8,004 results on '"Brown, P R"'
Search Results
252. Comparing functional outcomes in minimally invasive versus open inguinal hernia repair using the army physical fitness test
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Bozzay, J. D., Nelson, D. A., Clifton, D. R., Edgeworth, D. B., Deuster, P. A., Ritchie, J. D., Brown, S. R., and Kaplan, A. J.
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- 2023
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253. Evaluating temporal trends and the impact of surgical subspecialisation on patient outcomes following adhesional small bowel obstruction: a multicentre cohort study
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Green, Lewis, Stienstra, Roxane, Brown, Leo R., McLean, Ross C., Wilson, Michael S. J., Crumley, Andrew B. C., and Hendry, Paul O.
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- 2023
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254. Implementing a Large Scale Interprofessional Poverty Simulation
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Peterson, Dawn Taylor, Hitchcock, Laurel Iverson, Holt, R. Lynn, Brown, Michelle R., and White, Marjorie Lee
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This article shares one university's experience in deploying the Community Action Poverty Simulation (CAPS) for interprofessional learning. Little guidance exists for implementing large-scale interprofessional simulations in higher education, especially with students from various healthcare professions. We will present our efforts implementing CAPS with students from a variety of healthcare majors. First, we provide background about our institution and CAPS in an effort to describe our implementation initiative including learners and facilitators. Second, we cover the adaptation of CAPS to include best practices in simulation. Specifically, we review prebriefing and debriefing, as well as logistics in implementing the poverty simulation as an interprofessional activity at a large university. Finally, we discuss learning and institutional outcomes related to CAPS.
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- 2022
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255. Organizational Contexts Matter: A Multiple Case Study of College-Going Culture and Counselors in Charter and Traditional Public High Schools
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Brown, Danica R.
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High schools are viewed by policymakers, practitioners, and researchers alike as key institutions in facilitating access to college, especially for minoritized students from low-income families. A school-wide strategy for making college accessible is for high schools to establish a college-going culture that normalizes college attendance, elevates it as an attainable postsecondary option, and provides the support and resource structure students need to complete the college application process. Prior research has demonstrated a positive relationship between college-going culture and college enrollment. However, this work has not considered the ways in which various elements combine to make a strong, effective college-going culture. Nor has this research examined the broader policy contexts in which schools and counselors establish a college-going culture. I draw from multiple bodies of literature to examine the ways in which state, district, and school contexts shape college-going culture and counselors' work. I utilize a multiple case study of four Greater New Orleans charter and traditional public high schools. This included semi-structured interviews with school leaders, counselors, teachers, and teacher leaders, observations, and an analysis of data from documents, websites, and social media posts. Louisiana provided a critical context to examine these dynamics as one of the first states to enact policy changes and direct resources toward college readiness and access. I found that the availability of college practices/resources alone did not comprise a strong college-going culture. While all schools had numerous college-going supports, due in large part to Louisiana's policies, schools differed in the strength of their college-going cultures due to the influence of many overlapping organizational factors. Furthermore, counselors' ability to support students with the college process was shaped by the school, district-level, and state contexts determining their roles and the structure, resources, and college counseling norms they implemented in schools. As a result, counselors faced role conflict and role incongruity from the interaction of these contexts. This hindered their ability to provide direct college support to students. Case study findings illustrate the importance of cohesion within and among the various elements of college-going culture and among the contexts shaping school-wide college-going support and counselors' work. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]
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- 2022
256. Words Matter: A Qualitative Content Analysis of Campus Crime Alerts and Considerations for Best Practices
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Wesely, Jennifer K., Brown, Elizabeth R., and Phills, Curtis E.
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Objective: An impediment to an informed discussion of the impact that campus crime alerts have on college campuses is the dearth of research on the topic. This study explores the composition of campus crime alerts and the ways they convey and (re)produce meanings concerning victimization, perpetration, responsibility, and consent. Methods: This study uses an qualitative content analysis of a sample of 3,702 campus crime alerts from 55 universities in the United States. Results: Three themes (Central Actor, Overgendering, and Gratuitous Content) emerge. When the victim is portrayed as the alert subject using a passive voice and the crime is framed within a gendered, editorialized narrative, the alert focus shifts to the victim's rather than the perpetrator's identity and behaviors. Conclusions: The wording of alerts may compromise the safety of the campus community by reinforcing misguided expectations for behavior and shaping misleading perceptions of risk; considerations for best practices are explored.
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- 2022
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257. Comparing Graduate Student Civic Engagement Outcomes in Chile among Private For-Profit and Public Universities
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Brown, Lisa R.
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This mixed-methods research examined civic engagement in Chilean public and private for-profit universities and its representation among study volunteers. Focus groups of graduate students along with in-person interviews with university administrators were conducted. The study also used an online survey, which was completed by 202 participants who had at minimum completed their "título" (first university degree). The mean age of participants was 32.5 with a standard deviation of 7.1 years. The theoretical framework in this study, spiral dynamic theory (SDT), helped guide the research as data was organized by worldview categories. Findings were that civic engagement, broadly conceptualized, was not well integrated into the Chilean higher education mission. Additionally, the key civic engagement study variables were statistically lower among the participants within the for-profit university environments. Participants also evidenced more higher order thinking and individualism at the for-profit universities based on the SDT memetic indicator classifications.
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- 2018
258. Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
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Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian’an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O’Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimäki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietiläinen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josée, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., and Tobin, Martin D.
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- 2023
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259. Quantum Computer Systems for Scientific Discovery
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Alexeev, Yuri, Bacon, Dave, Brown, Kenneth R., Calderbank, Robert, Carr, Lincoln D., Chong, Frederic T., DeMarco, Brian, Englund, Dirk, Farhi, Edward, Fefferman, Bill, Gorshkov, Alexey V., Houck, Andrew, Kim, Jungsang, Kimmel, Shelby, Lange, Michael, Lloyd, Seth, Lukin, Mikhail D., Maslov, Dmitri, Maunz, Peter, Monroe, Christopher, Preskill, John, Roetteler, Martin, Savage, Martin, and Thompson, Jeff
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Quantum Physics ,Condensed Matter - Other Condensed Matter ,High Energy Physics - Lattice ,High Energy Physics - Theory ,Nuclear Theory - Abstract
The great promise of quantum computers comes with the dual challenges of building them and finding their useful applications. We argue that these two challenges should be considered together, by co-designing full-stack quantum computer systems along with their applications in order to hasten their development and potential for scientific discovery. In this context, we identify scientific and community needs, opportunities, a sampling of a few use case studies, and significant challenges for the development of quantum computers for science over the next 2--10 years. This document is written by a community of university, national laboratory, and industrial researchers in the field of Quantum Information Science and Technology, and is based on a summary from a U.S. National Science Foundation workshop on Quantum Computing held on October 21--22, 2019 in Alexandria, VA.
