Sample records for active lever responding

  1. Differential Acquisition of Lever Pressing in Inbred and Outbred Mice: Comparison of One-Lever and Two-Lever Procedures and Correlation with Differences in Locomotor Activity

    PubMed Central

    McKerchar, Todd L; Zarcone, Troy J; Fowler, Stephen C

    2005-01-01

    Recent progress in mouse genetics has led to an increased interest in developing procedures for assessing mouse behavior, but relatively few of the behavioral procedures developed involve positively reinforced operant behavior. When operant methods are used, nose poking, not lever pressing, is the target response. In the current study differential acquisition of milk-reinforced lever pressing was observed in five inbred strains (C57BL/6J, DBA/2J, 129X1/SvJ, C3H/HeJ, and BALB/cJ) and one outbred stock (CD-1) of mice. Regardless of whether one or two levers (an “operative” and “inoperative” lever) were in the operant chamber, a concomitant variable-time fixed-ratio schedule of milk reinforcement established lever pressing in the majority of mice within two 120-min sessions. Substantial differences in lever pressing were observed across mice and between procedures. Adding an inoperative lever retarded acquisition in C57BL/6J, DBA/2J, 129X1/SvJ, and C3H/HeJ mice, but not in CD-1 and BALB/cJ mice. Locomotor activity was positively correlated with number of lever presses in both procedures. Analyses of durations of the subcomponents (e.g., time to move from hopper to lever) of operant behavior revealed further differences among the six types of mice. Together, the data suggest that appetitively reinforced lever pressing can be acquired rapidly in mice and that a combination of procedural, behavioral, and genetic variables contributes to this acquisition. PMID:16596969

  2. Shoulder Muscular Demand During Lever-Activated Vs Pushrim Wheelchair Propulsion in Persons With Spinal Cord Injury

    PubMed Central

    Requejo, Philip Santos; Lee, Sharon E; Mulroy, Sara J; Haubert, Lisa Lighthall; Bontrager, Ernest L; Gronley, JoAnne K; Perry, Jacquelin

    2008-01-01

    Background/Objective: The high demand on the upper limbs during manual wheelchair (WC) use contributes to a high prevalence of shoulder pathology in people with spinal cord injury (SCI). Lever-activated (LEVER) WCs have been presented as a less demanding alternative mode of manual WC propulsion. The objective of this study was to evaluate the shoulder muscle electromyographic activity and propulsion characteristics in manual WC users with SCI propelling a standard pushrim (ST) and LEVER WC design. Methods: Twenty men with complete injuries (ASIA A or B) and tetraplegia (C6, n = 5; C7, n = 7) or paraplegia (n = 8) secondary to SCI propelled ST and LEVER WCs at 3 propulsion conditions on a stationary ergometer: self-selected free, self-selected fast, and simulated graded resistance. Average velocity, cycle distance, and cadence; median and peak electromyographic intensity; and duration of electromyography of anterior deltoid, pectoralis major, supraspinatus, and infraspinatus muscles were compared between LEVER and ST WC propulsion. Results: Significant decreases in pectoralis major and supraspinatus activity were recorded during LEVER compared with ST WC propulsion. However, anterior deltoid and infraspinatus intensities tended to increase during LEVER WC propulsion. Participants with tetraplegia had similar or greater anterior deltoid, pectoralis major, and infraspinatus activity for both ST and LEVER WC propulsion compared with the men with paraplegia. Conclusions: Use of the LEVER WC reduced and shifted the shoulder muscular demands in individuals with paraplegia and tetraplegia. Further studies are needed to determine the impact of LEVER WC propulsion on long-term shoulder function. PMID:19086715

  3. Extinction of Cocaine Seeking Requires a Window of Infralimbic Pyramidal Neuron Activity after Unreinforced Lever Presses

    PubMed Central

    Nett, Kelle E.; Cosme, Caitlin V.; Worth, Wensday R.; Wemmie, John A.

    2017-01-01

    The infralimbic cortex (IL) mediates extinction learning and the active suppression of cocaine-seeking behavior. However, the precise temporal relationship among IL activity, lever pressing, and extinction learning is unclear. To address this issue, we used activity-guided optogenetics in male Sprague Dawley rats to silence IL pyramidal neurons optically for 20 s immediately after unreinforced lever presses during early extinction training after cocaine self-administration. Optical inhibition of the IL increased active lever pressing during shortened extinction sessions, but did not alter the retention of the extinction learning as assessed in ensuing extinction sessions with no optical inhibition. During subsequent cued reinstatement sessions, rats that had previously received optical inhibition during the extinction sessions showed increased cocaine-seeking behavior. These findings appeared to be specific to inhibition during the post-lever press period because IL inhibition given in a noncontingent, pseudorandom manner during extinction sessions did not produce the same effects. Illumination alone (i.e., with no opsin expression) and food-seeking control experiments also failed to produce the same effects. In another experiment, IL inhibition after lever presses during cued reinstatement sessions increased cocaine seeking during those sessions. Finally, inhibition of the prelimbic cortex immediately after unreinforced lever presses during shortened extinction sessions decreased lever pressing during these sessions, but had no effect on subsequent reinstatement. These results indicate that IL activity immediately after unreinforced lever presses is necessary for normal extinction of cocaine seeking, suggesting that critical encoding of the new contingencies between a lever press and a cocaine reward occurs during that period. SIGNIFICANCE STATEMENT The infralimbic cortex (IL) contributes to the extinction of cocaine-seeking behavior, but the precise relationship

  4. Extinction of Cocaine Seeking Requires a Window of Infralimbic Pyramidal Neuron Activity after Unreinforced Lever Presses.

    PubMed

    Gutman, Andrea L; Nett, Kelle E; Cosme, Caitlin V; Worth, Wensday R; Gupta, Subhash C; Wemmie, John A; LaLumiere, Ryan T

    2017-06-21

    The infralimbic cortex (IL) mediates extinction learning and the active suppression of cocaine-seeking behavior. However, the precise temporal relationship among IL activity, lever pressing, and extinction learning is unclear. To address this issue, we used activity-guided optogenetics in male Sprague Dawley rats to silence IL pyramidal neurons optically for 20 s immediately after unreinforced lever presses during early extinction training after cocaine self-administration. Optical inhibition of the IL increased active lever pressing during shortened extinction sessions, but did not alter the retention of the extinction learning as assessed in ensuing extinction sessions with no optical inhibition. During subsequent cued reinstatement sessions, rats that had previously received optical inhibition during the extinction sessions showed increased cocaine-seeking behavior. These findings appeared to be specific to inhibition during the post-lever press period because IL inhibition given in a noncontingent, pseudorandom manner during extinction sessions did not produce the same effects. Illumination alone (i.e., with no opsin expression) and food-seeking control experiments also failed to produce the same effects. In another experiment, IL inhibition after lever presses during cued reinstatement sessions increased cocaine seeking during those sessions. Finally, inhibition of the prelimbic cortex immediately after unreinforced lever presses during shortened extinction sessions decreased lever pressing during these sessions, but had no effect on subsequent reinstatement. These results indicate that IL activity immediately after unreinforced lever presses is necessary for normal extinction of cocaine seeking, suggesting that critical encoding of the new contingencies between a lever press and a cocaine reward occurs during that period. SIGNIFICANCE STATEMENT The infralimbic cortex (IL) contributes to the extinction of cocaine-seeking behavior, but the precise relationship

  5. Lever conditioned stimulus-directed autoshaping induced by saccharin-ethanol unconditioned stimulus solution: effects of ethanol concentration and trial spacing.

    PubMed

    Tomie, Arthur; Festa, Eugene D; Sparta, Dennis R; Pohorecky, Larissa A

    2003-05-01

    Two experiments were designed to evaluate whether brief access to a saccharin-ethanol solution would function as an effective unconditioned stimulus (US) in Pavlovian-autoshaping procedures. In these experiments, the insertion of a lever conditioned stimulus (CS) was followed by the brief presentation of a sipper tube containing saccharin-ethanol US solution. Experience with this Pavlovian-autoshaping procedure engendered lever CS-directed autoshaping conditioned responses (CRs) in all rats. In Experiment 1, the concentration of ethanol [0%, 2%, 4%, 6%, or 8% (vol./vol.)] in 0.1% saccharin was systematically increased within subjects across autoshaping sessions to evaluate the relation between a rat's drinking and lever pressing. In Experiment 2, the mean intertrial interval (ITI) duration (60, 90, 120 s) was systematically increased within subjects across autoshaping sessions to evaluate the effect of ITI duration on drinking and lever pressing. A pseudoconditioning control group received lever CS randomly with respect to the saccharin-ethanol US solution. In Experiment 1, lever-press autoshaping CRs developed in all rats, and the tendency of a rat to drink an ethanol concentration was predictive of the performance of lever-press autoshaping CRs. In Experiment 2, longer ITIs induced more lever CS-directed responding, and CS-US paired procedures yielded more lever CS-directed responding than that observed in CS-US random procedures. Saccharin-ethanol is an effective US in Pavlovian-autoshaping procedures, inducing more CS-directed responding than in pseudoconditioning controls receiving CS-US random procedures. More lever CS-directed responding was observed when there was more drinking of the saccharin-ethanol US solution (Experiment 1); when the CS and US were paired, rather than random (Experiment 2); and with longer mean ITI durations (Experiment 2). This pattern of results is consistent with the hypothesis that lever CS-directed responding reflects performance

  6. Is induction produced by upcoming food-pellet reinforcement the outcome of an increase in overall activity or in operant responding?

    PubMed

    Weatherly, Jeffrey N; Arthur, Emily I L; Nurnberger, Jeri T

    2006-01-01

    Researchers have demonstrated that rats reliably increase their rates of pressing a lever for 1% liquid-sucrose reinforcement if they will soon have the opportunity to press a lever for food-pellet reinforcement. In the present experiments, the authors investigated if this increase in response rates occurred because the upcoming food pellets produced an increase in all behaviors (i.e., general arousal) or an increase in only the specific operant response (i.e., lever pressing). The results of Experiments 1 and 2 showed that the appearance of induction in rats' lever pressing for 1% sucrose reinforcement when food-pellet reinforcement was upcoming did not coincide with increases in the frequency of running in a wheel or making a nonreinforced nose-poke response. On the other hand, in Experiment 3, the authors found the appearance of induction coincided with increase nonreinforced lever presses on an adjacent lever. These results shed doubt on the idea that induction is a result of a general increase in all activity, and suggest instead that the increase in responding that occurs during induction is limited to the operant response.

  7. Stereotypes for lever-tap operation.

    PubMed

    Chan, Alan H S; Tsang, Steve N H; Hoffmann, Errol R

    2016-04-15

    Lever-operated taps have become more popular and are commonly used in operating theatres, food preparation areas and where users have poor strength; however, there is very little data available for user expectations on tap operation. Thus, an experiment on dual lever-operated water tap (faucets) was conducted with the aim of for providing information for improved design. This study aims to compare different lever-tap designs and their stereotypes adopted by the end-user to operate them also to verify the stereotypes for increasing or decreasing the water flow. 240 participants were requested to rotate the lever tap to indicate direction for increasing and decreasing water flow with simulated hardware, using actual taps placed at the top of a simulated washbasin. Nine initial positions of the lever were used for increasing and decreasing flows, ranging from the ends of both levers facing outward from the bowl center to the ends of both levers facing inward. All levers operated in the horizontal plane. Strong stereotypes (greater than 80%) for several initial lever orientations were found for increasing water flow, especially when the initial lever end positions were facing outwards. However, for different initial positions at which participants were told that the water was flowing and the flow was to be decreased, no strong stereotypes existed. The stereotypes for increasing water flow of dual-lever taps were strong, whereas those for decreasing water flow were weak and hence the stereotype reversibility was also weak. In terms of user expectations, lever taps do not show any great advantage over cross-taps in terms of operator expectations for increasing and decreasing water flow.

  8. Lightweight Seat Lever Operation Characteristics

    NASA Technical Reports Server (NTRS)

    Rajulu, Sudhakar

    1999-01-01

    In 1999, a Shuttle crew member was unable to operate the backrest lever for the lightweight seat in microgravity. It is essential that crew members can adjust this backrest lever, which is titled forward during launch and then moved backward upon reaching orbit. This adjustment is needed to cushion the crew members during an inadvertent crash landing situation. JSCs Anthropometry and Biomechanics Facility (ABF) performed an evaluation of the seat controls and provided recommendations on whether the seat lever positions and operations should be modified. The original Shuttle seats were replaced with new lightweight seats whose controls were moved, with one control at the front and the other at the back. The ABF designed a 12-person experiment to investigate the amount of pull force exerted by suited subjects, when controls were placed in the front and back of the lightweight seat. Each subject was asked to perform the pull test at least three times for each combination of lever position and suit pressure conditions. The results showed that, in general, the subjects were able to pull on the lever at the back position with only about half the amount of force that they were able to exert on the lever at the front position. In addition, the results also showed that subjects wearing the pressurized suit were unable to reach the seat lever when it was located at the back. The pull forces on the front lever diminished about 50% when subjects wore pressurized suits. Based on these results from this study, it was recommended that the levers should not be located in the back position. Further investigation is needed to determine whether the levers at the front of the seat could be modified or adjusted to increase the leverage for crew members wearing pressurized launch/escape suits.

  9. Effects of muscimol, amphetamine, and DAMGO injected into the nucleus accumbens shell on food-reinforced lever pressing by undeprived rats.

    PubMed

    Stratford, Thomas R; Wirtshafter, David

    2012-05-01

    Previous studies have shown that large increases in food intake in nondeprived animals can be induced by injections of both the GABA(A) agonist muscimol and the μ-opioid agonist DAMGO into the nucleus accumbens shell (AcbSh), while injections of the catecholamine agonist amphetamine have little effect. In the current study we examined whether injections of these drugs are able to increase food-reinforced lever pressing in nondeprived rats. Twelve subjects were trained to lever press on a continuous reinforcement schedule while food deprived and were then tested after being placed back on ad libitum feeding. Under these conditions, responding was markedly increased by injections of either muscimol or DAMGO, although the onset of the effects of the latter drug was delayed by 30-40 min. In contrast, amphetamine injections failed to increase reinforced lever pressing, although they did enhance responding on a non-reinforced lever, presumably reflecting alterations in behavioral activation. These results demonstrate that stimulation of GABA(A) and μ-opioid receptors within the AcbSh is able to promote not only food intake, but also food-directed operant behavior. In contrast, stimulation of AcbSh dopamine receptors may enhance behavioral arousal, but does not appear to specifically potentiate behaviors directed toward food procurement. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. An analysis of policy levers used to implement mental health reform in Australia 1992-2012.

    PubMed

    Grace, Francesca C; Meurk, Carla S; Head, Brian W; Hall, Wayne D; Carstensen, Georgia; Harris, Meredith G; Whiteford, Harvey A

    2015-10-24

    Over the past two decades, mental health reform in Australia has received unprecedented government attention. This study explored how five policy levers (organisation, regulation, community education, finance and payment) were used by the Australian Federal Government to implement mental health reforms. Australian Government publications, including the four mental health plans (published in 1992, 1998, 2003 and 2008) were analysed according to policy levers used to drive reform across five priority areas: [1] human rights and community attitudes; [2] responding to community need; [3] service structures; [4] service quality and effectiveness; and [5] resources and service access. Policy levers were applied in varying ways; with two or three levers often concurrently used to implement a single initiative or strategy. For example, changes to service structures were achieved using various combinations of all five levers. Attempts to improve service quality and effectiveness were instead made through a single lever-regulation. The use of some levers changed over time, including a move away from prescriptive, legislative use of regulation, towards a greater focus on monitoring service standards and consumer outcomes. Patterns in the application of policy levers across the National Mental Health Strategy, as identified in this analysis, represent a novel way of conceptualising the history of mental health reform in Australia. An improved understanding of the strategic targeting and appropriate utilisation of policy levers may assist in the delivery and evaluation of evidence-based mental health reform in the future.

  11. Differential Acquisition of Lever Pressing in Inbred and Outbred Mice: Comparison of One-Lever and Two-Lever Procedures and Correlation with Differences in Locomotor Activity

    ERIC Educational Resources Information Center

    McKerchar, Todd L.; Zarcone, Troy J.; Fowler, Stephen C.

    2005-01-01

    Recent progress in mouse genetics has led to an increased interest in developing procedures for assessing mouse behavior, but relatively few of the behavioral procedures developed involve positively reinforced operant behavior. When operant methods are used, nose poking, not lever pressing, is the target response. In the current study differential…

  12. A 3-lever discrimination procedure reveals differences in the subjective effects of low and high doses of MDMA.

    PubMed

    Harper, David N; Langen, Anna-Lena; Schenk, Susan

    2014-01-01

    Drug discrimination studies have suggested that the subjective effects of low doses of (±)3,4-methylenedioxymethamphetamine (MDMA) are readily differentiated from those of d-amphetamine (AMPH) and that the discriminative stimulus properties are mediated by serotonergic and dopaminergic mechanisms, respectively. Previous studies, however, have primarily examined responses to doses that do not produce substantial increases in extracellular dopamine. The present study determined whether doses of MDMA that produce increases in synaptic dopamine would also produce subjective effects that were more like AMPH and were sensitive to pharmacological manipulation of D1-like receptors. A three-lever drug discrimination paradigm was used. Rats were trained to respond on different levers following saline, AMPH (0.5mg/kg, IP) or MDMA (1.5mg/kg, IP) injections. Generalization curves were generated for a range of different doses of both drugs and the effect of the D1-like antagonist, SCH23390 on the discriminative stimulus effects of different doses of MDMA was determined. Rats accurately discriminated MDMA, AMPH and saline. Low doses of MDMA produced almost exclusive responding on the MDMA lever but at doses of 3.0mg/kg MDMA or higher, responding shifted to the AMPH lever. The AMPH response produced by higher doses of MDMA was attenuated by pretreatment with SCH23390. The data suggest that low doses and higher doses of MDMA produce distinct discriminative stimuli. The shift to AMPH-like responding following administration of higher doses of MDMA, and the decrease in this response following administration of SCH23390 suggests a dopaminergic component to the subjective experience of MDMA at higher doses. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Nicotine enhances operant responding for qualitatively distinct reinforcers under maintenance and extinction conditions.

