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1. Synthetic exendin-4 disrupts responding to reward predictive incentive cues in male rats

Author

Ken T. Wakabayashi, Ajay N. Baindur, Malte Feja, Mauricio Suarez, Karie Chen, Kimberly Bernosky-Smith, and Caroline E. Bass

Subjects
glucagon-like peptide-1, sucrose, incentive salience, pharmacokinetics, effective dose, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Synthetic exendin-4 (EX4, exenatide), is a GLP-1 receptor agonist used clinically to treat glycemia in Type-2 diabetes mellitus. EX4 also promotes weight loss and alters food reward-seeking behaviors in part due to activation of GLP-1 receptors in the mesolimbic dopamine system. Evidence suggests that GLP-1 receptor activity can directly attenuate cue-induced reward seeking. Here, we tested the effects of EX4 (0.6, 1.2, and 2.4 μg/kg, i.p.) on incentive cue (IC) responding, using a task where rats emit a nosepoke response during an intermittent reward-predictive IC to obtain a sucrose reward. EX4 dose-dependently attenuated responding to ICs and increased the latencies to respond to the IC and enter the sucrose reward cup. Moreover, EX4 dose-dependently decreased the total number of active port nosepokes for every cue presented. There was no effect of EX4 on the number of reward cup entries per reward earned, a related reward-seeking metric with similar locomotor demand. There was a dose-dependent interaction between the EX4 dose and session time on the responding to ICs and nosepoke response latency. The interaction indicated that effects of EX4 at the beginning and end of the session differed by the dose of EX4, suggesting dose-dependent pharmacokinetic effects. EX4 had no effect on free sucrose consumption behavior (i.e., total volume consumed, bout size, number of bouts) within the range of total sucrose volumes obtainable during the IC task (~3.5 ml). However, when rats were given unrestricted access for 1 h, where rats obtained much larger total volumes of sucrose (~30 ml), we observed some dose-dependent EX4 effects on drinking behavior, including decreases in total volume consumed. Together, these findings suggest that activation of the GLP-1 receptor modulates the incentive properties of cues attributed with motivational significance.

Published
2024
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2. Mobilization of endocannabinoids by midbrain dopamine neurons is required for the encoding of reward prediction

Author

Miguel Á. Luján, Dan P. Covey, Reana Young-Morrison, LanYuan Zhang, Andrew Kim, Fiorella Morgado, Sachin Patel, Caroline E. Bass, Carlos Paladini, and Joseph F. Cheer

Subjects
Science
Abstract

Abstract Brain levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) shape motivated behavior and nucleus accumbens (NAc) dopamine release. However, it is not clear whether mobilization of 2-AG specifically from midbrain dopamine neurons is necessary for dopaminergic responses to external stimuli predicting forthcoming reward. Here, we use a viral-genetic strategy to prevent the expression of the 2-AG-synthesizing enzyme diacylglycerol lipase α (DGLα) from ventral tegmental area (VTA) dopamine cells in adult mice. We find that DGLα deletion from VTA dopamine neurons prevents depolarization-induced suppression of excitation (DSE), a form of 2-AG-mediated synaptic plasticity, in dopamine neurons. DGLα deletion also decreases effortful, cue-driven reward-seeking but has no effect on non-cued or low-effort operant tasks and other behaviors. Moreover, dopamine recording in the NAc reveals that deletion of DGLα impairs the transfer of accumbal dopamine signaling from a reward to its earliest predictors. These results demonstrate that 2-AG mobilization from VTA dopamine neurons is a necessary step for the generation of dopamine-based predictive associations that are required to direct and energize reward-oriented behavior.

Published
2023
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3. Enhanced diffusion bonding of alloy 617 using electric field-assisted sintering

Author

Xinchang Zhang, Michael D. McMurtrey, Ryann E. Bass, Tate Patterson, Ninad Mohale, Thomas M. Lillo, and Jorgen F. Rufner

Subjects
Diffusion bonding, Electric-field-assisted sintering, Hot pressing, Alloy 617, Compact heat exchangers, Mining engineering. Metallurgy, TN1-997
Abstract

The development of compact heat exchangers (CHXs) has gained increasing interest in many industries owing to their high thermal efficiency and reduced size. Diffusion bonding (DB) is an advantageous technique for fabricating CHXs. Alloy 617 is a candidate for manufacturing CHXs for high-temperature advanced nuclear reactors due to its elevated-temperature properties. Previous endeavors in DB of Alloy 617 were conducted by hot pressing (HP), which reported precipitates at the diffusion-bond interface, limited grain boundary (GB) migration, and significantly reduced high-temperature mechanical properties. To overcome these challenges, this study investigated DB of Alloy 617 using electric field-assisted sintering (EFAS). Stacks composed of three sheets were bonded with EFAS using different temperatures, pressures, and hold times. DB using HP as the zero-current analog of EFAS was also performed for comparison. The result shows that Cr- and Mo-rich precipitates were formed at the interface of the hot-pressed samples. The electric current and temperature in EFAS play a significant role in precipitation and GB migration. The electric current coupled with correct temperatures can effectively prevent precipitate formation at the interface and achieve excellent GB migration. Nanoscale Al-rich oxide was formed at the interface of the samples made by both HP and EFAS, but grain boundaries can ignore the nanoscale Al-oxide and migrate across the interface. The temperature, pressure, and hold time also affected diffusion. The temperature is a prerequisite for a successful GB migration, and GB migration can be enhanced by increasing pressure and hold time.

Published
2023
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4. Assembly of an inexpensive rat jugular catheter button based on a split-septum needleless intravenous system

Author

Mauricio Suarez, Elizabeth J. Cantrell, Ken T. Wakabayashi, and Caroline E. Bass

Subjects
Self-administration, Jugular catheter, Cost effective, Surgery, Sterilize, In-house construction, Science
Abstract

Rat intravenous self-administration is a widely-used animal model in the study of substance use disorders. Rats are tethered to a drug delivery system usually through a port or button that interfaces the drug delivery system with a chronic indwelling jugular vein catheter. These buttons can be purchased commercially but are costly, presenting a significant economic barrier for many researchers. Many researchers manufacture buttons in-house from a combination of individual custom made and commercially available components, resulting in large variation in terms of how the animals are handled and the longevity of catheter patency. We have developed a jugular catheter button that uses a split septum port to provide snap-on entry of a blunt cannula allowing for quick and easy attachment of the i.v. tubing. The port is constructed from commercially available split septum ports, surgical mesh and small metal cannula. The system is “needleless” which decreases the risk of infection and improves safety. The split-septum buttons are easily sterilized in-house adding to the reliability and decreases in the risk of infection. We have used this easily constructed, and inexpensive button for i.v. self-administration experiments in which 80 % of the rats maintained patency for a minimum of 35 days. • Inexpensive method to construct a self-administration backport button. • Utilizes inexpensive components already found in a research laboratory or commercially available. • Can be sterilized in-house without degrading glue or components.

Published
2023
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5. Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes

Author

Lindsay E. Bass and Rachel H. Bonami

Subjects
type 1 diabetes, B lymphocytes, B cell receptor, T lymphocytes, insulin, autoantigen, Immunologic diseases. Allergy, RC581-607
Abstract

Islet autoantibodies predict type 1 diabetes (T1D) but can be transient in murine and human T1D and are not thought to be directly pathogenic. Rather, these autoantibodies signal B cell activity as antigen-presenting cells (APCs) that present islet autoantigen to diabetogenic T cells to promote T1D pathogenesis. Disrupting B cell APC function prevents T1D in mouse models and has shown promise in clinical trials. Autoantigen-specific B cells thus hold potential as sophisticated T1D biomarkers and therapeutic targets. B cell receptor (BCR) somatic hypermutation is a mechanism by which B cells increase affinity for islet autoantigen. High-affinity B and T cell responses are selected in protective immune responses, but immune tolerance mechanisms are known to censor highly autoreactive clones in autoimmunity, including T1D. Thus, different selection rules often apply to autoimmune disease settings (as opposed to protective host immunity), where different autoantigen affinity ceilings are tolerated based on variations in host genetics and environment. This review will explore what is currently known regarding B cell signaling, selection, and interaction with T cells to promote T1D pathogenesis.

Published
2024
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6. Hypocretin / Orexin Receptor 1 Knockdown in GABA or Dopamine Neurons in the Ventral Tegmental Area Differentially Impact Mesolimbic Dopamine and Motivation for Cocaine

Author

Emily M. Black, Shanna B. Samels, Wei Xu, Jessica R. Barson, Caroline E. Bass, Sandhya Kortagere, and Rodrigo A. España

Subjects
Addiction, Voltammetry, Mesolimbic, Motivation, Nucleus accumbens, mRNA, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

The hypocretins/orexins (HCRT) have been demonstrated to influence motivation for cocaine through actions on dopamine (DA) transmission. Pharmacological or genetic disruption of the hypocretin receptor 1 (Hcrtr1) reduces cocaine self-administration, blocks reinstatement of cocaine seeking, and decreases conditioned place preference for cocaine. These effects are likely mediated through actions in the ventral tegmental area (VTA) and resulting alterations in DA transmission. For example, HCRT drives VTA DA neuron activity and enhances the effects of cocaine on DA transmission, while disrupting Hcrtr1 attenuates DA responses to cocaine. These findings have led to the perspective that HCRT exerts its effects through Hcrtr1 actions in VTA DA neurons. However, this assumption is complicated by the observation that Hcrtr1 are present on both DA and GABA neurons in the VTA and HCRT drives the activity of both neuronal populations. To address this issue, we selectively knocked down Hcrtr1 on either DA or GABA neurons in the VTA and examined alterations in DA transmission and cocaine self-administration in female and male rats. We found that Hcrtr1 knockdown in DA neurons decreased DA responses to cocaine, increased days to acquire cocaine self-administration, and reduced motivation for cocaine. Although, Hcrtr1 knockdown in GABA neurons enhanced DA responses to cocaine, this manipulation did not affect cocaine self-administration. These observations indicate that while Hcrtr1 on DA versus GABA neurons exert opposing effects on DA transmission, only Hcrtr1 on DA neurons affected acquisition or motivation for cocaine – suggesting a complex interplay between DA transmission and behavior.

Published
2023
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7. DIII-D research to provide solutions for ITER and fusion energy

