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1. THE RELATION BETWEEN IMMUNE THROMBOCYTOPENIA AND CEREBRAL SINUS VENOUS THROMBOSIS IN PEDIATRIC POPULATION. A CASE SERIES

Author

LLE Souza, M Jackson, S Chowdhury, and S Williams

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background: Immune thrombocytopenia (ITP) is an acquired thrombocytopenia caused by auto-antibodies against platelet antigens. Over the last 20 years numerous reports of venous thromboembolic complications with ITP patients have been published, including several large-scale population-based studies. However, data in children is scarce. Herein we report four cases of pediatric patients who were found to have cerebral venous sinus thrombosis (CSVT) after ITP. These cases and prior literature raise the possibility of ITP, and or its treatment being a thrombotic risk factor. Aims: The present study sought to report 4 cases of CSVT in the setting of ITP. Methods: Chart review of 4 patients who presented with CSVT following a diagnosis of ITP were conducted. Parental consent was obtained. Results: Four male patients with mean age of CSVT presentation being 6 years (3-10 years of age), who developed CSVT post ITP, received therapeutic anticoagulation. They did not develop bleeding complications while on anticoagulation therapy. All had good clinical outcomes, with partial or complete radiological resolution of thrombosis. Recurrence or extension of CSVT occurred in 3 of 4 patients. Despite having intracranial hemorrhage at the time of the ITP presentation in 2 patients, anticoagulation was still initiated, and did not result in further bleeding. Conclusion: The etiology of the increased risk of venous thrombosis in patients with ITP is unclear, and it appears to be multifactorial as to why some patients may be prone to thrombosis and others not, and how important the role of treatment is in this complication. However, ITP and or the treatment of ITP may be contributing risk factors for thrombosis. Bleeding remains the most feared complication for patients with ITP. Nevertheless, anticoagulation can be administered, without further bleeding complications. An association between ITP and thrombosis, specifically CSVT in children is possible, but data is lacking in the literature. Further studies are needed to better describe associations between ITP, and thrombotic events in children.

Published
2024
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2. Higher burden of cardiometabolic and socioeconomic risk factors in women with type 2 diabetes: an analysis of the Glycemic Reduction Approaches in Diabetes (GRADE) baseline cohort

Author

C Wright, C Sanders, C Wilson, L Tucker, S Jones, S Douglass, C Patel, A Kumar, S Smith, A Ghosh, C Adams, R Hill, D Martin, J Hu, M Lee, N Patel, O Smith, J Cook, J Day, M Jackson, G Riera, P McGee, J Park, J Jiménez, S Yang, A Carlson, C Martin, H Liu, Y Li, A Krol, K Wright, S Golden, A Sood, J Martinez, D Sanchez, K Burton, Y Gao, S Martin, O Sanchez, C DeSouza, M Johnson, L Estrada, A Jackson, J Higgins, K Martin, J Craig, A Kuhn, L Ngo, Deborah J Wexler, R Chatterjee, E Walker, J Kerr, W Taylor, J Lim, M Perez, R Henry, Vanita R Aroda, R Fraser, Cyrus Desouza, E King, C Campbell, J González, E Diaz, P Zhang, J Marks, S Abraham, A Ross, M Khalid, T Young, J Myers, J Barzilay, B Chambers, G Montes, C Jensen, J McConnell, R Nelson, L Prosser, S Morton, M Curtis, P Wilson, L Young, M Fürst, S Warren, C Newman, S Kuo, N Rasouli, A Werner, L Morton, A Ghazi, M Salam, F Ismail-Beigi, P Kringas, C Baker, E Ellis, A Cherian, L Holloway, M Madden, B Hollis, G Fuller, B Steiner, K Stokes, R Ayala, T Lowe, K Chu, S Durán, D Dyer, A Alfred, J Leger, Nicole M Butera, T Hamilton, J Costello, E Burgess, R Garg, A Maxwell, C Stevens, W Ye, T Tran, L Fischer, M Hurtado, H Schneier, C Lund, R Lorch, M Mullen, J Bantle, K Arnold, D Wexler, A TURCHIN, MS Lee, D Howard, J Tejada, S Hernandez, Tasma Harindhanavudhi, E Schroeder, K Pham, S Kunkel, A Fagan, G Lord, H CHONG, A Smiley, E Debnam, H Petrovitch, M Bäckman, B Kauffman, V Jenkins, B Cramer, JP Crandall, MD McKee, S Behringer-Massera, J Brown-Friday, E Xhori, K Ballentine-Cargill, H Estrella, S Gonzalez de la torre, J Lukin, LS Phillips, D Olson, M Rhee, TS Raines, J Boers, C Gullett, M Maher-Albertelli, R Mungara, L Savoye, CA White, F Morehead, S Person, M Sibymon, S Tanukonda, A Balasubramanyam, R Gaba, P Hollander, E Roe, P Burt, K Chionh, C Falck-Ytter, L Sayyed Kassem, M Tiktin, T Kulow, KA Stancil, J Iacoboni, MV Kononets, L Colosimo, R Goland, J Pring, L Alfano, C Hausheer, K Gumpel, A Kirpitch, JB Green, H AbouAssi, MN Feinglos, J English Jones, RP Zimmer, BM Satterwhite, K Evans Kreider, CR Thacker, CN Mariash, KJ Mather, A Lteif, V Pirics, D Aguillar, S Hurt, R Bergenstal, T Martens, J Hyatt, H Willis, W Konerza, K Kleeberger, R Passi, S Fortmann, M Herson, K Mularski, H Glauber, J Prihoda, B Ash, C Carlson, PA Ramey, E Schield, B Torgrimson-Ojerio, E Panos, S Sahnow, K Bays, K Berame, D Ghioni, J Gluth, K Schell, J Criscola, C Friason, S Nazarov, N Rassouli, R Puttnam, B Ojoawo, C Sanders-Jones, Z El-Haqq, A Kolli, J Meigs, A Dushkin, G Rocchio, M Yepes, H Dulin, M Cayford, A DeManbey, M Hillard, N Thangthaeng, L Gurry, R Kochis, E Raymond, V Ripley, V Aroda, A Loveland, M Hamm, HJ Florez, WM Valencia, S Casula, L Oropesa-Gonzalez, L Hue, AK Riccio Veliz, R Nieto-Martinez, M Gutt, A Ahmann, D Aby-Daniel, F Joarder, V Morimoto, C Sprague, D Yamashita, N Cady, N Rivera-Eschright, P Kirchhoff, B Morales Gomez, J Adducci, A Goncharova, SH Hox, M Matwichyna, NO Bermudez, L Broadwater, RR Ishii, DS Hsia, WT Cefalu, FL Greenway, C Waguespack, N Haynes, A Thomassie, B Bourgeois, C Hazlett, S Mudaliar, S Boeder, J Pettus, D Garcia-Acosta, S Maggs, C DeLue, E Castro, J Krakoff, JM Curtis, T Killean, E Joshevama, K Tsingine, T Karshner, J Albu, FX Pi-Sunyer, S Frances, C Maggio, J Bastawrose, X Gong, MA Banerji, D Lorber, NM Brown, DH Josephson, LL Thomas, M Tsovian, MH Jacobson, MM Mishko, MS Kirkman, JB Buse, J Dostou, K Bergamo, A Goley, JF Largay, S Guarda, J Cuffee, D Culmer, H Almeida, S Coffer, L Kiker, K Josey, WT Garvey, A Agne, S McCullars, RM Cohen, MC Rogge, K Kersey, S Lipp, MB Vonder Meulen, C Underkofler, S Steiner, E Cline, WH Herman, R Pop-Busui, MH Tan, A Waltje, A Katona, L Goodhall, R Eggleston, K Whitley, S Bule, N Kessler, E LaSalle, ER Seaquist, A Bantle, T Harindhanavudhi, B Redmon, M Coe, M Mech, A Taddese, L Lesne, L Kuechenmeister, V Shivaswamy, AL Morales, K Seipel, J Eggert, R Tillson, DS Schade, A Adolphe, M Burge, E Duran-Valdez, P August, MG Rodriguez, O Griffith, A Naik, Barbara I Gulanski, Heidi Krause-Steinrauf, Judith H Lichtman, Jennifer B Green, Colleen E Suratt, Hiba AbouAssi, Andrew J Ahmann, E Gonzalez Hattery, A Ideozu, G McPhee, SA Khan, JB Kimpel, HM Ismail, ME Larkin, M Magee, A Ressing, L Manandhar, F Mwicigi, V Lagari-Libhaber, A Cuadot, YJ Kendal, B Veciana, G Fry, A Dragg, B Gildersleeve, J Arceneaux, M Pavlionis, A Stallings, S Machineni, AL Cherrington, MCR Lawson, C Adkins, T Onadeko, M Razzaghi, C Lyon, R Penaloza, WI Sivitz, LK Knosp, S Bojescu, S Burbach, A Bancroft, FA Jamaleddin Ahmad, D Hernandez McGinnis, B Pucchetti, E Scripsick, A Zamorano, RA DeFronzo, E Cersosimo, M Abdul-Ghani, C Triplitt, D Juarez, RI Garza, H Verastiqui, C Puckett, P Raskin, C Rhee, LF Jordan, S Sao, L Osornio Walker, L Schnurr-Breen, RB Kreymer, D Sturgess, KM Utzschneider, SE Kahn, L Alarcon-Casas Wright, EJ Boyko, EC Tsai, DL Trence, S Trikudanathan, BN Fattaleh, BK Montgomery, KM Atkinson, A Kozedub, T Concepcion, C Moak, N Prikhodko, S Rhothisen, TA Elasy, L Shackelford, R Goidel, N Hinkle, C Lovell, J Lipps Hogan, JB McGill, T Schweiger, S Kissel, C Recklein, MJ Clifton, W Tamborlane, A Camp, B Gulanski, SE Inzucchi, M Alguard, P Gatcomb, K Lessard, L Iannone, A Montosa, E Magenheimer, J Fradkin, HB Burch, AA Bremer, DM Nathan, JM Lachin, H Krause-Steinrauf, N Younes, I Bebu, N Butera, CJ Buys, MR Gramzinski, SD Hall, E Kazemi, E Legowski, C Suratt, M Tripputi, A Arey, J Bethepu, P Mangat Dhaliwal, E Mesimer, M Steffes, J Seegmiller, A Saenger, V Arends, D Gabrielson, T Conner, J Huminik, A Scrymgeour, EZ Soliman, Y Pokharel, ZM Zhang, L Keasler, S Hensley, R Mihalcea, DJ Min, V Perez-Rosas, K Resnicow, H Shao, J Luchsinger, S Assuras, E Groessl, F Sakha, N Hillery, BM Everett, I Abdouch, G Bahtiyar, P Brantley, FE Broyles, G Canaris, P Copeland, JJ Craine, WL Fein, A Gliwa, L Hope, R Meiners, V Meiners, H O’Neal, JE Park, A Sacerdote, E Sledge, L Soni, J Steppel-Reznik, B Brooks-Worrell, CS Hampe, JP Palmer, A Shojaie, L Doner Lotenberg, JM Gallivan, and DM Tuncer

