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1. Correction to: A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot–Marie–Tooth type 1A

Author

Shahram Attarian, Peter Young, Thomas H. Brannagan, David Adams, Philip Van Damme, Florian P. Thomas, Carlos Casanovas, Jafar Kafaie, Céline Tard, Maggie C. Walter, Yann Péréon, David Walk, Amro Stino, Marianne de Visser, Camiel Verhamme, Anthony Amato, Gregory Carter, Laurent Magy, Jeffrey M. Statland, and Kevin Felice

Subjects
Medicine
Published
2024
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2. A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot–Marie–Tooth type 1A

Author

Shahram Attarian, Peter Young, Thomas H. Brannagan, David Adams, Philip Van Damme, Florian P. Thomas, Carlos Casanovas, Jafar Kafaie, Céline Tard, Maggie C. Walter, Yann Péréon, David Walk, Amro Stino, Marianne de Visser, Camiel Verhamme, Anthony Amato, Gregory Carter, Laurent Magy, Jeffrey M. Statland, and Kevin Felice

Subjects
Charcot–Marie–Tooth, CMT1A, Neuromuscular disorder, Overall Neuropathy Limitations Scale, PMP22, PXT3003, Medicine
Abstract

Abstract Background Charcot–Marie–Tooth disease type 1A (CMT1A) is a rare, orphan, hereditary neuromuscular disorder with no cure and for which only symptomatic treatment is currently available. A previous phase 2 trial has shown preliminary evidence of efficacy for PXT3003 in treating CMT1A. This phase 3, international, randomized, double-blind, placebo-controlled study further investigated the efficacy and safety of high- or low-dose PXT3003 (baclofen/naltrexone/D-sorbitol [mg]: 6/0.70/210 or 3/0.35/105) in treating subjects with mild to moderate CMT1A. Methods In this study, 323 subjects with mild-to-moderate CMT1A were randomly assigned in a 1:1:1 ratio to receive 5 mL of high- or low-dose PXT3003, or placebo, orally twice daily for up to 15 months. Efficacy was assessed using the change in Overall Neuropathy Limitations Scale total score from baseline to months 12 and 15 (primary endpoint). Secondary endpoints included the 10-m walk test and other assessments. The high-dose group was discontinued early due to unexpected crystal formation in the high-dose formulation, which resulted in an unanticipated high discontinuation rate, overall and especially in the high-dose group. The statistical analysis plan was adapted to account for the large amount of missing data before database lock, and a modified full analysis set was used in the main analyses. Two sensitivity analyses were performed to check the interpretation based on the use of the modified full analysis set. Results High-dose PXT3003 demonstrated significant improvement in the Overall Neuropathy Limitations Scale total score vs placebo (mean difference: − 0.37 points; 97.5% CI [− 0.68 to − 0.06]; p = 0.008), and consistent treatment effects were shown in the sensitivity analyses. Both PXT3003 doses were safe and well-tolerated. Conclusion The high-dose group demonstrated a statistically significant improvement in the primary endpoint and a good safety profile. Overall, high-dose PXT3003 is a promising treatment option for patients with Charcot–Marie–Tooth disease type 1A.

Published
2021
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5. Neuromuscular Complications of COVID-19: Evidence from the Third Year of the Global Pandemic

Author

Joome Suh and Anthony Amato

Subjects
Neurology, Neurology (clinical)
Abstract

Accumulating evidence in the third year of the global pandemic suggests that coronavirus disease 2019 (COVID-19) can cause neuromuscular complications during or after the acute phase of infection. Direct viral infection and immune-mediated mechanisms have been hypothesized. Furthermore, in patients with underlying autoimmune neuromuscular diseases, COVID-19 infection may trigger a disease flare. COVID-19 vaccines appear to be safe and effective at preventing severe illness from COVID-19. Certain vaccines are associated with an increased risk of Guillain-Barré syndrome and possibly Bell's palsy, but the absolute incidence is low, and benefits likely outweigh the risks. Newer prophylactic therapies and treatments are also becoming available for patients who may not mount a sufficient response to vaccination or have contraindications. In this article, we discuss the current available evidence on neuromuscular complications of COVID-19 and clinical considerations regarding vaccination.

Published
2023

8. Posterior segmental fixation for thoraco-lumbar and lumbar fractures: a comparative outcome study between open and percutaneous techniques

Author

Anthony Amato-Watkins and Marco Teli

Subjects
medicine.medical_specialty, Percutaneous, business.industry, Percutaneous techniques, General Medicine, Perioperative, Surgery, Lumbar, Blood loss, Radiological weapon, Cohort, medicine, Neurology (clinical), business, Fixation (histology)
Abstract

Purpose Showing results of open and percutaneous surgical management of traumatic AO type A3, A4 and B2 thoracic and lumbar fractures. Methods Retrospective comparative analysis of traditional open fusion versus percutaneous navigated fixation of thoracic and lumbar spinal fractures. Minimum 24 months follow-up to collect ODI and VAS outcome scores for comparative analysis was required. Results Fifty-seven patients with a mean age of 39 years met the inclusion criteria. Twenty-six patients were in the open group (Group O) and 31 in the percutaneous group (Group P). The majority of fractures were either type A3 or A4; there were three type B chance fractures in Group O and one in Group P. VAS and ODI scores followed comparable trends in the two groups until the final follow-up. The main statistically significant result between the two groups was blood loss, which was lower in Group P (110 versus 270 ml in Group O on average), although this did not reflect into different clinical outcomes. Similar peri-operative measures of operating time and length of stay were found between the two groups. A significantly higher degree of loss of reduction was noted at follow-up in Group P (8° versus 5° in Group O on average). Conclusions Open and percutaneous posterior fixation techniques of thoracic and lumbar fractures in this cohort were associated with different perioperative blood losses as well as radiological measurements, but not with clinically meaningful differences in patient reported outcome measures at 24 months' follow-up.

Published
2021

9. Identification of Caveolae-Associated Protein 4 Autoantibodies as a Biomarker of Immune-Mediated Rippling Muscle Disease in Adults

Author

Divyanshu Dubey, Grayson Beecher, M. Bakri Hammami, Andrew M. Knight, Teerin Liewluck, James Triplett, Abhigyan Datta, Surendra Dasari, Youwen Zhang, Matthew M. Roforth, Calvin R. Jerde, Stephen J. Murphy, William J. Litchy, Anthony Amato, Vanda A. Lennon, Andrew McKeon, John R. Mills, Sean J. Pittock, and Margherita Milone

Subjects
Adult, Male, Middle Aged, Caveolae, Muscular Diseases, Immunoglobulin G, Myasthenia Gravis, Humans, Female, Neurology (clinical), Biomarkers, Aged, Autoantibodies, Retrospective Studies
Abstract

Immune-mediated rippling muscle disease (iRMD) is a rare myopathy characterized by wavelike muscle contractions (rippling) and percussion- or stretch-induced muscle mounding. A serological biomarker of this disease is lacking.To describe a novel autoantibody biomarker of iRMD and report associated clinicopathological characteristics.This retrospective cohort study evaluated archived sera from 10 adult patients at tertiary care centers at the Mayo Clinic, Rochester, Minnesota, and BrighamWomen's Hospital, Boston, Massachusetts, who were diagnosed with iRMD by neuromuscular specialists in 2000 and 2021, based on the presence of electrically silent percussion- or stretch-induced muscle rippling and percussion-induced rapid muscle contraction with or without muscle mounding and an autoimmune basis. Sera were evaluated for a common biomarker using phage immunoprecipitation sequencing. Myopathology consistent with iRMD was documented in most patients. The median (range) follow-up was 18 (1-30) months.Diagnosis of iRMD.Detection of a common autoantibody in serum of patients sharing similar clinical and myopathological features.Seven male individuals and 3 female individuals with iRMD were identified (median [range] age at onset, 60 [18-76] years). An IgG autoantibody specific for caveolae-associated protein 4 (cavin-4) was identified in serum of patients with iRMD using human proteome phage immunoprecipitation sequencing. Immunoassays using recombinant cavin-4 confirmed cavin-4 IgG seropositivity in 8 of 10 patients with iRMD. Results for healthy and disease-control individuals (n = 241, including myasthenia gravis and immune-mediated myopathies) were cavin-4 IgG seronegative. Six of the 8 individuals with cavin-4 IgG were male, and the median (range) age was 60 (18-76) years. Initial symptoms included rippling of lower limb muscles in 5 of 8 individuals or all limb muscles in 2 of 8 sparing bulbar muscles, fatigue in 9 of 10, mild proximal weakness in 3 of 8, and isolated myalgia in 1 of 8, followed by development of diffuse rippling. All patients had percussion-induced muscle rippling and half had percussion- or stretch-induced muscle mounding. Four of the 10 patients had proximal weakness. Plasma creatine kinase was elevated in all but 1 patient. Six of the 10 patients underwent malignancy screening; cancer was detected prospectively in only 1. Muscle biopsy was performed in 7 of the 8 patients with cavin-4 IgG; 6 of 6 specimens analyzed immunohistochemically revealed a mosaic pattern of sarcolemmal cavin-4 immunoreactivity. Three of 6 patients whose results were seropositive and who received immunotherapy had complete resolution of symptoms, 1 had mild improvement, and 2 had no change.The findings indicate that cavin-4 IgG may be the first specific serological autoantibody biomarker identified in iRMD. Depletion of cavin-4 expression in muscle biopsies of patients with iRMD suggests the potential role of this autoantigen in disease pathogenesis.

Published
2022

10. Manipulating the 3D organization of the largest synthetic yeast chromosome

Author

Weimin Zhang, Luciana Lazar-Stefanita, Hitoyoshi Yamashita, Michael J. Shen, Leslie A. Mitchell, Hikaru Kurasawa, Max A. B. Haase, Xiaoji Sun, Qingwen Jiang, Stephanie L. Lauer, Laura H. McCulloch, Yu Zhao, David Ichikawa, Nicole Easo, S. Jiaming Lin, Viola Fanfani, Brendan R. Camellato, Yinan Zhu, Jitong Cai, Zhuwei Xu, Maya Sacasa, Ryan Accardo, Ju Young Ahn, Surekha Annadanam, Leighanne A. Brammer Basta, Nicholas R. Bello, Lousanna Cai, Stephanie Cerritos, MacIntosh Cornwell, Anthony D’Amato, Maria Hacker, Kenneth Hersey, Emma Kennedy, Ardeshir Kianercy, Dohee Kim, Hong Seo Lim, Griffin McCutcheon, Kimiko McGirr, Nora Meaney, Lauren Meyer, Ally Moyer, Maisa Nimer, Carla Sabbatini, Lisa Scheifele, Lucas S. Shores, Cassandra Silvestrone, Arden Snee, Antonio Spina, Anthony Staiti, Matt Stuver, Elli Tian, Danielle Whearty, Calvin Zhao, Tony Zheng, Vivian Zhou, Karen Zeller, Joel S. Bader, Giovanni Stracquadanio, Samuel Deutsch, Junbiao Dai, Yasunori Aizawa, and Jef D. Boeke

Subjects
History, ComputingMethodologies_PATTERNRECOGNITION, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Abstract

SummaryWhether synthetic genomes can power life has attracted broad interest in the synthetic biology field, especially when the synthetic genomes are extensively modified with thousands of designer features. Here we report de novo synthesis of the largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp Saccharomyces cerevisiae chromosome resulting from extensive genome streamlining and modification. During the construction of synIV, we developed a megachunk assembly method, combined with a hierarchical integration strategy. This strategy significantly increased the accuracy and flexibility of synthetic chromosome construction and facilitated chromosome debugging. In addition to the drastic sequence changes made to synIV by rewriting it, we further manipulated the three-dimensional structure of synIV in the yeast nucleus to explore spatial gene regulation within the nuclear space. Surprisingly, we found few gene expression changes, suggesting that positioning inside the yeast nucleoplasm plays a minor role in gene regulation. Therefore, our manipulation of the spatial structure of the largest synthetic yeast chromosome shed light on higher-order architectural design of the synthetic genomes.