Author

C.T. Holcomb, for the DIII-D Team:, J. Abbate, A. Abe, A. Abrams, P. Adebayo-Ige, S. Agabian, S. Ahmed, N. Aiba, N. Akcay, T. Akiyama, R. Albosta, P. Aleynikov, S. Allen, H. Anand, J. Anderson, Y. Andrew, M. Ashburn, A. Ashourvan, M. Austin, G. Avdeeva, D. Ayala, M. Ayub, E. Bagdy, S. Banerjee, K. Barada, L. Bardoczi, O. Bardsley, J. Barr, E. Bass, A. Battey, Z. Bayler, L. Baylor, T. Bechtel, M. Beidler, E. Belli, T. Benedett, Z. Bergstrom, M. Berkel, T. Bernard, N. Bertelli, R. Bielajew, G. Bodner, J. Boedo, R. Boivin, T. Bolzonella, P. Bonoli, A. Bortolon, S. Bose, M. Boyer, W. Boyes, L. Bradley, R. Brambila, A. Braun, D. Brennan, S. Bringuier, L. Brodsky, M. Brookman, J. Brooks, D. Brower, W. Brown, J. Buck, S. Buczek, D. Burgess, M. Burke, K. Burrell, J. Butt, R. Buttery, I. Bykov, P. Byrne, A. Cacheris, K. Callahan, J. Callen, D. Campbell, J. Candy, J. Canik, L. Cappelli, T. Carlstrom, R. Carr, W. Carrig, B. Carter, T. Carter, I. Carvalho, W. Cary, L. Casali, L. Ceelen, M. Cengher, M. Cha, R. Chaban, V. Chan, B. Chapman, I. Char, J. Chen, R. Chen, X. Chen, Y. Chen, J. Chiriboga, E. Cho, G. Choi, W. Choi, H. Choudhury, S. Chowdhury, C. Chrystal, Y. Chung, R. Churchill, R. Clark, M. Clement, J. Coburn, S. Coda, R. Coffee, C. Collins, J. Colmenares-Fernandez, W. Conlin, R. Coon, T. Cote, A. Creely, N. Crocker, C. Crowe, B. Crowley, T. Crowley, M. Curie, D. Curreli, A. Dal Molin, J. Damba, E. Dart, A. Dautt-Silva, K. Davda, A. De, N. de Boucaud, Y. de Jong, P. DE VRIES, A. de-Villeroche, G. DeGrandchamp, J. deGrassie, D. Demers, S. Denk, E. DeShazer, S. Di Genova, A. Diallo, A. Dimits, R. Ding, S. Ding, D. Donovan, X. Du, J. Dunsmore, A. Dupuy, J. Duran, A. Dvorak, F. Effenberg, N. Eidietis, D. Elder, D. Eldon, Y. Elsey, D. Ennis, K. Erickson, D. Ernst, M. Fajardo, H. Farre-Kaga, M. Fenstermacher, N. Ferraro, J. Ferron, A. Feyrer, P. Fimognari, R. Finden, D. Finkenthal, R. Fitzpatrick, S. Flanagan, B. Ford, W. Fox, S. Freiberger, L. Fu, K. Gage, V. Gajaraj, I. Garcia, F. Garcia, A. Garcia, M. Garcia Munoz, D. Garnier, A. Garofalo, A. Gattuso, B. Geiger, K. Gentle, Y. Ghai, K. Gill, F. Glass, P. Gohil, X. Gong, J. Gonzalez-Martin, Y. Gorelov, V. Graber, R. Granetz, C. Gray, C. Greenfield, B. Grierson, R. Groebner, W. Grosnickle, M. Groth, S. Gu, H. Guo, J. Guterl, W. Guttenfelder, R. Hager, S. Hahn, M. Halfmoon, J. Hall, V. Hall-Chen, F. Halpern, G. Hammett, X. Han, C. Hansen, E. Hansen, J. Hanson, M. Hanson, A. Harris, R. Harvey, S. Haskey, D. Hatch, W. Hayashi, A. Hayes, W. Heidbrink, J. Herfindal, J. Hicok, E. Hinson, T. Hisakado, C. Holcomb, C. Holland, L. Holland, E. Hollmann, A. Holm, I. Holmes, K. Holtrop, R. Hong, R. Hood, L. Horvath, S. Houshmandyar, N. Howard, E. Howell, W. Hu, Y. Hu, Q. Hu, Y. Huang, J. Huang, A. Huang, A. Hubbard, J. Hughes, D. Humphreys, J. Hurtado, A. Hyatt, K. Imada, V. Izzo, A. Jalalvand, S. Jardin, A. Jarvinen, Y. Jeon, H. Ji, X. Jian, L. Jian, Y. Jiang, C. Johnson, J. Johnson, M. Jones, S. Joung, P. Jouzdani, E. Jung, E. Kallenberg, R. Kalling, D. Kaplan, A. Kaptanoglu, D. Kellman, J. Kennedy, F. Khabanov, J. Kim, H. Kim, E. Kim, S. Kim, K. Kim, C. Kim, T. Kim, J. King, A. Kinsey, D. Kirk, D. Klasing, A. Kleiner, M. Knolker, M. Kochan, B. Koel, J. Koenders, M. Koepke, R. Kolasinski, E. Kolemen, E. Kostadinova, M. Kostuk, G. Kramer, R. Kube, N. Kumar, R. La Haye, F. Laggner, C. Lahban, H. Lan, R. Landry, R. Lantsov, L. Lao, C. Lasnier, C. Lau, R. Leccacorvi, J. Leddy, M. Lee, S. Lee, K. Lee, R. Lee, M. Lehnen, A. Leonard, E. Leppink, M. LeSher, J. Lestz, J. Leuer, N. Leuthold, G. Li, X. Li, Y. Li, L. Li, N. Li, Z. Li, D. Lin, Z. Lin, Y. Lin, E. Linsenmayer, J. Liu, D. Liu, C. Liu, Z. Liu, Y. Liu, A. Loarte-Prieto, S. Loch, L. LoDestro, N. Logan, J. Lohr, J. Lore, U. Losada Rodriguez, J. Loughran, M. Lowell, T. Luce, N. Luhmann, P. Lunia, R. Lunsford, L. Lupin-Jimenez, A. Lvovskiy, B. Lyons, X. Ma, J. MacDonald, T. Macwan, R. Maingi, M. Major, L. Malhotra, M. Margo, C. Marini, A. Marinoni, A. Maris, E. Martin, J. Mateja, R. Mattes, R. Maurizio, D. Mauzey, L. McAllister, G. McArdle, J. McClenaghan, K. McCollam, G. McKee, K. McLaughlin, A. McLean, V. Mehta, E. Meier, S. Meitner, J. Menard, O. Meneghini, G. Merlo, S. Messer, W. Meyer, C. Michael, D. Miller, M. Miller, J. Mitchell, E. Mitra, C. Moeller, M. Mohamed, S. Molesworth, K. Montes, S. Mordijck, S. Morosohk, A. Moser, D. Mueller, S. Munaretto, C. Murphy, C. Muscatello, R. Myers, A. Nagy, D. Nath, M. Navarro, R. Nazikian, T. Neiser, A. Nelson, P. Nesbet, F. Nespoli, P. Nguyen, D. Nguyen, R. Nguyen, J. Nichols, M. Nocente, L. Nuckols, R. Nygren, T. Odstrcil, M. Okabayashi, E. Olofsson, D. Orlov, D. Orozco, N. Osborne, T. Osborne, F. OShea, D. Pace, D. Packard, A. Pajares Martinez, C. Pakosta, C. Pan, M. Pandya, D. Panici, A. Pankin, Y. Park, J. Park, C. Parker, S. Parker, P. Parks, M. Parsons, S. Paruchuri, C. Paz-Soldan, T. Pederson, W. Peebles, B. Penaflor, E. Perez, L. Periasamy, R. Perillo, C. Petty, M. Pharr, D. Pierce, C. Pierren, S. Pierson, A. Pigarov, L. Pigatto, D. Piglowski, S. Pinches, R. Pinsker, R. Pitts, J. Pizzo, M. Podesta, Z. Popovic, M. Porkolab, Q. Pratt, G. Prechel, I. Pusztai, P. Puthan-Naduvakkate, J. Qian, X. Qin, O. Ra, T. Raines, K. Rakers, K. Rath, J. Rauch, C. Rea, R. Reed, A. Reiman, M. Reinke, R. Reksoatmodjo, Q. Ren, J. Ren, Y. Ren, M. Rensink, T. Rhodes, N. Richner, J. Ridzon, G. Riggs, J. Riquezes, P. Rodriguez Fernandez, T. Rognlien, G. Ronchi, L. Rondini, R. Rosati, A. Rosenthal, M. Ross, J. Rost, A. Rothstein, J. Roveto, J. Ruane, D. Rudakov, R. Rupani, G. Rutherford, S. Sabbagh, J. Sachdev, N. Sadeghi, A. Salmi, F. Salvador, B. Sammuli, C. Samuell, A. Sandorfi, C. Sang, D. Santa, J. Sarff, O. Sauter, H. Savelli, C. Schaefer, H. Schamis, J. Schellpfeffer, D. Schissel, L. Schmitz, O. Schmitz, P. Schroeder, K. Schultz, E. Schuster, F. Sciortino, F. Scotti, J. Scoville, A. Seltzman, J. Seo, J. Serrano, I. Sfiligoi, M. Shafer, R. Shapov, H. Shen, N. Shi, D. Shiraki, B. Short, R. Shousha, H. Si, C. Sierra, G. Sinclair, P. Sinha, G. Sips, C. Skinner, T. Slendebroek, J. Slief, R. Smirnov, S. Smith, D. Smith, G. Snoep, P. Snyder, W. Solomon, X. Song, A. Sontag, V. Soukhanovskii, D. Spong, J. Squire, G. Staebler, L. Stagner, T. Stange, P. Stangeby, E. Starling, S. Stewart, T. Stoltzfus-Dueck, S. Storment, E. Strait, D. Su, L. Sugiyama, P. Sun, Y. Sun, X. Sun, C. Sung, W. Suttrop, Y. Suzuki, R. Sweeney, B. Taczak, Y. Takemura, S. Tang, W. Tang, G. Tardini, D. Taussig, K. Teixeira, K. Thackston, D. Thomas, K. Thome, Y. Tinguely, M. Tobin, J. Tooker, A. Torrezan de Sousa, P. Traverso, G. Trevisan, E. Trier, D. Truong, C. Tsui, F. Turco, A. Turnbull, L. Turner, E. Unterberg, B. Van Compernolle, R. van Kampen, M. Van Zeeland, B. Victor, R. Vieira, E. Viezzer, S. Vincena, D. Vollmer, J. Wai, M. Walker, R. Waltz, W. Wampler, L. Wang, Y. Wang, H. Wang, Z. Wang, G. Wang, A. Wang, J. Watkins, M. Watkins, T. Watts, L. Webber, K. Weber, W. Wehner, X. Wei, D. Weisberg, A. Welander, A. Welsh, A. White, R. Wilcox, G. Wilkie, T. Wilks, M. Willensdorfer, H. Wilson, A. Wingen, M. Wu, D. Wu, S. Wukitch, J. Xia, R. Xie, Z. Xing, G. Xu, X. Xu, Z. Yan, X. Yang, L. Yang, S. Yang, J. Yang, M. Yoo, G. YU, J. Yu, A. Zalzali, A. Zamengo, V. Zamkovska, S. Zamperini, K. Zarrabi, E. Zeger, K. Zeller, L. Zeng, X. Zhang, J. Zhang, B. Zhang, B. Zhao, C. Zhao, Y. Zheng, Y. Zhu, J. Zhu, J. Ziegel, J. Zimmerman, and C. Zuniga

Subjects
DIII-D, tokamak, overview, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

The DIII-D tokamak has elucidated crucial physics and developed projectable solutions for ITER and fusion power plants in the key areas of core performance, boundary heat and particle transport, and integrated scenario operation, with closing the core-edge integration knowledge gap being the overarching mission. New experimental validation of high-fidelity, multi-channel, non-linear gyrokinetic turbulent transport models for ITER provides strong confidence it will achieve Q ⩾ 10 operation. Experiments identify options for easing H-mode access in hydrogen, and give new insight into the isotopic dependence of transport and confinement. Analysis of 2,1 islands in unoptimized low-torque IBS demonstration discharges suggests their onset time occurs randomly in the constant β phase, most often triggered by non-linear 3-wave coupling, thus identifying an NTM seeding mechanism to avoid. Pure deuterium SPI for disruption mitigation is shown to provide favorable slow cooling, but poor core assimilation, suggesting paths for improved SPI on ITER. At the boundary, measured neutral density and ionization source fluxes are strongly poloidally asymmetric, implying a 2D treatment is needed to model pedestal fuelling. Detailed measurements of pedestal and SOL quantities and impurity charge state radiation in detached divertors has validated edge fluid modelling and new self-consistent ‘pedestal-to-divertor’ integrated modeling that can be used to optimize reactors. New feedback adaptive ELM control minimizes confinement reduction, and RMP ELM suppression with sustained high core performance was obtained for the first time with the outer strike point in a W-coated, compact and unpumped small-angle slot divertor. Advances have been made in integrated operational scenarios for ITER and power plants. Wide pedestal intrinsically ELM-free QH-modes are produced with more reactor-relevant conditions, Low torque IBS with W-equivalent radiators can exhibit predator-prey oscillations in T _e and radiation which need control. High- β _P scenarios with q _min > 2, q _95 –7.9, β _N > 4, β _T –3.3% and H _98y2 > 1.5 are sustained with high density ( $\bar n$ = 7E19 m ^−3 , f _G –1) for 6 τ _E , improving confidence in steady-state tokamak reactors. Diverted NT plasmas achieve high core performance with a non-ELMing edge, offering a possible highly attractive core-edge integration solution for reactors.

Published
2024
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8. Isotope impact on Alfvén eigenmodes and fast ion transport in DIII-D

Author

M.A. Van Zeeland, E. Bass, X.D. Du, W.W. Heidbrink, C. Chrystal, C. Crocker, G. DeGrandchamp, S. Haskey, D. Liu, J. Gonzalez-Martin, K.E. Thome, G. Yu, and Y. Zhu

Subjects
fast ions, Alfvén eigenmodes, energetic particles, tokamaks, DIII-D tokamak, isotopes, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Measurements of beam driven Alfvén Eigenmode (AE) activity in matched deuterium (D) and hydrogen (H) DIII-D plasmas show a dramatic difference in unstable mode activity and fast ion transport for a given injected beam power. The dependence of the unstable AE spectrum in reversed magnetic shear plasmas on beam and thermal species is investigated in the current ramp by varying beam power in a sequence of discharges for fixed thermal and beam species at fixed density. In general, a spectrum of Reversed Shear Alfvén Eigenmodes (RSAEs) and Toroidal Alfvén Eigenmodes (TAEs) are driven unstable with sub-Alfvénic D beam injection while primarily only RSAEs are driven unstable for the H beam cases investigated. Further, for a given beam power, the driven AE amplitude is always reduced with H beams relative to D and for H thermal plasma relative to pure D or mixed D/H plasmas. Estimates of the fast ion stored energy combined with modeling using the hybrid kinetic-MHD code MEGA indicate that the dominant mechanism contributing to the difference between H and D beam drive is the faster classical slowing down of H beam ions relative to D and the resultant lower beam ion pressure. Calculations of the AE induced stored energy deficits using the reduced critical gradient model TGLFEP show quantitative agreement with the observed dependencies on injected power, isotope and minimum safety factor.

Published
2024
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9. Who Votes among Asian American Ethnic Subgroups?

Author

Haifan Xiao and Loretta E. Bass

Subjects
Social Sciences, Sociology (General), HM401-1281
Abstract

The authors address the gap in what is known about voting among Asian American ethnic subgroups using National Asian American Survey 2016 Post-Election Survey data to investigate the propensity to vote in the 2016 presidential election across two samples: registered Asian Americans and registered naturalized Asian Americans. The authors use logistic regressions to examine voting behavior across 10 Asian ethnic subgroups for the first time. Across both samples of Asian Americans and naturalized Asian Americans, Chinese Americans demonstrate a lower propensity to vote than most other Asian ethnic subgroups, while Asian Indian and Bangladeshi Americans demonstrate a higher propensity to vote. Among all Asian Americans, being female, being older, and having more education all pattern higher rates of reported voting in the 2016 presidential election, while for naturalized Asians, time in the United States and higher levels of education are associated with a higher likelihood of voting in the 2016 presidential election.

Published
2021
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10. ATM Regulation of the Cohesin Complex Is Required for Repression of DNA Replication and Transcription in the Vicinity of DNA Double-Strand Breaks

Author

Thomas E. Bass, Donald E. Fleenor, Paige E. Burrell, and Michael B. Kastan

Subjects
Cancer Research, Oncology, Molecular Biology
Abstract

Ataxia-telangiectasia mutated (ATM) is an apical regulator of responses to DNA double-strand breaks (DSB). Using two complementary unbiased proteomic screens, we identified the cohesin complex proteins PDS5A, PDS5B, RAD21, NIPBL, and WAPL as apparent novel ATM interactors and substrates. ATM-dependent phosphorylation of PDS5A on Ser1278 following treatment with ionizing radiation is required for optimal cell survival, cell-cycle checkpoint activation, and chromosomal stability. Using a system that introduces site-specific DNA breaks, we found that ATM phosphorylation of cohesin proteins SMC1A, SMC3, and PDS5A are all required for repression of both RNA transcription and DNA replication within the vicinity of a DSB, the latter insight based on development of a novel localized S-phase cell-cycle checkpoint assay. These findings highlight the significance of interactions between ATM and cohesin in the regulation of DNA metabolic processes by altering the chromatin environment surrounding a DSB.Implications:Multiple members of the cohesin complex are involved in the regulation of DNA replication and transcription in the vicinity of DNA double-strand breaks and their role(s) are regulated by the ATM kinase.

Published
2022

11. Which men should undergo non-targeted systematic sampling in an mpMRI-targeted pathway – an analysis from 1,719 pre-biopsy mpMRI cases?