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Introduction Type 2 diabetes mellitus (T2DM) is a powerful risk factor for cardiovascular disease (CVD), conferring a greater relative risk in women than men. We sought to examine sex differences in cardiometabolic risk factors and management in the contemporary cohort represented by the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Research design and methods GRADE enrolled 5047 participants (1837 women, 3210 men) with T2DM on metformin monotherapy at baseline. The current report is a cross-sectional analysis of baseline data collected July 2013 to August 2017.Results Compared with men, women had a higher mean body mass index (BMI), greater prevalence of severe obesity (BMI≥40 kg/m2), higher mean LDL cholesterol, greater prevalence of low HDL cholesterol, and were less likely to receive statin treatment and achieve target LDL, with a generally greater prevalence of these risk factors in younger women. Women with hypertension were equally likely to achieve blood pressure targets as men; however, women were less likely to receive ACE inhibitors or angiotensin receptor blockers. Women were more likely to be divorced, separated or widowed, and had fewer years of education and lower incomes.Conclusions This contemporary cohort demonstrates that women with T2DM continue to have a greater burden of cardiometabolic and socioeconomic risk factors than men, particularly younger women. Attention to these persisting disparities is needed to reduce the burden of CVD in women.Trial registration number ClinicalTrials.gov (NCT01794143)

Published
2023
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3. Limited Scopes of Repair: Black Reparations Strategies and the Constraints of Local Redress Policy

Author

Elizabeth Jordie Davies, Jenn M. Jackson, and David J. Knight

Abstract

We consider two local reparations cases--the Evanston Restorative Housing Program and Chicago reparations for police torture survivors. We argue that the programs are shaped by the differing political opportunities, the local context, and the social location of their advocates given that one was constructed within government systems in Evanston and the other largely by grassroots organizers in Chicago. Furthermore, both programs are criticized to varying degrees as being exclusive in their design and implementation. We term this exclusion a process of deliberative marginalization, whereby some of the most vulnerable and most directly affected beneficiaries of a redress initiative are left out of deliberations and implementation decisions about the initiative's design. Subsequently, this study shows both the promise and constraints of reparations policy at the level of local government.

Published
2024

4. Community-based water demand management: socio-technical strategies for improving water security in Australian Indigenous communities

Author

C D Beal, M-S Bailey, M Hohenhaus, and M Jackson

Subjects
collaborative governance, WASH, water policy, Indigenous, demand management, socio-technical engagement, Environmental sciences, GE1-350
Abstract

Sustainable water management in remote Australian communities is a delicate balance between sufficient and acceptable supply options and appropriate and effective demand approaches. This paper focus on the evaluation of community-based water demand management strategies piloted in four remote Aboriginal and Torres Strait Island communities in Australia. Findings of the pilot demonstrate that from a systems perspective, community-based demand management centred around education and encouragement of residents to conserve and use water efficiently, provide greater opportunities for long-term sustainable water management outcomes that support building of social capital. To ensure truly transformative management outcomes, a toolbox of socio-technological strategies should be used including, where possible, smart metering of water consumption and use of water-efficient devices. A key element of this approach to demand management calls for a shift away from business-as-usual policy towards a flexible learning approach that involves genuine collaboration between water managers and Indigenous communities.

Published
2023
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5. Shape of the OGTT glucose response curve: relationship with β-cell function and differences by sex, race, and BMI in adults with early type 2 diabetes treated with metformin

Author

C Wright, C Sanders, C Wilson, L Tucker, S Jones, S Douglass, C Patel, A Kumar, S Smith, C Adams, R Hill, D Martin, M Lee, J Cook, M Jackson, G Riera, E González, J Park, S Yang, A Carlson, C Martin, A Krol, A Sood, J Martinez, C DeSouza, M Johnson, L Estrada, A Jackson, K Martin, SA Khan, J Craig, A Kuhn, Deborah J Wexler, R Chatterjee, J Kerr, W Taylor, R Henry, R Fraser, Kieren J Mather, M Larkin, E King, E Diaz, J Marks, A Ross, M Khalid, J Barzilay, B Chambers, G Montes, C Jensen, J McConnell, R Nelson, S Morton, M Curtis, P Wilson, L Young, M Fürst, C Newman, S Kuo, N Rasouli, A Werner, A Ghazi, F Ismail-Beigi, P Kringas, C Baker, E Ellis, Philip Raskin, A Cherian, L Holloway, M Madden, B Hollis, G Fuller, B Steiner, K Stokes, T Lowe, K Chu, S Durán, A Alfred, John M Lachin, T Hamilton, J Costello, E Burgess, R Garg, C Stevens, T Tran, M Hurtado, H Schneier, R Lorch, M Mullen, J Bantle, K Arnold, D Wexler, Neda Rasouli, D Howard, J Tejada, S Hernandez, E Schroeder, S Kunkel, G Lord, A Smiley, E Debnam, H Petrovitch, B Kauffman, V Jenkins, B Cramer, Kristina M Utzschneider, Naji Younes, Joshua I Barzilay, Mary Ann Banerji, Robert M Cohen, Erica V Gonzalez, Faramarz Ismail-Beigi, Steven E Kahn, JP Crandall, MD McKee, S Behringer-Massera, J Brown-Friday, E Xhori, K Ballentine-Cargill, H Estrella, S Gonzalez de la torre, J Lukin, LS Phillips, D Olson, M Rhee, TS Raines, J Boers, C Gullett, M Maher-Albertelli, R Mungara, L Savoye, CA White, F Morehead, S Person, M Sibymon, S Tanukonda, A Balasubramanyam, R Gaba, P Hollander, E Roe, P Burt, K Chionh, C Falck-Ytter, L Sayyed Kassem, M Tiktin, T Kulow, KA Stancil, J Iacoboni, MV Kononets, G McPhee AMaxwell, L Colosimo, R Goland, J Pring, L Alfano, C Hausheer, K Gumpel, A Kirpitch, JB Green, H AbouAssi, MN Feinglos, J English Jones, RP Zimmer, BM Satterwhite, K Evans Kreider, CR Thacker, CN Mariash, KJ Mather, A Lteif, V Pirics, D Aguillar, S Hurt, R Bergenstal, T Martens, J Hyatt, H Willis, W Konerza, K Kleeberger, R Passi, S Fortmann, M Herson, K Mularski, H Glauber, J Prihoda, B Ash, C Carlson, PA Ramey, E Schield, B Torgrimson-Ojerio, E Panos, S Sahnow, K Bays, K Berame, D Ghioni, J Gluth, K Schell, J Criscola, C Friason, S Nazarov, N Rassouli, R Puttnam, B Ojoawo, C Sanders-Jones, Z El-Haqq, A Kolli, J Meigs, A Dushkin, G Rocchio, M Yepes, H Dulin, M Cayford, A DeManbey, M Hillard, N Thangthaeng, L Gurry, R Kochis, E Raymond, V Ripley, V Aroda, Ann Ressing, A Loveland, M Hamm, F Mofor, HJ Florez, WM Valencia, S Casula, L Oropesa-Gonzalez, L Hue, AK Riccio Veliz, R Nieto-Martinez, M Gutt, A Ahmann, D Aby-Daniel, F Joarder, V Morimoto, C Sprague, D Yamashita, N Cady, N Rivera-Eschright, P Kirchhoff, B Morales Gomez, J Adducci, A Goncharova, SH Hox, M Matwichyna, NO Bermudez, L Broadwater, RR Ishii, DS Hsia, WT Cefalu, FL Greenway, C Waguespack, N Haynes, A Thomassie, B Bourgeois, C Hazlett, S Mudaliar, S Boeder, J Pettus, D Garcia-Acosta, S Maggs, C DeLue, E Castro, J Krakoff, JM Curtis, T Killean, E Joshevama, K Tsingine, T Karshner, J Albu, FX Pi-Sunyer, S Frances, C Maggio, J Bastawrose, X Gong, MA Banerji, D Lorber, NM Brown, DH Josephson, LL Thomas, M Tsovian, MH Jacobson, MM Mishko, MS Kirkman, JB Buse, J Dostou, K Bergamo, A Goley, JF Largay, S Guarda, J Cuffee, D Culmer, H Almeida, S Coffer, L Kiker, K Josey, WT Garvey, A Cherrington, D Golson, MC Robertson, A Agne, S McCullars, RM Cohen, MC Rogge, K Kersey, S Lipp, MB Vonder Meulen, C Underkofler, S Steiner, W Sivitz, E Cline, L Knosp, WH Herman, R Pop-Busui, MH Tan, A Waltje, A Katona, L Goodhall, R Eggleston, K Whitley, S Bule, N Kessler, E LaSalle, ER Seaquist, A Bantle, T Harindhanavudhi, B Redmon, M Coe, M Mech, A Taddese, L Lesne, L Kuechenmeister, V Shivaswamy, AL Morales, K Seipel, J Eggert, R Tillson, DS Schade, A Adolphe, M Burge, E Duran-Valdez, P August, MG Rodriguez, JB Kimpel, and O Griffith