Published
2022

11. Glasgow Neuro Society 2021 Conference Proceedings

Author

Mohammad, Ashraf, Hassan, Ismahel, Sytske, Lub, Eilidh, Middleton, Attika, Chaudhary, Ameerah, Gardee, Laulwa Al, Salloum, Eva, Szilagyi-Nagy, Rachel, Wales, Samia, Omar, Tracey Anne, Baird, Roddy, O'Kane, John, Holden, Mohamed, Abdelsadg, Pierce, Burr, Antony Ben, Decruz, Khaled, Badran, Anthony, Amato-Watkins, Likhith, Alakandy, Rosie, Boardman, Lynden, Nicely, Vasudha, Tandon, Sourav, Banerjee, Andrew, Keenlyside, Mark, Hughes, Jen Wae, Ho, Jake, Sieradzki, Elizabeth Phuong My, Phan, Niall John James, MacDougall, Aneesah Bashir Binti Azad, Bashir, Dana L, Hutton, Alexander S F, Doley, Krishna K, Oochit, Georgios, Kontorinis, and Yun Yang, Wong

Subjects
Surgery, Neurology (clinical)
Published
2022

12. Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

Author

Mantegazza, R., Wolfe, G. I., Muppidi, S., Wiendl, H., Fujita, K. P., O'Brien, F. L., Booth, H. D. E., Howard, J. F., Claudio Gabriel Mazia, Miguel, Wilken, Fabio, Barroso, Juliet, Saba, Marcelo, Rugiero, Mariela, Bettini, Marcelo, Chaves, Gonzalo, Vidal, Alejandra Dalila Garcia, Jan De Bleecker, Guy Van den Abeele, Kathy de Koning, Katrien De Mey, Rudy, Mercelis, Délphine, Mahieu, Linda, Wagemaekers, Philip Van Damme, Annelies, Depreitere, Caroline, Schotte, Charlotte, Smetcoren, Olivier, Stevens, Sien Van Daele, Nicolas, Vandenbussche, Annelies, Vanhee, Sarah, Verjans, Jan, Vynckier, Ann, D'Hont, Petra, Tilkin, Alzira Alves de Siqueira Carvalho, Igor Dias Brockhausen, David, Feder, Daniel, Ambrosio, Gabor Lovasamela César, Ana Paula Melo, Renata Martins Ribeiro, Rosana, Rocha, Bruno Bezerra Rosa, Thabata, Veiga, Luiz Augusto da Silva, Murilo Santos Engel, Jordana Gonçalves Geraldo, Maria da Penha Ananias Morita, Erica Nogueira Coelho, Gabriel, Paiva, Marina, Pozo, Natalia, Prando, Debora Dada Martineli Torres, Cristiani Fernanda Butinhao, Gustavo, Duran, Tomás Augusto Suriane Fialho, Tamires Cristina Gomes da Silva, Luiz Otavio Maia Gonçalves, Lucas Eduardo Pazetto, Luciana Renata Cubas Volpe, Luciana Souza Duca, Maurício AndréGheller Friedrich, Alexandre, Guerreiro, Henrique, Mohr, Maurer Pereira Martins, Daiane da Cruz Pacheco, Luciana, Ferreira, Ana Paula Macagnan, Graziela, Pinto, Aline de Cassia Santos, Acary Souza Bulle Oliveira, Ana Carolina Amaral de Andrade, Marcelo, Annes, Liene Duarte Silva, Valeria Cavalcante Lino, Wladimir, Pinto, Natália, Assis, Fernanda, Carrara, Carolina, Miranda, Iandra, Souza, Patrícia, Fernandes, Zaeem, Siddiqi, Cecile, Phan, Jeffrey, Narayan, Derrick, Blackmore, Ashley, Mallon, Rikki, Roderus, Elizabeth, Watt, Stanislav, Vohanka, Josef, Bednarik, Magda, Chmelikova, Marek, Cierny, Stanislava, Toncrova, Jana, Junkerova, Barbora, Kurkova, Katarina, Reguliova, Olga, Zapletalova, Jiri, Pitha, Iveta, Novakova, Michaela, Tyblova, Ivana, Jurajdova, Marcela, Wolfova, Henning, Andersen, Thomas, Harbo, Lotte, Vinge, Susanne, Krogh, Anita, Mogensen, John, Vissing, Joan, Højgaard, Nanna, Witting, Anne Mette Ostergaard Autzen, Jane, Pedersen, Juha-Pekka, Erälinna, Mikko, Laaksonen, Olli, Oksaranta, Tuula, Harrison, Jaana, Eriksson, Csilla, Rozsa, Melinda, Horvath, Gabor, Lovas, Judit, Matolcsi, Gedeonne, Jakab, Gyorgyi, Szabo, Brigitta, Szabadosne, Laszlo, Vecsei, Livia, Dezsi, Edina, Varga, Monika, Konyane, Antonini, Giovanni, Antonella Di Pasquale, Garibaldi, Matteo, Morino, Stefania, Troili, Fernanda, Fionda, Laura, Amelia, Evoli, Paolo Emilio Alboini, Valentina, D'Amato, Raffaele, Iorio, Inghilleri, Maurizio, Frasca, Vittorio, Elena, Giacomelli, Gori, MARIA CRISTINA, Diego, Lopergolo, Onesti, Emanuela, Maria, Gabriele, Francesco, Saccà, Alessandro, Filla, Teresa, Costabile, Enrico, Marano, Angiola, Fasanaro, Angela, Marsili, Giorgia, Puorro, Carlo, Antozzi, Silvia, Bonanno, Giorgia, Camera, Alberta, Locatelli, Lorenzo, Maggi, Maria, Pasanisi, Angela, Campanella, Akiyuki, Uzawa, Tetsuya, Kanai, Naoki, Kawaguchi, Masahiro, Mori, Yoko, Kaneko, Akiko, Kanzaki, Eri, Kobayashi, Hiroyuki, Murai, Katsuhisa, Masaki, Dai, Matsuse, Takuya, Matsushita, Taira, Uehara, Misa, Shimpo, Maki, Jingu, Keiko, Kikutake, Yumiko, Nakamura, Yoshiko, Sano, Kimiaki, Utsugisawa, Yuriko, Nagane, Ikuko, Kamegamori, Tomoko, Tsuda, Yuko, Fujii, Kazumi, Futono, Yukiko, Ozawa, Aya, Mizugami, Yuka, Saito, Makoto, Samukawa, Hidekazu, Suzuki, Miyuki, Morikawa, Sachiko, Kamakura, Eriko, Miyawaki, Meinoshin, Okumura, Soichiro, Funaka, Tomohiro, Kawamura, Masayuki, Nakamori, Masanori, Takahashi, Namie, Taichi, Tomoya, Hasuike, Eriko, Higuchi, Hisako, Kobayashi, Kaori, Osakada, Hirokazu, Shiraishi, Teiichiro, Miyazaki, Masakatsu, Motomura, Akihiro, Mukaino, Shunsuke, Yoshimura, Shizuka, Asada, Seiko, Yoshida, Shoko, Amamoto, Tomomi, Kobashikawa, Megumi, Koga, Maeda, Yasuko, Kazumi, Takada, Mihoko, Takada, Masako, Tsurumaru, Yumi, Yamashita, Yasushi, Suzuki, Tetsuya, Akiyama, Koichi, Narikawa, Ohito, Tano, Kenichi, Tsukita, Rikako, Kurihara, Fumie, Meguro, Yusuke, Fukuda, Miwako, Sato, Tomihiro, Imai, Emiko, Tsuda, Shun, Shimohama, Takashi, Hayashi, Shin, Hisahara, Jun, Kawamata, Takashi, Murahara, Masaki, Saitoh, Shuichiro, Suzuki, Daisuke, Yamamoto, Yoko, Ishiyama, Naoko, Ishiyama, Mayuko, Noshiro, Rumi, Takeyama, Kaori, Uwasa, Ikuko, Yasuda, Anneke van der Kooi, Marianne de Visser, Tamar, Gibson, Byung-Jo, Kim, Chang Nyoung Lee, Yong Seo Koo, Hung Youl Seok, Hoo Nam Kang, Hyejin, Ra, Byoung Joon Kim, Eun Bin Cho, Misong, Choi, Hyelim, Lee, Ju-Hong, Min, Jinmyoung, Seok, Jieun, Lee, Da Yoon Koh, Juyoung, Kwon, Sangae, Park, Eun Haw Choi, Yoon-Ho, Hong, So-Hyun, Ahn, Dae Lim Koo, Jae-Sung, Lim, Chae Won Shin, Ji Ye Hwang, Miri, Kim, Seung Min Kim, Ha-Neul, Jeong, Jinwoo, Jung, Yool-Hee, Kim, Hyung Seok Lee, Ha Young Shin, Eun Bi Hwang, Miju, Shin, Carlos, Casasnovas, Maria Antonia Alberti Aguilo, Christian, Homedes-Pedret, Natalia Julia Palacios, Laura Diez Porras, Valentina Velez Santamaria, Ana, Lazaro, Josep Gamez Carbonell, Pilar, Sune, Maria Salvado Figueras, Gisela, Gili, Gonzalo, Mazuela, Isabel, Illa, Elena Cortes Vicente, Jordi, Diaz-Manera, Luis Antonio Querol Gutiérrez, Ricardo Rojas Garcia, Nuria, Vidal, Elisabet, Arribas-Ibar, Exuperio Diez Tejedor, Pilar Gomez Salcedo, Mireya, Fernandez-Fournier, Pedro Lopez Ruiz, Francisco Javier Rodriguez de Rivera, Maria, Sastre, Fredrik, Piehl, Albert, Hietala, Lena, Bjarbo, Ihsan, Sengun, Arzu, Meherremova, Pinar, Ozcelik, Bengu, Balkan, Celal, Tuga, Muzeyyen, Ugur, Sevim, Erdem-Ozdamar, Can Ebru Bekircan-Kurt, Nazire Pinar Acar, Ezgi, Yilmaz, Yagmur, Caliskan, Gulsah, Orsel, Husnu, Efendi, Seda, Aydinlik, Hakan, Cavus, Ayse, Kutlu, Gulsah, Becerikli, Cansu, Semiz, Ozlem, Tun, Murat, Terzi, Baki, Dogan, Musa Kazim Onar, Sedat, Sen, Tugce Kirbas Cavdar, Adife, Veske, Fiona, Norwood, Aikaterini, Dimitriou, Jakit, Gollogly, Mohamed, Mahdi-Rogers, Arshira, Seddigh, Giannis, Sokratous, Gal, Maier, Faisal, Sohail, Saiju, Jacob, Girija, Sadalage, Pravin, Torane, Claire, Brown, Amna, Shah, Sivakumar, Sathasivam, Heike, Arndt, Debbie, Davies, Dave, Watling, Anthony, Amato, Thomas, Cochrane, Mohammed, Salajegheh, Kristen, Roe, Katherine, Amato, Shirli, Toska, Nicholas, Silvestri, Kara, Patrick, Karen, Zakalik, Jonathan, Katz, Robert, Miller, Marguerite, Engel, Dallas, Forshew, Elena, Bravver, Benjamin, Brooks, Mohammed, Sanjak, Sarah, Plevka, Maryanne, Burdette, Scott, Cunningham, Megan, Kramer, Joanne, Nemeth, Clara, Schommer, Tierney, Scott, Vern, Juel, Jeffrey, Guptill, Lisa, Hobson-Webb, Janice, Massey, Kate, Beck, Donna, Carnes, John, Loor, Amanda, Anderson, Robert, Pascuzzi, Cynthia, Bodkin, John, Kincaid, Riley, Snook, Sandra, Guingrich, Angela, Micheels, Vinay, Chaudhry, Andrea, Corse, Betsy, Mosmiller, Andrea, Kelley, Doreen, Ho, Jayashri, Srinivasan, Michal, Vytopil, Jordan, Jara, Nicholas, Ventura, Cynthia, Carter, Craig, Donahue, Carol, Herbert, Stephanie, Scala, Elaine, Weiner, Sharmeen, Alam, Jonathan, Mckinnon, Laura, Haar, Naya, Mckinnon, Karan, Alcon, Kaitlyn, Mckenna, Nadia, Sattar, Kevin, Daniels, Dennis, Jeffery, Miriam, Freimer, Joseph Chad Hoyle, John, Kissel, Julie, Agriesti, Sharon, Chelnick, Louisa, Mezache, Colleen, Pineda, Filiz, Muharrem, Chafic, Karam, Julie, Khoury, Tessa, Marburger, Harpreet, Kaur, Diana, Dimitrova, James, Gilchrist, Brajesh, Agrawal, Mona, Elsayed, Stephanie, Kohlrus, Angela, Ardoin, Taylor, Darnell, Laura, Golden, Barbara, Lokaitis, Jenna, Seelbach, Neelam, Goyal, Sarada, Sakamuri, Yuen, T So, Shirley, Paulose, Sabrina, Pol, Lesly, Welsh, Ratna, Bhavaraju-Sanka, Alejandro Tobon Gonzalez, Lorraine, Dishman, Floyd, Jones, Anna, Gonzalez, Patricia, Padilla, Amy, Saklad, Marcela, Silva, Sharon, Nations, Jaya, Trivedi, Steve, Hopkins, Mohamed, Kazamel, Mohammad, Alsharabati, Liang, Lu, Kenkichi, Nozaki, Sandi, Mumfrey-Thomas, Amy, Woodall, Tahseen, Mozaffar, Tiyonnoh, Cash, Namita, Goyal, Gulmohor, Roy, Veena, Mathew, Fatima, Maqsood, Brian, Minton, H James Jones, Jeffrey, Rosenfeld, Rebekah, Garcia, Laura, Echevarria, Sonia, Garcia, Michael, Pulley, Shachie, Aranke, Alan Ross Berger, Jaimin, Shah, Yasmeen, Shabbir, Lisa, Smith, Mary, Varghese, Laurie, Gutmann, Ludwig, Gutmann, Nivedita, Jerath, Christopher, Nance, Andrea, Swenson, Heena, Olalde, Nicole, Kressin, Jeri, Sieren, Richard, Barohn, Mazen, Dimachkie, Melanie, Glenn, April, Mcvey, Mamatha, Pasnoor, Jeffery, Statland, Yunxia, Wang, Tina, Liu, Kelley, Emmons, Nicole, Jenci, Jerry, Locheke, Alex, Fondaw, Kathryn, Johns, Gabrielle, Rico, Maureen, Walsh, Laura, Herbelin, Charlene, Hafer-Macko, Justin, Kwan, Lindsay, Zilliox, Karen, Callison, Valerie, Young, Beth, Disanzo, Kerry, Naunton, Michael, Benatar, Martin, Bilsker, Khema, Sharma, Anne, Cooley, Eliana, Reyes, Sara-Claude, Michon, Danielle, Sheldon, Julie, Steele, Rebecca, Traub, Manisha, Chopra, Tuan, Vu, Lara, Katzin, Terry, Mcclain, Brittany, Harvey, Adam, Hart, Kristin, Huynh, Said, Beydoun, Amaiak, Chilingaryan, Victor, Doan, Brian, Droker, Hui, Gong, Sanaz, Karimi, Frank, Lin, Krishna, Polaka, Akshay, Shah, Anh, Tran, Salma, Akhter, Ali, Malekniazi, Rup, Tandan, Michael, Hehir, Waqar, Waheed, Shannon, Lucy, Michael, Weiss, Jane, Distad, Susan, Strom, Sharon, Downing, Bryan, Kim, Tulio, Bertorini, Thomas, Arnold, Kendrick, Henderson, Rekha, Pillai, Liu, Ye, Lauren, Wheeler, Jasmine, Hewlett, Mollie, Vanderhook, Richard, Nowak, Daniel, Dicapua, Benison, Keung, Aditya, Kumar, Huned, Patwa, Kimberly, Robeson, Irene, Yang, Joan, Nye, and Hong, Vu

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Clinical Neurology, Antibodies, Monoclonal, Humanized, Placebo, Article, Antibodies, Post-intervention, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Refractory, law, Internal medicine, Monoclonal, Myasthenia Gravis, Medicine and Health Sciences, Humans, Medicine, Humanized, Science & Technology, business.industry, Middle Aged, Eculizumab, Complement Inactivating Agents, Female, Treatment Outcome, EFFICACY, medicine.disease, Myasthenia gravis, Clinical trial, 030104 developmental biology, SAFETY, Neurosciences & Neurology, Neurology (clinical), business, Life Sciences & Biomedicine, COMPLEMENT INHIBITOR ECULIZUMAB, 030217 neurology & neurosurgery, medicine.drug
Abstract

ObjectiveTo evaluate whether eculizumab helps patients with anti–acetylcholine receptor–positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension.MethodsPatients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study.ResultsA total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1–4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected.ConclusionEculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population.ClinicalTrials.gov IdentifierREGAIN, NCT01997229; REGAIN open-label extension, NCT02301624.Classification of EvidenceThis study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo.