Author

M.J. Connor, D. Eldred-Evans, F. Hosking-Jervis, E. Bass, D. Reddy, M. Bertoncelli Tanaka, H. Bhola-Stewart, W. Maynard, C. Khoo, T.T. Shah, J. Lee, D. Sri, L. Powell, S. Ahmad, M. Noureldin, S. Joshi, E. Pegers, K. Wong, H. Tam, D. Hrouda, M. Winkler, S. Gordon, H. Qazi, and H.U. Ahmed

Subjects
Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2020
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12. Indeterminate mpMRI lesions: Evaluating the optimal PSA density threshold for prostate biopsy

Author

D.T. Reddy, D. Eldred-Evans, M.J. Connor, F. Hosking-Jervis, M. Bertoncelli-Tanaka, H. Bhola-Stewart, W. Maynard, C. Khoo, T.T. Shah, E. Bass, J. Lee, D. Sri, L. Powell, S. Ahmad, M. Noureldin, S. Joshi, E. Pegers, K. Wong, H. Tam, D. Hrouda, M. Winkler, S. Gordon, H. Qazi, and H.U. Ahmed

Subjects
Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2020
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13. The RAPID risk model: A novel risk score to predict significant prostate cancer in men with an mpMRI lesion

Author

D. Eldred-Evans, M. Peters, M. Bertoncelli Tanaka, F. Hosking-Jervis, M.J Connor, D. Reddy, T.T Shah, C. Khoo, W. Maynard, E. Bass, J. Lee, D. Sri, H. Bhola-Stewart, L. Powell, S. Ahmad, S. Joshi, E. Pegers, K. Wong, H. Tam, D. Hrouda, M. Winkler, H. Qazi, S. Gordon, and H.U Ahmed

Subjects
Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2020
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14. Man vs machine: Comparative effectiveness of cognitive targeted and image-fusion targeted transperineal prostate biopsy

Author

C.C. Khoo, D. Eldred-Evans, M. Peters, F. Hosking-Jervis, M.J. Connor, D. Reddy, M. Bertoncelli Tanaka, H. Bhola-Stewart, W. Maynard, E. Bass, T.T. Shah, J. Lee, D. Sri, L. Powell, S. Ahmad, M. Noureldin, S. Joshi, E. Pegers, K. Wong, H. Tam, D. Hrouda, M. Winkler, S. Gordon, H. Qazi, and H.U. Ahmed

Subjects
Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2020
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15. Direct and marginal cost analysis of not aiming for the target in a MRI-targeted prostate biopsy pathway

Author

M.J. Connor, D. Eldred-Evans, F. Hosking-Jervis, E. Bass, D. Reddy, M. Bertoncelli Tanaka, H. Bhola-Stewart, C. Khoo, W. Maynard, T.T. Shah, J. Lee, D. Sri, L. Powell, S. Ahmad, S. Joshi, E. Pegers, W. Kathie, H. Tam, D. Hrouda, M. Winkler, S. Gordon, H. Qazi, J. Carton, and H.U. Ahmed

Subjects
Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2020
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16. Local anaesthetic transperineal prostate biopsy: Optimising patient selection

Author

W. Maynard, D. Eldred-Evans, M. Connor, D. Reddy, M. Bertoncelli Tanaka, H. Bhola-Stewart, C. Khoo, E. Bass, T. Shah, J. Lee, D. Sri, L. Powell, S. Ahmad, M. Noureldin, S. Joshi, E. Pegers, K. Wong, H. Tam, D. Hrouda, M. Winkler, S. Gordon, H. Qazi, and H. Ahmed

Subjects
Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2020
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17. Opposite Consequences of Tonic and Phasic Increases in Accumbal Dopamine on Alcohol-Seeking Behavior

Author

Evgeny A. Budygin, Caroline E. Bass, Valentina P. Grinevich, Alex L. Deal, Keith D. Bonin, and Jeff L. Weiner

Subjects
Science
Abstract

Summary: Despite many years of work on dopaminergic mechanisms of alcohol addiction, much of the evidence remains mostly correlative in nature. Fortunately, recent technological advances have provided the opportunity to explore the causal role of alterations in neurotransmission within circuits involved in addictive behaviors. Here, we address this critical gap in our knowledge by integrating an optogenetic approach and an operant alcohol self-administration paradigm to assess directly how accumbal dopamine (DA) release dynamics influences the appetitive (seeking) component of alcohol-drinking behavior. We show that appetitive reward-seeking behavior in rats trained to self-administer alcohol can be shaped causally by ventral tegmental area-nucleus accumbens (VTA-NAc) DA neurotransmission. Our findings reveal that phasic patterns of DA release within this circuit enhance a discrete measure of alcohol seeking, whereas tonic patterns of stimulation inhibit this behavior. Moreover, we provide mechanistic evidence that tonic-phasic interplay within the VTA-NAc DA circuit underlies these seemingly paradoxical effects. : Animal Physiology; Neuroscience; Behavioral Neuroscience Subject Areas: Animal Physiology, Neuroscience, Behavioral Neuroscience

Published
2020
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18. Risk Stratification of Oral Potentially Malignant Disorders in Fanconi Anemia Patients Using Autofluorescence Imaging and Cytology-On-A Chip Assay

Author

Timothy J. Abram, Curtis R. Pickering, Alexander K. Lang, Nancy E. Bass, Rameez Raja, Cynthia Meena, Amin M. Alousi, Jeffrey N. Myers, John T. McDevitt, Ann M. Gillenwater, and Nadarajah Vigneswaran

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

Fanconi anemia (FA) is a hereditary genomic instability disorder with a predisposition to leukemia and oral squamous cell carcinomas (OSCCs). Hematopoietic stem cell transplantation (HSCT) facilitates cure of bone marrow failure and leukemia and thus extends life expectancy in FA patients; however, survival of hematologic malignancies increases the risk of OSCC in these patients. We developed a “cytology-on-a-chip” (COC)–based brush biopsy assay for monitoring patients with oral potentially malignant disorders (OPMDs). Using this COC assay, we measured and correlated the cellular morphometry and Minichromosome Maintenance Complex Component 2 (MCM2) expression levels in brush biopsy samples of FA patients’ OPMD with clinical risk indicators such as loss of autofluorescence (LOF), HSCT status, and mutational profiles identified by next-generation sequencing. Statistically significant differences were found in several cytology measurements based on high-risk indicators such as LOF-positive and HSCT-positive status, including greater variation in cell area and chromatin distribution, higher MCM2 expression levels, and greater numbers of white blood cells and cells with enlarged nuclei. Higher OPMD risk scores were associated with differences in the frequency of nuclear aberrations and differed based on LOF and HSCT statuses. We identified mutation of FAT1 gene in five and NOTCH-2 and TP53 genes in two cases of FA patients’ OPMD. The high-risk OPMD of a non-FA patient harbored FAT1, CASP8, and TP63 mutations. Use of COC assay in combination with visualization of LOF holds promise for the early diagnosis of high-risk OPMD. These minimally invasive diagnostic tools are valuable for long-term surveillance of OSCC in FA patients and avoidance of unwarranted scalpel biopsies.

Published
2018
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19. Facilitating Healing for Black Women Experiencing Gendered Racism and Traumatic Stress: The Moderation of Psychosocial Resources

Author

Tiffany R. Williams, Christy L. Erving, Whitney Frierson, Fanchen Gao, Jeffery E Bass, Reniece Martin, and Taeja Mitchell

Abstract

Black women must navigate a tumultuous sociopolitical terrain while simultaneously managing their psychological health. Experiences of gendered racism increase Black women’s vulnerability to psychological distress. Gendered racial microaggressions, a specific type of microaggression, account for the intricate ways racism and sexism intersect. The association between Black women’s experiences of gendered racial microaggressions and traumatic stress was investigated among 201 Black female-identified undergraduate and graduate students attending a Historically Black College or University. Whether psychosocial resources (i.e., resilience, social support, mastery, self-esteem) moderated the linkage between gendered racial microaggressions and traumatic stress was also examined. Gendered racial microaggressions were positively associated with traumatic stress. The microaggression Assumptions of Beauty and Sexual Objectification was the most strongly associated with traumatic stress, followed by Angry Black Woman. Resilience and mastery were protective factors, reducing the influence of gendered racial microaggressions on traumatic stress. In addition, high levels of social support reduced the impact of Assumptions of Beauty and Sexual Objectification on traumatic stress. To foster healing and posttraumatic growth for Black women, psychologists must decolonize their understanding and treatment of mental illness. Practice and research implications are discussed.

Published
2023

21. Supplementary Figures 1-7 from ATM Regulation of the Cohesin Complex Is Required for Repression of DNA Replication and Transcription in the Vicinity of DNA Double-Strand Breaks

Author

Michael B. Kastan, Paige E. Burrell, Donald E. Fleenor, and Thomas E. Bass

Abstract

S1. Identification of novel ATM-interactors using BioID. S2.NIPBL, PDS5A, and PDS5B are required for chromosomal stability and viability after IR. S3. Mutation of Fok1 nuclease domain blocks DSB formation. S4. Low dose IR causes suppression of DNA replication within the vicinity of the DSBs. S5. Fok1-induced DSBs do not result in a decrease in nuclear DNA replication. S6. Repression of DNA replication around DSBs is dependent on ATM and not ATR or DNAPK. S7. ATM phosphorylation of cohesin is required for repression of DNA replication within the vicinity of a DSB.

Published
2023

26. Distinct limbic dopamine regulation across olfactory‐tubercle subregions through integration of in vivo fast‐scan cyclic voltammetry and optogenetics

Author

Rohan V. Bhimani, Ryan Yates, Caroline E. Bass, and Jinwoo Park

Subjects
Optogenetics, Cellular and Molecular Neuroscience, Dopamine, Olfactory Tubercle, Ventral Tegmental Area, Animals, Biochemistry, Article, Nucleus Accumbens, Rats
Abstract

The olfactory tubercle (OT), an important component of the ventral striatum and limbic system, is involved in multi-sensory integration of reward-related information in the brain. However, its functional roles are often overshadowed by the neighboring nucleus accumbens. Increasing evidence has highlighted that dense dopamine (DA) innervation of the OT from the ventral tegmental area (VTA) is implicated in encoding reward, natural reinforcers, and motivated behaviors. Recent studies have further suggested that OT subregions may have distinct roles in these processes due to their heterogeneous DA transmission. Currently, very little is known about regulation (release and clearance) of extracellular DA across OT subregions due to its limited anatomical accessibility and proximity to other DA-rich brain regions, making it difficult to isolate VTA-DA signaling in the OT with conventional methods. Herein, we characterized heterogeneous VTA-DA regulation in the medial (m) and lateral (l) OT in "wild-type," urethane-anesthetized rats by integrating in vivo fast-scan cyclic voltammetry with cell-type specific optogenetics to stimulate VTA-DA neurons. Channelrhodopsin-2 was selectively expressed in the VTA-DA neurons of wild-type rats and optical stimulating parameters were optimized to determine VTA-DA transmission across the OT. Our anatomical, neurochemical, and pharmacological results show that VTA-DA regulation in the mOT is less dependent on DA transporters and has greater DA transmission than the lOT. These findings establish the OT as a unique, compartmentalized structure and will aid in future behavioral characterization of the roles of VTA-DA signaling in the OT subregions in reward, drug addiction, and encoding behavioral outputs necessary for survival.

Published
2022

27. Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose Associated 90-day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE-III)

Author

Yahya Shehabi, Ary Serpa Neto, Rinaldo Bellomo, Belinda D. Howe, Yaseen M. Arabi, Michael Bailey, Frances E. Bass, Suhaini Bin Kadiman, Colin J. McArthur, Michael C. Reade, Ian M. Seppelt, Jukka Takala, Matt P. Wise, Steve A. Webb, C. Mashonganyika, H. McKee, A. Tonks, A. Donnelly, N. Hemmings, S. O’Kane, A. Blakemore, M. Butler, K. Cowdrey, J. Dalton, E. Gilder, S. Long, L. McCarthy, S. McGuinness, R. Parke, Y. Chen, C. McArthur, R. McConnochie, L. Newby, R. Bellomo, G. Eastwood, L. Peck, H. Young, C. Boschert, J. Edington, J. Fletcher, J. Smith, K. Nand, A. Raza, T. Sara, J. Bennett-Britton, J. Bewley, V. Bodenham, L. Cole, K. Driver, L. Grimmer, L. Howie, C. Searles, K. Sweet, D. Webster, A. van Berkel, H. Connor, J. Dennett, M. van Der Graaff, S. Henderson, J. Mehrtens, K. Miller, E. Minto, A. Morris, S. Noble, K. Parker, L. Bulfin, N. Hart, K. Shepherd, S. Vij, S. Dickson, E. Elloway, C. Ferguson, R. Jackson, P. MacNaughton, M. Marner, R. Squire, S. Waddy, P. Wafer, J. Welbourne, P. Ashcroft, D. Chambler, S. Dukes, A. Harris, S. Horton, S. Sharpe, P. Williams, S. Williams, M. Bailey, E. Blazquez, D. France, R. Hutchison, A. O’Connor, G. Comadira, M. Gough, M. Tallott, M. Bastick, R. Cameron, S. Donovan, K. Ellis, A. Gaur, R. Gregory, J. Naumoff, E. Turner, M. White, K. F. J. Au, J. Fratzia, S. Treloar, C. H. Lim, Y. Maseeda, A. P. Tan, C. L. Tang, C. Y. Yong, M. Akaltan, S. Berger, D. Blaser, L. Fazlija, M. L. Jong, M. Lensch, R. Ludwig, T. Merz, K. Nettelbeck, M. Roth, M. Schafer, J. Takala, A. Wehr, D. Zacharias, R. Amran, H. N. Ashraf, N. Azmi, N. Basri, H. Burhanuddin, Y. Hadinata, A. Hamdan, S. Kadiman, A. I. Y. M. Rashid, I. N. Sabran, S. Sulaiman, I. N. Zabidi, A. Al-Dawood, M. Aljuaid, H. Al Anizi, A. Al Saeedi, Y. Arabi, M. Dbsawy, A. Deeb, M. Hegazy, I. Magdi, E. Clarey, E. Corcoran, C. Finney, C. Harris, P. Hopkins, H. Noble, L. Thompson, T. Williams, L. A. Dumlao, R. Bassam, M. A. Hassan, N. Naseem, M. H. Al-Kurdi, A. M. Al-Harthy, S. Bernard, L. Sebafundi, C. Serban, S. K. Lim, N. Mazidah, N. Saidin, N. Sjamsuddin, I. T. A. Tan, N. Zabidi, M. Brain, S. Mineall, M. Kanhere, N. Soar, N. Abd Kadir, N. H. Abdullah, R. Awang, Z. Emperan, N. S. Husin, N. I. Ismail, S. Z. Ismail, F. N. A. Mohd Khadzali, M. F. Norddin, J. Aguila, C. Bold, B. Clatworthy, A. Dias, C. Hogan, A. Kazemi, V. Lai, R. Song, A. Williams, D. Bhatia, S. Elliot, P. Galt, K. Lavrans, P. Ritchie, A. Wang, R. Gresham, J. Lowrey, K. Masters, P. Palejs, I. Seppelt, F. Symonds, L. Weisbrodt, C. Whitehead, M. Babio-Galan, V. Calder, I. Clement, A. Harrison, I. McCullagh, C. Scott, R. Bevan, S. Caniba, D. Hacking, L. Maher, M. L. Azzolini, P. Beccaria, S. Colombo, G. Landoni, C. Leggieri, C. Luca, D. Mamo, E. Moizo, G. Monti, M. Mucci, A. Zangrillo, M. Albania, S. Arora, Y. Shi, A. Abudayah, G. Almekhlafi, E. Al Amodi, S. Al Samarrai, M. Badawi, R. Cubio Caba, O. Elffaki, Y. Mandourah, J. Valerio, C. Joyce, J. Meyer, E. Saylor, B. Venkatesh, E. Venz, J. Walsham, K. Wetzig, T. M. Khoo, J. E. S. Liew, A. N. Sakthi, A. Zulkurnain, A. Bamford, C. Bergin, R. Carrera, L. Cooper, L. Despy, S. Harkett, L. Mee, E. Reeves, C. Snelson, E. Spruce, G. Cooper, R. Hodgson, D. Pearson, M. Rosbergen, M. N. Ali, N. I. Bahar, A. Ismail, W. N. W. Ismail, N. M. Samat, N. S. M. Piah, R. Abd Rahman, M. Duroux, M. Ratcliffe, T. Warhurst, U. Buehner, E. Williams, N. Jacques, L. Keating, S. Macgill, K. L. Tamang, N. Tolan, A. Walden, R. Bower, J. Cranshaw, K. Molloy, S. Pitts, J. Butler, R. Dunlop, C. Fourie, P. Jarrett, M. Lassig-Smith, A. Livermore, S. O’Donoghue, M. Reade, T. Starr, J. Stuart, L. Campbell, M. Phillips, D. Stephens, J. Thomas, D. Cooper, R. McAllister, G. Andrew, L. Barclay, H. Dawson, D. M. Griffith, D. Hope, G. Wojcik, C. McCulloch, R. Paterson, L. Ascough, C. Paisley, J. Patrick-Heselton, D. Shaw, V. Waugh, K. Williams, I. Welters, D. Barge, A. Jordan, C. MacIsaac, T. Rechnitzer, F. Bass, J. Gatward, N. Hammond, P. Janin, W. Stedman, E. Yarad, N. A. Razak, N. Dzulkipli, S. L. Jong, K. Asen, W. L. Voon, S. Liew, J. Ball, V. Barnes, C. Dalton, S. Farnell-Ward, H. Farrah, K. Maher, J. Mellinghoff, C. Ryan, P. Shirley, L. Conlon, A. Glover, I. Martin-Loeches, E. O’Toole, J. Ewan, J. Ferrier, E. Litton, S. A. Webb, W. Berry, U. Blanco Alonso, A. Bociek, S. Campos, S. Jawara, F. Hanks, A. Kelly, K. Lei, C. McKenzie, M. Ostermann, R. Wan, S. Al-Soufi, S. Leow, K. McCann, C. Reynolds, K. Brickell, C. Fahey, L. Hays, N. Hyde, A. Nichol, D. Ryan, J. Brailsford, A. Buckley, L. Forbes, T. Maguire, J. Moore, L. Murray, A. Ghosh, M. Park, S. Said, A. Visser, H. Z. Abidin, S. Ali, M. H. Hassan, S. C. Omar, W. F. W. Shukeri, D. Brealey, G. Bercades, E. Blackburn, N. Macallum, A. Macklin, J. H. Ryu, K. Tam, D. Smyth, A. Arif, C. Bassford, C. Morgan, C. Swann, G. Ward, L. Wild, A. Bone, T. Elderkin, D. Green, D. Sach, T. Salerno, N. Simpson, F. Brohi, M. Clark, L. Williams, J. Brooks, E. Cocks, J. Cole, J. Curtin, R. Davies, H. Hill, M. Morgan, N. Palmer, C. Whitton, M. Wise, P. Baskaran, M. S. Hasan, L. Y. Tham, R. Sol Cruz, D. Dinsdale, S. Edney, C. Firkin, F. FitzJohn, G. Hill, A. Hunt, S. Hurford, G. Jones, H. Judd, C. Latimer-Bell, C. Lawrence, E. Lesona, L. Navarra, Y. Robertson, H. Smellie, A. M. Vucago, P. Young, P. Clark, J. Kong, J. Ho, V. Nayyar, and C. Skelly