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- 2019
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260. Quantum Simulators: Architectures and Opportunities
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Altman, Ehud, Brown, Kenneth R., Carleo, Giuseppe, Carr, Lincoln D., Demler, Eugene, Chin, Cheng, DeMarco, Brian, Economou, Sophia E., Eriksson, Mark A., Fu, Kai-Mei C., Greiner, Markus, Hazzard, Kaden R. A., Hulet, Randall G., Kollar, Alicia J., Lev, Benjamin L., Lukin, Mikhail D., Ma, Ruichao, Mi, Xiao, Misra, Shashank, Monroe, Christopher, Murch, Kater, Nazario, Zaira, Ni, Kang-Kuen, Potter, Andrew C., Roushan, Pedram, Saffman, Mark, Schleier-Smith, Monika, Siddiqi, Irfan, Simmonds, Raymond, Singh, Meenakshi, Spielman, I. B., Temme, Kristan, Weiss, David S., Vuckovic, Jelena, Vuletic, Vladan, Ye, Jun, and Zwierlein, Martin
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Quantum Physics ,Condensed Matter - Quantum Gases ,Condensed Matter - Strongly Correlated Electrons ,Physics - Computational Physics - Abstract
Quantum simulators are a promising technology on the spectrum of quantum devices from specialized quantum experiments to universal quantum computers. These quantum devices utilize entanglement and many-particle behaviors to explore and solve hard scientific, engineering, and computational problems. Rapid development over the last two decades has produced more than 300 quantum simulators in operation worldwide using a wide variety of experimental platforms. Recent advances in several physical architectures promise a golden age of quantum simulators ranging from highly optimized special purpose simulators to flexible programmable devices. These developments have enabled a convergence of ideas drawn from fundamental physics, computer science, and device engineering. They have strong potential to address problems of societal importance, ranging from understanding vital chemical processes, to enabling the design of new materials with enhanced performance, to solving complex computational problems. It is the position of the community, as represented by participants of the NSF workshop on "Programmable Quantum Simulators," that investment in a national quantum simulator program is a high priority in order to accelerate the progress in this field and to result in the first practical applications of quantum machines. Such a program should address two areas of emphasis: (1) support for creating quantum simulator prototypes usable by the broader scientific community, complementary to the present universal quantum computer effort in industry; and (2) support for fundamental research carried out by a blend of multi-investigator, multi-disciplinary collaborations with resources for quantum simulator software, hardware, and education., Comment: 41 pages -- references and acknowledgments added in v2
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- 2019
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261. Playing Pool with $|\psi \rangle$: from Bouncing Billiards to Quantum Search
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Brown, Adam R.
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Quantum Physics ,High Energy Physics - Theory - Abstract
In "Playing Pool with $\pi$", Galperin invented an extraordinary method to learn the digits of $\pi$ by counting the collisions of billiard balls. Here I demonstrate an exact isomorphism between Galperin's bouncing billiards and Grover's algorithm for quantum search. This provides an illuminating way to visualize Grover's algorithm., Comment: 11 pages, 8 figures, $d$ billiards; v2: minor improvements, as published
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- 2019
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262. The Python's Lunch: geometric obstructions to decoding Hawking radiation
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Brown, Adam R., Gharibyan, Hrant, Penington, Geoff, and Susskind, Leonard
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High Energy Physics - Theory ,General Relativity and Quantum Cosmology ,Quantum Physics - Abstract
According to Harlow and Hayden [arXiv:1301.4504] the task of distilling information out of Hawking radiation appears to be computationally hard despite the fact that the quantum state of the black hole and its radiation is relatively un-complex. We trace this computational difficulty to a geometric obstruction in the Einstein-Rosen bridge connecting the black hole and its radiation. Inspired by tensor network models, we conjecture a precise formula relating the computational hardness of distilling information to geometric properties of the wormhole - specifically to the exponential of the difference in generalized entropies between the two non-minimal quantum extremal surfaces that constitute the obstruction. Due to its shape, we call this obstruction the "Python's Lunch", in analogy to the reptile's postprandial bulge., Comment: 65 pages
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- 2019
263. Fault-tolerant Compass Codes
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Huang, Shilin and Brown, Kenneth R.
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Quantum Physics - Abstract
We study a class of gauge fixings of the Bacon-Shor code at the circuit level, which includes a subfamily of generalized surface codes. We show that for these codes, fault tolerance can be achieved by direct measurements of the stabilizers. By simulating our fault-tolerant scheme under biased noise, we show the possibility of optimizing the performance of the surface code by stretching the bulk stabilizer geometry. To decode the syndrome efficiently and accurately, we generalize the union-find decoder to biased noise models. Our decoder obtains a $0.83\%$ threshold value for the surface code in quadratic time complexity.
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- 2019
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264. Quantum Gravity in the Lab: Teleportation by Size and Traversable Wormholes
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Brown, Adam R., Gharibyan, Hrant, Leichenauer, Stefan, Lin, Henry W., Nezami, Sepehr, Salton, Grant, Susskind, Leonard, Swingle, Brian, and Walter, Michael
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Quantum Physics ,High Energy Physics - Theory - Abstract
With the long-term goal of studying models of quantum gravity in the lab, we propose holographic teleportation protocols that can be readily executed in table-top experiments. These protocols exhibit similar behavior to that seen in the recent traversable wormhole constructions of [1,2]: information that is scrambled into one half of an entangled system will, following a weak coupling between the two halves, unscramble into the other half. We introduce the concept of teleportation by size to capture how the physics of operator-size growth naturally leads to information transmission. The transmission of a signal through a semi-classical holographic wormhole corresponds to a rather special property of the operator-size distribution we call size winding. For more general systems (which may not have a clean emergent geometry), we argue that imperfect size winding is a generalization of the traversable wormhole phenomenon. In addition, a form of signalling continues to function at high temperature and at large times for generic chaotic systems, even though it does not correspond to a signal going through a geometrical wormhole, but rather to an interference effect involving macroscopically different emergent geometries. Finally, we outline implementations feasible with current technology in two experimental platforms: Rydberg atom arrays and trapped ions., Comment: 33 pages, 5 figures. This paper has a companion paper (Part II) by the same authors
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- 2019
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265. Single-ion addressing via trap potential modulation in global optical fields
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Seck, Christopher M., Meier, Adam M., Merrill, J. True, Hayden, Harley T., Sawyer, Brian C., Volin, Curtis E., and Brown, Kenton R.
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Quantum Physics ,Physics - Atomic Physics - Abstract
To date, individual addressing of ion qubits has relied primarily on local Rabi or transition frequency differences between ions created via electromagnetic field spatial gradients or via ion transport operations. Alternatively, it is possible to synthesize arbitrary local one-qubit gates by leveraging local phase differences in a global driving field. Here we report individual addressing of $^{40}$Ca$^+$ ions in a two-ion crystal using axial potential modulation in a global gate laser field. We characterize the resulting gate performance via one-qubit randomized benchmarking, applying different random sequences to each co-trapped ion. We identify the primary error sources and compare the results with single-ion experiments to better understand our experimental limitations. These experiments form a foundation for the universal control of two ions, confined in the same potential well, with a single gate laser beam., Comment: 27 pages, 3 figures
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- 2019
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266. Taylor state merging at SSX: experiment and simulation
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Brown, M. R., Gelber, K. D., and Mebratu, M.
