567 results on '"Thomas A Fox"'
Search Results
2. Flow and structure in a dendritic glacier with bedrock steps
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HESTER JISKOOT, THOMAS A FOX, and WESLEY VAN WYCHEN
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glacier flow ,glacier erosion ,glacier surges ,mountain glaciers ,structural glaciology ,Environmental sciences ,GE1-350 ,Meteorology. Climatology ,QC851-999 - Abstract
We analyse ice flow and structural glaciology of Shackleton Glacier, a dendritic glacier with multiple icefalls in the Canadian Rockies. A major tributary-trunk junction allows us to investigate the potential of tributaries to alter trunk flow and structure, and the formation of bedrock steps at confluences. Multi-year velocity-stake data and structural glaciology up-glacier from the junction were assimilated with glacier-wide velocity derived from Radarsat-2 speckle tracking. Maximum flow speeds are 65 m a−1 in the trunk and 175 m a−1 in icefalls. Field and remote-sensing velocities are in good agreement, except where velocity gradients are high. Although compression occurs in the trunk up-glacier of the tributary entrance, glacier flux is steady state because flow speed increases at the junction due to the funnelling of trunk ice towards an icefall related to a bedrock step. Drawing on a published erosion model, we relate the heights of the step and the hanging valley to the relative fluxes of the tributary and trunk. It is the first time that an extant glacier is used to test and support such model. Our study elucidates the inherent complexity of tributary/trunk interactions and provides a conceptual model for trunk flow restriction by a tributary in surge-type glaciers.
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- 2017
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3. Can new mobile technologies enable fugitive methane reductions from the oil and gas industry?
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Thomas A Fox, Chris H Hugenholtz, Thomas E Barchyn, Tyler R Gough, Mozhou Gao, and Marshall Staples
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fugitive methane ,leak detection and repair ,oil and gas ,screening technology ,LDAR-Sim ,Environmental technology. Sanitary engineering ,TD1-1066 ,Environmental sciences ,GE1-350 ,Science ,Physics ,QC1-999 - Abstract
New mobile platforms such as vehicles, drones, aircraft, and satellites have emerged to help identify and reduce fugitive methane emissions from the oil and gas sector. When deployed as part of leak detection and repair (LDAR) programs, most of these technologies use multi-visit LDAR (MVL), which consists of four steps: (a) rapidly screen all facilities, (b) triage by emission rate, (c) follow-up with close-range methods at the highest-emitting sites, and (d) conduct repairs. The proposed value of MVL is to identify large leaks soon after they arise. Whether MVL offers an improvement over traditional single-visit LDAR (SVL), which relies on undirected close-range surveys, remains poorly understood. We use the Leak Detection and Repair Simulator (LDAR-Sim) to examine the performance and cost-effectiveness of MVL relative to SVL. Results suggest that facility-scale MVL programs can achieve fugitive emission reductions equivalent to SVL, but that improved cost-effectiveness is not guaranteed. Under a best-case scenario, we find that screening must cost < USD 100 per site for MVL to achieve 30% cost reductions relative to SVL. In scenarios with non-target vented emissions and screening quantification uncertainty, triaging errors force excessive close-range follow-up to achieve emissions reduction equivalence. The viability of MVL as a cost-effective alternative to SVL for reducing fugitive methane emissions hinges on accurate triaging after the screening phase.
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- 2021
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4. A review of close-range and screening technologies for mitigating fugitive methane emissions in upstream oil and gas
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Thomas A Fox, Thomas E Barchyn, David Risk, Arvind P Ravikumar, and Chris H Hugenholtz
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natural gas leaks ,leak detection and repair ,fugitive emissions management ,methane emissions monitoring ,technology evaluation ,Environmental technology. Sanitary engineering ,TD1-1066 ,Environmental sciences ,GE1-350 ,Science ,Physics ,QC1-999 - Abstract
Fugitive methane emissions from the oil and gas industry are targeted using leak detection and repair (LDAR) programs. Until recently, only a limited number of measurement standards have been permitted by most regulators, with emphasis on close-range methods (e.g. Method-21, optical gas imaging). Although close-range methods are essential for source identification, they can be labor-intensive. To improve LDAR efficiency, there has been a policy shift in Canada and the United States towards incorporating alternative technologies. However, the suitability of these technologies for LDAR remains unclear. In this paper, we systematically review and compare six technology classes for use in LDAR: handheld instruments, fixed sensors, mobile ground labs (MGLs), unmanned aerial vehicles (UAVs), aircraft, and satellites. These technologies encompass broad spatial and temporal scales of measurement. Minimum detection limits for technology classes range from
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- 2019
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5. Erratum: A review of close-range and screening technologies for mitigating fugitive methane emissions in upstream oil and gas (2019 Environ. Res. Lett. 14 053002)
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Thomas A Fox, Thomas E Barchyn, David Risk, Arvind P Ravikumar, and Chris H Hugenholtz
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Environmental technology. Sanitary engineering ,TD1-1066 ,Environmental sciences ,GE1-350 ,Science ,Physics ,QC1-999 - Published
- 2019
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6. Improving access to gene therapy for rare diseases
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Thomas A. Fox and Claire Booth
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gene therapy ,inborn errors of immunity ,inborn errors of metabolism ,rare disease ,Medicine ,Pathology ,RB1-214 - Published
- 2024
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7. Improving Fairness in Adaptive Social Exergames via Shapley Bandits.
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Robert C. Gray, Jennifer Villareale, Thomas Boyd Fox, Diane H. Dallal, Santiago Ontañón, Danielle Arigo, Shahin Jabbari, and Jichen Zhu
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- 2023
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8. Parallel OPM: A Visualization System for Analyzing Peers Board States for Gameplay Reflection.
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Sai Siddartha Maram, Jennifer Villareale, Thomas Boyd Fox, Jichen Zhu, and Magy Seif El-Nasr
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- 2023
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9. iNNk: A Multi-Player Game to Deceive a Neural Network.
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Jennifer Villareale, Ana V. Acosta-Ruiz, Samuel Adam Arcaro, Thomas B. Fox, Evan Freed, Robert C. Gray, Mathias Löwe, Panote Nuchprayoon, Aleksanteri Sladek, Rush Weigelt, Yifu Li, Sebastian Risi, and Jichen Zhu
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- 2020
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10. Enhancing social exergames through idle game design.
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Jennifer Villareale, Robert C. Gray, Anushay Furqan, Thomas B. Fox, and Jichen Zhu
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- 2019
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11. Efficient AI System Design With Cross-Layer Approximate Computing.
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Swagath Venkataramani, Xiao Sun 0013, Naigang Wang, Chia-Yu Chen, Jungwook Choi, Mingu Kang, Ankur Agarwal, Jinwook Oh, Shubham Jain, Tina Babinsky, Nianzheng Cao, Thomas W. Fox, Bruce M. Fleischer, George Gristede, Michael Guillorn, Howard Haynie, Hiroshi Inoue, Kazuaki Ishizaki, Michael J. Klaiber, Shih-Hsien Lo, Gary W. Maier, Silvia M. Mueller, Michael Scheuermann, Eri Ogawa, Marcel Schaal, Mauricio J. Serrano, Joel Silberman, Christos Vezyrtzis, Wei Wang 0333, Fanchieh Yee, Jintao Zhang, Matthew M. Ziegler, Ching Zhou, Moriyoshi Ohara, Pong-Fei Lu, Brian W. Curran, Sunil Shukla, Vijayalakshmi Srinivasan, Leland Chang, and Kailash Gopalakrishnan
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- 2020
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12. Author Correction: Weather constraints on global drone flyability
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Mozhou Gao, Chris H. Hugenholtz, Thomas A. Fox, Maja Kucharczyk, Thomas E. Barchyn, and Paul R. Nesbit
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Medicine ,Science - Published
- 2021
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13. A 3.0 TFLOPS 0.62V Scalable Processor Core for High Compute Utilization AI Training and Inference.