Subjects
Pulmonary and Respiratory Medicine, Critical Care and Intensive Care Medicine
Abstract

Sedation Practice in Intensive Care Evaluation (SPICE-III) trial reported significant heterogeneity in mortality with dexmedetomidine treatment. Supplemental propofol was commonly used to achieve desirable sedation.to quantify the association of different infusion rates of dexmedetomidine or propofol, given in combination, with mortality and if this is modified by age.We included 1177 patients randomized in SPICE-III to receive dexmedetomidine and given supplemental propofol, stratified by age (65 or ≤65 years). We used double stratification analysis to produce quartiles of steady infusion rates of dexmedetomidine, while escalating propofol dose and vice versa. We used Cox proportional hazard and multivariable regression, adjusted for relevant clinical variable to evaluate the association of sedative dose with 90-day mortality.Younger patients 598/1177(50.8%) received a significantly higher dose of both sedatives compared with older patients, to achieve comparable sedation depth. On double stratification analysis, escalating infusion rates of propofol to 1.27 mg/kg/h at a steady dexmedetomidine infusion rate (0.54 mcg/kg/h) was associated with reduced adjusted mortality in younger, but not older patients. This was consistent with multivariable regression modelling [hazard ratio: 0.59(95% Confidence Interval 0.43-0.78),P0.0001], adjusted for baseline risk and interaction with dexmedetomidine dose. In contrast, among younger patients using multivariable regression, escalating dexmedetomidine infusion rate was associated with increased adjusted mortality [HR:1.30(95%CI 1.03-1.65), P=0.029].In patients ≤ 65 years sedated with dexmedetomidine and propofol combination, preferentially increasing the dose of propofol was associated with decreased adjusted 90-day mortality. Conversely, increasing dexmedetomidine may be associated with increased mortality. Clinical trial registration available at www.gov, ID: NCT01728558.

Published
2022

28. Distinct dose‐dependent effects of methamphetamine on real‐time dopamine transmission in the rat nucleus accumbens and behaviors

Author

Caroline E. Bass, Megan Vik, Caitlin Szalkowski, Jinwoo Park, Ken T. Wakabayashi, and Rohan V. Bhimani

Subjects
Male, Dopamine, Fast-scan cyclic voltammetry, Motor Activity, Pharmacology, Nucleus accumbens, Synaptic Transmission, Biochemistry, Article, Nucleus Accumbens, Methamphetamine, Rats, Sprague-Dawley, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Dopamine Uptake Inhibitors, medicine, Extracellular, Animals, Behavior, Animal, Dose-Response Relationship, Drug, Receptors, Dopamine D2, Chemistry, Meth, Rats, Systemic administration, Autoreceptor, Central Nervous System Stimulants, Neurotoxicity Syndromes, Stereotyped Behavior, medicine.drug
Abstract

Methamphetamine (METH) is a potent psychostimulant that exerts many of its physiological and psychomotor effects by increasing extracellular dopamine (DA) concentrations in limbic brain regions. While several studies have focused on how potent, neurotoxic doses of METH augment or attenuate DA transmission, the acute effects of lower and behaviorally-activating doses of METH on modulating DA regulation (release and clearance) through DA D2 autoreceptors and transporters remains to be elucidated. In this study, we investigated how systemic administration of escalating, sub-neurotoxic doses of METH (0.5 – 5 mg/kg, IP) alter extracellular DA regulation in the nucleus accumbens (NAc), in both anesthetized and awake-behaving rats through the use of in vivo fast-scan cyclic voltammetry. Pharmacological, electrochemical, and behavioral evidence show that lower doses (≤ 2.0 mg/kg, IP) of METH enhance extracellular phasic DA concentrations and locomotion as well as stereotypies. In contrast, higher doses (≥ 5.0 mg/kg) further increase both phasic and baseline DA concentrations and stereotypies but decrease horizontal locomotion. Importantly, our results suggest that acute METH-induced enhancement of extracellular DA concentrations dose-dependently activate D2 autoreceptors. Therefore, these different METH dose-dependent effects on mesolimbic DA transmission may distinctly impact METH induced behavioral changes. This study provides valuable insights regarding how low METH doses alter DA transmission and paves the way for future clinical studies on the reinforcing effects of METH.

Published
2021

29. "Flashback to a War Zone": A Qualitative Analysis of Black Women's Experiences during the Racial Pandemic.

Author

R. Williams, Tiffany, L. Erving, Christy, E. Bass, Jeffery, Mitchell, Taeja, Martin, Reniece, Blasingame, Miaya, and Hotz, Allison

Subjects
RACISM, SOCIAL dominance, SEXISM, SOCIAL support, FEMINISM, SOCIAL justice, VIOLENCE, EMOTIONAL trauma, MENTAL health, EXPERIENCE, QUALITATIVE research, STEREOTYPES, SELF-efficacy, INTERSECTIONALITY, MENTAL depression, THEMATIC analysis, ANXIETY, AFRICAN Americans, COVID-19 pandemic, REFLECTION (Philosophy)
Abstract

The pandemic in 2020 commenced a particularly turbulent era of racial unrest, social injustice, and violence toward Black women. Drawing from Black feminist and intersectionality theories, this qualitative inquiry explored Black women's experiences of racism and sexism during the racial pandemic. Two hundred forty-one Black women shared their narratives and reflections. The analysis revealed two major themes: (a) racialized violence and harassment (e.g., stereotypes, dominance) and (b) their psychological consequences (e.g., anxiety, depression, racial trauma). Clinical implications are offered to support and empower Black women. [ABSTRACT FROM AUTHOR]

Published
2023
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30. O-016 Outcomes after endovascular mechanical thrombectomy for low national institutes of health stroke scale (NIHSS): a multicenter study

Author

I Abecassis, E Almallouhi, R Chalhoub, S Kassab, E Bass, D Ding, I Maier, M Psychogios, J Liman, A Alawieh, S Wolfe, A Arthur, P Kan, J Kim, R De Leacy, J Osbun, P Jabbour, J Grossbereg, M Park, J Mascitelli, M Levitt, A Polifka, S Yoshimura, C Matouk, R Williamson, B Gory, M Mokin, I Fragata, D Romano, V Saini, M Moss, D Behme, K Limaye, A Spiotta, and R Starke

Published
2022

32. A Multicenter Study of the Clinical Utility of Nontargeted Systematic Transperineal Prostate Biopsies in Patients Undergoing Pre-Biopsy Multiparametric Magnetic Resonance Imaging

Author

M. Bertoncelli Tanaka, David Eldred-Evans, H. Tam, Martin J. Connor, M. Van Son, Feargus Hosking-Jervis, E. Bass, S. Joshi, L. Powell, Deepika Reddy, D. Hrouda, S. Ahmad, M. Winkler, Hashim U. Ahmed, E. Pegers, Kathie Wong, S. Gordon, D. Sri, and H. Qazi

Subjects
Image-Guided Biopsy, Male, medicine.medical_specialty, Urology, 030232 urology & nephrology, Perineum, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Prostate, Biopsy, medicine, Humans, In patient, Prospective Studies, Multiparametric Magnetic Resonance Imaging, Aged, medicine.diagnostic_test, business.industry, Prostatic Neoplasms, Magnetic resonance imaging, Middle Aged, Prostate-Specific Antigen, medicine.disease, medicine.anatomical_structure, Multicenter study, Kallikreins, Biopsy, Large-Core Needle, Radiology, business
Abstract

The added value of nontargeted systematic prostate biopsies when performed alongside magnetic resonance imaging targeted biopsies in men referred with a suspicion of prostate cancer is unclear. We aimed to determine the clinical utility of transperineal nontargeted systematic prostate biopsies, when performed alongside targeted systematic prostate biopsies, using pre-biopsy multiparametric magnetic resonance imaging.Consecutive patients referred with a suspicion of prostate cancer (April 2017 to October 2019) underwent pre-biopsy multiparametric magnetic resonance imaging. A transperineal biopsy was advised if multiparametric magnetic resonance imaging PI-RADS® (v.2.0) score was 4 or 5, and score 3 required a prostate specific antigen density 0.12 ng/ml or greater. Primary threshold for clinically significant prostate cancer was defined as any Gleason 3+4 or greater. Multivariable logistic regression analysis identified pre-biopsy predictors of clinically significant prostate cancer in nontargeted systematic prostate biopsies, regardless of targeted pathology (p0.05, R, version 3.5.1).A total of 1,719 men underwent a pre-biopsy multiparametric magnetic resonance imaging, with 679 (39.5%) proceeding to combined targeted systematic prostate biopsies and nontargeted systematic prostate biopsies. In these men clinically significant prostate cancer was detected in 333 (49%) and 139 (20.5%) with targeted systematic prostate biopsies and nontargeted systematic prostate biopsies, respectively. In those men with clinically significant prostate cancer in targeted systematic prostate biopsies, clinically significant prostate cancer was also present in nontargeted systematic prostate biopsies in 117 (17.2%); Gleason 3+3 was present in 50 (7.4%). In 287 men without any cancer in the targeted systematic prostate biopsies, 13 (1.9%) had clinically significant prostate cancer in nontargeted systematic prostate biopsies. In addition 18/679 (2.7%) had Gleason 3+3 disease and no Gleason greater than 4+3 was detected. Predictors associated with clinically significant prostate cancer in nontargeted systematic prostate biopsies were prostate specific antigen 5 ng/ml or greater (OR 2.05, 95% CI 1.13-3.73, p=0.02), PI-RADS score 5 (OR 2.26, 95% CI 1.51-3.38, p0.001) and prostate volume less than 50 cc (OR 2.47, 95% CI 1.57-3.87, p0.001).Detection of clinically significant prostate cancer in exclusively nontargeted transperineal systematic biopsies in a pre-biopsy multiparametric magnetic resonance imaging pathway was low (1.9%).

Published
2020

33. Evaluation of Insulin Infusion Rates for the Treatment of Diabetic Ketoacidosis in the Emergency Department

Author

Megan E. Bass, Nicole Paavola, Tyree H. Kiser, Garth Wright, and Gabrielle Jacknin

Subjects
Management of Technology and Innovation
Abstract

There is minimal literature to support the appropriate dosing for the initiation of IV regular insulin therapy in DKA patients. A 0.1 unit/kg bolus followed by 0.1 units/kg/hour or 0.14 units/kg/hour is commonly utilized and recommended in guidelines.We sought to assess clinical and safety outcomes associated with various insulin infusion starting doses in patients diagnosed with DKA in the emergency department in an effort to help guide prescribing.A retrospective cohort study was conducted within an academic emergency department and included patients who received continuous infusion regular insulin with an ICD-10 code for DKA between January 2016 and January 2019. A predictive regression model was applied to test if predefined lab values influenced the starting insulin infusion rates. Clinical and safety outcomes were evaluated by starting insulin infusion rate. Data was analyzed based on starting insulin infusion rates.347 patients met inclusion criteria with 92 (26.5%) patients receiving0.07 units/kg/hr, 123 (35.4%) patients receiving 0.07 to 0.099 units/kg/hr, 123 (35.4%) patients receiving 0.10 to 0.139 units/kg/hr, and 9 (2.6%) patients receiving ≥0.14 units/kg/hr. After adjusting for baseline labs, glucose was the only significant predictor of the initial infusion rate (p0.001). For every 100 mg/dL increase in the baseline glucose value, the initial infusion rate increased by 0.005 units/kg/hr. There was no difference between insulin starting infusion rates and length of stay, rates of hypoglycemia, hypokalemia, or dysrhythmias.Glucose levels significantly influenced the insulin starting infusion rate, with no identified differences in adverse effects or clinical outcomes.