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Physics - Plasma Physics - Abstract
We describe experiments and simulations of dynamical merging with two Taylor state plasmas in the SSX device. Taylor states are formed by magnetized plasma guns at opposite ends of the device. We have performed experiments with Taylor states of either sense of magnetic helicity (right-handed twist or left-handed twist). We present results of both counter-helicity merging (one side left-handed, the other right-handed) and co-helicity merging (both sides left-handed). Experiments show significant ion heating, consistent with magnetic reconnection. Magnetohydrodynamic simulations of these experiments reveal the structure of the final relaxed, merged state., Comment: 12 pages, 8 figures, submitted to MDPI Plasma. arXiv admin note: text overlap with arXiv:1811.07008
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- 2019
267. Logical Performance of 9 Qubit Compass Codes in Ion Traps with Crosstalk Errors
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Debroy, Dripto M., Li, Muyuan, Huang, Shilin, and Brown, Kenneth R.
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Quantum Physics - Abstract
We simulate four quantum error correcting codes under error models inspired by realistic noise sources in near-term ion trap quantum computers: $T_2$ dephasing, gate overrotation, and crosstalk. We use this data to find preferred codes for given error parameters along with logical error biases and a pseudothreshold which compares the physical and logical gate failure rates for a CNOT gate. Using these results we conclude that Bacon-Shor-13 is the most promising near term candidate as long as the impact of crosstalk can be mitigated through other means., Comment: 12 pages, 10 figures
- Published
- 2019
268. A direct measurement of the 17O(a,g)21Ne reaction in inverse kinematics and its impact on heavy element production
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Taggart, M. P., Akers, C., Laird, A. M., Hager, U., Ruiz, C., Hutcheon, D. A., Bentley, M. A., Brown, J. R., Buchmann, L., Chen, A. A., Chen, J., Chipps, K. A., Choplin, A., D'Auria, J. M., Davids, B., Davis, C., Diget, C. Aa., Erikson, L., Fallis, J., Fox, S. P., Frischknecht, U., Fulton, B. R., Galinski, N., Greife, U., Hirschi, R., Howell, D., Martin, L., Mountford, D., Murphy, A. St. J., Ottewell, D., Pignatari, M., Reeve, S., Ruprecht, G., Sjue, S., Veloce, L., and Williams, M.
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Nuclear Experiment - Abstract
During the slow neutron capture process in massive stars, reactions on light elements can both produce and absorb neutrons thereby influencing the final heavy element abundances. At low metallicities, the high neutron capture rate of 16-O can inhibit s-process nucleosynthesis unless the neutrons are recycled via the 17O(a,n)20Ne reaction. The efficiency of this neutron recycling is determined by competition between the 17O(a,n)20Ne and 17O(a,g)21Ne reactions. While some experimental data are available on the former reaction, no data exist for the radiative capture channel at the relevant astrophysical energies. The 17O(a,g)21Ne reaction has been studied directly using the DRAGON recoil separator at the TRIUMF Laboratory. The reaction cross section has been determined at energies between 0.6 and 1.6 MeV Ecm, reaching into the Gamow window for core helium burning for the first time. Resonance strengths for resonances at 0.63, 0.721, 0.81 and 1.122 MeV Ecm have been extracted. The experimentally based reaction rate calculated represents a lower limit, but suggests that significant s-process nucleosynthesis occurs in low metallicity massive stars., Comment: 7 pages, 5 figures
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- 2019
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269. Generating Fault-Tolerant Cluster States from Crystal Structures
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Newman, Michael, de Castro, Leonardo Andreta, and Brown, Kenneth R.
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Quantum Physics - Abstract
Measurement-based quantum computing (MBQC) is a promising alternative to traditional circuit-based quantum computing predicated on the construction and measurement of cluster states. Recent work has demonstrated that MBQC provides a more general framework for fault-tolerance that extends beyond foliated quantum error-correcting codes. We systematically expand on that paradigm, and use combinatorial tiling theory to study and construct new examples of fault-tolerant cluster states derived from crystal structures. Included among these is a robust self-dual cluster state requiring only degree-3 connectivity. We benchmark several of these cluster states in the presence of circuit-level noise, and find a variety of promising candidates whose performance depends on the specifics of the noise model. By eschewing the distinction between data and ancilla, this malleable framework lays a foundation for the development of creative and competitive fault-tolerance schemes beyond conventional error-correcting codes., Comment: 37 pages, edits and expanded descriptions
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- 2019
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270. One-proton and one-neutron knockout reactions from $N = Z = 28$ $^{56}$Ni to the $A = 55$ mirror pair $^{55}$Co and $^{55}$Ni
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Spieker, M., Gade, A., Weisshaar, D., Brown, B. A., Tostevin, J. A., Longfellow, B., Adrich, P., Bazin, D., Bentley, M. A., Brown, J. R., Campbell, C. M., Diget, C. Aa., Elman, B., Glasmacher, T., Hill, M., Pritychenko, B., Ratkiewicz, A., and Rhodes, D.
- Subjects
Nuclear Experiment ,Nuclear Theory - Abstract
We present a high-resolution in-beam $\gamma$-ray spectroscopy study of excited states in the mirror nuclei $^{55}$Co and $^{55}$Ni following one-nucleon knockout from a projectile beam of $^{56}$Ni. The newly determined partial cross sections and the $\gamma$-decay properties of excited states provide a test of state-of-the-art nuclear structure models and probe mirror symmetry in unique ways. A mirror asymmetry for the partial cross sections leading to the two lowest $3/2^-$ states in the $A = 55$ mirror pair was identified as well as a significant difference in the $E1$ decays from the $1/2^+_1$ state to the same two $3/2^-$ states. The mirror asymmetry in the partial cross sections cannot be reconciled with the present shell-model picture or small mixing introduced in a two-state model. The observed mirror asymmetry in the $E1$ decay pattern, however, points at stronger mixing between the two lowest $3/2^-$ states in $^{55}$Co than in its mirror $^{55}$Ni.
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- 2019
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271. A hybrid ion-atom trap with integrated high resolution mass spectrometer
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Jyothi, S, Egodapitiya, Kisra N, Bondurant, Brad, Jia, Zhubing, Pretzsch, Eric, Chiappina, Piero, Shu, Gang, and Brown, Kenneth R
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Physics - Atomic Physics ,Quantum Physics - Abstract
In this article we describe the design, construction and implementation of our ion-atom hybrid system incorporating a high resolution time of flight mass spectrometer (TOFMS). Potassium atoms ($^{39}$K) in a Magneto Optical Trap (MOT) and laser cooled calcium ions ($^{40}$Ca$^+$) in a linear Paul trap are spatially overlapped and the combined trap is integrated with a TOFMS for radial extraction and detection of reaction products. We also present some experimental results showing interactions between $^{39}$K$^+$ and $^{39}$K, $^{40}$Ca$^+$ and $^{39}$K$^+$ as well as $^{40}$Ca$^+$ and $^{39}$K pairs. Finally, we discuss prospects for cooling CaH$^+$ molecular ions in the hybrid ion-atom system.
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- 2019
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272. A Pseudo-Marginal Metropolis-Hastings Algorithm for Estimating Generalized Linear Models in the Presence of Missing Data
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Brown, Taylor R., McMurry, Timothy L., and Langevin, Alexander
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Statistics - Methodology - Abstract
The missing data issue often complicates the task of estimating generalized linear models (GLMs). We describe why the pseudo-marginal Metropolis-Hastings algorithm, used in this setting, is an effective strategy for parameter estimation. This approach requires fewer assumptions, it provides joint inferences on the parameters in the likelihood, the covariate model, and the parameters of the missingness-mechanism, and there is no logical inconsistency of assuming that there are multiple posterior distributions. Moreover, this approach is asymptotically exact, just like most other Markov chain Monte Carlo techniques. We discuss computing strategies, conduct a simulation study demonstrating how standard errors change as a function of percent missingness, and we use our approach on a "real-world" data set to describe how a collection of variables influences the car crash outcomes.