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Published
2021
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7. CampETEC Hyperimmune Bovine Colostrum (HBC)

Author

Naval Medical Research Center, United States Department of Defense, and The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc

Published
2024

10. Leading with Emotional Intelligence: How Campus Leadership Skills Impact School Culture

Author

Garrett M. Jackson

Abstract

Successful leadership in the educational setting requires a unique and multifaceted skillset. It is a person-centric job with layered nuances which present challenges unique to the educational setting. The principal's responsibility to ensure positive outcomes and successful student achievement is beholden to creating and sustaining a safe environment and a culture conducive to learning. A myriad of leadership skills is required to accomplish this task. This qualitative phenomenological study identified the relationship between a positive school culture and the leadership skills of campus principals. This study explored the connection between teachers' perceptions of their principals' leadership skills and the campus culture. Further, this study suggested that the principal who exhibited skills related to the major components of emotional intelligence led a campus that teachers described as having a positive school culture. Additionally, this study examined the connection between principals' perceived leadership skills and the components of emotional intelligence.

Published
2023

12. PiPT in ADSM With MSD

Author

United States Department of Defense, United States Naval Medical Center, Portsmouth, and Henry M. Jackson Foundation for the Advancement of Military Medicine

Published
2024

14. Pathways and Barriers to Human Development and Family Science Student Engagement in Undergraduate Research

Author

Kari Morgan, Melinda Stafford Markham, Garrett M. Jackson, and Alexis Luinstra

Abstract

The value of high-impact practices in undergraduate higher education is well documented. However, very little is known about high-impact practices in Human Development and Family Science (HDFS) programs. The goal of this study was to explore one specific high-impact practice: undergraduate research. Specifically, our study explored the benefits and barriers of undergraduate research for HDFS students as well as the pathways HDFS students use to become involved in undergraduate research. College student identity theory served as a guide for our inquiry. Semi-structured interviews were conducted with 22 undergraduate HDFS students, 13 of whom had participated in undergraduate research and nine who had not. Results revealed three pathways students took to participate in undergraduate research: interest in a specific research topic, connection with the researcher, and preparation for graduate school. Enhanced learning, professional skills, personal growth, and relationships with others were identified as benefits of participation in undergraduate research. Barriers to participation in research included time, lack of awareness, and feelings of fear or intimidation. Specific processes for students and faculty to overcome these barriers are suggested. It is recommended that HDFS faculty and administrators provide multiple pathways and supports for undergraduate students to become involved in research.

Published
2023

15. When Diversity Isn't the Point: Mirrors, Windows, and Sliding Glass Doors in the Classroom

Author

Kaitlin M. Jackson

Abstract

This article looks past the gifted classics of children's literature to explore the incredible opportunity that is missed all too often: an opportunity to intentionally choose books in which diversity is not the point but showcase much-needed representation. Drawing on the concepts of mirrors, windows, and sliding glass doors this article explores how shifting titles for better representation is a seemingly small choice but one that classroom teachers can make to better engage the identities and possibilities for early childhood engagement.

Published
2023

17. Ankle Foot Orthosis Comparative Effect (AFOCE)

Author

Minneapolis Veterans Affairs Medical Center, Walter Reed National Military Medical Center, Henry M. Jackson Foundation for the Advancement of Military Medicine, Center for Veterans Research and Education, University of Delaware, Johns Hopkins Bloomberg School of Public Health, and Jason Wilken, Principal Investigator

Published
2024

27. A Controlled Trial of Losartan in Posttraumatic Stress Disorder (LOSe-PTSD)

Author

Mclean Hospital, Massachusetts General Hospital, Henry M. Jackson Foundation, Walter Reed National Military Medical Center, Foundation for Atlanta Veterans Education and Research, Inc., NYU Langone Health, George Washington University, and Murray B. Stein, Professor of Psychiatry, Family Medicine and Public Health