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Jinwook Oh, Sae Kyu Lee, Mingu Kang, Matthew M. Ziegler, Joel Silberman, Ankur Agrawal, Swagath Venkataramani, Bruce M. Fleischer, Michael Guillorn, Jungwook Choi, Wei Wang 0333, Silvia M. Mueller, Shimon Ben-Yehuda, James Bonanno, Nianzheng Cao, Robert Casatuta, Chia-Yu Chen, Matt Cohen, Ophir Erez, Thomas W. Fox, George Gristede, Howard Haynie, Vicktoria Ivanov, Siyu Koswatta, Shih-Hsien Lo, Martin Lutz, Gary W. Maier, Alex Mesh, Yevgeny Nustov, Scot Rider, Marcel Schaal, Michael Scheuermann, Xiao Sun 0013, Naigang Wang, Fanchieh Yee, Ching Zhou, Vinay Shah, Brian W. Curran, Vijayalakshmi Srinivasan, Pong-Fei Lu, Sunil Shukla, Kailash Gopalakrishnan, and Leland Chang
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- 2020
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14. A methane emissions reduction equivalence framework for alternative leak detection and repair programs
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Thomas A. Fox, Arvind P. Ravikumar, Chris H. Hugenholtz, Daniel Zimmerle, Thomas E. Barchyn, Matthew R. Johnson, David Lyon, and Tim Taylor
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Fugitive emissions ,Leak detection and repair ,Emissions equivalence ,Methane emissions ,Upstream oil and gas ,Natural gas ,Environmental sciences ,GE1-350 - Abstract
Fugitive methane emissions from the oil and gas sector are typically addressed through periodic leak detection and repair surveys. These surveys, conducted manually using handheld leak detection technologies, are time-consuming. To improve the speed and cost-effectiveness of leak detection, technology developers are introducing innovative solutions using mobile platforms, close-range portable systems, and permanent installations. Many of these new approaches promise faster, cheaper, or more effective leak detection than conventional methods. However, ensuring mitigation targets are achieved requires demonstrating that alternative approaches are at least as effective in reducing emissions as current approaches – a concept known as emissions reduction equivalence. Here, we propose a five-stage framework for demonstrating equivalence that combines controlled testing, simulation modeling, and field trials. The framework was developed in consultation with operators, regulators, academics, solution providers, consultants, and non-profit groups from Canada and the U.S. We present the equivalence framework and discuss challenges to implementation.
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- 2019
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15. Artificial Intelligence Neural Network Consistently Interprets Lung Ultrasound Artifacts in Hospitalized Patients: A Prospective Observational Study
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Thomas H. Fox, Gautam R. Gare, Laura E. Hutchins, Victor S. Perez, Ricardo Rodriguez, David L. Smith, Francisco X. Brito-Encarnacion, Raman Danrad, Hai V. Tran, Peter B. Lowery, David J. Montgomery, Kevin A. Zamorra, Amita Krishnan, John M. Galeotti, and Bennett P. deBoisblanc
- Abstract
BackgroundInterpretation of lung ultrasound artifacts by clinicians can be inconsistent. Artificial intelligence (AI) may perform this task more consistently.Research QuestionCan AI characterize lung ultrasound artifacts similarly to humans, and can AI interpretation be corroborated by clinical data?Study Design and MethodsLung sonograms (n=665) from a convenience sample of 172 subjects were prospectively obtained using a pre-specified protocol and matched to clinical and radiographic data. Three investigators scored sonograms for A-lines and B-lines. AI was trained using 142 subjects and then tested on a separate dataset of 30 patients. Three radiologists scored similar anatomic regions of contemporary radiographs for interstitial and alveolar infiltrates to corroborate sonographic findings. The ratio of oxyhemoglobin saturation:fraction of inspired oxygen (S/F) was also used for comparison. The primary outcome was the intraclass correlation coefficient (ICC) between the median investigator scoring of artifacts and AI interpretation.ResultsIn the test set, the correlation between the median investigator score and the AI score was moderate to good for A lines (ICC 0.73, 95% CI [0.53-0.89]), and moderate for B lines (ICC 0.66, 95% CI [0.55-0.75]). The degree of variability between the AI score and the median investigator score for each video was similar to the variability between each investigator’s score and the median score. The correlation among radiologists was moderate (ICC 0.59, 95% CI [0.52-0.82]) for interstitial infiltrates and poor for alveolar infiltrates (ICC 0.33, 95% CI [0.07-0.58]). There was a statistically significant correlation between AI scored B-lines and the degree of interstitial opacities for five of six lung zones. Neither AI nor human-scored artifacts were consistently associated with S/F.InterpretationUsing a limited dataset, we showed that AI can interpret lung ultrasound A-lines and B-lines in a fashion that could be clinically useful.
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- 2023
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16. [18F]Florbetaben PET-CT confirms AL amyloidosis in a patient with Waldenström’s Macroglobulinemia
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Thomas A. Fox, Michael Lunn, Ashutosh Wechalekar, Jamshed Bomanji, Simon Wan, and Shirley D’Sa
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2018
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17. A Scalable Multi- TeraOPS Deep Learning Processor Core for AI Trainina and Inference.
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Bruce M. Fleischer, Sunil Shukla, Matthew M. Ziegler, Joel Silberman, Jinwook Oh, Vijayalakshmi Srinivasan, Jungwook Choi, Silvia M. Mueller, Ankur Agrawal, Tina Babinsky, Nianzheng Cao, Chia-Yu Chen, Pierce Chuang, Thomas W. Fox, George Gristede, Michael Guillorn, Howard Haynie, Michael J. Klaiber, Dongsoo Lee, Shih-Hsien Lo, Gary W. Maier, Michael Scheuermann, Swagath Venkataramani, Christos Vezyrtzis, Naigang Wang, Fanchieh Yee, Ching Zhou, Pong-Fei Lu, Brian W. Curran, Leland Chang, and Kailash Gopalakrishnan
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- 2018
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18. Across the Stack Opportunities for Deep Learning Acceleration.
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Vijayalakshmi Srinivasan, Bruce M. Fleischer, Sunil Shukla, Matthew M. Ziegler, Joel Silberman, Jinwook Oh, Jungwook Choi, Silvia M. Mueller, Ankur Agrawal, Tina Babinsky, Nianzheng Cao, Chia-Yu Chen, Pierce Chuang, Thomas W. Fox, George Gristede, Michael Guillorn, Howard Haynie, Michael J. Klaiber, Dongsoo Lee, Shih-Hsien Lo, Gary W. Maier, Michael Scheuermann, Swagath Venkataramani, Christos Vezyrtzis, Naigang Wang, Fanchieh Yee, Ching Zhou, Pong-Fei Lu, Brian W. Curran, Leland Chang, and Kailash Gopalakrishnan
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- 2018
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19. Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles
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Emma Touizer, Aljawharah Alrubbayi, Rosemarie Ford, Noshin Hussain, Pehuén Pereyra Gerber, Hiu-Long Shum, Chloe Rees-Spear, Luke Muir, Ester Gea-Mallorquí, Jakub Kopycinski, Dylan Jankovic, Christopher Pinder, Thomas A Fox, Ian Williams, Claire Mullender, Irfaan Maan, Laura Waters, Margaret Johnson, Sara Madge, Michael Youle, Tristan Barber, Fiona Burns, Sabine Kinloch, Sarah Rowland-Jones, Richard Gilson, Nicholas J Matheson, Emma Morris, Dimitra Peppa, and Laura E McCoy
- Abstract
People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can have residual immune dysfunction and often display poorer responses to vaccination. We assessed in a cohort of PLWH (n=110) and HIV negative controls (n=64) the humoral and spike-specific B-cell responses following 1, 2 or 3 SARS-CoV-2 vaccine doses. PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls at all studied timepoints. Moreover, their neutralization breadth was reduced with fewer individuals developing a neutralizing response against the Omicron variant (BA.1) relative to controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs) and pronounced B cell dysfunction. Improved neutralization breadth was seen after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global, but not spike-specific, MBC dysfunction. In contrast to the inferior antibody responses, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, a subset of PLWH with low or absent neutralization had detectable functional T cell responses. These individuals had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3+CD127+CD8+T cells after two doses of SARS-CoV-2 vaccination, which may compensate for sub-optimal serological responses in the event of infection. Therefore, normalisation of B cell homeostasis could improve serological responses to vaccines in PLWH and evaluating T cell immunity could provide a more comprehensive immune status profile in these individuals and others with B cell imbalances.