    PubMed

    Barret, Scott T; Bevins, Rick A

    2013-12-01

    Nicotine enhancement of reward has been implicated as an important contributor to tobacco addiction. Despite the attention that reward enhancement has received, the behavioral mechanisms whereby nicotine enhances operant responding remain largely unknown. The present study sought to extend previous work by evaluating the effects of nicotine on responding for two qualitatively different rewards (visual stimulation (VS) and 4% sucrose solution) under fixed-ratio (FR) maintenance and extinction conditions. Sprague–Dawley rats were trained to press an active lever for VS (Experiment 1) or 4% sucrose solution (Experiment 2) and evaluated over 15 sessions on a FR5 schedule of reinforcement. Nicotine (0.4 mg base/kg, SC) or saline were administered 5 min before each session; the alternate solution was given in the home cage after the session. The effects of nicotine on extinction responding were then assessed over 5 sessions and rats were divided into 4 groups based on drug of injection received during FR-maintenance and extinction phases (maintenance–extinction): Nic–Nic, Nic–Sal, Sal–Sal, and Sal–Nic. Nicotine increased active lever response rates for both VS and 4% sucrose under FR5 maintenance conditions. Nicotine also increased response rates in the Nic–Nic group relative to all other groups under extinction conditions in both experiments, though this effect had greater longevity following VS maintenance conditions than sucrose. Enhancement of responding during extinction does not appear dependent upon locomotor activation by nicotine.

  14. Effects of contingent and noncontingent nicotine on lever pressing for liquids and consumption in water-deprived rats.

    PubMed

    Frenk, Hanan; Martin, Jeffrey; Vitouchanskaia, Cristina; Dar, Reuven; Shalev, Uri

    2017-01-05

    Nicotine has been proposed to be a primary reinforcer and a reinforcement enhancer. To date, no studies have examined whether nicotine enhances consummatory behaviors or only operant responding (appetitive behaviors). Experiments were designed to test whether contingent and noncontingent nicotine enhance lever pressing for and consumption of fluids in water-deprived rats. Animals were water-deprived throughout all experiments. They were trained to press two levers under a variable interval (VI-20, 1-35s). Their lever pressing and water consumption were measured after noncontingent subcutaneous (s.c.) injection of nicotine (1mg/kg), and in 3 choice conditions (water and quinine solution (18µg/ml); water and nicotine (32µg/ml) solution; quinine (18µg/ml) and nicotine (32µg/ml) solutions) where nicotine was thus delivered contingently upon lever pressing. The effects of nicotine (1mg/kg; s.c.) on the consumption of water in a time-limited free access (1h) paradigm were assessed. Nicotine significantly increased lever pressing and the number of earned reinforcements on both levers in the two choice conditions and when administered s.c. compared to all groups that did not receive nicotine. However, under no condition did animals consume more fluids than baseline. Under the time-limited free access condition nicotine reduced water consumption. Although our findings do not support a reinforcing effect for nicotine, they are consistent with the incentive-amplification hypothesis. Its relevance for human smoking is yet unclear. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. 14. INTERIOR OF MAIN DECKNOTE LEVERS FROM CEILING CONTROLLED BY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. INTERIOR OF MAIN DECK--NOTE LEVERS FROM CEILING CONTROLLED BY OPERATOR. LEFT HAND LEVER CONTROLLED THROTTLE, RIGHT HAND LEVER CONTROLLED SHOT GUN SWINGER. - Dredge CINCINNATI, Docked on Ohio River at foot of Lighthill Street, Pittsburgh, Allegheny County, PA

  16. What role does performance information play in securing improvement in healthcare? a conceptual framework for levers of change

    PubMed Central

    Levesque, Jean-Frederic; Sutherland, Kim

    2017-01-01

    Objective Across healthcare systems, there is consensus on the need for independent and impartial assessment of performance. There is less agreement about how measurement and reporting performance improves healthcare. This paper draws on academic theories to develop a conceptual framework—one that classifies in an integrated manner the ways in which change can be leveraged by healthcare performance information. Methods A synthesis of published frameworks. Results The framework identifies eight levers for change enabled by performance information, spanning internal and external drivers, and emergent and planned processes: (1) cognitive levers provide awareness and understanding; (2) mimetic levers inform about the performance of others to encourage emulation; (3) supportive levers provide facilitation, implementation tools or models of care to actively support change; (4) formative levers develop capabilities and skills through teaching, mentoring and feedback; (5) normative levers set performance against guidelines, standards, certification and accreditation processes; (6) coercive levers use policies, regulations incentives and disincentives to force change; (7) structural levers modify the physical environment or professional cultures and routines; (8) competitive levers attract patients or funders. Conclusion This framework highlights how performance measurement and reporting can contribute to eight different levers for change. It provides guidance into how to align performance measurement and reporting into quality improvement programme. PMID:28851769

  17. A wheelchair with lever propulsion control for climbing up and down stairs.

    PubMed

    Sasaki, Kai; Eguchi, Yosuke; Suzuki, Kenji

    2016-08-01

    This study proposes a novel stair-climbing wheelchair based on lever propulsion control using the human upper body. Wheelchairs are widely used as supporting locomotion devices for people with acquired lower limb disabilities. However, steps and stairs are critical obstacles to locomotion, which restrict their activities when using wheelchairs. Previous research focused on power-assisted, stair-climbing wheelchairs, which were large and heavy due to its large actuators and mechanisms. In the previous research, we proposed a wheelchair with lever propulsion mechanism and presented its feasibility of climbing up the stairs. The developed stair-climbing wheelchair consists of manual wheels with casters for planar locomotion and a rotary-leg mechanism based on lever propulsion that is capable of climbing up stairs. The wheelchair also has a passive mechanism powered by gas springs for posture transition to shift the user's center of gravity between the desired positions for planar locomotion and stair-climbing. In this paper, we present an advanced study on both climbing up and going down using lever propulsion control by the user's upper body motion. For climbing down the stairs, we reassembled one-way clutches used for the rotary-leg mechanism to help a user climb down the stairs through lever operation. We also equipped the wheelchair with sufficient torque dampers. The frontal wheels were fixed while climbing down the stairs to ensure safety. Relevant experiments were then performed to investigate its performance and verify that the wheelchair users can operate the proposed lever propulsion mechanism.

  18. Regulatory light chain mutants linked to heart disease modify the cardiac myosin lever arm.

    PubMed

    Burghardt, Thomas P; Sikkink, Laura A

    2013-02-19

    Myosin is the chemomechanical energy transducer in striated heart muscle. The myosin cross-bridge applies impulsive force to actin while consuming ATP chemical energy to propel myosin thick filaments relative to actin thin filaments in the fiber. Transduction begins with ATP hydrolysis in the cross-bridge driving rotary movement of a lever arm converting torque into linear displacement. Myosin regulatory light chain (RLC) binds to the lever arm and modifies its ability to translate actin. Gene sequencing implicated several RLC mutations in heart disease, and three of them are investigated here using photoactivatable GFP-tagged RLC (RLC-PAGFP) exchanged into permeabilized papillary muscle fibers. A single-lever arm probe orientation is detected in the crowded environment of the muscle fiber by using RLC-PAGFP with dipole orientation deduced from the three-spatial dimension fluorescence emission pattern of the single molecule. Symmetry and selection rules locate dipoles in their half-sarcomere, identify those at the minimal free energy, and specify active dipole contraction intermediates. Experiments were performed in a microfluidic chamber designed for isometric contraction, total internal reflection fluorescence detection, and two-photon excitation second harmonic generation to evaluate sarcomere length. The RLC-PAGFP reports apparently discretized lever arm orientation intermediates in active isometric fibers that on average produce the stall force. Disease-linked mutants introduced into RLC move intermediate occupancy further down the free energy gradient, implying lever arms rotate more to reach stall force because mutant RLC increases lever arm shear strain. A lower free energy intermediate occupancy involves a lower energy conversion efficiency in the fiber relating a specific myosin function modification to the disease-implicated mutant.

  19. What role does performance information play in securing improvement in healthcare? a conceptual framework for levers of change.

    PubMed

    Levesque, Jean-Frederic; Sutherland, Kim

    2017-08-28

    Across healthcare systems, there is consensus on the need for independent and impartial assessment of performance. There is less agreement about how measurement and reporting performance improves healthcare. This paper draws on academic theories to develop a conceptual framework-one that classifies in an integrated manner the ways in which change can be leveraged by healthcare performance information. A synthesis of published frameworks. The framework identifies eight levers for change enabled by performance information, spanning internal and external drivers, and emergent and planned processes: (1) cognitive levers provide awareness and understanding; (2) mimetic levers inform about the performance of others to encourage emulation; (3) supportive levers provide facilitation, implementation tools or models of care to actively support change; (4) formative levers develop capabilities and skills through teaching, mentoring and feedback; (5) normative levers set performance against guidelines, standards, certification and accreditation processes; (6) coercive levers use policies, regulations incentives and disincentives to force change; (7) structural levers modify the physical environment or professional cultures and routines; (8) competitive levers attract patients or funders. This framework highlights how performance measurement and reporting can contribute to eight different levers for change. It provides guidance into how to align performance measurement and reporting into quality improvement programme. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Using clinical governance levers to support change in a cancer care reform.

    PubMed

    Brault, Isabelle; Denis, Jean-Louis; Sullivan, Terrence James

    2015-01-01

    Introducing change is a difficult issue facing all health care systems. The use of various clinical governance levers can facilitate change in health care systems. The purpose of this paper is to define clinical governance levers, and to illustrate their use in a large-scale transformation. The empirical analysis deals with the in-depth study of a specific case, which is the organizational model for Ontario's cancer sector. The authors used a qualitative research strategy and drew the data from three sources: semi-structured interviews, analysis of documents, and non-participative observations. From the results, the authors identified three phases and several steps in the reform of cancer services in this province. The authors conclude that a combination of clinical governance levers was used to transform the system. These levers operated at different levels of the system to meet the targeted objectives. To exercise clinical governance, managers need to acquire new competencies. Mobilizing clinical governance levers requires in-depth understanding of the role and scope of clinical governance levers. This study provides a better understanding of clinical governance levers. Clinical governance levers are used to implement an organizational environment that is conducive to developing clinical practice, as well as to act directly on practices to improve quality of care.

  1. Effects of exposure to 56Fe particles or protons on fixed-ratio operant responding in rats

    NASA Technical Reports Server (NTRS)

    Rabin, Bernard M.; Buhler, Lynn L.; Joseph, James A.; Shukitt-Hale, Barbara; Jenkins, Daniel G.

    2002-01-01

    On long-duration trips outside of the magnetosphere, astronauts will be exposed to protons and to heavy particles which can affect their performance of required tasks. It is essential to determine the range of behaviors that might be affected by exposure to these types of radiation in order to understand the nature of behavioral deficits and to develop effective countermeasures. The present experiment examined the ability of rats to make an operant response following exposure to protons (250 MeV, 4 Gy) or 56Fe particles (1 GeV/n, 1 or 2 Gy). Following irradiation, rats were trained to press a lever in order to obtain food reinforcement. They were then placed on an ascending fixed-ratio schedule from FR-1 (each lever press rewarded with a food pellet) through FR-35 (35 lever presses required for 1 food pellet). Rats exposed to 4 Gy of protons or 1 Gy of 56Fe particles responded similarly to controls, increasing their rate of responding as the ratio increased. However, rats exposed to 2 Gy of 56Fe particles failed to increase their rate of responding at ratios greater than FR-20, indicating that rats exposed to 2 Gy of 56Fe particles cannot respond appropriately to increasing work requirements.

  2. Response-food delay gradients for lever pressing and schedule-induced licking in rats.

    PubMed

    Pellón, Ricardo; Pérez-Padilla, Angeles

    2013-06-01

    Eight food-deprived Wistar rats developed stable patterns of lever pressing and licking when exposed to a fixed-time 30-s schedule of food pellet presentation. The rats were trained to lever press by presenting the lever 10 s before the programmed food delivery, with the food pellet being delivered immediately upon a lever press. The operant contingency was then removed and the lever was inserted through the entire interfood interval, being withdrawn with food delivery and reinserted 2 s later. On successive phases of the study, a protective contingency postponed food delivery if responses (lever presses or licks) occurred within the last 1, 2, 5, 10, 20, or 25 s of the interfood interval. Lever pressing was reduced at much shorter response-food delays than those that reduced licking. These results demonstrate that reinforcement contributes to the maintenance of different response patterns on periodic schedules, and that different responses are differentially sensitive to delays.

  3. Effect of Light/Dark Cycle on Wheel Running and Responding Reinforced by the Opportunity to Run Depends on Postsession Feeding Time

    ERIC Educational Resources Information Center

    Belke, T. W.; Mondona, A. R.; Conrad, K. M.; Poirier, K. F.; Pickering, K. L.

    2008-01-01

    Do rats run and respond at a higher rate to run during the dark phase when they are typically more active? To answer this question, Long Evans rats were exposed to a response-initiated variable interval 30-s schedule of wheel-running reinforcement during light and dark cycles. Wheel-running and local lever-pressing rates increased modestly during…

  4. 49 CFR 236.340 - Electromechanical interlocking machine; locking between electrical and mechanical levers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical interlocking machine, locking between electric and mechanical levers shall be maintained so that mechanical...

  5. Noninvasive determination of optical lever sensitivity in atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Higgins, M. J.; Proksch, R.; Sader, J. E.; Polcik, M.; Mc Endoo, S.; Cleveland, J. P.; Jarvis, S. P.

    2006-01-01

    Atomic force microscopes typically require knowledge of the cantilever spring constant and optical lever sensitivity in order to accurately determine the force from the cantilever deflection. In this study, we investigate a technique to calibrate the optical lever sensitivity of rectangular cantilevers that does not require contact to be made with a surface. This noncontact approach utilizes the method of Sader et al. [Rev. Sci. Instrum. 70, 3967 (1999)] to calibrate the spring constant of the cantilever in combination with the equipartition theorem [J. L. Hutter and J. Bechhoefer, Rev. Sci. Instrum. 64, 1868 (1993)] to determine the optical lever sensitivity. A comparison is presented between sensitivity values obtained from conventional static mode force curves and those derived using this noncontact approach for a range of different cantilevers in air and liquid. These measurements indicate that the method offers a quick, alternative approach for the calibration of the optical lever sensitivity.

  6. Effects of lesions of the amygdala central nucleus on autoshaped lever pressing

    PubMed Central

    Chang, Stephen E.; Wheeler, Daniel S.; Holland, Peter C.

    2012-01-01

    Neutral cues paired with rewards often appear to acquire motivational significance, as if the incentive motivational value of the reward is transferred to the cue. Such cues have been reported to modulate the performance of instrumental action (Pavlovian-instrumental transfer, PIT), serve as conditioned reinforcers in the establishment of new learning, and be the targets of approach and other cue-directed behaviors. Here we examined the effects of lesions of the amygdala central nucleus (CeA) on the acquisition of discriminative autoshaped lever-pressing. Insertion of one lever into the experimental chamber was reinforced by sucrose delivery, but insertion of another lever was not reinforced. Although sucrose delivery was not contingent on lever pressing, both CeA- and sham-lesioned rats rapidly came to press the reinforced but not the nonreinforced lever. Despite their showing little evidence of impairments in autoshaped lever pressing, these same CeA-lesioned rats showed significant deficits in the expression of PIT in a subsequent phase of the experiment. The lack of impaired autoshaping in CeA-lesioned rats contrasts with effects previously reported for conditioned orienting responses (ORs) and for other putative measures of incentive learning including PIT and conditioned approach to visual cues. PMID:22386516

  7. Learning not to respond: Role of the hippocampus in withholding responses during omission training.

    PubMed

    White, Norman M; Naeem, Maliha

    2017-02-01

    Autoshaping is a Pavlovian learning paradigm in which rats experience pairings of a CS and a US independently of their behavior. When the CS is a lever inserted into the test cage and the US is food delivered to an adjacent magazine, many rats acquire a lever-pressing response called 'sign-tracking' even though that response has no effect on the occurrence of either the CS or the US. Since these lever presses are always followed by the US, it has been suggested that sign-tracking could be due to unintended reinforcement of the response. To eliminate the possibility of such instrumental learning the omission schedule, in which a response to the CS cancels the US, was introduced. Previous research has shown that training rats on autoshaping and switching them to an omission schedule generally reduces but does not eliminate sign-tracking, suggesting that it may be due to both Pavlovian and instrumental learning. In the present study naive rats trained on an omission schedule sign-tracked less than a control group exposed to random, unpaired CS and US presentations, suggesting that they learned to withhold the lever press response because of the negative contingency between that response and the US. In a second experiment rats with dorsal hippocampus lesions sign-tracked more than sham-lesioned rats on omission schedules, suggesting that this case of learning not to respond is hippocampus-based. This conclusion is consistent with many previous findings on the inability of hippocampal rats to withhold or suppress responding, and with studies suggesting that one form of extinction of learned responses in normal rats is due to competition from hippocampus-based learning not to respond. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Effects of an ethanol-paired CS on responding for ethanol and food: Comparisons with a stimulus in a Truly-Random-Control group and to a food-paired CS on responding for food.