Published
2021

28. Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC

Author

A. Abed Abud, B. Abi, R. Acciarri, M. A. Acero, M. R. Adames, G. Adamov, M. Adamowski, D. Adams, M. Adinolfi, A. Aduszkiewicz, J. Aguilar, Z. Ahmad, J. Ahmed, B. Aimard, B. Ali-Mohammadzadeh, T. Alion, K. Allison, S. Alonso Monsalve, M. AlRashed, C. Alt, A. Alton, R. Alvarez, P. Amedo, J. Anderson, C. Andreopoulos, M. Andreotti, M. Andrews, F. Andrianala, S. Andringa, N. Anfimov, A. Ankowski, M. Antoniassi, M. Antonova, A. Antoshkin, S. Antusch, A. Aranda-Fernandez, L. Arellano, L. O. Arnold, M. A. Arroyave, J. Asaadi, L. Asquith, A. Aurisano, V. Aushev, D. Autiero, V. Ayala Lara, M. Ayala-Torres, F. Azfar, A. Back, H. Back, J. J. Back, C. Backhouse, I. Bagaturia, L. Bagby, N. Balashov, S. Balasubramanian, P. Baldi, B. Baller, B. Bambah, F. Barao, G. Barenboim, P. Barham Alzas, G. Barker, W. Barkhouse, C. Barnes, G. Barr, J. Barranco Monarca, A. Barros, N. Barros, J. L. Barrow, A. Basharina-Freshville, A. Bashyal, V. Basque, C. Batchelor, E. Batista das Chagas, J. B. R. Battat, F. Battisti, F. Bay, M. C. Q. Bazetto, J. L. L. Bazo Alba, J. F. Beacom, E. Bechetoille, B. Behera, C. Beigbeder, L. Bellantoni, G. Bellettini, V. Bellini, O. Beltramello, N. Benekos, C. Benitez Montiel, F. Bento Neves, J. Berger, S. Berkman, P. Bernardini, R. M. Berner, A. Bersani, S. Bertolucci, M. Betancourt, A. Betancur Rodríguez, A. Bevan, Y. Bezawada, T. J. C. Bezerra, A. Bhardwaj, V. Bhatnagar, M. Bhattacharjee, D. Bhattarai, S. Bhuller, B. Bhuyan, S. Biagi, J. Bian, M. Biassoni, K. Biery, B. Bilki, M. Bishai, A. Bitadze, A. Blake, F. Blaszczyk, G. C. Blazey, E. Blucher, J. Boissevain, S. Bolognesi, T. Bolton, L. Bomben, M. Bonesini, M. Bongrand, C. Bonilla-Diaz, F. Bonini, A. Booth, F. Boran, S. Bordoni, A. Borkum, N. Bostan, P. Bour, C. Bourgeois, D. Boyden, J. Bracinik, D. Braga, D. Brailsford, A. Branca, A. Brandt, J. Bremer, D. Breton, C. Brew, S. J. Brice, C. Brizzolari, C. Bromberg, J. Brooke, A. Bross, G. Brunetti, M. Brunetti, N. Buchanan, H. Budd, I. Butorov, I. Cagnoli, T. Cai, D. Caiulo, R. Calabrese, P. Calafiura, J. Calcutt, M. Calin, S. Calvez, E. Calvo, A. Caminata, M. Campanelli, D. Caratelli, D. Carber, J. C. Carceller, G. Carini, B. Carlus, M. F. Carneiro, P. Carniti, I. Caro Terrazas, H. Carranza, T. Carroll, J. F. Castaño Forero, A. Castillo, C. Castromonte, E. Catano-Mur, C. Cattadori, F. Cavalier, G. Cavallaro, F. Cavanna, S. Centro, G. Cerati, A. Cervelli, A. Cervera Villanueva, M. Chalifour, A. Chappell, E. Chardonnet, N. Charitonidis, A. Chatterjee, S. Chattopadhyay, M. S. S. Chavarry Neyra, H. Chen, M. Chen, Y. Chen, Z. Chen, Z. Chen-Wishart, Y. Cheon, D. Cherdack, C. Chi, S. Childress, R. Chirco, A. Chiriacescu, G. Chisnall, K. Cho, S. Choate, D. Chokheli, P. S. Chong, A. Christensen, D. Christian, G. Christodoulou, A. Chukanov, M. Chung, E. Church, V. Cicero, P. Clarke, G. Cline, T. E. Coan, A. G. Cocco, J. A. B. Coelho, N. Colton, E. Conley, R. Conley, J. Conrad, M. Convery, S. Copello, P. Cova, L. Cremaldi, L. Cremonesi, J. I. Crespo-Anadón, M. Crisler, E. Cristaldo, J. Crnkovic, R. Cross, A. Cudd, C. Cuesta, Y. Cui, D. Cussans, O. Dalager, H. da Motta, L. Da Silva Peres, C. David, Q. David, G. S. Davies, S. Davini, J. Dawson, K. De, S. De, P. Debbins, I. De Bonis, M. P. Decowski, A. De Gouvêa, P. C. De Holanda, I. L. De Icaza Astiz, A. Deisting, P. De Jong, A. Delbart, D. Delepine, M. Delgado, A. Dell’Acqua, N. Delmonte, P. De Lurgio, J. R. T. de Mello Neto, D. M. DeMuth, S. Dennis, C. Densham, G. W. Deptuch, A. De Roeck, V. De Romeri, G. De Souza, R. Devi, R. Dharmapalan, M. Dias, F. Diaz, J. S. Díaz, S. Di Domizio, L. Di Giulio, P. Ding, L. Di Noto, G. Dirkx, C. Distefano, R. Diurba, M. Diwan, Z. Djurcic, D. Doering, S. Dolan, F. Dolek, M. Dolinski, L. Domine, Y. Donon, D. Douglas, D. Douillet, A. Dragone, G. Drake, F. Drielsma, L. Duarte, D. Duchesneau, K. Duffy, P. Dunne, B. Dutta, H. Duyang, O. Dvornikov, D. Dwyer, A. Dyshkant, M. Eads, A. Earle, D. Edmunds, J. Eisch, L. Emberger, S. Emery, P. Englezos, A. Ereditato, T. Erjavec, C. Escobar, G. Eurin, J. J. Evans, E. Ewart, A. C. Ezeribe, K. Fahey, A. Falcone, M. Fani’, C. Farnese, Y. Farzan, D. Fedoseev, J. Felix, Y. Feng, E. Fernandez-Martinez, P. Fernandez Menendez, M. Fernandez Morales, F. Ferraro, L. Fields, P. Filip, F. Filthaut, M. Fiorini, V. Fischer, R. S. Fitzpatrick, W. Flanagan, B. Fleming, R. Flight, S. Fogarty, W. Foreman, J. Fowler, W. Fox, J. Franc, K. Francis, D. Franco, J. Freeman, J. Freestone, J. Fried, A. Friedland, F. Fuentes Robayo, S. Fuess, I. K. Furic, K. Furman, A. P. Furmanski, A. Gabrielli, A. Gago, H. Gallagher, A. Gallas, A. Gallego-Ros, N. Gallice, V. Galymov, E. Gamberini, T. Gamble, F. Ganacim, R. Gandhi, R. Gandrajula, F. Gao, S. Gao, D. Garcia-Gamez, M. Á. García-Peris, S. Gardiner, D. Gastler, J. Gauvreau, G. Ge, N. Geffroy, B. Gelli, A. Gendotti, S. Gent, Z. Ghorbani-Moghaddam, P. Giammaria, T. Giammaria, N. Giangiacomi, D. Gibin, I. Gil-Botella, S. Gilligan, C. Girerd, A. K. Giri, D. Gnani, O. Gogota, M. Gold, S. Gollapinni, K. Gollwitzer, R. A. Gomes, L. V. Gomez Bermeo, L. S. Gomez Fajardo, F. Gonnella, D. Gonzalez-Diaz, M. Gonzalez-Lopez, M. C. Goodman, O. Goodwin, S. Goswami, C. Gotti, E. Goudzovski, C. Grace, R. Gran, E. Granados, P. Granger, A. Grant, C. Grant, D. Gratieri, P. Green, L. Greenler, J. Greer, J. Grenard, W. C. Griffith, M. Groh, J. Grudzinski, K. Grzelak, W. Gu, E. Guardincerri, V. Guarino, M. Guarise, R. Guenette, E. Guerard, M. Guerzoni, D. Guffanti, A. Guglielmi, B. Guo, A. Gupta, V. Gupta, K. K. Guthikonda, R. Gutierrez, P. Guzowski, M. M. Guzzo, S. Gwon, C. Ha, K. Haaf, A. Habig, H. Hadavand, R. Haenni, A. Hahn, J. Haiston, P. Hamacher-Baumann, T. Hamernik, P. Hamilton, J. Han, D. A. Harris, J. Hartnell, T. Hartnett, J. Harton, T. Hasegawa, C. Hasnip, R. Hatcher, K. W. Hatfield, A. Hatzikoutelis, C. Hayes, K. Hayrapetyan, J. Hays, E. Hazen, M. He, A. Heavey, K. M. Heeger, J. Heise, S. Henry, M. A. Hernandez Morquecho, K. Herner, J. Hewes, C. Hilgenberg, T. Hill, S. J. Hillier, A. Himmel, E. Hinkle, L. R. Hirsch, J. Ho, J. Hoff, A. Holin, E. Hoppe, G. A. Horton-Smith, M. Hostert, A. Hourlier, B. Howard, R. Howell, J. Hoyos, I. Hristova, M. S. Hronek, J. Huang, Z. Hulcher, G. Iles, N. Ilic, A. M. Iliescu, R. Illingworth, G. Ingratta, A. Ioannisian, B. Irwin, L. Isenhower, R. Itay, C. M. Jackson, V. Jain, E. James, W. Jang, B. Jargowsky, F. Jediny, D. Jena, Y. S. Jeong, C. Jesús-Valls, X. Ji, L. Jiang, S. Jiménez, A. Jipa, R. Johnson, W. Johnson, N. Johnston, B. Jones, S. Jones, M. Judah, C. K. Jung, T. Junk, Y. Jwa, M. Kabirnezhad, A. Kaboth, I. Kadenko, I. Kakorin, A. Kalitkina, D. Kalra, F. Kamiya, N. Kaneshige, D. M. Kaplan, G. Karagiorgi, G. Karaman, A. Karcher, M. Karolak, Y. Karyotakis, S. Kasai, S. P. Kasetti, L. Kashur, N. Kazaryan, E. Kearns, P. Keener, K. J. Kelly, E. Kemp, O. Kemularia, W. Ketchum, S. H. Kettell, M. Khabibullin, A. Khotjantsev, A. Khvedelidze, D. Kim, B. King, B. Kirby, M. Kirby, J. Klein, A. Klustova, T. Kobilarcik, K. Koehler, L. W. Koerner, D. H. Koh, S. Kohn, P. P. Koller, L. Kolupaeva, D. Korablev, M. Kordosky, T. Kosc, U. Kose, V. A. Kostelecký, K. Kothekar, R. Kralik, L. Kreczko, F. Krennrich, I. Kreslo, W. Kropp, T. Kroupova, S. Kubota, Y. Kudenko, V. A. Kudryavtsev, S. Kulagin, J. Kumar, P. Kumar, P. Kunze, N. Kurita, C. Kuruppu, V. Kus, T. Kutter, J. Kvasnicka, D. Kwak, A. Lambert, B. Land, C. E. Lane, K. Lang, T. Langford, M. Langstaff, J. Larkin, P. Lasorak, D. Last, A. Laundrie, G. Laurenti, A. Lawrence, I. Lazanu, R. LaZur, M. Lazzaroni, T. Le, S. Leardini, J. Learned, P. LeBrun, T. LeCompte, C. Lee, S. Y. Lee, G. Lehmann Miotto, R. Lehnert, M. A. Leigui de Oliveira, M. Leitner, L. M. Lepin, S. W. Li, Y. Li, H. Liao, C. S. Lin, Q. Lin, S. Lin, R. A. Lineros, J. Ling, A. Lister, B. R. Littlejohn, J. Liu, Y. Liu, S. Lockwitz, T. Loew, M. Lokajicek, I. Lomidze, K. Long, T. Lord, J. M. LoSecco, W. C. Louis, X.