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1. Diagnostic performance of point-of-care ubiquitin carboxy-terminal Hydrolase-L1 assay in distinguishing imaging abnormalities in traumatic brain injury: A TRACK-TBI cohort study

Author

Kevin K. Wang, Jennifer C. Munoz-Pareja, Lauren A. Lautenslager, J. Adrian Tyndall, Zhihui Yang, Maria R. Kerrigan, Ramon Diaz-Arrastia, Frederick K. Korley, David Okonkwo, Ava M. Puccio, John K. Yue, Sabrina R. Taylor, Pratik Mukherjee, Esther L. Yuh, Nancy R. Temkin, Claudia S. Robertson, Xiaoying Sun, Sonia Jain, Amy J. Markowitz, Geoffrey T. Manley, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, V Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J Claude Hemphill, Gillian Hotz, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Lindsay Nelson, Laura Ngwenya, Eva Palacios, Daniel Perl, Miri Rabinowitz, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, and Ross Zafonte

Subjects
TBI, Biomarkers, UCH-L1, Point of care, Mild TBI, NSE, Toxicology. Poisons, RA1190-1270, Biotechnology, TP248.13-248.65, Biology (General), QH301-705.5
Abstract

The use of UCH-L1 detection with point-of-care (POC) assay alone has not been characterized for clinical use. This study compares the accuracies of POC UCH-L1 and Neuron-Specific Enolase (NSE) Elecsys® levels for identifying TBI patients with structural abnormalities on neuroimaging.The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Phase 1 Cohort, enrolled 1375 TBI patients (GCS 3–15) presenting to one of 18 US Level I trauma centers within 24 h of injury who had an admission head CT; blood samples were collected, along with 122 orthopedic and 209 healthy controls. The TBI cohort consisted of 810 CT-negative (CT-) and 549 CT-positive (CT+) subjects. Of the CT- subjects who had MRIs, 121 were MRI-positive (MRI+) and 333 were MRI-negative (MRI-). UCH-L1 POC showed best diagnostic performance for CT + versus CT-, 0–8 h post-injury with an AUC of 0·779 [0·708–0.850] when compared to the 0–25 h interval, with an AUC of 0.684 [0.655–0.712]. NSE assay has an AUC of 0.695 [0.619–0.770] for the 0–8 h interval and 0.634 [0.603–0.665] for the 0–25 h interval. During the first 8 after injury, POC UCH-L1 outperforms NSE in identifying TBI patients with structural abnormalities on neuroimaging.

Published
2023
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2. Online Case Study: The Clinical and Pathological Differential Diagnosis of Encephalopathy ('The Mysterious Case of ‘John Doe’')

Author

Huaibin Mabel Ko, Daniel Perl, Stephen Krieger, Reena Karani, Robert Fallar, Merril Schindler, and Margret Magid

Subjects
CNS, Encephalopathy, Hepatic Artery, Alcohol, Wernicke, Online, Medicine (General), R5-920, Education
Abstract

Abstract Introduction This online clinical case was designed to complement and reinforce material covered in the module on Nutritional/Metabolic disturbances in a second-year brain and behavior course. The goal of this exercise was to have the student apply important concepts previously presented in class to a realistic patient. It could also be utilized during the clinical years for a review of the basic science underlying encephalopathy. Methods The module was created to be an enjoyable, interactive, multimedia experience that guides the student through clinical decision making in a patient presenting with confusion. A brief discussion of this disorder concludes the exercise. Case efficacy was evaluated through a posttest and a student survey. Results The case was available to half of the class of 143 students (Group 1) for a period of 6 days following completion of the Nutritional/Metabolic Disturbances module. The remaining 72 students (Group 2) did not initially have access to the case. After the case was closed, an elective seven multiple-choice question online quiz was opened to all 143 students. The average total score (out of max of 7) for Group 1 was 5.58, while the score of Group 2 was 4.57 (p = .0004). For the survey, feedback was incorporated into an anonymous postcourse evaluation. Seven questions about the exercise were evaluated on a Likert scale from 1–5. In addition, free-text comments were solicited. Fifty-three students completed the survey. The quiz and survey results indicate that the case is both well-received and effective for short-term learning. Discussion The significance of the work is the integration of basic science/pathology and clinical medicine in the format of an engaging case review of encephalopathy. The case is appropriate both for preclinical students learning about clinical workup, as well as for students in the clerkship and post-clerkship years reviewing the underpinnings of basic science in clinical medicine.

Published
2013
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3. Low-Dose Brain Radiation: Lowering hyperphosphorylated-Tau without Increasing DNA Damage or Oncogenic Activation

Author

Diego Iacono, Erin Murphy, Cheryl Stimpson, Daniel Perl, and Regina Day

Abstract

Brain radiation has been medically used to alter the metabolism of cancerous cells and induce their elimination. Rarely, though, brain radiation has been used to interfere with the pathomechanisms of non-cancerous brain disorders, especially neurodegenerative disorders. Data from low-dose radiation (LDR) on swine brains demonstrated reduced levels of phosphorylated-tau (CP13) and amyloid precursor protein (APP) in radiated (RAD) vs. sham (SH) animals. Phosphorylated-tau and APP are involved in Alzheimer’s disease (AD) pathogenesis. We determined if the expression levels of hyperphosphorylated-tau, 3R-tau, 4R-tau, synaptic, intraneuronal damage, and DNA damage/oncogenic activation markers were altered in RAD vs. SH swine brains. Quantitative analyses demonstrated reduced levels of AT8 and 3R-tau in hippocampus (H) and striatum (Str), increased levels of synaptophysin and PSD-95 in frontal cortex (FCtx), and reduced levels of NF-L in cerebellum (CRB) of RAD vs. SH swine. DNA damage and oncogene activation marker levels did not differ between RAD and SH animals, except for histone-H3 (increased in FCtx and CRB, decreased in Str), and p53 (reduced in FCtx, Str, H and CRB). These findings confirm the region-based effects of sLDR on proteins normally expressed in larger mammalian brains and support the potential applicability of LDR to beneficially interfere against neurodegenerative mechanisms.

Published
2023
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4. A genome-wide association study of outcome from traumatic brain injury

Author

Mart Kals, Kevin Kunzmann, Livia Parodi, Farid Radmanesh, Lindsay Wilson, Saef Izzy, Christopher D. Anderson, Ava M. Puccio, David O. Okonkwo, Nancy Temkin, Ewout W. Steyerberg, Murray B. Stein, Geoff T. Manley, Andrew I.R. Maas, Sylvia Richardson, Ramon Diaz-Arrastia, Aarno Palotie, Samuli Ripatti, Jonathan Rosand, David K. Menon, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Coburn, Jonathan P. Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire DahyotFizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, GuyLoup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J.A. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Jiyao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Kornaropoulos, LarsOwe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Ana M. CastañoLeón, Marc Maegele, Marek Majdan, Alex Manara, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia F.J. Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Paul M. Parizel, JeanFrançois Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Isabel Retel Helmrich, Jonathan Rhodes, Sophie Richter, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan SanchezPorras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest van Veen, Thijs Vande Vyvere, Roel P.J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Janek Frantzén, Ari Katila, Henna-Rikka Maanpää, Jussi Tallus, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Jason Barber, Yelena Bodien, Randall Chesnut, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, Claude Hemphill, Gillian Hotz, Sonia Jain, Dirk Keene, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Geoffrey T. Manley, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B Ngwenya, Florence Noel, Amber Nolan, David Okonkwo, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Mark Sherer, Murray Stein, Sabrina Taylor, Arthur Toga, Alex Valadka, Mary Vassar, John K. Yue, Esther Yuh, Ross Zafonte, Public Health, Cell biology, Ragauskas, Arminas, Ročka, Saulius, Tamošuitis, Tomas, Vilcinis, Rimantas, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J. A., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Jiyao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, LarsOwe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., CastañoLeón, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David K., Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia F. J., Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, JeanFrançois, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Raj, Rahul, Rambadagalla, Malinka, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, SanchezPorras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, van Veen, Ernest, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Åkerlund, Cecilia, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Amrein, Krisztina, Ziverte, Agate, Zoerle, Tommaso, Izzy, Saef, Radmanesh, Farid, Frantzén, Janek, Katila, Ari, Maanpää, Henna-Rikka, Tallus, Jussi, Adeoye, Opeolu, Badjatia, Neeraj, Andelic, Nada, Boase, Kim, Barber, Jason, Bodien, Yelena, Chesnut, Randall, Corrigan, John D., Crawford, Karen, Diaz-Arrastia, Ramon, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Andreassen, Lasse, Feeser, Ramana, Ferguson, Adam R., Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Anke, Audny, Hemphill, Claude, Hotz, Gillian, Jain, Sonia, Keene, Dirk, Korley, Frederick K., Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Antoni, Anna, Madden, Christopher, Manley, Geoffrey T., Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Mukherjee, Pratik, Nelson, Lindsay, Ngwenya, Laura B., Noel, Florence, Audibert, Gérard, Nolan, Amber, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Azouvi, Philippe, Schnyer, David, Seabury, Seth, Sherer, Mark, Stein, Murray, Taylor, Sabrina, Temkin, Nancy, Toga, Arthur, Valadka, Alex, Vassar, Mary, Yue, John K., Azzolini, Maria Luisa, Yuh, Esther, Zafonte, Ross, Carroll, Ellen, Chatfield, Doris A., Coles, Jonathan P., Helmy, Adel, Manktelow, Anne, Outtrim, Joanne G., Bartels, Ronald, Takala, Rikka, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, DahyotFizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, GuyLoup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Molecular Neuroscience and Ageing Research (MOLAR), Kals, M, Kunzmann, K, Parodi, L, Radmanesh, F, Wilson, L, Izzy, S, Anderson, C, Puccio, A, Okonkwo, D, Temkin, N, Steyerberg, E, Stein, M, Manley, G, Citerio, G, Genetic Associations In Neurotrauma (GAIN) Consortium, CENTER-TBI, CABI, MGB, TBIcare Studies, TRACK-TBI, „Elsevier Science' grupė, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, Institute for Molecular Medicine Finland, Complex Disease Genetics, Research Programs Unit, Centre of Excellence in Complex Disease Genetics, Genomics of Neurological and Neuropsychiatric Disorders, Faculty Common Matters (Faculty of Social Sciences), Department of Public Health, and Biostatistics Helsinki