    PubMed

    Lamb, R J; Ginsburg, Brett C; Schindler, Charles W

    2016-12-01

    Motivational increases due to exposure to alcohol-paired Conditioned Stimuli (CS) are central to some accounts of alcoholism. However, few studies isolate a stimulus's function as a CS from its other potential functions. Pavlovian-Instrumental-Transfer (PIT) procedures isolate a stimulus's function as a CS from its other functions. Though there are several relevant studies using PIT, knowledge gaps exist. Particularly, it is not clear that an alcohol-paired CS will increase alcohol seeking compared to the same stimulus in a Truly-Random-Control group, nor whether such increases are specific to alcohol seeking. To address these knowledge gaps in Experiment 1, rats responded for ethanol (0.1 ml 8% w/v) under an RI 30-sec schedule, then the lever was removed and half the rats had ethanol delivered during occasional 120-sec light presentations, while the remainder had ethanol and the light presented under independent RT schedules. Later the lever was returned and the light was presented during responding in extinction (PIT test). Following this test, levers were again removed and the light was presented without ethanol (light extinction), following again by a PIT test. Responding in the two groups during light presentations did not differ in either PIT test. Experiment 2 repeated Experiment 1 using food instead of ethanol. In Experiment 2, responding during light presentations increased in the paired group. In Experiment 3, rats were trained on a concurrent FR schedule of food and ethanol delivery. Ethanol was delivered following 5 responses and the response requirement for food adjusted so that similar numbers of food and ethanol deliveries were obtained. Subsequently, rats underwent conditioning, control and testing procedures identical to those in Experiment 1. In Experiment 3, the ethanol-paired CS increased ethanol-responding, but not food-responding. These results are most easily interpreted as changes in responding resulting from CS-elicited behavior rather

  9. Ergonomic Evaluation of Space Shuttle Light-Weight Seat Lever Position and Operation

    NASA Technical Reports Server (NTRS)

    Maida, J.; Rajulu, Sudhakar L.; Bond, Robert L. (Technical Monitor)

    2000-01-01

    During a Shuttle flight in the early part of 1999, one of the crewmembers was unable to operate the backrest lever for the light-weight seat in microgravity. It is essential that the crewmembers are able to adjust this back-rest lever, which is titled forward 2 degrees from vertical during launch and then moved backwards to 10 degrees aft of vertical upon reaching orbit. This adjustment is needed to cushion the crewmembers during an inadvertent crash landing situation. The original Shuttle seats, which had seat controls located on the front left and right sides of the seat, were replaced recently with the new light-weight seats. The controls for these new, seats were moved to the night side with one control at the front and the other at the back. While it was uncertain whether the problem encountered was unique to that crewmember or not it was clear to the personnel responsible for maintaining the Shuttle seats that not knowing the cause of the problem posed a safety concern for NASA. Hence the Anthropometry and Biomechanics Facility (ABF) of the Johnson Space Center was requested to perform an evaluation of the seat controls and provide NASA with appropriate recommendations on whether the seat lever positions and operations should be modified. The ABF designed an experiment to investigate the amount of pull force exerted by subjects, wearing an unpressurized or pressurized crew launch escape suit, when controls were placed in the front and back (on the right side) of the light-weight seat. Single-axis load cells were attached to the seat levers, which measured the maximum static pull forces that were exerted by the subjects. Twelve subjects, six male and six female, participated in this study. Each subject was asked to perform the pull test at least three times for each combination of lever position and suit pressure conditions. The results from this study showed that as a whole (or in general), the subjects were able to pull on the lever at the back position with

  10. Mechanical efficiency of two commercial lever-propulsion mechanisms for manual wheelchair locomotion.

    PubMed

    Lui, Jordon; MacGillivray, Megan K; Sheel, A William; Jeyasurya, Jeswin; Sadeghi, Mahsa; Sawatzky, Bonita Jean

    2013-01-01

    The purpose of this study was to (1) evaluate the mechanical efficiency (ME) of two commercially available lever-propulsion mechanisms for wheelchairs and (2) compare the ME of lever propulsion with hand rim propulsion within the same wheelchair. Of the two mechanisms, one contained a torsion spring while the other used a roller clutch design. We hypothesized that the torsion spring mechanism would increase the ME of propulsion due to a passive recovery stroke enabled by the mechanism. Ten nondisabled male participants with no prior manual wheeling experience performed submaximal exercise tests using both lever-propulsion mechanisms and hand rim propulsion on two different wheelchairs. Cardiopulmonary parameters including oxygen uptake (VO2), heart rate (HR), and energy expenditure (En) were determined. Total external power (Pext) was measured using a drag test protocol. ME was determined by the ratio of Pext to En. Results indicated no significant effect of lever-propulsion mechanism for all physiological measures tested. This suggests that the torsion spring did not result in a physiological benefit compared with the roller clutch mechanism. However, both lever-propulsion mechanisms showed decreased VO2 and HR and increased ME (as a function of slope) compared with hand rim propulsion (p < 0.001). This indicates that both lever-propulsion mechanisms tested are more mechanically efficient than conventional hand rim propulsion, especially when slopes are encountered.

  11. The Effects of Lever Arm (Instrument Offset) Error on GRAV-D Airborne Gravity Data

    NASA Astrophysics Data System (ADS)

    Johnson, J. A.; Youngman, M.; Damiani, T.

    2017-12-01

    High quality airborne gravity collection with a 2-axis, stabilized platform gravity instrument, such as with a Micro-g LaCoste Turnkey Airborne Gravity System (TAGS), is dependent on the aircraft's ability to maintain "straight and level" flight. However, during flight there is constant rotation about the aircraft's center of gravity. Standard practice is to install the scientific equipment close to the aircraft's estimated center of gravity to minimize the relative rotations with aircraft motion. However, there remain small offsets between the instruments. These distance offsets, the lever arm, are used to define the rigid-body, spatial relationship between the IMU, GPS antenna, and airborne gravimeter within the aircraft body frame. The Gravity for the Redefinition of the American Vertical Datum (GRAV-D) project, which is collecting airborne gravity data across the U.S., uses a commercial software package for coupled IMU-GNSS aircraft positioning. This software incorporates a lever arm correction to calculate a precise position for the airborne gravimeter. The positioning software must do a coordinate transformation to relate each epoch of the coupled GNSS-IMU derived position to the position of the gravimeter within the constantly-rotating aircraft. This transformation requires three inputs: accurate IMU-measured aircraft rotations, GNSS positions, and lever arm distances between instruments. Previous studies show that correcting for the lever arm distances improves gravity results, but no sensitivity tests have been done to investigate how error in the lever arm distances affects the final airborne gravity products. This research investigates the effects of lever arm measurement error on airborne gravity data. GRAV-D lever arms are nominally measured to the cm-level using surveying equipment. "Truth" data sets will be created by processing GRAV-D flight lines with both relatively small lever arms and large lever arms. Then negative and positive incremental

  12. Dual Optical Levers for Atomic Force Microscopy

    NASA Astrophysics Data System (ADS)

    Kawakatsu, Hideki; Bleuler, Hannes; Saito, Takashi; Hiroshi, Kougami

    1995-06-01

    Development of micro machined cantilever and optical lever detection system has greatly facilitated the operation of atomic force microscopy. However, since the detection system measures only the deflection of the cantilever at one set point where the laser beam is focused, care must be taken in implementing force control or in interpreting the acquired data. In this paper, a dual optical lever detection system is introduced, which has the potential to resolve the deformation of the cantilever with multidegree of freedom and thus detect the position of the tip end point with resolution in the 10 pm order. The detection system proved to be effective in real-time monitoring of the behavior of the tip end point while scanning, and in explaining the scanning direction dependence of the acquired images.

  13. Three-axis lever actuator with flexure hinges for an optical disk system

    NASA Astrophysics Data System (ADS)

    Han, Chang-Soo; Kim, Soo-Hyun

    2002-10-01

    A three-axis lever actuator with a flexure hinge has been designed and fabricated. This actuator is driven by electromagnetic force based on a coil-magnet system and can be used as a high precision actuator and, especially as a pickup head actuator in optical disks. High precision and low sensitivity to external vibration are the major advantages of this lever actuator. An analysis model was found and compared to the finite element method. Dynamic characteristics of the three-axis lever actuator were measured. The results are in very close agreement to those predicted by the model and finite element analysis.

  14. Self-calibration method of the inner lever-arm parameters for a tri-axis RINS

    NASA Astrophysics Data System (ADS)

    Song, Tianxiao; Li, Kui; Sui, Jie; Liu, Zengjun; Liu, Juncheng

    2017-11-01

    A rotational inertial navigation system (RINS) could improve navigation performance by modulating the inertial sensor errors with rotatable gimbals. When an inertial measurement unit (IMU) rotates, the deviations between the accelerometer-sensitive points and the IMU center will lead to an inner lever-arm effect. In this paper, a self-calibration method of the inner lever-arm parameters for a tri-axis RINS is proposed. A novel rotation scheme with variable angular rate rotation is designed to motivate the velocity errors caused by the inner lever-arm effect. By extending all inner lever-arm parameters as filter states, a Kalman filter with velocity errors as measurement is established to achieve the calibration. The accuracy and feasibility of the proposed method are illustrated by both simulations and experiments. The final results indicate that the inner lever-arm effect is significantly restrained after compensation by the calibration results.

  15. Ethanol induces impulsive-like responding in a delay-of-reward operant choice procedure: impulsivity predicts autoshaping.

    PubMed

    Tomie, A; Aguado, A S; Pohorecky, L A; Benjamin, D

    1998-10-01

    Autoshaping conditioned responses (CRs) are reflexive and targeted motor responses expressed as a result of experience with reward. To evaluate the hypothesis that autoshaping may be a form of impulsive responding, within-subjects correlations between performance on autoshaping and impulsivity tasks were assessed in 15 Long-Evans hooded rats. Autoshaping procedures [insertion of retractable lever conditioned stimulus (CS) followed by the response-independent delivery of food (US)] were followed by testing for impulsive-like responding in a two-choice lever-press operant delay-of-reward procedure (immediate small food reward versus delayed large food reward). Delay-of-reward functions revealed two distinct subject populations. Subjects in the Sensitive group (n=7) were more impulsive-like, increasing immediate reward choices at longer delays for large reward, while those in the Insensitive group (n=8) responded predominantly on only one lever. During the prior autoshaping phase, the Sensitive group had performed more autoshaping CRs, and correlations revealed that impulsive subjects acquired the autoshaping CR in fewer trials. In the Sensitive group, acute injections of ethanol (0, 0.25, 0.50, 1.00, 1.50 g/kg) given immediately before delay-of-reward sessions yielded an inverted U-shaped dose-response curve with increased impulsivity induced by the 0.25, 0.50, and 1.00 g/kg doses of ethanol, while choice strategy of the Insensitive group was not influenced by ethanol dose. Ethanol induced impulsive-like responding only in rats that were flexible in their response strategy (Sensitive group), and this group also performed more autoshaping CRs. Data support the hypothesis that autoshaping and impulsivity are linked.

  16. 49 CFR 236.340 - Electromechanical interlocking machine; locking between electrical and mechanical levers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Electromechanical interlocking machine; locking between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical...

  17. 49 CFR 236.340 - Electromechanical interlocking machine; locking between electrical and mechanical levers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Electromechanical interlocking machine; locking between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical...

  18. 49 CFR 236.340 - Electromechanical interlocking machine; locking between electrical and mechanical levers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Electromechanical interlocking machine; locking between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical...

  19. 49 CFR 236.340 - Electromechanical interlocking machine; locking between electrical and mechanical levers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Electromechanical interlocking machine; locking between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical...

  20. Measuring How Muscles Function in Levers.

    ERIC Educational Resources Information Center

    DeMont, M. Edwin

    1996-01-01

    Presents an exercise that examines the lever systems that function in the chelae of the American lobster. Involves calculating the mechanical and distance advantages of the crusher and pincer chelae and estimating the actual forces generated by the contraction of the muscles and the magnitude of the forces transmitted around the fulcrum to the tip…

  1. In Vivo Orientation of Single Myosin Lever Arms in Zebrafish Skeletal Muscle

    PubMed Central

    Sun, Xiaojing; Ekker, Stephen C.; Shelden, Eric A.; Takubo, Naoko; Wang, Yihua; Burghardt, Thomas P.

    2014-01-01

    Cardiac and skeletal myosin assembled in the muscle lattice power contraction by transducing ATP free energy into the mechanical work of moving actin. Myosin catalytic/lever-arm domains comprise the transduction/mechanical coupling machinery that move actin by lever-arm rotation. In vivo, myosin is crowded and constrained by the fiber lattice as side chains are mutated and otherwise modified under normal, diseased, or aging conditions that collectively define the native myosin environment. Single-myosin detection uniquely defines bottom-up characterization of myosin functionality. The marriage of in vivo and single-myosin detection to study zebrafish embryo models of human muscle disease is a multiscaled technology that allows one-to-one registration of a selected myosin molecular alteration with muscle filament-sarcomere-cell-fiber-tissue-organ- and organism level phenotypes. In vivo single-myosin lever-arm orientation was observed at superresolution using a photoactivatable-green-fluorescent-protein (PAGFP)-tagged myosin light chain expressed in zebrafish skeletal muscle. By simultaneous observation of multiphoton excitation fluorescence emission and second harmonic generation from myosin, we demonstrated tag specificity for the lever arm. Single-molecule detection used highly inclined parallel beam illumination and was verified by quantized photoactivation and photobleaching. Single-molecule emission patterns from relaxed muscle in vivo provided extensive superresolved dipole orientation constraints that were modeled using docking scenarios generated for the myosin (S1) and GFP crystal structures. The dipole orientation data provided sufficient constraints to estimate S1/GFP coordination. The S1/GFP coordination in vivo is rigid and the lever-arm orientation distribution is well-ordered in relaxed muscle. For comparison, single myosins in relaxed permeabilized porcine papillary muscle fibers indicated slightly differently oriented lever arms and rigid S1

  2. Repeated Cocaine Experience Facilitates Sucrose-Reinforced Operant Responding in Enriched and Isolated Rats

    ERIC Educational Resources Information Center

    Klein, Emily D.; Gehrke, Brenda J.; Green, Thomas A.; Zentall, Thomas R.; Bardo, Michael T.

    2007-01-01

    The purpose of the present experiment was to determine whether repeated cocaine exposure differentially affects sucrose-reinforced operant responding in rats raised in an enriched condition (EC) or an isolated condition (IC). Specifically, the performance of EC and IC rats pressing a lever for sucrose under a high fixed-ratio schedule (FR 30)…

  3. Effects of Post-Session Wheel Running on Within-Session Changes in Operant Responding

    ERIC Educational Resources Information Center

    Aoyama, Kenjiro

    2007-01-01

    This study tested the effects of post-session wheel running on within-session changes in operant responding. Lever-pressing by six rats was reinforced by a food pellet under a continuous reinforcement (CRF) schedule in 30-min sessions. Two different flavored food pellets were used as reinforcers. In the wheel conditions, 30-min operant-sessions…

  4. Levers for Change in Educational Development in Canada: Looking Back, Looking Forward

    ERIC Educational Resources Information Center

    Dawson, Debra L.

    2017-01-01

    This paper examines levers or drivers that have influenced the direction of educational development in Canada over the last 40 years and also tries to predict what will be the impact of some current levers on changing the work of developers in the next 20 years. Reflecting on those years, it is apparent our work in the 1980s was very focused on…

  5. Responding for sucrose and wheel-running reinforcement: effect of body weight manipulation.

    PubMed

    Belke, Terry W

    2004-02-27

    As body weight increases, the excitatory strength of a stimulus signaling an opportunity to run should weaken to a greater degree than that of a stimulus signaling an opportunity to eat. To test this hypothesis, six male albino Wistar rats were placed in running wheels and exposed to a fixed interval 30-s schedule that produced either a drop of 15% sucrose solution or the opportunity to run for 15s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. The effect of varying body weight on responding maintained by these two reinforcers was investigated by systematically increasing and decreasing post-session food amounts. The initial body weight was 335 g. Body weights were increased to approximately 445 g and subsequently returned to 335 g. As body weight increased, overall and local lever-pressing rates decreased while post-reinforcement pauses lengthened. Analysis of post-reinforcement pauses and local lever-pressing rates in terms of transitions between successive reinforcers revealed that local response rates in the presence of stimuli signaling upcoming wheel and sucrose reinforcers were similarly affected. However, pausing in the presence of the stimulus signaling a wheel-running reinforcer lengthened to a greater extent than did pausing in the presence of the stimulus signaling sucrose. This result suggests that as body weight approaches ad-lib levels, the likelihood of initiation of responding to obtain an opportunity to run approaches zero and the animal "rejects" the opportunity to run in a manner similar to the rejection of less preferred food items in studies of food selectivity.

  6. Effects of sucrose concentration and water deprivation on Pavlovian conditioning and responding for conditioned reinforcement.

    PubMed

    Tabbara, Rayane I; Maddux, Jean-Marie N; Beharry, Priscilla F; Iannuzzi, Jessica; Chaudhri, Nadia

    2016-04-01

    An appetitive Pavlovian conditioned stimulus (CS) can predict an unconditioned stimulus (US) and acquire incentive salience. We tested the hypothesis that US intensity and motivational state of the subject would influence Pavlovian learning and impact the attribution of incentive salience to an appetitive Pavlovian CS. To this end, we examined the effects of sucrose concentration and water deprivation on the acquisition of Pavlovian conditioning and responding for a conditioned reinforcer. Male Long-Evans rats (Harlan; 220-240 g) receiving 3% (3S) or 20% (20S) sucrose were either non-water deprived or given water for 1 hr per day. During Pavlovian conditioning sessions, half the rats in each concentration and deprivation condition received a 10-s CS paired with 0.2 ml of sucrose (16 trials/session; 3.2 ml/session). The remainder received unpaired CS and US presentations. Entries into a port where sucrose was delivered were recorded. Next, responding for conditioned reinforcement was tested, wherein pressing an active lever produced the CS and pressing an inactive lever had no consequences. CS-elicited port entries increased, and latency to the first CS-elicited port entry decreased across sessions in paired groups. Water deprivation augmented these effects, whereas sucrose concentration had no significant impact on behavior. Responding for conditioned reinforcement was observed in the 20S water-deprived, paired group. Thus, water deprivation can facilitate the acquisition of Pavlovian conditioning, potentially by enhancing motivational state, and a high-intensity US and a high motivational state can interact to heighten the attribution of incentive salience to an appetitive Pavlovian CS. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  7. Effects of orbitofrontal cortex lesions on autoshaped lever pressing and reversal learning.