Published
2022

34. DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy

Author

M. E. Fenstermacher, J. Abbate, S. Abe, T. Abrams, M. Adams, B. Adamson, N. Aiba, T. Akiyama, P. Aleynikov, E. Allen, S. Allen, H. Anand, J. Anderson, Y. Andrew, T. Andrews, D. Appelt, R. Arbon, N. Ashikawa, A. Ashourvan, M. Aslin, Y. Asnis, M. Austin, D. Ayala, J. Bak, I. Bandyopadhyay, S. Banerjee, K. Barada, L. Bardoczi, J. Barr, E. Bass, D. Battaglia, A. Battey, W. Baumgartner, L. Baylor, J. Beckers, M. Beidler, E. Belli, J. Berkery, T. Bernard, N. Bertelli, M. Beurskens, R. Bielajew, S. Bilgili, B. Biswas, S. Blondel, J. Boedo, I. Bogatu, R. Boivin, T. Bolzonella, M. Bongard, X. Bonnin, P. Bonoli, M. Bonotto, A. Bortolon, S. Bose, N. Bosviel, S. Bouwmans, M. Boyer, W. Boyes, L. Bradley, R. Brambila, D. Brennan, S. Bringuier, L. Brodsky, M. Brookman, J. Brooks, D. Brower, G. Brown, W. Brown, M. Burke, K. Burrell, K. Butler, R. Buttery, I. Bykov, P. Byrne, A. Cacheris, K. Callahan, J. Callen, G. Campbell, J. Candy, J. Canik, P. Cano-Megias, N. Cao, L. Carayannopoulos, T. Carlstrom, W. Carrig, T. Carter, W. Cary, L. Casali, M. Cengher, G. Cespedes Paz, R. Chaban, V. Chan, B. Chapman, I. Char, A. Chattopadhyay, R. Chen, J. Chen, X. Chen, M. Chen, Z. Chen, M. Choi, W. Choi, G. Choi, L. Chousal, C. Chrobak, C. Chrystal, Y. Chung, R. Churchill, M. Cianciosa, J. Clark, M. Clement, S. Coda, A. Cole, C. Collins, W. Conlin, A. Cooper, J. Cordell, B. Coriton, T. Cote, J. Cothran, A. Creely, N. Crocker, C. Crowe, B. Crowley, T. Crowley, D. Cruz-Zabala, D. Cummings, M. Curie, D. Curreli, A. Dal Molin, B. Dannels, A. Dautt-Silva, K. Davda, G. De Tommasi, P. De Vries, G. Degrandchamp, J. Degrassie, D. Demers, S. Denk, S. Depasquale, E. Deshazer, A. Diallo, S. Diem, A. Dimits, R. Ding, S. Ding, W. Ding, T. Do, J. Doane, G. Dong, D. Donovan, J. Drake, W. Drews, J. Drobny, X. Du, H. Du, V. Duarte, D. Dudt, C. Dunn, J. Duran, A. Dvorak, F. Effenberg, N. Eidietis, D. Elder, D. Eldon, R. Ellis, W. Elwasif, D. Ennis, K. Erickson, D. Ernst, M. Fasciana, D. Fedorov, E. Feibush, N. Ferraro, J. Ferreira, J. Ferron, P. Fimognari, D. Finkenthal, R. Fitzpatrick, P. Fox, W. Fox, L. Frassinetti, H. Frerichs, H. Frye, Y. Fu, K. Gage, J. Galdon Quiroga, A. Gallo, Q. Gao, A. Garcia, M. Garcia Munoz, D. Garnier, A. Garofalo, A. Gattuso, D. Geng, K. Gentle, D. Ghosh, L. Giacomelli, S. Gibson, E. Gilson, C. Giroud, F. Glass, A. Glasser, D. Glibert, P. Gohil, R. Gomez, S. Gomez, X. Gong, E. Gonzales, A. Goodman, Y. Gorelov, V. Graber, R. Granetz, T. Gray, D. Green, C. Greenfield, M. Greenwald, B. Grierson, R. Groebner, W. Grosnickle, M. Groth, H. Grunloh, S. Gu, W. Guo, H. Guo, P. Gupta, J. Guterl, W. Guttenfelder, T. Guzman, S. Haar, R. Hager, S. Hahn, M. Halfmoon, T. Hall, K. Hallatschek, F. Halpern, G. Hammett, H. Han, E. Hansen, C. Hansen, M. Hansink, J. Hanson, M. Hanson, G. Hao, A. Harris, R. Harvey, S. Haskey, E. Hassan, A. Hassanein, D. Hatch, R. Hawryluk, W. Hayashi, W. Heidbrink, J. Herfindal, J. Hicok, D. Hill, E. Hinson, C. Holcomb, L. Holland, C. 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Peebles, S. Pelton, R. Perillo, C. Petty, Y. Peysson, D. Pierce, A. Pigarov, L. Pigatto, D. Piglowski, S. Pinches, R. Pinsker, P. Piovesan, N. Piper, A. Pironti, R. Pitts, J. Pizzo, U. Plank, M. Podesta, E. Poli, F. Poli, D. Ponce, Z. Popovic, M. Porkolab, G. Porter, C. Powers, S. Powers, R. Prater, Q. Pratt, I. Pusztai, J. Qian, X. Qin, O. Ra, T. Rafiq, T. Raines, R. Raman, J. Rauch, A. Raymond, C. Rea, M. Reich, A. Reiman, S. Reinhold, M. Reinke, R. Reksoatmodjo, Q. Ren, Y. Ren, J. Ren, M. Rensink, J. Renteria, T. Rhodes, J. Rice, R. Roberts, J. Robinson, P. Rodriguez Fernandez, T. Rognlien, A. Rosenthal, S. Rosiello, J. Rost, J. Roveto, W. Rowan, R. Rozenblat, J. Ruane, D. Rudakov, J. Ruiz Ruiz, R. Rupani, S. Saarelma, S. Sabbagh, J. Sachdev, J. Saenz, S. Saib, M. Salewski, A. Salmi, B. Sammuli, C. Samuell, A. Sandorfi, C. Sang, J. Sarff, O. Sauter, K. Schaubel, L. Schmitz, O. Schmitz, J. Schneider, P. Schroeder, K. Schultz, E. Schuster, J. Schwartz, F. Sciortino, F. Scotti, J. 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Thornton, A. Ti, M. Tillack, N. Timchenko, R. Tinguely, R. Tompkins, J. Tooker, A. Torrezan De Sousa, G. Trevisan, S. Tripathi, A. Trujillo Ochoa, D. Truong, C. Tsui, F. Turco, A. Turnbull, M. Umansky, E. Unterberg, P. Vaezi, P. Vail, J. Valdez, W. Valkis, B. Van Compernolle, J. Van Galen, R. Van Kampen, M. Van Zeeland, G. Verdoolaege, N. Vianello, B. Victor, E. Viezzer, S. Vincena, M. Wade, F. Waelbroeck, J. Wai, T. Wakatsuki, M. Walker, G. Wallace, R. Waltz, W. Wampler, L. Wang, H. Wang, Y. Wang, Z. Wang, G. Wang, S. Ward, M. Watkins, J. Watkins, W. Wehner, Y. Wei, M. Weiland, D. Weisberg, A. Welander, A. White, R. White, S. Wiesen, R. Wilcox, T. Wilks, M. Willensdorfer, H. Wilson, A. Wingen, M. Wolde, M. Wolff, K. Woller, A. Wolz, H. Wong, S. Woodruff, M. Wu, Y. Wu, S. Wukitch, G. Wurden, W. Xiao, R. Xie, Z. Xing, X. Xu, C. Xu, G. Xu, Z. Yan, X. Yang, S. Yang, T. Yokoyama, R. Yoneda, M. Yoshida, K. You, T. Younkin, J. Yu, M. Yu, G. Yu, Q. Yuan, L. Zaidenberg, L. Zakharov, A. 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E., Abbate, J., Abe, S., Abrams, T., Adams, M., Adamson, B., Aiba, N., Akiyama, T., Aleynikov, P., Allen, E., Allen, S., Anand, H., Anderson, J., Andrew, Y., Andrews, T., Appelt, D., Arbon, R., Ashikawa, N., Ashourvan, A., Aslin, M., Asnis, Y., Austin, M., Ayala, D., Bak, J., Bandyopadhyay, I., Banerjee, S., Barada, K., Bardoczi, L., Barr, J., Bass, E., Battaglia, D., Battey, A., Baumgartner, W., Baylor, L., Beckers, J., Beidler, M., Belli, E., Berkery, J., Bernard, T., Bertelli, N., Beurskens, M., Bielajew, R., Bilgili, S., Biswas, B., Blondel, S., Boedo, J., Bogatu, I., Boivin, R., Bolzonella, T., Bongard, M., Bonnin, X., Bonoli, P., Bonotto, M., Bortolon, A., Bose, S., Bosviel, N., Bouwmans, S., Boyer, M., Boyes, W., Bradley, L., Brambila, R., Brennan, D., Bringuier, S., Brodsky, L., Brookman, M., Brooks, J., Brower, D., Brown, G., Brown, W., Burke, M., Burrell, K., Butler, K., Buttery, R., Bykov, I., Byrne, P., Cacheris, A., Callahan, K., Callen, J., Campbell, G., Candy, J., Canik, 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J., Nocente, M., Nogami, S., Noraky, S., Norausky, N., Nornberg, M., Nygren, R., Odstrcil, T., Ogas, D., Ogorman, T., Ohdachi, S., Ohtani, Y., Okabayashi, M., Okamoto, M., Olavson, L., Olofsson, E., Omullane, M., Oneill, R., Orlov, D., Orvis, W., Osborne, T., Pace, D., Paganini Canal, G., Pajares Martinez, A., Palacios, L., Pan, C., Pan, Q., Pandit, R., Pandya, M., Pankin, A., Park, Y., Park, J., Parker, S., Parks, P., Parsons, M., Patel, B., Pawley, C., Paz-Soldan, C., Peebles, W., Pelton, S., Perillo, R., Petty, C., Peysson, Y., Pierce, D., Pigarov, A., Pigatto, L., Piglowski, D., Pinches, S., Pinsker, R., Piovesan, P., Piper, N., Pironti, A., Pitts, R., Pizzo, J., Plank, U., Podesta, M., Poli, E., Poli, F., Ponce, D., Popovic, Z., Porkolab, M., Porter, G., Powers, C., Powers, S., Prater, R., Pratt, Q., Pusztai, I., Qian, J., Qin, X., Ra, O., Rafiq, T., Raines, T., Raman, R., Rauch, J., Raymond, A., Rea, C., Reich, M., Reiman, A., Reinhold, S., Reinke, M., Reksoatmodjo, R., Ren, Q., Ren, Y., Ren, J., Rensink, M., Renteria, J., Rhodes, T., Rice, J., Roberts, R., Robinson, J., Rodriguez Fernandez, P., Rognlien, T., Rosenthal, A., Rosiello, S., Rost, J., Roveto, J., Rowan, W., Rozenblat, R., Ruane, J., Rudakov, D., Ruiz Ruiz, J., Rupani, R., Saarelma, S., Sabbagh, S., Sachdev, J., Saenz, J., Saib, S., Salewski, M., Salmi, A., Sammuli, B., Samuell, C., Sandorfi, A., Sang, C., Sarff, J., Sauter, O., Schaubel, K., Schmitz, L., Schmitz, O., Schneider, J., Schroeder, P., Schultz, K., Schuster, E., Schwartz, J., Sciortino, F., Scotti, F., Scoville, J., Seltzman, A., Seol, S., Sfiligoi, I., Shafer, M., Sharapov, S., Shen, H., Sheng, Z., Shepard, T., Shi, S., Shibata, Y., Shin, G., Shiraki, D., Shousha, R., Si, H., Simmerling, P., Sinclair, G., Sinha, J., Sinha, P., Sips, G., Sizyuk, T., Skinner, C., Sladkomedova, A., Slendebroek, T., Slief, J., Smirnov, R., Smith, J., Smith, S., Smith, D., Snipes, J., Snoep, G., Snyder, A., Snyder, P., Solano, E., Solomon, W., Song, J., Sontag, A., Soukhanovskii, V., Spendlove, J., Spong, D., Squire, J., Srinivasan, C., Stacey, W., Staebler, G., Stagner, L., Stange, T., Stangeby, P., Stefan, R., Stemprok, R., Stephan, D., Stillerman, J., Stoltzfus-Dueck, T., Stonecipher, W., Storment, S., Strait, E., Su, D., Sugiyama, L., Sun, Y., Sun, P., Sun, Z., Sun, A., Sundstrom, D., Sung, C., Sungcoco, J., Suttrop, W., Suzuki, Y., Suzuki, T., Svyatkovskiy, A., Swee, C., Sweeney, R., Sweetnam, C., Szepesi, G., Takechi, M., Tala, T., Tanaka, K., Tang, X., Tang, S., Tao, Y., Tao, R., Taussig, D., Taylor, T., Teixeira, K., Teo, K., Theodorsen, A., Thomas, D., Thome, K., Thorman, A., Thornton, A., Ti, A., Tillack, M., Timchenko, N., Tinguely, R., Tompkins, R., Tooker, J., Torrezan De Sousa, A., Trevisan, G., Tripathi, S., Trujillo Ochoa, A., Truong, D., Tsui, C., Turco, F., Turnbull, A., Umansky, M., Unterberg, E., Vaezi, P., Vail, P., Valdez, J., Valkis, W., Van Compernolle, B., Van Galen, J., Van Kampen, R., Van Zeeland, M., Verdoolaege, G., Vianello, N., Victor, B., Viezzer, E., Vincena, S., Wade, M., Waelbroeck, F., Wai, J., Wakatsuki, T., Walker, M., Wallace, G., Waltz, R., Wampler, W., Wang, L., Wang, H., Wang, Y., Wang, Z., Wang, G., Ward, S., Watkins, M., Watkins, J., Wehner, W., Wei, Y., Weiland, M., Weisberg, D., Welander, A., White, A., White, R., Wiesen, S., Wilcox, R., Wilks, T., Willensdorfer, M., Wilson, H., Wingen, A., Wolde, M., Wolff, M., Woller, K., Wolz, A., Wong, H., Woodruff, S., Wu, M., Wu, Y., Wukitch, S., Wurden, G., Xiao, W., Xie, R., Xing, Z., Xu, X., Xu, C., Xu, G., Yan, Z., Yang, X., Yang, S., Yokoyama, T., Yoneda, R., Yoshida, M., You, K., Younkin, T., Yu, J., Yu, M., Yu, G., Yuan, Q., Zaidenberg, L., Zakharov, L., Zamengo, A., Zamperini, S., Zarnstorff, M., Zeger, E., Zeller, K., Zeng, L., Zerbini, M., Zhang, L., Zhang, X., Zhang, R., Zhang, B., Zhang, J., Zhao, L., Zhao, B., Zheng, Y., Zheng, L., Zhu, B., Zhu, J., Zhu, Y., Zsutty, M., Zuin, M., Fenstermacher, M, Abbate, J, 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S, Kulchar, J, Kwon, K, La Haye, R, Laggner, F, Lan, H, Lantsov, R, Lao, L, Esquisabel, A, Lasnier, C, Lau, C, Leard, B, Lee, J, Lee, R, Lee, M, Lee, Y, Lee, C, Lee, S, Lehnen, M, Leonard, A, Leppink, E, Lesher, M, Lestz, J, Leuer, J, Leuthold, N, Li, X, Li, K, Li, E, Li, G, Li, L, Li, Z, Li, J, Li, Y, Lin, Z, Lin, D, Liu, X, Liu, J, Liu, Y, Liu, T, Liu, C, Liu, Z, Liu, D, Liu, A, Loarte-Prieto, A, Lodestro, L, Logan, N, Lohr, J, Lombardo, B, Lore, J, Luan, Q, Luce, T, Di Cortemiglia, T, Luhmann, N, Lunsford, R, Luo, Z, Lvovskiy, A, Lyons, B, Ma, X, Madruga, M, Madsen, B, Maggi, C, Maheshwari, K, Mail, A, Mailloux, J, Maingi, R, Major, M, Makowski, M, Manchanda, R, Marini, C, Marinoni, A, Maris, A, Markovic, T, Marrelli, L, Martin, E, Mateja, J, Matsunaga, G, Maurizio, R, Mauzey, P, Mauzey, D, Mcardle, G, Mcclenaghan, J, Mccollam, K, Mcdevitt, C, Mckay, K, Mckee, G, Mclean, A, Mehta, V, Meier, E, Menard, J, Meneghini, O, Merlo, G, Messer, S, Meyer, W, Michael, C, Michoski, C, Milne, P, Minet, G, Misleh, A, Mitrishkin, Y, Moeller, C, Montes, K, Morales, M, Mordijck, S, Moreau, D, Morosohk, S, Morris, P, Morton, L, Moser, A, Moyer, R, Moynihan, C, Mrazkova, T, Mueller, D, Munaretto, S, Burgos, J, Murphy, C, Murphy, K, Muscatello, C, Myers, C, Nagy, A, Nandipati, G, Navarro, M, Nave, F, Navratil, G, Nazikian, R, Neff, A, Neilson, G, Neiser, T, Neiswanger, W, Nelson, D, Nelson, A, Nespoli, F, Nguyen, R, Nguyen, L, Nguyen, X, Nichols, J, Nocente, M, Nogami, S, Noraky, S, Norausky, N, Nornberg, M, Nygren, R, Odstrcil, T, Ogas, D, Ogorman, T, Ohdachi, S, Ohtani, Y, Okabayashi, M, Okamoto, M, Olavson, L, Olofsson, E, Omullane, M, Oneill, R, Orlov, D, Orvis, W, Osborne, T, Pace, D, Canal, G, Martinez, A, Palacios, L, Pan, C, Pan, Q, Pandit, R, Pandya, M, Pankin, A, Park, Y, Park, J, Parker, S, Parks, P, Parsons, M, Patel, B, Pawley, C, Paz-Soldan, C, Peebles, W, Pelton, S, Perillo, R, Petty, C, Peysson, Y, Pierce, D, Pigarov, A, Pigatto, L, Piglowski, D, Pinches, S, Pinsker, R, Piovesan, P, Piper, N, Pironti, A, Pitts, R, Pizzo, J, Plank, U, Podesta, M, Poli, E, Poli, F, Ponce, D, Popovic, Z, Porkolab, M, Porter, G, Powers, C, Powers, S, Prater, R, Pratt, Q, Pusztai, I, Qian, J, Qin, X, Ra, O, Rafiq, T, Raines, T, Raman, R, Rauch, J, Raymond, A, Rea, C, Reich, M, Reiman, A, Reinhold, S, Reinke, M, Reksoatmodjo, R, Ren, Q, Ren, Y, Ren, J, Rensink, M, Renteria, J, Rhodes, T, Rice, J, Roberts, R, Robinson, J, Fernandez, P, Rognlien, T, Rosenthal, A, Rosiello, S, Rost, J, Roveto, J, Rowan, W, Rozenblat, R, Ruane, J, Rudakov, D, Ruiz, J, Rupani, R, Saarelma, S, Sabbagh, S, Sachdev, J, Saenz, J, Saib, S, Salewski, M, Salmi, A, Sammuli, B, Samuell, C, Sandorfi, A, Sang, C, Sarff, J, Sauter, O, Schaubel, K, Schmitz, L, Schmitz, O, Schneider, J, Schroeder, P, Schultz, K, Schuster, E, Schwartz, J, Sciortino, F, Scotti, F, Scoville, J, Seltzman, A, Seol, S, Sfiligoi, I, Shafer, M, Sharapov, S, Shen, H, Sheng, Z, Shepard, T, Shi, S, Shibata, Y, Shin, G, Shiraki, D, Shousha, R, Si, H, Simmerling, P, Sinclair, G, Sinha, J, Sinha, P, Sips, G, Sizyuk, T, Skinner, C, Sladkomedova, A, Slendebroek, T, Slief, J, Smirnov, R, Smith, J, Smith, S, Smith, D, Snipes, J, Snoep, G, Snyder, A, Snyder, P, Solano, E, Solomon, W, Song, J, Sontag, A, Soukhanovskii, V, Spendlove, J, Spong, D, Squire, J, Srinivasan, C, Stacey, W, Staebler, G, Stagner, L, Stange, T, Stangeby, P, Stefan, R, Stemprok, R, Stephan, D, Stillerman, J, Stoltzfus-Dueck, T, Stonecipher, W, Storment, S, Strait, E, Su, D, Sugiyama, L, Sun, Y, Sun, P, Sun, Z, Sun, A, Sundstrom, D, Sung, C, Sungcoco, J, Suttrop, W, Suzuki, Y, Suzuki, T, Svyatkovskiy, A, Swee, C, Sweeney, R, Sweetnam, C, Szepesi, G, Takechi, M, Tala, T, Tanaka, K, Tang, X, Tang, S, Tao, Y, Tao, R, Taussig, D, Taylor, T, Teixeira, K, Teo, K, Theodorsen, A, Thomas, D, Thome, K, Thorman, A, Thornton, A, Ti, A, Tillack, M, Timchenko, N, Tinguely, R, Tompkins, R, Tooker, J, De Sousa, A, Trevisan, G, Tripathi, S, Ochoa, A, Truong, D, Tsui, C, Turco, F, Turnbull, A, Umansky, M, Unterberg, E, Vaezi, P, Vail, P, Valdez, J, Valkis, W, Van Compernolle, B, Van Galen, J, Van Kampen, R, Van Zeeland, M, Verdoolaege, G, Vianello, N, Victor, B, Viezzer, E, Vincena, S, Wade, M, Waelbroeck, F, Wai, J, Wakatsuki, T, Walker, M, Wallace, G, Waltz, R, Wampler, W, Wang, L, Wang, H, Wang, Y, Wang, Z, Wang, G, Ward, S, Watkins, M, Watkins, J, Wehner, W, Wei, Y, Weiland, M, Weisberg, D, Welander, A, White, A, White, R, Wiesen, S, Wilcox, R, Wilks, T, Willensdorfer, M, Wilson, H, Wingen, A, Wolde, M, Wolff, M, Woller, K, Wolz, A, Wong, H, Woodruff, S, Wu, M, Wu, Y, Wukitch, S, Wurden, G, Xiao, W, Xie, R, Xing, Z, Xu, X, Xu, C, Xu, G, Yan, Z, Yang, X, Yang, S, Yokoyama, T, Yoneda, R, Yoshida, M, You, K, Younkin, T, Yu, J, Yu, M, Yu, G, Yuan, Q, Zaidenberg, L, Zakharov, L, Zamengo, A, Zamperini, S, Zarnstorff, M, Zeger, E, Zeller, K, Zeng, L, Zerbini, M, Zhang, L, Zhang, X, Zhang, R, Zhang, B, Zhang, J, Zhao, L, Zhao, B, Zheng, Y, Zheng, L, Zhu, B, Zhu, J, Zhu, Y, Zsutty, M, Zuin, M, Lawrence Livermore National Laboratory, Princeton Plasma Physics Laboratory, Princeton University, General Atomics, Max-Planck-Institut für Plasmaphysik, Imperial College London, National Institute for Fusion Science, Universidade de São Paulo, University of Texas at Austin, ITER, College of William and Mary, University of California Los Angeles, University of California San Diego, Columbia University, Massachusetts Institute of Technology, Oak Ridge National Laboratory, Eindhoven University of Technology, Oak Ridge Associated Universities, West Virginia University, University of Tennessee, Knoxville, National Research Council of Italy, Stony Brook University, Purdue University, University of Seville, University of Science and Technology of China, Carnegie Mellon University, Institute for Plasma Research, Peking University, University of California Davis, University of California Irvine, Commonwealth Fusion Systems, University of Liverpool, University of Illinois at Urbana-Champaign, University of Milan - Bicocca, Georgia Institute of Technology, Southwestern Institute of Physics, University of Toronto, Auburn University, Polytechnic University of Turin, Universidade Lisboa, Association CCFE, KTH Royal Institute of Technology, San Diego State University, Durham University, Lehigh University, Fusion and Plasma Physics, University of Washington, Department of Applied Physics, Sandia National Laboratories, Ghent University, Technical University of Denmark, CEA, University of Colorado Boulder, Harvard University, National Technical University of Athens, Coventry University, University of Stuttgart, Czech Academy of Sciences, Harvey Mudd College, Seoul National University, Donghua University, University of York, Dalian University of Technology, University of California Berkeley, Los Alamos National Laboratory, United States Department of Energy, University of British Columbia, Pacific Northwest National Laboratory, University of Wisconsin, Michigan State University, University of Strathclyde, Pennsylvania State University, Rensselaer Polytechnic Institute, University of Southern California, Chalmers University of Technology, University of Virginia, University of Naples Federico II, University of Oxford, VTT Technical Research Centre of Finland, National Institute of Technology, University of Connecticut, DIFFER, CIEMAT, Hanyang University, Brigham Young University, UiT The Arctic University of Norway, Australian National University, Russian Research Centre Kurchatov Institute, Forschungszentrum Jülich, Zhejiang University, The University of Tokyo, University of Michigan, Agenzia nazionale per le nuove tecnologie, l'energia e lo sviluppo economico sostenibile, Aalto-yliopisto, Aalto University, DIII-D Team, Complex Ionized Media, Elementary Processes in Gas Discharges, Applied Physics and Science Education, Science and Technology of Nuclear Fusion, and Control Systems Technology