Published
2020

13. Opening and closure of intraventricular neuroendoscopic procedures in infants under 1 year of age: institutional technique, case series and review of the literature

Author

Anthony Amato-Watkins, Michael D. Cearns, R O'Kane, Maya Kommer, Thomas Beez, and E Campbell

Subjects
medicine.medical_specialty, Leak, business.industry, Endoscopic third ventriculostomy, General Medicine, medicine.disease, Surgery, Shunt (medical), Hydrocephalus, Cerebrospinal fluid, Pediatrics, Perinatology and Child Health, medicine, Original Article, Neurology (clinical), Csf leakage, Neurosurgery, CSF leak, Single institution, business
Abstract

Purpose Intraventricular neuroendoscopic techniques, particularly third ventriculostomy, are employed increasingly in the management of infantile hydrocephalus. However, surgical access to the ventricular cavities is associated with a risk of post-operative cerebrospinal fluid (CSF) leak. Here, we describe a structured, multi-layered approach to wound opening and closure which aims to maximise the natural tissue barriers against CSF leakage. We present a series of patients undergoing this technique and subsequently review the literature regarding opening and closure techniques in paediatric intraventricular neuroendoscopic procedures. Methods We performed a retrospective case series analysis of patients under 1 year of age who underwent intraventricular neuroendoscopic procedures in a single institution over a 5-year period. Patients were identified from an institutional operative database, and operation notes and clinical records were subsequently reviewed. Results 28 patients fulfilled the inclusion criteria for this study. The mean age at operation was 9 weeks. 27 patients underwent endoscopic third ventriculostomy whilst 1 underwent endoscopic septostomy, and all patients underwent our structured, multi-layered opening and closure technique. Follow-up ranged from 4 months to 5 years. There were no cases of post-operative CSF leak, infection or wound breakdown. 12 patients remained shunt-free at the last follow-up, with the remaining 16 requiring shunt insertion for progressive hydrocephalus at a mean of 24 days post-operatively. Conclusion Various methods aiming to prevent post-operative CSF leak have been reported in the literature. We propose that our institutional technique may be of benefit in minimising this risk in infants undergoing endoscopic third ventriculostomy and similar intraventricular neuroendoscopic procedures.

Published
2020

15. Caveolae-Associated Protein (cavin)-4 Autoantibodies in Immune Mediated Rippling Muscle Disease

Author

M Bakri Hammami, Grayson Beecher, Andrew Knight, Teerin Liewluck, James Triplett, Abhigyan Datta, Surendra Dasari, Youwen Zhang, Matthew Roforth, Calvin Jerde, Stephen Murphy, William Litchy, Anthony Amato, Vanda Lennon, Andrew McKeon, John Mills, Sean Pittock, Margherita Milone, and Divyanshu Dubey

Subjects
Neurology (clinical)
Abstract

ObjectiveTo describe a novel autoantibody biomarker of Immune mediated rippling muscle disease (iRMD).BackgroundiRMD is a rare immunotherapy-responsive myopathy characterized by wave-like muscle contractions (rippling) and percussion/stretch-induced muscle mounding. However, serological biomarker of this disease is lacking.Design/MethodsA Retrospective review was done to identify iRMD patients with stored sera in Mayo Neuroimmunology laboratory. Archived sera from IRMD patients were evaluated for a common biomarker of IRMD using phage immunoprecipitation sequencing (PhIP-Seq).ResultsArchival sera from 10 patients with clinical diagnosis of iRMD were retrieved. Whole human proteome PhIP-Seq identified peptides corresponding to different regions of the cavin-4 in sera of iRMD patients. Eight of the ten iRMD cases were positive for cavin-4 IgG by immunofluorescent cell-based-assay (CBA) using cavin-4-transfected COS7 cells. The cavin-4-reactive IgG in all 8 positive sera was of IgG1 subclass. None of the disease control sera (98 immune-mediated myopathy/neuromuscular junction disorders, 20 autoimmune CNS diseases and 123 healthy subjects) contained cavin-4-reactive IgG. Furthermore, none of the iRMD patients' sera were positive for caveolin-3 IgG. The majority of seropositive cases were males (6/8, 75%) with median age of 51 years (range 18-76). Three seropositive patients had co-existing myasthenia gravis (38%). Creatine Kinase was elevated in 6/7 tested patients (median 771 U/L, range: 132-2625 U/L). Muscle biopsy was performed in 7 of the 8 cavin-4 IgG seropositive patients; 6/6 specimens analyzed immunohistochemically revealed a mosaic pattern of sarcolemmal cavin-4 immunoreactivity. Three of 6 seropositive patients who received immunotherapy had complete resolution of symptoms; one had mild improvement and two had no change.ConclusionsCavin-4 IgG is a novel and specific serological autoantibody biomarker identified in iRMD. Depletion of cavin-4 expression in iRMD patient muscle biopsies suggests the potential role of this autoantigen in disease pathogenesis.

Published
2022

16. Potential impacts of emerald ash borer and adaptation strategies on wildlife communities in black ash wetlands

Author

Alexis Grinde, Melissa Youngquist, Robert Slesak, Stephen Kolbe, Josh Bednar, Brian Palik, and Anthony D'Amato

Subjects
Birds, Coleoptera, Mammals, Ecology, Fraxinus, Larva, Wetlands, Animals, Animals, Wild, Trees
Abstract

Black ash wetlands cover approximately 1.2 million ha of wetland forest in the western Great Lakes region, providing critical habitat for wildlife. The future of these wetlands is critically threatened by a variety of factors, including emerald ash borer (Agrilus planipennis; emerald ash borer [EAB]), which has been eliminating native populations of otherwise healthy ash throughout the Great Lakes region since it was discovered in 2002. To quantify the potential impacts of tree mortality from EAB on wildlife communities, we measured seasonal bird, mammal, and amphibian diversity in black ash wetlands using a dual approach: (1) documenting bird and amphibian species across 27 mature reference black ash wetlands in northern Minnesota, USA and (2) assessing how bird, mammal, and amphibian communities respond to experimental manipulations of black ash forests that emulate mortality and management strategies related to the potential impact of EAB. In total, 85 wildlife species were recorded for the entire study including 57 bird species, 5 amphibian species, and 23 mammal species. Results from the reference sites show that hydrologic regime, percentage of ash canopy cover, and understory cover were important habitat characteristics for bird and amphibian communities. Results from the experimental sites show there may be short-term increases in species richness for mammal and bird communities associated with changes in forest structure due to ash mortality; however, anticipated changes resulting from EAB-caused mortality, particularly the conversion of these sites to non-forested wetlands, will lead to significant shifts in bird and mammal community composition. Loss of ash may cause declines in forest-dependent species and increases in open-canopy and wetland-associated species. Additionally, whereas increased ponding extent and longer hydroperiods may be beneficial for some amphibian species, the loss of the forest canopy will result in an overall decrease in bird diversity and reduce forest connectivity for all species. Our results indicate the potential for significant large-scale impacts of black ash mortality on forest-associated wildlife. Management strategies that focus on establishing alternative trees species to maintain long-term forest cover and structural complexity in these wetlands will help to maintain and conserve wildlife diversity.

Published
2021

17. Telemetric Intracranial Pressure: A Snapshot Does not Give the Full Story

Author

Maya, Kommer, Richard G, Boulton, Lynette, Loi, Sophie, Robinson, Christopher, Hawthorne, Martin, Shaw, Ian, Piper, Laura, Moss, Anthony, Amato-Watkins, Emer, Campbell, Meharpal, Sangra, and Roddy, O'Kane

Subjects
Pseudotumor Cerebri, Intracranial Pressure, Humans, Telemetry, Hydrocephalus, Monitoring, Physiologic
Abstract

Telemetric intracranial pressure (ICP) monitors are useful tools in the management of complex hydrocephalus and idiopathic intracranial hypertension (IIH). Clinicians may use them as a "snapshot" screening tool to assess shunt function or ICP. We compared "snapshot" telemetric ICP recordings with extended, in-patient periods of monitoring to determine whether this practice is safe and useful for clinical decision making.

Published
2021

18. Use of Direct Intracranial Pressure and Brain Tissue Oxygen Monitoring in Perioperative Management of Patients with Moyamoya Disease

Author

Maya, Kommer, Michael, Canty, Emer, Campbell, Meharpal, Sangra, Anthony, Amato-Watkins, Simon, Young, Christopher, Hawthorne, Laura, Moss, Ian, Piper, Martin, Shaw, and Roddy, O'Kane

Subjects
Oxygen, Cerebral Revascularization, Intracranial Pressure, Cerebrovascular Circulation, Brain, Humans, Moyamoya Disease
Abstract

Intracranial pressure monitoring and brain tissue oxygen monitoring are commonly used in head injury for goal-directed therapies, but there may be more indications for its use. Moyamoya disease involves progressive stenosis of the arterial circulation and formation of collateral vessels that are at risk of hemorrhage. The risk of ischemic events during revascularization surgery and postoperatively is high. Impaired cerebral autoregulation may be one of the factors that are implicated. We present our experience with monitoring of cerebral oxygenation and autoregulation in the pathological hemisphere during the perioperative period in four patients with moyamoya disease.

Published
2021

19. Books to Read Before You Graduate High School

Author

Sonya Fabricius, Kenneth C. Gorson, Richard J. Barohn, Ted M. Burns, Karen Easton, John T. Kissel, Marc Wallis, Richard Dubinsky, Gretchen Ayer, Jeffrey M. Burns, Carlayne E. Jackson, Omar Jawdat, Anthony Amato, Gil I. Wolfe, Joshua Freeman, Todd Levine, Aziz Shaibani, Dave Saperstein, Russel Swerdlow, Mamatha Pasnoor, Tahseen Mozafar, J. Statland, Walter Anderson, Erik R. Ensrud, Mazen M. Dimachkie, Laura Herbelin, Joel Barohn, and Jonathan S. Katz

Subjects
General Medicine
Published
2021

20. Use of Direct Intracranial Pressure and Brain Tissue Oxygen Monitoring in Perioperative Management of Patients with Moyamoya Disease

Author

I. R. Piper, Michael Canty, Maya Kommer, Meharpal Sangra, Martin Shaw, Emer Campbell, Christopher Hawthorne, Simon Young, Anthony Amato-Watkins, Laura Moss, and Roddy O'Kane

Subjects
medicine.medical_specialty, Revascularization surgery, business.industry, Head injury, Perioperative, medicine.disease, Cerebral autoregulation, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Cardiology, medicine, Intracranial pressure monitoring, Autoregulation, Moyamoya disease, business, 030217 neurology & neurosurgery, Intracranial pressure
Abstract

Intracranial pressure monitoring and brain tissue oxygen monitoring are commonly used in head injury for goal-directed therapies, but there may be more indications for its use. Moyamoya disease involves progressive stenosis of the arterial circulation and formation of collateral vessels that are at risk of hemorrhage. The risk of ischemic events during revascularization surgery and postoperatively is high. Impaired cerebral autoregulation may be one of the factors that are implicated. We present our experience with monitoring of cerebral oxygenation and autoregulation in the pathological hemisphere during the perioperative period in four patients with moyamoya disease.

