503 results on '"J. McNulty"'
Search Results
2. Nitrogen accountancy in space agriculture
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Kevin Yates, Aaron J. Berliner, Georgios Makrygiorgos, Farrah Kaiyom, Matthew J. McNulty, Imran Khan, Paul Kusuma, Claire Kinlaw, Diogo Miron, Charles Legg, James Wilson, Bruce Bugbee, Ali Mesbah, Adam P. Arkin, Somen Nandi, and Karen A. McDonald
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Biotechnology ,TP248.13-248.65 ,Physiology ,QP1-981 - Abstract
Abstract Food production and pharmaceutical synthesis are posited as essential biotechnologies for facilitating human exploration beyond Earth. These technologies not only offer critical green space and food agency to astronauts but also promise to minimize mass and volume requirements through scalable, modular agriculture within closed-loop systems, offering an advantage over traditional bring-along strategies. Despite these benefits, the prevalent model for evaluating such systems exhibits significant limitations. It lacks comprehensive inventory and mass balance analyses for crop cultivation and life support, and fails to consider the complexities introduced by cultivating multiple crop varieties, which is crucial for enhancing food diversity and nutritional value. Here we expand space agriculture modeling to account for nitrogen dependence across an array of crops and demonstrate our model with experimental fitting of parameters. By adding nitrogen limitations, an extended model can account for potential interruptions in feedstock supply. Furthermore, sensitivity analysis was used to distill key consequential parameters that may be the focus of future experimental efforts.
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- 2024
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3. Combining RNAscope and immunohistochemistry to visualize inflammatory gene products in neurons and microglia
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Jayson B. Ball, Connor J. McNulty, Suzanne M. Green-Fulgham, Joseph M. Dragavon, Igor R. Correia Rocha, Maggie R. Finch, Emily D. Prévost, Imaad I. Siddique, Brodie J. Woodall, Linda R. Watkins, Michael V. Baratta, and David H. Root
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hybridization ,spinal cord ,neuroinflammation ,NLRP3 ,interleukin-1beta ,Imaris ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
A challenge for central nervous system (CNS) tissue analysis in neuroscience research has been the difficulty to codetect and colocalize gene and protein expression in the same tissue. Given the importance of identifying gene expression relative to proteins of interest, for example, cell-type specific markers, we aimed to develop a protocol to optimize their codetection. RNAscope fluorescent in situ hybridization (FISH) combined with immunohistochemistry (IHC) in fixed (CNS) tissue sections allows for reliable quantification of gene transcripts of interest within IHC-labeled cells. This paper describes a new method for simultaneous visualization of FISH and IHC in thicker (14-μm), fixed tissue samples, using spinal cord sections. This method’s effectiveness is shown by the cell-type-specific quantification of two genes, namely the proinflammatory cytokine interleukin-1beta (IL-1b) and the inflammasome NLR family pyrin domain containing 3 (NLRP3). These genes are challenging to measure accurately using immunohistochemistry (IHC) due to the nonspecificity of available antibodies and the hard-to-distinguish, dot-like visualizations of the labeled proteins within the tissue. These measurements were carried out in spinal cord sections after unilateral chronic constriction injury of the sciatic nerve to induce neuroinflammation in the spinal cord. RNAscope is used to label transcripts of genes of interest and IHC is used to label cell-type specific antigens (IBA1 for microglia, NeuN for neurons). This combination allowed for labeled RNA transcripts to be quantified within cell-type specific boundaries using confocal microscopy and standard image analysis methods. This method makes it easy to answer empirical questions that are intractable with standard IHC or in situ hybridization alone. The method, which has been optimized for spinal cord tissue and to minimize tissue preparation time and costs, is described in detail from tissue collection to image analysis. Further, the relative expression changes in inflammatory genes NLRP3 and IL-1b in spinal cord microglia vs. neurons of somatotopically relevant laminae are described for the first time.
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- 2023
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4. Functionalizing silica sol–gel with entrapped plant virus-based immunosorbent nanoparticles
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Matthew J. McNulty, Naomi Hamada, Jesse Delzio, Liber McKee, Somen Nandi, Marjorie L. Longo, and Karen A. McDonald
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Virus-based nanomaterial ,Molecular pharming ,Nanobiotechnology ,Tobamovirus ,Plant-made pharmaceuticals ,Silica sol–gel ,Biotechnology ,TP248.13-248.65 ,Medical technology ,R855-855.5 - Abstract
Abstract Advancements in understanding and engineering of virus-based nanomaterials (VBNs) for biomedical applications motivate a need to explore the interfaces between VBNs and other biomedically-relevant chemistries and materials. While several strategies have been used to investigate some of these interfaces with promising initial results, including VBN-containing slow-release implants and VBN-activated bioceramic bone scaffolds, there remains a need to establish VBN-immobilized three dimensional materials that exhibit improved stability and diffusion characteristics for biosensing and other analyte-capture applications. Silica sol–gel chemistries have been researched for biomedical applications over several decades and are well understood; various cellular organisms and biomolecules (e.g., bacteria, algae, enzymes) have been immobilized in silica sol-gels to improve viability, activity, and form factor (i.e., ease of use). Here we present the immobilization of an antibody-binding VBN in silica sol–gel by pore confinement. We have shown that the resulting system is sufficiently diffuse to allow antibodies to migrate in and out of the matrix. We also show that the immobilized VBN is capable of antibody binding and elution functionality under different buffer conditions for multiple use cycles. The promising results of the VBN and silica sol–gel interface indicate a general applicability for VBN-based bioseparations and biosensing applications. Graphical Abstract
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- 2022
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5. The Living With a Star Space Environment Testbed Payload
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C S Dyer, K A Ryden, P A Morris, A D P Hands, P J McNulty, J R Vaille, L Dusseau, G Cellere, Alessandro Paccagnella, H J Barnaby, A R Benedetto, R Velazco, R Possamai Bastos, D. Brewer, J L Barth, K A LaBel, M J Campola, Y Zheng, and M A Xapsos
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Space Radiation - Abstract
The objectives, instrumentation, methods and data leading up to launch of the NASA Living With a Star (LWS) Space Environment Testbed (SET) payload onboard the Air Force Research Laboratory Demonstration and Science Experiments (DSX) spacecraft are described. The experiments characterize the space radiation environment and how it affects hardware performance. The payload consists of a compact space weather instrument and a carrier containing four board experiments.