    PubMed

    Chang, Stephen E

    2014-10-15

    A cue associated with a rewarding event can trigger behavior towards the cue itself due to the cue acquiring incentive value through its pairing with the rewarding outcome (i.e., sign-tracking). For example, rats will approach, press, and attempt to "consume" a retractable lever conditioned stimulus (CS) that signals delivery of a food unconditioned stimulus (US). Attending to food-predictive CSs is important when seeking out food, and it is just as important to be able to modify one's behavior when the relationships between CSs and USs are changed. Using a discriminative autoshaping procedure with lever CSs, the present study investigated the effects of orbitofrontal cortex (OFC) lesions on sign-tracking and reversal learning. Insertion of one lever was followed by sucrose delivery upon retraction, and insertion of another lever was followed by nothing. After the acquisition phase, the contingencies between the levers and outcomes were reversed. Bilateral OFC lesions had no effect on the acquisition of sign-tracking. However, OFC-lesioned rats showed substantial deficits in acquiring sign-tracking compared to sham-lesioned rats once the stimulus-outcome contingencies were reversed. Over the course of reversal learning, OFC-lesioned rats were able to reach comparable levels of sign-tracking as sham-lesioned rats. These findings suggest that OFC is not necessary for the ability of a CS to acquire incentive value and provide more evidence that OFC is critical for modifying behavior appropriately following a change in stimulus-outcome contingencies. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Examining the Reinforcement-Enhancement Effects of Phencyclidine and Its Interactions with Nicotine on Lever-Pressing for a Visual Stimulus

    PubMed Central

    Swalve, Natashia; Barrett, Scott T.; Bevins, Rick A.; Li, Ming

    2015-01-01

    Nicotine is a widely-abused drug, yet its primary reinforcing effect does not seem potent as other stimulants such as cocaine. Recent research on the contributing factors toward chronic use of nicotine-containing products has implicated the role of reinforcement-enhancing effects of nicotine. The present study investigates whether phencyclidine (PCP) may also possess a reinforcement-enhancement effect and how this may interact with the reinforcement-enhancement effect of nicotine. PCP was tested for two reasons: 1) it produces discrepant results on overall reward, similar to that seen with nicotine and 2) it may elucidate how other compounds may interact with the reinforcement-enhancement of nicotine. Adult male Sprague-Dawley rats were trained to lever press for brief visual stimulus presentations under fixed-ratio (FR) schedules of reinforcement and then were tested with nicotine (0.2 or 0.4 mg/kg) and/or PCP (2.0 mg/kg) over six increasing FR values. A selective increase in active lever-pressing for the visual stimulus with drug treatment was considered evidence of a reinforcement-enhancement effect. PCP and nicotine separately increased active lever pressing for a visual stimulus in a dose-dependent manner and across the different FR schedules. The addition of PCP to nicotine did not increase lever-pressing for the visual stimulus, possibly due to a ceiling effect. The effect of PCP may be driven largely by its locomotor stimulant effects, whereas the effect of nicotine was independent of locomotor stimulation. This dissociation emphasizes that distinct pharmacological properties contribute to the reinforcement-enhancement effects of substances. PMID:26026783

  9. [Equivalent Lever Principle of Ossicular Chain and Amplitude Reduction Effect of Internal Ear Lymph].

    PubMed

    Zhao, Xiaoyan; Qin, Renjia

    2015-04-01

    This paper makes persuasive demonstrations on some problems about the human ear sound transmission principle in existing physiological textbooks and reference books, and puts forward the authors' view to make up for its literature. Exerting the knowledge of lever in physics and the acoustics theory, we come up with an equivalent simplified model of manubrium mallei which is to meet the requirements as the long arm of the lever. We also set up an equivalent simplified model of ossicular chain--a combination of levers of ossicular chain. We disassemble the model into two simple levers, and make full analysis and demonstration on them. Through the calculation and comparison of displacement amplitudes in both external auditory canal air and internal ear lymph, we may draw a conclusion that the key reason, which the sound displacement amplitude is to be decreased to adapt to the endurance limit of the basement membrane, is that the density and sound speed in lymph is much higher than those in the air.

  10. Dopamine efflux in the nucleus accumbens during within-session extinction, outcome-dependent, and habit-based instrumental responding for food reward.

    PubMed

    Ahn, Soyon; Phillips, Anthony G

    2007-04-01

    Dopamine (DA) activity in the nucleus accumbens (NAc) is related to the general motivational effects of rewarding stimuli. Dickinson and colleagues have shown that initial acquisition of instrumental responding reflects action-outcome relationships based on instrumental incentive learning, which establishes the value of an outcome. Given that the sensitivity of responding to outcome devaluation is not affected by NAc lesions, it is unlikely that incentive learning during the action-outcome phase is mediated by DA activity in the NAc. DA efflux in the NAc after limited and extended training was compared on the assumption that comparable changes would be observed during both action-outcome- and habit-based phases of instrumental responding for food. This study also tested the hypothesis that increase in NAc DA activity is correlated with instrumental responding during extinction maintained by a conditioned stimulus paired with food. Rats were trained to lever press for food (random-interval 30 s schedule). On the 5th and 16th day of training, microdialysis samples were collected from the NAc or mediodorsal striatum (a control site for generalized activity) during instrumental responding in extinction and then for food reward, and analyzed for DA content using high performance liquid chromatography. Increase in DA efflux in the NAc accompanied responding for food pellets on both days 5 and 16, with the magnitude of increase significantly enhanced on day 16. DA efflux was also significantly elevated during responding in extinction only on day 16. These results support a role for NAc DA activity in Pavlovian, but not instrumental, incentive learning.

  11. Examining the reinforcement-enhancement effects of phencyclidine and its interactions with nicotine on lever-pressing for a visual stimulus.

    PubMed

    Swalve, Natashia; Barrett, Scott T; Bevins, Rick A; Li, Ming

    2015-09-15

    Nicotine is a widely-abused drug, yet its primary reinforcing effect does not seem potent as other stimulants such as cocaine. Recent research on the contributing factors toward chronic use of nicotine-containing products has implicated the role of reinforcement-enhancing effects of nicotine. The present study investigates whether phencyclidine (PCP) may also possess a reinforcement-enhancement effect and how this may interact with the reinforcement-enhancement effect of nicotine. PCP was tested for two reasons: (1) it produces discrepant results on overall reward, similar to that seen with nicotine and (2) it may elucidate how other compounds may interact with the reinforcement-enhancement of nicotine. Adult male Sprague-Dawley rats were trained to lever press for brief visual stimulus presentations under fixed-ratio (FR) schedules of reinforcement and then were tested with nicotine (0.2 or 0.4 mg/kg) and/or PCP (2.0mg/kg) over six increasing FR values. A selective increase in active lever-pressing for the visual stimulus with drug treatment was considered evidence of a reinforcement-enhancement effect. PCP and nicotine separately increased active lever pressing for a visual stimulus in a dose-dependent manner and across the different FR schedules. The addition of PCP to nicotine did not increase lever-pressing for the visual stimulus, possibly due to a ceiling effect. The effect of PCP may be driven largely by its locomotor stimulant effects, whereas the effect of nicotine was independent of locomotor stimulation. This dissociation emphasizes that distinct pharmacological properties contribute to the reinforcement-enhancement effects of substances. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Error analysis and correction of lever-type stylus profilometer based on Nelder-Mead Simplex method

    NASA Astrophysics Data System (ADS)

    Hu, Chunbing; Chang, Suping; Li, Bo; Wang, Junwei; Zhang, Zhongyu

    2017-10-01

    Due to the high measurement accuracy and wide range of applications, lever-type stylus profilometry is commonly used in industrial research areas. However, the error caused by the lever structure has a great influence on the profile measurement, thus this paper analyzes the error of high-precision large-range lever-type stylus profilometry. The errors are corrected by the Nelder-Mead Simplex method, and the results are verified by the spherical surface calibration. It can be seen that this method can effectively reduce the measurement error and improve the accuracy of the stylus profilometry in large-scale measurement.

  13. The jaw is a second-class lever in Pedetes capensis (Rodentia: Pedetidae)

    PubMed Central

    2017-01-01

    The mammalian jaw is often modelled as a third-class lever for the purposes of biomechanical analyses, owing to the position of the resultant muscle force between the jaw joint and the teeth. However, it has been proposed that in some rodents the jaws operate as a second-class lever during distal molar bites, owing to the rostral position of the masticatory musculature. In particular, the infraorbital portion of the zygomatico-mandibularis (IOZM) has been suggested to be of major importance in converting the masticatory system from a third-class to a second-class lever. The presence of the IOZM is diagnostic of the hystricomorph rodents, and is particularly well-developed in Pedetes capensis, the South African springhare. In this study, finite element analysis (FEA) was used to assess the lever mechanics of the springhare masticatory system, and to determine the function of the IOZM. An FE model of the skull of P. capensis was constructed and loaded with all masticatory muscles, and then solved for biting at each tooth in turn. Further load cases were created in which each masticatory muscle was removed in turn. The analyses showed that the mechanical advantage of the springhare jaws was above one at all molar bites and very close to one during the premolar bite. Removing the IOZM or masseter caused a drop in mechanical advantage at all bites, but affected strain patterns and cranial deformation very little. Removing the ZM had only a small effect on mechanical advantage, but produced a substantial reduction in strain and deformation across the skull. It was concluded that the masticatory system of P. capensis acts as a second class lever during bites along almost the entire cheek tooth row. The IOZM is clearly a major contributor to this effect, but the masseter also has a part to play. The benefit of the IOZM is that it adds force without substantially contributing to strain or deformation of the skull. This may help explain why the hystricomorphous morphology

  14. THE DIAGNOSTIC ACCURACY OF THE LEVER SIGN FOR DETECTING ANTERIOR CRUCIATE LIGAMENT INJURY

    PubMed Central

    Anderson, Amanda; Watson, Seth; Dimeff, Robert J.

    2017-01-01

    Background An alternative physical examination procedure for evaluating the integrity of the anterior cruciate ligament (ACL) has been proposed in the literature but has not been validated in a broad population of patients with a symptomatic complaint of knee pain for its diagnostic value. Purpose To investigate the diagnostic accuracy of the Lever Sign to detect ACL tears and compare the results to Lachman testing in both supine and prone positions. Study design Prospective, blinded, diagnostic accuracy study. Methods Sixty-two consecutive patients with a complaint of knee pain were independently evaluated for the status of the ACL's integrity with the Lever Sign and the Lachman test in a prone and supine by a blinded examiner before any other diagnostic assessments were completed. Results Twenty-four of the 60 patients included in the analysis had a torn ACL resulting in a prevalence of 40%. The sensitivity of the Lever Sign, prone, and supine Lachman tests were 38, 83, and 67 % respectively and the specificity was 72, 89, and 97% resulting in positive likelihood ratios of 1.4, 7.5, and 24 and negative likelihood ratios of 0.86, 0.19, and 0.34 respectively. The positive predictive values were 47, 83, and 94% and the negative predictive values were 63, 89, and 81% respectively. The diagnostic odds ratios were 1.6, 40, and 70 with a number needed to diagnose of 10.3, 1.4, and 1.6 respectively. Conclusions The results of this study suggest that Lever Sign, in isolation, does not accurately detect the status of the ACL. During the clinical examination, the Lever Sign should be used as an adjunct to the gold standard assessment technique of anterior tibial translation assessment as employed in the Lachman tests in either prone or supine position. Level of Evidence 2 PMID:29234557

  15. Analysis of Porosity Defects in Aluminum as Part Handle Motor Vehicle Lever Processed by High-pressure Die Casting

    NASA Astrophysics Data System (ADS)

    Anggraini, L.; Sugeng

    2018-05-01

    This research discusses the testing and analysis of cracking Aluminum (Al) material. Al as a handle lever was used for a braking device on a motor vehicle. Cracking of handle lever due to the part content of porosity from hydrogen gas. The existence of the H2 can be caused by the casting process and dies design that is less perfect, especially at the gate or brisket and overflow. This research is to optimize the process of making Al part handle lever, and the construction dies by following the standard. The results of these improvements were reevaluated through the chemical and mechanical testing properties stages, such as density test and tensile test on the workpiece as part handle lever. The loads on the tensile test are 25 kg and 35 kg, and the tensile test result has met the standard set by the motor vehicle company. The optimization result has the porosity defect can be reduced by 99 %. Therefore the best part handle lever can be produced.

  16. 35. END VIEW, INTERIOR, SHOWING SWITCHING LEVERS, BERK SWITCH TOWER, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    35. END VIEW, INTERIOR, SHOWING SWITCHING LEVERS, BERK SWITCH TOWER, SOUTH NORWALK - New York, New Haven & Hartford Railroad, Automatic Signalization System, Long Island Sound shoreline between Stamford & New Haven, Stamford, Fairfield County, CT

  17. Coupling of Lever Arm Swing and Biased Brownian Motion in Actomyosin

    PubMed Central

    Nie, Qing-Miao; Togashi, Akio; Sasaki, Takeshi N.; Takano, Mitsunori; Sasai, Masaki; Terada, Tomoki P.

    2014-01-01

    An important unresolved problem associated with actomyosin motors is the role of Brownian motion in the process of force generation. On the basis of structural observations of myosins and actins, the widely held lever-arm hypothesis has been proposed, in which proteins are assumed to show sequential structural changes among observed and hypothesized structures to exert mechanical force. An alternative hypothesis, the Brownian motion hypothesis, has been supported by single-molecule experiments and emphasizes more on the roles of fluctuating protein movement. In this study, we address the long-standing controversy between the lever-arm hypothesis and the Brownian motion hypothesis through in silico observations of an actomyosin system. We study a system composed of myosin II and actin filament by calculating free-energy landscapes of actin-myosin interactions using the molecular dynamics method and by simulating transitions among dynamically changing free-energy landscapes using the Monte Carlo method. The results obtained by this combined multi-scale calculation show that myosin with inorganic phosphate (Pi) and ADP weakly binds to actin and that after releasing Pi and ADP, myosin moves along the actin filament toward the strong-binding site by exhibiting the biased Brownian motion, a behavior consistent with the observed single-molecular behavior of myosin. Conformational flexibility of loops at the actin-interface of myosin and the N-terminus of actin subunit is necessary for the distinct bias in the Brownian motion. Both the 5.5–11 nm displacement due to the biased Brownian motion and the 3–5 nm displacement due to lever-arm swing contribute to the net displacement of myosin. The calculated results further suggest that the recovery stroke of the lever arm plays an important role in enhancing the displacement of myosin through multiple cycles of ATP hydrolysis, suggesting a unified movement mechanism for various members of the myosin family. PMID:24762409

  18. Coupling of lever arm swing and biased Brownian motion in actomyosin.

    PubMed

    Nie, Qing-Miao; Togashi, Akio; Sasaki, Takeshi N; Takano, Mitsunori; Sasai, Masaki; Terada, Tomoki P

    2014-04-01

    An important unresolved problem associated with actomyosin motors is the role of Brownian motion in the process of force generation. On the basis of structural observations of myosins and actins, the widely held lever-arm hypothesis has been proposed, in which proteins are assumed to show sequential structural changes among observed and hypothesized structures to exert mechanical force. An alternative hypothesis, the Brownian motion hypothesis, has been supported by single-molecule experiments and emphasizes more on the roles of fluctuating protein movement. In this study, we address the long-standing controversy between the lever-arm hypothesis and the Brownian motion hypothesis through in silico observations of an actomyosin system. We study a system composed of myosin II and actin filament by calculating free-energy landscapes of actin-myosin interactions using the molecular dynamics method and by simulating transitions among dynamically changing free-energy landscapes using the Monte Carlo method. The results obtained by this combined multi-scale calculation show that myosin with inorganic phosphate (Pi) and ADP weakly binds to actin and that after releasing Pi and ADP, myosin moves along the actin filament toward the strong-binding site by exhibiting the biased Brownian motion, a behavior consistent with the observed single-molecular behavior of myosin. Conformational flexibility of loops at the actin-interface of myosin and the N-terminus of actin subunit is necessary for the distinct bias in the Brownian motion. Both the 5.5-11 nm displacement due to the biased Brownian motion and the 3-5 nm displacement due to lever-arm swing contribute to the net displacement of myosin. The calculated results further suggest that the recovery stroke of the lever arm plays an important role in enhancing the displacement of myosin through multiple cycles of ATP hydrolysis, suggesting a unified movement mechanism for various members of the myosin family.