Published
2021

21. Telemetric Intracranial Pressure: A Snapshot Does not Give the Full Story

Author

Lynette Loi, Meharpal Sangra, Emer Campbell, Laura Moss, Anthony Amato-Watkins, Richard G. Boulton, Christopher Hawthorne, Sophie Robinson, Ian Piper, Roddy O'Kane, Maya Kommer, and Martin Shaw

Subjects
medicine.medical_specialty, integumentary system, business.industry, musculoskeletal, neural, and ocular physiology, medicine.disease, humanities, nervous system diseases, 030218 nuclear medicine & medical imaging, Shunt (medical), Hydrocephalus, 03 medical and health sciences, 0302 clinical medicine, Clinical decision making, medicine, Snapshot (computer storage), Screening tool, Intensive care medicine, business, 030217 neurology & neurosurgery, Intracranial pressure
Abstract

Telemetric intracranial pressure (ICP) monitors are useful tools in the management of complex hydrocephalus and idiopathic intracranial hypertension (IIH). Clinicians may use them as a “snapshot” screening tool to assess shunt function or ICP. We compared “snapshot” telemetric ICP recordings with extended, in-patient periods of monitoring to determine whether this practice is safe and useful for clinical decision making.

Published
2021

22. Response to eculizumab in patients with myasthenia gravis recently treated with chronic IVIg: a subgroup analysis of REGAIN and its open-label extension study

Author

Saiju Jacob, Hiroyuki Murai, Kimiaki Utsugisawa, Richard J. Nowak, Heinz Wiendl, Kenji P. Fujita, Fanny O’Brien, James F. Howard, Claudio Gabriel Mazia, Miguel Wilken, Fabio Barroso, Juliet Saba, Jan De Bleecker, Guy Van den Abeele, Kathy de Koning, Katrien De Mey, Alzira Alves de Siqueira Carvalho, Igor Dias Brockhausen, David Feder, Daniel Ambrosio, Pamela César, Ana Paula Melo, Renata Martins Ribeiro, Rosana Rocha, Bruno Bezerra Rosa, Thabata Veiga, Luiz Augusto da Silva, Murilo Santos Engel, Jordana Gonçalves Geraldo, Yuriko Nagane, Ikuko Kamegamori, Tomoko Tsuda, Yuko Fujii, Kazumi Futono, Yukiko Ozawa, Aya Mizugami, Yuka Saito, Anneke van der Kooi, Marianne de Visser, Tamar Gibson, Seung Min Kim, JinWoo Jeong, Ha-Neul Jung, Yool-hee Kim, Hyung Seok Lee, Ha Young Shin, Eun Bi Hwang, Miju Shin, Josep Gamez Carbonell, Pilar Sune, Maria Salvado Figueras, Gisela Gili, Gonzalo Mazuela, Fredrik Piehl, Albert Hietala, Lena Bjarbo, Sevim Erdem-Ozdamar, Can Ebru Bekircan-Kurt, Nazire Pinar Acar, Ezgi Yilmaz, Yagmur Caliskan, Gulsah Orsel, Anthony Amato, Thomas Cochrane, Mohammed Salajegheh, Kristen Roe, Katherine Amato, Shirli Toska, Jonathan McKinnon, Laura Haar, Naya McKinnon, Karan Alcon, Kaitlyn McKenna, Nadia Sattar, Kevin Daniels, Dennis Jeffery, Tahseen Mozaffar, Tiyonnoh Cash, Namita Goyal, Gulmohor Roy, Veena Mathew, Fatima Maqsood, Brian Minton, Charlene Hafer-Macko, Justin Kwan, Lindsay Zilliox, Karen Callison, Valerie Young, Beth DiSanzo, Kerry Naunton, Tuan Vu, Lara Katzin, Terry McClain, Brittany Harvey, Adam Hart, Kristin Huynh, Said Beydoun, Amaiak Chilingaryan, Victor Doan, Brian Droker, Hui Gong, Sanaz Karimi, Frank Lin, Krishna Polaka, Akshay Shah, Anh Tran, Salma Akhter, Ali Malekniazi, Rup Tandan, Michael Hehir, Waqar Waheed, Shannon Lucy, Tulio Bertorini, Thomas Arnold, Kendrick Hendersen, Rekha Pillai, Ye Liu, Lauren Wheeler, Jasmine Hewlett, and Mollie Vanderhook

Subjects
IVIg, 0301 basic medicine, medicine.medical_specialty, REGAIN, Subgroup analysis, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Refractory, intravenous immunoglobulin, Internal medicine, medicine, In patient, Generalized myasthenia, RC346-429, Original Research, Pharmacology, myasthenia gravis, business.industry, Extension study, Eculizumab, medicine.disease, Myasthenia gravis, 030104 developmental biology, Neurology, eculizumab, Neurology (clinical), Neurology. Diseases of the nervous system, Open label, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background: In the phase III eculizumab for refractory generalized myasthenia gravis REGAIN study [ClinicalTrials.gov identifier: NCT01997229] and its open-label extension (OLE) [ClinicalTrials.gov identifier: NCT02301624], patients with treatment-refractory antiacetylcholine receptor antibody-positive generalized myasthenia gravis had clinically meaningful improvements with eculizumab versus placebo. This subgroup analysis evaluated data from patients with a recent history of chronic intravenous immunoglobulin (IVIg) use before study entry. Methods: The subgroup comprised patients who had received IVIg at least four times in 1 year, with at least one IVIg treatment cycle during the 6 months before the first REGAIN study dose. Data from REGAIN and the OLE were analyzed. Response to eculizumab versus placebo was assessed using four validated, disease-specific measures. Incidences of exacerbations and safety endpoints were recorded. Results: The subgroup had similar patient and disease characteristics as the overall REGAIN population. Clinical assessments showed sustained eculizumab efficacy during REGAIN and the OLE over 18 months. Patients receiving placebo in REGAIN experienced rapid improvements in assessment scores when treated with eculizumab in the OLE. There was a lower rate of disease exacerbations with eculizumab than with placebo during REGAIN, and eculizumab was well tolerated. Conclusion: Eculizumab treatment, compared with placebo, results in meaningful clinical improvements and fewer disease exacerbations for patients who previously received chronic IVIg. Trial registration: REGAIN [ClinicalTrials.gov identifier: NCT01997229]; REGAIN open-label extension [ClinicalTrials.gov identifier: NCT02301624].

Published
2020

23. A Fully Automated Periodicity Detection in Time Series

Author

Matthieu Boussard, Tom Puech, Anthony D’Amato, and Gaëtan Millerand

Subjects
symbols.namesake, Fourier transform, Series (mathematics), Fully automated, Computer science, Autocorrelation, symbols, State (computer science), Cluster analysis, Algorithm, Signal
Abstract

This paper presents a method to autonomously find periodicities in a signal. It is based on the same idea of using Fourier Transform and autocorrelation function presented in [12]. While showing interesting results this method does not perform well on noisy signals or signals with multiple periodicities. Thus, our method adds several new extra steps (hints clustering, filtering and detrending) to fix these issues. Experimental results show that the proposed method outperforms state of the art algorithms.