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- 2023
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6. Molecular pharming to support human life on the moon, mars, and beyond
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Matthew J. McNulty, Yongao (Mary) Xiong, Kevin Yates, Kalimuthu Karuppanan, Jacob M. Hilzinger, Aaron J. Berliner, Jesse Delzio, Adam P. Arkin, Nancy E. Lane, Somen Nandi, and Karen A. McDonald
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- 2021
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7. Space bioprocess engineering on the horizon
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Aaron J. Berliner, Isaac Lipsky, Davian Ho, Jacob M. Hilzinger, Gretchen Vengerova, Georgios Makrygiorgos, Matthew J. McNulty, Kevin Yates, Nils J. H. Averesch, Charles S. Cockell, Tyler Wallentine, Lance C. Seefeldt, Craig S. Criddle, Somen Nandi, Karen A. McDonald, Amor A. Menezes, Ali Mesbah, and Adam P. Arkin
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- 2022
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8. Crisis Meta-Leadership and the Practice of Disaster Medicine
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Leonard Jay Marcus, Eric J. McNulty, and Jennifer O. Grimes
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- 2024
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9. Contributors
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Axel Adams, Clara Affun-Adegbulu, Rakan S. Al-Rasheed, Yasser A. Alaska, Abdulaziz D. Aldawas, Saleh Ali Alesa, George A. Alexander, Abdullah Ahmed Alhadhira, Fahad Saleha Alhajjaj, Hazem H. Alhazmi, Zainab Abdullah Alhussaini, Nawfal Aljerian, Majed Aljohani, Khaldoon H. AlKhaldi, Eyad Alkhattabi, Bryant Allen, Austin Almand, Moza M. Alnoaimi, Mohammad Alotaibi, Evan Avraham Alpert, Yasir A. Alrusayni, Mai Alshammari, Loui K. Alsulimani, Siraj Amanullah, Arian Anderson, David Arastehmanesh, Ali Ardalan, Killiam A. Argote-Araméndiz, Andrew W. Artenstein, Olivia E. Bailey, Russell Baker, Satchit Balsari, Gregory T. Banner, Fermin Barrueto M, Susan A. Bartels, Joshua J. Baugh, Frederic Berg, Vijai Bhola, William Binder, Michelangelo Bortolin, Vincent Bounes, Michael Bouton, Natasha Brown, Frederick M. Burkle, Jr, Lynn Barkley Burnett, Michele M. Burns, Nicholas V. Cagliuso, Sr, John Cahill, David W. Callaway, Duane C. Caneva, Srihari Cattamanchi, Alejandra Caycedo, Edward W. Cetaruk, Sneha Chacko, James C. Chang, Crystal Chiang, David T. Chiu, Gregory R. Ciottone, Jonathan Peter Ciottone, Melissa A. Ciottone, Robert A. Ciottone, Robert G. Ciottone, Vigen G. Ciottone, Alexander Clark, Jonathan Clark, Sean P. Conley, Joanne Cono, Arthur Cooper, Scott B. Cormier, Michael F. Court, Cord W. Cunningham, Fabrice Czarnecki, Supriya Davis, Timothy E. Davis, Gerard DeMers, Sharon Dilling, Ahmadreza Djalali, Timothy Donahoe, Joseph Donahue, Caleb Dresser, Jason Dylik, Benjamin Easter, Alexander Eastman, Laura Ebbeling, Chigozie Emetarom, Nir Eyal, Andrew J. Eyre, David J. Freeman, Franklin D. Friedman, Christie Fritz, Frederick Fung, Fiona E. Gallahue, Stephanie Chow Garbern, Mark E. Gebhart, William A. Gluckman, Craig Goolsby, Robert M. Gougelet, Fredrik Granholm, P. Gregg Greenough, Jennifer O. Grimes, Steve Grosse, Shamai A. Grossman, John T. Groves Jr, Tee L. Guidotti, George Guo, Sarah Haessler, Matthew M. Hall, John W. Hardin, Mason Harrell, Alexander Hart, MD, Melissa Harvey, Attila J. Hertelendy, PhD, Nishanth S. Hiremath, Jordan Hitchens, Christopher P. Holstege, Simon T. Horne, Steven Horng, Amer Hosin, Hans R. House, Pier Luigi Ingrassia, Fadi S. Issa, Irving 'Jake' Jacoby, Rajnish Jaiswal, Gregory Jay, J. Lee Jenkins, Josh W. Joseph, Shane Kappler, Mark E. Keim, Julie Kelman, Andrew R. Ketterer, Anas A. Khan, Ramu Kharel, Chetan U. Kharod, Thomas D. Kirsch, Anita Knopov, Max Kravitz, J. Austin Lee, Jay Lemery, Evan L. Leventhal, Jesse Loughlin, Stephanie Ludy, Brian J. Maguire, Selwyn E. Mahon, Paul M. Maniscalco, Philip Manners, Leonard Jay Marcus, Colton Margus, Taha M. Masri, Jeff Matthews, Sean D. McKay, Zeke J. McKinney, Robert K. McLellan, Eric J. McNulty, Faroukh Mehkri, Mandana Mehta, Rebecca A. Mendelsohn, Ofer Merin, Andrew Milsten, Dale M. Molé, Michael Sean Molloy, Ilaria Morelli, Jerry L. Mothershead, John Mulhern, Nicole F. Mullendore, Nicholas J. Musisca, Sonya Naganathan, Larry A. Nathanson, Erica L. Nelson, Lewis S. Nelson, Bradford A. Newbury, Kimberly Newbury, Ansley O’Neill, Robert Obernier, Jacopo M. Olagnero, Leonie Oostrom-Shah, Catherine Y. Ordun, Scott Parazynski, Andrew J. Park, Robert Partridge, Jeffrey S, James P. Phillips, Emily Pinter, David P. Polatty IV, Patrick Popieluszko, William Porcaro, Lawrence Proano, Peter B. Pruitt, Moiz Qureshi, Luca Ragazzoni, Murtaza Rashid, Paul Patrick Rega, Michael J. Reilly, Marc C. Restuccia, James J. Rifino, Paul M. Robben, Joy L. Rosenblatt, Kevin M. Ryan, Heather Rybasack-Smith, Richard James Salway, Daniel Samo, Leon D. Sanchez, Shawn M. Sanford, Ritu R. Sarin, Deesha Sarma, Jesse Schacht, Valarie Schwind, Geoffrey L. Shapiro, Joshua Sheehan, Brian Shreve, Grigor Simonyan, Devin M. Smith, E. Reed Smith, MD, Jack E. Smith, MA, Montray Smith, Peter B. Smulowitz, Angela M. Snyder, Joshua J. Solano, Bryan A. Stenson, Charles Stewart, M. Kathleen Stewart, Patrick Sullivan, Jared S. Supple, Derrick Tin, Jonathan Harris Valente, Kathryn M. Vear, P.R. Vidyalakshmi, Faith Vilas, Gary M. Vilke, Janna H. Villano, Amalia Voskanyan, C. James Watson, Nancy Weber, Scott G. Weiner, Brielle Weinstein, Eric S. Weinstein, Jordan R. Werner, Roy Karl Werner, MD, James D. Whitledge, Sage W. Wiener, Lauren Wiesner, Kenneth A. Williams, Robyn Wing, Richard E. Wolfe, Wendy Hin-Wing Wong, Robert Woolard, Prasit Wuthisuthimethawee, and Nadine A. Youssef
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- 2024
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10. Research ethics systems, processes, and awareness across Europe: Radiography research ethics standards for Europe (RRESFE)
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S. Bockhold, J. McNulty, E. Abdurakman, P. Bezzina, N. Drey, A. England, D. Flinton, R. Khine, M. McEntee, N. Mekiš, H. Precht, L. Rainford, C. Sá dos Reis, A. Santos, V. Syrgiamiotis, S. Willis, J. Woodley, C. Beardmore, R. Harris, T. O'Regan, and C. Malamateniou
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Europe ,Radiography ,Cross-Sectional Studies ,Surveys and Questionnaires ,HA ,Humans ,Research ethics, Radiography, Standards, Processes ,Radiology, Nuclear Medicine and imaging ,Podiatry ,RC ,Ethics, Research - Abstract
INTRODUCTION: The Radiography Research Ethics Standards for Europe (RRESFE) project aims to provide a cross-sectional snapshot of current research ethics systems, processes, and awareness of such, across Europe together with identifying the associated challenges, education, and training needs. \ud \ud METHODS: A cross-sectional online survey targeting radiography researchers in Europe was conducted. Data collection took place between April 26 and July 12, 2021, using a snowball sampling approach. Descriptive and analytical statistics were used to identify trends in research ethics frameworks across Europe. \ud \ud RESULTS: 285 responses were received across 33 European and 23 non-European countries. Most (n = 221; 95%) European respondents stated ethics approval is required before commencing research in their country. Requirements around research ethics approval and awareness of such requirements varied by European region (X2 (2, n = 129) = 7.234, p = 0.013) and were found to differ depending on the type of research participant and study design. Additionally, European respondents reported ethics approval is a national requirement more often than their non-European counterparts (X2 (1, n = 282) = 4.316, p = 0.049). Requirements for ethics approval were also associated with the undergraduate programme duration (2-year vs. 3-year vs. 3.5 year vs. 4-year vs. multiple programme durations; X2 (4, n = 231) = 10.075, p = 0.016) and availability of postgraduate training (postgraduate training available vs. postgraduate training not available; X2 (1, n = 231) = 15.448, p =
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- 2022
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11. Elevated prefrontal dopamine interferes with the stress-buffering properties of behavioral control in female rats
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Connor J. McNulty, Isabella P. Fallon, Jose Amat, Rory J. Sanchez, Nathan R. Leslie, David H. Root, Steven F. Maier, and Michael V. Baratta
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Pharmacology ,Psychiatry and Mental health - Published
- 2022
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12. Spinal Metastases from Colorectal Cancer at Mass General Brigham: A Twenty-Year Case Series with Literature Review
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Alexander G. Yearley, Jack J. McNulty, Eric J. Chalif, Joshua I. Chalif, Suk Joon Lee, Neil Klinger, and Hasan A. Zaidi
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Surgery ,Neurology (clinical) - Published
- 2023
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13. Temporal trends in the prevalence and severity of aortic stenosis within a contemporary and diverse community-based cohort
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Andrew P. Ambrosy, Alan S. Go, Thomas K. Leong, Elisha A. Garcia, Alex J. Chang, Justin J. Slade, Edward J. McNulty, Jacob M. Mishell, Andrew N. Rassi, Ivy A. Ku, David C. Lange, Femi Philip, Benjamin Z. Galper, Natalia Berry, and Matthew D. Solomon
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Cardiology and Cardiovascular Medicine - Published
- 2023
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14. DIME-2 Flown as Part of NASA’s SET-1 on the DSX Satellite