Subjects
Traumatic, Physical Injury - Accidents and Adverse Effects, Clinical Sciences, LOCI, SUSCEPTIBILITY, Traumatic Brain Injury (TBI), Mannose-Binding Lectin, DISEASE, General Biochemistry, Genetics and Molecular Biology, Traumatic brain injury, Consortia, Recovery, Brain Injuries, Traumatic, Genetics, 2.1 Biological and endogenous factors, Humans, Prospective Studies, Aetiology, Traumatic Head and Spine Injury, Outcome, Human Genome, 3112 Neurosciences, Neurosciences, General Medicine, LECTIN, Brain Disorders, Good Health and Well Being, consortia, genome-wide association study, outcome, recovery, traumatic brain injury, Brain Injuries, Genetic Associations In Neurotrauma (GAIN) Consortium, Public Health and Health Services, Human medicine, Transcriptome, Genome-Wide association study
Abstract

EBioMedicine 77, 103933 (2022). doi:10.1016/j.ebiom.2022.103933, Published by Elsevier, Amsterdam [u.a.]

Published
2022
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5. Life After Mild Traumatic Brain Injury: Widespread Structural Brain Changes Associated With Psychological Distress Revealed With Multimodal Magnetic Resonance Imaging

Author

Francesca Sibilia, Rachel M. Custer, Andrei Irimia, Farshid Sepehrband, Arthur W. Toga, Ryan P. Cabeen, Opeolu Adeoye, Neeraj Badjatia, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Laura B. Ngwenya, Florence Noel, David Okonkwo, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Sabrina Taylor, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, Kevin Wang, John K. Yue, and Ross Zafonte

Subjects
General Medicine
Published
2022
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6. Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain

Author

Anthony Fernández-Castañeda, Peiwen Lu, Anna C. Geraghty, Eric Song, Myoung-Hwa Lee, Jamie Wood, Belgin Yalçın, Kathryn R. Taylor, Selena Dutton, Lehi Acosta-Alvarez, Lijun Ni, Daniel Contreras-Esquivel, Jeff R. Gehlhausen, Jon Klein, Carolina Lucas, Tianyang Mao, Julio Silva, Mario A. Peña-Hernández, Alexandra Tabachnikova, Takehiro Takahashi, Laura Tabacof, Jenna Tosto-Mancuso, Erica Breyman, Amy Kontorovich, Dayna McCarthy, Martha Quezado, Marco Hefti, Daniel Perl, Rebecca Folkerth, David Putrino, Avi Nath, Akiko Iwasaki, and Michelle Monje

Subjects
myelin, COVID-19, long-COVID, microglia, oligodendrocytes, hippocampal neurogenesis, Article, cognitive impairment, neuroinflammation
Abstract

Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed of information processing and memory. This long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI. We hypothesized that similar cellular mechanisms may contribute to the persistent neurological symptoms associated with even mild SARS-CoV-2 respiratory infection. Here, we explored neuroinflammation caused by mild respiratory SARS-CoV-2 infection – without neuroinvasion - and effects on hippocampal neurogenesis and the oligodendroglial lineage. Using a mouse model of mild respiratory SARS-CoV-2 infection induced by intranasal SARS-CoV-2 delivery, we found white matter-selective microglial reactivity, a pattern observed in CRCI. Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function. Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice. Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.

Published
2022

7. Effect of frailty on 6-month outcome after traumatic brain injury: a multicentre cohort study with external validation

Author

Stefania Galimberti, Francesca Graziano, Andrew I R Maas, Giulia Isernia, Fiona Lecky, Sonia Jain, Xiaoying Sun, Raquel C Gardner, Sabrina R Taylor, Amy J Markowitz, Geoffrey T Manley, Maria Grazia Valsecchi, Giuseppe Bellelli, Giuseppe Citerio, Cecilia Ackerlund, Hadie Adams, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M. Castaño-León, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Hans Clusmann, Mark Steven Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Covic, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Marc Maegele, Marek Majdan, Alex Manara, Hugues Maréchal, Costanza Martino, Julia Mattern, Charles McFadyen, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Matej Oresic, Fabrizio Ortolano, Olubukola Otesile, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Veronika Rehorčíková, Isabel Retel Helmrich, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Ranjit D. Singh, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolijn Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Mathieu van der Jagt, Joukje van der Naalt, Gregory Van der Steen, Jeroen T.J.M. van Dijck, Inge A. van Erp, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest van Veen, Roel van Wijk, Thijs Vande Vyvere, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Peter Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Agate Ziverte, Tommaso Zoerle, Opeolu Adeoye, Neeraj Badjatia, Jason Barber, Michael Bergin, Kim Boase, Yelena Bodien, Randall Chesnut, John Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, Venkata Feeser, Adam R Ferguson, Brandon Foreman, Etienne Gaudette, Joseph Giacino, Luis Gonzalez, Shankar Gopinath, Ramesh Grandhi, Rao Gullapalli, Claude Hemphill, Gillian Hotz, Russell Huie, Ruchira Jha, C. Dirk Keene, Ryan Kitagawa, Frederick Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B. 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I. R., Isernia, G., Lecky, F., Jain, S., Sun, X., Gardner, R. C., Taylor, S. R., Markowitz, A. J., Manley, G. T., Valsecchi, M. G., Bellelli, G., Citerio, G., Ackerlund, C., Adams, H., Amrein, K., Andelic, N., Andreassen, L., Anke, A., Antoni, A., Audibert, G., Azouvi, P., Azzolini, M. L., Bartels, R., Barzo, P., Beauvais, R., Beer, R., Bellander, B. -M., Belli, A., Benali, H., Berardino, M., Beretta, L., Blaabjerg, M., Bragge, P., Brazinova, A., Brinck, V., Brooker, J., Brorsson, C., Buki, A., Bullinger, M., Cabeleira, M., Caccioppola, A., Calappi, E., Calvi, M. R., Cameron, P., Carbayo Lozano, G., Carbonara, M., Castano-Leon, A. M., Cavallo, S., Chevallard, G., Chieregato, A., Clusmann, H., Coburn, M. S., Coles, J., Cooper, J. 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P., Puybasset, L., Radoi, A., Ragauskas, A., Raj, R., Rambadagalla, M., Rehorcikova, V., Retel Helmrich, I., Rhodes, J., Richardson, S., Richter, S., Ripatti, S., Rocka, S., Roe, C., Roise, O., Rosenfeld, J., Rosenlund, C., Rosenthal, G., Rossaint, R., Rossi, S., Rueckert, D., Rusnak, M., Sahuquillo, J., Sakowitz, O., Sanchez-Porras, R., Sandor, J., Schafer, N., Schmidt, S., Schoechl, H., Schoonman, G., Schou, R. F., Schwendenwein, E., Sewalt, C., Singh, R. D., Skandsen, T., Smielewski, P., Sorinola, A., Stamatakis, E., Stanworth, S., Stevens, R., Stewart, W., Steyerberg, E. W., Stocchetti, N., Sundstrom, N., Takala, R., Tamas, V., Tamosuitis, T., Taylor, M. S., Te Ao, B., Tenovuo, O., Theadom, A., Thomas, M., Tibboel, D., Timmers, M., Tolias, C., Trapani, T., Tudora, C. M., Unterberg, A., Vajkoczy, P., Valeinis, E., Vallance, S., Vamos, Z., van der Jagt, M., van der Naalt, J., Van der Steen, G., van Dijck, J. T. J. M., van Erp, I. A., van Essen, T. 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Subjects
Male, Traumatic/therapy, Frailty, Brain Injuries, Traumatic/therapy, traumatic brain injury, Reproducibility of Results, Middle Aged, Cohort Studies, Brain Injuries, Brain Injuries, Traumatic, outcome, Humans, Glasgow Coma Scale, Neurology (clinical), Human medicine, Prospective Studies, Aged
Abstract