Published
2020

24. Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study

Author

Hiroyuki Murai, Akiyuki Uzawa, Yasushi Suzuki, Tomihiro Imai, Hirokazu Shiraishi, Hidekazu Suzuki, Meinoshin Okumura, Fanny O’Brien, Jing-Jing Wang, Kenji P. Fujita, Kimiaki Utsugisawa, Claudio Gabriel Mazia, Miguel Wilken, Fabio Barroso, Juliet Saba, Marcelo Rugiero, Mariela Bettini, Marcelo Chaves, Gonzalo Vidal, Alejandra Dalila Garcia, Jan De Bleecker, Guy Van den Abeele, Kathy de Koning, Katrien De Mey, Rudy Mercelis, Délphine Mahieu, Linda Wagemaekers, Philip Van Damme, Annelies Depreitere, Caroline Schotte, Charlotte Smetcoren, Olivier Stevens, Sien Van Daele, Nicolas Vandenbussche, Annelies Vanhee, Sarah Verjans, Jan Vynckier, Ann D'Hondt, Petra Tilkin, Alzira Alves de Siqueira Carvalho, Igor Dias Brockhausen, David Feder, Daniel Ambrosio, Pamela César, Ana Paula Melo, Renata Martins Ribeiro, Rosana Rocha, Bruno Bezerra Rosa, Thabata Veiga, Luiz Augusto da Silva, Murilo Santos Engel, Jordana Gonçalves Geraldo, Maria da Penha Ananias Morita, Erica Nogueira Coelho, Gabriel Paiva, Marina Pozo, Natalia Prando, Debora Dada Martineli Torres, Cristiani Fernanda Butinhao, Gustavo Duran, Tamires Cristina Gomes da Silva, Luiz Otavio Maia Gonçalves, Lucas Eduardo Pazetto, Tomás Augusto Suriane Fialho, Luciana Renata Cubas Volpe, Luciana Souza Duca, Acary Souza Bulle Oliveira, Ana Carolina Amaral Andrade, Marcelo Annes, Liene Duarte Silva, Valeria Cavalcante Lino, Wladimir Pinto, Natália Assis, Fernanda Carrara, Carolina Miranda, Iandra Souza, Patricia Fernandes, Zaeem Siddiqi, Cecile Phan, Jeffrey Narayan, Derrick Blackmore, Ashley Mallon, Rikki Roderus, Elizabeth Watt, Jana Junkerova, Barbora Kurkova, Katarina Reguliova, Olga Zapletalova, Jiri Pitha, Iveta Novakova, Michaela Tyblova, Ivana Jurajdova, Marcela Wolfova, Henning Andersen, Thomas Harbo, Lotte Vinge, Susanne Krogh, Anita Mogensen, John Vissing, Joan Højgaard, Nanna Witting, Anne Mette Ostergaard Autzen, Jane Pedersen, Juha-Pekka Eralinna, Mikko Laaksonen, Olli Oksaranta, Tuula Harrison, Jaana Eriksson, Csilla Rozsa, Melinda Horvath, Gabor Lovas, Judit Matolcsi, Gyorgyi Szabo, Gedeonne Jakab, Brigitta Szabadosne, Giovanni Antonini, Antonella Di Pasquale, Matteo Garibaldi, Stefania Morino, Fernanda Troili, Laura Fionda, Allessandro Filla, Teresa Costabile, Enrico Marano, Francesco Saccà, Angiola Fasanaro, Angela Marsili, Giorgia Puorro, Renato Mantegazza, Carlo Antozzi, Silvia Bonanno, Giorgia Camera, Alberta Locatelli, Lorenzo Maggi, Maria Pasanisi, Angela Campanella, Amelia Evoli, Paolo Emilio Alboini, Valentina D'Amato, Raffaele Iorio, Tetsuya Kanai, Naoki Kawaguchi, Masahiro Mori, Yoko Kaneko, Akiko Kanzaki, Eri Kobayashi, Katsuhisa Masaki, Dai Matsuse, Takuya Matsushita, Taira Uehara, Misa Shimpo, Maki Jingu, Keiko Kikutake, Yumiko Nakamura, Yoshiko Sano, Yuriko Nagane, Ikuko Kamegamori, Tomoko Tsuda, Yuko Fujii, Kazumi Futono, Yukiko Ozawa, Aya Mizugami, Yuka Saito, Miyuki Morikawa, Makoto Samukawa, Sachiko Kamakura, Eriko Miyawaki, Teiichiro Mitazaki, Masakatsu Motomura, Akihiro Mukaino, Shunsuke Yoshimura, Shizuka Asada, Seiko Yoshida, Shoko Amamoto, Tomomi Kobashikawa, Megumi Koga, Yasuko Maeda, Kazumi Takada, Mihoko Takada, Masako Tsurumaru, Yumi Yamashita, Tetsuya Akiyama, Koichi Narikawa, Ohito Tano, Kenichi Tsukita, Rikako Kurihara, Fumie Meguro, Yusuke Fukuda, Miwako Sato, Soichiro Funaka, Tomohiro Kawamura, Masayuki Makamori, Masanori Takahashi, Namie Taichi, Tomoya Hasuike, Eriko Higuchi, Hisako Kobayashi, Kaori Osakada, Emiko Tsuda, Shun Shimohama, Takashi Hayashi, Shin Hisahara, Jun Kawamata, Takashi Murahara, Masaki Saitoh, Shuichiro Suzuki, Daisuke Yamamoto, Yoko Ishiyama, Naoko Ishiyama, Mayuko Noshiro, Rumi Takeyama, Kaori Uwasa, Ikuko Yasuda, Anneke van der Kooi, Marianne de Visser, Tamar Gibson, Carlos Casasnovas, Maria Antonia Alberti Aguilo, Christian Homedes-Pedret, Natalia Julia Palacios, Laura Diez Porras, Valentina Velez Santamaria, Ana Lazaro, Exuperio Diez Tejedor, Pilar Gomez Salcedo, Mireya Fernandez-Fournier, Pedro Lopez Ruiz, Francisco Javier Rodriguez de Rivera, Maria Sastre, Josep Gamez, Pilar Sune, Maria Salvado, Gisela Gili, Gonzalo Mazuela, Isabel Illa, Elena Cortes Vicente, Jordi Diaz-Manera, Luis Antonio Querol Gutierrez, Ricardo Rojas Garcia, Nuria Vidal, Elisabet Arribas-Ibar, Fredrik Piehl, Albert Hietala, Lena Bjarbo, Ihsan Sengun, Arzu Meherremova, Pinar Ozcelik, Bengu Balkan, Celal Tuga, Muzeyyen Ugur, Sevim Erdem-Ozdamar, Can Ebru Bekircan-Kurt, Nazire Pinar Acar, Ezgi Yilmaz, Yagmur Caliskan, Gulsah Orsel, Husnu Efendi, Seda Aydinlik, Hakan Cavus, Ayse Kutlu, Gulsah Becerikli, Cansu Semiz, Ozlem Tun, Murat Terzi, Baki Dogan, Musa Kazim Onar, Sedat Sen, Tugce Kirbas Cavdar, Adife Veske, Fiona Norwood, Aikaterini Dimitriou, Jakit Gollogly, Mohamed Mahdi-Rogers, Arshira Seddigh, Giannis Sokratous, Gal Maier, Faisal Sohail, Saiju Jacob, Girija Sadalage, Pravin Torane, Claire Brown, Amna Shah, Sivakumar Sathasivam, Heike Arndt, Debbie Davies, Dave Watling, Anthony Amato, Thomas Cochrane, Mohammed Salajegheh, Kristen Roe, Katherine Amato, Shirli Toska, Gil Wolfe, Nicholas Silvestri, Kara Patrick, Karen Zakalik, Jonathan Katz, Robert Miller, Marguerite Engel, Dallas Forshew, Elena Bravver, Benjamin Brooks, Sarah Plevka, Maryanne Burdette, Scott Cunningham, Mohammad Sanjak, Megan Kramer, Joanne Nemeth, Clara Schommer, Scott Tierney, Vern Juel, Jeffrey Guptill, Lisa Hobson-Webb, Janice Massey, Kate Beck, Donna Carnes, John Loor, Amanda Anderson, Robert Pascuzzi, Cynthia Bodkin, John Kincaid, Riley Snook, Sandra Guingrich, Angela Micheels, Vinay Chaudhry, Andrea Corse, Betsy Mosmiller, Andrea Kelley, Doreen Ho, Jayashri Srinivasan, Michal Vytopil, Jordan Jara, Nicholas Ventura, Stephanie Scala, Cynthia Carter, Craig Donahue, Carol Herbert, Elaine Weiner, Sharmeen Alam, Jonathan McKinnon, Laura Haar, Naya McKinnon, Karan Alcon, Kaitlyn McKenna, Nadia Sattar, Kevin Daniels, Dennis Jeffery, Miriam Freimer, Joseph Chad Hoyle, John Kissel, Julie Agriesti, Sharon Chelnick, Louisa Mezache, Colleen Pineda, Filiz Muharrem, Chafic Karam, Julie Khoury, Tessa Marburger, Harpreet Kaur, Diana Dimitrova, James Gilchrist, Brajesh Agrawal, Mona Elsayed, Stephanie Kohlrus, Angela Andoin, Taylor Darnell, Laura Golden, Barbara Lokaitis, Jenna Seelback, Srikanth Muppidi, Neelam Goyal, Sarada Sakamuri, Yuen T. So, Shirley Paulose, Sabrina Pol, Lesly Welsh, Ratna Bhavaraju-Sanka, Alejandro Tobon Gonzales, Lorraine Dishman, Floyd Jones, Anna Gonzalez, Patricia Padilla, Amy Saklad, Marcela Silva, Mohamed Kazamel, Mohammad Alsharabati, Liang Lu, Kenkichi Nozaki, Sandi Mumfrey-Thomas, Amy Woodall, Tahseen Mozaffar, Tiyonnoh Cash, Namita Goyal, Gulmohor Roy, Veena Mathew, Fatima Maqsood, Brian Minton, H. James Jones, Jeffrey Rosenfeld, Rebekah Garcia, Laura Echevarria, Sonia Garcia, Michael Pulley, Shachie Aranke, Alan Ross Berger, Jaimin Shah, Yasmeen Shabbir, Lisa Smith, Mary Varghese, Laurie Gutmann, Ludwig Gutmann, Nivedita Jerath, Christopher Nance, Andrea Swenson, Heena Olalde, Nicole Kressin, Jeri Sieren, Richard Barohn, Mazen Dimachkie, Melanie Glenn, April McVey, Mamatha Pasnoor, Jeffery Statland, Yunxia Wang, Tina Liu, Kelley Emmons, Nicole Jenci, Jerry Locheke, Alex Fondaw, Kathryn Johns, Gabrielle Rico, Maureen Walsh, Laura Herbelin, Charlene Hafer-Macko, Justin Kwan, Lindsay Zilliox, Karen Callison, Valerie Young, Beth DiSanzo, Kerry Naunton, Michael Benatar, Martin Bilsker, Khema Sharma, Anne Cooley, Eliana Reyes, Sara-Claude Michon, Danielle Sheldon, Julie Steele, James Howard Jr, Manisha Chopra, Rebecca Traub, Tuan Vu, Lara Katzin, Terry McClain, Brittany Harvey, Adam Hart, Kristin Huynh, Said Beydoun, Amaiak Chilingaryan, Victor Doan, Brian Droker, Hui Gong, Sanaz Karimi, Frank Lin, Krishna Pokala, Akshay Shah, Anh Tran, Salma Akhter, Ali Malekniazi, Rup Tandan, Michael Hehir, Waqar Waheed, Shannon Lucy, Michael Weiss, Jane Distad, Susan Strom, Sharon Downing, Bryan Kim, Richard Nowak, Daniel Dicapua, Benison Keung, Aditya Kumar, Huned Patwa, Kimberly Robeson, Irene Yang, Joan Nye, Hong Vu, H., Murai, A., Uzawa, Y., Suzuki, T., Imai, H., Shiraishi, H., Suzuki, M., Okumura, F., O'Brien, J. -J., Wang, K. P., Fujita, K., Utsugisawa, Gabriel Mazia 11, Claudio, Wilken 11, Miguel, Barroso 11, Fabio, Saba 11, Juliet, Rugiero 12, Marcelo, Bettini 12, Mariela, Chaves 12, Marcelo, Vidal 12, Gonzalo, Dalila Garcia 12, Alejandra, De Bleecker 13, Jan, Van den Abeele 13, Guy, de Koning 13, Kathy, De Mey 13, Katrien, Mercelis 14, Rudy, Mahieu 14, Délphine, Wagemaekers 14, Linda, Van Damme 15, Philip, Depreitere 16, Annelie, Schotte 16, Caroline, Smetcoren 16, Charlotte, Stevens 16, Olivier, Van Daele 16, Sien, Vandenbussche 16, Nicola, Vanhee 16, Annelie, Verjans 16, Sarah, Vynckier 16, Jan, D'Hondt 16, Ann, Tilkin 16, Petra, Alves de Siqueira Carvalho 17, Alzira, Dias Brockhausen 17, Igor, Feder 17, David, Ambrosio 17, Daniel, César 17, Pamela, Paula Melo 17, Ana, Martins Ribeiro 17, Renata, Rocha 17, Rosana, Bezerra Rosa 17, Bruno, Veiga 17, Thabata, Augusto da Silva 17, Luiz, Santos Engel 17, Murilo, Gonçalves Geraldo 17, Jordana, da Penha Ananias Morita 18, Maria, Nogueira Coelho 18, Erica, Paiva 18, Gabriel, Pozo 18, Marina, Prando 18, Natalia, Dada Martineli Torres 18, Debora, Fernanda Butinhao 18, Cristiani, Duran 18, Gustavo, Cristina Gomes da Silva 18, Tamire, Otavio Maia Gonçalves 18, Luiz, Eduardo Pazetto 18, Luca, Augusto Suriane Fialho 18, Tomá, Renata Cubas Volpe 18, Luciana, Souza Duca 18, Luciana, Souza Bulle Oliveira 19, Acary, Carolina Amaral Andrade 19, Ana, Annes 19, Marcelo, Duarte Silva 19, Liene, Cavalcante Lino 19, Valeria, Pinto 19, Wladimir, Assis 19, Natália, Carrara 19, Fernanda, Miranda 19, Carolina, Souza 19, Iandra, Fernandes 19, Patricia, Siddiqi 20, Zaeem, Phan 20, Cecile, Narayan 20, Jeffrey, Blackmore 20, Derrick, Mallon 20, Ashley, Roderus 20, Rikki, Watt 20, Elizabeth, Junkerova 21, Jana, Kurkova 21, Barbora, Reguliova 21, Katarina, Zapletalova 21, Olga, Pitha 22, Jiri, Novakova 22, Iveta, Tyblova 22, Michaela, Jurajdova 22, Ivana, Wolfova 22, Marcela, Andersen 23, Henning, Harbo 23, Thoma, Vinge 23, Lotte, Krogh 23, Susanne, Mogensen 23, Anita, Vissing 24, John, Højgaard 24, Joan, Witting 24, Nanna, Mette Ostergaard Autzen 24, Anne, Pedersen 24, Jane, Eralinna 25, Juha-Pekka, Laaksonen 25, Mikko, Oksaranta 25, Olli, Harrison 25, Tuula, Eriksson 25, Jaana, Rozsa 26, Csilla, Horvath 26, Melinda, Lovas 26, Gabor, Matolcsi 26, Judit, Szabo 26, Gyorgyi, Jakab 26, Gedeonne, Szabadosne 26, Brigitta, Antonini 27, Giovanni, Di Pasquale 27, Antonella, Garibaldi 27, Matteo, Morino 27, Stefania, Troili 27, Fernanda, Fionda 27, Laura, Filla, Allessandro, Costabile, Teresa, Marano, Enrico, Sacca', Francesco, Fasanaro, Angiola, Marsili, Angela, Puorro, Giorgia, Mantegazza 29, Renato, Antozzi 29, Carlo, Bonanno 29, Silvia, Camera 29, Giorgia, Locatelli 29, Alberta, Maggi 29, Lorenzo, Pasanisi 29, Maria, Campanella 29, Angela, Evoli 30, Amelia, Emilio Alboini 30, Paolo, D'Amato 30, Valentina, Iorio 30, Raffaele, Kanai 31, Tetsuya, Kawaguchi 31, Naoki, Mori 31, Masahiro, Kaneko 31, Yoko, Kanzaki 31, Akiko, Kobayashi 31, Eri, Masaki 32, Katsuhisa, Matsuse 32, Dai, Matsushita 32, Takuya, Uehara 32, Taira, Shimpo 32, Misa, Jingu 32, Maki, Kikutake 32, Keiko, Nakamura 32, Yumiko, Sano 32, Yoshiko, Nagane 33, Yuriko, Kamegamori 33, Ikuko, Tsuda 33, Tomoko, Fujii 33, Yuko, Futono 33, Kazumi, Ozawa 33, Yukiko, Mizugami 33, Aya, Saito 33, Yuka, Morikawa 34, Miyuki, Samukawa 34, Makoto, Kamakura 34, Sachiko, Miyawaki 34, Eriko, Mitazaki 35, Teiichiro, Motomura 35, Masakatsu, Mukaino 35, Akihiro, Yoshimura 35, Shunsuke, Asada 35, Shizuka, Yoshida 35, Seiko, Amamoto 35, Shoko, Kobashikawa 35, Tomomi, Koga 35, Megumi, Maeda 35, Yasuko, Takada 35, Kazumi, Takada 35, Mihoko, Tsurumaru 35, Masako, Yamashita 35, Yumi, Akiyama 36, Tetsuya, Narikawa 36, Koichi, Tano 36, Ohito, Tsukita 36, Kenichi, Kurihara 36, Rikako, Meguro 36, Fumie, Fukuda 36, Yusuke, Sato 36, Miwako, Funaka 37, Soichiro, Kawamura 37, Tomohiro, Makamori 37, Masayuki, Takahashi 37, Masanori, Taichi 37, Namie, Hasuike 37, Tomoya, Higuchi 37, Eriko, Kobayashi 37, Hisako, Osakada 37, Kaori, Tsuda 38, Emiko, Shimohama 38, Shun, Hayashi 38, Takashi, Hisahara 38, Shin, Kawamata 38, Jun, Murahara 38, Takashi, Saitoh 38, Masaki, Suzuki 38, Shuichiro, Yamamoto 38, Daisuke, Ishiyama 38, Yoko, Ishiyama 38, Naoko, Noshiro 38, Mayuko, Takeyama 38, Rumi, Uwasa 38, Kaori, Yasuda 38, Ikuko, van der Kooi 39, Anneke, de Visser 39, Marianne, Gibson 39, Tamar, Casasnovas 40, Carlo, Antonia Alberti Aguilo 40, Maria, Homedes-Pedret 40, Christian, Julia Palacios 40, Natalia, Diez Porras 40, Laura, Velez Santamaria 40, Valentina, Lazaro 40, Ana, Diez Tejedor 41, Exuperio, Gomez Salcedo 41, Pilar, Fernandez-Fournier 41, Mireya, Lopez Ruiz 41, Pedro, Javier Rodriguez de Rivera 41, Francisco, Sastre 41, Maria, Gamez 42, Josep, Sune 42, Pilar, Salvado 42, Maria, Gili 42, Gisela, Mazuela 42, Gonzalo, Illa 43, Isabel, Cortes Vicente 43, Elena, Diaz-Manera 43, Jordi, Antonio Querol Gutierrez 43, Lui, Rojas Garcia 43, Ricardo, Vidal 43, Nuria, Arribas-Ibar 43, Elisabet, Piehl 44, Fredrik, Hietala 44, Albert, Bjarbo 44, Lena, Sengun 45, Ihsan, Meherremova 45, Arzu, Ozcelik 45, Pinar, Balkan 45, Bengu, Tuga 45, Celal, Ugur 45, Muzeyyen, Erdem-Ozdamar 46, Sevim, Ebru Bekircan-Kurt 46, Can, Pinar Acar 46, Nazire, Yilmaz 46, Ezgi, Caliskan 46, Yagmur, Orsel 46, Gulsah, Efendi 47, Husnu, Aydinlik 47, Seda, Cavus 47, Hakan, Kutlu 47, Ayse, Becerikli 47, Gulsah, Semiz 47, Cansu, Tun 47, Ozlem, Terzi 48, Murat, Dogan 48, Baki, Kazim Onar 48, Musa, Sen 48, Sedat, Kirbas Cavdar 48, Tugce, Veske 48, Adife, Norwood 49, Fiona, Dimitriou 49, Aikaterini, Gollogly 49, Jakit, Mahdi-Rogers 49, Mohamed, Seddigh 49, Arshira, Sokratous 49, Gianni, Maier 49, Gal, Sohail 49, Faisal, Jacob 50, Saiju, Sadalage 50, Girija, Torane 50, Pravin, Brown 50, Claire, Shah 50, Amna, Sathasivam 51, Sivakumar, Arndt 51, Heike, Davies 51, Debbie, Watling 51, Dave, Amato 52, Anthony, Cochrane 52, Thoma, Salajegheh 52, Mohammed, Roe 52, Kristen, Amato 52, Katherine, Toska 52, Shirli, Wolfe 53, Gil, Silvestri 53, Nichola, Patrick 53, Kara, Zakalik 53, Karen, Katz 54, Jonathan, Miller 54, Robert, Engel 54, Marguerite, Forshew 54, Dalla, Bravver 55, Elena, Brooks 55, Benjamin, Plevka 55, Sarah, Burdette 55, Maryanne, Cunningham 55, Scott, Sanjak 55, Mohammad, Kramer 55, Megan, Nemeth 55, Joanne, Schommer 55, Clara, Tierney 55, Scott, Juel 56, Vern, Guptill 56, Jeffrey, Hobson-Webb 56, Lisa, Massey 56, Janice, Beck 56, Kate, Carnes 56, Donna, Loor 56, John, Anderson 56, Amanda, Pascuzzi 57, Robert, Bodkin 57, Cynthia, Kincaid 57, John, Snook 57, Riley, Guingrich 57, Sandra, Micheels 57, Angela, Chaudhry 58, Vinay, Corse 58, Andrea, Mosmiller 58, Betsy, Kelley 58, Andrea, Ho 59, Doreen, Srinivasan 59, Jayashri, Vytopil 59, Michal, Jara 59, Jordan, Ventura 59, Nichola, Scala 59, Stephanie, Carter 59, Cynthia, Donahue 59, Craig, Herbert 59, Carol, Weiner 59, Elaine, Alam 59, Sharmeen, McKinnon 60, Jonathan, Haar 60, Laura, McKinnon 60, Naya, Alcon 60, Karan, McKenna 60, Kaitlyn, Sattar 60, Nadia, Daniels 60, Kevin, Jeffery 60, Denni, Freimer 61, Miriam, Chad Hoyle 61, Joseph, Kissel 61, John, Agriesti 61, Julie, Chelnick 61, Sharon, Mezache 61, Louisa, Pineda 61, Colleen, Muharrem 61, Filiz, Karam 62, Chafic, Khoury 62, Julie, Marburger 62, Tessa, Kaur 62, Harpreet, Dimitrova 62, Diana, Gilchrist 63, Jame, Agrawal 63, Brajesh, Elsayed 63, Mona, Kohlrus 63, Stephanie, Andoin 63, Angela, Darnell 63, Taylor, Golden 63, Laura, Lokaitis 63, Barbara, Seelback 63, Jenna, Muppidi 64, Srikanth, Goyal 64, Neelam, Sakamuri 64, Sarada, T So 64, Yuen, Paulose 64, Shirley, Pol 64, Sabrina, Welsh 64, Lesly, Bhavaraju-Sanka 65, Ratna, Tobon Gonzales 65, Alejandro, Dishman 65, Lorraine, Jones 65, Floyd, Gonzalez 65, Anna, Padilla 65, Patricia, Saklad 65, Amy, Silva 65, Marcela, Kazamel 66, Mohamed, Alsharabati 66, Mohammad, Lu 66, Liang, Nozaki 66, Kenkichi, Mumfrey-Thomas 66, Sandi, Woodall 66, Amy, Mozaffar 67, Tahseen, Cash 67, Tiyonnoh, Goyal 67, Namita, Roy 67, Gulmohor, Mathew 67, Veena, Maqsood 67, Fatima, Minton 67, Brian, James Jones 68, H, Rosenfeld 68, Jeffrey, Garcia 68, Rebekah, Echevarria 68, Laura, Garcia 68, Sonia, Pulley 69, Michael, Aranke 69, Shachie, Ross Berger 69, Alan, Shah 69, Jaimin, Shabbir 69, Yasmeen, Smith 69, Lisa, Varghese 69, Mary, Gutmann 70, Laurie, Gutmann 70, Ludwig, Jerath 70, Nivedita, Nance 70, Christopher, Swenson 70, Andrea, Olalde 70, Heena, Kressin 70, Nicole, Sieren 70, Jeri, Barohn 71, Richard, Dimachkie 71, Mazen, Glenn 71, Melanie, McVey 71, April, Pasnoor 71, Mamatha, Statland 71, Jeffery, Wang 71, Yunxia, Liu 71, Tina, Emmons 71, Kelley, Jenci 71, Nicole, Locheke 71, Jerry, Fondaw 71, Alex, Johns 71, Kathryn, Rico 71, Gabrielle, Walsh 71, Maureen, Herbelin 71, Laura, Hafer-Macko 72, Charlene, Kwan 72, Justin, Zilliox 72, Lindsay, Callison 72, Karen, Young 72, Valerie, DiSanzo 72, Beth, Naunton 72, Kerry, Benatar 73, Michael, Bilsker 73, Martin, Sharma 73, Khema, Cooley 73, Anne, Reyes 73, Eliana, Michon 73, Sara-Claude, Sheldon 73, Danielle, Steele 73, Julie, Howard Jr 74, Jame, Karam 74, Chafic, Chopra 74, Manisha, Traub 74, Rebecca, Vu 75, Tuan, Katzin 75, Lara, McClain 75, Terry, Harvey 75, Brittany, Hart 75, Adam, Huynh 75, Kristin, Beydoun 76, Said, Chilingaryan 76, Amaiak, Doan 76, Victor, Droker 76, Brian, Gong 76, Hui, Karimi 76, Sanaz, Lin 76, Frank, McClain 76, Terry, Pokala 76, Krishna, Shah 76, Akshay, Tran 76, Anh, Akhter 76, Salma, Malekniazi 76, Ali, Tandan 77, Rup, Hehir 77, Michael, Waheed 77, Waqar, Lucy 77, Shannon, Weiss 78, Michael, Distad 78, Jane, Strom 78, Susan, Downing 78, Sharon, Kim 78, Bryan, Nowak 79, Richard, Dicapua 79, Daniel, Keung 79, Benison, Kumar 79, Aditya, Patwa 79, Huned, Robeson 79, Kimberly, Yang 79, Irene, Nye 79, Joan, and Hong Vu