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Peter J. McNulty, Kelvin F. Poole, and John O. Poole
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Nuclear and High Energy Physics ,Nuclear Energy and Engineering ,Electrical and Electronic Engineering - Published
- 2022
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15. The DIME-1 Experiment Flown as Part of NASA’s SET-1 Project on the DSX Satellite
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Kelvin F. Poole, Peter J. McNulty, and John O. Poole
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Nuclear and High Energy Physics ,Nuclear Energy and Engineering ,Electrical and Electronic Engineering - Published
- 2022
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16. Research ethics training, challenges, and suggested improvements across Europe: Radiography research ethics standards for Europe (RRESFE)
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S. Bockhold, J. McNulty, E. Abdurakman, P. Bezzina, N. Drey, A. England, D. Flinton, R. Khine, M. McEntee, N. Mekiš, H. Precht, L. Rainford, C. Sá dos Reis, A. Santos, V. Syrgiamiotis, S. Willis, J. Woodley, C. Beardmore, R. Harris, T. O'Regan, and C. Malamateniou
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Europe ,Radiography ,Cross-Sectional Studies ,Humans ,Radiology, Nuclear Medicine and imaging ,Curriculum ,Podiatry ,Research ethics Radiography Education and training Challenges Improvements ,R1 ,Ethics, Research - Abstract
INTRODUCTION: The Radiography Research Ethics Standards for Europe (RRESFE) project aimed to provide a cross-sectional view of the current state of radiography research ethics across Europe. This included investigating education and training in research ethics, and identifying the key challenges and potential improvements associated with using existing research ethics frameworks. \ud \ud METHODS: This cross-sectional online survey targeting radiography researchers in Europe was conducted between April 26 and July 12, 2021. Descriptive and analytical statistics were used to identify research ethics education and training trends. Content analysis of qualitative responses was employed to identify significant challenges and proposed improvements in research ethics frameworks of practice. \ud \ud RESULTS: There were 232 responses received across 33 European countries. Most (n = 132; 57%) respondents had received some research ethics training; however, fewer participants had received training on safeguarding vulnerable patients (n = 72; 38%), diversity and inclusivity (n = 62; 33%), or research with healthy volunteers (n = 60; 32%). Training was associated with a greater perceived importance of the need for research ethics review (p = 0.031) and with the establishment of EQF Level 6 training (p = 0.038). The proportion of formally trained researchers also varied by region (p =
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- 2022
17. Ventral tegmental area glutamate neurons mediate nonassociative consequences of stress
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Dillon J. McGovern, Annie Ly, Koy L. Ecton, David T. Huynh, Emily D. Prévost, Shamira C. Gonzalez, Connor J. McNulty, Andrew R. Rau, Shane T. Hentges, Tanya L. Daigle, Bosiljka Tasic, Michael V. Baratta, and David H. Root
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Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Molecular Biology - Published
- 2022
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18. 273 ‘HOME ON TIME’: MULTIDISCIPLINARY INTERVENTION REDUCES LENGTH OF STAY AND DELAYS IN CARE TRANSFERS ON AN ACUTE GERIATRIC MEDICINE WARD
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B Mealy, A Nevin, A Lavan, AL Jariol, V Roll, SO Connor, DO Donnell, AG Cummiskey, J McNulty, MO Malley, and R Briggs
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Aging ,General Medicine ,Geriatrics and Gerontology - Abstract
Background Unnecessarily prolonged hospital admission can have a profound effect on a frail, older person’s confidence, mood, functional status and cognition.This study examined whether a structured multidisciplinary intervention, embedded within an acute geriatric medicine ward, could reduce unnecessary days in hospital for acutely unwell older patients. Methods The study site is a 28-bed acute geriatric medicine ward in a large urban teaching hospital; data was collected from 1/1/22 to 11/4/22. Patients aged ≥70 years and admitted to the ward were randomly allocated to the Home On Time (HOT) Pathway (n=50) or usual care (n=100). All patients were cared for by a specialist geriatric team. The HOT Pathway involved daily multidisciplinary team (physiotherapy, nursing, occupational therapy, social work and medical) huddles focusing on enhanced communication, early discharge planning and identification of barriers to discharge home. Huddles typically lasted for Results Almost two-thirds (92/150) of the study sample (mean age 83 years, 60% female) were discharged directly from the ward while one-fifth (29/150) were transferred for rehabilitation and one-tenth ultimately to long term care (16/150). The average acute ward Length-of-Stay (LOS) for HOT pathway patients was 10.4 days, compared to 14.4 days for usual care. The average LOS for HOT pathway patients discharged directly home (i.e. not via rehabilitation or to long-term care) was 8.0 days, compared to 10.2 days for usual care. One-fifth (10/50) of HOT pathway patients were discharged home within 48 hours of admission compared to one tenth (10/100) of usual care patients. Conclusion A structured, multidisciplinary intervention focusing on enhanced communication and early discharge planning within a geriatric medicine ward can reduce length of inpatient stay, delays in transitions of care and increase the rate of discharge home within 48 hours, potentially averting complications related to prolonged hospital admission.
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- 2022
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19. Cohort Study of ECG Left Ventricular Hypertrophy Trajectories: Ethnic Disparities, Associations With Cardiovascular Outcomes, and Clinical Utility
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Carlos Iribarren, Alfred D. Round, Meng Lu, Peter M. Okin, and Edward J. McNulty
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cohort study ,Cornell voltage product ,electrocardiography ,left ventricular hypertrophy ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundECG left ventricular hypertrophy (LVH) is a well‐known predictor of cardiovascular disease. However, no prior study has characterized patterns of presence/absence of ECG LVH (“ECG LVH trajectories”) across the adult lifespan in both sexes and across ethnicities. We examined: (1) correlates of ECG LVH trajectories; (2) the association of ECG LVH trajectories with incident coronary heart disease, transient ischemic attack, ischemic stroke, hemorrhagic stroke, and heart failure; and (3) reclassification of cardiovascular disease risk using ECG LVH trajectories. Methods and ResultsWe performed a cohort study among 75 412 men and 107 954 women in the Northern California Kaiser Permanente Medical Care Program who had available longitudinal exposures of ECG LVH and covariates, followed for a median of 4.8 (range
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- 2017
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20. Tempered by war: the military experiences of Vietnam decision-makers
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Aurélie Basha i Novosejt and Christopher J. McNulty
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Cultural Studies ,History ,Sociology and Political Science ,JK - Abstract
The article focuses on three senior decision-makers in the John F. Kennedy and Lyndon B. Johnson administrations that each played a key role in the escalation in Vietnam, namely Walt W. Rostow, Roger Hilsman, and John T. McNaughton. It builds on Andrew Preston’s argument in this journal that the dichotomy between ‘hawks’ and ‘doves’ might caricature Vietnam War advisors to suggest the same for the dichotomy between ‘civilians’ and ‘veterans’. Using new material, most notably McNaughton’s wartime diaries and Hilsman’s OSS files, the article suggests that wartime experience was clearly an important formative experience for civilian advisors but in different ways. First, where political scientists tell us that veterans are more likely to espouse certain views, and in particular resist the use force, these examples suggest that proximity to combat - i.e. how much active combat they experienced - mattered more. Second, there was no uniform ‘military’ experience: these advisors were more likely to support the types of tools – i.e. air power or irregular forces - with which they were familiar and only then, if they had become invested in the underlying bureaucratic project of the agency in which they were deployed. In other words, a process of socialization or indoctrination into the armed services happened unevenly. Put together, the examples suggest that the formative experiences in the Second World War cast a long shadow onto the Vietnam War decisions but did so in complex ways.
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- 2022
21. Sequential Imaging of a Rapidly Progressive Rheumatoid Vasculitis: A Unique Depiction
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Stephanie S. Kim, Vidal A. Villela, and Nancy J. McNulty
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Rheumatology ,Immunology ,Immunology and Allergy - Abstract
Rheumatoid vasculitis is a clinically heterogenous complication of rheumatoid arthritis (RA), primarily affecting small- and medium-sized vessels.1A 63-year-old man with long-standing seropositive erosive RA presented to our emergency department with abdominal pain and diarrhea.