Subjects
Nuclear and High Energy Physics, Tokamak, Technology and Engineering, DIII-D, Nuclear engineering, TOKAMAKS, MITIGATION, law.invention, Plasma physics, mitigation, law, plasma physic, tokamak, Physics, Core-edge integration, Basis (linear algebra), plasma physics, core-edge integration, scenarios, Fusion power, Condensed Matter Physics, SCENARIOS, fusion energy, Fusion energy
Abstract

Funding Information: This material is based upon work supported by the US Department of Energy, Office of Science, Office of Fusion Energy Sciences, using the DIII-D National Fusion Facility, a DOE Office of Science user facility, under Awards DE-FC02-04ER54698 and DE-AC52-07NA27344. Publisher Copyright: © 2022 IAEA, Vienna. DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.

Published
2022

35. Enhancing GABAergic Tone in the Rostral Nucleus of the Solitary Tract Reconfigures Sensorimotor Neural Activity

Author

Joshua D. Sammons, Jonathan D. Victor, Caroline E. Bass, and Patricia M. Di Lorenzo

Subjects
Male, Taste, Sensation, Motor Activity, Inhibitory postsynaptic potential, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Solitary Nucleus, medicine, Animals, Premovement neuronal activity, gamma-Aminobutyric Acid, Research Articles, Fluorescent Dyes, 030304 developmental biology, 0303 health sciences, Glutamate Decarboxylase, Chemistry, General Neuroscience, Solitary tract, Taste Perception, Electrodes, Implanted, Electrophysiological Phenomena, Rats, Electrophysiology, medicine.anatomical_structure, GABAergic, Female, Brainstem, Licking, Nucleus, Neuroscience, Photic Stimulation, 030217 neurology & neurosurgery
Abstract

Recent work has shown that most cells in the rostral, gustatory portion of the nucleus tractus solitarius (rNTS) in awake, freely licking rats show lick-related firing. However, the relationship between taste-related and lick-related activity in rNTS remains unclear. Here, we tested if GABA-derived inhibitory activity regulates the balance of lick- and taste-driven neuronal activity. Combinatorial viral tools were used to restrict expression of ChR2-EYFP to GAD1+ GABAergic neurons. Viral infusions were bilateral in rNTS. 2-4wks later, an optical fiber attached to 8-16 drivable microwires was implanted into the rNTS. After recovery, water-deprived rats were presented with taste stimuli in an experimental chamber. Trials were 5 consecutive taste licks [NaCl, KCl, NH4Cl, sucrose, MSG/IMP, citric acid, quinine, or artificial saliva (AS)] separated by 5 AS licks on a VR5 schedule. Each taste lick triggered a 1s train of laser light (25Hz; 473nm; 8-10mW) in a random half of the trials. In all, 113 cells were recorded in the rNTS, 50 responded to one or more taste stimuli without GABA enhancement. Selective changes in response magnitude (spike count) within cells shifted across unit patterns but preserved inter-stimulus relationships. Cells where enhanced GABAergic tone increased lick coherence conveyed more information distinguishing basic taste qualities and different salts than other cells. In addition, GABA activation significantly amplified the amount of information that discriminated palatable vs. unpalatable tastants. By dynamically regulating lick coherence and remodeling the across-unit response patterns to taste, enhancing GABAergic tone in rNTS reconfigures the neural activity reflecting sensation and movement.Significance StatementThe rostral nucleus tractus solitarius (rNTS) is the first structure in the central gustatory pathway. Electrophysiological recordings from the rNTS in awake, freely-licking animals show that cells in this area have lick- as well as taste-related activity, but the relationship between these characteristics is not well understood. Here, we showed evidence that GABA activation can dynamically regulate both of these two properties in rNTS cells to enhance the information conveyed, especially about palatable vs. unpalatable tastants. These data provide insights into the role of inhibitory activity in the rNTS.