Subjects
Male, Pediatrics, Myasthenia gravi, Open-label extension study, Complement inhibitor, 0302 clinical medicine, Quality of life, Japan, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, Myasthenia gravis, education.field_of_study, MG-ADL, Japanese patient, Eculizumab, Middle Aged, HLA, MG-QoL15, Treatment Outcome, Neurology, Female, Life Sciences & Biomedicine, COMPLEMENT INHIBITOR ECULIZUMAB, medicine.drug, Adult, medicine.medical_specialty, Population, Clinical Neurology, Subgroup analysis, Placebo, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Refractory, Asian People, Myasthenia Gravis, Humans, education, Aged, Science & Technology, business.industry, Neurosciences, medicine.disease, Complement Inactivating Agents, Japanese patients, ONSET, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery
Abstract

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52-week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with open-label eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (-2.4 [1.34] and - 3.3 [0.65]); Quantitative Myasthenia Gravis (-2.9 [1.98] and - 4.3 [0.79]); Myasthenia Gravis Composite (-4.5 [2.63] and - 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (-8.6 [5.68] and - 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population. ispartof: JOURNAL OF THE NEUROLOGICAL SCIENCES vol:407 ispartof: location:Netherlands status: published

Published
2019

25. 224th ENMC International Workshop

Author

Yves Allenbach, Andrew L. Mammen, Olivier Benveniste, Werner Stenzel, Anthony Amato, Audrey Aussey, Jan De Bleecker, Ingrid de Groot, Marianne de Visser, Hans Goebel, Baptiste Hervier, Norina Fischer, David Hilton-Jones, Janice Lamb, Ingrid Lundberg, Andrew Mammen, Tahseen Mozaffar, Ichizo Nishino, Alan Pestronk, Ulrike Schara, and Werner Stenzelr

Subjects
030203 arthritis & rheumatology, Pathology, medicine.medical_specialty, Immune mediated necrotizing myopathy, business.industry, MEDLINE, Dermatology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Neurology, Pediatrics, Perinatology and Child Health, medicine, Neurology (clinical), business, Pathological, 030217 neurology & neurosurgery, Genetics (clinical)
Published
2018

26. Outcomes of ventriculoperitoneal shunt insertion in the management of idiopathic intracranial hypertension in children

Author

Paul Leach, Frances Gibbon, J. Te Water Naude, Anthony Amato-Watkins, Ronak Ved, J. Heyman, and I. Bhatti

Subjects
Male, medicine.medical_specialty, Pediatrics, Visual acuity, Adolescent, Pseudotumor cerebri, VP, Population, Visual Acuity, Shunt, Ventriculoperitoneal Shunt, Body Mass Index, Perceptual Disorders, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, IIH, Child, education, Papilledema, Retrospective Studies, Original Paper, Pseudotumor Cerebri, education.field_of_study, business.industry, Headache, Retrospective cohort study, Prostheses and Implants, General Medicine, medicine.disease, Surgery, Treatment Outcome, Paediatric, Pediatrics, Perinatology and Child Health, 030221 ophthalmology & optometry, Etiology, Female, Neurology (clinical), Neurosurgery, medicine.symptom, business, 030217 neurology & neurosurgery, Shunt (electrical)
Abstract

Purpose The ventriculoperitoneal (VP) shunt has become the\ud procedure of choice for treatment of idiopathic intracranial\ud hypertension (IIH). We aimed to assess the efficacy of\ud frameless stereotactic placement of VP shunts for the management of medically resistant IIH in children and to assess the role of gender and obesity in the aetiology of the condition.\ud Methods This is a retrospective analysis of the case notes of 10 patients treated surgically at the University Hospital of\ud Wales in Cardiff, from May 2006 to September 2012.\ud Results VP shunts were successful in relieving headache,\ud papilloedema and stabilising vision. No sex predilection was\ud identified, and increased BMI was a feature throughout the\ud population, regardless of age.\ud Conclusions Neuronavigated VP shunt insertion is an effective mode of treatment for medically resistant IIH in children. The aetiological picture in children does not seem to be dominated by obesity, as in adults. Literature on childhood IIH is sparse, and larger scale, comparative studies would be of benefit to treating clinicians.

Published
2017

27. Idiopathic inflammatory myopathy:Interrater variability in muscle biopsy reading

Author

Romain K. Gherardi, Florieke J. Berfelo, Monika Hofer, Eleonora Aronica, David Hilton-Jones, Werner Stenzel, Anthony Amato, Henrik Daa Schrøder, Marianne de Visser, Boel De Paepe, Roos Colman, Hans H. Goebel, Janice L. Holton, Jan De Bleecker, Pieter Olivier, Eduard Gallardo, Dalia Dimitri, Duygu Selcen, Pathology, APH - Aging & Later Life, APH - Mental Health, Neurology, and AII - Inflammatory diseases

Subjects
medicine.medical_specialty, Biopsy, Connective tissue, Disease, Polymyositis, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Muscle, Skeletal, Myositis, Observer Variation, 030203 arthritis & rheumatology, Muscle biopsy, medicine.diagnostic_test, business.industry, Dermatomyositis, medicine.disease, medicine.anatomical_structure, Homogeneous, Idiopathic Inflammatory Myopathy, Neurology (clinical), Radiology, business, 030217 neurology & neurosurgery
Abstract

ObjectiveTo determine interrater variability in diagnosing individual muscle biopsy abnormalities and diagnosis.MethodsWe developed a scoring tool to analyze consensus in muscle biopsy reading of an ad hoc workgroup of international experts. Twenty-four samples from patients with suspected idiopathic inflammatory myopathy (IIM) were randomly selected, providing sections that were stained with standard histologic and immunohistochemical methods. Sections were made available on an online platform, and experts were queried about myopathologic features within 4 pathologic domains: muscle fibers, inflammation, connective tissue, and vasculature. A short clinical presentation of cases was included, and experts were asked to give a tentative diagnosis of polymyositis, dermatomyositis, inclusion-body myositis, antisynthetase syndrome–related myositis, immune-mediated necrotizing myopathy, nonspecific myositis, or other disease. Fleiss κ values, scoring interrater variability, showed the highest agreement within the muscle fiber and connective tissue domains.ResultsDespite overall low κ values, moderate agreement was achieved for tentative diagnosis, supporting the idea of using holistic muscle biopsy interpretation rather than adding up individual features.ConclusionThe assessment of individual pathologic features needs to be standardized and harmonized and should be measured for sensitivity and specificity for subgroup classification. Standardizing the process of diagnostic muscle biopsy reading would allow identification of more homogeneous patient cohorts for upcoming treatment trials.