-G. Lu, K. B. Luk, B. Lunday, X. Luo, E. Luppi, T. Lux, V. P. Luzio, J. Maalmi, D. MacFarlane, A. A. Machado, P. Machado, C. T. Macias, J. R. Macier, A. Maddalena, A. Madera, P. Madigan, S. Magill, K. Mahn, A. Maio, A. Major, J. A. Maloney, G. Mandrioli, R. C. Mandujano, J. Maneira, L. Manenti, S. Manly, A. Mann, K. Manolopoulos, M. Manrique Plata, V. N. Manyam, L. Manzanillas, M. Marchan, A. Marchionni, W. Marciano, D. Marfatia, C. Mariani, J. Maricic, R. Marie, F. Marinho, A. D. Marino, D. Marsden, M. Marshak, C. Marshall, J. Marshall, J. Marteau, J. Martín-Albo, N. Martinez, D. A. Martinez Caicedo, P. Martínez Miravé, S. Martynenko, V. Mascagna, K. Mason, A. Mastbaum, F. Matichard, S. Matsuno, J. Matthews, C. Mauger, N. Mauri, K. Mavrokoridis, I. Mawby, R. Mazza, A. Mazzacane, E. Mazzucato, T. McAskill, E. McCluskey, N. McConkey, K. S. McFarland, C. McGrew, A. McNab, A. Mefodiev, P. Mehta, P. Melas, O. Mena, H. Mendez, P. Mendez, D. P. Méndez, A. Menegolli, G. Meng, M. D. Messier, W. Metcalf, T. Mettler, M. Mewes, H. Meyer, T. Miao, G. Michna, T. Miedema, V. Mikola, R. Milincic, G. Miller, W. Miller, J. Mills, O. Mineev, A. Minotti, O. G. Miranda, S. Miryala, C. S. Mishra, S. R. Mishra, A. Mislivec, M. Mitchell, D. Mladenov, I. Mocioiu, K. Moffat, N. Moggi, R. Mohanta, T. A. Mohayai, N. Mokhov, J. Molina, L. Molina Bueno, E. Montagna, A. Montanari, C. Montanari, D. Montanari, L. M. Montañno Zetina, S. H. Moon, M. Mooney, A. F. Moor, D. Moreno, D. Moretti, C. Morris, C. Mossey, M. Mote, E. Motuk, C. A. Moura, J. Mousseau, G. Mouster, W. Mu, L. Mualem, J. Mueller, M. Muether, S. Mufson, F. Muheim, A. Muir, M. Mulhearn, D. Munford, H. Muramatsu, S. Murphy, J. Musser, J. Nachtman, S. Nagu, M. Nalbandyan, R. Nandakumar, D. Naples, S. Narita, A. Nath, A. Navrer-Agasson, N. Nayak, M. Nebot-Guinot, K. Negishi, J. K. Nelson, J. Nesbit, M. Nessi, D. Newbold, M. Newcomer, H. Newton, R. Nichol, F. Nicolas-Arnaldos, A. Nikolica, E. Niner, K. Nishimura, A. Norman, A. Norrick, R. Northrop, P. Novella, J. A. Nowak, M. Oberling, J. Ochoa-Ricoux, A. Olivier, A. Olshevskiy, Y. Onel, Y. Onishchuk, J. Ott, L. Pagani, G. Palacio, O. Palamara, S. Palestini, J. M. Paley, M. Pallavicini, C. Palomares, W. Panduro Vazquez, E. Pantic, V. Paolone, V. Papadimitriou, R. Papaleo, A. Papanestis, S. Paramesvaran, S. Parke, E. Parozzi, Z. Parsa, M. Parvu, S. Pascoli, L. Pasqualini, J. Pasternak, J. Pater, C. Patrick, L. Patrizii, R. B. Patterson, S. J. Patton, T. Patzak, A. Paudel, B. Paulos, L. Paulucci, Z. Pavlovic, G. Pawloski, D. Payne, V. Pec, S. J. M. Peeters, A. Pena Perez, E. Pennacchio, A. Penzo, O. L. G. Peres, J. Perry, D. Pershey, G. Pessina, G. Petrillo, C. Petta, R. Petti, V. Pia, F. Piastra, L. Pickering, F. Pietropaolo, V. L. Pimentel, G. Pinaroli, K. Plows, R. Plunkett, R. Poling, F. Pompa, X. Pons, N. Poonthottathil, F. Poppi, S. Pordes, J. Porter, M. Potekhin, R. Potenza, B. V. K. S. Potukuchi, J. Pozimski, M. Pozzato, S. Prakash, T. Prakash, M. Prest, S. Prince, F. Psihas, D. Pugnere, X. Qian, J. L. Raaf, V. Radeka, J. Rademacker, B. Radics, A. Rafique, E. Raguzin, M. Rai, M. Rajaoalisoa, I. Rakhno, A. Rakotonandrasana, L. Rakotondravohitra, R. Rameika, M. A. Ramirez Delgado, B. Ramson, A. Rappoldi, G. Raselli, P. Ratoff, S. Raut, R. F. Razakamiandra, E. M. Rea, J. S. Real, B. Rebel, R. Rechenmacher, M. Reggiani-Guzzo, J. Reichenbacher, S. D. Reitzner, H. Rejeb Sfar, A. Renshaw, S. Rescia, F. Resnati, M. Ribas, S. Riboldi, C. Riccio, G. Riccobene, L. C. J. Rice, J. S. Ricol, A. Rigamonti, Y. Rigaut, E. V. Rincón, H. Ritchie-Yates, D. Rivera, A. Robert, L. Rochester, M. Roda, P. Rodrigues, M. J. Rodriguez Alonso, E. Rodriguez Bonilla, J. Rodriguez Rondon, S. Rosauro-Alcaraz, M. Rosenberg, P. Rosier, B. Roskovec, M. Rossella, M. Rossi, J. Rout, P. Roy, A. Rubbia, C. Rubbia, B. Russell, D. Ruterbories, A. Rybnikov, A. Saa-Hernandez, R. Saakyan, S. Sacerdoti, T. Safford, N. Sahu, K. Sakashita, P. Sala, N. Samios, O. Samoylov, M. C. Sanchez, V. Sandberg, D. A. Sanders, D. Sankey, S. Santana, M. Santos-Maldonado, N. Saoulidou, P. Sapienza, C. Sarasty, I. Sarcevic, G. Savage, V. Savinov, A. Scaramelli, A. Scarff, A. Scarpelli, T. Schefke, H. Schellman, S. Schifano, P. Schlabach, D. Schmitz, A. W. Schneider, K. Scholberg, A. Schukraft, E. Segreto, A. Selyunin, C. R. Senise, J. Sensenig, A. Sergi, D. Sgalaberna, M. H. Shaevitz, S. Shafaq, F. Shaker, M. Shamma, R. Sharankova, H. R. Sharma, R. Sharma, R. K. Sharma, T. Shaw, K. Shchablo, C. Shepherd-Themistocleous, A. Sheshukov, S. Shin, I. Shoemaker, D. Shooltz, R. Shrock, H. Siegel, L. Simard, J. Sinclair, G. Sinev, J. Singh, L. Singh, P. Singh, V. Singh, R. Sipos, F. W. Sippach, G. Sirri, A. Sitraka, K. Siyeon, K. Skarpaas, A. Smith, E. Smith, P. Smith, J. Smolik, M. Smy, E. Snider, P. Snopok, D. Snowden-Ifft, M. Soares Nunes, H. Sobel, M. Soderberg, S. Sokolov, C. J. Solano Salinas, S. Söldner-Rembold, S. R. Soleti, N. Solomey, V. Solovov, W. E. Sondheim, M. Sorel, A. Sotnikov, J. Soto-Oton, F. A. Soto Ugaldi, A. Sousa, K. Soustruznik, F. Spagliardi, M. Spanu, J. Spitz, N. J. C. Spooner, K. Spurgeon, M. Stancari, L. Stanco, C. Stanford, R. Stein, H. M. Steiner, A. F. Steklain Lisbôa, J. Stewart, B. Stillwell, J. Stock, F. Stocker, T. Stokes, M. Strait, T. Strauss, L. Strigari, A. Stuart, J. G. Suarez, J. M. Suárez Sunción, H. Sullivan, D. Summers, A. Surdo, V. Susic, L. Suter, C. M. Sutera, R. Svoboda, B. Szczerbinska, A. M. Szelc, H. Tanaka, S. Tang, A. Tapia, B. Tapia Oregui, A. Tapper, S. Tariq, E. Tarpara, N. Tata, E. Tatar, R. Tayloe, A. M. Teklu, P. Tennessen, M. Tenti, K. Terao, C. A. Ternes, F. Terranova, G. Testera, T. Thakore, A. Thea, J. L. Thompson, C. Thorn, S. C. Timm, V. Tishchenko, L. Tomassetti, A. Tonazzo, D. Torbunov, M. Torti, M. Tortola, F. Tortorici, N. Tosi, D. Totani, M. Toups, C. Touramanis, R. Travaglini, J. Trevor, S. Trilov, W. H. Trzaska, Y. Tsai, Y.-T. Tsai, Z. Tsamalaidze, K. V. Tsang, N. Tsverava, S. Tufanli, C. Tull, E. Tyley, M. Tzanov, L. Uboldi, M. A. Uchida, J. Urheim, T. Usher, S. Uzunyan, M. R. Vagins, P. Vahle, S. Valder, G. D. A. Valdiviesso, E. Valencia, R. Valentim, Z. Vallari, E. Vallazza, J. W. F. Valle, S. Vallecorsa, R. Van Berg, R. G. Van de Water, D. Vanegas Forero, D. Vannerom, F. Varanini, D. Vargas Oliva, G. Varner, J. Vasel, S. Vasina, G. Vasseur, N. Vaughan, K. Vaziri, S. Ventura, A. Verdugo, S. Vergani, M. A. Vermeulen, M. Verzocchi, M. Vicenzi, H. Vieira de Souza, C. Vignoli, C. Vilela, B. Viren, T. Vrba, T. Wachala, A. V. Waldron, M. Wallbank, C. Wallis, H. Wang, J. Wang, L. Wang, M. H. L. S. Wang, X. Wang, Y. Wang, K. Warburton, D. Warner, M. O. Wascko, D. Waters, A. Watson, K. Wawrowska, P. Weatherly, A. Weber, M. Weber, H. Wei, A. Weinstein, D. Wenman, M. Wetstein, A. White, L. H. Whitehead, D. Whittington, M. J. Wilking, A. Wilkinson, C. Wilkinson, Z. Williams, F. Wilson, R. J. Wilson, W. Wisniewski, J. Wolcott, T. Wongjirad, A. Wood, K. Wood, E. Worcester, M. Worcester, K. Wresilo, C. Wret, W. Wu, Y. Xiao, F. Xie, B. Yaeggy, E. Yandel, G. Yang, K. Yang, T. Yang, A. Yankelevich, N. Yershov, K. Yonehara, Y. S. Yoon, T. Young, B. Yu, H. Yu, J. Yu, Y. Yu, W. Yuan, R. Zaki, J. Zalesak, L. Zambelli, B. Zamorano, A. Zani, L. Zazueta, G. P. Zeller, J. Zennamo, K. Zeug, C. Zhang, S. Zhang, Y. Zhang, M. Zhao, E. Zhivun, G. Zhu, E. D. Zimmerman, S. Zucchelli, J. Zuklin, V. Zutshi, R. Zwaska, and DUNE Collaboration