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- 2019
273. Real-time calibration with spectator qubits
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Majumder, Swarnadeep, de Castro, Leonardo Andreta, and Brown, Kenneth R.
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Quantum Physics - Abstract
Accurate control of quantum systems requires precise measurement of the parameters that govern the dynamics, including control fields and interactions with the environment. Parameters will drift in time and experiments interleave protocols that perform parameter estimation with protocols that measure the dynamics of interest. Here we specialize to a system made of qubits where the dynamics correspond to a quantum computation. We propose setting aside some qubits, which we call spectator qubits, to be measured periodically during the computation, to act as probes of the changing experimental and environmental parameters. By using control strategies that minimize the sensitivity of the qubits involved in the computation, we can acquire sufficient information from the spectator qubits to update our estimates of the parameters and improve our control. As a result, we can increase the length of experiment where the dynamics of the data qubits are highly reliable. In particular, we simulate how spectator qubits can keep the error level of operations on data qubits below a $10^{-4}$ threshold in two scenarios involving coherent errors: a classical magnetic field gradient dynamically decoupled with sequences of two or four $\pi$-pulses, and laser beam instability detected via crosstalk with neighboring atoms in an ion trap., Comment: 17 pages, 8 figures, comments welcome
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- 2019
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274. The Differences Between Consecutive Primes. V
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Heath-Brown, D. R.
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Mathematics - Number Theory - Abstract
We show that \[\sum_{\substack{p_n\le x\\ p_{n+1}-p_n\ge\sqrt{p_n}}}(p_{n+1}-p_n)\ll_{\varepsilon} x^{3/5+\varepsilon}\] for any fixed $\varepsilon>0$. This improves a result of Matom\"{a}ki, in which the exponent was $2/3$.
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- 2019
275. Asymptotic Improvements to Quantum Circuits via Qutrits
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Gokhale, Pranav, Baker, Jonathan M., Duckering, Casey, Brown, Natalie C., Brown, Kenneth R., and Chong, Frederic T.
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Quantum Physics ,Computer Science - Emerging Technologies - Abstract
Quantum computation is traditionally expressed in terms of quantum bits, or qubits. In this work, we instead consider three-level qu$trits$. Past work with qutrits has demonstrated only constant factor improvements, owing to the $\log_2(3)$ binary-to-ternary compression factor. We present a novel technique using qutrits to achieve a logarithmic depth (runtime) decomposition of the Generalized Toffoli gate using no ancilla--a significant improvement over linear depth for the best qubit-only equivalent. Our circuit construction also features a 70x improvement in two-qudit gate count over the qubit-only equivalent decomposition. This results in circuit cost reductions for important algorithms like quantum neurons and Grover search. We develop an open-source circuit simulator for qutrits, along with realistic near-term noise models which account for the cost of operating qutrits. Simulation results for these noise models indicate over 90% mean reliability (fidelity) for our circuit construction, versus under 30% for the qubit-only baseline. These results suggest that qutrits offer a promising path towards scaling quantum computation., Comment: In ISCA '19: 46th International Symposium on Computer Architecture, 13 pages, 11 figures
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- 2019
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276. Two-qubit entangling gates within arbitrarily long chains of trapped ions
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Landsman, Kevin A., Wu, Yukai, Leung, Pak Hong, Zhu, Daiwei, Linke, Norbert M., Brown, Kenneth R., Duan, Luming, and Monroe, Christopher R.
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Physics - Atomic Physics - Abstract
Ion trap systems are a leading platform for large scale quantum computers. Trapped ion qubit crystals are fully-connected and reconfigurable, owing to their long range Coulomb interaction that can be modulated with external optical forces. However, the spectral crowding of collective motional modes could pose a challenge to the control of such interactions for large numbers of qubits. Here, we show that high-fidelity quantum gate operations are still possible with very large trapped ion crystals, simplifying the scaling of ion trap quantum computers. To this end, we present analytical work that determines how parallel entangling gates produce a crosstalk error that falls off as the inverse cube of the distance between the pairs. We also show experimental work demonstrating entangling gates on a fully-connected chain of seventeen $^{171}{\rm{Yb}}^{+}$ ions with fidelities as high as $97(1)\%$., Comment: 10 pages, 6 figures
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- 2019
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277. Leakage mitigation for quantum error correction using a mixed qubit scheme
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Brown, Natalie C. and Brown, Kenneth R.
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Quantum Physics - Abstract
Leakage errors take qubits out of the computational subspace and will accumulate if not addressed. A leaked qubit will reduce the effectiveness of quantum error correction protocols due to the cost of implementing leakage reduction circuits and the harm caused by interacting leaked states with qubit states. Ion trap qubits driven by Raman gates have a natural choice between qubits encoded in magnetically insensitive hyperfine states that can leak and qubits encoded in magnetically sensitive Zeeman states of the electron spin that cannot leak. In our previous work, we compared these two qubits in the context of the toric code with a depolarizing leakage error model and found that for magnetic field noise with a standard deviation less than 32 $\mu$G that the $^{174}$Yb$^+$ Zeeman qubit outperforms the $^{171}$Yb$^+$ hyperfine qubit. Here we examine a physically motivated leakage error model based on ions interacting via the Molmer-Sorenson gate. We find that this greatly improves the performance of hyperfine qubits but the Zeeman qubits are more effective for magnetic field noise with a standard deviation less than 10 $\mu$G. At these low magnetic fields, we find that the best choice is a mixed qubit scheme where the hyperfine qubits are the ancilla and the leakage is handled without the need of an additional leakage reduction circuit., Comment: 8 pages, 6 figures, comments welcome
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- 2019
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278. THz Superradiance from a GaAs: ErAs Quantum Dot Array at Room Temperature
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Zhang, W-D., Brown, E. R., Mingardi, A., Mirin, R. P., Jahed, N., and Saeedkia, D.
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Condensed Matter - Mesoscale and Nanoscale Physics - Abstract
We report experimental evidence that an ErAs quantum-dot array in a GaAs matrix under 1550 nm pulsed excitation produces cooperative spontaneous emission-Dicke superradiance-in the terahertz frequency region at room temperature., Comment: 8 pages, 4 figures
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- 2019
279. The Complexity Geometry of a Single Qubit
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Brown, Adam R. and Susskind, Leonard
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High Energy Physics - Theory - Abstract
The computational complexity of a quantum state quantifies how hard it is to make. `Complexity geometry', first proposed by Nielsen, is an approach to defining computational complexity using the tools of differential geometry. Here we demonstrate many of the attractive features of complexity geometry using the example of a single qubit, which turns out to be rich enough to be illustrative but simple enough to be illuminating., Comment: 45 pages, 8 figures, 1 qubit. v2: added extraneous appendix about optimal shapes for tunnels bored through Earth
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- 2019
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280. [Plasma 2020 Decadal] The essential role of multi-point measurements in turbulence investigations: the solar wind beyond single scale and beyond the Taylor Hypothesis
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Matthaeus, W. H., Bandyopadhyay, R., Brown, M. R., Borovsky, J., Carbone, V., Caprioli, D., Chasapis, A., Chhiber, R., Dasso, S., Dmitruk, P., Del Zanna, L., Dmitruk, P. A., Franci, Luca, Gary, S. P., Goldstein, M. L., Gomez, D., Greco, A., Horbury, T. S., Ji, Hantao, Kasper, J. C., Klein, K. G., Landi, S., Li, Hui, Malara, F., Maruca, B. A., Mininni, P., Oughton, Sean, Papini, E., Parashar, T. N., Petrosyan, Arakel, Pouquet, Annick, Retino, A., Roberts, Owen, Ruffolo, David, Servidio, Sergio, Spence, Harlan, Smith, C. W., Stawarz, J. E., TenBarge, Jason, Vasquez1, B. J., Vaivads, Andris, Valentini, F., Velli, Marco, Verdini, A., Verscharen, Daniel, Whittlesey, Phyllis, Wicks, Robert, Bruno, R., and Zimbardo, G.