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- 2023
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22. Technoeconomic Modeling and Simulation for Plant-Based Manufacturing of Recombinant Proteins
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Matthew J, McNulty, Somen, Nandi, and Karen A, McDonald
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Computer Simulation ,Plants ,Recombinant Proteins - Abstract
Technoeconomic modeling and simulation is a critical step in defining a manufacturing process for evaluation of commercial viability and to focus experimental process research and development efforts. Technoeconomic analysis (TEA) is increasingly demanded alongside scientific innovation by both public and private funding agencies to maximize efficiency of resource allocation. It is particularly important for plant-based manufacturing, and other nontraditional recombinant protein production platforms, to explicitly demonstrate the manufacturing potential and to identify critical technical and economic challenges through robust technoeconomic analysis. In addition, in silico process modeling and TEA of scaled biomanufacturing facilities allows rapid evaluation of the impacts of process and economic changes on capital expenditures (CAPEX, also sometimes referred to as total capital investment), operational expenditures (OPEX, also known as total manufacturing costs or total production costs), cost of goods sold (COGS, also known as unit production costs), and profitability metrics such as net present value (NPV) and discounted cash flow rate of return (DCROR, also known as internal rate of return or IRR). These models can also be used to assess environmental, health, and safety impact of a designed biomanufacturing facility to evaluate its sustainability and environmental-friendliness. Here we describe a general method for performing technoeconomic modeling and simulation for and environmental assessment of plant-based manufacturing of recombinant proteins.
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- 2022
23. Affinity Sedimentation and Magnetic Separation With Plant-Made Immunosorbent Nanoparticles for Therapeutic Protein Purification
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Aaron Jacobson, A. M. Schwartz, Abhaya M. Dandekar, Karen A. McDonald, Kalimuthu Karuppanan, Olivia Hart, Somen Nandi, Matthew J. McNulty, Jesse Delzio, Anatoli Giritch, and Yuri Gleba
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Histology ,bio-functionalized magnetic particle ,Chemistry ,bioprocessing ,Medical Biotechnology ,Magnetic separation ,Biomedical Engineering ,Nanoparticle ,Therapeutic protein ,Nanotechnology ,Bioengineering ,virus-based nanomaterial ,Crop cultivation ,molecular pharming ,monoclonal antibody ,protein purification ,Therapeutic antibody ,Protein purification ,Magnetic nanoparticles ,bionanotechnology ,Other Biological Sciences ,Biosensor ,Fc-fusion protein ,Biotechnology - Abstract
The virus-based immunosorbent nanoparticle is a nascent technology being developed to serve as a simple and efficacious agent in biosensing and therapeutic antibody purification. There has been particular emphasis on the use of plant virions as immunosorbent nanoparticle chassis for their diverse morphologies and accessible, high yield manufacturing via plant cultivation. To date, studies in this area have focused on proof-of-concept immunosorbent functionality in biosensing and purification contexts. Here we consolidate a previously reported pro-vector system into a single Agrobacterium tumefaciens vector to investigate and expand the utility of virus-based immunosorbent nanoparticle technology for therapeutic protein purification. We demonstrate the use of this technology for Fc-fusion protein purification, characterize key nanomaterial properties including binding capacity, stability, reusability, and particle integrity, and present an optimized processing scheme with reduced complexity and increased purity. Furthermore, we present a coupling of virus-based immunosorbent nanoparticles with magnetic particles as a strategy to overcome limitations of the immunosorbent nanoparticle sedimentation-based affinity capture methodology. We report magnetic separation results which exceed the binding capacity reported for current industry standards by an order of magnitude.
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- 2022
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24. Plasma DNA as a 'liquid biopsy' incompletely complements tumor biopsy for identification of mutations in a case series of four patients with oligometastatic breast cancer
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Ananta Bhatt, Todd W. Miller, Jason D. Wells, Nancy J. McNulty, Richard J. Barth, Jennifer R. Bean, Jiang Gui, Mary D. Chamberlin, Wendy A. Wells, Peter A. Kaufman, Jonathan D. Marotti, Michael J. Tsapakos, John M Gemery, Fred W. Kolling, Gary N. Schwartz, Kevin Shee, Bradley A. Arrick, and Heidi W. Trask
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0301 basic medicine ,Cancer Research ,Breast Neoplasms ,Article ,DNA sequencing ,Circulating Tumor DNA ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Biopsy ,Biomarkers, Tumor ,medicine ,Humans ,Neoplasm Metastasis ,Liquid biopsy ,Massive parallel sequencing ,medicine.diagnostic_test ,business.industry ,Liquid Biopsy ,High-Throughput Nucleotide Sequencing ,Cancer ,DNA, Neoplasm ,Prognosis ,medicine.disease ,030104 developmental biology ,Oncology ,Cell-free fetal DNA ,DNA profiling ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,Female ,business - Abstract
PURPOSE: Circulating tumor DNA in plasma may present a minimally invasive opportunity to identify tumor-derived mutations to inform selection of targeted therapies for individual patients, particularly in cases of oligometastatic disease where biopsy of multiple tumors is impractical. To assess the utility of plasma DNA as a “liquid biopsy” for precision oncology, we tested whether sequencing of plasma DNA is a reliable surrogate for sequencing of tumor DNA to identify targetable genetic alterations. METHODS: Blood and biopsies of 1–3 tumors were obtained from 4 evaluable patients with advanced breast cancer. One patient provided samples from an additional 7 tumors post-mortem. DNA extracted from plasma, tumor tissues, and buffy coat of blood were used for probe-directed capture of all exons in 149 cancer-related genes and massively parallel sequencing. Somatic mutations in DNA from plasma and tumors were identified by comparison to buffy coat DNA. RESULTS: Sequencing of plasma DNA identified 27.94 +/− 11.81% (mean +/− SD) of mutations detected in a tumor(s) from the same patient; such mutations tended to be present at high allelic frequency. The majority of mutations found in plasma DNA were not found in tumor samples. Mutations were also found in plasma that matched clinically undetectable tumors found post-mortem. CONCLUSIONS: The incomplete overlap of genetic alteration profiles of plasma and tumors warrants caution in the sole reliance of plasma DNA to identify therapeutically targetable alterations in patients, and indicates that analysis of plasma DNA complements, but does not replace, tumor DNA profiling. TRIAL REGISTRATION: Subjects were prospectively enrolled in trial NCT01836640 (registered April 22, 2013).
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- 2020
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25. Functionalizing silica sol-gel with entrapped plant virus-based immunosorbent nanoparticles
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Marjorie L. Longo, Karen A. McDonald, Somen Nandi, Liber McKee, Jesse Delzio, Matthew J. McNulty, and Naomi Hamada
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Monoclonal antibody ,Technology ,Materials science ,Nanoparticle ,Silica Gel ,Nanotechnology ,Bioengineering ,Bioceramic ,Buffer (optical fiber) ,Nanomaterials ,Plant Viruses ,Bioseparations ,Silica sol-gel ,Nanoscience & Nanotechnology ,Sol-gel ,chemistry.chemical_classification ,Elution ,Biosensing ,Biomolecule ,Tobamovirus ,Nanobiotechnology ,Silicon Dioxide ,Antibody purification ,Plant-made pharmaceuticals ,chemistry ,Silica sol–gel ,Nanoparticles ,Virus-based nanomaterial ,Immunosorbents ,Molecular pharming ,Biosensor ,Gels - Abstract
Advancements in understanding and engineering of virus-based nanomaterials (VBNs) for biomedical applications motivate a need to explore the interfaces between VBNs and other biomedically-relevant chemistries and materials. While several strategies have been used to investigate some of these interfaces with promising initial results, including VBN-containing slow-release implants and VBN-activated bioceramic bone scaffolds, there remains a need to establish VBN-immobilized three dimensional materials that exhibit improved stability and diffusion characteristics for biosensing and other analyte-capture applications. Silica sol-gel chemistries have been researched for biomedical applications over several decades and are well understood; various cellular organisms and biomolecules (e.g., bacteria, algae, enzymes) have been immobilized in silica sol-gels to improve viability, activity, and form factor (i.e., ease of use). Here we present the immobilization of an antibody-binding VBN in silica sol-gel by pore confinement. We have shown that the resulting system is sufficiently diffuse to allow antibodies to migrate in and out of the matrix. We also show that the immobilized VBN is capable of antibody binding and elution functionality under different buffer conditions for multiple use cycles. The promising results of the VBN and silica sol-gel interface indicate a general applicability for VBN-based bioseparations and biosensing applications.