Background: Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients’ outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good performance to predict clinical outcomes. However, each is specific to a particular clinical context. We aimed to develop a frailty index to predict 6-month outcomes in patients after a traumatic brain injury. Methods: A cumulative deficit approach was used to create a novel frailty index based on 30 items dealing with disease states, current medications, and laboratory values derived from data available from CENTER-TBI, a prospective, longitudinal observational study of patients with traumatic brain injury presenting within 24 h of injury and admitted to a ward or an intensive care unit at 65 centres in Europe between Dec 19, 2014, and Dec 17, 2017. From the individual cumulative CENTER-TBI frailty index (range 0–30), we obtained a standardised value (range 0–1), with high scores indicating higher levels of frailty. The effect of frailty on 6-month outcome evaluated with the extended Glasgow Outcome Scale (GOSE) was assessed through a proportional odds logistic model adjusted for known outcome predictors. An unfavourable outcome was defined as death or severe disability (GOSE score ≤4). External validation was performed on data from TRACK-TBI, a prospective observational study co-designed with CENTER-TBI, which enrolled patients with traumatic brain injury at 18 level I trauma centres in the USA from Feb 26, 2014, to July 27, 2018. CENTER-TBI is registered with ClinicalTrials.gov, NCT02210221; TRACK-TBI is registered at ClinicalTrials.gov, NCT02119182. Findings: 2993 participants (median age was 51 years [IQR 30–67], 2058 [69%] were men) were included in this analysis. The overall median CENTER-TBI frailty index score was 0·07 (IQR 0·03–0·15), with a median score of 0·17 (0·08–0·27) in older adults (aged ≥65 years). The CENTER-TBI frailty index score was significantly associated with the probability of an increasingly unfavourable outcome (cumulative odds ratio [OR] 1·03, 95% CI 1·02–1·04; p

Published
2022
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8. Tarot als Ratgeber für Finanzen

Author

Daniel Perl and Daniel Perl

Abstract

Als studierter Volkswirt habe ich während meines Studiums sämtliche mathematischen und statistischen Modelle kennen gelernt, mit denen man versucht, die Entwicklung von Aktienkursen, Edelmetallkursen und anderen Kursen zu analysieren und vorherzusagen. Ich habe Programme zur Analyse von Zeitreihen und Finanzmarktdaten in R und Python geschrieben aber bald gemerkt, dass selbst modernste Computer und Programmiersprachen und sogar die Mathematik nicht in der Lage sind, die Entwicklung von Aktienkursen oder anderen Finanzprodukten oder der Weltwirtschaft als Ganzes vorherzusagen. Aus diesem Grund habe ich mich nach Alternativen umgesehen, die ich zu Rate ziehen kann in finanziellen Fragen und bin so auf die Tarot Karten aufmerksam geworden. Die Weisheit der Karten gibt nützliche Ratschläge für sämtliche finanzielle Situationen und Entwicklungen. Man kann mit ihnen sogar die Weltwirtschaft oder Aktienkurse oder Gold und Silber analysieren oder wie sich Geschäftspartner verhalten werden. Für diese Zwecke werden in diesem Buch viele nützliche Legesysteme vorgestellt und erläutert sowie die volkswirtschaftlichen Grundlagen dahinter erklärt. Das Buch enthält auch allgemeine Erklärungen der Tarotkarten und kann auch abseits von finanziellen Themen verwendet werden, jedoch liegt er Fokus ganz klar auf finanziellen Themen und Anwendungen.

Published
2024

9. Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations

Author

J. Russell Huie, Stefania Mondello, Christopher J. Lindsell, Luca Antiga, Esther L. Yuh, Elisa R. Zanier, Serge Masson, Bedda L. Rosario, Adam R. Ferguson, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, Sonia Jain, Frederick Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Joan Machamer, Christopher Madden, Geoffrey T. Manley, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, David Okonkwo, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, David Schnyer, Seth Seabury, Murray Stein, Sabrina Taylor, Nancy Temkin, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, Kevin Wang, John K. Yue, Ross Zafonte, Cecilia Ackerlund, Hadie Adams, Vanni Agnoletti, Judith Allanson, Krisztina Amrein, Norberto Andaluz, Nada Andelic, Lasse Andreassen, Audny Anke, Azasevac Antun, Anna Antoni, Hilko Ardon, Kaspars Auslands, Philippe Azouvi, Maria Luisa Azzolini, Camelia Baciu, Rafael Badenes, Ronald Bartels, Pál Barzó, Ursula Bauerfeind, Romuald Beauvais, Ronny Beer, Francisco Javier Belda, Bo Michael Bellander, Antonio Belli, Rémy Bellier, Habib Benali, Thierry Benard, Maurizio Berardino, Luigi Beretta, Christopher Beynon, Federico Bilotta, Harald Binder, Erta Biqiri, Morten Blaabjerg, Hugo den Boogert, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Lozano Guillermo Carbayo, Marco Carbonara, Elsa Carise, K. Carpenter, Ana M. Castaño León, Francesco Causin, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Maryse Cnossen, Mark Coburn, Jonathan Coles, Lizzie Coles-Kemp, Johnny Collett, Jamie D. Cooper, Marta Correia, Amra Covic, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot Fizelier, François Damas, Pierre Damas, Helen Dawes, Véronique De Keyser, Francesco Della Corte, Bart Depreitere, Godard C.W. de Ruiter, Dula Dilvesi, Shenghao Ding, Diederik Dippel, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy Loup Dulière, Heiko Engemann, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Junfeng Feng, Kelly Foks, Francesca Fossi, Gilles Francony, Ulderico Freo, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Karin Geleijns, Pradeep George, Alexandre Ghuysen, Lelde Giga, Benoit Giraud, Ben Glocker, Jagos Golubovic, Pedro A. Gomez, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Asta Kristine Håberg, Bram Jacobs, Iain Haitsma, Jed A. Hartings, Raimund Helbok, Eirik Helseth, Daniel Hertle, Astrid Hoedemaekers, Stefan Hoefer, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Stefan Jankowski, Mike Jarrett, Bojan Jelaca, Ji yao Jiang, Kelly Jones, Konstantinos Kamnitsas, Mladen Karan, Ari Katila, Maija Kaukonen, Thomas Kerforne, Riku Kivisaari, Angelos G. Kolias, Bálint Kolumbán, Erwin Kompanje, Ksenija Kolundzija, Daniel Kondziella, Lars Owe Koskinen, Noémi Kovács, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Christian Ledig, Rolf Lefering, Valerie Legrand, Jin Lei, Leon Levi, Roger Lightfoot, Hester Lingsma, Dirk Loeckx, Angels Lozano, Andrew I.R. Maas, Stephen MacDonald, Marc Maegele, Majdan Marek, Sebastian Major, Alex Manara, Geoffrey Manley, Didier Martin, Leon Francisco Martin, Costanza Martino, Hugues Maréchal, Armando Maruenda, Alessandro Masala, Julia Mattern, Charles McFadyen, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Cristina Morganti Kossmann, Davide Mulazzi, Holger Mühlan, Visakh Muraleedharan, Lynnette Murray, Nandesh Nair, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, Quentin Noirhomme, József Nyirádi, Mauro Oddo, Annemarie Oldenbeuving, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Adriana Patruno, Jean François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Floury Sébastien Pili, Matti Pirinen, Horia Ples, Maria Antonia Poca, Suzanne Polinder, Inigo Pomposo, Jussi Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Ruben Real, Veronika Rehorčíková, Jonathan Rhodes, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Gerwin Roks, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Marco Sacchi, Barbara Sahakian, Juan Sahuquillo, Oliver Sakowitz, Francesca Sala, Renan Sanchez Porras, Janos Sandor, Edgar Santos, Luminita Sasu, Davide Savo, Nadine Schäffer, Inger Schipper, Barbara Schlößer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Michael Schöll, Charlie Sewalt, Özcan Sir, Toril Skandsen, Lidwien Smakman, Dirk Smeets, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Nicole Steinbüchel, Ana Stevanovic, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Fabio Silvio Taccone, Riikka Takala, Viktória Tamás, Päivi Tanskanen, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Ralph Telgmann, Guido Teodorani, Alice Theadom, Matt Thomas, Dick Tibboel, Christos Tolias, Jean Flory Luaba Tshibanda, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Gregory Van der Steen, Mathieu van der Jagt, JV de Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Julia Van Waesberghe, Audrey Vanhaudenhuyse, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Giacinta Vizzino, Carmen Vleggeert Lankamp, Victor Volovici, Daphne Voormolen, Peter Vulekovic, Zoltán Vámos, Derick Wade, Kevin K.W. Wang, Lei Wang, Lars Wessels, Eveline Wiegers, Eno Wildschut, Guy Williams, Lindsay Wilson, Maren K.L. Winkler, Stefan Wolf, Peter Ylén, Alexander Younsi, Menashe Zaaroor, Frederik Zeiler, Yang Zhihui, Agate Ziverte, Fabrizio Zumbo, Huie, J Russell, Mondello, Stefania, Lindsell, Christopher J, Antiga, Luca, Yuh, Esther L, Zanier, Elisa R, Masson, Serge, Rosario, Bedda L, Ferguson, Adam R (Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators), Beretta, Luigi, Huie, J, Mondello, S, Lindsell, C, Antiga, L, Yuh, E, Zanier, E, Masson, S, Rosario, B, Ferguson, A, Citerio, G, and Molecular Neuroscience and Ageing Research (MOLAR)