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- 2022
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20. Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles
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Emma Touizer, Aljawharah Alrubayyi, Rosemarie Ford, Noshin Hussain, Pehuén Pereyra Gerber, Hiu-Long Shum, Chloe Rees-Spear, Luke Muir, Ester Gea-Mallorquí, Jakub Kopycinski, Dylan Jankovic, Anna Jeffery-Smith, Christopher L. Pinder, Thomas A. Fox, Ian Williams, Claire Mullender, Irfaan Maan, Laura Waters, Margaret Johnson, Sara Madge, Michael Youle, Tristan J. Barber, Fiona Burns, Sabine Kinloch, Sarah Rowland-Jones, Richard Gilson, Nicholas J. Matheson, Emma Morris, Dimitra Peppa, Laura E. McCoy, Muir, Luke [0000-0002-7834-6066], Morris, Emma [0000-0003-4834-1130], and Apollo - University of Cambridge Repository
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Multidisciplinary ,FOS: Clinical medicine ,Virology ,Immunology - Abstract
We assessed a cohort of people living with human immunodeficiency virus (PLWH) (n = 110) and HIV negative controls (n = 64) after 1, 2 or 3 SARS-CoV-2 vaccine doses. At all timepoints, PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs). Improved neutralization breadth was seen against the Omicron variant (BA.1) after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global MBC dysfunction. In contrast, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, individuals with low or absent neutralization had detectable functional T cell responses. These PLWH had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3+CD127+CD8+T cells after two doses of SARS-CoV-2 vaccination.
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- 2022
21. Spatial variability in tree-ring carbon isotope discrimination in response to local drought across the entire loblolly pine natural range
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Madison Akers, Jean-Christophe Domec, Timothy A. Martin, Cassandra R. Meek, Asko Noormets, Lisa J. Samuelson, Marshall A. Laviner, Rodney E. Will, Thomas R. Fox, Jason G. Vogel, John D. Marshall, Wen Lin, Ge Sun, John S. King, Steve McNulty, and Josh Cucinella
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Carbon Isotopes ,Spatial correlation ,δ13C ,Physiology ,Water ,Pinus taeda ,Plant Science ,Deserts and xeric shrublands ,Atmospheric sciences ,Acclimatization ,Droughts ,Trees ,Isotopes of carbon ,Dendrochronology ,Environmental science ,Spatial variability ,Water use - Abstract
Considering the temporal responses of carbon isotope discrimination (Δ13C) to local water availability in the spatial analysis of Δ13C is essential for evaluating the contribution of environmental and genetic facets of plant Δ13C. Using tree-ring Δ13C from years with contrasting water availability at 76 locations across the natural range of loblolly pine, we decomposed site-level Δ13C signals to maximum Δ13C in well-watered conditions (Δ13Cmax) and isotopic drought sensitivity (m) as a change in Δ13C per unit change of Palmer’s Drought Severity Index (PDSI). Site water status, especially the tree lifetime average PDSI, was the primary factor affecting Δ13Cmax. The strong spatial correlation exhibited by m was related to both genetic and environmental factors. The long-term average water availability during the period relevant to trees as indicated by lifetime average PDSI correlated with Δ13Cmax, suggesting acclimation in tree gas-exchange traits, independent of incident water availability. The positive correlation between lifetime average PDSI and m indicated that loblolly pines were more sensitive to drought at mesic than xeric sites. The m was found to relate to a plant’s stomatal control and may be employed as a genetic indicator of efficient water use strategies. Partitioning Δ13C to Δ13Cmax and m provided a new angle for understanding sources of variation in plant Δ13C, with several fundamental and applied implications.
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- 2021
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22. Methane emissions from above-ground natural gas distribution facilities in the urban environment: A fence line methodology and case study in Calgary, Alberta, Canada
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Clay Wearmouth, Thomas E. Barchyn, Chris H. Hugenholtz, Coleman Vollrath, Thomas A. Fox, Chandler Billinghurst, and Tyler R. Gough
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Fence (finance) ,Air Pollutants ,Meteorology ,business.industry ,Test method ,Natural Gas ,Management, Monitoring, Policy and Law ,Methane ,Alberta ,Trace gas ,Geolocation ,chemistry.chemical_compound ,chemistry ,Anemometer ,Natural gas ,Global Positioning System ,Humans ,Environmental science ,business ,Waste Management and Disposal ,Environmental Monitoring - Abstract
The occurrence and emissions of methane (CH4) from above-ground urban natural gas infrastructure is poorly understood. Compared to below-ground infrastructure, these facilities are relatively easy to monitor and maintain and present an opportunity for cost-effective CH4 reductions. We present a case study and methodology for detecting, attributing, and quantifying CH4 emissions from fence line measurements at above-ground natural gas facilities in the City of Calgary, Alberta, Canada. We produced bounding-box concentration maps by walking around the outer fence of 33 facilities with a backpack-configured trace gas analyzer and a tablet with integrated GPS. Wind measurements were acquired simultaneously from a fixed location on site with a 3D sonic anemometer. We fused geolocation, CH4 concentration, and wind data to determine the likelihood each facility was emitting. We found one definitive leak by carrying out measurements directly alongside an exposed section of pipe. Based on the presence of methyl mercaptan (CH3SH) odor, peak ΔCH4, and the difference between downwind and upwind ΔCH4, we interpret a high plausibility that 22 facilities were emitting CH4, followed by 2 with a medium plausibility, and 8 with a low plausibility. Once verified to plausibly emit, these data were used to estimate emissions flux at six facilities where near-field obstructions were limited. The estimated emissions flux for six facilities was 66.31 mg CH4 s-1, or 2.1 tonnes CH4 yr-1 if this flux remained constant. Overall, this study indicates most above-ground natural gas facilities surveyed in Calgary were emitting CH4. These facilities represent easy mitigation targets for reducing CH4 emissions and improving environmental performance. To our knowledge, this is the first study to integrate qualitative and quantitative information to predict detection plausibility in a complex measurement setting.Implications: The fence line methodology outlined in this study represents an extension of source assessment modes in the US EPA's Other Test Method 33A for human portable systems. This has implications for standardization of emissions measurement in situations where other platforms (e.g., vehicles) are less effective due to access limitations. We believe the methodology presented could become a recognized standard based on performance from controlled testing and added to the regulatory toolkit for emissions verification and compliance.
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- 2021
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23. Research and Innovation in the Private Forestry Sector: Past Successes and Future Opportunities
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Lauren Magalska, Thomas R. Fox, Eric B. Sucre, and Jessica A. Homyack
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Economic growth ,Forestry ,Plant Science ,Business - Abstract
The private forestry sector faces enormous challenges from complex environmental issues concurrent with societal concerns about intensive forest management and application of silvicultural tools. At the same time, research and development spending and the scientific workforce in the forestry sector has declined. However, the forestry sector has a long history of strategic deployment of science and technology to manage timberlands for many uses, including ecological services. To address science and societal needs from future forests, we describe past successes and potential future innovations of the forestry sector across (1) genetics, (2) silviculture and productivity, (3) harvesting and logging technology, (4) environmental sustainability, and (5) remote sensing and unmanned aerial vehicles. Developing technology is only one component, however; progressing towards sector goals of diversifying the workforce, explicitly valuing research collaborations, and integrating big data across ownerships to guide management decisions will hasten innovation. With the growing complexity of social-ecological-economic challenges, the private forestry sector must enact a tactical approach to addressing stressors with evolving research structures. We offer a vision of a vibrant private forestry sector poised to integrate technological innovation to continue meeting society’s needs through the intersecting effects of climate change and other challenges.