- Published
- 2022
26. Technoeconomic Modeling and Simulation for Plant-Based Manufacturing of Recombinant Proteins
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Matthew J. McNulty, Somen Nandi, and Karen A. McDonald
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- 2022
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27. PHYSICIAN ASSESSMENT OF AORTIC STENOSIS SEVERITY AND LONG-TERM OUTCOMES: RESULTS FROM THE KP-VALVE PROJECT
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Matthew D. Solomon, Grace H. Tabada, Sue Hee Sung, Amanda Allen, Jacob M. Mishell, Andrew N. Rassi, Edward J. McNulty, Femi Philip, David Christopher Lange, Andrew P. Ambrosy, Jonathan G. Zaroff, Ashok Krishnaswami, Catherine Lee, Anthony N. DeMaria, and Alan S. Go
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Cardiology and Cardiovascular Medicine - Published
- 2023
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28. TEMPORAL TRENDS IN THE PREVALENCE AND SEVERITY OF AORTIC STENOSIS WITHIN AN INTEGRATED HEALTH CARE DELIVERY SYSTEM
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Andrew P. Ambrosy, Alan S. Go, Thomas Kiichi Leong, Elisha Garcia, Kathy Le, Alex Chang, Justin J. Slade, Edward J. McNulty, Jacob M. Mishell, Andrew N. Rassi, David Christopher Lange, Femi Philip, Benjamin Zev Galper, Natalia Berry, and Matthew D. Solomon
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Cardiology and Cardiovascular Medicine - Published
- 2023
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29. Outcomes of Adults with Severe Aortic Stenosis Undergoing Urgent or Emergent vs. Elective Transcatheter Aortic Valve Replacement Within an Integrated Health Care Delivery System
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Justin J. Slade, Andrew P. Ambrosy, Thomas K. Leong, Sue Hee Sung, Elisha A. Garcia, Ivy A. Ku, Matthew D. Solomon, Edward J. McNulty, Andrew N. Rassi, David C. Lange, Femi Philip, Alan S. Go, and Jacob M. Mishell
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Cardiology and Cardiovascular Medicine - Published
- 2023
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30. The Meta-Leadership Model for Crisis Leadership
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Eric J. McNulty, Leonard Marcus, Jennifer O. Grimes, Joseph Henderson, and Richard Serino
- Abstract
Meta-leadership is a framework and practice method for broad, overarching leadership that meets the demands of modern organizations that have evolved beyond purely hierarchical structures and face complex crisis situations. The meta-leadership framework consists of three dimensions: the Person, or the characteristics and behaviors of the leader; the Situation, or the context in which the leader operates with its inherent challenges and contingencies; and Connectivity, the relationships and interconnections among the full range of stakeholders. Such an overarching model guides self-assessment by the leader, multidimensional analysis of the problem, and collective action to achieve a shared goal. It assists the leader in navigating complexity, understanding diverging perspectives, and recognizing opportunities to leverage overlapping interests as well as distinct capacities and capabilities among stakeholders in order to generate benefits for all. Using the dimensions as lenses for thinking and levers of action, the leader envisages and encourages cohesive efforts within the organization and encourages buy-in from potential external collaborators. Meta-leaders take a systemic view, exercising formal authority as well as influence well beyond that authority, leading “down” to subordinates; “up” to superiors; “across” to peers; and “beyond” to entities outside of the organization. Encompassed within each dimension are leadership techniques and tools for navigating the difficulties of competing interests, framing solution sets to influence the trajectory of events, and maintaining order amidst seeming chaos. The desired outcome is a “swarm,” where autonomous entities operate in swift synchrony to address threats and seize opportunities, overcoming the limitations and confounds of a “command-and-control” approach amidst the confusion of crises. This evidence-based framework has been envisioned and refined by both interdisciplinary research and the pragmatic experience of crisis leaders and organizational executives. While well suited to the intense environment of crises, meta-leadership has also proven useful in everyday leadership in situations involving diverse stakeholders facing a shared challenge.
- Published
- 2021
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31. Evaluating the Cost of Pharmaceutical Purification for a Long-Duration Space Exploration Medical Foundry
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Matthew J. McNulty, Aaron J. Berliner, Patrick G. Negulescu, Liber McKee, Olivia Hart, Kevin Yates, Adam P. Arkin, Somen Nandi, and Karen A. McDonald
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Microbiology (medical) ,Environmental Science and Management ,Computer science ,in situ resource utilization ,equivalent system mass ,space systems bioengineering ,space exploration medical foundry ,techno-economic analysis ,Microbiology ,Space exploration ,Scheduling (computing) ,Resource (project management) ,International Space Station ,Life support system ,Reusability ,Original Research ,monoclonal antibody purification ,In situ resource utilization ,QR1-502 ,Quality management system ,human exploration mission ,Soil Sciences ,Systems engineering ,pharmaceutical foundry ,Generic health relevance - Abstract
There are medical treatment vulnerabilities in longer-duration space missions present in the current International Space Station crew health care system with risks, arising from spaceflight-accelerated pharmaceutical degradation and resupply lag times. Bioregenerative life support systems may be a way to close this risk gap by leveraging in situ resource utilization (ISRU) to perform pharmaceutical synthesis and purification. Recent literature has begun to consider biological ISRU using microbes and plants as the basis for pharmaceutical life support technologies. However, there has not yet been a rigorous analysis of the processing and quality systems required to implement biologically-produced pharmaceuticals for human medical treatment. In this work, we use the equivalent system mass (ESM) metric to evaluate pharmaceutical purification processing strategies for longer-duration space exploration missions. Monoclonal antibodies, representing a diverse therapeutic platform capable of treating multiple space-relevant disease states, were selected as the target products for this analysis. We investigate the ESM resource costs (mass, volume, power, cooling, and crew time) of an affinity-based capture step for monoclonal antibody purification as a test case within a manned Mars mission architecture. We compare six technologies (three biotic capture methods and three abiotic capture methods), optimize scheduling to minimize ESM for each technology, and perform scenario analysis to consider a range of input stream compositions and pharmaceutical demand. We also compare the base case ESM to scenarios of alternative mission configuration, equipment models, and technology reusability. Throughout the analyses, we identify key areas for development of pharmaceutical life support technology and improvement of the ESM framework for assessment of bioregenerative life support technologies.
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- 2021
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32. Techno-economic process modelling and Monte Carlo simulation data of uncertainty quantification in field-grown plant-based manufacturing
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Kirolos Kelada, Debashis Paul, Somen Nandi, Matthew J. McNulty, and Karen A. McDonald
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Agricultural production ,Multidisciplinary ,Process modeling ,Science (General) ,Process (engineering) ,Computer science ,Monte Carlo method ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Techno economic ,Plant based ,Industrial engineering ,Field (computer science) ,Process simulation tool ,Plant-based manufacturing ,Q1-390 ,Plant molecular farming ,Research article ,Uncertainty quantification ,Data Article ,Techno-economic analysis - Abstract
This data article is related to the research article, "M.J. McNulty, K. Kelada, D. Paul, S. Nandi, and K.A. McDonald, Introducing uncertainty quantification to techno-economic models of manufacturing field-grown plant-made products, Food Bioprod. Process. 128 (2021) 153-165." The raw and analyzed data presented are related to generation, analysis, and optimization of ultra-large-scale field-grown plant-based manufacturing of high-value recombinant protein under uncertainty. The data have been acquired using deterministic techno-economic process model simulation in SuperPro Designer integrated with stochastic Monte Carlo-based simulation in Microsoft Excel using the Crystal Ball plug-in. The purpose of the article is to make techno-economic and associated uncertainty data available to be leveraged and adapted for other research purposes.