Subjects
Traumatic, 030506 rehabilitation, Data Interpretation, Data management, data sharing, TERMINAL HYDROLASE-L1, Big data, Poison control, 0302 clinical medicine, Brain Injuries, Traumatic, TBI, Medicine, Biomarker discovery, Common Data Elements, traumatic brain injury, Injuries and accidents, Statistical, Reference Standards, NET RECLASSIFICATION INDEX, Data Interpretation, Statistical, Biomarker (medicine), biomarker, 0305 other medical science, Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators, CT, The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators, medicine.medical_specialty, Physical Injury - Accidents and Adverse Effects, Clinical Sciences, Context (language use), Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Traumatic Brain Injury (TBI), Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators, 03 medical and health sciences, MICROARRAY, Special Section: Statistical Methods in Tbi Research, Humans, biomarkers, Intensive care medicine, Traumatic Head and Spine Injury, Neurology & Neurosurgery, business.industry, Information Dissemination, OUTCOME PREDICTION, Neurosciences, COMMON DATA ELEMENTS, Precision medicine, Brain Disorders, DIFFUSE AXONAL INJURY, Data sharing, Good Health and Well Being, Brain Injuries, DISCOVERY, TRACK, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Contains fulltext : 238746.pdf (Publisher’s version ) (Closed access) Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.

Published
2021

10. Pathological Computed Tomography Features Associated with Adverse Outcomes after Mild Traumatic Brain Injury

Author

Esther L. Yuh, Sonia Jain, Xiaoying Sun, Dana Pisicǎ, Mark H. Harris, Sabrina R. Taylor, Amy J. Markowitz, Pratik Mukherjee, Jan Verheyden, Joseph T. Giacino, Harvey S. Levin, Michael McCrea, Murray B. Stein, Nancy R. Temkin, Ramon Diaz-Arrastia, Claudia S. Robertson, H.F. (Hester) Lingsma, David O. Okonkwo, Andrew I.R. Maas, Geoffrey T. Manley, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, C. Dirk Keene, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan MacHamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, Amber Nolan, Eva Palacios, Daniel Perl, Miri Rabinowitz, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur W. Toga, Alex Valadka, Mary Vassar, Ross Zafonte, Esther L. Yuh, Sonia Jain, Xiaoying Sun, Dana Pisicǎ, Mark H. Harris, Sabrina R. Taylor, Amy J. Markowitz, Pratik Mukherjee, Jan Verheyden, Joseph T. Giacino, Harvey S. Levin, Michael McCrea, Murray B. Stein, Nancy R. Temkin, Ramon Diaz-Arrastia, Claudia S. Robertson, H.F. (Hester) Lingsma, David O. Okonkwo, Andrew I.R. Maas, Geoffrey T. Manley, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, C. Dirk Keene, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan MacHamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, Amber Nolan, Eva Palacios, Daniel Perl, Miri Rabinowitz, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur W. Toga, Alex Valadka, Mary Vassar, and Ross Zafonte

Abstract

Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective: To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures: Acute nonpenetrating head trauma. Main Outcomes and Measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months. Results: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; int

Published
2021
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11. Die Geschichte des Hakenheinz 2 - Gefahr aus dem Strudel

Author

Daniel Perl and Daniel Perl

Abstract

Im zweiten Teil der Geschichte des Hakenheinz muss der Hakenheinz gegen einen noch stärkeren Gegner als das Seeungeheuer kämpfen, der aus dem Strudel im Meer aufsteigt. Durch die 30 farbigen Abbildungen kann man das Abenteuer des Hakenheinz hautnah mitverfolgen. Unterstützt wird er dabei wieder von seinen Freunden Theo und Bernhard sowie einer neuen Freundin. Mit ihr findet der Hakenheinz das Schiff mit der Kraft des Waldes und bekämpft damit seinen neuen Gegner, aber auch seine alten Feinde wie den schiefen Sepp, den geraden Georg, den ominösen Otto und den Cousin des Königs. Bevor es zum großen Kampf gegen alle seine Feinde kommt, muss der Hakenheinz wieder viele Abenteuer und Kämpfe überstehen, durch die er aber noch stärker wird und zum Schluss so stark wie 39 Männer ist. Mit dieser unglaublichen Kraft und der Unterstützung seine Freunde schafft er es aber auch dieses Mal, alle seine Feinde zu besiegen.

Published
2023

12. Papa verschwindet auf den Mond

Author

Daniel Perl and Daniel Perl

Abstract

Als ihre Lieblingsspielzeuge entführt werden und ihr Papa aufgrund eines technischen Defekts mit seinem fahrbaren Stuhl auf den Mond fliegt, ist für die beiden Kinder Marlon und Aurelia klar, dass sie ihre Lieblingsspielzeuge und ihren Papa retten müssen. Auf dem Mond erleben sie mit einer kämpfenden Nudel, einem Stromausfall, einer Kartoffel, die sich Haare wünscht, und vielen anderen Mondbewohnern ein großes Abenteuer. Leider ist ihr Papa immer schon verschwunden, wenn die Kinder glauben ihn gefunden zu haben. Doch zum Schluss wird natürlich alles wieder gut, aber erst nachdem die Kinder mit ihren neuen Freunden um die Freiheit ihres Papas gekämpft haben.

Published
2023

13. Die Faszination des Bösen - Kriminelle und ihr Einfluss auf Kultur und Gesellschaft - Ted Bundy und Jack Unterweger: 2 Fallstudien

Author

Daniel Perl and Daniel Perl

Abstract

Diese Seminararbeit behandelt den Einfluss der zwei Serienmörder Ted Bundy und Johann'Jack'Unterweger auf die moderne Gesellschaft und Kultur. Im Vordergrund dieser Arbeit steht ein Vergleich des Kannibalen Hannibal Lecter und des Serienmörders Buffalo Bill aus dem Film'Das Schweigen der Lämmer'mit dem Serienmörder Ted Bundy, der als Vorlage für diese Filmfiguren diente. Außerdem ist eine kurze Analyse einer Facebook-Serienmörderfangruppe Bestandteil dieser Seminararbeit. Auch wird analysiert, warum Serienmörder auf die Menschheit und insbesondere auf Frauen so eine große Faszination ausüben.