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- 2021
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24. Therapeutic gene editing of T cells to correct CTLA-4 insufficiency
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Thomas Andrew Fox, Benjamin Christopher Houghton, Lina Petersone, Erin Waters, Natalie Mona Edner, Alex McKenna, Olivier Preham, Claudia Hinze, Cayman Williams, Adriana Silva de Albuquerque, Alan Kennedy, Anne Maria Pesenacker, Pietro Genovese, Lucy Sarah Kate Walker, Siobhan Oisin Burns, David Michael Sansom, Claire Booth, and Emma Catherine Morris
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Gene Editing ,Mice ,DNA, Complementary ,Antigens, CD ,T-Lymphocytes ,B7-1 Antigen ,Humans ,Animals ,CTLA-4 Antigen ,General Medicine ,B7-2 Antigen ,Lymphocyte Activation - Abstract
Heterozygous mutations inCTLA-4result in an inborn error of immunity with an autoimmune and frequently severe clinical phenotype. Autologous T cell gene therapy may offer a cure without the immunological complications of allogeneic hematopoietic stem cell transplantation. Here, we designed a homology-directed repair (HDR) gene editing strategy that inserts theCTLA-4cDNA into the first intron of theCTLA-4genomic locus in primary human T cells. This resulted in regulated expression of CTLA-4 in CD4+T cells, and functional studies demonstrated CD80 and CD86 transendocytosis. Gene editing of T cells isolated from three patients with CTLA-4 insufficiency also restored CTLA-4 protein expression and rescued transendocytosis of CD80 and CD86 in vitro. Last, gene-corrected T cells fromCTLA-4−/−mice engrafted and prevented lymphoproliferation in an in vivo murine model of CTLA-4 insufficiency. These results demonstrate the feasibility of a therapeutic approach using T cell gene therapy for CTLA-4 insufficiency.
- Published
- 2022
25. Design methodology for semi custom processor cores.
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Victor V. Zyuban, Sameh W. Asaad, Thomas W. Fox, Anne-Marie Haen, Daniel Littrell, and Jaime H. Moreno
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- 2004
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26. A 4R2W register file for a 2.3GHz wire-speed POWER™ processor with double-pumped write operation.
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Gary S. Ditlow, Robert K. Montoye, Salvatore N. Storino, Sherman M. Dance, Sebastian Ehrenreich, Bruce M. Fleischer, Thomas W. Fox, Kyle M. Holmes, Junichi Mihara, Yutaka Nakamura, Shohji Onishi, Robert Shearer, Dieter F. Wendel, and Leland Chang
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- 2011
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27. Allogeneic stem cell transplantation compared to conservative management in adults with inborn errors of immunity
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Morgane Cheminant, Thomas A. Fox, Mickael Alligon, Olivier Bouaziz, Bénédicte Neven, Despina Moshous, Stéphane Blanche, Aurélien Guffroy, Claire Fieschi, Marion Malphettes, Nicolas Schleinitz, Antoinette Perlat, Jean-François Viallard, Nathalie Dhedin, Françoise Sarrot-Reynauld, Isabelle Durieu, Sébastien Humbert, Fanny Fouyssac, Vincent Barlogis, Benjamin Carpenter, Rachael Hough, Arian Laurence, Ambroise Marçais, Ronjon Chakraverty, Olivier Hermine, Alain Fischer, Siobhan O. Burns, Nizar Mahlaoui, Emma C. Morris, and Felipe Suarez
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Adult ,Transplantation Conditioning ,Immunology ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Cell Biology ,Hematology ,Granulomatous Disease, Chronic ,Conservative Treatment ,Biochemistry ,Young Adult ,Humans ,Transplantation, Homologous ,Retrospective Studies ,Stem Cell Transplantation - Abstract
Allogeneic hematopoietic stem cell transplantation (alloSCT) is curative for severe inborn errors of immunity (IEIs), with recent data suggesting alloSCT in adulthood is safe and effective in selected patients. However, questions remain regarding the indications for and optimal timing of transplant. We retrospectively compared outcomes of transplanted vs matched nontransplanted adults with severe IEIs. Seventy-nine patients (aged ≥ 15 years) underwent alloSCT between 2008 and 2018 for IEIs such as chronic granulomatous disease (n = 20) and various combined immune deficiencies (n = 59). A cohort of nontransplanted patients from the French Centre de Référence Déficits Immunitaires Héréditaires registry was identified blindly for case-control analysis, with ≤3 matched controls per index patient, without replacement. The nontransplanted patients were matched for birth decade, age at last review greater than index patient age at alloSCT, chronic granulomatous disease or combined immune deficiencies, and autoimmune/lymphoproliferative complications. A total of 281 patients were included (79 transplanted, 202 nontransplanted). Median age at transplant was 21 years. Transplant indications were mainly lymphoproliferative disease (n = 23) or colitis (n = 15). Median follow-up was 4.8 years (interquartile range, 2.5-7.2). One-year transplant-related mortality rate was 13%. Estimated disease-free survival at 5 years was higher in transplanted patients (58% vs 33%; P = .007). Nontransplanted patients had an ongoing risk of severe events, with an increased mean cumulative number of recurrent events compared with transplanted patients. Sensitivity analyses removing patients with common variable immune deficiency and their matched transplanted patients confirm these results. AlloSCT prevents progressive morbidity associated with IEIs in adults, which may outweigh the negative impact of transplant-related mortality.
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- 2022
28. Haematological Disease
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Thomas A. Fox and Emma C. Morris
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- 2022
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29. The IBM Blue Gene/Q Compute Chip.
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Ruud A. Haring, Martin Ohmacht, Thomas W. Fox, Michael Gschwind, David L. Satterfield, Krishnan Sugavanam, Paul Coteus, Philip Heidelberger, Matthias A. Blumrich, Robert W. Wisniewski, Alan Gara, George L.-T. Chiu, Peter A. Boyle, Norman H. Christ, and Changhoan Kim
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- 2012
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30. Gene therapy for primary immunodeficiencies
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Claire Booth and Thomas A. Fox
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Gene Editing ,Severe combined immunodeficiency ,business.industry ,Genetic enhancement ,Hematopoietic Stem Cell Transplantation ,Genetic Therapy ,Hematology ,Disease ,medicine.disease ,Bioinformatics ,Transplantation ,03 medical and health sciences ,Haematopoiesis ,0302 clinical medicine ,Immune system ,Genome editing ,Agammaglobulinemia ,030220 oncology & carcinogenesis ,Humans ,Medicine ,Severe Combined Immunodeficiency ,Stem cell ,Autografts ,business ,030215 immunology - Abstract
Primary immunodeficiencies (PIDs) are a group of rare inherited disorders of the immune system. Many PIDs are devastating and require a definitive therapy to prevent progressive morbidity and premature mortality. Allogeneic haematopoietic stem cell transplantation (alloHSCT) is curative for many PIDs, and while advances have resulted in improved outcomes, the procedure still carries a risk of mortality and morbidity from graft failure or graft-versus-host disease (GvHD). Autologous haematopoietic stem cell gene therapy (HSC GT) has the potential to correct genetic defects across haematopoietic lineages without the complications of an allogeneic approach. HSC GT for PID has been in development for the last two decades and the first licensed HSC-GT product for adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) is now available. New gene editing technologies have the potential to circumvent some of the problems associated with viral gene-addition. HSC GT for PID shows great promise, but requires a unique approach for each disease and carries risks, notably insertional mutagenesis from gamma-retroviral gene addition approaches and possible off-target toxicities from gene-editing techniques. In this review, we discuss the development of HSC GT for PID and outline the current state of clinical development before discussing future developments in the field.
