphael, Guye, Marie-Laurence, Lilien, Charlotte, Olliver, Gwenn, Gilabert, Stephanie, Borell, Sabine, Wider, Sabine, Stein, Sabine, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Department of Paediatrics, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Vall d'Hebron University Hospital [Barcelona], CIBER de Enfermedades Raras (CIBERER), Handicaps génétiques de l'enfant (Inserm U393), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Seoul National University Hospital, Max-Planck-Institut für Mikrostrukturphysik (MPI-HALLE), Max-Planck-Gesellschaft, The University of Tokyo (UTokyo), Institut de Chimie Organique et Analytique (ICOA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institute of Plasma Physics, Chinese Academy of Sciences (ASIPP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de mécanique des solides (LMS), École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), CureSMA [Elk Grove Village, IL, USA], Harvard Medical School [Boston] (HMS), Institute for Marine and Antarctic Studies [Hobart] (IMAS), University of Tasmania [Hobart, Australia] (UTAS), The Hospital for sick children [Toronto] (SickKids), University of Toronto, The Open University [Milton Keynes] (OU), Department of Pediatrics, Feinberg School of Medicine, Northwestern University [Evanston]-Northwestern University [Evanston]-Northwestern University, University Hospital Basel [Basel], McGill University Health Center [Montreal] (MUHC), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service of Clinical Trials and Databases, Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Groupe de Recherche sur l'Analyse Multimodale de la Fonction Cérébrale - UMR INSERM_S 1105 (GRAMFC), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Oxford, Schara, Ulrike (Beitragende*r), Koelbel, Heike (Beitragende*r), Rupprich, Katrin (Beitragende*r), Gangfuss, Andrea (Beitragende*r), Della Marina, Adela (Beitragende*r), and Sponemann, Nina (Beitragende*r)

Subjects
0301 basic medicine, Male, [SDV]Life Sciences [q-bio], spinal, Medizin, Oligonucleotides, Spinal Muscular Atrophies of Childhood, Pediatrics, law.invention, Age of Onset, Child, Child, Preschool, Double-Blind Method, Female, Humans, Infant, Injections, Spinal, Least-Squares Analysis, Motor Skills, Oligonucleotides, Antisense, Medicine (all), 0302 clinical medicine, age of onset, Randomized controlled trial, law, Clinical endpoint, inglese, injections, Motor skill, motor skills, General Medicine, SMA, Settore MED/26 - NEUROLOGIA, medicine.anatomical_structure, female, Anesthesia, Nusinersen, Spinal, antisense, preschool, Injections, 03 medical and health sciences, least-squares analysis, Settore MED/39 - NEUROPSICHIATRIA INFANTILE, Settore MED/41 - ANESTESIOLOGIA, medicine, Antisense, Preschool, business.industry, Spinal muscular atrophy, Motor neuron, medicine.disease, 030104 developmental biology, Age of onset, business, 030217 neurology & neurosurgery
Abstract

Background: Nusinersen is an antisense oligonucleotide drug that modulates pre–messenger RNA splicing of the survival motor neuron 2 (SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). Methods: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale–Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills. Results: In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by –1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P Conclusions: Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials.gov number, NCT02292537. opens in new tab.)

Published
2018

18. Cyanobacterial neurotoxin BMAA and brain pathology in stranded dolphins

Author

Davis, David A., primary, Mondo, Kiyo, additional, Stern, Erica, additional, Annor, Ama K., additional, Murch, Susan J., additional, Coyne, Thomas M., additional, Brand, Larry E., additional, Niemeyer, Misty E., additional, Sharp, Sarah, additional, Bradley, Walter G., additional, Cox, Paul Alan, additional, and Mash, Deborah C., additional

Published
2019
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19. Microbial cell factories for the production of specialised plant metabolites

Author

De Bruyn, Frederik, Van Brempt, Maarten, De Paepe, Brecht, Maertens, Jo, Bauwens, David, Coussement, Pieter, Lim, Chin Giaw, Biggs, Bradley Walter, Philippe, Ryan, Ajikumar, Parayil Kumaran, and De Mey, Marjan

Subjects
microbial cell factories, Biology and Life Sciences, plant metabolites
Published
2017

24. Phase I clinical trial of safety of L-serine for ALS patients

Author

Levine, Todd D., Miller, Robert G., Bradley, Walter G., Moore, Dan H., Saperstein, David S., Flynn, Lynne E., Katz, Jonathan S., Forshew, Dallas A., Metcalf, James S., Banack, Sandra A., and Cox, Paul A.