Published
2023

14. Die Geschichte des Hakenheinz

Author

Daniel Perl and Daniel Perl

Abstract

Der wilde und mutige Draufgänger Hakenheinz will nur mit einem Haken bewaffnet den Schatz von Captain Müffelbart finden. Um diesen zu bekommen, muss er das Seeungeheuer besiegen. Bis er dies jedoch schafft, muss er viele Feinde besiegen und mit seinen neuen Freunden viele Abenteuer bestehen. Sein Schiff wird zerstört, er verliert sein ganzes Gold und wird sogar im Armdrücken besiegt. Obwohl ihn das Glück aber oft verlässt, gibt er niemals auf, da er der stärkste und mutigste Seeräuber ist, den es gibt. Selbst als er verraten und verbannt wird, gibt der Hakenheinz nicht auf und wird zum Schluss sogar König.

Published
2023

15. The Fascination of Evil - Criminals and Their Influence on Cultur and Society - Ted Bundy and Jack Unterweger: 2 Case Studies

Author

Daniel Perl and Daniel Perl

Abstract

This term paper deals with the influence of Ted Bundy and Jack Unterweger on culture and society. The main part of this term paper is the comparison between the cannibal Hannibal Lecter and serial killer Buffalo Bill of the movie'The silence of the lambs'with serial killer Ted Bundy. Apart from that there is a analysis of a Ted Bundy Facebook fan group and an explanation why so many people, especially women, are fascinated by serial killers.

Published
2023

16. Smaller Regional Brain Volumes Predict Posttraumatic Stress Disorder at 3 Months after Mild Traumatic Brain Injury

Author

Murray B. Stein, Esther Yuh, Sonia Jain, David O. Okonkwo, Christine L. Mac Donald, Harvey Levin, Joseph T. Giacino, Sureyya Dikmen, Mary J. Vassar, Ramon Diaz-Arrastia, Claudia S. Robertson, Lindsay D. Nelson, Michael McCrea, Xiaoying Sun, Nancy Temkin, Sabrina R. Taylor, Amy J. Markowitz, Geoffrey T. Manley, Pratik Mukherjee, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Jason Barber, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, C. Dirk Keene, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Laura B. Ngwenya, Florence Noel, Amber Nolan, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur Toga, Alex Valadka, Paul Vespa, Kevin Wang, John K. Yue, and Ross Zafonte

Subjects
Traumatic brain injury, Cognitive Neuroscience, Hippocampus, behavioral disciplines and activities, Amygdala, 050105 experimental psychology, Article, Stress Disorders, Post-Traumatic, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Biological Psychiatry, Brain Concussion, Cognitive reserve, medicine.diagnostic_test, business.industry, 05 social sciences, Glasgow Coma Scale, Brain, Magnetic resonance imaging, Emergency department, medicine.disease, medicine.anatomical_structure, Anesthesia, Neurology (clinical), business, Insula, 030217 neurology & neurosurgery
Abstract

Background Brain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury. Methods Using data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13–15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices. Results Overall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors. Conclusions Results, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury.

Published
2020

17. Reduction of pTau and APP Levels in Mammalian Brain After Low-Dose Radiation

Author

Diego Iacono, Erin Murphy, Soundarya Avantsa, Daniel Perl, and Regina Day

Abstract

Brain radiation can occur from treatment of brain tumors or accidental exposure. Brain radiation has been rarely considered, though, as a possible tool to alter proteins involved in neurodegenerative disorders. We analyzed molecular and neuropathology changes of phosphorylated-Tau (pTau), all-Tau forms, β-tubulin, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ionized calcium binding adaptor molecule 1 (IBA-1), myelin basic protein (MBP), and GAP43 in Frontal Cortex (FC), Hippocampus (H) and Cerebellum (CRB) of swine brains 4 weeks following total-body radiation (1.79 Gy). Radiated-animals showed lower levels of pTau in FC and H, APP in H and CRB, GAP43 in CRB, and higher level of GFAP in H vs. sham-animals. These changes were not accompanied by obvious neurohistological changes, except for astrogliosis in the H. These findings are novel, and might open new perspectives on brain radiation as a therapeutic tool for interfering with the pathogenesis of various neurodegenerative disorders.

Published
2020
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18. Risk of Posttraumatic Stress Disorder and Major Depression in Civilian Patients After Mild Traumatic Brain Injury: A TRACK-TBI Study

Author

Murray B, Stein, Sonia, Jain, Joseph T, Giacino, Harvey, Levin, Sureyya, Dikmen, Lindsay D, Nelson, Mary J, Vassar, David O, Okonkwo, Ramon, Diaz-Arrastia, Claudia S, Robertson, Pratik, Mukherjee, Michael, McCrea, Christine L, Mac Donald, John K, Yue, Esther, Yuh, Xiaoying, Sun, Laura, Campbell-Sills, Nancy, Temkin, Geoffrey T, Manley, Opeolu, Adeoye, Neeraj, Badjatia, Kim, Boase, Yelena, Bodien, M Ross, Bullock, Randall, Chesnut, John D, Corrigan, Karen, Crawford, Ann-Christine, Duhaime, Richard, Ellenbogen, V Ramana, Feeser, Adam, Ferguson, Brandon, Foreman, Raquel, Gardner, Etienne, Gaudette, Luis, Gonzalez, Shankar, Gopinath, Rao, Gullapalli, J Claude, Hemphill, Gillian, Hotz, Frederick, Korley, Joel, Kramer, Natalie, Kreitzer, Chris, Lindsell, Joan, Machamer, Christopher, Madden, Alastair, Martin, Thomas, McAllister, Randall, Merchant, Florence, Noel, Eva, Palacios, Daniel, Perl, Ava, Puccio, Miri, Rabinowitz, Jonathan, Rosand, Angelle, Sander, Gabriela, Satris, David, Schnyer, Seth, Seabury, Mark, Sherer, Sabrina, Taylor, Arthur, Toga, Alex, Valadka, Paul, Vespa, Kevin, Wang, and Ross, Zafonte

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Traumatic brain injury, Comorbidity, behavioral disciplines and activities, Stress Disorders, Post-Traumatic, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, mental disorders, Brain Injuries, Traumatic, Prevalence, Medicine, Humans, Glasgow Coma Scale, Longitudinal Studies, Prospective Studies, Young adult, Psychiatry, Prospective cohort study, Depression (differential diagnoses), Original Investigation, Depressive Disorder, Major, business.industry, Emergency department, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Case-Control Studies, Major depressive disorder, Female, business, Emergency Service, Hospital, 030217 neurology & neurosurgery
Abstract

IMPORTANCE: Traumatic brain injury (TBI) has been associated with adverse mental health outcomes, such as posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), but little is known about factors that modify risk for these psychiatric sequelae, particularly in the civilian sector. OBJECTIVE: To ascertain prevalence of and risk factors for PTSD and MDD among patients evaluated in the emergency department for mild TBI (mTBI). DESIGN, SETTING, AND PARTICIPANTS: Prospective longitudinal cohort study (February 2014 to May 2018). Posttraumatic stress disorder and MDD symptoms were assessed using the PTSD Checklist for DSM-5 and the Patient Health Questionnaire-9 Item. Risk factors evaluated included preinjury and injury characteristics. Propensity score weights-adjusted multivariable logistic regression models were performed to assess associations with PTSD and MDD. A total of 1155 patients with mTBI (Glasgow Coma Scale score, 13-15) and 230 patients with nonhead orthopedic trauma injuries 17 years and older seen in 11 US hospitals with level 1 trauma centers were included in this study. MAIN OUTCOMES AND MEASURES: Probable PTSD (PTSD Checklist for DSM-5 score, ≥33) and MDD (Patient Health Questionnaire-9 Item score, ≥15) at 3, 6, and 12 months postinjury. RESULTS: Participants were 1155 patients (752 men [65.1%]; mean [SD] age, 40.5 [17.2] years) with mTBI and 230 patients (155 men [67.4%]; mean [SD] age, 40.4 [15.6] years) with nonhead orthopedic trauma injuries. Weights-adjusted prevalence of PTSD and/or MDD in the mTBI vs orthopedic trauma comparison groups at 3 months was 20.0% (SE, 1.4%) vs 8.7% (SE, 2.2%) (P