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- 2020
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31. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients
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John Riches, Jeffrey I. Zwicker, Halil Yildiz, William A. Wood, Inna Y. Gong, Jerome Razanamahery, Fernando Martín-Moro, Raphaël Lattenist, Rushad Patell, Marie-Christiane Mb Vekemans, Stephen Booth, Bruno Fattizzo, Abi Vijenthira, Lydia Scarfò, Lisa K. Hicks, Ioannis Mantzaris, Gordon Cook, Thomas Andrew Fox, Thomas Chatzikonstantinou, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de médecine interne générale, UCL - (SLuc) Service d'hématologie, Vijenthira, Abi, Gong, Inna Y, Fox, Thomas A, Booth, Stephen, Cook, Gordon, Fattizzo, Bruno, Martin Moro, Fernando, Razanamahery, Jerome, Riches, John Charle, Zwicker, Jeffrey I, Patell, Rushad, Vekemans, Marie-Christiane Mb, Scarfo, Lydia, Chatzikonstantinou, Thoma, Yildiz, Halil, Lattenist, Raphaël, Mantzaris, Ioanni, Wood, William A, and Hicks, Lisa K
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medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Clinical Trials and Observations ,Immunology ,MEDLINE ,Malignancy ,Biochemistry ,law.invention ,law ,Internal medicine ,medicine ,Humans ,Survival rate ,SARS-CoV-2 ,business.industry ,Vaccination ,Hematopoietic Stem Cell Transplantation ,COVID-19 ,Cell Biology ,Hematology ,Prognosis ,medicine.disease ,Intensive care unit ,Confidence interval ,Hospitalization ,Survival Rate ,Intensive Care Units ,Hematologic Neoplasms ,Meta-analysis ,Relative risk ,business - Abstract
Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched PubMed and EMBASE up to 20 August 2020 to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of intensive care unit admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-four adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14 of 34 adult studies included only hospitalized patients). Risk of death among adult patients was 34% (95% CI, 28-39; N = 3240) in this sample of predominantly hospitalized patients. Patients aged ≥60 years had a significantly higher risk of death than patients, Key Points • Adult patients with hematologic malignancy and COVID-19 found a 34% risk of death, whereas pediatric patients had a 4% risk of death. • Patients on systemic anticancer therapy had a similar risk of death to patients on no treatment (RR, 1.17; 95% CI, 0.83-1.64).
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- 2020
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32. A 50-Year Retrospective of the Forest Productivity Cooperative in the Southeastern United States: Regionwide Trials
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Rafael Rubilar, Thomas R. Fox, Otávio Camargo Campoe, H. Lee Allen, Timothy J. Albaugh, Rachel L. Cook, and David R. Carter
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0106 biological sciences ,Geography ,010504 meteorology & atmospheric sciences ,Forestry ,Plant Science ,01 natural sciences ,Productivity ,Agricultural economics ,010606 plant biology & botany ,0105 earth and related environmental sciences - Abstract
In 2019, the Forest Productivity Cooperative (FPC) celebrated its 50th anniversary. The mission of the FPC is and has been creating innovative solutions to enhance forest productivity and value through the sustainable management of site resources. This industry-government-university partnership has generated seminal research with sweeping implications for increasing productivity throughout the southeastern United States and Latin America. To commemorate this semicentennial, we highlighted some of the pivotal findings in the southeastern United States from the past 50 years derived from our large, regional experiments: regionwide trials.
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- 2020
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33. Efficient AI System Design With Cross-Layer Approximate Computing
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Michael J. Klaiber, George D. Gristede, Shih-Hsien Lo, Hiroshi Inoue, Leland Chang, Christos Vezyrtzis, Jungwook Choi, Gary W. Maier, Fanchieh Yee, Shubham Jain, Brian W. Curran, Jintao Zhang, Mingu Kang, Howard M. Haynie, Mauricio J. Serrano, Pong-Fei Lu, Silvia Melitta Mueller, Matthew M. Ziegler, Bruce M. Fleischer, Kazuaki Ishizaki, Kailash Gopalakrishnan, Michael R. Scheuermann, Ankur Agarwal, Xiao Sun, Sunil Shukla, Thomas W. Fox, Vijayalakshmi Srinivasan, Tina Babinsky, Swagath Venkataramani, Michael A. Guillorn, Ching Zhou, Nianzheng Cao, Eri Ogawa, Naigang Wang, Moriyoshi Ohara, Joel Abraham Silberman, Jinwook Oh, Marcel Schaal, Chia-Yu Chen, and Wei Wang
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Instruction set ,Computer architecture ,Artificial neural network ,Computer science ,Quantization (signal processing) ,Hardware acceleration ,Operational efficiency ,Systems design ,Compiler ,Electrical and Electronic Engineering ,Architecture ,computer.software_genre ,computer - Abstract
Advances in deep neural networks (DNNs) and the availability of massive real-world data have enabled superhuman levels of accuracy on many AI tasks and ushered the explosive growth of AI workloads across the spectrum of computing devices. However, their superior accuracy comes at a high computational cost, which necessitates approaches beyond traditional computing paradigms to improve their operational efficiency. Leveraging the application-level insight of error resilience, we demonstrate how approximate computing (AxC) can significantly boost the efficiency of AI platforms and play a pivotal role in the broader adoption of AI-based applications and services. To this end, we present RaPiD, a multi-tera operations per second (TOPS) AI hardware accelerator core (fabricated at 14-nm technology) that we built from the ground-up using AxC techniques across the stack including algorithms, architecture, programmability, and hardware. We highlight the workload-guided systematic explorations of AxC techniques for AI, including custom number representations, quantization/pruning methodologies, mixed-precision architecture design, instruction sets, and compiler technologies with quality programmability, employed in the RaPiD accelerator.
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- 2020
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34. Assessing the accuracy of octanol–water partition coefficient predictions in the SAMPL6 Part II log P Challenge
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Mehtap Işık, David L. Mobley, Teresa Danielle Bergazin, John D. Chodera, Thomas R. Fox, and Andrea Rizzi
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Octanols ,Research groups ,Mean squared error ,Subset and superset ,Molecular Dynamics Simulation ,01 natural sciences ,Article ,Mixed approach ,Cyclohexanes ,Prediction methods ,0103 physical sciences ,Drug Discovery ,Statistics ,Limit (mathematics) ,Physical and Theoretical Chemistry ,Mathematics ,Molecular Structure ,010304 chemical physics ,Water ,0104 chemical sciences ,Computer Science Applications ,Partition coefficient ,010404 medicinal & biomolecular chemistry ,Models, Chemical ,Solubility ,Solvents ,Octanol water partition ,Quantum Theory ,Thermodynamics - Abstract
The SAMPL Challenges aim to focus the biomolecular and physical modeling community on issues that limit the accuracy of predictive modeling of protein-ligand binding for rational drug design. In the SAMPL5 log D Challenge, designed to benchmark the accuracy of methods for predicting drug-like small molecule transfer free energies from aqueous to nonpolar phases, participants found it difficult to make accurate predictions due to the complexity of protonation state issues. In the SAMPL6 log P Challenge, we asked participants to make blind predictions of the octanol-water partition coefficients of neutral species of 11 compounds and assessed how well these methods performed absent the complication of protonation state effects. This challenge builds on the SAMPL6 p[Formula: see text] Challenge, which asked participants to predict p[Formula: see text] values of a superset of the compounds considered in this log P challenge. Blind prediction sets of 91 prediction methods were collected from 27 research groups, spanning a variety of quantum mechanics (QM) or molecular mechanics (MM)-based physical methods, knowledge-based empirical methods, and mixed approaches. There was a 50% increase in the number of participating groups and a 20% increase in the number of submissions compared to the SAMPL5 log D Challenge. Overall, the accuracy of octanol-water log P predictions in SAMPL6 Challenge was higher than cyclohexane-water log D predictions in SAMPL5, likely because modeling only the neutral species was necessary for log P and several categories of method benefited from the vast amounts of experimental octanol-water log P data. There were many highly accurate methods: 10 diverse methods achieved RMSE less than 0.5 log P units. These included QM-based methods, empirical methods, and mixed methods with physical modeling supported with empirical corrections. A comparison of physical modeling methods showed that QM-based methods outperformed MM-based methods. The average RMSE of the most accurate five MM-based, QM-based, empirical, and mixed approach methods based on RMSE were 0.92 ± 0.13, 0.48 ± 0.06, 0.47 ± 0.05, and 0.50 ± 0.06, respectively.