Subjects
Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Abstract DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6 $$\times $$ × 6 $$\times $$ × 6 m $$^3$$ 3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019–2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the LArTPC is collected by photomultiplier tubes placed up to 7 m away from the ionizing track. In this paper, the ProtoDUNE-DP photon detection system performance is evaluated with a particular focus on the different wavelength shifters, such as PEN and TPB, and the use of Xe-doped LAr, considering its future use in giant LArTPCs. The scintillation light production and propagation processes are analyzed and a comparison of simulation to data is performed, improving understanding of the liquid argon properties.

Published
2022
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29. The TIP60-ATM axis regulates replication fork stability in BRCA-deficient cells

Author

Emily M. Schleicher, Ashna Dhoonmoon, Lindsey M. Jackson, Jude B. Khatib, Claudia M. Nicolae, and George-Lucian Moldovan

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Maintenance of replication fork stability is essential for genome preservation. Stalled replication forks can be reversed by translocases such as SMARCAL1, and unless protected through the activity of the BRCA pathway, are subsequently subjected to nucleolytic degradation. The ATM and ATR kinases are master regulators of the DNA damage response. ATM activation upon DNA damage is mediated by the acetyltransferase TIP60. Here, we show that the TIP60-ATM pathway promotes replication fork reversal by recruiting SMARCAL1 to stalled forks. This enables fork degradation in BRCA-deficient cells. We also show that this ATM activity is not shared by ATR. Moreover, we performed a series of genome-wide CRISPR knockout genetic screens to identify genetic determinants of the cellular sensitivity to ATM inhibition in wildtype and BRCA2-knockout cells, and validated the top hits from multiple screens. We provide a valuable list of common genes which regulate the response to multiple ATM inhibitors. Importantly, we identify a differential response of wildtype and BRCA2-deficient cells to these inhibitors. In BRCA2-knockout cells, DNA repair genes (including RAD17, MDC1, and USP28) were essential for survival upon ATM inhibitor treatment, which was not the case in wild-type cells. These findings may eventually help guide the way for rational deployment of ATM inhibitors in the clinic.

Published
2022
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30. Portalvein reconstruction with a cadaveric descending thoracic aortic homograft

Author

Ann C. Gaffey, MD, MS, Jason Zhang, MD, Major K. Lee, MD, PhD, Robert Roses, MD, Benjamin M. Jackson, MD, and Jon G. Quatromoni, MD

Subjects
Homograft, Oncologic reconstruction, Portal vein reconstruction, Surgery, RD1-811, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Improvements in chemoradiotherapy have rendered complex pancreatic cancers involving the portal vein (PV) amenable to resection. PV reconstruction (PVR) is an essential component. Various conduits have been proposed; however, the optimal choice remains unknown. Fourteen patients underwent PVR with a cadaveric descending thoracic aortic homograft from 2014 to 2020. The primary diagnosis was pancreatic cancer. The splenic vein was ligated in seven patients (50%). The 30-day and 3-, 12-, and 24-month primary patency rates were 100%, 86%, 76%, and 76%, respectively. We found a cadaveric descending thoracic aortic homograft is an excellent conduit for PVR, given the optimal size, rapidly availability, favorable risk profile, and absence of harvest site complications.

Published
2022
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33. Rapid transition from primary to secondary crust building on the Moon explained by mantle overturn

Author

Tabb C. Prissel, Nan Zhang, Colin R. M. Jackson, and Haoyuan Li

Subjects
Geosciences (General), Lunar and Planetary Science and Exploration
Abstract

Geochronology indicates a rapid transition (tens of Myrs) from primary to secondary crust building on the Moon. The processes responsible for initiating secondary magmatism, however, remain in debate. Here we test the hypothesis that the earliest secondary crust (Mg-suite) formed as a direct consequence of density-driven mantle overturn, and advance 3D mantle convection models to quantify the resulting extent of lower mantle melting. Our modeling demonstrates that overturn of thin ilmenite-bearing cumulates ≤ 100 km triggers a rapid and short-lived episode of lower mantle melting which explains the key volume, geochronological, and spatial characteristics of early secondary crust building without contributions from other energy sources, namely KREEP (potassium, rare earth elements, phosphorus, radiogenic U, Th). Observations of globally distributed Mg-suite eliminate degree-1 overturn scenarios. We propose that gravitational instabilities in magma ocean cumulate piles are major driving forces for the onset of mantle convection and secondary crust building on differentiated bodies.

Published
2023
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34. Exposure to lead-free frangible firing emissions containing copper and ultrafine particulates leads to increased oxidative stress in firing range instructors

Author

Ryan J. McNeilly, Jennifer A. Schwanekamp, Logan S. Hyder, John P. Hatch, Brett T. Edwards, Jacob A. Kirsh, Jerimiah M. Jackson, Thomas Jaworek, Mark M. Methner, and Christin M. Duran

Subjects
Exposure assessment, Biomarkers, Ultrafine particulate, Firing range, Carbon monoxide, Copper, Toxicology. Poisons, RA1190-1270, Industrial hygiene. Industrial welfare, HD7260-7780.8
Abstract

Abstract Background Since the introduction of copper based, lead-free frangible (LFF) ammunition to Air Force small arms firing ranges, instructors have reported symptoms including chest tightness, respiratory irritation, and metallic taste. These symptoms have been reported despite measurements determining that instructor exposure does not exceed established occupational exposure limits (OELs). The disconnect between reported symptoms and exposure limits may be due to a limited understanding of LFF firing byproducts and subsequent health effects. A comprehensive characterization of exposure to instructors was completed, including ventilation system evaluation, personal monitoring, symptom tracking, and biomarker analysis, at both a partially enclosed and fully enclosed range. Results Instructors reported symptoms more frequently after M4 rifle classes compared to classes firing only the M9 pistol. Ventilation measurements demonstrated that airflow velocities at the firing line were highly variable and often outside established standards at both ranges. Personal breathing zone air monitoring showed exposure to carbon monoxide, ultrafine particulate, and metals. In general, exposure to instructors was higher at the partially enclosed range compared to the fully enclosed range. Copper measured in the breathing zone of instructors, on rare occasions, approached OELs for copper fume (0.1 mg/m3). Peak carbon monoxide concentrations were 4–5 times higher at the partially enclosed range compared to the enclosed range and occasionally exceeded the ceiling limit (125 ppm). Biological monitoring showed that lung function was maintained in instructors despite respiratory symptoms. However, urinary oxidative stress biomarkers and urinary copper measurements were increased in instructors compared to control groups. Conclusions Consistent with prior work, this study demonstrates that symptoms still occurred despite exposures below OELs. Routine monitoring of symptoms, urinary metals, and oxidative stress biomarkers can help identify instructors who are particularly affected by exposures. These results can assist in guiding protective measures to reduce exposure and protect instructor health. Further, a longitudinal study is needed to determine the long-term health consequences of LFF firing emissions exposure.

Published
2022
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35. Durability of Antibody Response and Frequency of SARS-CoV-2 Infection 6 Months after COVID-19 Vaccination in Healthcare Workers

Author

Eric D. Laing, Carol D. Weiss, Emily C. Samuels, Si’Ana A. Coggins, Wei Wang, Richard Wang, Russell Vassell, Spencer L. Sterling, Marana S. Tso, Tonia Conner, Emilie Goguet, Matthew Moser, Belinda M. Jackson-Thompson, Luca Illinik, Julian Davies, Orlando Ortega, Edward Parmelee, Monique Hollis-Perry, Santina E. Maiolatesi, Gregory Wang, Kathleen F. Ramsey, Anatalio E. Reyes, Yolanda Alcorta, Mimi A. Wong, Alyssa R. Lindrose, Christopher A. Duplessis, David R. Tribble, Allison M.W. Malloy, Timothy H. Burgess, Simon D. Pollett, Cara H. Olsen, Christopher C. Broder, and Edward Mitre

Subjects
COVID-19, coronavirus disease, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, viruses, respiratory infections, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies decay but persist 6 months postvaccination; lower levels of neutralizing titers persist against Delta than wild-type virus. Of 227 vaccinated healthcare workers tested, only 2 experienced outpatient symptomatic breakthrough infections, despite 59/227 exhibiting serologic evidence of SARS-CoV-2 infection, defined as presence of nucleocapsid protein antibodies.