Published
2019

28. Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial

Author

Gil I Wolfe, Henry J Kaminski, Inmaculada B Aban, Greg Minisman, Hui-Chien Kuo, Alexander Marx, Philipp Ströbel, Claudio Mazia, Joel Oger, J Gabriel Cea, Jeannine M Heckmann, Amelia Evoli, Wilfred Nix, Emma Ciafaloni, Giovanni Antonini, Rawiphan Witoonpanich, John O King, Said R Beydoun, Colin H Chalk, Alexandru C Barboi, Anthony A Amato, Aziz I Shaibani, Bashar Katirji, Bryan R F Lecky, Camilla Buckley, Angela Vincent, Elza Dias-Tosta, Hiroaki Yoshikawa, Márcia Waddington-Cruz, Michael T Pulley, Michael H Rivner, Anna Kostera-Pruszczyk, Robert M Pascuzzi, Carlayne E Jackson, Jan J G M Verschuuren, Janice M Massey, John T Kissel, Lineu C Werneck, Michael Benatar, Richard J Barohn, Rup Tandan, Tahseen Mozaffar, Nicholas J Silvestri, Robin Conwit, Joshua R Sonett, Alfred Jaretzki, John Newsom-Davis, Gary R Cutter, Gary Cutter, Inmaculada Aban, Michelle Feese, Gil Wolfe, Henry Kaminski, Joshua Sonett, Valeria Saluto, Moises Rosenberg, Valeria Alvarez, Lisa Rey, John King, Helmut Butzkueven, John Goldblatt, John Carey, John Pollard, Stephen Reddel, Nicholas Handel, Brian McCaughan, Linda Pallot, Ricardo Novis, Carlos Boasquevisque, Rubens Morato-Fernandez, Manoel Ximenes, Lineu Werneck, Rosana Scola, Paulo Soltoski, Colin Chalk, Fraser Moore, David Mulder, Lisa Wadup, Michele Mezei, Kenneth Evans, Theresa Jiwa, Anne Schaffar, Chris White, Cory Toth, Gary Gelfand, Susan Wood, Elizabeth Pringle, Jocelyn Zwicker, Donna Maziak, Farid Shamji, Sudhir Sundaresan, Andrew Seely, Gabriel Cea, Renato Verduga, Alberto Aguayo, Sebastian Jander, Philipp Zickler, Michael Klein, Cleo-Aron Weis, Arthur Melms, Felix Bischof, Hermann Aebert, Gerhard Ziemer, Björn Thümler, Thomas Wilhem-Schwenkmezger, Eckhard Mayer, Berthold Schalke, Peter Pöschel, Gisela Hieber, Karsten Wiebe, Alessandro Clemenzi, Vanessa Ceschin, Erino Rendina, Federico Venuta, Stefania Morino, Elisabetta Bucci, Luca Durelli, Alessia Tavella, Marinella Clerico, Giulia Contessa, Piero Borasio, Serenella Servidei, Pierluigi Granone, Renato Mantegazza, Emilia Berta, Lorenzo Novellino, Luisa Spinelli, Masakatsu Motomura, Hidenori Matsuo, Takeshi Nagayasu, Masaharu Takamori, Makoto Oda, Isao Matsumoto, Yutaka Furukawa, Daisuke Noto, Yuko Motozaki, Kazuo Iwasa, Daisuke Yanase, Guillermo Garcia Ramos, Bernardo Cacho, Lorenzo de la Garza, Anne Kostera-Pruszczyk, Marta Lipowska, Hubert Kwiecinski, Anna Potulska-Chromik, Tadeusz Orlowski, Ana Silva, Marta Feijo, António Freitas, Jeannine Heckmann, Andrew Frost, Edward Pan, Lawrence Tucker, Johan Rossouw, Fiona Drummond, Isabel Illa, Jorge Diaz, Carlos Leon, Jiann-Horng Yeh, Hou-Chang Chiu, Yei-San Hsieh, Supoch Tunlayadechanont, Sukasom Attanavanich, Jan Verschuuren, Chiara Straathof, Maarten Titulaer, Michel Versteegh, Arda Pels, Yvonne Krum, M. Isabel Leite, David Hilton-Jones, Chandi Ratnatunga, Maria Farrugia, Richard Petty, James Overell, Alan Kirk, Andrew Gibson, Chris McDermott, David Hopkinson, Bryan Lecky, David Watling, Dot Marshall, Sam Saminaden, Deborah Davies, Charlotte Dougan, Siva Sathasivam, Richard Page, Jon Sussman, John Ealing, Peter Krysiak, Anthony Amato, Mohammad Salajegheh, Michael Jaklitsch, Kristen Roe, Tetsuo Ashizawa, Robert Glenn Smith, Joseph Zwischenberg, Penny Stanton, Alexandru Barboi, Safwan Jaradeh, William Tisol, Mario Gasparri, George Haasler, Mary Yellick, Cedric Dennis, Richard Barohn, Mamatha Pasnoor, Mazen Dimachkie, April McVey, Gary Gronseth, Arthur Dick, Jeffrey Kramer, Melissa Currence, Laura Herbelin, Jerry Belsh, George Li, John Langenfeld, Mary Ann Mertz, Taylor Harrison, Seth Force, Sharon Usher, Said Beydoun, Frank Lin, Steve DeMeester, Salem Akhter, Ali Malekniazi, Gina Avenido, Brian Crum, Margherita Milone, Stephen Cassivi, Janet Fisher, Chad Heatwole, Thomas Watson, James Hilbert, Alexis Smirnow, B. Jane Distad, Michael Weiss, Douglas Wood, Joanna Haug, Raina Ernstoff, Jingyang Cao, Gary Chmielewski, Robert Welsh, Robin Duris, Laurie Gutmann, Gauri Pawar, Geoffrey Marc Graeber, Patricia Altemus, Christopher Nance, Ludwig Gutmann, Carlayne Jackson, Patrick Grogan, John Calhoon, Pamela Kittrell, Deborah Myers, Ghazala Hayat, Keith Naunheim, Susan Eller, Eve Holzemer, Amer Alshekhlee, Jason Robke, Brenda Karlinchak, Jonathan Katz, Robert Miller, Ralph Roan, Dallas Forshew, John Kissel, Bakri Elsheikh, Patrick Ross, Sharon Chelnick, Richard Lewis, Agnes Acsadi, Frank Baciewicz, Stacey Masse, Janice Massey, Vern Juel, Mark Onaitis, James Lowe, Bernadette Lipscomb, Gaby Thai, Jeffrey Milliken, Veronica Martin, Ronnie Karayan, Suraj Muley, Gareth Parry, Sara Shumway, Shin Oh, Gwen Claussen, Liang Lu, Robert Cerfolio, Angela Young, Marla Morgan, Robert Pascuzzi, John Kincaid, Kenneth Kesler, Sandy Guingrich, Angi Michaels, Lawrence Phillips, Ted Burns, David Jones, Cindy Fischer, Michael Pulley, Alan Berger, Harry D'Agostino, Lisa Smith, Michael Rivner, Jerry Pruitt, Kevin Landolfo, Demetric Hillman, Aziz Shaibani, Angelo Sermas, Ross Ruel, Farah Ismail, Mark Sivak, Martin Goldstein, Jorge Camunas, Joan Bratton, Hill Panitch, Bruce Leavitt, Marilee Jones, Srikanth Muppidi, Steven Vernino, Sharon Nations, Dan Meyer, and Nina Gorham

Subjects
0301 basic medicine, Male, medicine.medical_treatment, Edrophonium, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Prednisone, Longitudinal Studies, MGTX Study Group, Thymectomy, 3. Good health, Settore MED/26 - NEUROLOGIA, Editorial Commentary, Treatment Outcome, 6.1 Pharmaceuticals, Female, medicine.drug, Adult, medicine.medical_specialty, Clinical Trials and Supportive Activities, Clinical Sciences, Autoimmune Disease, Article, 03 medical and health sciences, Young Adult, Rare Diseases, Clinical Research, Internal medicine, Myasthenia Gravis, medicine, Humans, Adverse effect, myasthenia gravis, mgtx extension study, Intention-to-treat analysis, Neurology & Neurosurgery, business.industry, Neurosciences, Evaluation of treatments and therapeutic interventions, medicine.disease, Myasthenia gravis, Clinical trial, 030104 developmental biology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Summary Background The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Published
2019

29. One year failure rates for de-novo ventriculo-peritoneal shunts in under 3-month-old children

Author

Anthony Amato-Watkins, I. Bhatti, J Lang, Paul Leach, Gulam Zilani, Ronak Ved, and E Bentley

Subjects
Male, Pediatrics, medicine.medical_specialty, Catheters, macromolecular substances, Peritoneal shunts, Shunt infection, Ventriculoperitoneal Shunt, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Medicine, Humans, Surgical Wound Infection, Treatment Failure, Retrospective Studies, business.industry, Infant, Newborn, Infant, General Medicine, medicine.disease, Infection rate, Hydrocephalus, Anti-Bacterial Agents, 030220 oncology & carcinogenesis, Surgery, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Shunt (electrical)
Abstract

Introduction: Ventriculo-peritoneal shunts (VPS) are still the mainstay treatment for hydrocephalus in children. It is generally accepted that VPS failure and infection rates are higher for neonates than for older children. We compared our 1-year failure and infection rates in under 3-month-old children compared with older children in our department. Results: We identified 58 children under 3 months of age who underwent VPS insertion between January 2007 and December 2016. They had a 29.3% (17) shunt failure rate over the first year. There were two confirmed shunt infections (3.4%). Discussion: The 1-year shunt failure rate at our institution for VPS insertion in children over 3 months is 26.1% and the infection rate is 4.3% (9). The literature suggests that the outcome for VPS in younger children is worse than for older children. Our work shows similar outcomes for all children compared to those under 3 months at time of VPS insertion alone. Conclusion: Children under 3-months-old undergoing VPS insertion should not automatically expect an increased 1-year failure or infection rate compared with older children. The reasons for this may be as a result of increased subspecialisation, the more widespread use of antibiotic-impregnated catheters and improved neonatal care.

Published
2019

30. Free middle turbinate mucosal graft reconstruction after primary endoscopic endonasal pituitary surgery

Author

Caroline Hayhurst, Anthony Amato-Watkins, and Samuel J. C. Fishpool

Subjects
Adenoma, Adult, Male, Natural Orifice Endoscopic Surgery, medicine.medical_specialty, Pituitary gland, Free Tissue Flaps, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Lumbar, Cerebrospinal fluid, Quality of life, medicine, Humans, Pituitary Neoplasms, Prospective Studies, 030223 otorhinolaryngology, Cerebrospinal Fluid Leak, business.industry, General Medicine, Length of Stay, Plastic Surgery Procedures, Surgery, Skull, Treatment Outcome, medicine.anatomical_structure, Otorhinolaryngology, Neurosurgery, business, Pituitary surgery, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

The objective is to assess whether free middle turbinate (FMT) graft reconstruction, after endoscopic endonasal pituitary surgery, combines an acceptably low post-operative cerebrospinal fluid (CSF) leak rate with acceptable rhinological morbidity. This study identified 50 patients who underwent endoscopic endonasal pituitary surgery by the senior author in our teaching hospital between May 2011 and June 2012. FMT graft reconstruction was used in 32 cases. 18 patients were judged pre-operatively as not suitable for FMT reconstruction according to a novel skull base reconstructive algorithm. Outcomes examined were: length of inpatient stay; post-operative CSF leak rate; volume of gross tumour resection; and rhinological morbidity. The rhinological morbidity was measured by the completion of the 22 item sinonasal outcome test (SNOT-22) questionnaire by all 32 patients at 6 weeks and 6 months post-surgery. 32 patients were included in the study. 9 patients had functioning microadenomas and 23 macroadenomas. The median inpatient stay was 2 days. There were no post-operative CSF leaks. The rate of gross tumour resection, confirmed on post-operative MRI, was 87.5 %. The mean SNOT-22 score was 31.9 at 6 weeks and 23.4 at 6 months post-operation-a statistically significant drop. The use of the FMT graft in the reconstruction of the sella defect after endonasal endoscopic pituitary surgery provides a robust dural repair with an acceptable rhinological morbidity profile. FMT grafting as part of a defined skull base reconstructive algorithm results in a CSF leak rate of zero and allows early patient discharge without the need for nasal packing or lumbar drains.

Published
2016

31. Cruise Controller with Fuel Optimization Based on Adaptive Nonlinear Predictive Control

Author

John Ottavio Michelini, Jaroslav Pekar, Ondrej Santin, Jaroslav Beran, Engin Ozatay, Anthony D'Amato, Steven Joseph Szwabowski, and Dimitar Petrov Filev

Subjects
050210 logistics & transportation, 0209 industrial biotechnology, Computer science, 05 social sciences, Cruise, Control engineering, 02 engineering and technology, 020901 industrial engineering & automation, Control and Systems Engineering, Control theory, 0502 economics and business, Automotive Engineering, Nonlinear predictive control, Electrical and Electronic Engineering, Safety, Risk, Reliability and Quality
Published
2016

32. Pathology of Skeletal Muscle

Author

Hart G.W. Lidov, Romain K. Gherardi, Umberto De Girolami, and Anthony Amato

Subjects
Pathology, medicine.medical_specialty, medicine.anatomical_structure, business.industry, Medicine, Skeletal muscle, business
Abstract

This chapter offers a contemporary approach to the classification of diseases of skeletal muscle and describes and illustrates the pathology of muscle disease, particularly from the perspective of the muscle biopsy. After an introductory exposition of the relevant laboratory techniques and a synopsis of the normal appearance of skeletal muscle, the basic reactions to injury are described. The ranges of diseases of skeletal muscle are then systematically considered and their specific morphologic, biochemical, and molecular genetic abnormalities are discussed in detail. The approach is to subdivide muscle disease into two broad categories: conditions that result in denervation of muscle (i.e., neurogenic atrophy) and diseases where the primary abnormality is in the muscle cell itself (i.e. myopathies). Genetically determined diseases of skeletal muscle discussed include muscular dystrophies, congenital myopathies, myofibrillar myopathies, and metabolic myopathies. Next described are the inflammatory myopathies, which are divided into two groups according to whether the causative agent is a known microorganisms or whether the inflammatory process is believed to be an autoimmune phenomenon.