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- 2021
33. Renegotiating Health Care: Resolving Conflict to Build Collaboration
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Leonard J. Marcus, Barry C. Dorn, Eric J. McNulty
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- 2011
34. Partner SRLs for improved shift register diagnostics.
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James L. Schafer, Fred A. Policastri, and Richard J. McNulty
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- 1992
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35. Molecular pharming to support human life on the moon, mars, and beyond
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Jesse Delzio, Kevin Yates, Somen Nandi, Nancy E Lane, Yongao Xiong, Karen A. McDonald, Jacob M. Hilzinger, Aaron J. Berliner, Matthew J. McNulty, Adam P. Arkin, and Kalimuthu Karuppanan
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0106 biological sciences ,Pharming ,Technology ,space medicine ,biomanufacturing ,Process (engineering) ,Molecular Farming ,Space (commercial competition) ,01 natural sciences ,Applied Microbiology and Biotechnology ,Plant molecular pharming ,Space exploration ,03 medical and health sciences ,010608 biotechnology ,Humans ,Duration (project management) ,Moon ,030304 developmental biology ,0303 health sciences ,Spacecraft ,business.industry ,medical countermeasure ,Space medicine ,General Medicine ,medical foundry ,Plants ,Space Flight ,Biological Sciences ,Risk analysis (engineering) ,Life support ,Pharmaceutical manufacturing ,Generic health relevance ,synthetic biology ,business ,oxygenic photoautotroph ,space exploration ,Biotechnology - Abstract
Space missions have always assumed that the risk of spacecraft malfunction far outweighs the risk of human system failure. This assumption breaks down for longer duration exploration missions and exposes vulnerabilities in space medical systems. Space agencies can no longer reduce the majority of the human health and performance risks through crew members selection process and emergency re-supply or evacuation. No mature medical solutions exist to address this risk. With recent advances in biotechnology, there is promise for lessening this risk by augmenting a space pharmacy with a biologically-based space foundry for the on-demand manufacturing of high-value medical products. Here we review the challenges and opportunities of molecular pharming, the production of pharmaceuticals in plants, as the basis of a space medical foundry to close the risk gap in current space medical systems. Plants have long been considered to be an important life support object in space and can now also be viewed as programmable factories in space. Advances in molecular pharming-based space foundries will have widespread applications in promoting simple and accessible pharmaceutical manufacturing on Earth.
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- 2021
36. International practice variation in perioperative laboratory testing in glioblastoma patients-a retrospective cohort study
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Joeky T. Senders, Sybren L. N. Maas, Kaspar Draaisma, John J. McNulty, Joanna L. Ashby, Imo Hofer, Wouter W. van Solinge, Maarten ten Berg, Tom J. Snijders, Tatjana Seute, Pierre A. Robe, William B. Gormley, Timothy R. Smith, and Marike L. D. Broekman
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Brain tumor ,Laboratory testing ,Odds Ratio ,Humans ,Surgery ,Female ,Neurology (clinical) ,Practice variation ,Glioblastoma ,Hospitals ,Retrospective Studies - Abstract
Purpose Although standard-of-care has been defined for the treatment of glioblastoma patients, substantial practice variation exists in the day-to-day clinical management. This study aims to compare the use of laboratory tests in the perioperative care of glioblastoma patients between two tertiary academic centers—Brigham and Women’s Hospital (BWH), Boston, USA, and University Medical Center Utrecht (UMCU), Utrecht, the Netherlands. Methods All glioblastoma patients treated according to standard-of-care between 2005 and 2013 were included. We compared the number of blood drawings and laboratory tests performed during the 70-day perioperative period using a Poisson regression model, as well as the estimated laboratory costs per patient. Additionally, we compared the likelihood of an abnormal test result using a generalized linear mixed effects model. Results After correction for age, sex, IDH1 status, postoperative KPS score, length of stay, and survival status, the number of blood drawings and laboratory tests during the perioperative period were 3.7-fold (p p p p Conclusions Our results suggest a substantially lower clinical threshold for ordering laboratory tests in BWH compared to UMCU. Further investigating the clinical consequences of laboratory testing could identify over and underuse, decrease healthcare costs, and reduce unnecessary discomfort that patients are exposed to.
- Published
- 2021
37. What does the Detroit tests of learning abilities, fifth edition measure? Revelations from a hierarchical exploratory factor analysis
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Randy G. Floyd and Richard J. McNulty
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Psychometrics ,Developmental and Educational Psychology ,Measure (physics) ,Structural validity ,Cognition ,Learning abilities ,Factor structure ,Psychology ,Exploratory factor analysis ,Education ,Cognitive psychology - Published
- 2021
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38. Introducing Uncertainty Quantification to Techno-economic Models of Manufacturing Field-Grown Plant-Made Products
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Somen Nandi, Matthew J. McNulty, Kirolos Kelada, Karen A. McDonald, and Debashis Paul
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0106 biological sciences ,Computer science ,bepress|Engineering ,General Chemical Engineering ,Internal rate of return ,04 agricultural and veterinary sciences ,Environmental economics ,040401 food science ,01 natural sciences ,Biochemistry ,Product (business) ,0404 agricultural biotechnology ,engrXiv|Engineering ,010608 biotechnology ,Scalability ,Production (economics) ,Capital intensity ,Biomanufacturing ,Uncertainty quantification ,Barriers to entry ,Food Science ,Biotechnology - Abstract
There is a growing demand for large-market natural and biotechnological products driven by shifting consumer preferences in food and calls for decentralized vaccine and medication production capabilities. The current paradigm of bioreactor-based biomanufacturing faces difficulties of scalability and a high entry barrier of capital intensity and workforce specialization. Field-grown plant-based manufacturing, as an inexpensive and readily scalable platform, is a promising strategy to meet this call. Despite some successes in field-grown bioproducts manufacturing, concerns, including process variability, have largely stymied adoption. Here we report on the development of techno-economic modeling coupled with Monte Carlo simulation as an effective tool to quantify, and mitigate, the impact of variation in field-grown plant-based manufacturing on profitability-related (internal rate of return, cost of goods) and process performance (product purity, annual throughput) forecast variables. In the base case, we observe 80.8% certainty of meeting all forecast variable specifications, defined generically to represent those of a high-volume food-grade commodity product. We observe an internal rate of return (with a selling price of $2275/kg bioproduct) as low as 10.7% and as high as 47.9% across facility scenarios. We also demonstrate optimization under uncertainty in a facility retrofitting to find a profitability-optimal chromatography column diameter of 1.2 m.
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- 2021
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39. Bioprinting transgenic plant cells for production of a recombinant biodefense agent
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Matthew J. McNulty, Karen A. McDonald, Hawi B. Gemeda, Somen Nandi, Jennifer M. Knipe, and Varma A
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Chemistry ,Transgene ,Organophosphate ,Plant cell ,Genetically modified rice ,law.invention ,chemistry.chemical_compound ,Biochemistry ,law ,Bioreactor ,medicine ,Recombinant DNA ,Butyrylcholinesterase ,Nerve agent ,medicine.drug - Abstract
Transgenic rice cells (Oryza sativa) producing recombinant butyrylcholinesterase (BChE) as a prophylactic/therapeutic against organophosphate nerve agent poisoning, cocaine toxicity, and neurodegenerative diseases like Alzheimer’s were immobilized in a polyethylene glycol-based hydrogel. The cells were sustained for 14 days in the semi-solid matrix, undergoing a growth phase from days 0-6, a BChE production phase in sugar-free medium from days 6-12, and a growth/recovery phase from days 12-14. Throughout this period, the cells maintained similar viability to those in suspension cultures and displayed analogous sugar consumption trends. The rice cells in the bioprintable hydrogel also produced a significant amount of active BChE, comparable to the levels produced in liquid cultures. A considerable fraction of this BChE was secreted into the media, allowing for easier product separation. Overall, we demonstrate a simple, efficient, robust, modular, and potentially field-deployable bioreactor system for the manufacture of biologics.