  19. Evaluation of study design variables and their impact on food-maintained operant responding in mice.

    PubMed

    Haluk, Desirae M; Wickman, Kevin

    2010-03-05

    Operant conditioning paradigms are useful for studying factors involved in reward, particularly when combined with the tools of genetic manipulation in mice. Published operant studies involving mice vary widely with respect to design, and insight into the consequences of design choices on performance in mice is limited. Here, we evaluated the impact of five design variables on the performance of inbred male mice in operant tasks involving solid food pellets as reinforcing agents. We found that the use of lever-press or nose-poke during FR1 sessions did not impact the performance of C57BL/6 mice, but that the lever-press approach correlated with enhanced performance during PR testing. While FR1 session duration had a notable impact on the rate of acquisition of food-maintained responding, performance during FR1 and PR sessions was largely unaffected. Higher order schedules of reinforcement (FR3 and FR5) led to elevated responding during both FR and PR sessions, and improved the correspondence between rewards earned and consumed. Single and group-housed mice performed indistinguishably during FR1 and PR sessions, while environmental enrichment combined with group housing accelerated the rate of acquisition of food-maintained responding while decreasing responding during PR testing. Finally, while C57BL/6 and 129/Sv mice exhibited comparable behavior during FR1 sessions, C57BL/6 mice tended to acquire food-maintained responding faster than 129/Sv counterparts, and exhibited elevated responding during PR testing. Altogether, our findings indicate that while operant performance for food in mice is relatively insensitive to many study parameters, experimental outcomes can be shaped predictably with proper design decisions. Copyright 2009 Elsevier B.V. All rights reserved.

  20. The Relationship between State Policy Levers and Student Mobility

    ERIC Educational Resources Information Center

    Gross, Jacob P. K.; Berry, Matthew S.

    2016-01-01

    To address conceptual and methodological shortcomings in the extant literature on student mobility, this study employs event history modeling to describe and explain how state policy levers, specifically state grant aid, relates to mobility and baccalaureate degree completion. We find that state grant aid reduces mobility, but less so than…

  1. Rotational foot placement specifies the lever arm of the ground reaction force during the push-off phase of walking initiation.

    PubMed

    Erdemir, Ahmet; Piazza, Stephen J

    2002-06-01

    The lever arm of the ground reaction force (GRF) about the talocrural joint axis is a functionally important indicator of the nature of foot loading. Walking initiation experiments (ten subjects; age, 23-29 years) were completed to demonstrate that rotational foot placement is a possible strategy to specify the lever arm. Externally-rotated foot placement resulted in larger lever arms during push-off. A computer simulation of push-off revealed that a decreased lever arm reduces the plantarflexion moment necessary to maintain a constant forward velocity, while increasing the required plantarflexion velocity. Shortening of the foot thus diminishes the muscular force demand but also requires high muscle fiber shortening velocities that may limit the force generating capacity of plantar flexors. Decreased plantar flexion moment and slow walking previously noted in partial-foot amputees may result from shortened lever arms in this manner.

  2. Disconnection of basolateral amygdala and insular cortex disrupts conditioned approach in Pavlovian lever autoshaping.

    PubMed

    Nasser, Helen M; Lafferty, Danielle S; Lesser, Ellen N; Bacharach, Sam Z; Calu, Donna J

    2018-01-01

    Previously established individual differences in appetitive approach and devaluation sensitivity observed in goal- and sign-trackers may be attributed to differences in the acquisition, modification, or use of associative information in basolateral amygdala (BLA) pathways. Here, we sought to determine the extent to which communication of associative information between BLA and anterior portions of insular cortex (IC) supports ongoing Pavlovian conditioned approach behaviors in sign- and goal-tracking rats, in the absence of manipulations to outcome value. We hypothesized that the BLA mediates goal-, but not sign- tracking approach through interactions with the IC, a brain region involved in supporting flexible behavior. We first trained rats in Pavlovian lever autoshaping to determine their sign- or goal-tracking tendency. During alternating test sessions, we gave unilateral intracranial injections of vehicle or a cocktail of gamma-aminobutyric acid (GABA) receptor agonists, baclofen and muscimol, unilaterally into the BLA and contralaterally or ipsilaterally into the IC prior to reinforced lever autoshaping sessions. Consistent with our hypothesis we found that contralateral inactivation of BLA and IC increased the latency to approach the food cup and decreased the number of food cup contacts in goal-trackers. While contralateral inactivation of BLA and IC did not affect the total number of lever contacts in sign-trackers, this manipulation increased the latency to approach the lever. Ipsilateral inactivation of BLA and IC did not impact approach behaviors in Pavlovian lever autoshaping. These findings, contrary to our hypothesis, suggest that communication between BLA and IC maintains a representation of initially learned appetitive associations that commonly support the initiation of Pavlovian conditioned approach behavior regardless of whether it is directed at the cue or the location of reward delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. A Lever Coupling Mechanism in Dual-Mass Micro-Gyroscopes for Improving the Shock Resistance along the Driving Direction.

    PubMed

    Gao, Yang; Li, Hongsheng; Huang, Libin; Sun, Hui

    2017-04-30

    This paper presents the design and application of a lever coupling mechanism to improve the shock resistance of a dual-mass silicon micro-gyroscope with drive mode coupled along the driving direction without sacrificing the mechanical sensitivity. Firstly, the mechanical sensitivity and the shock response of the micro-gyroscope are theoretically analyzed. In the mechanical design, a novel lever coupling mechanism is proposed to change the modal order and to improve the frequency separation. The micro-gyroscope with the lever coupling mechanism optimizes the drive mode order, increasing the in-phase mode frequency to be much larger than the anti-phase one. Shock analysis results show that the micro-gyroscope structure with the designed lever coupling mechanism can notably reduce the magnitudes of the shock response and cut down the stress produced in the shock process compared with the traditional elastic coupled one. Simulations reveal that the shock resistance along the drive direction is greatly increased. Consequently, the lever coupling mechanism can change the gyroscope's modal order and improve the frequency separation by structurally offering a higher stiffness difference ratio. The shock resistance along the driving direction is tremendously enhanced without loss of the mechanical sensitivity.

  4. A Lever Coupling Mechanism in Dual-Mass Micro-Gyroscopes for Improving the Shock Resistance along the Driving Direction

    PubMed Central

    Gao, Yang; Li, Hongsheng; Huang, Libin; Sun, Hui

    2017-01-01

    This paper presents the design and application of a lever coupling mechanism to improve the shock resistance of a dual-mass silicon micro-gyroscope with drive mode coupled along the driving direction without sacrificing the mechanical sensitivity. Firstly, the mechanical sensitivity and the shock response of the micro-gyroscope are theoretically analyzed. In the mechanical design, a novel lever coupling mechanism is proposed to change the modal order and to improve the frequency separation. The micro-gyroscope with the lever coupling mechanism optimizes the drive mode order, increasing the in-phase mode frequency to be much larger than the anti-phase one. Shock analysis results show that the micro-gyroscope structure with the designed lever coupling mechanism can notably reduce the magnitudes of the shock response and cut down the stress produced in the shock process compared with the traditional elastic coupled one. Simulations reveal that the shock resistance along the drive direction is greatly increased. Consequently, the lever coupling mechanism can change the gyroscope’s modal order and improve the frequency separation by structurally offering a higher stiffness difference ratio. The shock resistance along the driving direction is tremendously enhanced without loss of the mechanical sensitivity. PMID:28468288

  5. Five Policy Levers To Meet The Value Challenge In Cancer Care.

    PubMed

    Callahan, Ryan; Darzi, Ara

    2015-09-01

    The burden of cancer on public finances is a serious concern for policy makers. More people are developing cancer, and as standards of care have risen, more are surviving and requiring longer-term care. Precision medicine promises better outcomes but demands commensurately higher payments for care. As both incidence and per case costs rise, we suggest that the task of expanding access to high-quality cancer care poses a "value challenge" that policies in many countries are inadequate to meet. Policy makers should respond with a new approach. We explore questions that policy makers will need to consider regarding objectives, barriers, and levers for policy development. We use transparency and accountability as cornerstones of a new approach to promote value-based decision making. Although barriers to advancing this agenda are formidable, we recommend that governments define common standards for value-based accounting; serve as information brokers for evidence development; pioneer value-based procurement of goods and services; engage in deliberative democracy in cancer care; and educate communities to facilitate knowledge sharing between communities of patients, their caretakers, and researchers. Project HOPE—The People-to-People Health Foundation, Inc.

  6. Single-Lever Power Control for General Aviation Aircraft Promises Improved Efficiency and Simplified Pilot Controls

    NASA Technical Reports Server (NTRS)

    Musgrave, Jeffrey L.

    1997-01-01

    General aviation research is leading to major advances in internal combustion engine control systems for single-engine, single-pilot aircraft. These advances promise to increase engine performance and fuel efficiency while substantially reducing pilot workload and increasing flight safety. One such advance is a single-lever power control (SLPC) system, a welcome departure from older, less user-friendly, multilever engine control systems. The benefits of using single-lever power controls for general aviation aircraft are improved flight safety through advanced engine diagnostics, simplified powerplant operations, increased time between overhauls, and cost-effective technology (extends fuel burn and reduces overhaul costs). The single-lever concept has proven to be so effective in preliminary studies that general aviation manufacturers are making plans to retrofit current aircraft with the technology and are incorporating it in designs for future aircraft.

  7. 26. VIEW FROM EAST IN BRIDGE TENDER'S HOUSE, LEVERS FOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. VIEW FROM EAST IN BRIDGE TENDER'S HOUSE, LEVERS FOR GASOLINE ENGINE OPERATION FOR BRIDGE AND THEIR CONNECTIONS TO CONTROL RODS ON DOWNSTREAM SIDE OF SWING-SPAN; new bridge located in background - Tipers Bridge, Spanning Great Wicomico River at State Route 200, Kilmarnock, Lancaster County, VA

  8. 25. VIEW EAST IN BRIDGE TENDER'S HOUSE, (left) ORIGINAL LEVERS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    25. VIEW EAST IN BRIDGE TENDER'S HOUSE, (left) ORIGINAL LEVERS FOR GASOLINE ENGINE OPERATION OF SWING-SPAN, (right) PANEL F ELECTRIC OPERATION OF GATES AND SWING-SPAN; new bridge located in background - Tipers Bridge, Spanning Great Wicomico River at State Route 200, Kilmarnock, Lancaster County, VA

  9. A Lever for Life: How I Lost 150 Pounds and Learned the Catalytic Power of School Community

    ERIC Educational Resources Information Center

    Ebner, Steven J.

    2011-01-01

    The quotation, attributed to the Greek mathematician Archimedes, about the power of levers to move the world has been quoted many times with slight variations, but usually the point is the same: "With the right lever, one can move the earth." However, the actual quotation attributed to Archimedes comes in the writings of another Greek…

  10. Modified compensation algorithm of lever-arm effect and flexural deformation for polar shipborne transfer alignment based on improved adaptive Kalman filter

    NASA Astrophysics Data System (ADS)

    Wang, Tongda; Cheng, Jianhua; Guan, Dongxue; Kang, Yingyao; Zhang, Wei

    2017-09-01

    Due to the lever-arm effect and flexural deformation in the practical application of transfer alignment (TA), the TA performance is decreased. The existing polar TA algorithm only compensates a fixed lever-arm without considering the dynamic lever-arm caused by flexural deformation; traditional non-polar TA algorithms also have some limitations. Thus, the performance of existing compensation algorithms is unsatisfactory. In this paper, a modified compensation algorithm of the lever-arm effect and flexural deformation is proposed to promote the accuracy and speed of the polar TA. On the basis of a dynamic lever-arm model and a noise compensation method for flexural deformation, polar TA equations are derived in grid frames. Based on the velocity-plus-attitude matching method, the filter models of polar TA are designed. An adaptive Kalman filter (AKF) is improved to promote the robustness and accuracy of the system, and then applied to the estimation of the misalignment angles. Simulation and experiment results have demonstrated that the modified compensation algorithm based on the improved AKF for polar TA can effectively compensate the lever-arm effect and flexural deformation, and then improve the accuracy and speed of TA in the polar region.

  11. A Learning Center on the Lever for Young Children.

    ERIC Educational Resources Information Center

    Keislar, Evan R.; Luckenbill, Maryann

    This document describes a project designed to explore the possibilities of children's learning in mechanics. The principle of the lever, one example of a simple machine, was used in the form of a balance toy. The apparatus was set up as a game in a specially devised learning center. The children made non-verbal predictions as to which way the bar…

  12. Rats do not respond differently in the presence of stimuli signaling wheel-running reinforcers of different durations.

    PubMed

    Belke, Terry W

    2007-05-01

    Rats were exposed to a fixed interval 30 s schedule that produced opportunities to run of equal or unequal durations to assess the effect of differences in duration on responding. Each duration was signaled by a different stimulus. Wheel-running reinforcer duration pairs were 30 s 30 s, 50 s 10 s, and 55 s 5 s. An analysis of median postreinforcement pause duration and mean local lever-pressing rates broken down by previous reinforcer duration and duration of signaled upcoming reinforcer showed that postreinforcement pause duration was affected by the duration of the previous reinforcer but not by the stimulus signaling the duration of the upcoming reinforcer. Local lever-pressing rates were not affected by either previous or upcoming reinforcer duration. In general, the results are consistent with indifference between these durations obtained using a concurrent choice procedure.

  13. Effects of naltrexone and LY255582 on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats.

    PubMed

    Dhaher, Ronnie; Toalston, Jamie E; Hauser, Sheketha R; Bell, Richard L; McKinzie, David L; McBride, William J; Rodd, Zachary A

    2012-02-01

    Research indicates opioid antagonists can reduce alcohol drinking in rodents. However, tests examining the effects of opioid antagonists on ethanol seeking and relapse behavior have been limited. The present study examined the effects of two opioid antagonists on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats. Adult P rats were self-trained in two-lever operant chambers to self-administer 15% (vol/vol) ethanol on a fixed-ratio 5 (FR5) versus water on a FR1 concurrent schedule of reinforcement in daily 1-h sessions. After 10 weeks, rats underwent extinction training, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without ethanol or water to measure responses on the ethanol and water levers for four sessions. After a subsequent 2 weeks in the home cage, without access to ethanol, rats were returned to the operant chambers with ethanol and water available. Effects of antagonists on maintenance responding were tested after several weeks of daily 1-h sessions. Naltrexone (NAL; 1-10mg/kg, subcutaneously [s.c.]; n=8/dose), LY255582 (LY; 0.03-1mg/kg, s.c.; n=8/dose), or vehicle were injected 30min before the first session (in the absence of ethanol), following 2 weeks in their home cages, and for four consecutive sessions of ethanol self-administration under maintenance and relapse conditions. Both NAL and LY reduced responses on the ethanol lever without any fluids present, and ethanol self-administration under relapse and on-going drinking conditions, with LY being more potent than NAL. Both NAL and LY were less effective in reducing responding in the absence of ethanol than in reducing ethanol self-administration. Overall, the results indicate that the opioid system is involved in mediating ethanol seeking, and ethanol self-administration under relapse and on-going alcohol drinking, but that different neurocircuits may underlie these behaviors. Published by Elsevier Inc.

  14. Effect of short-term prefeeding and body weight on wheel running and responding reinforced by the opportunity to run in a wheel.

    PubMed

    Belke, Terry W; Pierce, W David; Jensen, K

    2004-07-30

    A biobehavioural analysis of activity anorexia suggests that the motivation for physical activity is regulated by food supply and body weight. In the present experiment, food allocation was varied within subjects by prefeeding food-deprived rats 0, 5, 10 and 15 g of food before sessions of lever pressing for wheel-running reinforcement. The experiment assessed the effects of prefeeding on rates of wheel running, lever pressing, and postreinforcement pausing. Results showed that prefeeding animals 5 g of food had no effect. Prefeeding 10 g of food reduced lever pressing for wheel running and rates of wheel running without a significant change in body weight; the effect was, however, transitory. Prefeeding 15 g of food increased the animals' body weights, resulting in a sustained decrease of wheel running and lever pressing, and an increase in postreinforcement pausing. Overall the results indicate that the motivation for physical activity is regulated by changes in local food supply, but is sustained only when there is a concomitant change in body weight.

  15. Individualized tracking of self-directed motor learning in group-housed mice performing a skilled lever positioning task in the home cage.

    PubMed

    Silasi, Gergely; Boyd, Jamie D; Bolanos, Federico; LeDue, Jeff M; Scott, Stephen H; Murphy, Timothy H

    2018-01-01

    Skilled forelimb function in mice is traditionally studied through behavioral paradigms that require extensive training by investigators and are limited by the number of trials individual animals are able to perform within a supervised session. We developed a skilled lever positioning task that mice can perform within their home cage. The task requires mice to use their forelimb to precisely hold a lever mounted on a rotary encoder within a rewarded position to dispense a water reward. A Raspberry Pi microcomputer is used to record lever position during trials and to control task parameters, thus making this low-footprint apparatus ideal for use within animal housing facilities. Custom Python software automatically increments task difficulty by requiring a longer hold duration, or a more accurate hold position, to dispense a reward. The performance of individual animals within group-housed mice is tracked through radio-frequency identification implants, and data stored on the microcomputer may be accessed remotely through an active internet connection. Mice continuously engage in the task for over 2.5 mo and perform ~500 trials/24 h. Mice required ~15,000 trials to learn to hold the lever within a 10° range for 1.5 s and were able to further refine movement accuracy by limiting their error to a 5° range within each trial. These results demonstrate the feasibility of autonomously training group-housed mice on a forelimb motor task. This paradigm may be used in the future to assess functional recovery after injury or cortical reorganization induced by self-directed motor learning. NEW & NOTEWORTHY We developed a low-cost system for fully autonomous training of group-housed mice on a forelimb motor task. We demonstrate the feasibility of tracking both end-point, as well as kinematic performance of individual mice, with each performing thousands of trials over 2.5 mo. The task is run and controlled by a Raspberry Pi microcomputer, which allows for cages to be

  16. Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Thanos, P.K.; Wang, G.; Thanos, P.K.