Abstract

We performed a randomized, double-blind phase I clinical trial for six months on the effects of oral L-serine in patients with ALS. The protocol called for enrollment of patients with a diagnosis of probable or definite ALS, age 18–85 years, disease duration of less than three years and forced vital capacity (FVC) ≥ 60%. Patients were randomly assigned to four different oral twice-daily dose regimens (0.5, 2.5, 7.5, or 15 g/dose). Blood, urine and CSF samples, ALS Functional Rating Scale-Revised (ALSFRS-R) scores and forced vital capacity (FVC) were obtained throughout the trial. Disease progression was compared with matched historical placebo controls from five previous ALS therapeutic trials. Of 20 patients enrolled, one withdrew before receiving study drug and two withdrew with gastro-intestinal problems. Three patients died during the trial. L-serine was generally well tolerated by the patients and L-serine did not appear to accelerate functional decline of patients as measured by slope of their ALSFRS-R scores. Based on this small study, L-serine appears to be generally safe for patients with ALS.

Published
2016
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26. Estimation of environmental exposure: interpolation, kernel density estimation or snapshotting.

Author

Shi, Xun, Li, Meifang, Hunter, Olivia, Guetti, Bart, Andrew, Angeline, Stommel, Elijah, Bradley, Walter, and Karagas, Margaret

Subjects
ENVIRONMENTAL exposure, ENVIRONMENTAL health, SPATIAL analysis (Statistics), POLLUTION, INTERPOLATION
Abstract

In environmental health researches and practices, spatial analysis became an important approach to estimation of environmental exposure of human subjects under concern. A typical situation in this kind of application is that the data of pollution are available only at certain locations, and thus, inference is needed to convert a limited number of values at discrete locations into a continuous surface. This paper intends to clarify the distinction among three methods that can be used to achieve this conversion, namely interpolation, kernel density estimation and snapshotting. Due to the apparent similarity of the three, they may cause confusions that lead to misuses. We compare and contrast the three methods, in terms of nature of the input data, mathematical process of the inference, and essential meaning of the output. For each method, we suggest appropriate applications within the context of estimation of environmental exposure. [ABSTRACT FROM AUTHOR]

Published
2019
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27. Gene-Environment-Time Interactions in Neurodegenerative Diseases: Hypotheses and Research Approaches

Author

Bradley, Walter G., Andrew, Angeline S., Traynor, Bryan J., Chiò, Adriano, Butt, Tanya H., and Stommel, Elijah W.

Abstract

Background: Amyotrophic lateral sclerosis (ALS), Alzheimer’s, and Parkinson’s diseases are age-related neurodegenerative diseases. ALS is not a single entity but a syndrome with many different causes. In all 3 diseases, gene mutations account for only 10–15% of cases. Many environmental and lifestyle factors have been implicated as risk factors for ALS, though none have been proven to cause the disease. It is generally believed that ALS results from interactions between environmental risk factors and genetic predisposing factors. The advent of next-generation sequencing and recent advances in research into environmental risk factors offer the opportunity to investigate these interactions. Summary: We propose a hypothesis to explain the syndrome of ALS based on the interaction of many individual environmental risk factors with many individual genetic predisposing factors. We hypothesize that there are many such combinations of individual, specific, genetic, and environmental factors, and that each combination can lead to the development of the syndrome of ALS. We also propose a hypothesis that explains the overlap between the age-related neurodegenerations and their genetic underpinnings. Age and duration of exposure are crucial factors in these age-related neurodegenerative diseases, and we consider how these may relate to gene-environment interactions. Key Messages: To date, genetic studies and environmental studies have investigated the causes of ALS separately. We argue that this univariate approach will not lead to discoveries of important gene-environment interactions. We propose new research approaches to investigating gene-environment interactions based on these hypotheses.

Published
2019
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34. Microbial Degradation at Stressed Fiber Reinforced Polymeric Composites.

Author

HITACHI LTD KANAGAWA (JAPAN) PRODUCTION ENGINEERING RESEARCH LAB, Wagner, Patricia, Ray, Richard, Hart, Kevin, Little, Brenda, Bradley, Walter, HITACHI LTD KANAGAWA (JAPAN) PRODUCTION ENGINEERING RESEARCH LAB, Wagner, Patricia, Ray, Richard, Hart, Kevin, Little, Brenda, and Bradley, Walter

Abstract

Reduction of tensile strength was demonstrated for carbon fiber reinforced epoxy resin composite strips after exposure to sulfate-reducing bacteria (SRB) in batch culture. Composite strips were maintained in a stressed condition in 3- and 4-point bend fixtures before and during exposure. Exposed surfaces were examined microscopically for bacterial colonization, fiber disruption and disbonding. Mechanical testing and acoustic emission (AE) examinations were used to evaluate degradation of tensile strength.