Published
2020

36. A systematic review and meta-analysis of the diagnostic accuracy of biparametric prostate MRI for prostate cancer in men at risk

Author

A Pantovic, E. Bass, Henry Tam, Anwar R. Padhani, M. Winkler, Andrea Rockall, Martin J. Connor, Rhian Gabe, Hashim U. Ahmed, Heminder Sokhi, Cancer Research UK, Imperial College Healthcare NHS Trust- BRC Funding, and Wellcome Trust

Subjects
Cancer Research, medicine.medical_specialty, Prostate biopsy, ENDORECTAL COIL, Urology, medicine.medical_treatment, ANTIGEN, 030232 urology & nephrology, TUMOR-DETECTION, VERSION 2, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Prostate, Biopsy, MULTIPARAMETRIC MRI, medicine, 1112 Oncology and Carcinogenesis, 3 T, Multiparametric Magnetic Resonance Imaging, Science & Technology, medicine.diagnostic_test, business.industry, Prostatectomy, Cancer, COEFFICIENT MAP, Urology & Nephrology, medicine.disease, medicine.anatomical_structure, Oncology, DIFFUSION-WEIGHTED MRI, 030220 oncology & carcinogenesis, Meta-analysis, PHASED-ARRAY COIL, BIOPSY, Radiology, business, Life Sciences & Biomedicine
Abstract

Introduction Multiparametric magnetic resonance imaging (mpMRI), the use of three multiple imaging sequences, typically T2-weighted, diffusion weighted (DWI) and dynamic contrast enhanced (DCE) images, has a high sensitivity and specificity for detecting significant cancer. Current guidance now recommends its use prior to biopsy. However, the impact of DCE is currently under debate regarding test accuracy. Biparametric MRI (bpMRI), using only T2 and DWI has been proposed as a viable alternative. We conducted a contemporary systematic review and meta-analysis to further examine the diagnostic performance of bpMRI in the diagnosis of any and clinically significant prostate cancer. Methods A systematic review of the literature from 01/01/2017 to 06/07/2019 was performed by two independent reviewers using predefined search criteria. The index test was biparametric MRI and the reference standard whole-mount prostatectomy or prostate biopsy. Quality of included studies was assessed by the QUADAS-2 tool. Statistical analysis included pooled diagnostic performance (sensitivity; specificity; AUC), meta-regression of possible covariates and head-to-head comparisons of bpMRI and mpMRI where both were performed in the same study. Results Forty-four articles were included in the analysis. The pooled sensitivity for any cancer detection was 0.84 (95% CI, 0.80-0.88), specificity 0.75 (95% CI, 0.68-0.81) for bpMRI. The summary ROC curve yielded a high AUC value (AUC = 0.86). The pooled sensitivity for clinically significant prostate cancer was 0.87 (95% CI, 0.78-0.93), specificity 0.72 (95% CI, 0.56-0.84) and the AUC value was 0.87. Meta-regression analysis revealed no difference in the pooled diagnostic estimates between bpMRI and mpMRI. Conclusions This meta-analysis on contemporary studies shows that bpMRI offers comparable test accuracies to mpMRI in detecting prostate cancer. These data are broadly supportive of the bpMRI approach but heterogeneity does not allow definitive recommendations to be made. There is a need for prospective multicentre studies of bpMRI in biopsy naive men.

Published
2020

38. Diagnostic accuracy of magnetic resonance imaging targeted biopsy techniques compared to transrectal ultrasound guided biopsy of the prostate: a systematic review and meta-analysis

Author

E. Bass, M. Winkler, Hashim U. Ahmed, A Pantovic, Ardeshir R. Rastinehad, Martin J. Connor, Rhian Gabe, Stacy Loeb, Wellcome Trust, and University College London Hospitals Charity

Subjects
Cancer Research, medicine.medical_specialty, CANCER-DETECTION, Urology, ANTIGEN, 030232 urology & nephrology, urologic and male genital diseases, law.invention, 03 medical and health sciences, Prostate cancer, ULTRASONOGRAPHY, 0302 clinical medicine, Cog, IN-BORE, Randomized controlled trial, Prostate, law, Biopsy, medicine, 1112 Oncology and Carcinogenesis, Science & Technology, medicine.diagnostic_test, GUIDANCE, business.industry, MEN, Magnetic resonance imaging, Urology & Nephrology, EFFICACY, medicine.disease, 3. Good health, FUSION BIOPSY, medicine.anatomical_structure, Systematic review, Oncology, 030220 oncology & carcinogenesis, Meta-analysis, EXPERIENCE, Radiology, business, Life Sciences & Biomedicine, MRI
Abstract

Background Multiparametric MRI localizes cancer in the prostate, allowing for MRI guided biopsy (MRI-GB) 43 alongside transrectal ultrasound-guided systematic biopsy (TRUS-GB). Three MRI-GB approaches exist; visual estimation (COG-TB); fusion software-assisted (FUS-TB) and MRI ‘in-bore’ biopsy (IB-TB). It is unknown whether any of these are superior. We conducted a systematic review and meta-analysis to address three questions. First, whether MRI-GB is superior to TRUS-GB at detecting clinically significant PCa (csPCa). Second, whether MRI-GB is superior to TRUS-GB at avoiding detection of insignificant PCa. Third, whether any MRI-GB strategy is superior at detecting csPCa. Methods A systematic literature review from 2015 to 2019 was performed in accordance with the START recommendations. Studies reporting PCa detection rates, employing MRI-GB and TRUS-GB were included and evaluated using the QUADAS-2 checklist. 1553 studies were found, of which 43 were included in the meta-analysis. Results For csPCa, MRI-GB was superior in detection to TRUS-GB (0.83 vs. 0.63 [p = 0.02]). MRI-GB was superior in detection to TRUS-GB at avoiding detection of insignificant PCa. No MRI-GB technique was superior at detecting csPCa (IB-TB 0.87; COG TB 0.81; FUS-TB 0.81, [p = 0.55]). There was significant heterogeneity observed between the included studies. Conclusions In patients with suspected PCa on MRI, MRI-GB offers superior rates of csPCa detection and reduces detection of insignificant PCa compared to TRUS-GB. No individual MRI-GB technique was found to be better in csPCa detection. Prospective adequately powered randomized controlled trials are required.

Published
2021

39. MP34-16 SWITCHING FROM SEDATION TO LOCAL ANAESTHETIC TRANSPERINEAL PROSTATE BIOPSIES: A COST-BENEFIT ANALYSIS

Author

Stuart McCracken, E. Pegers, S. Gordon, Deepa Leelamany, Kathie Wong, M. Winkler, Feargus Hosking-Jervis, H. Qazi, William Maynard, H. Bhola-Stewart, S. Ahmad, Hashim U. Ahmed, P. Sarkar, E. Bass, Henry Tam, Martin J. Connor, M. Bertoncelli Tanaka, David Hrouda, David Eldred-Evans, U. Walters, and L. Powell

Subjects
Local anaesthetic, medicine.anatomical_structure, Cost–benefit analysis, business.industry, Prostate, Urology, Anesthesia, Sedation, medicine, medicine.symptom, business
Published
2021

40. Targeted genetic manipulations of neuronal subtypes using promoter-specific combinatorial AAVs for use in wild-type animals

Author

Heinrich S Gompf, Evgeny A Budygin, Patrick M Fuller, and Caroline E Bass

Subjects
aav, optogenetic, Cre recombinase, DREADD, ventral tegmental area (VTA), Tyrosine hydroxylase (th), Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Techniques to genetically manipulate the activity of defined neuronal subpopulations have been useful in elucidating function, however applicability to translational research beyond transgenic mice is limited. Subtype targeted transgene expression can be achieved using specific promoters, but often currently available promoters are either too large to package into many vectors, in particular adeno-associated virus (AAV), or do not drive expression at levels sufficient to alter behavior. To permit neuron subtype specific gene expression in wildtype animals, we developed a combinatorial AAV targeting system that drives, in combination, subtype specific Cre-recombinase expression with a strong but non-specific Cre-conditional transgene. Using this system we demonstrate that the tyrosine hydroxylase promoter (TH-Cre-AAV) restricted expression of channelrhodopsin-2 (EF1α-DIO-ChR2-mCherry-AAV) to the rat ventral tegmental area (VTA), or an activating DREADD (hSyn-DIO-hM3Dq-mCherry-AAV) to the rat locus coeruleus (LC). High expression levels were achieved in both regions. Immunohistochemistry (IHC) showed the majority of ChR2+ neurons (>93%) colocalized with TH in the VTA, and optical stimulation evoked striatal dopamine release. Activation of TH neurons in the LC produced sustained EEG and behavioral arousal. TH-specific hM3Dq expression in the LC was further compared with 1) a Cre construct driven by a strong but non-specific promoter (non-targeting), and 2) a retrogradely-transported WGA-Cre delivery mechanism (targeting a specific projection). IHC revealed that the area of c-fos activation after CNO treatment in the LC and peri-LC neurons appeared proportional to the resulting increase in wakefulness (non-targeted > targeted > ACC to LC projection restricted). Our dual AAV targeting system effectively overcomes the large size and weak activity barrier prevalent with many subtype specific promoters by functionally separating subtype specificity from promoter strength.

Published
2015
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41. O-011 outcomes of mechanical thrombectomy in stroke patients presenting with low aspects in the early and late window-insight from STAR

Author

Amir Shaban, Ansaar T Rai, Roberto Crosa, Min S. Park, E Bass, Maxim Mokin, Adam J. Polifka, Guilherme B. F. Porto, Isabel Fragata, Travis M. Dumont, Jonathan A Grossberg, Z Hubbard, Michael R. Levitt, Pascal Jabbour, Joshua W. Osbun, R De Leacy, Marios Psychogios, Joon-Tae Kim, Charles C. Matouk, Reda M. Chalhoub, S Al Kasab, Eyad Almallouhi, Adam S Arthur, Justin R Mascitelli, Alex Spiotta, Stacey Q Wolfe, Ilko Maier, Walter Casagrande, Daniel M S Raper, Albert J Yoo, Ali Alawieh, and Robert M. Starke

Subjects
medicine.medical_specialty, business.industry, Penumbra, medicine.disease, Surgery, Mechanical thrombectomy, Aneurysm, Modified Rankin Scale, medicine.artery, Middle cerebral artery, Occlusion, medicine, Internal carotid artery, business, Stroke
Abstract

Introduction Limited data is available about the outcomes of mechanical thrombectomy (MT) in stroke patients presenting with a large core infarct. We aim to investigate the safety and efficacy of MT in patients with large vessel occlusion and Alberta Stroke Program Early CT Score (ASPECTS) of 2-5. Methods Data from Stroke Thrombectomy and Aneurysm Registry (STAR), which combined the prospectively maintained databases of 28 thrombectomy-capable stroke centers in the US, Europe, and Asia, was interrogated. We identified thrombectomy patients presenting with an occlusion in the Internal carotid artery (ICA) or M1 segment of the middle cerebral artery (MCA). Multivariable regression analysis was performed to assess factors associated with favorable 90-day outcome (modified Rankin scale 0-3), including interaction terms between ASPECTS 2-5 and receiving MT in the extended window (≥ 6 hours from symptom-onset). Results Among MT patients who presented with ICA or M1 occlusion, 2132 had ASPECTS≥6 and 213 patients had ASPECTS 2-5. Patients in the low ASPECTS group were younger (70 vs. 72 years old, P=0.003) and more likely to present with an ICA occlusion (47.9% vs. 28.8%, P Conclusion More than one in three patients presenting with ASPECTS (2-5) may achieve favorable 90-day functional outcome following MT. Favorable outcome was 4 times higher in low ASPECTS patients who had successful recanalization. The effect of low ASPECTS on 90-day outcome did not differ in patients presenting in the early versus extended MT window. Disclosures E. Almallouhi: None. S. Al Kasab: None. Z. Hubbard: None. G. Porto: None. A. Alawieh: None. R. Chalhoub: None. E. Bass: None. P. Jabbour: None. R. Starke: None. S. Wolfe: None. A. Arthur: None. I. Maier: None. J. Grossberg: None. A. Rai: None. M. Park: None. J. Mascitelli: None. M. Psychogios: None. R. De Leacy: None. D. Raper: None. T. Dumont: None. M. Levitt: None. A. Polifka: None. J. Osbun: None. R. Crosa: None. J. Kim: None. W. Casagrande: None. M. Mokin: None. C. Matouk: None. A. Shaban: None. I. Fragata: None. A. Yoo: None. A. Spiotta: 1; C; Stryker, Penumbra, and Medtronic. 2; C; Penumbra, Stryker, Cerenovus, Terumo.

Published
2021

44. Academic entitlement: its relationship with academic behaviors and attitudes

Author

Teresa L. Davis, Mary Ellen Fromuth, David B. Kelly, Jeffery E. Bass, and Kin Leong Chan

Subjects
ComputingMilieux_THECOMPUTINGPROFESSION, Sociology and Political Science, Social Psychology, media_common.quotation_subject, Psychological research, 05 social sciences, Attendance, 050301 education, Academic achievement, Entitlement, Locus of control, Luck, Scale (social sciences), ComputingMilieux_COMPUTERSANDEDUCATION, Developmental and Educational Psychology, 0501 psychology and cognitive sciences, Psychology, Sociology of Education, 0503 education, Social psychology, 050104 developmental & child psychology, media_common
Abstract

The current study examined the relationship of academic entitlement with student attitudes (e.g., locus of control, motivation) and academic behavior. Participants were 272 (96 men, 176 women) undergraduate students enrolled in general psychology and recruited from a psychology research pool. In groups, participants individually completed a lengthy survey, which included an academic entitlement scale, a locus of control scale, an academic motivation scale, and items related to academic behaviors and attitudes. Academic entitlement was correlated with a more external locus of control and lower academic motivation. Significant correlations also emerged between academic entitlement and perceptions of factors that might help and hinder academic performance. For example, regarding factors perceived as helping academic performance, academic entitlement was positively correlated with endorsing luck as a helpful factor, but negatively correlated with endorsing class attendance as a helpful factor. Regarding factors perceived as hindering academic performance, academic entitlement was positively correlated with external factors such as bad luck and perceiving there to be too much work in the course. Results are discussed in terms of the need to consider academic entitlement as an academic risk factor.