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Physics - Space Physics ,Astrophysics - Solar and Stellar Astrophysics - Abstract
This paper briefly reviews a number of fundamental measurements that need to be made in order to characterize turbulence in space plasmas such as the solar wind. It has long been known that many of these quantities require simultaneous multipoint measurements to attain a proper characterization that would reveal the fundamental physics of plasma turbulence. The solar wind is an ideal plasma for such an investigation, and it now appears to be technologically feasible to carry out such an investigation, following the pioneering Cluster and MMS missions. Quantities that need to be measured using multipoint measurements include the two-point, two-time second correlation function of velocity, magnetic field and density, and higher order statistical objects such as third and fourth order structure functions. Some details of these requirements are given here, with a eye towards achieving closure on fundamental questions regarding the cascade rate, spectral anisotropy, characteristic coherent structures, intermittency, and dissipation mechanisms that describe plasma turbuelence, as well as its variability with plasma parameters in the solar wind. The motivation for this discussion is the current planning for a proposed Helioswarm mission that would be designed to make these measurements,leading to breakthrough understanding of the physics of space and astrophysical turbulence., Comment: White paper submitted to the PLASMA 2020 Decadal Survey Committee
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- 2019
281. Astro2020 Decadal Science White Paper: Gravitational Wave Survey of Galactic Ultra Compact Binaries
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Littenberg, Tyson B., Breivik, Katelyn, Brown, Warren R., Eracleous, Michael, Hermes, J. J., Holley-Bockelmann, Kelly, Kremer, Kyle, Kupfer, Thomas, and Larson, Shane L.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
Ultra-compact binaries (UCBs) are systems containing compact or degenerate stars with orbital periods less than one hour. Tens of millions of UCBs are predicted to exist within theGalaxy emitting gravitational waves (GWs) at mHz frequencies. Combining GW searches with electromagnetic (EM) surveys like Gaia and LSST will yield a comprehensive, multimessenger catalog of UCBs in the galaxy. Joint EM and GW observations enable measurements of masses, radii, and orbital dynamics far beyond what can be achieved by independent EM or GW studies. GW+EM surveys of UCBs in the galaxy will yield a trove of unique insights into the nature of white dwarfs, the formation of compact objects, dynamical interactions in binaries, and energetic, accretion-driven phenomena like Type Ia superonovae., Comment: 5 pages, 1 figure, submitted to the Astro2020 call for science white papers
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- 2019
282. Handling Leakage with Subsystem Codes
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Brown, Natalie C., Newman, Michael, and Brown, Kenneth R.
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Quantum Physics - Abstract
Leakage is a particularly damaging error that occurs when a qubit state falls out of its two-level computational subspace. Compared to independent depolarizing noise, leaked qubits may produce many more configurations of harmful correlated errors during error-correction. In this work, we investigate different local codes in the low-error regime of a leakage gate error model. When restricting to bare-ancilla extraction, we observe that subsystem codes are good candidates for handling leakage, as their locality can limit damaging correlated errors. As a case study, we compare subspace surface codes to the subsystem surface codes introduced by Bravyi et al. In contrast to depolarizing noise, subsystem surface codes outperform same-distance subspace surface codes below error rates as high as $\lessapprox 7.5 \times 10^{-4}$ while offering better per-qubit distance protection. Furthermore, we show that at low to intermediate distances, Bacon-Shor codes offer better per-qubit error protection against leakage in an ion-trap motivated error model below error rates as high as $\lessapprox 1.2 \times 10^{-3}$. For restricted leakage models, this advantage can be extended to higher distances by relaxing to unverified two-qubit cat state extraction in the surface code. These results highlight an intrinsic benefit of subsystem code locality to error-corrective performance., Comment: 22 pages, comments welcome
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- 2019
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283. A Factor Stochastic Volatility Model with Markov-Switching Panic Regimes
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Brown, Taylor R.
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Statistics - Applications - Abstract
The use of factor stochastic volatility models requires choosing the number of latent factors used to describe the dynamics of the financial returns process; however, empirical evidence suggests that the number and makeup of pertinent factors is time-varying and economically situational. We present a novel factor stochastic volatility model that allows for random subsets of assets to have their members experience non-market-wide panics. These participating assets will experience an increase in their variances and within-group covariances. We also give an estimation algorithm for this model that takes advantage of recent results on Particle Markov chain Monte Carlo techniques.
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- 2019
284. Ground-state energy estimation of the water molecule on a trapped ion quantum computer
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Nam, Yunseong, Chen, Jwo-Sy, Pisenti, Neal C., Wright, Kenneth, Delaney, Conor, Maslov, Dmitri, Brown, Kenneth R., Allen, Stewart, Amini, Jason M., Apisdorf, Joel, Beck, Kristin M., Blinov, Aleksey, Chaplin, Vandiver, Chmielewski, Mika, Collins, Coleman, Debnath, Shantanu, Ducore, Andrew M., Hudek, Kai M., Keesan, Matthew, Kreikemeier, Sarah M., Mizrahi, Jonathan, Solomon, Phil, Williams, Mike, Wong-Campos, Jaime David, Monroe, Christopher, and Kim, Jungsang
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Quantum Physics ,Computer Science - Emerging Technologies - Abstract
Quantum computing leverages the quantum resources of superposition and entanglement to efficiently solve computational problems considered intractable for classical computers. Examples include calculating molecular and nuclear structure, simulating strongly-interacting electron systems, and modeling aspects of material function. While substantial theoretical advances have been made in mapping these problems to quantum algorithms, there remains a large gap between the resource requirements for solving such problems and the capabilities of currently available quantum hardware. Bridging this gap will require a co-design approach, where the expression of algorithms is developed in conjunction with the hardware itself to optimize execution. Here, we describe a scalable co-design framework for solving chemistry problems on a trapped ion quantum computer, and apply it to compute the ground-state energy of the water molecule. The robust operation of the trapped ion quantum computer yields energy estimates with errors approaching the chemical accuracy, which is the target threshold necessary for predicting the rates of chemical reaction dynamics., Comment: 14 pages, 7 figures
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- 2019
285. The DECam Minute Cadence Survey II: 49 Variables but No Planetary Transits of a White Dwarf
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Dame, Kyra, Belardi, Claudia, Kilic, Mukremin, Rest, Armin, Gianninas, A., Barber, Sara, and Brown, Warren R.