    Dopamine (DA) and DAD{sub 2} receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and amore » progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.« less

  17. 70. DETAIL OF TRACTION CABLE ENGAGEMENT DEVICE. SMALL, KNOBBED LEVER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    70. DETAIL OF TRACTION CABLE ENGAGEMENT DEVICE. SMALL, KNOBBED LEVER ON BUCKET HANGER WAS PULLED DOWN BY A CAMEL (FIXED CAM RAIL AT CENTER) AS BUCKET ROLLED PAST IT, CAUSING A CLAMP TO CLOSE AGAINST TRACTION CABLE. A SIMILAR CAMEL (NO LONGER EXTANT) DISENGAGED CLAMP ON RECEIVING SIDE. - Shenandoah-Dives Mill, 135 County Road 2, Silverton, San Juan County, CO

  18. High-temperature fiber-optic lever microphone

    NASA Technical Reports Server (NTRS)

    Zuckerwar, Allan J.; Cuomo, Frank W.; Nguyen, Trung D.; Rizzi, Stephen A.; Clevenson, Sherman A.

    1995-01-01

    The design and construction of a fiber-optic lever microphone, capable of operating continuously at temperatures up to 538 C (1000 F) are described. The design is based on the theoretical sensitivities of each of the microphone system components, namely, a cartridge containing a stretched membrane, an optical fiber probe, and an optoelectronic amplifier. Laboratory calibrations include the pistonphone sensitivity and harmonic distortion at ambient temperature, and frequency response, background noise, and optical power transmission at both ambient and elevated temperatures. A field test in the Thermal Acoustic Fatigue Apparatus at Langley Research Center, in which the microphone was subjected to overall sound-pressure levels in the range of 130-160 dB and at temperatures from ambient to 538 C, revealed good agreement with a standard probe microphone.

  19. Punishment and the potential for negative reinforcement with histamine injection.

    PubMed

    Mayer, Paulo César Morales; de Carvalho Neto, Marcus Bentes; Katz, Jonathan L

    2018-03-01

    The present study examined punishment of responding with histamine injection, and its potential to generate avoidance of punishment. Sprague-Dawley rats were trained under concurrent schedules in which responses on one lever (the punishment lever) produced food under a variable-interval schedule, and under some conditions intermittent injections of histamine, which suppressed behavior. Responses on a second (avoidance) lever prevented histamine injections scheduled on the punishment lever. After stabilization of punished responding, a variable-interval 15-s schedule of cancellation of histamine (avoidance) was added for responding on the second/avoidance lever, without subsequent acquisition of responding on that lever. Progressive decreases in the length of the punishment variable-interval schedule increased suppression on the punishment lever without increases in response rates on the avoidance lever. Exchanging contingencies on the levers ensured that response rates on the avoidance lever were sufficiently high to decrease the histamine injection frequency; nonetheless response rates on the avoidance lever decreased over subsequent sessions. Under no condition was responding maintained on the avoidance lever despite continued punishing effectiveness of histamine throughout. The present results suggest that avoidance conditioning is not a necessary condition for effective punishment, and confirm the importance of empirical rather than presumed categorization of behavioral effects of stimulus events. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  20. A conflict rat model of cue-induced relapse to cocaine seeking.

    PubMed

    Cooper, Ayelet; Barnea-Ygael, Noam; Levy, Dino; Shaham, Yavin; Zangen, Abraham

    2007-09-01

    Relapse to drug use in humans can be induced by exposure to drug-associated cues. The ability of drug cues to provoke 'relapse' has been studied in laboratory animals using a reinstatement model in which resumption of drug seeking is assessed after extinction of drug-reinforced responding. In this model, there are no adverse consequences of drug-seeking behavior. However, in humans, abstinence is often self-imposed, and relapse episodes likely involve making a choice between the desire for the drug and the negative consequences of pursuing it (a conflict situation). In this paper, we describe a conflict model of cue-induced relapse in rats that approximate the human condition. Rats were trained to lever press for cocaine; infusions were paired with a discrete light cue. An 'electric barrier' was then introduced by electrifying the floor area near the levers. Responding decreased over days with increasing shock intensities, until the rats did not approach the levers for 3 days. Subsequently, the effect of intermittent noncontingent light-cue presentations on resumption of lever responding (relapse) was assessed in extinction tests, with the electric barrier remaining activated; during testing, lever presses led to contingent light-cue presentations. Noncontingent cue exposure led to resumption of lever presses during the relapse tests in 14 of the 24 rats. Surprisingly, 24 h later, 11 of the 24 rats resumed lever responding in a subsequent post-noncontingent cue test under similar extinction conditions. Large individual differences in responding were observed during both tests. At its current stage of development, the conflict relapse model appears particularly suitable for studying individual differences in cue-induced relapse to cocaine seeking or factors that promote this relapse.

  1. A compensation method of lever arm effect for tri-axis hybrid inertial navigation system based on fiber optic gyro

    NASA Astrophysics Data System (ADS)

    Liu, Zengjun; Wang, Lei; Li, Kui; Gao, Jiaxin

    2017-05-01

    Hybrid inertial navigation system (HINS) is a new kind of inertial navigation system (INS), which combines advantages of platform INS, strap-down INS and rotational INS. HINS has a physical platform to isolate the angular motion as platform INS does, HINS also uses strap-down attitude algorithms and applies rotation modulation technique. Tri-axis HINS has three gimbals to isolate the angular motion in the dynamic base, in which way the system can reduce the effects of angular motion and improve the positioning precision. However, the angular motion will affect the compensation of some error parameters, especially for the lever arm effect. The lever arm effect caused by position errors between the accelerometers and rotation center cannot be ignored due to the rapid rotation of inertial measurement unit (IMU) and it will cause fluctuation and stage in velocity in HINS. The influences of angular motion on the lever arm effect compensation are analyzed firstly in this paper, and then the compensation method of lever arm effect based on the photoelectric encoders in dynamic base is proposed. Results of experiments on turntable show that after compensation, the fluctuations and stages in velocity curve disappear.

  2. Dissociation in effects of lesions of the nucleus accumbens core and shell on appetitive pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by D-amphetamine.

    PubMed

    Parkinson, J A; Olmstead, M C; Burns, L H; Robbins, T W; Everitt, B J

    1999-03-15

    Dopamine release within the nucleus accumbens (NAcc) has been associated with both the rewarding and locomotor-stimulant effects of abused drugs. The functions of the NAcc core and shell were investigated in mediating amphetamine-potentiated conditioned reinforcement and locomotion. Rats were initially trained to associate a neutral stimulus (Pavlovian CS) with food reinforcement (US). After excitotoxic lesions that selectively destroyed either the NAcc core or shell, animals underwent additional CS-US training sessions and then were tested for the acquisition of a new instrumental response that produced the CS acting as a conditioned reinforcer (CR). Animals were infused intra-NAcc with D-amphetamine (0, 1, 3, 10, or 20 microg) before each session. Shell lesions affected neither Pavlovian nor instrumental conditioning but completely abolished the potentiative effect of intra-NAcc amphetamine on responding with CR. Core-lesioned animals were impaired during the Pavlovian retraining sessions but showed no deficit in the acquisition of responding with CR. However, the selectivity in stimulant-induced potentiation of the CR lever was reduced, as intra-NAcc amphetamine infusions dose-dependently increased responding on both the CR lever and a nonreinforced (control) lever. Shell lesions produced hypoactivity and attenuated amphetamine-induced activity. In contrast, core lesions resulted in hyperactivity and enhanced the locomotor-stimulating effect of amphetamine. These results indicate a functional dissociation of subregions of the NAcc; the shell is a critical site for stimulant effects underlying the enhancement of responding with CR and locomotion after intra-NAcc injections of amphetamine, whereas the core is implicated in mechanisms underlying the expression of CS-US associations.

  3. Pharmacological specificity of N-methyl-D-aspartate discrimination in rats.

    PubMed

    Grech, D M; Willetts, J; Balster, R L

    1993-04-01

    The purpose of this study was to provide further information on the usefulness of N-methyl-D-aspartate (NMDA) discrimination in rats as a behavioral model for NMDA receptor activation. The pharmacological specificity of the NMDA discriminative stimulus was examined in rats trained to discriminate 30 mg/kg, i.p. NMDA from saline using a 2-lever fixed-ratio (FR) 32 food reinforcement schedule. Pharmacologically diverse centrally-acting agents were examined for their ability to substitute for NMDA. Morphine did not substitute for NMDA; neither did the central stimulants, caffeine and (+)-amphetamine, which produced a maximum mean of only 16 and 35% NMDA-lever responding, respectively. Pentylenetetrazol and picrotoxin also did not substitute for NMDA. Compounds interacting with cholinergic neurotransmission including nicotine, physostigmine, arecoline and mecamylamine, produced at best, only intermediate levels of NMDA-lever responding (32-61%), with the highest levels of NMDA-lever responding generally occurring at doses that also reduced rates of responding. These results suggest that the discriminative stimulus properties of NMDA are dissimilar from those of a number of centrally-acting drugs. Combined with the results of studies indicating that the NMDA discriminative stimulus can be antagonized by competitive NMDA antagonists, these results provide further evidence that NMDA receptor activation is the basis of NMDA discrimination and that this model may be useful for studying site-selective NMDA agonists and antagonists.

  4. Effects of environmental enrichment on extinction and reinstatement of amphetamine self-administration and sucrose-maintained responding.

    PubMed

    Stairs, Dustin J; Klein, Emily D; Bardo, Michael T

    2006-11-01

    The current experiments aimed to determine whether differential rearing alters extinction and/or reinstatement of amphetamine self-administration or sucrose-maintained responding. Male Sprague-Dawley rats were raised in either an enriched condition or an isolated condition. Rats were then trained to lever press on a continuous reinforcement schedule across either 15 daily amphetamine self-administration sessions or 15 sucrose-reinforced sessions, followed by 10 sessions of extinction. After the extinction sessions, priming doses of amphetamine (0, 0.25 or 1.0 mg/kg) were administered 15 min before the session, or sucrose (one or 10 pellets) was delivered non-contingently at the beginning of the session. Enriched condition rats showed greater extinction for amphetamine and sucrose-maintained responding than isolated condition rats. When primed with amphetamine, isolated condition rats reinstated responding following 0.25 mg/kg of amphetamine, whereas enriched condition rats only reinstated responding after 1.0 mg/kg of amphetamine. Isolated condition rats failed to reinstate responding following sucrose delivery, while enriched condition rats reinstated responding following the delivery of 10 sucrose pellets. These results indicate that environmental enrichment enhanced the extinction of both amphetamine and sucrose-maintained responding. Environmental enrichment also raised the reinstatement threshold specific to the amphetamine prime, suggesting a reduction in the incentive motivational effect of amphetamine.

  5. Implementing a University E-Learning Strategy: Levers for Change within Academic Schools

    ERIC Educational Resources Information Center

    Sharpe, Rhona; Benfield, Greg; Francis, Richard

    2006-01-01

    This paper describes the implementation of an e-learning strategy at a single higher education institution in terms of the levers used to promote effective uptake and ensure sustainable embedding. The focus of this work was at the level of the academic school using a range of change practices including the appointment of school-based learning…

  6. Disinhibition by propranolol and chlordiazepoxide of nonrewarded lever-pressing in the rat is unaffected by dorsal noradrenergic bundle lesion.

    PubMed

    Salmon, P; Tsaltas, E; Gray, J A

    1989-03-01

    Ten male Sprague-Dawley rats received 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle and 10 others underwent control operations. The lesion depleted levels of noradrenaline in the hippocampus to 2% of those in the controls. All rats were then trained for 16 sessions to lever-press in a Skinner box on a variable interval 18 sec schedule of food-reinforcement, then for 42 days on a successive discrimination between periods of variable interval (VI 18 sec) food-reinforcement and periods of extinction. This report describes the effects of chlordiazepoxide (CDP; 5 mg/kg) and propranolol (5 and 10 mg/kg) injected intraperitoneally in both groups on modified ABBA designs after this training. Both drugs increased the response rates in extinction periods. The effect of propranolol was similar at each dose and smaller than that of CDP. Although CDP and propranolol (5 mg/kg) increased variable interval response rates also, this could not account for the effect on extinction response rates. Responding did not differ between the lesioned and control animals and the effects of drugs were similar in each group. It is unlikely that CDP or propranolol release nonrewarded responding by disrupting transmission in the dorsal noradrenergic bundle.

  7. Electron microscopic evidence for the myosin head lever arm mechanism in hydrated myosin filaments using the gas environmental chamber

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Minoda, Hiroki; CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012; Okabe, Tatsuhiro

    2011-02-25

    Research highlights: {yields} We succeeded in recording structural changes of hydrated myosin cross-bridges. {yields} We succeeded in position-marking the cross-bridges with site-directed antibodies. {yields} We recorded cross-bridge movement at different regions in individual cross-bridge. {yields} The movement was smallest at the cross-bridge-subfragment two boundary. {yields} The results provide evidence for the cross-bridge lever arm mechanism. -- Abstract: Muscle contraction results from an attachment-detachment cycle between the myosin heads extending from myosin filaments and the sites on actin filaments. The myosin head first attaches to actin together with the products of ATP hydrolysis, performs a power stroke associated with release ofmore » hydrolysis products, and detaches from actin upon binding with new ATP. The detached myosin head then hydrolyses ATP, and performs a recovery stroke to restore its initial position. The strokes have been suggested to result from rotation of the lever arm domain around the converter domain, while the catalytic domain remains rigid. To ascertain the validity of the lever arm hypothesis in muscle, we recorded ATP-induced movement at different regions within individual myosin heads in hydrated myosin filaments, using the gas environmental chamber attached to the electron microscope. The myosin head were position-marked with gold particles using three different site-directed antibodies. The amplitude of ATP-induced movement at the actin binding site in the catalytic domain was similar to that at the boundary between the catalytic and converter domains, but was definitely larger than that at the regulatory light chain in the lever arm domain. These results are consistent with the myosin head lever arm mechanism in muscle contraction if some assumptions are made.« less

  8. REINSTATEMENT OF ETHANOL AND SUCROSE SEEKING BY THE NEUROSTEROID ALLOPREGNANOLONE IN C57BL/6 MICE

    PubMed Central

    Finn, Deborah A.; Mark, Gregory P.; Fretwell, Andrea M.; Gililland, Katherine R.; Strong, Moriah N.; Ford, Matthew M.

    2016-01-01

    Rationale Recent work in our laboratory documented that the “sipper” method of operant ethanol self-administration produced high ethanol intake and blood ethanol concentrations as well as the typical extinction “burst” in responding under non-reinforced conditions in male C57BL/6 mice. However, the neurochemical basis for reinstatement of responding following extinction has not been examined in mice with this model. Objectives Based on findings that the GABAergic neurosteroid allopregnanolone (ALLO) significantly increased the consummatory phase of ethanol self-administration, the present study determined the effect of ALLO on reinstatement of extinguished ethanol-seeking behavior and compared this effect to reinstatement of responding for sucrose reward. Methods Separate groups of male C57BL/6 mice were trained to lever press for access to a 10% ethanol (10E) or a 5% sucrose (5S) solution. A single response requirement of 16 presses (RR16) on an active lever resulted in 30 min of continuous access to the 10E or 5S solution. After the animals responded on the RR16 schedule for 14 weeks, mice were exposed to 30 min extinction sessions where responding had no scheduled consequence. Once responding stabilized below the pre-extinction baseline, mice received an IP injection of ALLO (0, 3.2, 5.6, 10 or 17 mg/kg) 15 min prior to the extinction session in a within-subjects design. Results ALLO produced a dose-dependent increase in responding under non-reinforced conditions in both the 10E and 5S groups. Additional work documented the ability of a conditioned cue light or a compound cue (light+lever retraction) to reinstate non-reinforced responding on the previously active lever. Conclusions These findings definitively show that conditioned cues and priming with ALLO are potent stimuli for reinstating both ethanol and sucrose seeking behavior in C57BL/6 mice. PMID:18758755

  9. Ca2+-Induced Rigidity Change of the Myosin VIIa IQ Motif-Single α Helix Lever Arm Extension.

    PubMed

    Li, Jianchao; Chen, Yiyun; Deng, Yisong; Unarta, Ilona Christy; Lu, Qing; Huang, Xuhui; Zhang, Mingjie

    2017-04-04

    Several unconventional myosins contain a highly charged single α helix (SAH) immediately following the calmodulin (CaM) binding IQ motifs, functioning to extend lever arms of these myosins. How such SAH is connected to the IQ motifs and whether the conformation of the IQ motifs-SAH segments are regulated by Ca 2+ fluctuations are not known. Here, we demonstrate by solving its crystal structure that the predicted SAH of myosin VIIa (Myo7a) forms a stable SAH. The structure of Myo7a IQ5-SAH segment in complex with apo-CaM reveals that the SAH sequence can extend the length of the Myo7a lever arm. Although Ca 2+ -CaM remains bound to IQ5-SAH, the Ca 2+ -induced CaM binding mode change softens the conformation of the IQ5-SAH junction, revealing a Ca 2+ -induced lever arm flexibility change for Myo7a. We further demonstrate that the last IQ motif of several other myosins also binds to both apo- and Ca 2+ -CaM, suggesting a common Ca 2+ -induced conformational regulation mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Effect of cantilever geometry on the optical lever sensitivities and thermal noise method of the atomic force microscope.

    PubMed

    Sader, John E; Lu, Jianing; Mulvaney, Paul

    2014-11-01

    Calibration of the optical lever sensitivities of atomic force microscope (AFM) cantilevers is especially important for determining the force in AFM measurements. These sensitivities depend critically on the cantilever mode used and are known to differ for static and dynamic measurements. Here, we calculate the ratio of the dynamic and static sensitivities for several common AFM cantilevers, whose shapes vary considerably, and experimentally verify these results. The dynamic-to-static optical lever sensitivity ratio is found to range from 1.09 to 1.41 for the cantilevers studied - in stark contrast to the constant value of 1.09 used widely in current calibration studies. This analysis shows that accuracy of the thermal noise method for the static spring constant is strongly dependent on cantilever geometry - neglect of these dynamic-to-static factors can induce errors exceeding 100%. We also discuss a simple experimental approach to non-invasively and simultaneously determine the dynamic and static spring constants and optical lever sensitivities of cantilevers of arbitrary shape, which is applicable to all AFM platforms that have the thermal noise method for spring constant calibration.