Published
2019

19. Characterizing the Ordinary Broad-line Type Ic SN 2023pel from the Energetic GRB 230812B

Author

Gokul P. Srinivasaragavan, Vishwajeet Swain, Brendan O’Connor, Shreya Anand, Tomás Ahumada, Daniel Perley, Robert Stein, Jesper Sollerman, Christoffer Fremling, S. Bradley Cenko, S. Antier, Nidhal Guessoum, Thomas Hussenot-Desenonges, Patrice Hello, Stephen Lesage, Erica Hammerstein, M. Coleman Miller, Igor Andreoni, Varun Bhalerao, Joshua S. Bloom, Anirban Dutta, Avishay Gal-Yam, K-Ryan Hinds, Amruta Jaodand, Mansi Kasliwal, Harsh Kumar, Alexander S. Kutyrev, Fabio Ragosta, Vikram Ravi, Kritti Sharma, Rishabh Singh Teja, Sheng Yang, G. C. Anupama, Eric C. Bellm, Michael W. Coughlin, Ashish A. Mahabal, Frank J. Masci, Utkarsh Pathak, Josiah Purdum, Oliver J. Roberts, Roger Smith, and Avery Wold

Subjects
Gamma-ray bursts, Core-collapse supernovae, Relativistic jets, Astrophysics, QB460-466
Abstract

We report observations of the optical counterpart of the long gamma-ray burst (GRB) GRB 230812B and its associated supernova (SN) SN 2023pel. The proximity ( z = 0.36) and high energy ( E _γ _,iso ∼ 10 ^53 erg) make it an important event to study as a probe of the connection between massive star core collapse and relativistic jet formation. With a phenomenological power-law model for the optical afterglow, we find a late-time flattening consistent with the presence of an associated SN. SN 2023pel has an absolute peak r -band magnitude of M _r = −19.46 ± 0.18 mag (about as bright as SN 1998bw) and evolves on quicker timescales. Using a radioactive heating model, we derive a nickel mass powering the SN of M _Ni = 0.38 ± 0.01 M _⊙ and a peak bolometric luminosity of L _bol ∼ 1.3 × 10 ^43 erg s ^−1 . We confirm SN 2023pel’s classification as a broad-line Type Ic SN with a spectrum taken 15.5 days after its peak in the r band and derive a photospheric expansion velocity of v _ph = 11,300 ± 1600 km s ^−1 at that phase. Extrapolating this velocity to the time of maximum light, we derive the ejecta mass M _ej = 1.0 ± 0.6 M _⊙ and kinetic energy ${E}_{\mathrm{KE}}={1.3}_{-1.2}^{+3.3}\times {10}^{51}\,\mathrm{erg}$ . We find that GRB 230812B/SN 2023pel has SN properties that are mostly consistent with the overall GRB-SN population. The lack of correlations found in the GRB-SN population between SN brightness and E _γ _,iso for their associated GRBs across a broad range of 7 orders of magnitude provides further evidence that the central engine powering the relativistic ejecta is not coupled to the SN powering mechanism in GRB-SN systems.

Published
2024
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20. The Effect of Spaced Repetition Learning Through Anki on Medical Board Exam Performance

Author

Spencer Cooper, Nicole Twardowski, Michael Vogel, Daniel Perling, and Rebecca Ryznar

Subjects
Education, Medical, Cohort Studies, Instructional Materials/Methods, Medical school, Basic Science Knowledge, Clinical Knowledge, Medicine (General), R5-920, Public aspects of medicine, RA1-1270
Abstract

Background: Spaced repetition learning is a method of learning that relies on a fixed formula for spacing out flashcards to ensure long term retention of a topic. Anki is one such application available online that utilizes spaced repetition learning. This retrospective cohort study analyzed incorporating Anki with medical school curriculum and its effect on board examination scores. The hypothesis is that students who engaged in spaced repetition learning through Anki scored higher on licensing board exams and achieved higher GPAs than students who did not engage with this method. Methods: The hypothesis was tested through comparison of USMLE Step 1 scores, COMLEX Level 1 scores, and GPA. The samples were selected from the Rocky Vista University Class of 2023 and split between 35 students in the Anki Cohort and 268 students in the non-Anki cohort. Results: 1 (2.8%) student failed USMLE Step 1 in the Anki cohort compared to 28 (10.94%) students who failed Step 1 in the non-Anki cohort (p > 0.05) The Anki cohort achieved a higher mean USMLE Step 1 (223.71 versus 222.58) and COMLEX Level 1 (569.51 versus 559.99). The non-Anki cohort had a higher GPA (85.60) than the Anki cohort (83.82) (p < 0.01). Conclusion: This is the first study to evaluate for a correlation between COMLEX level 1 scores with use of spaced repetition learning. Although this study was unable to find any significant correlation between Anki use and licensing exam scores, further investigations with better control and sample size are needed.

Published
2023

21. Optical and Radio Analysis of Systematically Classified Broad-lined Type Ic Supernovae from the Zwicky Transient Facility

Author

Gokul P. Srinivasaragavan, Sheng Yang, Shreya Anand, Jesper Sollerman, Anna Y. Q. Ho, Alessandra Corsi, S. Bradley Cenko, Daniel Perley, Steve Schulze, Marquice Sanchez-Fleming, Jack Pope, Nikhil Sarin, Conor Omand, Kaustav K. Das, Christoffer Fremling, Igor Andreoni, Rachel Bruch, Kevin B. Burdge, Kishalay De, Avishay Gal-Yam, Anjasha Gangopadhyay, Matthew J. Graham, Jacob E. Jencson, Viraj Karambelkar, Mansi M. Kasliwal, S. R. Kulkarni, Julia Martikainen, Yashvi S. Sharma, Anastasios Tzanidakis, Lin Yan, Yuhan Yao, Eric C. Bellm, Steven L. Groom, Frank J. Masci, Guy Nir, Josiah Purdum, Roger Smith, and Niharika Sravan

Subjects
Type Ic supernovae, Relativistic jets, Astrophysics, QB460-466
Abstract

We study a magnitude-limited sample of 36 broad-lined type Ic supernovae (SNe Ic-BL) from the Zwicky Transient Facility Bright Transient Survey (detected between 2018 March and 2021 August), which is the largest systematic study of SNe Ic-BL done in literature thus far. We present the light curves (LCs) for each of the SNe and analyze the shape of the LCs to derive empirical parameters, along with the explosion epochs for every event. The sample has an average absolute peak magnitude in the r band of ${\overline{{M}}}_{{\rm{r}},\max }=-18.51\pm 0.15$ mag. Using spectra obtained around peak light, we compute expansion velocities from the Fe ii 5169 Å line for each event with high enough signal-to-noise ratio spectra, and find an average value of $\bar{{v}_{\mathrm{ph}}}=16,100\pm 1100$ km s ^−1 . We also compute bolometric LCs, study the blackbody temperature and radii evolution over time, and derive the explosion properties of the SNe. The explosion properties of the sample have average values of ${\overline{{M}}}_{\mathrm{Ni}}={0.37}_{-0.06}^{+0.08}\,{{M}}_{\odot }$ , ${\overline{{M}}}_{\mathrm{ej}}={2.45}_{-0.41}^{+0.47}\,{{M}}_{\odot }$ , and ${\overline{{E}}}_{{\rm{K}}}=({4.02}_{-1.00}^{+1.37})\times {10}^{51}$ erg. Thirteen events have radio observations from the Very Large Array, with eight detections and five non-detections. We find that the populations that have radio detections and radio non-detections are indistinct from one another with respect to their optically inferred explosion properties, and there are no statistically significant correlations present between the events’ radio luminosities and optically inferred explosion properties. This provides evidence that the explosion properties derived from optical data alone cannot give inferences about the radio properties of SNe Ic-BL and likely their relativistic jet formation mechanisms.