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- 2021
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40. Towards a Biomanufactory on Mars
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Aaron J. Berliner, Jacob M. Hilzinger, Anthony J. Abel, Matthew J. McNulty, George Makrygiorgos, Nils J. H. Averesch, Soumyajit Sen Gupta, Alexander Benvenuti, Daniel F. Caddell, Stefano Cestellos-Blanco, Anna Doloman, Skyler Friedline, Davian Ho, Wenyu Gu, Avery Hill, Paul Kusuma, Isaac Lipsky, Mia Mirkovic, Jorge Luis Meraz, Vincent Pane, Kyle B. Sander, Fengzhe Shi, Jeffrey M. Skerker, Alexander Styer, Kyle Valgardson, Kelly Wetmore, Sung-Geun Woo, Yongao Xiong, Kevin Yates, Cindy Zhang, Shuyang Zhen, Bruce Bugbee, Douglas S. Clark, Devin Coleman-Derr, Ali Mesbah, Somen Nandi, Robert M. Waymouth, Peidong Yang, Craig S. Criddle, Karen A. McDonald, Lance C. Seefeldt, Amor A. Menezes, and Adam P. Arkin
- Subjects
0106 biological sciences ,Engineering ,biomanufacturing ,in situ resource utilization ,Astronomy ,Geophysics. Cosmic physics ,Context (language use) ,QB1-991 ,space systems bioengineering ,Biology ,01 natural sciences ,Astrobiology ,03 medical and health sciences ,Leverage (negotiation) ,human exploration ,Biomanufacturing ,Life support system ,automotive_engineering ,030304 developmental biology ,0303 health sciences ,business.industry ,QC801-809 ,Astronomy and Astrophysics ,In situ resource utilization ,Mars Exploration Program ,life support systems ,Systems engineering ,business ,Biotechnology ,010606 plant biology & botany - Abstract
A crewed mission to and from Mars may include an exciting array of enabling biotechnologies that leverage inherent mass, power, and volume advantages over traditional abiotic approaches. In this perspective, we articulate the scientific and engineering goals and constraints, along with example systems, that guide the design of a surface biomanufactory. Extending past arguments for exploiting stand-alone elements of biology, we argue for an integrated biomanufacturing plant replete with modules for microbial \textit{in situ} resource utilization, production, and recycling of food, pharmaceuticals, and biomaterials required for sustaining future intrepid astronauts. We also discuss aspirational technology trends in each of these target areas in the context of human and robotic exploration missions in the coming century.
- Published
- 2021
41. Dietary goals and current challenges in the management of classical homocystinuria: insights from multinational real-world experience
- Author
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C Burns, F Greblikas, D Green, A Hall, A Jung, J McNulty, M Sellos-Moura, and S Hollander
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Genetics ,Molecular Biology ,Biochemistry - Published
- 2022
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42. A-47 | P2Y12 Inhibitors in Acute Coronary Syndromes: A Real-World, Community-Based Comparison of Ischemic and Bleeding Outcomes
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Amit Sachdeva, Ratnabhushan Mutyala, Matthew D. Solomon, Edward J. Mcnulty, Shiyun Zhu, and Neha Mantri
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- 2022
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43. PO-1856 Artificial intelligence: the opinions of radiation therapists in Ireland
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T. O'Donovan, J. McNulty, and M. Ryan
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Oncology ,Radiology, Nuclear Medicine and imaging ,Hematology - Published
- 2022
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44. Alpha-1 antitrypsin deficiency and recombinant protein sources with focus on plant sources: Updates, challenges and perspectives
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Brooks Kuhn, David Z. Silberstein, Somen Nandi, Karen A. McDonald, Carroll E. Cross, Hal S. Padgett, and Matthew J. McNulty
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0301 basic medicine ,Lung Diseases ,medicine.medical_treatment ,Disease ,Biochemistry ,law.invention ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,law ,Physiology (medical) ,alpha 1-Antitrypsin Deficiency ,medicine ,Humans ,Serine protease ,Alpha 1-antitrypsin deficiency ,Protease ,biology ,business.industry ,Investigational New Drug ,medicine.disease ,Recombinant Proteins ,Clinical trial ,030104 developmental biology ,Pulmonary Emphysema ,alpha 1-Antitrypsin ,Immunology ,Recombinant DNA ,biology.protein ,business ,030217 neurology & neurosurgery - Abstract
Alpha-1 antitrypsin deficiency (A1ATD) is an autosomal recessive disease characterized by low plasma levels of A1AT, a serine protease inhibitor representing the most abundant circulating antiprotease normally present at plasma levels of 1–2 g/L. The dominant clinical manifestations include predispositions to early onset emphysema due to protease/antiprotease imbalance in distal lung parenchyma and liver disease largely due to unsecreted polymerized accumulations of misfolded mutant A1AT within the endoplasmic reticulum of hepatocytes. Since 1987, the only FDA licensed specific therapy for the emphysema component has been infusions of A1AT purified from pooled human plasma at the 2020 cost of up to US $200,000/year with the risk of intermittent shortages. In the past three decades various, potentially less expensive, recombinant forms of human A1AT have reached early stages of development, one of which is just reaching the stage of human clinical trials. The focus of this review is to update strategies for the treatment of the pulmonary component of A1ATD with some focus on perspectives for therapeutic production and regulatory approval of a recombinant product from plants. We review other competitive technologies for treating the lung disease manifestations of A1ATD, highlight strategies for the generation of data potentially helpful for securing FDA Investigational New Drug (IND) approval and present challenges in the selection of clinical trial strategies required for FDA licensing of a New Drug Approval (NDA) for this disease.
- Published
- 2020
45. Cover Image
- Author
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Jasmine M. Corbin, Matthew J. McNulty, Kantharakorn Macharoen, Karen A. McDonald, and Somen Nandi
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Bioengineering ,Applied Microbiology and Biotechnology ,Biotechnology - Published
- 2020
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46. Resting Metabolic Rate in Female Rugby Players: Differences in Measured Versus Predicted Values
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Senan J McNulty, Katy Horner, Domenico Crognale, Ciara S Walsh, Martha E Corish, Jack Eoin Rua G OʼNeill, and Hannah C Gantly
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Adult ,Adolescent ,Population ,Physical Therapy, Sports Therapy and Rehabilitation ,Muscle damage ,Measured RMR ,Fat mass ,Body Mass Index ,Young Adult ,Animal science ,Low energy ,Humans ,Orthopedics and Sports Medicine ,education ,Whole-body air displacement plethysmography ,Mathematics ,education.field_of_study ,biology ,Calorimetry, Indirect ,General Medicine ,Plethysmography ,Basal metabolic rate ,biology.protein ,Body Composition ,Creatine kinase ,Female ,Basal Metabolism ,Rugby ,Energy Metabolism - Abstract
O'Neill, JERG, Walsh, CS, McNulty, SJ, Gantly, HC, Corish, ME, Crognale, D, and Horner, K. Resting metabolic rate in female rugby players: differences in measured versus predicted values. J Strength Cond Res XX(X): 000-000, 2020-This study investigated (a) the accuracy of resting metabolic rate (RMR) prediction equations in female rugby players and (b) factors that might explain poor prediction accuracy in some individuals. Resting metabolic rate was assessed in 36 female elite and subelite rugby players (age: 18-35 years, fat-free mass (FFM): 43-63 kg, fat mass %: 15-41%). After pretest standardization (24-hour exercise avoidance and 12-hour overnight fast), RMR was measured by indirect calorimetry and compared with predicted values determined by Harris-Benedict, Cunningham, Ten Haaf, Jagim and Watson equations. Body composition was assessed by air displacement plethysmography, muscle damage indicated by creatine kinase, and risk of low energy availability (LEA) by LEA in Females Questionnaire. Measured RMR was 1,651 ± 167 kcal·d. The Cunningham, Ten Haaf, and Watson (body mass) predicted values did not differ from measured (p > 0.05), while all other predicted values differed significantly (p < 0.001). Individually, prediction accuracy to within 10% varied widely depending on the equation used (range 44% [n = 16] to 86% [n = 31]). Three of the 5 individuals whose values were outside 10% of the measured value using the best performing Ten Haaf FFM equation could be explained by muscle damage or LEA. These measures may be useful to assist in understanding why measured RMR may be lower or higher than predicted in some athletes. Overall, the Ten Haaf equations showed the best accuracy, suggesting these equations may be most suitable for this population. The findings demonstrate the importance of considering the population studied when determining the most appropriate prediction equation to use.
- Published
- 2020
47. Technoeconomic analysis of semicontinuous bioreactor production of biopharmaceuticals in transgenic rice cell suspension cultures
- Author
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Jasmine M. Corbin, Kantharakorn Macharoen, Matthew J. McNulty, Karen A. McDonald, and Somen Nandi
- Subjects
0106 biological sciences ,0301 basic medicine ,technoeconomic analysis ,Cell Culture Techniques ,Bioengineering ,Biology ,01 natural sciences ,Applied Microbiology and Biotechnology ,Suspension culture ,biopharmaceutical ,Article ,03 medical and health sciences ,Bioreactors ,010608 biotechnology ,Plant cell culture ,Plant Cells ,Bioreactor ,Production (economics) ,Computer Simulation ,Transgenes ,Bioprocess ,Biological Products ,plant cell culture ,semicontinuous ,Oryza ,Genetically modified rice ,Culture Media ,Perfusion ,Chemically defined medium ,030104 developmental biology ,Biopharmaceutical ,butyrylcholinesterase ,Biochemical engineering ,Biotechnology - Abstract
Biopharmaceutical protein production using transgenic plant cell bioreactor processes offers advantages over microbial and mammalian cell culture platforms in its ability to produce complex biologics with simple chemically defined media and reduced biosafety concerns. A disadvantage of plant cells from a traditional batch bioprocessing perspective is their slow growth rate which has motivated us to develop semicontinuous and/or perfusion processes. Although the economic benefits of plant cell culture bioprocesses are often mentioned in the literature, to our knowledge no rigorous technoeconomic models or analyses have been published. Here we present technoeconomic models in SuperPro Designer® for the large-scale production of recombinant butyrylcholinesterase (BChE), a prophylactic/therapeutic bioscavenger against organophosphate nerve agent poisoning, in inducible transgenic rice cell suspension cultures. The base facility designed to produce 25 kg BChE per year utilizing two-stage semicontinuous bioreactor operation manufactures a single 400 mg dose of BChE for $263. Semicontinuous operation scenarios result in 4-11% reduction over traditional two-stage batch operation scenarios. In addition to providing a simulation tool that will be useful to the plant-made pharmaceutical community, the model also provides a computational framework that can be used for other semicontinuous or batch bioreactor-based processes.