Published
2022
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36. A High-Eccentricity Warm Jupiter Orbiting TOI-4127

Author

Arvind F. Gupta, Jonathan M. Jackson, Guillaume Hébrard, Andrea S. J. Lin, Keivan G. Stassun, Jiayin Dong, Steven Villanueva Jr, Diana Dragomir, Suvrath Mahadevan, Jason T. Wright, Jose M. Almenara, Cullen H. Blake, Isabelle Boisse, Pía Cortés-Zuleta, Paul A. Dalba, Rodrigo F. Díaz, Eric B. Ford, Thierry Forveille, Robert Gagliano, Samuel Halverson, Neda Heidari, Shubham Kanodia, Flavien Kiefer, David W. Latham, Michael W. McElwain, Ismael Mireles, Claire Moutou, Joshua Pepper, George R. Ricker, Paul Robertson, Arpita Roy, Martin Schlecker, Christian Schwab, S. Seager, Avi Shporer, Guđmundur Stefánsson, Ryan C. Terrien, Eric B. Ting, Joshua N. Winn, and Allison Ann Youngblood

Subjects
Astronomy, Astrophysics
Abstract

We report the discovery of TOI-4127 b, which is a transiting, Jupiter-sized exoplanet on a long period (P=56.39879 +0.00010-0.00010days) and a high-eccentricity orbit around a late F-type dwarf star. This warm Jupiter was first detected and identified as a promising candidate from a search for single-transit signals in TESS Sector 20 data and was later characterized as a planet following two subsequent transits (TESS Sectors 26 and 53) and follow-up ground-based RV observations with the NEID and SOPHIE spectrographs. We jointly fit the transit and RV data to constrain the physical (Rp=1.096+0.039-0.032RJ, Mp=2.30+0.11-0.11MJ) and orbital parameters of the exoplanet. Given its high orbital eccentricity (𝓮=0.7471+0.0078-0.0086), TOI-4127 b is a compelling candidate for studies of warm Jupiter populations and of hot Jupiter formation pathways. We show that the present periastron separation of TOI-4127 b is too large for high-eccentricity tidal migration to circularize its orbit, and that TOI-4127 b is unlikely to be a hot Jupiter progenitor unless it is undergoing angular momentum exchange with an undetected outer companion. Although we find no evidence for an external companion, the available observational data are insufficient to rule out the presence of a perturber that can excite eccentricity oscillations and facilitate tidal migration.

Published
2023
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37. HIV Vaccine Trial in Thai Adults

Author

United States Army Medical Materiel Development Activity, Armed Forces Research Institute of Medical Sciences, Thailand, Walter Reed Army Institute of Research (WRAIR), MCM Vaccines B.V., VaxGen, The Emmes Company, LLC, Ministry of Health, Thailand, Mahidol University, Royal Thai Army Medical Department, Tripler Army Medical Center, and Henry M. Jackson Foundation for the Advancement of Military Medicine

Published
2019

40. The Translational Potential of Microglia and Monocyte-Derived Macrophages in Ischemic Stroke

Author

Elizabeth E. Wicks, Kathleen R. Ran, Jennifer E. Kim, Risheng Xu, Ryan P. Lee, and Christopher M. Jackson

Subjects
microglia, monocyte-derived macrophages, ischemic stroke, polarization, clinical therapy/immunology, immune response, Immunologic diseases. Allergy, RC581-607
Abstract

The immune response to ischemic stroke is an area of study that is at the forefront of stroke research and presents promising new avenues for treatment development. Upon cerebral vessel occlusion, the innate immune system is activated by danger-associated molecular signals from stressed and dying neurons. Microglia, an immune cell population within the central nervous system which phagocytose cell debris and modulate the immune response via cytokine signaling, are the first cell population to become activated. Soon after, monocytes arrive from the peripheral immune system, differentiate into macrophages, and further aid in the immune response. Upon activation, both microglia and monocyte-derived macrophages are capable of polarizing into phenotypes which can either promote or attenuate the inflammatory response. Phenotypes which promote the inflammatory response are hypothesized to increase neuronal damage and impair recovery of neuronal function during the later phases of ischemic stroke. Therefore, modulating neuroimmune cells to adopt an anti-inflammatory response post ischemic stroke is an area of current research interest and potential treatment development. In this review, we outline the biology of microglia and monocyte-derived macrophages, further explain their roles in the acute, subacute, and chronic stages of ischemic stroke, and highlight current treatment development efforts which target these cells in the context of ischemic stroke.

Published
2022
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42. Synthesizing Molecular and Immune Characteristics to Move Beyond WHO Grade in Meningiomas: A Focused Review

Author

Nivedha V. Kannapadi, Pavan P. Shah, Dimitrios Mathios, and Christopher M. Jackson

Subjects
meningioma, immunotherapy, immune microenvironment, prognostic model, risk score, meningioma WHO grade I, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

No portion of this manuscript has previously been presented. Meningiomas, the most common primary intracranial tumors, are histologically categorized by the World Health Organization (WHO) grading system. While higher WHO grade is generally associated with poor clinical outcomes, a significant subset of grade I tumors recur or progress, indicating a need for more reliable models of meningioma behavior. Several groups have developed risk scores based on molecular or immunologic characteristics. These classification schemes show promise, with several models preliminarily demonstrating similar or superior accuracy to WHO grading. Improved understanding of immune system recognition and targeting of meningioma subtypes is necessary to advance the predictive power, as well as develop new therapies. Here, we characterize meningioma molecular drivers, predictive of recurrence and progression, and describe specific aspects of the immune response to meningiomas while highlighting critical questions and ongoing research. Relevant manuscripts of interest were identified using a systematic approach and synthesized into this focused review. Finally, we summarize the ongoing and completed clinical trials for immunotherapy in meningiomas and offer perspective on future directions.

Published
2022
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43. Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC)

Author

Isaac M. Jackson, So Jeong Lee, Alexandra R. Sowa, Melissa E. Rodnick, Laura Bruton, Mara Clark, Sean Preshlock, Jill Rothley, Virginia E. Rogers, Leslie E. Botti, Bradford D. Henderson, Brian G. Hockley, Jovany Torres, David M. Raffel, Allen F. Brooks, Kirk A. Frey, Michael R. Kilbourn, Robert A. Koeppe, Xia Shao, and Peter J. H. Scott

Subjects
PET imaging, Regulatory oversight, Dosimetry, RDRC, IND, Radiopharmaceuticals, Medical physics. Medical radiology. Nuclear medicine, R895-920, Therapeutics. Pharmacology, RM1-950
Abstract

Abstract Background In the US, EU and elsewhere, basic clinical research studies with positron emission tomography (PET) radiotracers that are generally recognized as safe and effective (GRASE) can often be conducted under institutional approval. For example, in the United States, such research is conducted under the oversight of a Radioactive Drug Research Committee (RDRC) as long as certain requirements are met. Firstly, the research must be for basic science and cannot be intended for immediate therapeutic or diagnostic purposes, or to determine the safety and effectiveness of the PET radiotracer. Secondly, the PET radiotracer must be generally recognized as safe and effective. Specifically, the mass dose to be administered must not cause any clinically detectable pharmacological effect in humans, and the radiation dose to be administered must be the smallest dose practical to perform the study and not exceed regulatory dose limits within a 1-year period. In our experience, the main barrier to using a PET radiotracer under RDRC approval is accessing the required information about mass and radioactive dosing. Results The University of Michigan (UM) has a long history of using PET radiotracers in clinical research studies. Herein we provide dosing information for 55 radiotracers that will enable other PET Centers to use them under the approval of their own RDRC committees. Conclusions The data provided herein will streamline future RDRC approval, and facilitate further basic science investigation of 55 PET radiotracers that target functionally relevant biomarkers in high impact disease states.

Published
2020
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44. Promoting Well-being Among Neurology Residents: A Data-Driven Approach

Author

Vijay K Ramanan, MD, PhD, Jery D. Inbarasu, MD, Lauren M. Jackson, MD, Lyell K. Jones, Jr., MD;, and James P. Klaas, MD

Subjects
Medicine (General), R5-920
Abstract

Objective: To assess whether the creation of a formal structure to measure and promote wellness among neurology residents would facilitate the development of interventions associated with measurable improvements. Methods: In 2018 we founded the Resident Wellness Committee for the Department of Neurology at our institution. The Resident Wellness Committee was led by resident and staff neurologist co-chairs and had as its vision to promote well-being through initiatives centered in work-life integration, emotional and physical well-being, and social engagement. Web-based surveys assessing various aspects of well-being were administered at baseline and 1 year after launch, comprising the period June 21, 2018, through June 30, 2019. Results: Response rates were high at baseline (21 of 34; 62%) and follow-up (25 of 33; 76%). Interventions pursued in the interim included education on handling unexpected absences, adjustments to holiday schedule policies, infrastructure for nutrition and respite, and a team-based department fitness challenge, among others. Overall, at both timepoints more than 80% (18 of 21; 21 of 25) of respondents endorsed at least mild burnout symptoms, although clinical workload, independence, and education were overwhelmingly viewed positively throughout. Notable improvements at follow-up included greater comfort with adjusting schedules at times of need, increased camaraderie within the program, and a smaller proportion of respondents endorsing substantial burnout symptoms. Conclusion: Through deliberate and sustained efforts backed by data, our work demonstrates that concrete changes can be successfully pursued to promote well-being among neurology residents. Given that Neurology has one of the highest burnout rates among medical specialties, our approach may serve as a model for other programs to replicate.

Published
2020
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45. A novel mouse model expressing human forms for complement receptors CR1 and CR2

Author

Harriet M. Jackson, Kate E. Foley, Rita O’Rourke, Timothy M. Stearns, Dina Fathalla, B. Paul Morgan, and Gareth R. Howell

Subjects
Complement cascade, Complement regulators, Immune cells, Alzheimer’s disease, Lupus, Hematopoietic cells, Genetics, QH426-470
Abstract

Abstract Background The complement cascade is increasingly implicated in development of a variety of diseases with strong immune contributions such as Alzheimer’s disease and Systemic Lupus Erythematosus. Mouse models have been used to determine function of central components of the complement cascade such as C1q and C3. However, species differences in their gene structures mean that mice do not adequately replicate human complement regulators, including CR1 and CR2. Genetic variation in CR1 and CR2 have been implicated in modifying disease states but the mechanisms are not known. Results To decipher the roles of human CR1 and CR2 in health and disease, we engineered C57BL/6J (B6) mice to replace endogenous murine Cr2 with human complement receptors, CR1 and CR2 (B6.CR2CR1). CR1 has an array of allotypes in human populations and using traditional recombination methods (Flp-frt and Cre-loxP) two of the most common alleles (referred to here as CR1 long and CR1 short ) can be replicated within this mouse model, along with a CR1 knockout allele (CR1 KO ). Transcriptional profiling of spleens and brains identified genes and pathways differentially expressed between mice homozygous for either CR1 long , CR1 short or CR1 KO . Gene set enrichment analysis predicts hematopoietic cell number and cell infiltration are modulated by CR1 long , but not CR1 short or CR1 KO . Conclusion The B6.CR2CR1 mouse model provides a novel tool for determining the relationship between human-relevant CR1 alleles and disease.