Published
1995

35. Practice Parameter: The Care of the Patient with Amyotrophic Lateral Sclerosis (An Evidence-Based Review): Report of the Quality Standards Subcommittee of the American Academy of Neurology

Author

Miller, Robert G., primary, Rosenberg, Jay A., additional, Gelinas, Deborah E., additional, Mitsumoto, Hiroshi, additional, Newman, Daniel, additional, Sufit, Robert L., additional, Borasio, Gian D., additional, Bradley, Walter G., additional, Bromberg, Mark B., additional, Brooks, Benjamin R., additional, Kasarskis, Edward J., additional, Munsat, Theodore L., additional, and Oppenheimer, Edward A., additional

Published
1999
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42. Cytochrome c Association with the Inner Mitochondrial Membrane Is Impaired in the CNS of G93A-SOD1 Mice.

Author

Kirkinezos, Ilias G., Bacman, Sandra R., Hernandez, Dayami, Oca-Cossio, Jose, Arias, Laura J., Perez-Pinzon, Miguel A., Bradley, Walter G., and Moraes, Carlos T.

Subjects
CYTOCHROME c, SUPEROXIDE dismutase, AMYOTROPHIC lateral sclerosis, GENES, MOTOR neurons, APOPTOSIS
Abstract

A "gain-of-function" toxic property of mutant Cu-Zn superoxide dismutase 1 (SOD1) is involved in the pathogenesis of some familial cases of amyotrophic lateral sclerosis (ALS). Expression of a mutant form of the human SOD1 gene in mice causes a degeneration of motor neurons, leading to progressive muscle weakness and hindlimb paralysis. Transgenic mice overexpressing a mutant human SOD1 gene (G93A-SOD1) were used to examine the mitochondrial involvement in familial ALS. We observed a decrease in mitochondrial respiration in brain and spinal cord of the G93A-SOD1 mice. This decrease was significant only at the last step of the respiratory chain (complex IV), and it was not observed in transgenic wild-type SOD1 and nontransgenic mice. Interestingly, this decrease was evident even at a very early age in mice, long before any clinical symptoms arose. The effect seemed to be CNS specific, because no decrease was observed in liver mitochondria. Differences in complex IV respiration between brain mitochondria of G93A-SOD1 and control mice were abolished when reduced cytochrome c was used as an electron donor, pinpointing the defect to cytochrome c. Submitochondrial studies showed that cytochrome c in the brain of G93A-SOD1 mice had a reduced association with the inner mitochondrial membrane (IMM). Brain mitochondrial lipids, including cardiolipin, had increased peroxidation in G93A-SOD1 mice. These results suggest a mechanism by which mutant SOD1 can disrupt the association of cytochrome c with the IMM, thereby priming an apoptotic program. [ABSTRACT FROM AUTHOR]

Published
2005
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44. Longitudinal fibre splitting in muscular dystrophy: a serial cinematographic study.

Author

Isaacs, Edward R., Bradley, Walter G., Henderson, Gerald, Isaacs, E R, Bradley, W G, and Henderson, G

Subjects
ANIMAL experimentation, BIOLOGICAL models, MICE, MOTION pictures, MUSCLES, MUSCULAR dystrophy
Abstract

A technique of block surface-staining and serial cinematography was modified to review serial sections of normal and dystrophic muscle from the Bar Harbor 129 Re strain of mice as a preliminary study of fibre splitting in dystrophic muscle. Using this technique, muscle fibres were reconstructed for up to 1·5 mm of their length without difficulty. Split fibres were identified only when the actual separation of fibres was observed. Splitting was seen to be a significant cause of the variations in fibre diameter and was at times responsible for the formation of groups of small atrophic fibres which resembled those seen in denervation atrophy. Complex multiple splitting and recombination of daughter and parent fibres was also observed and reconstructed to scale. These results may have considerable significance for the interpretation of physiological data on both human and murine dystrophic muscle. [ABSTRACT FROM AUTHOR]

Published
1973

45. Determination of the effect of seawater on the interfacial strength of an interlayer E-glass/graphite/epoxy composite by in situobservation of transverse cracking in an environmental SEM

Author

Wood, Catherine A. and Bradley, Walter L.