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Astrophysics - Solar and Stellar Astrophysics - Abstract
We present minute cadence photometry of 31732 point sources observed in one 3 $deg^{2}$ DECam pointing centred at RA = 09:03:02 and Dec = -04:35:00 over eight consecutive half-nights. We use these data to search for eclipse-like events consistent with a planetary transit of a white dwarf and other sources of stellar variability within the field. We do not find any significant evidence for minute-long transits around our targets, hence we rule out planetary transits around ~370 white dwarfs that should be present in this field. Additionally, we identify 49 variables, including 40 new systems. These include 23 detached or contact stellar binaries, 1 eclipsing white dwarf + M dwarf binary, 16 $\delta$ Scuti, three RR Lyrae, and two ZZ Ceti pulsators. Results from the remaining two fields in our survey will allow us to place more stringent constraints on the frequency of planets orbiting white dwarfs in the habitable zone., Comment: 11 pages, 14 figures, 1 table. Accepted for publication in Monthly Notices of the Royal Astronomical Society Main Journal
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- 2019
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286. Risk factors for grade 3/4 transaminase elevation in patients with chronic lymphocytic leukemia treated with idelalisib
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Brown, Jennifer R, Zelenetz, Andrew, Furman, Richard, Lamanna, Nicole, Mato, Anthony, Montillo, Marco, O’Brien, Susan, Dubowy, Ronald, Gu, Lin, Munugalavadla, Veerendra, Robak, Tadeusz, and Hillmen, Peter
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Antineoplastic Agents ,Humans ,Leukemia ,Lymphocytic ,Chronic ,B-Cell ,Purines ,Quinazolinones ,Risk Factors ,Transaminases ,Clinical Sciences ,Immunology ,Cardiovascular medicine and haematology ,Clinical sciences ,Oncology and carcinogenesis - Published
- 2020
287. STROBE-metagenomics: a STROBE extension statement to guide the reporting of metagenomics studies
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Bharucha, Tehmina, Oeser, Clarissa, Balloux, Francois, Brown, Julianne R, Carbo, Ellen C, Charlett, Andre, Chiu, Charles Y, Claas, Eric CJ, de Goffau, Marcus C, de Vries, Jutte JC, Eloit, Marc, Hopkins, Susan, Huggett, Jim F, MacCannell, Duncan, Morfopoulou, Sofia, Nath, Avindra, O'Sullivan, Denise M, Reoma, Lauren B, Shaw, Liam P, Sidorov, Igor, Simner, Patricia J, Van Tan, Le, Thomson, Emma C, van Dorp, Lucy, Wilson, Michael R, Breuer, Judith, and Field, Nigel
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Biomedical and Clinical Sciences ,Epidemiology ,Clinical Sciences ,Health Sciences ,Medical Microbiology ,Genetics ,Human Genome ,Good Health and Well Being ,Computational Biology ,Humans ,Metagenomics ,Molecular Epidemiology ,Research Design ,Public Health and Health Services ,Microbiology ,Clinical sciences ,Medical microbiology - Abstract
The term metagenomics refers to the use of sequencing methods to simultaneously identify genomic material from all organisms present in a sample, with the advantage of greater taxonomic resolution than culture or other methods. Applications include pathogen detection and discovery, species characterisation, antimicrobial resistance detection, virulence profiling, and study of the microbiome and microecological factors affecting health. However, metagenomics involves complex and multistep processes and there are important technical and methodological challenges that require careful consideration to support valid inference. We co-ordinated a multidisciplinary, international expert group to establish reporting guidelines that address specimen processing, nucleic acid extraction, sequencing platforms, bioinformatics considerations, quality assurance, limits of detection, power and sample size, confirmatory testing, causality criteria, cost, and ethical issues. The guidance recognises that metagenomics research requires pragmatism and caution in interpretation, and that this field is rapidly evolving.
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- 2020
288. Distinct evolutionary paths in chronic lymphocytic leukemia during resistance to the graft-versus-leukemia effect
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Bachireddy, Pavan, Ennis, Christina, Nguyen, Vinhkhang N, Gohil, Satyen H, Clement, Kendell, Shukla, Sachet A, Forman, Juliet, Barkas, Nikolaos, Freeman, Samuel, Bavli, Natalie, Elagina, Liudmila, Leshchiner, Ignaty, Mohammad, Arman W, Mathewson, Nathan D, Keskin, Derin B, Rassenti, Laura Z, Kipps, Thomas J, Brown, Jennifer R, Getz, Gad, Ho, Vincent T, Gnirke, Andreas, Neuberg, Donna, Soiffer, Robert J, Ritz, Jerome, Alyea, Edwin P, Kharchenko, Peter V, and Wu, Catherine J
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Stem Cell Research ,Hematology ,Rare Diseases ,Cancer ,Stem Cell Research - Nonembryonic - Human ,Lymphoma ,Transplantation ,Genetics ,Stem Cell Research - Nonembryonic - Non-Human ,Graft vs Host Disease ,Graft vs Leukemia Effect ,HLA Antigens ,Hematopoietic Stem Cell Transplantation ,Humans ,Leukemia ,Lymphocytic ,Chronic ,B-Cell ,Transplantation ,Homologous ,Biological Sciences ,Medical and Health Sciences - Abstract
Leukemic relapse remains a major barrier to successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aggressive hematologic malignancies. The basis for relapse of advanced lymphoid malignancies remains incompletely understood and may involve escape from the graft-versus-leukemia (GvL) effect. We hypothesized that for patients with chronic lymphocytic leukemia (CLL) treated with allo-HSCT, leukemic cell-intrinsic features influence transplant outcomes by directing the evolutionary trajectories of CLL cells. Integrated genetic, transcriptomic, and epigenetic analyses of CLL cells from 10 patients revealed that the clinical kinetics of post-HSCT relapse are shaped by distinct molecular dynamics. Early relapses after allo-HSCT exhibited notable genetic stability; single CLL cell transcriptional analysis demonstrated a cellular heterogeneity that was static over time. In contrast, CLL cells relapsing late after allo-HSCT displayed notable genetic evolution and evidence of neoantigen depletion, consistent with marked single-cell transcriptional shifts that were unique to each patient. We observed a greater rate of epigenetic change for late relapses not seen in early relapses or relapses after chemotherapy alone, suggesting that the selection pressures of the GvL bottleneck are unlike those imposed by chemotherapy. No selective advantage for human leukocyte antigen (HLA) loss was observed, even when present in pretransplant subpopulations. Gain of stem cell modules was a common signature associated with leukemia relapse regardless of posttransplant relapse kinetics. These data elucidate the biological pathways that underlie GvL resistance and posttransplant relapse.