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- 2020
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35. Impaired platelet‐dependent thrombin generation associated with thrombocytopenia is improved by prothrombin complex concentrates in vitro
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Pratima Chowdary, Colleen Hamid, Alex Gatt, Keith Gomez, Thomas A. Fox, Edgar Brodkin, Richard W Morris, John H. McVey, Jonathan H. Foley, David A. Slatter, Fox, Thomas A [0000-0002-1163-2295], and Apollo - University of Cambridge Repository
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medicine.medical_specialty ,blood platelets ,thrombocytopenia ,Blood platelets ,Thrombin ,Internal medicine ,Original Articles: Hemostasis ,medicine ,Coagulopathy ,Platelet ,prothrombin complex concentrates ,lcsh:RC633-647.5 ,Chemistry ,Area under the curve ,lcsh:Diseases of the blood and blood-forming organs ,Hematology ,medicine.disease ,thrombin ,Thrombocytopenia ,In vitro ,Endocrinology ,Coagulation ,Blood coagulation disorders ,Original Article ,Prothrombin ,acquired coagulopathy ,blood coagulation disorders ,Analysis of variance ,Ex vivo ,medicine.drug - Abstract
Background: Impaired thrombin generation (TG) in patients with acquired coagulop-athy, is due to low coagulation factors and thrombocytopenia. The latter is typically treated with platelet transfusions and the former with plasma and occasionally with prothrombin complex concentrates (PCCs). We hypothesized that manipulating the concentrations of coagulation factors might result in restoration of platelet-depend-ent TG over and above that of simple replacement therapy.Objective: To investigate the influence of PCCs on impaired TG secondary to thrombocytopenia.Methods: TG was evaluated by thrombin generation assay using a thrombocytopenia model in which normal plasma samples with varying platelet counts (20-300 × 109/L) were spiked with PCCs (25%-150% increase in plasma PCC levels).Results: PCCs and platelets significantly increased TG in a dose-dependent manner in vitro. Two-way repeated measures of analysis of variance showed variance in peak height, area under the curve, time to peak, and velocity. This variance explained, respectively, by levels of PCC was 47, 59, 25 and 53%; by platelet count was 45, 28, 44, and 14%; by the combination was 80, 67, 70, and 62% variance; and a combi-nation with additional interaction was 91, 84, 76, and 68%. TG at a platelet count 40 × 109/L with an approximate 25% increase in PCC concentration was similar to TG at 150 × 109/L. Similarly, patient samples spiked ex vivo with PCCs also showed highly significant improvements in TG.Conclusions: Impaired TG of thrombocytopenia is improved by PCCs, supporting the need for additional studies in complex coagulopathies characterized by mild to mod-erate thrombocytopenia and abnormal coagulation, Objective: To investigate the influence of PCCs on impaired TG secondary to thrombocytopenia., Methods: TG was evaluated by thrombin generation assay using a thrombocytopenia model in which normal plasma samples with varying platelet counts (20-300 × 109/L) were spiked with PCCs (25%-150% increase in plasma PCC levels)., Results: PCCs and platelets significantly increased TG in a dose-dependent manner in vitro. Two-way repeated measures of analysis of variance showed variance in peak height, area under the curve, time to peak, and velocity. This variance explained, respectively, by levels of PCC was 47, 59, 25 and 53%; by platelet count was 45, 28, 44, and 14%; by the combination was 80, 67, 70, and 62% variance; and a combi-nation with additional interaction was 91, 84, 76, and 68%. TG at a platelet count 40 × 109/L with an approximate 25% increase in PCC concentration was similar to TG at 150 × 109/L. Similarly, patient samples spiked ex vivo with PCCs also showed highly significant improvements in TG., Conclusions: Impaired TG of thrombocytopenia is improved by PCCs, supporting the need for additional studies in complex coagulopathies characterized by mild to moderate thrombocytopenia and abnormal coagulation., peer-reviewed
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- 2020
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36. SQUAMOUS CELL CARCINOMA WITH SUSPECTED METASTASES TO THE MYOCARDIAL WALL AS EVIDENCED BY CONTRAST TRANSTHORACIC ECHOCARDIOGRAM
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Trent Davidge, Shashitha Gavini, Thomas H. Fox, and Mehnaz Rahman
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Cardiology and Cardiovascular Medicine - Published
- 2023
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37. In the Shadow of the Holocaust
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Thomas C. Fox
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History ,The Holocaust ,Judaism ,Ancient history ,Communism ,Shadow (psychology) - Abstract
This study investigates six German Jewish writers' negotiation of Jewish-German-Communist identity in post-Holocaust East Germany.
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- 2022
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38. The Design of High-Performance Microprocessors at Digital.
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Thomas F. Fox
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- 1994
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39. Retrospective, Landmark Analysis of Long-term Adult Morbidity Following Allogeneic HSCT for Inborn Errors of Immunity in Infancy and Childhood
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James W. Day, Reem Elfeky, Bethany Nicholson, Rupert Goodman, Rachel Pearce, Thomas A. Fox, Austen Worth, Claire Booth, Paul Veys, Ben Carpenter, Rachael Hough, H. Bobby Gaspar, Penny Titman, Deborah Ridout, Sarita Workman, Fernando Hernandes, Kit Sandford, Arian Laurence, Mari Campbell, Siobhan O. Burns, and Emma C. Morris
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Adult ,Transplantation Conditioning ,Immunology ,Hematopoietic Stem Cell Transplantation ,Immunology and Allergy ,Graft vs Host Disease ,Humans ,Morbidity ,Chimerism ,Retrospective Studies - Abstract
Abstract Purpose Allogeneic hematopoietic stem cell transplant (HSCT) remains the treatment of choice for patients with inborn errors of immunity (IEI). There is little published medical outcome data assessing late medical complications following transition to adult care. We sought to document event-free survival (EFS) in transplanted IEI patients reaching adulthood and describe common late-onset medical complications and factors influencing EFS. Methods In this landmark analysis, 83 adults surviving 5 years or more following prior HSCT in childhood for IEI were recruited. The primary endpoint was event-free survival, defined as time post-first HSCT to graft failure, graft rejection, chronic infection, life-threatening or recurrent infections, malignancy, significant autoimmune disease, moderate to severe GVHD or major organ dysfunction. All events occurring less than 5 years post-HSCT were excluded. Results EFS was 51% for the whole cohort at a median of 20 years post HSCT. Multivariable analysis identified age at transplant and whole blood chimerism as independent predictors of long-term EFS. Year of HSCT, donor, conditioning intensity and underlying diagnosis had no significant impact on EFS. 59 events occurring beyond 5 years post-HSCT were documented in 37 patients (45% cohort). A total of 25 patients (30% cohort) experienced ongoing significant complications requiring active medical intervention at last follow-up. Conclusion Although most patients achieved excellent, durable immune reconstitution with infrequent transplant-related complications, very late complications are common and associated with mixed chimerism post-HSCT. Early intervention to correct mixed chimerism may improve long-term outcomes and adult health following HSCT for IEI in childhood.
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- 2021
40. An innovative low-power high-performance programmable signal processor for digital communications.
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Jaime H. Moreno, Victor V. Zyuban, Uzi Shvadron, Fredy D. Neeser, Jeff H. Derby, Malcolm S. Ware, Krishnan Kailas, Ayal Zaks, Amir B. Geva, Shay Ben-David, Sameh W. Asaad, Thomas W. Fox, Daniel Littrell, Marina Biberstein, Dorit Naishlos, and Hillery C. Hunter
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- 2003
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41. Active Memory Cube: A processing-in-memory architecture for exascale systems.