  11. Enhancement of a visual reinforcer by D-amphetamine and nicotine in adult rats: relation to habituation and food restriction.

    PubMed

    Wright, Jennifer M; Ren, Suelynn; Constantin, Annie; Clarke, Paul B S

    2018-03-01

    Nicotine and D-amphetamine can strengthen reinforcing effects of unconditioned visual stimuli. We investigated whether these reinforcement-enhancing effects reflect a slowing of stimulus habituation and depend on food restriction. Adult male rats pressed an active lever to illuminate a cue light during daily 60-min sessions. Depending on the experiment, rats were challenged with fixed or varying doses of D-amphetamine (0.25-2 mg/kg IP) and nicotine (0.025-0.2 mg/kg SC) or with the tobacco constituent norharman (0.03-10 μg/kg IV). Experiment 1 tested for possible reinforcement-enhancing effects of D-amphetamine and norharman. Experiment 2 investigated whether nicotine and amphetamine inhibited the spontaneous within-session decline in lever pressing. Experiment 3 assessed the effects of food restriction. Amphetamine (0.25-1 mg/kg) and nicotine (0.1 mg/kg) increased active lever pressing specifically (two- to threefold increase). The highest doses of nicotine and amphetamine also affected inactive lever responding (increase and decrease, respectively). With the visual reinforcer omitted, responding was largely extinguished. Neither drug appeared to slow habituation, as assessed by the within-session decline in lever pressing, and reinforcement-enhancing effects still occurred if the drugs were given after this decline had occurred. Food restriction enhanced the reinforcement-enhancing effect of amphetamine but not that of nicotine. Responding remained goal-directed after several weeks of testing. Low doses of D-amphetamine and nicotine produced reinforcement enhancement even in free-feeding subjects, independent of the spontaneous within-session decline in responding. Reinforcement enhancement by amphetamine, but not nicotine, was enhanced by concurrent subchronic food restriction.

  12. The role of the lateral habenula in punishment.

    PubMed

    Jean-Richard Dit Bressel, Philip; McNally, Gavan P

    2014-01-01

    The lateral habenula (LHb) is a small epithalamic structure that projects via the fasciculus retroflexus to the midbrain. The LHb is known to modulate midbrain dopamine (DA) neurons, including inhibition of ventral tegmental area (VTA) neurons via glutamatergic excitation of the GABAergic rostromedial tegmental nucleus (RMTg). A variety of lines of evidence show activity in LHb and the LHb-RMTg pathway is correlated with, and is sufficient to support, punishment learning. However, it is not immediately clear whether LHb is necessary for punishment. Here we used a within-subjects punishment task to assess the role of LHb in the acquisition and expression of punishment as well as in aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of an AMPA receptor antagonist (NBQX) into LHb had no effect on the acquisition or expression of this punishment, or on aversive choice, but did increase locomotion. Infusion of the sodium channel blocker bupivacaine likewise had no effect on expression of punishment. However, infusion of the calcium channel blocker mibefradil did affect expression of punishment by significantly decreasing the latency with which rats responded on the punished lever and significantly increasing unpunished lever-pressing. Taken together, these findings indicate that the LHb plays a limited role in punishment, influencing only latency to respond. This role is linked to calcium channel permeability and not AMPA receptor or sodium channel permeability.

  13. The Role of the Lateral Habenula in Punishment

    PubMed Central

    Jean-Richard Dit Bressel, Philip; McNally, Gavan P.

    2014-01-01

    The lateral habenula (LHb) is a small epithalamic structure that projects via the fasciculus retroflexus to the midbrain. The LHb is known to modulate midbrain dopamine (DA) neurons, including inhibition of ventral tegmental area (VTA) neurons via glutamatergic excitation of the GABAergic rostromedial tegmental nucleus (RMTg). A variety of lines of evidence show activity in LHb and the LHb-RMTg pathway is correlated with, and is sufficient to support, punishment learning. However, it is not immediately clear whether LHb is necessary for punishment. Here we used a within-subjects punishment task to assess the role of LHb in the acquisition and expression of punishment as well as in aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of an AMPA receptor antagonist (NBQX) into LHb had no effect on the acquisition or expression of this punishment, or on aversive choice, but did increase locomotion. Infusion of the sodium channel blocker bupivacaine likewise had no effect on expression of punishment. However, infusion of the calcium channel blocker mibefradil did affect expression of punishment by significantly decreasing the latency with which rats responded on the punished lever and significantly increasing unpunished lever-pressing. Taken together, these findings indicate that the LHb plays a limited role in punishment, influencing only latency to respond. This role is linked to calcium channel permeability and not AMPA receptor or sodium channel permeability. PMID:25365401

  14. Stimulus- and response-reinforcer contingencies in autoshaping, operant, classical, and omission training procedures in rats.

    PubMed

    Atnip, G W

    1977-07-01

    Separate groups of rats received 500 trials of lever-press training under autoshaping (food delivery followed 10-second lever presentations, or occurred immediately following a response); operant conditioning (responding was necessary for food delivery); and classical conditioning (food followed lever presentations regardless of responding). Each group then received 500 trials on an omission procedure in which food was omitted on trials with a response. Another group received 1000 trials on the omission procedure, and a fifth group, random control, received 1000 uncorrelated presentations of lever and food. The autoshaping, operant, and classical groups reached high response levels by the end of initial training. Acquisition was fastest in the autoshaping group. Responding remained consistently low in the control group. The omission group responded at a level between the control group and the other three groups. During omission training, responding in these three groups declined to the omission-group level. During omission training, the rats continued contacting the lever frequently after lever pressing had declined. Response maintenance under omission training seems not to require topographic similarity between the response and reinforcer-elicited consummatory behaviors.

  15. The relationship between involuntary pelvic floor muscle activity, muscle awareness and experienced threat in women with and without vaginismus.

    PubMed

    van der Velde, J; Everaerd, W

    2001-04-01

    This study assessed the relationship between involuntary pelvic floor muscle activity, muscle awareness and experienced threat in women with and without vaginismus. Information about this relationship may help understand the mechanism of vaginismus. Twenty-two women with vaginismus and seven control women participated in the study. Women were exposed to four emotion-inducing film excerpts. Vaginal electromyography was recorded. Experienced threat was continuously monitored with the use of a lever. Women responded with increased pelvic floor muscle activity to the threatening and sexually-threatening film excerpt. No changes occurred during the neutral and erotic excerpt. The subjective experienced threat as indicated with the lever showed the same response pattern. However, awareness of changes in muscle activity showed a slightly different pattern. Individual data were inspected. In general, agreement was found between recorded changes in muscle activity and experienced threat. The results of the erotic excerpt showed that awareness of changes in muscle activity is not only determined by information from the pelvic floor muscles, but also by other factors like situational information and the expectations of the women. The data support the idea of a general defense reaction as a mechanism of involuntary pelvic floor muscle activity.

  16. Dopaminergic modulation of effort-related choice behavior as assessed by a progressive ratio chow feeding choice task: pharmacological studies and the role of individual differences.

    PubMed

    Randall, Patrick A; Pardo, Marta; Nunes, Eric J; López Cruz, Laura; Vemuri, V Kiran; Makriyannis, Alex; Baqi, Younis; Müller, Christa E; Correa, Mercè; Salamone, John D

    2012-01-01

    Mesolimbic dopamine (DA) is involved in behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. In the present study, the effects of several drug treatments were assessed using a progressive ratio (PROG)/chow feeding concurrent choice task. With this task, rats can lever press on a PROG schedule reinforced by a preferred high-carbohydrate food pellet, or alternatively approach and consume the less-preferred but concurrently available laboratory chow. Rats pass through each ratio level 15 times, after which the ratio requirement is incremented by one additional response. The DA D(2) antagonist haloperidol (0.025-0.1 mg/kg) reduced number of lever presses and highest ratio achieved but did not reduce chow intake. In contrast, the adenosine A(2A) antagonist MSX-3 increased lever presses and highest ratio achieved, but decreased chow consumption. The cannabinoid CB1 inverse agonist and putative appetite suppressant AM251 decreased lever presses, highest ratio achieved, and chow intake; this effect was similar to that produced by pre-feeding. Furthermore, DA-related signal transduction activity (pDARPP-32(Thr34) expression) was greater in nucleus accumbens core of high responders (rats with high lever pressing output) compared to low responders. Thus, the effects of DA antagonism differed greatly from those produced by pre-feeding or reduced CB1 transmission, and it appears unlikely that haloperidol reduces PROG responding because of a general reduction in primary food motivation or the unconditioned reinforcing properties of food. Furthermore, accumbens core signal transduction activity is related to individual differences in work output.

  17. Probing muscle myosin motor action: x-ray (m3 and m6) interference measurements report motor domain not lever arm movement.

    PubMed

    Knupp, Carlo; Offer, Gerald; Ranatunga, K W; Squire, John M

    2009-07-10

    The key question in understanding how force and movement are produced in muscle concerns the nature of the cyclic interaction of myosin molecules with actin filaments. The lever arm of the globular head of each myosin molecule is thought in some way to swing axially on the actin-attached motor domain, thus propelling the actin filament past the myosin filament. Recent X-ray diffraction studies of vertebrate muscle, especially those involving the analysis of interference effects between myosin head arrays in the two halves of the thick filaments, have been claimed to prove that the lever arm moves at the same time as the sliding of actin and myosin filaments in response to muscle length or force steps. It was suggested that the sliding of myosin and actin filaments, the level of force produced and the lever arm angle are all directly coupled and that other models of lever arm movement will not fit the X-ray data. Here, we show that, in addition to interference across the A-band, which must be occurring, the observed meridional M3 and M6 X-ray intensity changes can all be explained very well by the changing diffraction effects during filament sliding caused by heads stereospecifically attached to actin moving axially relative to a population of detached or non-stereospecifically attached heads that remain fixed in position relative to the myosin filament backbone. Crucially, and contrary to previous interpretations, the X-ray interference results provide little direct information about the position of the myosin head lever arm; they are, in fact, reporting relative motor domain movements. The implications of the new interpretation are briefly assessed.

  18. Behavioral characteristics and neural mechanisms mediating performance in a rodent version of the Balloon Analog Risk Task.

    PubMed

    Jentsch, James David; Woods, Jason A; Groman, Stephanie M; Seu, Emanuele

    2010-07-01

    The tendency for some individuals to partake in high-risk behaviors (eg, substance abuse, gambling, risky sexual activities) is a matter of great public health concern, yet the characteristics and neural bases of this vulnerability are largely unknown. Recent work shows that this susceptibility can be partially predicted by laboratory measures of reward seeking under risk, including the Balloon Analog Risk Task. Rats were trained to respond on two levers: one of which (the 'add lever') increased the size of a potential food reward and a second (the 'cash-out lever') that led to delivery of accrued reward. Crucially, each add-lever response was also associated with a risk that the trial would fail and no reward would be delivered. The relative probabilities that each add-lever press would lead to an addition food pellet or to trial failure (risk) were orthogonally varied. Rats exhibited a pattern of responding characteristic of incentive motivation and risk aversion, with a subset of rats showing traits of high-risk taking and/or suboptimal responding. Neural inactivation studies suggest that the orbitofrontal cortex supports greater reward seeking in the presence or absence of risk, whereas the medial prefrontal cortex is required for optimization of patterns of responding. These findings provide new information about the neural circuitry of decision making under risk and reveal new insights into the biological determinants of risk-taking behaviors that may be useful in developing biomarkers of vulnerability.

  19. Toward Development of a Fibromyalgia Responder Index and Disease Activity Score: OMERACT Module Update

    PubMed Central

    Mease, PJ; Clauw, DJ; Christensen, R; Crofford, L; Gendreau, M; Martin, SA; Simon, L; Strand, V; Williams, DA; Arnold, LM

    2012-01-01

    Following development of the core domain set for fibromyalgia (FM) in OMERACT 7–9, the FM working group has progressed toward the development of an FM responder index and a disease activity score based on these domains, utilizing outcome indices of these domains from archived randomized clinical trials (RCTs) in FM. Possible clinical domains that could be included in a responder index and disease activity score include: pain, fatigue, sleep disturbance, cognitive dysfunction, mood disturbance, tenderness, stiffness, and functional impairment. Outcome measures for these domains demonstrate good to adequate psychometric properties, although measures of cognitive dysfunction need to be further developed. The approach used in the development of responder indices and disease activity scores for rheumatoid arthritis and ankylosing spondylitis represent heuristic models for our work, but FM is challenging in that there is no clear algorithm of treatment that defines disease activity based on treatment decisions, nor are there objective markers that define thresholds of severity or response to treatment. The process of developing candidate dichotomous responder definitions and continuous quantitative disease activity measures is described, as is participant discussion that transpired at OMERACT 10. Final results of this work will be published in a separate manuscript pending completion of analyses. PMID:21724721

  20. Individual differences in the energizing effects of caffeine on effort-based decision-making tests in rats.

    PubMed

    SanMiguel, Noemí; Pardo, Marta; Carratalá-Ros, Carla; López-Cruz, Laura; Salamone, John D; Correa, Mercè

    2018-06-01

    Motivated behavior is characterized by activation and high work output. Nucleus accumbens (Nacb) modulates behavioral activation and effort-based decision-making. Caffeine is widely consumed because of its energizing properties. This methylxanthine is a non-selective adenosine A 1 /A 2A receptor antagonist. Adenosine receptors are highly concentrated in Nacb. Adenosine agonists injected into Nacb, shift preference towards low effort alternatives. The present studies characterized effort-related effects of caffeine in a concurrent progressive ratio (PROG)/free reinforcer choice procedure that requires high levels of work output, and generates great variability among different animals. Male Sprague-Dawley rats received an acute dose of caffeine (2.5-20.0 mg/kg, IP) and 30 min later were tested in operant boxes. One group was food-restricted and had to lever pressed for high carbohydrate pellets, another group was non-food-restricted and lever pressed for a high sucrose solution. Caffeine (2.5 and 5.0 mg/kg) increased lever pressing in food-restricted animals that were already high responders. However, in non-restricted animals, caffeine (5.0 and 10.0 mg/kg) increased work output only among low responders. In fact, caffeine (10.0 and 20.0 mg/kg) in non-restricted animals, reduced lever pressing among high responders in the PROG task, and also in a different group of animals lever pressing in an easy task (fixed ratio 7 schedule) that uniformly generates high levels of responding. Caffeine did not modify sucrose preference or consumption under free access conditions. Thus, when animals do not have a homeostatic need, caffeine can help those not very intrinsically motivated to work harder for a more palatable reward. However, caffeine can disrupt performance of animals intrinsically motivated to work hard for a better reward. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Individual differences in pavlovian autoshaping of lever pressing in rats predict stress-induced corticosterone release and mesolimbic levels of monoamines.

    PubMed

    Tomie, A; Aguado, A S; Pohorecky, L A; Benjamin, D

    2000-03-01

    Pavlovian autoshaping CRs are directed and reflexive consummatory responses targeted at objects repeatedly paired with rewarding substances. To evaluate the hypothesis that autoshaping may provide an animal learning model of vulnerability to drug abuse, this study relates individual differences in lever-press autoshaping CR performance in rats to stress-induced corticosterone release and tissue monoamine levels in the mesolimbic dopamine tract. Long-Evans rats (n = 14) were given 20 sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of food US. Large between-subjects differences in lever-press autoshaping CR performance were observed, with group high CR frequency (n = 5) performing many more lever press CRs than group low CR frequency (n = 9). Tail-blood samples were obtained before and after the 20th autoshaping session, then 24 h later the rats were sacrificed and dissection yielded tissue samples of nucleus accumbens (NAC), prefrontal cortex (PFC), caudate putamen (CP), and ventral tegmental area (VTA). Serum levels of postsession corticosterone were elevated in group high CR frequency. HPLC revealed that group high CR frequency had higher tissue levels of dopamine and DOPAC in NAC, lower levels of DOPAC/DA turnover in CP, and lower levels of 5-HIAA and lower 5-HIAA/5-HT turnover in VTA. The neurochemical profile of rats that perform more autoshaping CRs share some features of vulnerability to drug abuse.

  2. Parallel learning in an autoshaping paradigm.

    PubMed

    Naeem, Maliha; White, Norman M

    2016-08-01

    In an autoshaping task, a single conditioned stimulus (CS; lever insertion) was repeatedly followed by the delivery of an unconditioned stimulus (US; food pellet into an adjacent food magazine) irrespective of the rats' behavior. After repeated training trials, some rats responded to the onset of the CS by approaching and pressing the lever (sign-trackers). Lesions of dorsolateral striatum almost completely eliminated responding to the lever CS while facilitating responding to the food magazine (US). Lesions of the dorsomedial striatum attenuated but did not eliminate responding to the lever CS. Lesions of the basolateral or central nucleus of the amygdala had no significant effects on sign-tracking, but combined lesions of the 2 structures impaired sign-tracking by significantly increasing latency to the first lever press without affecting the number of lever presses. Lesions of the dorsal hippocampus had no effect on any of the behavioral measures. The findings suggest that sign-tracking with a single lever insertion as the CS may consist of 2 separate behaviors learned in parallel: An amygdala-mediated conditioned orienting and approach response and a dorsal striatum-mediated instrumental response. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  3. Stimulus- and response-reinforcer contingencies in autoshaping, operant, classical, and omission training procedures in rats

    PubMed Central

    Atnip, Gilbert W.