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- 2020
289. Use of the dapivirine vaginal ring and effect on cervical cytology abnormalities.
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Reddy, Krishnaveni, Kelly, Cliff, Brown, Elizabeth R, Jeenarain, Nitesha, Naidoo, Logashvari, Siva, Samantha, Bekker, Linda-Gail, Nair, Gonasagrie, Makanani, Bonus, Chinula, Lameck, Mgodi, Nyaradzo, Chirenje, Zvavahera, Kiweewa, Flavia Matovu, Marrazzo, Jeanne, Bunge, Katherine, Soto-Torres, Lydia, Piper, Jeanna, Baeten, Jared M, and Palanee-Phillips, Thesla
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Topical Microbicides ,Prevention ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Anti-HIV Agents ,Contraceptive Devices ,Female ,Double-Blind Method ,Female ,HIV Infections ,HIV Seropositivity ,HIV-1 ,Humans ,Pyrimidines ,Vagina ,Young Adult ,cytology ,dapivirine ,preexposure prophylaxis ,vaginal ring ,MTN-020/ASPIRE and MTN-003/VOICE Study Teams ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectiveWe aimed to determine if the dapivirine vaginal ring and the ring device alone (flexible silicone matrix polymer) was associated with the development of cervical cytology abnormalities.DesignSecondary analysis comparing cervical cytology results between two randomized controlled microbicide trials (MTN-020/ASPIRE and MTN-003/VOICE).MethodsData from ASPIRE, a phase III, placebo-controlled trial of the dapivirine vaginal ring, were used in this analysis. Cervical cytology smears were evaluated at baseline and at the final visit with product use. We compared cytology results between women randomized to dapivirine versus placebo vaginal ring. We further assessed for the effect of the vaginal ring device on cervical cytology by comparing results with data from the oral placebo arm of VOICE, a prior HIV-1 prevention trial conducted in a similar population.ResultsCervical cytology results for 2394 women from ASPIRE (1197 per study arm) were used in this analysis; median time between baseline and final visit with product use was 22.1 months. Cytology smear findings were comparable between dapivirine and placebo vaginal ring arms: at final visit, normal: 90.6 versus 91.5%, ASC-US//LSIL: 7.8 versus 7.4%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 1.7 versus 1.1%, P = 0.44. Cytology data from VOICE had findings (normal: 87.8%, ASC-US/LSIL: 9.8%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 2.4%) comparable with that of both dapivirine (P = 0.93) and placebo vaginal ring arms (P = 0.24).ConclusionThese findings indicate that neither use of the dapivirine vaginal ring nor the vaginal ring device alone, over a period of 2 years, is associated with development of cervical cytology abnormalities that could lead to precancerous or cancerous lesions.
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- 2020
290. Evaluation of non-reducing end pathologic glycosaminoglycan detection method for monitoring therapeutic response to enzyme replacement therapy in human mucopolysaccharidosis I
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Vera, Moin U, Le, Steven Q, Victoroff, Alla, Passage, Merry B, Brown, Jillian R, Crawford, Brett E, Polgreen, Lynda E, Chen, Agnes H, and Dickson, Patricia I
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Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,Clinical Research ,Rare Diseases ,Mucopolysaccharidoses (MPS) ,Biomarkers ,Clinical Laboratory Techniques ,Drug Monitoring ,Enzyme Replacement Therapy ,Glycosaminoglycans ,Humans ,Iduronidase ,Mucopolysaccharidosis I ,Mucopolysaccharidosis ,Lysosomal storage disorder ,Enzyme replacement therapy ,Hurler ,Glycosaminoglycan ,Clinical Sciences ,Genetics & Heredity ,Genetics ,Clinical sciences - Abstract
Therapeutic development and monitoring require demonstration of effects on disease phenotype. However, due to the complexity of measuring clinically-relevant effects in rare multisystem diseases, robust biomarkers are essential. For the mucopolysaccharidoses (MPS), the measurement of glycosaminoglycan levels is relevant as glycosaminoglycan accumulation is the primary event that occurs due to reduced lysosomal enzyme activity. Traditional dye-based assays that measure total glycosaminoglycan levels have a high background, due to a normal, baseline glycosaminoglycan content in unaffected individuals. An assay that selectively detects the disease-specific non-reducing ends of heparan sulfate glycosaminoglycans that remain undegraded due to deficiency of a specific enzyme in the catabolic pathway avoids the normal background, increasing sensitivity and specificity. We evaluated glycosaminoglycan content by dye-based and non-reducing end methods using urine, serum, and cerebrospinal fluid from MPS I human samples before and after treatment with intravenous recombinant human alpha-l-iduronidase. We found that both urine total glycosaminoglycans and serum heparan sulfate derived non-reducing end levels were markedly decreased compared to baseline after 26 weeks and 52 weeks of therapy, with a significantly greater percentage reduction in serum non-reducing end (89.8% at 26 weeks and 81.3% at 52 weeks) compared to urine total glycosaminoglycans (68.3% at 26 weeks and 62.4% at 52 weeks, p
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- 2020
291. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.
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Shah, Sonia, Henry, Albert, Roselli, Carolina, Lin, Honghuang, Sveinbjörnsson, Garðar, Fatemifar, Ghazaleh, Hedman, Åsa K, Wilk, Jemma B, Morley, Michael P, Chaffin, Mark D, Helgadottir, Anna, Verweij, Niek, Dehghan, Abbas, Almgren, Peter, Andersson, Charlotte, Aragam, Krishna G, Ärnlöv, Johan, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Brandimarto, Jeffrey, Brown, Michael R, Buckbinder, Leonard, Carey, David J, Chasman, Daniel I, Chen, Xing, Chen, Xu, Chung, Jonathan, Chutkow, William, Cook, James P, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Dörr, Marcus, Dudley, Samuel C, Dunn, Michael E, Engström, Gunnar, Esko, Tõnu, Felix, Stephan B, Finan, Chris, Ford, Ian, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Guðbjartsson, Daníel F, Gutmann, Rebecca, Haggerty, Christopher M, van der Harst, Pim, Hyde, Craig L, Ingelsson, Erik, Jukema, J Wouter, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Køber, Lars, Koekemoer, Andrea, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Margulies, Kenneth B, März, Winfried, Melander, Olle, Mordi, Ify R, Morgan, Thomas, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Niessner, Alexander, Niiranen, Teemu, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin NA, Parry, Helen M, Perola, Markus, Portilla-Fernandez, Eliana, Psaty, Bruce M, Regeneron Genetics Center, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon PR, Rotter, Jerome I, Salo, Perttu, Salomaa, Veikko, van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stender, Steen, and Stott, David J
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Regeneron Genetics Center ,Humans ,Atrial Fibrillation ,Cardiomyopathies ,Microfilament Proteins ,Adaptor Proteins ,Signal Transducing ,Carrier Proteins ,Muscle Proteins ,Risk Factors ,Case-Control Studies ,Ventricular Function ,Left ,Cyclin-Dependent Kinase Inhibitor p21 ,Apoptosis Regulatory Proteins ,Coronary Artery Disease ,Heart Failure ,Genome-Wide Association Study ,Mendelian Randomization Analysis ,Adaptor Proteins ,Signal Transducing ,Ventricular Function ,Left - Abstract
Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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- 2020
292. Genetic loci associated with prevalent and incident myocardial infarction and coronary heart disease in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
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Hahn, Julie, Fu, Yi-Ping, Brown, Michael R, Bis, Joshua C, de Vries, Paul S, Feitosa, Mary F, Yanek, Lisa R, Weiss, Stefan, Giulianini, Franco, Smith, Albert Vernon, Guo, Xiuqing, Bartz, Traci M, Becker, Diane M, Becker, Lewis C, Boerwinkle, Eric, Brody, Jennifer A, Chen, Yii-Der Ida, Franco, Oscar H, Grove, Megan, Harris, Tamara B, Hofman, Albert, Hwang, Shih-Jen, Kral, Brian G, Launer, Lenore J, Markus, Marcello RP, Rice, Kenneth M, Rich, Stephen S, Ridker, Paul M, Rivadeneira, Fernando, Rotter, Jerome I, Sotoodehnia, Nona, Taylor, Kent D, Uitterlinden, André G, Völker, Uwe, Völzke, Henry, Yao, Jie, Chasman, Daniel I, Dörr, Marcus, Gudnason, Vilmundur, Mathias, Rasika A, Post, Wendy, Psaty, Bruce M, Dehghan, Abbas, O’Donnell, Christopher J, and Morrison, Alanna C
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Heart Disease ,Heart Disease - Coronary Heart Disease ,Human Genome ,Aging ,Clinical Research ,Cardiovascular ,2.4 Surveillance and distribution ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Coronary Artery Disease ,Cross-Sectional Studies ,Europe ,Genetic Loci ,Genome-Wide Association Study ,Humans ,Myocardial Infarction ,Polymorphism ,Single Nucleotide ,Prospective Studies ,White People ,General Science & Technology - Abstract
BackgroundGenome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome.Methods and resultsUsing samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event.ConclusionThis study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.