Published
2024
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22. Collapsars as Sites of r-process Nucleosynthesis: Systematic Photometric Near-infrared Follow-up of Type Ic-BL Supernovae

Author

Shreya Anand, Jennifer Barnes, Sheng Yang, Mansi M. Kasliwal, Michael W. Coughlin, Jesper Sollerman, Kishalay De, Christoffer Fremling, Alessandra Corsi, Anna Y. Q. Ho, Arvind Balasubramanian, Conor Omand, Gokul P. Srinivasaragavan, S. Bradley Cenko, Tomás Ahumada, Igor Andreoni, Aishwarya Dahiwale, Kaustav Kashyap Das, Jacob Jencson, Viraj Karambelkar, Harsh Kumar, Brian D. Metzger, Daniel Perley, Nikhil Sarin, Tassilo Schweyer, Steve Schulze, Yashvi Sharma, Tawny Sit, Robert Stein, Leonardo Tartaglia, Samaporn Tinyanont, Anastasios Tzanidakis, Jan van Roestel, Yuhan Yao, Joshua S. Bloom, David O. Cook, Richard Dekany, Matthew J. Graham, Steven L. Groom, David L. Kaplan, Frank J. Masci, Michael S. Medford, Reed Riddle, and Chaoran Zhang

Subjects
Supernovae, Nucleosynthesis, Transient sources, R-process, Explosive nucleosynthesis, Time domain astronomy, Astrophysics, QB460-466
Abstract

One of the open questions following the discovery of GW170817 is whether neutron star (NS) mergers are the only astrophysical sites capable of producing r -process elements. Simulations have shown that 0.01–0.1 M _⊙ of r -process material could be generated in the outflows originating from the accretion disk surrounding the rapidly rotating black hole that forms as a remnant to both NS mergers and collapsing massive stars associated with long-duration gamma-ray bursts (collapsars). The hallmark signature of r -process nucleosynthesis in the binary NS merger GW170817 was its long-lasting near-infrared (NIR) emission, thus motivating a systematic photometric study of the light curves of broad-lined stripped-envelope (Ic-BL) supernovae (SNe) associated with collapsars. We present the first systematic study of 25 SNe Ic-BL—including 18 observed with the Zwicky Transient Facility and 7 from the literature—in the optical/NIR bands to determine what quantity of r -process material, if any, is synthesized in these explosions. Using semi-analytic models designed to account for r -process production in SNe Ic-BL, we perform light curve fitting to derive constraints on the r -process mass for these SNe. We also perform independent light curve fits to models without the r -process. We find that the r -process-free models are a better fit to the light curves of the objects in our sample. Thus, we find no compelling evidence of r -process enrichment in any of our objects. Further high-cadence infrared photometric studies and nebular spectroscopic analysis would be sensitive to smaller quantities of r -process ejecta mass or indicate whether all collapsars are completely devoid of r -process nucleosynthesis.

Published
2024
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23. Military Blast Exposure and Chronic Neurodegeneration: Summary of Working Groups and Expert Panel Findings and Recommendations

Author

Nitin Daphalapurkar, Meghan Robinson, Laurel Ng, Philip Montenigro, Jamie B Grimes, Peethambaran Arun, B. Christie Vu, Daniel Perl, Sandi Chapman, Tara Cozzarelli, Shaleish Ganpule, Chandler Sours, Walter Carr, Gregory Elder, David L. Brody, Michael Leggieri, Erick Ishii, Iren Horkayne-Szakaly, John Wu, Joan Cmarik, Frank Tortella, Julie L. Proctor, Patricio F. Reyes, Savita Nigam, Steven Broglio, Jessica Gill, Josh Duckworth, Regina Armstrong, Jason Harrington, Anthony Santago, Thuvan Piehler, Nikki Zander, Reza Fazel-Rezai, Robert Cantu, James R. Stone, John F. Glenn, Amy Hein, Douglas S. DeWitt, Elizabeth Brokaw, Therese A. West, Colin Greene, Adam Fournier, Mat Philippens, Avraham Yitzhak, Gail Rosseau, David Borkholder, Kun Ping Lu, Robert Labutta, Felicia Qashu, Elaine R. Peskind, Alexander Razumovsky, Robert V. Jones, Robert C. Latta, Marten Risling, Jaques Reifman, Uade Olaghere da Silva, Ghodrat Karami, Charles L. Rosen, Sidney R. Hinds, Joseph McCabe, Andrzej Przekwas, David Tweedie, Patrick Bellgowan, Mike Thomas, Chad Haering, Carey D. Balaban, Elisabeth A. Wilde, Victoria Tepe, Gary Fiskum, Stephanie Maxfield Panker, Brian Colder, Jeff Colombe, Kathy Helmick, Ramona Hicks, Daniel C. Krawczyk, Dale Vander Hamm, Denes Agoston, James C. DeMar, Matt Aldag, Nigel Greig, David O. Okonkwo, David G. Cook, Mike Templin, Murray A. Raskind, Laila Zai, Bernard Dardzinski, Fabio Leonessa, Geoffrey Ling, Stuart Hoffman, Tom DeGraba, Ying Wang, Theresa Lattimore, Michael Fine, Debra Babcock, Diego Iacono, James Zheng, Peter Thielen, Andrew C. Merkle, Mariusz Ziejewski, Bryan Pfister, Richard Shoge, Michel A. Audette, Ingrid Pauli, Gary P. Mueller, Dara Dickstein, Adam Willis, Paul Rigby, Kelley A. Brix, Laura B. Tucker, Thomas Timmes, Alexander Lin, Matt Long, Tyler Rooks, Rohan Banton, John O'Donnell, and Wendy Sammons-Jackson

Subjects
021110 strategic, defence & security studies, Medical education, Research program, Area studies, business.industry, 0211 other engineering and technologies, 02 engineering and technology, medicine.disease, Blast injury, Scientific evidence, Body of knowledge, 03 medical and health sciences, Subject-matter expert, Chronic traumatic encephalopathy, 0302 clinical medicine, medicine, Neurology (clinical), business, Working group, 030217 neurology & neurosurgery
Abstract

The potential relationship between chronic traumatic encephalopathy (CTE) and head injuries such as blast-related traumatic brain injury (TBI) is an important area of study, particularly for military and contact sports populations, yet little is known about this relationship. To address this topic, the Department of Defense (DoD) Blast Injury Research Program Coordinating Office organized the 2015 International State-of-The-Science Meeting, which brought together subject matter experts from the DoD, other federal agencies, academia, industry, foreign allies, and the sports community. Over the course of the meeting, this community of experts reached a consensus regarding the current body of knowledge and the future of the field. The overarching finding was that there is insufficient existing scientific evidence to link blast-related TBI with CTE. The meeting's Expert Panel also agreed on 13 additional findings describing research and knowledge gaps, clinical gaps, and research opportunities that, if addressed with focused effort, would further the understanding of the relationship between blast-related TBI and CTE. To this end, the Expert Panel also developed six recommendations for advancing research, each with short-and long-Term goals. Among the six recommendations, the Expert Panel identified the first four as highest priority for addressing pressing research needs. These four high-priority recommendations include, in order of priority: (1) more collection and study of clinical neuropathology samples, (2) standardization of clinical diagnostic criteria, (3) development of clinically appropriate and standardized animal models, and (4) development of noninvasive serial assessment strategies (i.e., imaging or biospecimen biomarkers). © Copyright 2017, Mary Ann Liebert, Inc. 2017.

Published
2017
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24. Online Case Study: The Clinical and Pathological Differential Diagnosis of Encephalopathy ('The Mysterious Case of ‘John Doe’')

Author

Merril Schindler, Daniel Perl, Robert Fallar, Reena Karani, Stephen Krieger, Huaibin Mabel Ko, and Margret Magid

Subjects
Medicine (General), business.industry, education, Encephalopathy, Metabolic Brain Disease, General Medicine, medicine.disease, Bioinformatics, Education, Complement (complexity), Hepatic Artery, R5-920, Wernicke, Medicine, Online, Clinical case, CNS, Differential diagnosis, Alcohol, business, Pathological, Neuroscience
Abstract

Introduction This online clinical case was designed to complement and reinforce material covered in the module on Nutritional/Metabolic disturbances in a second-year brain and behavior course. The goal of this exercise was to have the student apply important concepts previously presented in class to a realistic patient. It could also be utilized during the clinical years for a review of the basic science underlying encephalopathy. Methods The module was created to be an enjoyable, interactive, multimedia experience that guides the student through clinical decision making in a patient presenting with confusion. A brief discussion of this disorder concludes the exercise. Case efficacy was evaluated through a posttest and a student survey. Results The case was available to half of the class of 143 students (Group 1) for a period of 6 days following completion of the Nutritional/Metabolic Disturbances module. The remaining 72 students (Group 2) did not initially have access to the case. After the case was closed, an elective seven multiple-choice question online quiz was opened to all 143 students. The average total score (out of max of 7) for Group 1 was 5.58, while the score of Group 2 was 4.57 (p = .0004). For the survey, feedback was incorporated into an anonymous postcourse evaluation. Seven questions about the exercise were evaluated on a Likert scale from 1–5. In addition, free-text comments were solicited. Fifty-three students completed the survey. The quiz and survey results indicate that the case is both well-received and effective for short-term learning. Discussion The significance of the work is the integration of basic science/pathology and clinical medicine in the format of an engaging case review of encephalopathy. The case is appropriate both for preclinical students learning about clinical workup, as well as for students in the clerkship and post-clerkship years reviewing the underpinnings of basic science in clinical medicine.