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Ravi Nair, Samuel Antão, Carlo Bertolli, Pradip Bose, José R. Brunheroto, Tong Chen 0001, Chen-Yong Cher, Carlos H. A. Costa, J. Doi, Constantinos Evangelinos, Bruce M. Fleischer, Thomas W. Fox, Diego S. Gallo, Leopold Grinberg, John A. Gunnels, Arpith C. Jacob, P. Jacob, Hans M. Jacobson, Tejas Karkhanis, C. Kim, Jaime H. Moreno, John K. O'Brien, Martin Ohmacht, Yoonho Park, Daniel A. Prener, Bryan S. Rosenburg, Kyung Dong Ryu, Olivier Sallenave, Mauricio J. Serrano, P. D. M. Siegl, Krishnan Sugavanam, and Zehra Sura
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- 2015
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42. Author Correction: Weather constraints on global drone flyability
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Thomas A. Fox, Mozhou Gao, Thomas E. Barchyn, Chris H. Hugenholtz, Maja Kucharczyk, and Paul Ryan Nesbit
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Multidisciplinary ,Aeronautics ,Computer science ,Science ,Medicine ,Author Correction ,Drone - Abstract
Small aerial drones are used in a growing number of commercial applications. However, drones cannot fly in all weather, which impacts their reliability for time-sensitive operations. The magnitude and global variability of weather impact is poorly understood. We explore weather-limited drone flyability (the proportion of time drones can fly safely) by comparing historical wind speed, temperature, and precipitation data to manufacturer-reported thresholds of common commercial and weather-resistant drones with a computer simulation. We show that global flyability is highest in warm and dry continental regions and lowest over oceans and at high latitudes. Median global flyability for common drones is low: 5.7 h/day or 2.0 h/day if restricted to daylight hours. Weather-resistant drones have higher flyability (20.4 and 12.3 h/day, respectively). While these estimates do not consider all weather conditions, results suggest that improvements to weather resistance can increase flyability. An inverse analysis for major population centres shows the largest flyability gains for common drones can be achieved by increasing maximum wind speed and precipitation thresholds from 10 to 15 m/s and 0-1 mm/h, respectively.
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- 2021
43. Low seropositivity and suboptimal neutralisation rates in patients fully vaccinated against COVID-19 with B-cell malignancies
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Shirley D'Sa, Suzanne O Arulogun, Satyen H. Gohil, Robert S. Heyderman, Laura E. McCoy, Jenny O'Nions, Siobhan O. Burns, Emma C. Morris, Kate Cwynarski, Kirit M. Ardeshna, Thomas A. Fox, Janki Kavi, Louise Enfield, Maeve A O'Reilly, Amy A Kirkwood, William Townsend, Kirsty Thomson, Tommy Rampling, Mahdad Noursadeghi, and Evan Vitsaras
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Adult ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunotherapy, Adoptive ,Neutralization ,CAR‐T ,ChAdOx1 nCoV-19 ,Correspondence ,Agammaglobulinaemia Tyrosine Kinase ,Medicine ,Humans ,In patient ,B cell malignancy ,B cell ,BNT162 Vaccine ,Aged ,Aged, 80 and over ,Covid‐19 ,business.industry ,SARS-CoV-2 ,Vaccination ,Immunity ,COVID-19 ,Hematology ,Middle Aged ,Virology ,Leukemia, Lymphocytic, Chronic, B-Cell ,Lymphocyte Subsets ,medicine.anatomical_structure ,Logistic Models ,Case-Control Studies ,Spike Glycoprotein, Coronavirus ,business ,B‐cell malignancy - Published
- 2021
44. Utility of 18F-FDG-PET/CT in lymphoblastic lymphoma
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Emma Nicholson, Asim Khwaja, Callum Wright, Marc R. Mansour, Ben Carpenter, Johnathon Elliot, Mary Taj, Ben Uttenthal, Martha Perisoglou, Rachael Hough, Victoria Grandage, Adele K. Fielding, Richard Halsey, Anna Castleton, and Thomas A Fox
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Cancer Research ,Pathology ,medicine.medical_specialty ,Lymphoblastic Leukemia ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,immune system diseases ,Positron Emission Tomography Computed Tomography ,hemic and lymphatic diseases ,medicine ,Humans ,business.industry ,Lymphoma, Non-Hodgkin ,Lymphoblastic lymphoma ,hemic and immune systems ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Lymphoma ,Oncology ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Fdg pet ct ,Radiopharmaceuticals ,business ,030215 immunology - Abstract
Lymphoblastic lymphoma (LBL) is a rare, malignant disorder of precursor T- or B- cells, which forms the lymphoma variant of acute lymphoblastic leukemia (ALL). Whilst morphologically and immunophen...
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- 2020
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45. Outcomes of Adult and Pediatric Patients with Hematologic Malignancies and COVID-19: A Systematic Review and Meta-Analysis of 1847 Patients
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Halil Yildiz, Raphael Lattenist, Gordon Cook, Inna Gong, Bruno Fattizzo, Jerome Razanamahery, Rushad Patell, Stephen Booth, Lydia Scarfò, Thomas A Fox, Thomas Chatzikonstantinou, Lisa K. Hicks, Fernando Martin Moro, Jeffrey I. Zwicker, Marie Christiane Vekemans, John Riches, William A. Wood, Ioannis Mantzaris, and Abi Vijenthira
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Mechanical ventilation ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,902.Health Services Research-Malignant Conditions (Lymphoid Disease) ,Immunology ,Cell Biology ,Hematology ,Malignancy ,medicine.disease ,Biochemistry ,Confidence interval ,Dyscrasia ,Risk Estimate ,Relative risk ,Meta-analysis ,Internal medicine ,Medicine ,Population study ,business - Abstract
Introduction: Clinical outcomes for patients with hematologic malignancy and COVID-19 have not been aggregated. We completed a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. Methods: We searched Pubmed and EMBASE up to July 25, 2020, to identify reports of patients with hematologic malignancy and COVID-19 (including papers where the patients with hematologic malignancy were a subset of the total study population). The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included pooled estimates for the risk of ICU admission, mechanical ventilation, and non-invasive ventilation in hospitalized patients. Mortality data were stratified by age, treatment status, and malignancy subtype. For treatment status, "systemic anti-cancer therapy (SACT)" was defined as patients on any anti-cancer therapy. "Cytotoxic SACT" was defined as patients on cytotoxic therapy only. "Not on treatment" was defined as patients on observation or those who were at least 28 days beyond their last active treatment. Sensitivity analyses were conducted on the primary outcomes limiting to studies with low risk of bias, and to studies including both outpatients and hospitalized patients. Due to data limitations, only the primary outcome was assessed for pediatric studies. Pooled prevalence and risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model using MetaXL and Revman 5.4 software. Results: A total of 25 adult studies and 4 pediatric studies comprising 1847 patients from China, Europe, the United Kingdom, and North America were included (Figure 1 and Table 1). The majority of patients were hospitalized (83%). The overall risk of death amongst all patients was 36% (95% CI 31-41, N=1763), and amongst hospitalized patients was 40% (95% CI 36-45, 24 studies with 1295 patients) (Figure 2). Patients aged >60 years had a significantly higher risk of death than patients The risk of ICU admission among hospitalized adult patients was 23% (95% CI 17-29, N=1165); mechanical ventilation 16% (95% CI 12-21, N= 826); and non-invasive ventilation 16% (95% CI 9-26%, N=373). The estimated RR of death among patients on SACT compared to no treatment was 1.22 (95% CI 0.84-1.78; N=457, Figure 3a). The RR of death among patients on cytotoxic SACT versus no treatment was similar at 1.29 (95% CI 0.78-2.15; N=176, Figure 3b). All subgroups of hematologic malignancy had high risks of overall mortality: acquired bone marrow dysfunction syndromes 57% (95% CI 42-72, 11 studies, 42 patients); leukemias 44% (95% CI 31-58, 15 studies, 159 patients), plasma cell dyscrasias 38% (95% CI 29-47, 18 studies, 387 patients); lymphomas (including CLL) 32% (95% CI 26-38, 16 studies, 696 patients); lymphomas (excluding CLL) 32% (95% CI 18-48, 11 studies, 156 patients); CLL 31% (95% CI 24-39, 13 studies, 457 patients); myeloproliferative neoplasms 37% (95% CI 25-49, 9 studies, 62 patients). Sensitivity analysis including only studies with a low risk of bias showed a similar estimate for risk of death among all patients (37% (95% CI 31-42, 20 studies with 1412 patients)) compared to all studies. Sensitivity analysis including only studies reporting on a combination of outpatients and hospitalized patients also showed a similar estimate for risk of death among all patients (38% (95% CI 32-44), 11 studies with 1214 patients) compared to all studies. Conclusion: Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, appear to experience a high risk of dying (pooled risk estimate 36%). Older patients experience higher mortality, and pediatric patients appear to be relatively spared. Importantly, based on the observational data available to date, recent cancer treatment does not appear to significantly increase the risk of dying. These data highlight the need for robust strategies to prevent patients with hematologic malignancy from contracting COVID-19, and may help inform discussions about prevention strategies, treatment, and goals of care. Disclosures Cook: Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; IQVIA: Research Funding; Sanofi: Consultancy; Amgen: Consultancy; Roche: Consultancy; Karyopharm: Consultancy. Zwicker:Dova: Honoraria, Other: Advisory board; Portola: Honoraria, Other: Advisory board; Incyte: Research Funding; Quercegen: Research Funding; Parexel: Consultancy; Sanofi: Consultancy; CSL: Consultancy; Pfizer/BMS: Honoraria, Other: Advisory board. Scarfo:Gilead: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Wood:Pfizer: Research Funding; Best Doctors/Teladoc: Consultancy; Koneksa Health: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Elektra Labs: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; ASH Research Collaborative: Honoraria; Genentech: Research Funding. Hicks:Gilead Sciences: Research Funding.