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- 2020
293. Plactic key agreement (insecure?)
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Brown Daniel R. L.
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cryptography ,key exchange ,plactic monoid ,94a60 ,Mathematics ,QA1-939 - Abstract
Plactic key agreement is a new type of cryptographic key agreement that uses Knuth’s multiplication of semistandard tableaux from combinatorial algebra. The security of plactic key agreement relies on the difficulty of some computational problems, particularly the division of semistandard tableaux. Tableau division can be used to find the private key from its public key or to find the shared secret from the two exchanged public keys. Monico found a fast division algorithm, which could be a polynomial time in the length of the tableaux. Monico’s algorithm solved a challenge that had been previously estimated to cost 2128 steps to break, which is an infeasibly large number for any foreseeable computing power on earth. Monico’s algorithm solves this challenge in only a few minutes. Therefore, Monico’s attack likely makes the plactic key agreement insecure. If it were not for Monico’s attack, plactic key agreement with 1,000-byte public keys might perhaps have provided 128-bit security, with a runtime of a millisecond. But Monico’s attack breaks these public keys’ sizes in minutes.
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- 2023
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294. Transition Strengths and Needs of High School Students with Emotional and Behavioral Disorders
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Yeager, Kristopher Hawk, Morgan, Joseph John, Brown, Monica R., Higgins, Kyle, and Jackson, Iesha
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A strengths-based approach to transition assessment and planning can ensure that special education services are person-centered. To better understand the strengths and needs of students with emotional and behavioral disorders (EBD), we compared the perceptions of students and their teachers from three public high schools. A convergent mixed-methods analysis of transition assessments, interviews, and educational documents revealed significant differences between perspectives. On the "Transition Planning Inventory-2," student ratings (n = 8) were higher than teacher ratings (n = 8) on 8 out of 11 domains. Interview transcripts and transition plan documents revealed differences in strengths and needs related to career-related skills, academic subjects and skills, and personal characteristics. Based on these findings, we provide suggestions for further research and implications for practice.
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- 2021
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295. Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants
- Author
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Aragam, Krishna G., Jiang, Tao, Goel, Anuj, Kanoni, Stavroula, Wolford, Brooke N., Atri, Deepak S., Weeks, Elle M., Wang, Minxian, Hindy, George, Zhou, Wei, Grace, Christopher, Roselli, Carolina, Marston, Nicholas A., Kamanu, Frederick K., Surakka, Ida, Venegas, Loreto Muñoz, Sherliker, Paul, Koyama, Satoshi, Ishigaki, Kazuyoshi, Åsvold, Bjørn O., Brown, Michael R., Brumpton, Ben, de Vries, Paul S., Giannakopoulou, Olga, Giardoglou, Panagiota, Gudbjartsson, Daniel F., Güldener, Ulrich, Haider, Syed M. Ijlal, Helgadottir, Anna, Ibrahim, Maysson, Kastrati, Adnan, Kessler, Thorsten, Kyriakou, Theodosios, Konopka, Tomasz, Li, Ling, Ma, Lijiang, Meitinger, Thomas, Mucha, Sören, Munz, Matthias, Murgia, Federico, Nielsen, Jonas B., Nöthen, Markus M., Pang, Shichao, Reinberger, Tobias, Schnitzler, Gavin, Smedley, Damian, Thorleifsson, Gudmar, von Scheidt, Moritz, Ulirsch, Jacob C., Arnar, David O., Burtt, Noël P., Costanzo, Maria C., Flannick, Jason, Ito, Kaoru, Jang, Dong-Keun, Kamatani, Yoichiro, Khera, Amit V., Komuro, Issei, Kullo, Iftikhar J., Lotta, Luca A., Nelson, Christopher P., Roberts, Robert, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Webb, Thomas R., Baras, Aris, Björkegren, Johan L. M., Boerwinkle, Eric, Dedoussis, George, Holm, Hilma, Hveem, Kristian, Melander, Olle, Morrison, Alanna C., Orho-Melander, Marju, Rallidis, Loukianos S., Ruusalepp, Arno, Sabatine, Marc S., Stefansson, Kari, Zalloua, Pierre, Ellinor, Patrick T., Farrall, Martin, Danesh, John, Ruff, Christian T., Finucane, Hilary K., Hopewell, Jemma C., Clarke, Robert, Gupta, Rajat M., Erdmann, Jeanette, Samani, Nilesh J., Schunkert, Heribert, Watkins, Hugh, Willer, Cristen J., Deloukas, Panos, Kathiresan, Sekar, and Butterworth, Adam S.
- Published
- 2022
- Full Text
- View/download PDF
296. Understanding Cancer Cachexia and Its Implications in Upper Gastrointestinal Cancers
- Author
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Brown, Leo R., Laird, Barry J. A., Wigmore, Stephen J., and Skipworth, Richard J. E.
- Published
- 2022
- Full Text
- View/download PDF
297. Treatment of recurrent rectal prolapse after a laparoscopic ventral mesh rectopexy
- Author
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Brown, S. R., Pearson, K., Hainsworth, A., and Williams, A.
- Published
- 2022
- Full Text
- View/download PDF
298. Stepped-wedge randomized controlled trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation
- Author
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Grossi, U., Lacy-Colson, J., Brown, S. R., Cross, S., Eldridge, S., Jordan, M., Mason, J., Norton, C., Scott, S. M., Stevens, N., Taheri, S., and Knowles, C. H.
- Published
- 2022
- Full Text
- View/download PDF
299. Passive Treatment of Circumneutral Mine Drainage from the St. Louis Mine Tunnel, Rico CO: Part 3—Horizontal Wetlands Treatment Train Pilot Study
- Author
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Sobolewski, Andre B., Riese, Arthur C., Moore, Terry J., and Brown, Anthony R.
- Published
- 2022
- Full Text
- View/download PDF
300. Passive Treatment of Circumneutral Mine Drainage from the St. Louis Mine Tunnel, Rico CO: Part 2—Vertical Biotreatment Train Pilot Study
- Author
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Dean, Daniel M., Fricke, James R., Riese, Arthur C., Moore, Terry J., and Brown, Anthony R.
- Published
- 2022
- Full Text
- View/download PDF
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