Published
2020
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46. Development of a CD19 PET tracer for detecting B cells in a mouse model of multiple sclerosis

Author

Marc Y. Stevens, Haley C. Cropper, Katherine L. Lucot, Aisling M. Chaney, Kendra J. Lechtenberg, Isaac M. Jackson, Marion S. Buckwalter, and Michelle L. James

Subjects
PET, Multiple sclerosis, EAE mice, B cells, CD19, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real-time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer, and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE). Methods Female C57BL/6 J mice were induced with EAE through immunization with myelin oligodendrocyte glycoprotein (MOG1–125). PET imaging of naïve and EAE mice was performed 19 h after administration of [64Cu]CD19-mAb. Thereafter, radioactivity in organs of interest was determined by gamma counting, followed by ex vivo autoradiography of central nervous system (CNS) tissues. Anti-CD45R (B220) immunostaining of brain tissue from EAE and naïve mice was also conducted. Results Radiolabelling of DOTA-conjugated CD19-mAb with 64Cu was achieved with a radiochemical purity of 99% and molar activity of 2 GBq/μmol. Quantitation of CD19 PET images revealed significantly higher tracer binding in whole brain of EAE compared to naïve mice (2.02 ± 0.092 vs. 1.68 ± 0.06 percentage of injected dose per gram, % ID/g, p = 0.0173). PET findings were confirmed by ex vivo gamma counting of perfused brain tissue (0.22 ± 0.020 vs. 0.12 ± 0.003 % ID/g, p = 0.0010). Moreover, ex vivo autoradiography of brain sections corresponded with PET imaging results and the spatial distribution of B cells observed in B220 immunohistochemistry—providing further evidence that [64Cu]CD19-mAb enables visualization of B cell infiltration into the CNS of EAE mice. Conclusion CD19-PET imaging can be used to detect elevated levels of B cells in the CNS of EAE mice, and has the potential to impact the way we study, monitor, and treat clinical MS.

Published
2020
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47. Theia: an advanced optical neutrino detector

Author

M. Askins, Z. Bagdasarian, N. Barros, E. W. Beier, E. Blucher, R. Bonventre, E. Bourret, E. J. Callaghan, J. Caravaca, M. Diwan, S. T. Dye, J. Eisch, A. Elagin, T. Enqvist, V. Fischer, K. Frankiewicz, C. Grant, D. Guffanti, C. Hagner, A. Hallin, C. M. Jackson, R. Jiang, T. Kaptanoglu, J. R. Klein, Yu. G. Kolomensky, C. Kraus, F. Krennrich, T. Kutter, T. Lachenmaier, B. Land, K. Lande, J. G. Learned, V. Lozza, L. Ludhova, M. Malek, S. Manecki, J. Maneira, J. Maricic, J. Martyn, A. Mastbaum, C. Mauger, F. Moretti, J. Napolitano, B. Naranjo, M. Nieslony, L. Oberauer, G. D. Orebi Gann, J. Ouellet, T. Pershing, S. T. Petcov, L. Pickard, R. Rosero, M. C. Sanchez, J. Sawatzki, S. H. Seo, M. Smiley, M. Smy, A. Stahl, H. Steiger, M. R. Stock, H. Sunej, R. Svoboda, E. Tiras, W. H. Trzaska, M. Tzanov, M. Vagins, C. Vilela, Z. Wang, J. Wang, M. Wetstein, M. J. Wilking, L. Winslow, P. Wittich, B. Wonsak, E. Worcester, M. Wurm, G. Yang, M. Yeh, E. D. Zimmerman, S. Zsoldos, and K. Zuber

Subjects
Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Abstract New developments in liquid scintillators, high-efficiency, fast photon detectors, and chromatic photon sorting have opened up the possibility for building a large-scale detector that can discriminate between Cherenkov and scintillation signals. Such a detector could reconstruct particle direction and species using Cherenkov light while also having the excellent energy resolution and low threshold of a scintillator detector. Situated deep underground, and utilizing new techniques in computing and reconstruction, this detector could achieve unprecedented levels of background rejection, enabling a rich physics program spanning topics in nuclear, high-energy, and astrophysics, and across a dynamic range from hundreds of keV to many GeV. The scientific program would include observations of low- and high-energy solar neutrinos, determination of neutrino mass ordering and measurement of the neutrino CP-violating phase $$\delta $$ δ , observations of diffuse supernova neutrinos and neutrinos from a supernova burst, sensitive searches for nucleon decay and, ultimately, a search for neutrinoless double beta decay, with sensitivity reaching the normal ordering regime of neutrino mass phase space. This paper describes Theia, a detector design that incorporates these new technologies in a practical and affordable way to accomplish the science goals described above.

Published
2020
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48. Transcriptional analyses of adult and pediatric adamantinomatous craniopharyngioma reveals similar expression signatures regarding potential therapeutic targets

Author

Eric Prince, Ros Whelan, Andrew Donson, Susan Staulcup, Astrid Hengartner, Trinka Vijmasi, Chibueze Agwu, Kevin O. Lillehei, Nicholas K. Foreman, James M. Johnston, Luca Massimi, Richard C. E. Anderson, Mark M. Souweidane, Robert P. Naftel, David D. Limbrick, Gerald Grant, Toba N. Niazi, Roy Dudley, Lindsay Kilburn, Eric M. Jackson, George I. Jallo, Kevin Ginn, Amy Smith, Joshua J. Chern, Amy Lee, Annie Drapeau, Mark D. Krieger, Michael H. Handler, Todd C. Hankinson, and on behalf of the Advancing Treatment for Pediatric Craniopharyngioma Consortium

Subjects
Adamantinomatous Craniopharyngioma, Transcriptional analysis, Age-related therapy, Pediatric Craniopharyngioma, Suprasellar tumor, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential therapies identified through the study of pediatric ACP may also have a role in adult ACP. Using our compiled transcriptome dataset of 27 pediatric and 9 adult ACPs, obtained through the Advancing Treatment for Pediatric Craniopharyngioma Consortium, we interrogated potential age-related transcriptional differences using several rigorous mathematical analyses. These included: canonical differential expression analysis; divisive, agglomerative, and probabilistic based hierarchical clustering; information theory based characterizations; and the deep learning approach, HD Spot. Our work indicates that there is no therapeutically relevant difference in ACP gene expression based on age. As such, potential therapeutic targets identified in pediatric ACP are also likely to have relvance for adult patients.

Published
2020
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49. A risk-based model to assess environmental justice and coronary heart disease burden from traffic-related air pollutants

Author

James P. Fabisiak, Erica M. Jackson, LuAnn L. Brink, and Albert A. Presto

Subjects
Environmental justice, Air pollution, Nitrogen dioxide, Black carbon, Coronary heart disease, Risk assessment, Industrial medicine. Industrial hygiene, RC963-969, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Communities need to efficiently estimate the burden from specific pollutants and identify those most at risk to make timely informed policy decisions. We developed a risk-based model to estimate the burden of black carbon (BC) and nitrogen dioxide (NO2) on coronary heart disease (CHD) across environmental justice (EJ) and non-EJ populations in Allegheny County, PA. Methods Exposure estimates in census tracts were modeled via land use regression and analyzed in relation to US Census data. Tracts were ranked into quartiles of exposure (Q1-Q4). A risk-based model for estimating the CHD burden attributed to BC and NO2 was developed using county health statistics, census tract level exposure estimates, and quantitative effect estimates available in the literature. Results For both pollutants, the relative occurrence of EJ tracts (> 20% poverty and/or > 30% non-white minority) in Q2 – Q4 compared to Q1 progressively increased and reached a maximum in Q4. EJ tracts were 4 to 25 times more likely to be in the highest quartile of exposure compared to the lowest quartile for BC and NO2, respectively. Pollutant-specific risk values (mean [95% CI]) for CHD mortality were higher in EJ tracts (5.49 × 10− 5 [5.05 × 10− 5 – 5.92 × 10− 5]; 5.72 × 10− 5 [5.44 × 10− 5 – 6.01 × 10− 5] for BC and NO2, respectively) compared to non-EJ tracts (3.94 × 10− 5 [3.66 × 10− 5 – 4.23 × 10− 5]; 3.49 × 10− 5 [3.27 × 10− 5 – 3.70 × 10− 5] for BC and NO2, respectively). While EJ tracts represented 28% of the county population, they accounted for about 40% of the CHD mortality attributed to each pollutant. EJ tracts are disproportionately skewed toward areas of high exposure and EJ residents bear a greater risk for air pollution-related disease compared to other county residents. Conclusions We have combined a risk-based model with spatially resolved long-term exposure estimates to predict CHD burden from air pollution at the census tract level. It provides quantitative estimates of effects that can be used to assess possible health disparities, track temporal changes, and inform timely local community policy decisions. Such an approach can be further expanded to include other pollutants and adverse health endpoints.

Published
2020
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