Published
2018

35. Whales: Their Emerging Right to Life

Author

Sudhir K. Chopra and Anthony D'Amato

Subjects
Resource (biology), Pet therapy, Political science, Environmental ethics, Entitlement, Right to life, Humanism, International law, Human animal bond
Abstract

We have contended in this article that the evolution of the opinio juris of nations has encompassed five, and perhaps six, inexorable qualitative stages: free resource, regulation, conservation, protection, preservation and entitlement. We have argued that assigning whales an entitlement to life is the consequence of an emerging humanist right in international law m an example of the merging of the qisq and the qoughtq of the law in the process of legitimization

Published
2017

36. A Method for Rapid Durability Test Development

Author

Harpreet Grewal, Anthony D'Amato, and Kathleen Rossie

Subjects
020303 mechanical engineering & transports, 0203 mechanical engineering, Computer science, 020302 automobile design & engineering, 02 engineering and technology, Durability, Reliability engineering, Test (assessment)
Published
2017

37. Anthony D’Amato Responds

Author

Anthony D'Amato

Subjects
Political science, Political Science and International Relations, Law
Published
2014

38. Groundwork for International Law

Author

Anthony D'Amato

Subjects
050502 law, International relations, Autopoiesis, Heuristic, Field (Bourdieu), 05 social sciences, International law, 0506 political science, Epistemology, Meaning (philosophy of language), Systems theory, Political Science and International Relations, 050602 political science & public administration, Cybernetics, Sociology, Law, 0505 law
Abstract

International law is a system; its environment is the field of international relations. Although the word system is often used generically, it has a formal meaning in “general systems theory,” an interdisciplinary methodology that grew out of cybernetics research in the 1970S. Since then, general systems theory has proved to be a significant heuristic in hundreds of disparate research areas. In describing international law from the viewpoint of an autopoietic system (to be defined shortly), this article intends not just to reexamine the foundations of international law but also to help litigators and negotiators make their international-law arguments sounder and more persuasive.

Published
2014

39. P104 One year failure rates for de novo ventriculo-peritonealshunts in under 3- month-old children

Author

Gulam Zilani, Paul Leach, E Bentley, Ronak Ved, Anthony Amato-Watkins, I. Bhatti, and J Lang

Subjects
Pediatrics, medicine.medical_specialty, business.industry, Shunt malfunction, Infection rate, Shunt (medical), Psychiatry and Mental health, Single centre, medicine, Surgery, Case note, In patient, Neurology (clinical), business, Survival analysis
Abstract

ObjectivesHistorically VPS failure and infection rates are higher for neonates than for older children. We compared our one year VPS failure and infection rates in under 3-month-olds with those of older children.DesignA retrospective, single centre study comparing 1 year survival and infection rates of VPS in under 3-month-olds verses older children.Subjects58 children under 3 months of age underwent VPS insertion between January 2007 and December 2016.MethodsData was collected by three independent reviewers from electronic files and case notes. Data was analysed using descriptive statistics and one year shunt survival curves were produced.ResultsFor children under 3 months there was a 29.3% one-year shunt failure rate, of which 2 were shunt infections (3.4%). In patients greater than 3 months, the shunt malfunction rate was 23.4% and the infection rate was 4.3%. There were no shunt-related mortalities in either group.ConclusionsChildren under 3-months-old undergoing VPS insertion should not automatically expect an increased 1 year failure or infection rate compared with older children. Reasons for this may be increased sub-specialisation, improved neonatal care and use of antibiotic impregnated catheters.

Published
2019

41. Cerebellar pilocytic astrocytoma in adults: a management paradigm for a rare tumour

Author

Alistair Lammie, Anthony Amato-Watkins, Paul Leach, Caroline Hayhurst, and Antonia Wade

Subjects
Adult, Male, medicine.medical_specialty, Pathology, Proliferation index, Astrocytoma, Young Adult, Median follow-up, medicine, Humans, Cerebellar Neoplasms, Aged, Retrospective Studies, Neuroradiology, Cerebellar Pilocytic Astrocytoma, medicine.diagnostic_test, Pilocytic astrocytoma, business.industry, Retrospective cohort study, Interventional radiology, Middle Aged, medicine.disease, Ki-67 Antigen, Treatment Outcome, Female, Surgery, Neurology (clinical), Radiology, Neurosurgery, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

Pilocytic astrocytoma is one of the commonest subtypes of glioma to affect children. However, they are rarely diagnosed in patients over the age of 18 years. In adults, these tumours appear more frequently supra-tentorially than in the cerebellum and some reports suggest a different clinical course in adults. We reviewed ten patients aged 18 or over who had been operated on for cerebellar pilocytic astrocytoma to assess the impact of tumour biology and extent of resection on outcome in adults. Patients were identified from a neuropathology database and a retrospective chart review of ten patients was performed. Recorded data included patient demographics, tumour location, presenting features, radiological appearance, extent of surgical resection, tumour recurrence and Ki-67 proliferation index. Nine patients were men and one patient was a woman. Median follow up is 41.5 months (range 15–334 months). Complete surgical resection was achieved in nine of the patients operated in our institution. One patient had prior subtotal resection elsewhere. Tumour recurrence was seen only in the two patients with subtotal resection, at 7 and 25 years. Ki-67 ranged from

Published
2013

42. Retrospective Cost Optimization for Adaptive State Estimation, Input Estimation, and Model Refinement

Author

Anthony D'Amato, Asad A. Ali, Aaron J. Ridley, and Dennis S. Bernstein

Subjects
Estimation, 0209 industrial biotechnology, Mathematical optimization, Adaptive control, Model refinement, 010504 meteorology & atmospheric sciences, Computer science, input estimation, 02 engineering and technology, 01 natural sciences, Synthetic data, Cost optimization, Physics::Geophysics, 020901 industrial engineering & automation, Input estimation, Physics::Space Physics, General Earth and Planetary Sciences, state estimation, State (computer science), 0105 earth and related environmental sciences, General Environmental Science
Abstract

Retrospective cost optimization was originally developed for adaptive control. In this paper, we show how this technique is applicable to three distinct but related problems, namely, state estimation, input estimation, and model refinement. To illustrate these techniques, we give two examples. In the first example, retrospective cost model refinement is used with synthetic data to estimate the cooling dynamics that are missing from a model of the ionosphere-thermosphere. In the second example, retrospective cost adaptive state estimation is used with data from a satellite to estimate a solar driver in the ionosphere- thermosphere, with performance gauged by using data from a second satellite.

Published
2013

43. Forgetting Methods for White Box Learning

Author

Matthieu Boussard and Anthony D’Amato

Subjects
Forgetting, Computer science, business.industry, Decision tree, Context (language use), 02 engineering and technology, User expectations, Domain (software engineering), User experience design, Order (business), Human–computer interaction, 020204 information systems, 0202 electrical engineering, electronic engineering, information engineering, 020201 artificial intelligence & image processing, White box, business
Abstract

In the Internet of Things (IoT) domain, being able to propose a contextualized and personalized user experience is a major issue. The explosion of connected objects makes it possible to gather more and more information about users and therefore create new, more innovative services that are truly adapted to users. To attain these goals, and meet the user expectations, applications must learn from user behavior and continuously adapt this learning accordingly. To achieve this, we propose a solution that provides a simple way to inject this kind of behavior into IoT applications by pairing a learning algorithm (C4.5) with Behavior Trees. In this context, this paper presents new forgetting methods for the C4.5 algorithm in order to continuously adapt the learning.

Published
2016

46. An observational pilot study of CSF diversion in subarachnoid haemorrhage

Author

Michael L. James, Carmelo Graffagnino, Margaret E. Zomorodi, DaiWai M. Olson, Anthony Amato, Gavin W. Britz, and Ali R. Zomorodi

Subjects
Male, medicine.medical_specialty, Intracranial Pressure, Pilot Projects, Critical Care Nursing, law.invention, Randomized controlled trial, law, medicine, Humans, Vasospasm, Intracranial, Prospective Studies, cardiovascular diseases, Prospective cohort study, Monitoring, Physiologic, Intracranial pressure, business.industry, Incidence (epidemiology), Vasospasm, Middle Aged, Subarachnoid Hemorrhage, medicine.disease, Cerebrospinal Fluid Shunts, nervous system diseases, Surgery, Catheter, Treatment Outcome, Anesthesia, Drainage, Female, Observational study, Neurosurgery, business
Abstract

Background: A primary focus of hospital treatment following admission for subarachnoid haemorrhage (SAH) is a prevention of cerebral artery vasospasm, which may result in ischaemic stroke. Intraventricular catheter (IVC) insertion to facilitate cerebral spinal fluid (CSF) drainage and intracranial pressure (ICP) monitoring may reduce the incidence or severity of vasospasm, but insufficient evidence exists from which clinicians may determine the best practice of CSF management. Aims: The aim of this study was to provide the pilot data to explore the impact of different methods of CSF drainage on outcomes in patients with SAH. Methods: In this non-randomized observational study, patients diagnosed with SAH who had ICP monitoring in situ were prospectively enrolled. Group assignment was determined by the method of external ventricular drainage (EVD) management prescribed by the attending physician prior to enrollment. Results: The 37 subjects were disproportionately divided: open-EVD group (N = 24) and monitor-ICP group (N = 13). There were no statistically significant differences by group assignment with respect to vasospasm, length of stay (LOS), highest average ICP, total CSF drained and disability upon discharge between groups. Conclusions: Although not significant, our results show that the monitor-ICP group trended towards improved clinical outcomes. These results provide sufficient equipoise to support further research in ICP management in patients with SAH using a randomized clinical trial. Relevance to clinical practice: This study provides a solid foundation for the development of a randomized trial exploring two different methods of ICP monitoring and CSF diversion during the acute phase of care following aneurysm rupture.

Published
2011

47. Retrospective-cost-based adaptive model refinement for the ionosphere and thermosphere

Author

Aaron J. Ridley, Anthony D'Amato, and Dennis S. Bernstein

Subjects
Model refinement, Mathematical model, Computer science, Process (engineering), Truth model, media_common.quotation_subject, System identification, Fidelity, computer.software_genre, Computer Science Applications, Data mining, Ionosphere, Thermosphere, computer, Analysis, Information Systems, media_common
Abstract

Mathematical models of physical phenomena are of critical importance in virtually all applications of science and technology. This paper addresses the problem of how to use data to improve the fidelity of a given model. We approach this problem using retrospective cost optimization, which uses data to recursively update an unknown subsystem interconnected to a known system. Applications of this technique are relevant to applications that depend on large-scale models based on first-principles physics, such as the global ionosphere–thermosphere model (GITM). Using GITM as the truth model, we demonstrate that measurements can be used to identify unknown physics. Specifically, we estimate static thermal conductivity parameters, as well as a dynamic cooling process. © 2011 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 4: 446–458, 2011 © 2011 Wiley Periodicals, Inc.

Published
2011

48. Semi-parametric identification of Wiener systems using a single harmonic input and retrospective cost optimisation

Author

Anthony D'Amato, Bruno O. S. Teixeira, and Dennis S. Bernstein

Subjects
Mathematical optimization, Control and Optimization, Linear system, Nonparametric statistics, System identification, Computer Science Applications, Semiparametric model, Human-Computer Interaction, symbols.namesake, Wiener process, Control and Systems Engineering, Control theory, Parametric model, Piecewise, Harmonic, symbols, Electrical and Electronic Engineering, Mathematics
Abstract

The authors present a two-step method for identifying single-input, single-output (SISO) Wiener systems. First, using a single harmonic input, they estimate a non-parametric model of the static non-linearity, which is assumed to be only piecewise continuous. Second, using the identified non-parametric map, the authors use retrospective cost optimisation to identify a parametric model of the linear dynamic system. This method is demonstrated on several examples of increasing complexity.

Published
2011

49. Comments on ‘output feedback adaptive command following and disturbance rejection for nonminimum phase uncertain dynamical systems’

Author

Dennis S. Bernstein, Jesse B. Hoagg, Anthony D'Amato, and Mario A. Santillo

Subjects
Output feedback, Engineering, Adaptive control, Disturbance (geology), Dynamical systems theory, business.industry, Phase (waves), Control engineering, Control and Systems Engineering, Control theory, Signal Processing, Convergence (routing), Electrical and Electronic Engineering, business, Reference model
Abstract

We provide numerical examples and analysis to show that the adaptive controller given by Theorem 3.1 of Yucelen et al.1 may fail to stabilize plants under the stated conditions. Copyright © 2011 John Wiley & Sons, Ltd.

Published
2011

50. New Approaches to Customary International Law

Author

Anthony D'Amato

Subjects
Legalism (Western philosophy), Law, Political science, Political Science and International Relations, Customary international law, International law
Abstract

Reviews Eric A. Posner, The Perils of Global Legalism; Andrew T. Guzman, How International Law Works; Brian A. Lepard, Customary International Law.After a century of benign neglect, international theorizing has taken off. The three contributors to legal theory reviewed here can be placed along a linear spectrum with Posner at the extreme political science end, Lepard at the opposite international law end and Andrew Guzman holding up the middle.

Published
2011

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