- Published
- 2020
48. Automating Clinical Chart Review: An Open-Source Natural Language Processing Pipeline Developed on Free-Text Radiology Reports From Patients With Glioblastoma
- Author
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Logan D. Cho, Joeky T. Senders, Joanna L Ashby, Ahmad Kareem Almekkawi, Timothy R. Smith, Alireza Mehrtash, John J McNulty, Omar Arnaout, William B. Gormley, Marike L. D. Broekman, Isabelle S Schulte, and Paola Calvachi
- Subjects
Research Report ,Medical Records Systems, Computerized ,Computer science ,MEDLINE ,Medical information ,Neuroimaging ,computer.software_genre ,03 medical and health sciences ,Automation ,0302 clinical medicine ,Text mining ,Chart review ,medicine ,Text messaging ,Data Mining ,Humans ,030212 general & internal medicine ,Natural Language Processing ,business.industry ,General Medicine ,medicine.disease ,Pipeline (software) ,Open source ,030220 oncology & carcinogenesis ,Artificial intelligence ,business ,Glioblastoma ,Radiology ,computer ,Natural language processing - Abstract
PURPOSE The aim of this study was to develop an open-source natural language processing (NLP) pipeline for text mining of medical information from clinical reports. We also aimed to provide insight into why certain variables or reports are more suitable for clinical text mining than others. MATERIALS AND METHODS Various NLP models were developed to extract 15 radiologic characteristics from free-text radiology reports for patients with glioblastoma. Ten-fold cross-validation was used to optimize the hyperparameter settings and estimate model performance. We examined how model performance was associated with quantitative attributes of the radiologic characteristics and reports. RESULTS In total, 562 unique brain magnetic resonance imaging reports were retrieved. NLP extracted 15 radiologic characteristics with high to excellent discrimination (area under the curve, 0.82 to 0.98) and accuracy (78.6% to 96.6%). Model performance was correlated with the inter-rater agreement of the manually provided labels (ρ = 0.904; P < .001) but not with the frequency distribution of the variables of interest (ρ = 0.179; P = .52). All variables labeled with a near perfect inter-rater agreement were classified with excellent performance (area under the curve > 0.95). Excellent performance could be achieved for variables with only 50 to 100 observations in the minority group and class imbalances up to a 9:1 ratio. Report-level classification accuracy was not associated with the number of words or the vocabulary size in the distinct text documents. CONCLUSION This study provides an open-source NLP pipeline that allows for text mining of narratively written clinical reports. Small sample sizes and class imbalance should not be considered as absolute contraindications for text mining in clinical research. However, future studies should report measures of inter-rater agreement whenever ground truth is based on a consensus label and use this measure to identify clinical variables eligible for text mining.
- Published
- 2020
49. Accuracy of resting metabolic rate prediction equations in female rugby players
- Author
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Martha E Corish, Senan J McNulty, Jack O'Neill, Katy Horner, Ciara S Walsh, Hannah C Gantly, and Domenico Crognale
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medicine.medical_specialty ,Nutrition and Dietetics ,Internal medicine ,Basal metabolic rate ,medicine ,Cardiology ,Medicine (miscellaneous) ,Biology - Abstract
This study aimed to investigate (1) the accuracy of resting metabolic rate (RMR) prediction equations in female rugby players on a group and individual level; and (2) whether individual differences in the accuracy of prediction equations is associated with muscle damage or energy availability.RMR was assessed in 14 female provincial and club rugby players (Age: 20–34 years, FFM: 47–63 kg, FM: 15–37%) training a minimum of twice per week. Participants attended the laboratory following an overnight fast and having avoided strenuous exercise for 24 hours. RMR was measured over 30 minutes by indirect calorimetry, and taken as the 10 minutes with the lowest variation. Body composition was assessed by air displacement plethysmography, muscle damage indicated by creatine kinase (CK) and risk of low energy availability assessed by the Low Energy Availability in Females Questionnaire. Accuracy of RMR prediction equations relevant to the general population and athletes were assessed including the Harris Benedict (1919), Cunningham (1980) and Ten Haaf FFM (2014) based equations.Measured RMR was 1748 ± 146 kcal/day (range: 1474–2010 kcal/day). Predicted RMR determined by the Harris-Benedict equation (1601 ± 120 kcal/day) was significantly lower than measured RMR (p < 0.001), whereas predicted RMR using the Cunningham (1753 ± 146 kcal/day, p = 0.89) and the Ten Haaf (1781 ± 115 kcal/day, p = 0.33) equations did not differ from measured RMR. On an individual level, 50% (n = 7), 86% (n = 12) and 79% (n = 11) of participants fell within 10% of the measured RMR value when RMR was predicted by Harris-Benedict, Cunningham and Ten Haaf equations respectively. CK values were 182 ± 155U/L (range: 25–490U/L). When correlations of the whole group were studied, the difference between predicted and measured RMR was not associated with CK (r = 0.13). However, in the two individuals who fell outside the 10% range of that predicted by the Cunningham equation, one above and one below, CK values were 428U/L and 166U/L respectively. Muscle damage (as indicated by a high CK value) could therefore be one potential explanation for the higher measured RMR in the individual who was above the Cunningham predicted value.In this cohort of female rugby players, the Cunningham equation showed the best accuracy on a group and individual level, suggesting this may be the most suitable prediction equation for this population. Further studies with larger sample sizes and investigating underlying reasons for why RMR measured values may differ from predicted values are needed.
- Published
- 2020
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50. Immobilization of transgenic plant cells towards bioprinting for production of a recombinant biodefense agent
- Author
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Matthew J. McNulty, Anika Varma, Somen Nandi, Jennifer M. Knipe, Karen A. McDonald, and Hawi B. Gemeda
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Chemistry ,Transgene ,Bioprinting ,Heterologous ,Oryza ,General Medicine ,Plants, Genetically Modified ,Plant cell ,Applied Microbiology and Biotechnology ,Genetically modified rice ,Recombinant Proteins ,law.invention ,Biochemistry ,law ,Butyrylcholinesterase ,Plant Cells ,Recombinant DNA ,medicine ,Bioreactor ,Molecular Medicine ,Nerve agent ,medicine.drug - Abstract
Transgenic rice cells (Oryza sativa) producing recombinant butyrylcholinesterase (BChE) as a prophylactic/therapeutic against organophosphate nerve agent poisoning, cocaine toxicity, and neurodegenerative diseases like Alzheimer's were immobilized in a polyethylene glycol-based hydrogel. The cells were sustained for 14 days in the semi-solid matrix, undergoing a growth phase from days 0-6, a BChE production phase in sugar-free medium from days 6-12, and a growth/recovery phase from days 12-14. Throughout this period, the cells maintained similar viability to those in suspension cultures and displayed analogous sugar consumption trends. The rice cells in the hydrogel also produced a significant amount of active BChE, comparable to the levels produced in liquid cultures. A considerable fraction of this BChE was secreted into the media, allowing for easier product separation. To the best of our knowledge, this proof-of-concept is the first report of immobilization of recombinant plant cells for continuous production of high-value heterologous proteins. This work serves as a foundation for further investigation towards plant cell bioprinting and the development of a simple, efficient, robust, modular, and potentially field-deployable bioreactor system for the manufacture of biologics. This article is protected by copyright. All rights reserved.
- Published
- 2021
- Full Text
- View/download PDF
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