Published
2019

45. Kappa Opioid Receptors Drive a Tonic Aversive Component of Chronic Pain

Author

Anna M.W. Taylor, Lindsay M. Lueptow, F. Ivy Carroll, Inés Ibarra-Lecue, Tuan Trang, Joshua K. Hakimian, Kristina Komarek, Frances M. Leslie, Anne M. Andrews, Amie L. Severino, Shiwei Liu, Sarah Pickens, Caroline E. Bass, Hongyan Yang, Christopher Cook, Wendy Walwyn, Nicole E. Burma, Catherine M. Cahill, Christopher J. Evans, Lihua Xue, and Mary C. Olmstead

Subjects
Male, 0301 basic medicine, Emotions, Dynorphin, Bioinformatics, κ-opioid receptor, Mice, 03 medical and health sciences, 0302 clinical medicine, Dopamine, medicine, Animals, Rats, Long-Evans, Research Articles, business.industry, Receptors, Opioid, kappa, General Neuroscience, Chronic pain, Pain Perception, medicine.disease, Rats, Mice, Inbred C57BL, 030104 developmental biology, Anxiogenic, Opioid, Anxiety, Female, Chronic Pain, medicine.symptom, Opiate, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Pain is a multidimensional experience and negative affect, or how much the pain is “bothersome”, significantly impacts the sufferers' quality of life. It is well established that the κ opioid system contributes to depressive and dysphoric states, but whether this system contributes to the negative affect precipitated by the occurrence of chronic pain remains tenuous. Using a model of persistent pain, we show by quantitative real-time-PCR, florescencein situhybridization, Western blotting and GTPgS autoradiography an upregulation of expression and the function of κ opioid receptors (KORs) and its endogenous ligand dynorphin in the mesolimbic circuitry in animals with chronic pain compared with surgical controls. Usingin vivomicrodialysis and microinjection of drugs into the mesolimbic dopamine system, we demonstrate that inhibiting KORs reinstates evoked dopamine release and reward-related behaviors in chronic pain animals. Chronic pain enhanced KOR agonist-induced place aversion in a sex-dependent manner. Using various place preference paradigms, we show that activation of KORs drives pain aversive states in male but not female mice. However, KOR antagonist treatment was effective in alleviating anxiogenic and depressive affective-like behaviors in both sexes. Finally, ablation of KORs from dopamine neurons using AAV-TH-cre in KORloxPmice prevented pain-induced aversive states as measured by place aversion assays. Our results strongly support the use of KOR antagonists as therapeutic adjuvants to alleviate the emotional, tonic-aversive component of chronic pain, which is argued to be the most significant component of the pain experience that impacts patients' quality of life.SIGNIFICANCE STATEMENTWe show that KORs are sufficient to drive the tonic-aversive component of chronic pain; the emotional component of pain that is argued to significantly impact a patient's quality of life. The impact of our study is broadly relevant to affective disorders associated with disruption of reward circuitry and thus likely contributes to many of the devastating sequelae of chronic pain, including the poor response to treatment of many patients, debilitating affective disorders (other disorders including anxiety and depression that demonstrate high comorbidity with chronic pain) and substance abuse. Indeed, coexisting psychopathology increases pain intensity, pain-related disability and effectiveness of treatments (Jamison and Edwards, 2013).

Published
2019

46. Influence of a whole yeast product (Pichia guilliermondii) fed throughout gestation and lactation on performance and immune parameters of the sow and litter

Author

Jason W. Frank, Jeff Chewning, David Holzgraefe, Tsungcheng Tsai, B. E. Bass, Charles V Maxwell, Victor G Perez, and Hong Yang

Subjects
Litter (animal), Neutrophils, Swine, animal diseases, Lymphocyte, Population, Weaning, Non Ruminant Nutrition, Biology, Pichia, 03 medical and health sciences, Animal science, Pregnancy, Lactation, White blood cell, Genetics, medicine, Animals, Lymphocytes, education, 030304 developmental biology, 0303 health sciences, education.field_of_study, Colostrum, Parturition, 0402 animal and dairy science, 04 agricultural and veterinary sciences, General Medicine, Animal Feed, 040201 dairy & animal science, Diet, Milk, medicine.anatomical_structure, Dietary Supplements, Gestation, Female, Animal Science and Zoology, Food Science
Abstract

A study was conducted using 3 groups of gestating gilts and sows (n = 98) to determine the effects of Pichia guilliermondii (Pg), a whole cell-inactivated yeast product (CitriStim; ADM Alliance Nutrition), on performance and immune parameters of dams and litters. Within 24 h of breeding, gilts and sows were allotted to 1 of 3 treatments consisting of a control (SC) diet or SC diet supplemented with 0.1 (S1) or 0.2% (S2) Pg. Dietary treatments were maintained through lactation. Colostrum and milk (day 14) samples were collected for IgA, IgG, and IgM analysis. Blood samples were collected from sows on day 110 of gestation (group 3 only), while at weaning for all 3 groups, and from piglets at 14 d of age for peripheral white blood cell counts and serum IgA, IgG, and IgM analysis. Inclusion of Pg resulted in an increase in number born alive as the level of Pg increased (12.49, 13.33, and 13.43 born alive per litter for SC, S1, and S2, respectively; linear effect [LS], P = 0.003). Additionally, the percentage of piglets weighing less than 0.9 kg at birth was reduced in sows provided Pg at 0.1% or 0.2% compared with control (LS, P = 0.006). Sows receiving Pg during gestation and lactation also weaned a greater number of piglets (10.31, 10.55, and 10.60 weaned per litter in control, 0.1% and 0.2% Pg, respectively; LS, P = 0.02). However, percent preweaning mortality was 17.58%, 19.38%, and 19.61% for control, 0.1%, and 0.2% Pg, respectively (LS, P = 0.02). There were no differences in gestation BW gain, farrowing (days 110 to 48 h postfarrowing) or lactation (day 110 to weaning) BW loss, number of mummies or stillborn, or piglets' individual birth or weaning weight. On day 110 of gestation, the neutrophil concentration (quadratic effect [QS], P = 0.03) and neutrophil:lymphocyte ratio (QS, P = 0.04) in peripheral blood were greater in S1 than SC, with S2 being intermediate. At weaning there was a linear increase in neutrophil concentration (P = 0.03), neutrophil:lymphocyte ratio (P = 0.01), and percentage of neutrophils in the leukocyte population (P = 0.01) as level of Pg increased in sow diets. In conclusion, Pg inclusion in sow diets linearly increased total number born alive and weaned, with no change in average birth or weaning weight, and decreased the number of lightweight pigs at birth. However, inclusion of Pg had no effect on immune parameters measured in milk, colostrum, or day 14 piglet serum, but increased the peripheral blood neutrophil concentration of gilts and sows.

Published
2019

47. Supplementation of a Lactobacillus acidophilus fermentation product can attenuate the acute phase response following a lipopolysaccharide challenge in weaned pigs

Author

N. C. Burdick Sanchez, Jeffery A. Carroll, B. E. Bass, Jason W. Frank, and Paul R Broadway

Subjects
Lipopolysaccharides, Lipopolysaccharide, 040301 veterinary sciences, Sus scrofa, Biology, SF1-1100, law.invention, 0403 veterinary science, Blood cell, Probiotic, chemistry.chemical_compound, Lactobacillus acidophilus, Animal science, Starter, Stress, Physiological, law, Lipopolysaccharide challenge, medicine, Animals, Acute-Phase Reaction, Swine Diseases, 0402 animal and dairy science, Acute-phase protein, temperature, swine, 04 agricultural and veterinary sciences, Animal Feed, 040201 dairy & animal science, Diet, Animal culture, medicine.anatomical_structure, chemistry, Dietary Supplements, Fermentation, innate immune response, Animal Science and Zoology, probiotic, pro-inflammatory response
Abstract

Lactobacillus acidophilus fermentation products have been used to improve the performance of nursery pigs. However, research on the influence of this supplement on health is lacking. This study was designed to determine if feeding a Lactobacillus acidophilus fermentation product to weaned pigs would reduce stress and acute phase responses (APR) following a lipopolysaccharide (LPS) challenge. Pigs (n=30; 6.4±0.1 kg) were individually housed in stainless steel pens with ad libitum access to feed and water. Pigs were weighed upon arrival, assigned to one of three groups (n=10/treatment), and fed for 18 days: (1) Control, fed a non-medicated starter diet; (2) Control diet with the inclusion of a Lactobacillus acidophilus fermentation product at 1 kg/metric ton (SGX1) and (3) Control diet with the inclusion of a Lactobacillus acidophilus fermentation product at 2 kg/metric ton (SGX2). On day 7 pigs were anesthetized for insertion of an i.p. temperature device, and similarly on day 14 for insertion of a jugular catheter. Pigs were challenged i.v. with LPS (25 µg/kg BW) on day 15. Blood samples were collected at 0.5 h (serum) and 1 h (complete blood cell counts) intervals from -2 to 8 h and at 24 h relative to LPS administration at 0 h. Pigs and feeders were weighed on days 7, 14 and 18. The supplemented pigs had increased BW and average daily gain before the challenge. In response to LPS, there was a greater increase in i.p. temperature in Control pigs compared with supplemented pigs. In addition, cortisol was reduced in SGX2 pigs while cortisol was elevated in SGX1 pigs at several time points post-challenge. White blood cells, neutrophils and lymphocytes were decreased in SGX1 and SGX2 compared with Control pigs. Furthermore, the pro-inflammatory cytokine response varied by treatment and dose of treatment. Specifically, serum TNF-α was greatest in SGX2, intermediate in Control, and least in SGX1 pigs, while the magnitude and temporal pattern of IFN-γ in SGX2 pigs was delayed and reduced. In contrast, IL-6 concentrations were reduced in both SGX treatment groups compared with Control pigs. These data demonstrate that different supplementation feed inclusion rates produced differential responses, and that feeding SynGenX to weaned pigs attenuated the APR to an LPS challenge.

Published
2019

48. Genetic modifiers of neurofibromatosis type 1-associated café-au-lait macule count identified using multi-platform analysis.

Author

Alexander Pemov, Heejong Sung, Paula L Hyland, Jennifer L Sloan, Sarah L Ruppert, Andrea M Baldwin, Joseph F Boland, Sara E Bass, Hyo Jung Lee, Kristine M Jones, Xijun Zhang, NISC Comparative Sequencing Program, James C Mullikin, Brigitte C Widemann, Alexander F Wilson, and Douglas R Stewart

Subjects
Genetics, QH426-470
Abstract

Neurofibromatosis type 1 (NF1) is an autosomal dominant, monogenic disorder of dysregulated neurocutaneous tissue growth. Pleiotropy, variable expressivity and few NF1 genotype-phenotype correlates limit clinical prognostication in NF1. Phenotype complexity in NF1 is hypothesized to derive in part from genetic modifiers unlinked to the NF1 locus. In this study, we hypothesized that normal variation in germline gene expression confers risk for certain phenotypes in NF1. In a set of 79 individuals with NF1, we examined the association between gene expression in lymphoblastoid cell lines with NF1-associated phenotypes and sequenced select genes with significant phenotype/expression correlations. In a discovery cohort of 89 self-reported European-Americans with NF1 we examined the association between germline sequence variants of these genes with café-au-lait macule (CALM) count, a tractable, tumor-like phenotype in NF1. Two correlated, common SNPs (rs4660761 and rs7161) between DPH2 and ATP6V0B were significantly associated with the CALM count. Analysis with tiled regression also identified SNP rs4660761 as significantly associated with CALM count. SNP rs1800934 and 12 rare variants in the mismatch repair gene MSH6 were also associated with CALM count. Both SNPs rs7161 and rs4660761 (DPH2 and ATP6V0B) were highly significant in a mega-analysis in a combined cohort of 180 self-reported European-Americans; SNP rs1800934 (MSH6) was near-significant in a meta-analysis assuming dominant effect of the minor allele. SNP rs4660761 is predicted to regulate ATP6V0B, a gene associated with melanosome biology. Individuals with homozygous mutations in MSH6 can develop an NF1-like phenotype, including multiple CALMs. Through a multi-platform approach, we identified variants that influence NF1 CALM count.

Published
2014
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49. Comparative effectiveness of direct oral anticoagulants and warfarin for the treatment of left ventricular thrombus

Author

Megan E, Bass, Tyree H, Kiser, Robert L, Page, Colleen K, McIlvennan, Larry A, Allen, Garth, Wright, and Courtney, Shakowski

Subjects
Stroke, Thromboembolism, Atrial Fibrillation, Administration, Oral, Anticoagulants, Humans, Hemorrhage, Thrombosis, Warfarin, Retrospective Studies
Abstract

Left ventricular (LV) thrombus is a complication of acute endomyocardial injury and chronic ventricular wall hypokinesis, resulting in increased risk of thromboembolic complications. Observational studies support the general safety and efficacy of warfarin for this indication. Limited data exists regarding the use of direct oral anticoagulants (DOACs) for LV thrombus. This retrospective cohort study sought to compare the incidence of thromboembolic events, bleeding rates, and blood product administration in patients receiving a DOAC versus warfarin. A total of 949 patients met inclusion, 180 (19%) received a DOAC and 769 (81%) warfarin. For the primary endpoint of new onset thromboembolic stroke, no difference existed between treatments (DOAC: 7.8% vs warfarin: 11.7%, p = 0.13). When compared to warfarin, no difference existed in the composite of thromboembolic events (33% vs 30.6%, p = 0.53, respectively) or in GUSTO bleeding (10.9% vs 7.8%, p = 0.40, respectively). More patients on warfarin received blood products compared to those taking a DOAC (25.8% vs 13.9%, p 0.001).DOACs may be an alternative to warfarin for the treatment of LV thrombus based on a retrospective assessment of thromboembolic events and GUSTO bleeding events within 90 days of diagnosis of LV thrombus. However, further prospective studies are warranted.

Published
2020

50. Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration

Author

Caroline E Bass, Valentina P Grinevich, Dominic eGioia, Jon eDay-Brown, Keith D Bonin, Garret D Stuber, Jeff L Weiner, and Evgeny eBudygin

Subjects
Dopamine, Nucleus Accumbens, optogenetics, VTA, ethanol self-administration, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

There is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA) dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive. Here, we sought to address these gaps in our knowledge using a newly developed viral-mediated gene delivery strategy to selectively express Channelrhodopsin-2 (ChR2) on dopamine cells in the VTA of wild-type rats. We then used this approach to precisely control VTA dopamine transmission during voluntary ethanol drinking sessions. The results confirmed that ChR2 was selectively expressed on VTA dopamine cells and delivery of blue light pulses to the VTA induced dopamine release in accumbal terminal fields with very high temporal and spatial precision. Brief high frequency VTA stimulation induced phasic patterns of dopamine release in the nucleus accumbens. Lower frequency stimulation, applied for longer periods mimicked tonic increases in accumbal dopamine. Notably, using this optogenetic approach in rats engaged in an intermittent ethanol drinking procedure, we found that tonic, but not phasic, stimulation of VTA dopamine cells selectively attenuated ethanol drinking behaviors. Collectively, these data demonstrate the effectiveness of a novel viral targeting strategy that can be used to restrict opsin expression to dopamine cells in standard outbred animals and provide the first causal evidence demonstrating that tonic activation of VTA dopamine neurons selectively decreases ethanol self-administration behaviors.

Published
2013
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