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- 2020
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46. Multifocal Osteomyelitis in a Child Presenting With a Mediastinal Mass
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Bryana Ferris, Carol M. Kao, Thomas G. Fox, and Mark D. Gonzalez
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medicine.medical_specialty ,business.industry ,Osteomyelitis ,Antitubercular Agents ,Mediastinum ,MEDLINE ,Mediastinal mass ,medicine.disease ,Magnetic Resonance Imaging ,Abscess ,Diagnosis, Differential ,Pediatrics, Perinatology and Child Health ,Mediastinal Diseases ,medicine ,Humans ,Tuberculosis ,Female ,Spinal Diseases ,Whole Body Imaging ,Radiology ,Bone Diseases ,Child ,Tomography, X-Ray Computed ,business - Published
- 2020
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47. Rapid clinical response to adjuvant corticosteroids in chronic disseminated candidiasis complicated by granulomas and persistent fever in acute leukemia patients
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Asim Khwaja, Vanya Gant, Rachael Hough, Victoria Grandage, Sabine Pomplun, Richard Halsey, Thomas A. Fox, and Marc R. Mansour
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Cancer Research ,medicine.medical_specialty ,Antifungal Agents ,medicine.medical_treatment ,Persistent fever ,Chronic disseminated candidiasis ,03 medical and health sciences ,0302 clinical medicine ,Adrenal Cortex Hormones ,medicine ,Humans ,In patient ,Clinical scenario ,Acute leukemia ,Granuloma ,Leukemia ,business.industry ,Candidiasis ,Hematology ,Dermatology ,Leukemia, Myeloid, Acute ,Oncology ,030220 oncology & carcinogenesis ,business ,Adjuvant ,030215 immunology - Abstract
We report successful resolution, using adjuvant corticosteroids, of a challenging clinical scenario in patients undergoing treatment for acute leukemia who developed chronic disseminated candidiasi...
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- 2019
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48. Crown architecture, crown leaf area distribution, and individual tree growth efficiency vary across site, genetic entry, and planting density
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Rafael Rubilar, Otávio Camargo Campoe, Marco A. Yáñez, Thomas R. Fox, David R. Carter, Chris A. Maier, Timothy J. Albaugh, Eric D. Carbaugh, Rachel L. Cook, and Forest Resources and Environmental Conservation
- Subjects
Crown architecture ,0106 biological sciences ,Physiology ,Distribution (economics) ,Stand density ,Plant Science ,Biology ,Genetic entry ,01 natural sciences ,Branch number ,Crown closure ,Ecology ,business.industry ,Significant difference ,Crown (botany) ,Sowing ,Forestry ,04 agricultural and veterinary sciences ,Horticulture ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,Crown length ,Tree (set theory) ,business ,Growth efficiency ,010606 plant biology & botany - Abstract
We examined crown architecture and within crown leaf area distribution effects on Pinus taeda L. growth in North Carolina (NC), Virginia (VA), and Brazil (BR) to better understand why P. taeda can grow much better in Brazil than in the southeastern United States. The NC, VA, and BR sites were planted in 2009, 2009, and 2011, respectively. At all sites, we planted the same two genetic entries at 618, 1236, and 1854 trees ha(-1). In 2013, when trees were still open grown, the VA and NC sites had greater branch diameter (24%), branch number (14%), live crown length (44%), foliage mass (82%), and branch mass (91%), than the BR site. However, in 2017, after crown closure and when there was no significant difference in tree size, site did not significantly affect these crown variables. In 2013, site significantly affected absolute leaf area distribution, likely due to differences in live crown length and leaf area, such that there was more foliage at a given level in the crown at the VA and NC sites than at the BR site. In 2017, site was still a significant factor explaining leaf area distribution, although at this point, with crown closure and similar sized trees, there was more foliage at the BR site at a given level in the crown compared to the VA and NC sites. In 2013 and 2017, when including site, genetic entry, stand density, and leaf area distribution parameters as independent variables, site significantly affected individual tree growth efficiency, indicating that something other than leaf area distribution was influencing the site effect. Better BR P. taeda growth is likely due to a combination of factors, including leaf area distribution, crown architecture, and other factors that have been identified as influencing the site effect (heat sum), indicating that future work should include a modeling analysis to examine all known contributing factors. Public domain – authored by a U.S. government employee
- Published
- 2019
- Full Text
- View/download PDF
49. Successful Use of Tissue Plasminogen Activator in an Adolescent Male with Pyogenic Liver Abscess
- Author
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Sonal Patel, Janine E. Zee-Cheng, Samer Abu-Sultaneh, and Thomas G. Fox
- Subjects
Pyogenic liver abscess ,medicine.medical_specialty ,Abdominal pain ,Percutaneous ,business.industry ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,Catheter Obstruction ,Case Report ,lcsh:RC86-88.9 ,Critical Care and Intensive Care Medicine ,medicine.disease ,Tissue plasminogen activator ,Surgery ,03 medical and health sciences ,Catheter ,0302 clinical medicine ,030220 oncology & carcinogenesis ,medicine ,Chills ,030212 general & internal medicine ,medicine.symptom ,business ,Liver abscess ,medicine.drug - Abstract
Large pyogenic liver abscess is a rare and difficult to treat entity in pediatric patients. Percutaneous drainage rather than open surgical drainage has become more common in recent years, even for large abscesses. Percutaneous drainage can be complicated by catheter obstruction. We present the case of a 16-year-old male presenting with abdominal pain, fever, and chills. He was diagnosed with a 9-centimeter liver abscess. A CT-guided percutaneous drainage was placed. The catheter initially drained well, but then became occluded. Tissue plasminogen activator was instilled into the catheter every 6 hours for a total of five doses, resulting in increased drainage and improved clinical state of the patient. To our knowledge, this is the first reported use of tissue plasminogen activator in pyogenic liver abscess in the pediatric population.
- Published
- 2019
- Full Text
- View/download PDF
50. A regional assessment of permanganate oxidizable carbon for potential use as a soil health indicator in managed pine plantations
- Author
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Fernanda C. C. Oliveira, Allan Bacon, Thomas R. Fox, Eric J. Jokela, Michael B. Kane, Timothy A. Martin, Asko Noormets, C. Wade Ross, Jason Vogel, and Daniel Markewitz
- Subjects
History ,Polymers and Plastics ,Forestry ,Business and International Management ,Management, Monitoring, Policy and Law ,Industrial and Manufacturing Engineering ,Nature and Landscape Conservation - Published
- 2022
- Full Text
- View/download PDF
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