Published
2013
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28. Extrinsic tumors

Author

Daniel Perl

Subjects
Fetus, Pathology, medicine.medical_specialty, business.industry, Medicine, Neuropathology, business
Published
2006
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29. Histology

Author

Daniel Perl

Subjects
Pathology, medicine.medical_specialty, business.industry, medicine, Myelitis, medicine.disease, business, Encephalitis
Published
2006
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31. Dementia

Author

Daniel Perl

Subjects
Nervous system, medicine.anatomical_structure, business.industry, medicine, Bioinformatics, business
Published
2006
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33. Hydrocephalus, cysts and syrinxes

Author

Daniel Perl

Subjects
Pathology, medicine.medical_specialty, medicine.anatomical_structure, business.industry, Peripheral nervous system, medicine, business, Peripheral
Published
2006
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34. Multiple sclerosis

Author

Daniel Perl

Subjects
medicine.medical_specialty, business.industry, medicine, Radiology, medicine.disease, business, Hydrocephalus
Published
2006
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36. SN 2022joj: A Peculiar Type Ia Supernova Possibly Driven by an Asymmetric Helium-shell Double Detonation

Author

Chang Liu, Adam A. Miller, Samuel J. Boos, Ken J. Shen, Dean M. Townsley, Steve Schulze, Luke Harvey, Kate Maguire, Joel Johansson, Thomas G. Brink, Umut Burgaz, Georgios Dimitriadis, Alexei V. Filippenko, Saarah Hall, K-Ryan Hinds, Andrew Hoffman, Viraj Karambelkar, Charles D. Kilpatrick, Daniel Perley, Neil Pichay, Huei Sears, Jesper Sollerman, Robert Stein, Jacco H. Terwel, WeiKang Zheng, Matthew J. Graham, Mansi M. Kasliwal, Leander Lacroix, Josiah Purdum, Benjamin Rusholme, and Avery Wold

Subjects
Supernovae, Type Ia supernovae, White dwarf stars, Observational astronomy, Surveys, Astrophysics, QB460-466
Abstract

We present observations of SN 2022joj, a peculiar Type Ia supernova discovered by the Zwicky Transient Facility. SN 2022joj exhibits an unusually red g _ZTF − r _ZTF color at early times and a rapid blueward evolution afterward. Around maximum brightness, SN 2022joj shows a high luminosity ( ${M}_{{g}_{\mathrm{ZTF}},\max }\simeq -19.7$ mag), a blue broadband color ( g _ZTF − r _ZTF ≃ −0.2 mag), and shallow Si ii absorption lines, consistent with those of overluminous, SN 1991T-like events. The maximum-light spectrum also shows prominent absorption around 4200 Å, which resembles the Ti ii features in subluminous, SN 1991bg-like events. Despite the blue optical-band colors, SN 2022joj exhibits extremely red ultraviolet minus optical colors at maximum luminosity ( u − v ≃ 0.6 mag and uvw 1 − v ≃ 2.5 mag), suggesting a suppression of flux at ∼2500–4000 Å. Strong C ii lines are also detected at peak. We show that these unusual spectroscopic properties are broadly consistent with the helium-shell double detonation of a sub-Chandrasekhar mass ( M ≃ 1 M _⊙ ) carbon/oxygen white dwarf from a relatively massive helium shell ( M _s ≃ 0.04–0.1 M _⊙ ), if observed along a line of sight roughly opposite to where the shell initially detonates. None of the existing models could quantitatively explain all the peculiarities observed in SN 2022joj. The low flux ratio of [Ni ii ] λ 7378 to [Fe ii ] λ 7155 emission in the late-time nebular spectra indicates a low yield of stable Ni isotopes, favoring a sub-Chandrasekhar mass progenitor. The significant blueshift measured in the [Fe ii ] λ 7155 line is also consistent with an asymmetric chemical distribution in the ejecta, as is predicted in double-detonation models.

Published
2023
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37. The Prevalence and Influence of Circumstellar Material around Hydrogen-rich Supernova Progenitors

Author

Rachel J. Bruch, Avishay Gal-Yam, Ofer Yaron, Ping Chen, Nora L. Strotjohann, Ido Irani, Erez Zimmerman, Steve Schulze, Yi Yang, Young-Lo Kim, Mattia Bulla, Jesper Sollerman, Mickael Rigault, Eran Ofek, Maayane Soumagnac, Frank J. Masci, Christoffer Fremling, Daniel Perley, Jakob Nordin, S. Bradley Cenko, Anna Y. Q. Ho, S. Adams, Igor Adreoni, Eric C. Bellm, Nadia Blagorodnova, Kevin Burdge, Kishalay De, Richard G. Dekany, Suhail Dhawan, Andrew J. Drake, Dmitry A. Duev, Matthew Graham, Melissa L. Graham, Jacob Jencson, Emir Karamehmetoglu, Mansi M. Kasliwal, Shrinivas Kulkarni, A. A. Miller, James D. Neill, Thomas A. Prince, Reed Riddle, Benjamin Rusholme, Y. Sharma, Roger Smith, Niharika Sravan, Kirsty Taggart, Richard Walters, and Lin Yan

Subjects
Core-collapse supernovae, Type II supernovae, Supernovae, Massive stars, Circumstellar matter, Astrophysics, QB460-466
Abstract

Narrow transient emission lines (flash-ionization features) in early supernova (SN) spectra trace the presence of circumstellar material (CSM) around the massive progenitor stars of core-collapse SNe. The lines disappear within days after the SN explosion, suggesting that this material is spatially confined, and originates from enhanced mass loss shortly (months to a few years) prior to the explosion. We performed a systematic survey of H-rich (Type II) SNe discovered within less than 2 days from the explosion during the first phase of the Zwicky Transient Facility survey (2018–2020), finding 30 events for which a first spectrum was obtained within 36% at the 95% confidence level) confirms that elevated mass loss in massive stars prior to SN explosion is common. We find that SNe II showing flash-ionization features are not significantly brighter, nor bluer, nor more slowly rising than those without. This implies that CSM interaction does not contribute significantly to their early continuum emission, and that the CSM is likely optically thin. We measured the persistence duration of flash-ionization emission and find that most SNe show flash features for ≈5 days. Rarer events, with persistence timescales >10 days, are brighter and rise longer, suggesting these may be intermediate between regular SNe II and strongly interacting SNe IIn.

Published
2023
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38. Impact of Intracoastal Waterway maintenance dredging on a mud bottom benthos community

Author

Robert R. Stickney and Daniel Perl-Mutter

Subjects
education.field_of_study, geography, geography.geographical_feature_category, fungi, Population, Sediment, Dredging, Fishery, Water column, Habitat, Benthos, Benthic zone, Environmental science, education, Ecology, Evolution, Behavior and Systematics, Channel (geography), Nature and Landscape Conservation
Abstract

The effects of hydraulic dredging on the benthic infauna of a mud bottom area were investigated in Georgia in the Atlantic Intracoastal Waterway. Complete displacement of the benthic community was caused by dredging; however, the community began to recover within a month following the cessation of dredging. Within two months the diversity and species composition of the dredged channel were similar to that of a control area and little change in sediment composition resulted. Thus, no apparent limitation was imposed on the normal benthic population by habitat alteration. Recolonisation was too rapid to have been caused by the settling of immature or larval stages from the water column alone. Bank slumping and migration of adult forms have been postulated as other means of recolonisation.

Published
1975
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