Abstract

In an effort to understand the failure behaviour and to determine the effects of seawater on composites, a program has been developed to determine the interfacial strength (normal to the fiber) of an interlayer hybrid composite which has been exposed to seawater for two different lengths of time. Specimens were tested in transverse tension in an environmental scanning electron microscope. The specimens were tested in the as-received condition, after they reached saturation, and 8 months after they reached saturation. Observations revealed that damage was initiated at the boundaries of resin-rich regions, regardless of the conditioning process. Analytical results obtained by linear superposition to determine the stress at the fiber/matrix interface revealed several interesting findings. For example, as moisture is added to a composite, the hydrothermal residual stresses in resin-rich inhomogeneities change from tensile to compressive. Assuming a constant interfacial strength, this should make it more difficult to initiate damage in conditioned specimens. As this was not the case, moisture appeared to have a slight degrading effect on the interfacial strength. However, propagation of damage away from the resin-rich regions requires a higher stress than that required to initiate this damage. Moisture actually helped to arrest damage growth causing the ply stress required to cause transverse cracking to increase with increased moisture content and with increased aging time.

Published
1997
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46. Automated system for the analysis of muscle and nerve biopsies

Author

Brenner, John F., Zahniser, David J., Ziegelmiller, Daniel W., Adelman, Lester S., Munsat, Theodore L., and Bradley, Walter G.

Abstract

An automated system has been developed for morphometric analysis of muscle and nerve fibers as seen in routine biopsy tissue preparations. This system, which is suitable both for research and clinical applications, is now in routine use at New England Medical Center Hospital. It is designed around commonly available hardware and uses our own custom software. Special sample preparation is not required, and the system will process almost any biopsy that is free from obvious artifact and suitable for manual assessment. In a typical biopsy, the system provides nearly full automation for the edge (boundary) determination of over 90% of the fibers encountered. An efficient, interactive mode allows for rapid analysis of the remaining 10%. Once fiber boundaries are determined, the system provides fully automatic measurement of the usual parameters such as fiber diameter, as well as a number of parameters not routinely measured with existing manual techniques. Typical analysis times are 35 min for muscle and 2 h for nerve. Complete report generation is provided, with hardcopy available in the pathologist's office. This paper describes the operational aspects of the use of the automated analysis system in routine biopsy work.

Published
1987

47. Delamination Fracture in Graphite/Epoxy Materials.

Author

TEXAS A AND M UNIV COLLEGE STATION DEPT OF MECHANICAL ENGINEERING, Bradley,Walter L, TEXAS A AND M UNIV COLLEGE STATION DEPT OF MECHANICAL ENGINEERING, and Bradley,Walter L

Abstract

Contents: Objectives; Summary Work Statement; Summary of Accomplishments by Areas in Work Statement: In-situ Fracture Observations, Crack tip Strain Field Measurements, Fracture Mechanics Characterization, Micromechanics Modeling, Fractography and Failure Analysis, Publications Resulting in Whole or in Part from Work Supported by AFOSR; Professional Personnel Associated with Research Effort; Presentations; Summary of Significance of Accomplishments; Papers: Micromechanics of Fracture in Toughened Graphite/Epoxy Laminates, A Comparison of the Crack Tip Damage Zone for Fracture of Hexcell F185 Neat Resin and T6C145/F185 Composite, The Relationship of Resin Ductility and Composite Delamination, Delamination Analysis of Composites with Distributed Damage using a J integral, Correlation Between Micromechanical Failure Processes and the Delamination Fracture Toughness of Graphite/Epoxy Composite, The Meaning and Significance of Hackles in Composite Materials Failure Analysis.

Published
1986

48. Letters between Walter H. Bradley and William Kerr's secretary

Author

Bradley, Walter H. and Stephens, D. E.

Subjects
recommendation, University of Madrid, Utah Agricultural College, position, instructor, professor, teacher, modern languages department
Abstract

Letters concerning a position in the modern languages department at Utah Agricultural College.

Published
1906

49. Laddie [binding]

Author

Whitaker, Evelyn, Brill, George Reiter, 1867-1918, Bradley, Walter Cooper, Whitaker, Evelyn, Brill, George Reiter, 1867-1918, and Bradley, Walter Cooper

Abstract

Deep orange yellow (C69) calico-texture cloth; older woman holding package and umbrella in front of door, lettering to right, all within single rule border, all in red, white, black and greenish-blue; six florets, rules and lettering on spine in red H: 19.3 cm.; W: 13.8 cm.; D: 2.4 cm.

Published
1903

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