    1977-01-01

    Separate groups of rats received 500 trials of lever-press training under autoshaping (food delivery followed 10-second lever presentations, or occurred immediately following a response); operant conditioning (responding was necessary for food delivery); and classical conditioning (food followed lever presentations regardless of responding). Each group then received 500 trials on an omission procedure in which food was omitted on trials with a response. Another group received 1000 trials on the omission procedure, and a fifth group, random control, received 1000 uncorrelated presentations of lever and food. The autoshaping, operant, and classical groups reached high response levels by the end of initial training. Acquisition was fastest in the autoshaping group. Responding remained consistently low in the control group. The omission group responded at a level between the control group and the other three groups. During omission training, responding in these three groups declined to the omission-group level. During omission training, the rats continued contacting the lever frequently after lever pressing had declined. Response maintenance under omission training seems not to require topographic similarity between the response and reinforcer-elicited consummatory behaviors. PMID:16812014

  4. The importance of a compound stimulus in conditioned drug-seeking behavior following one week of extinction from self-administered cocaine in rats.

    PubMed

    See, R E; Grimm, J W; Kruzich, P J; Rustay, N

    1999-11-01

    Previous studies have demonstrated that conditioned stimuli can increase responding on a drug-associated lever after extinction from drug self-administration. The present study investigated singular stimuli (tone or light) or a compound stimulus (tone + light) for their ability to increase extinguished responding following chronic cocaine self-administration. Rats self-administered cocaine for 2 weeks on a fixed ratio (FR1) schedule of reinforcement, in which lever responding resulted in varied presentation of a tone, light, or tone + light combination. The rats were then exposed to 1 week of daily extinction sessions. Presentation of the tone + light on day 8 of extinction in the absence of cocaine reinforcement resulted in a significant increase in responding, while either stimulus component alone was much weaker or failed to produce any changes from extinction rates of responding. In addition, changing the duration of the single elements of the compound did not affect the magnitude of increased responding to the compound. Following three final extinction sessions, robust lever responding for cocaine infusions on day 12 of extinction was seen across all groups. These findings suggest that compound stimuli may be critical to fully activate drug-seeking behavior in conditions of craving and relapse following prolonged extinction.

  5. Altered operant responding for motor reinforcement and the determination of benchmark doses following perinatal exposure to low-level 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    PubMed

    Markowski, V P; Zareba, G; Stern, S; Cox, C; Weiss, B

    2001-06-01

    Pregnant Holtzman rats were exposed to a single oral dose of 0, 20, 60, or 180 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the 18th day of gestation. Their adult female offspring were trained to respond on a lever for brief opportunities to run in specially designed running wheels. Once they had begun responding on a fixed-ratio 1 (FR1) schedule of reinforcement, the fixed-ratio requirement for lever pressing was increased at five-session intervals to values of FR2, FR5, FR10, FR20, and FR30. We examined vaginal cytology after each behavior session to track estrous cyclicity. Under each of the FR values, perinatal TCDD exposure produced a significant dose-related reduction in the number of earned opportunities to run, the lever response rate, and the total number of revolutions in the wheel. Estrous cyclicity was not affected. Because of the consistent dose-response relationship at all FR values, we used the behavioral data to calculate benchmark doses based on displacements from modeled zero-dose performance of 1% (ED(01)) and 10% (ED(10)), as determined by a quadratic fit to the dose-response function. The mean ED(10) benchmark dose for earned run opportunities was 10.13 ng/kg with a 95% lower bound of 5.77 ng/kg. The corresponding ED(01) was 0.98 ng/kg with a 95% lower bound of 0.83 ng/kg. The mean ED(10) for total wheel revolutions was calculated as 7.32 ng/kg with a 95% lower bound of 5.41 ng/kg. The corresponding ED(01) was 0.71 ng/kg with a 95% lower bound of 0.60. These values should be viewed from the perspective of current human body burdens, whose average value, based on TCDD toxic equivalents, has been calculated as 13 ng/kg.

  6. Inactivation of the Prelimbic Cortex Attenuates Context-Dependent Operant Responding

    PubMed Central

    Shipman, Megan L.; Bouton, Mark E.

    2017-01-01

    Operant responding in rats provides an analog to voluntary behavior in humans and is used to study maladaptive behaviors, such as overeating, drug taking, or relapse. In renewal paradigms, extinguished behavior recovers when tested outside the context where extinction was learned. Inactivation of the prelimbic (PL) region of the medial prefrontal cortex by baclofen/muscimol (B/M) during testing attenuates renewal when tested in the original acquisition context after extinction in another context (ABA renewal). Two experiments tested the hypothesis that the PL is important in context-dependent responding learned during conditioning. In the first, rats learned to lever-press for a sucrose-pellet reward. Following acquisition, animals were infused with either B/M or vehicle in the PL and tested in the acquisition context (A) and in a different context (B). All rats showed a decrement in responding when switched from Context A to Context B, but PL inactivation decreased responding only in Context A. Experiment 2a examined the effects of PL inactivation on ABC renewal in the same rats. Here, following reacquisition of the response, responding was extinguished in a new context (C). Following infusions of B/M or vehicle in the PL, responding was tested in Context C and another new context (D). The rats exhibited ACD renewal regardless of PL inactivation. Experiment 2b demonstrated that PL inactivation attenuated the ABA renewal effect in the same animals, replicating earlier results and demonstrating that cannulae were still functional. The results suggest that, rather than attenuating renewal generally, PL inactivation specifically affects ABA renewal by reducing responding in the conditioning context. SIGNIFICANCE STATEMENT Extinguished operant behavior can recover (“renew”) when tested outside the extinction context. This suggests that behaviors, such as overeating or drug taking, might be especially prone to relapse following treatment. In rats, inactivation of

  7. Linking Science with Design and Technology in a Stimulating Approach to Teaching about Levers

    ERIC Educational Resources Information Center

    Davenport, Carol

    2015-01-01

    Changes in the National Curriculum for England in 2014 included the introduction of levers, gears, and pulleys into primary science. Although simple mechanisms had been part of the design and technology (DT) curriculum for some time, it was the first time that the science behind the mechanisms had been included at the primary school level. These…

  8. 75 FR 48921 - Administrative Guidance for Multistate Extension Activities and Integrated Research and Extension...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-12

    .... Section 105 of AREERA amended the Smith-Lever Act to require that a specified amount of agricultural... Hatch Act and Smith-Lever Act to require that a specified amount of agricultural research and extension... Smith- Lever Act funds on multistate extension activities and 25 percent on integrated research and...

  9. Extinction of Chained Instrumental Behaviors: Effects of Procurement Extinction on Consumption Responding

    PubMed Central

    Thrailkill, Eric A.; Bouton, Mark E.

    2015-01-01

    Instrumental behavior often consists of sequences or chains of responses that minimally include procurement behaviors that enable subsequent consumption behaviors. In such chains, behavioral units are linked by access to one another and eventually to a primary reinforcer, such as food or a drug. The present experiments examined the effects of extinguishing procurement responding on consumption responding after training of a discriminated heterogeneous instrumental chain. Rats learned to make a procurement response (e.g., pressing a lever) in the presence of a distinctive discriminative stimulus; making that response led to the presentation of a second discriminative stimulus that set the occasion for a consumption response (e.g., pulling a chain), which then produced a food-pellet reinforcer. Experiment 1 showed that extinction of either the full procurement-consumption chain or procurement alone weakened the consumption response tested in isolation. Experiment 2 replicated the procurement extinction effect and further demonstrated that the opportunity to make the procurement response, as opposed to simple exposure to the procurement stimulus alone, was required. In Experiment 3, rats learned 2 distinct discriminated heterogeneous chains; extinction of 1 procurement response specifically weakened the consumption response that had been associated with it. The results suggest that learning to inhibit the procurement response may produce extinction of consumption responding through mediated extinction. The experiments suggest the importance of an associative analysis of instrumental behavior chains. PMID:25915751

  10. The effects of physical activity on impulsive choice: Influence of sensitivity to reinforcement amount and delay

    PubMed Central

    Strickland, Justin C.; Feinstein, Max A.; Lacy, Ryan T.; Smith, Mark A.

    2016-01-01

    Impulsive choice is a diagnostic feature and/or complicating factor for several psychological disorders and may be examined in the laboratory using delay-discounting procedures. Recent investigators have proposed using quantitative measures of analysis to examine the behavioral processes contributing to impulsive choice. The purpose of this study was to examine the effects of physical activity (i.e., wheel running) on impulsive choice in a single-response, discrete-trial procedure using two quantitative methods of analysis. To this end, rats were assigned to physical activity or sedentary groups and trained to respond in a delay-discounting procedure. In this procedure, one lever always produced one food pellet immediately, whereas a second lever produced three food pellets after a 0, 10, 20, 40, or 80-second delay. Estimates of sensitivity to reinforcement amount and sensitivity to reinforcement delay were determined using (1) a simple linear analysis and (2) an analysis of logarithmically transformed response ratios. Both analyses revealed that physical activity decreased sensitivity to reinforcement amount and sensitivity to reinforcement delay. These findings indicate that (1) physical activity has significant but functionally opposing effects on the behavioral processes that contribute to impulsive choice and (2) both quantitative methods of analysis are appropriate for use in single-response, discrete-trial procedures. PMID:26964905

  11. Bupropion differentially impacts acquisition of methamphetamine self-administration and sucrose-maintained behavior

    PubMed Central

    Reichel, Carmela M.; Linkugel, Jessica D.; Bevins, Rick A.

    2010-01-01

    Bupropion reduces the subjective effects and cue-induced craving for methamphetamine in humans. Given these effects of bupropion on methamphetamine in humans and its widespread clinical use, a preclinical model of drug-taking was used to determine if pretreatment with bupropion would alter the acquisition of methamphetamine self-administration. During acquisition, rats were given saline or bupropion (30 or 60 mg/kg, IP) 5 min before a 60-min session. For the first 8 days, each response on the active lever produced an infusion of methamphetamine (0.025 mg/kg). Responding on the inactive lever had no programmed consequence. This FR1 schedule was then increased to an FR3 for 4 more days. In a parallel study, the identical procedures were used to test the impact of bupropion on sucrose-maintained responding. Bupropion pretreatment decreased the number of methamphetamine infusions and sucrose deliveries earned on an FR1 and FR3. However, bupropion pretreatment only delayed discrimination between the active and inactive levers in the methamphetamine self-administration rats. Discrimination between active and inactive levers was acquired in all groups in the sucrose experiment regardless of pretreatment condition. Combined, these results suggest that bupropion has a more general effect within the appetitive/reward system of the brain rather than having complete specificity for methamphetamine. PMID:18329085

  12. Sterile Reverse Osmosis Water Combined with Friction Are Optimal for Channel and Lever Cavity Sample Collection of Flexible Duodenoscopes.

    PubMed

    Alfa, Michelle J; Singh, Harminder; Nugent, Zoann; Duerksen, Donald; Schultz, Gale; Reidy, Carol; DeGagne, Patricia; Olson, Nancy

    2017-01-01

    Simulated-use buildup biofilm (BBF) model was used to assess various extraction fluids and friction methods to determine the optimal sample collection method for polytetrafluorethylene channels. In addition, simulated-use testing was performed for the channel and lever cavity of duodenoscopes. BBF was formed in polytetrafluorethylene channels using Enterococcus faecalis, Escherichia coli , and Pseudomonas aeruginosa . Sterile reverse osmosis (RO) water, and phosphate-buffered saline with and without Tween80 as well as two neutralizing broths (Letheen and Dey-Engley) were each assessed with and without friction. Neutralizer was added immediately after sample collection and samples concentrated using centrifugation. Simulated-use testing was done using TJF-Q180V and JF-140F Olympus duodenoscopes. Despite variability in the bacterial CFU in the BBF model, none of the extraction fluids tested were significantly better than RO. Borescope examination showed far less residual material when friction was part of the extraction protocol. The RO for flush-brush-flush (FBF) extraction provided significantly better recovery of E. coli ( p  = 0.02) from duodenoscope lever cavities compared to the CDC flush method. We recommend RO with friction for FBF extraction of the channel and lever cavity of duodenoscopes. Neutralizer and sample concentration optimize recovery of viable bacteria on culture.

  13. Rats' Memory for Time and Relational Responding in the Duration-Comparison Procedure

    ERIC Educational Resources Information Center

    Santi, Angelo; Hoover, Claire; Simmons, Sabrina

    2011-01-01

    Rats were trained in a duration-comparison task to press one lever if the comparison duration ("c") was 1.2-s shorter than a standard duration ("s"), and another lever if c was 1.2-s longer than s. The interval between s and c duration was 1 s. The 10 duration pairs used during training controlled for the absolute duration of "c" and the total…

  14. Responding for sucrose and wheel-running reinforcement: effect of pre-running.

    PubMed

    Belke, Terry W

    2006-01-10

    Six male albino Wistar rats were placed in running wheels and exposed to a fixed interval 30-s schedule that produced either a drop of 15% sucrose solution or the opportunity to run for 15s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. To assess the effect of pre-running, animals were allowed to run for 1h prior to a session of responding for sucrose and running. Results showed that, after pre-running, response rates in the later segments of the 30-s schedule decreased in the presence of a wheel-running stimulus and increased in the presence of a sucrose stimulus. Wheel-running rates were not affected. Analysis of mean post-reinforcement pauses (PRP) broken down by transitions between successive reinforcers revealed that pre-running lengthened pausing in the presence of the stimulus signaling wheel running and shortened pauses in the presence of the stimulus signaling sucrose. No effect was observed on local response rates. Changes in pausing in the presence of stimuli signaling the two reinforcers were consistent with a decrease in the reinforcing efficacy of wheel running and an increase in the reinforcing efficacy of sucrose. Pre-running decreased motivation to respond for running, but increased motivation to work for food.

  15. Inactivation of the Prelimbic Cortex Attenuates Context-Dependent Operant Responding.

    PubMed

    Trask, Sydney; Shipman, Megan L; Green, John T; Bouton, Mark E

    2017-03-01

    Operant responding in rats provides an analog to voluntary behavior in humans and is used to study maladaptive behaviors, such as overeating, drug taking, or relapse. In renewal paradigms, extinguished behavior recovers when tested outside the context where extinction was learned. Inactivation of the prelimbic (PL) region of the medial prefrontal cortex by baclofen/muscimol (B/M) during testing attenuates renewal when tested in the original acquisition context after extinction in another context (ABA renewal). Two experiments tested the hypothesis that the PL is important in context-dependent responding learned during conditioning. In the first, rats learned to lever-press for a sucrose-pellet reward. Following acquisition, animals were infused with either B/M or vehicle in the PL and tested in the acquisition context (A) and in a different context (B). All rats showed a decrement in responding when switched from Context A to Context B, but PL inactivation decreased responding only in Context A. Experiment 2a examined the effects of PL inactivation on ABC renewal in the same rats. Here, following reacquisition of the response, responding was extinguished in a new context (C). Following infusions of B/M or vehicle in the PL, responding was tested in Context C and another new context (D). The rats exhibited ACD renewal regardless of PL inactivation. Experiment 2b demonstrated that PL inactivation attenuated the ABA renewal effect in the same animals, replicating earlier results and demonstrating that cannulae were still functional. The results suggest that, rather than attenuating renewal generally, PL inactivation specifically affects ABA renewal by reducing responding in the conditioning context. SIGNIFICANCE STATEMENT Extinguished operant behavior can recover ("renew") when tested outside the extinction context. This suggests that behaviors, such as overeating or drug taking, might be especially prone to relapse following treatment. In rats, inactivation of the

  16. Parrotfish grazing ability: interspecific differences in relation to jaw-lever mechanics and relative weight of adductor mandibulae on an Okinawan coral reef

    PubMed Central

    2016-01-01

    Parrotfishes (family Labridae: Scarini) are regarded to have important roles for maintaining the ecosystem balance in coral reefs due to their removal of organic matter and calcic substrates by grazing. The purpose of the present study was to clarify the interspecific differences in grazing ability of five parrotfish species (Chlorurus sordidus, C. bowersi, Scarus rivulatus, S. niger and S. forsteni) in relation to interspecific differences in jaw-lever mechanics and the relative weight of the adductor mandibulae (muscles operating jaw closing). The grazing ability was calculated by using stomach contents (CaCO3 weight/organic matter weight) defined as the grazing ability index (GAI). There were significant interspecific differences in GAI (C. sordidus = C. bowersi > S. rivulatus > S. niger = S. forsteni). Teeth of C. sordidus and C. bowersi were protrusive-shape whereas teeth of S. rivulatus, S. niger and S. forsteni were flat-shape. C. sordidus and C. bowersihave jaw-lever mechanics producing a greater biting force and have a larger weight of adductor mandibulae. S. rivulatus has jaw-lever mechanics producing a greater biting force but a smaller weight of adductor mandibulae that produce an intermediate biting force. In contrast, S. niger and S. forsteni have jaw-lever mechanics producing a lesser biting force and have a smaller weight of adductor mandibulae. Feeding rates and foray size of S. rivulatus, S. niger and S. forsteni were greater than C. sordidus and C. bowersi. The degree in bioerosion (GAI × feeding rate) was the largest for S. rivulatusand the smallest for S. forsteni. The degree in bioerosion for C. sordidus was larger than S. niger whereas relatively equal between C. bowersi and S. niger. These results suggest that interspecific difference in GAI was explained by interspecific differences in teeth shape, jaw-lever mechanics and relative weight of adductor mandibulae. The interspecific difference in the degree of bioerosion suggests the

  17. Parrotfish grazing ability: interspecific differences in relation to jaw-lever mechanics and relative weight of adductor mandibulae on an Okinawan coral reef.

    PubMed

    Nanami, Atsushi

    2016-01-01

    Parrotfishes (family Labridae: Scarini) are regarded to have important roles for maintaining the ecosystem balance in coral reefs due to their removal of organic matter and calcic substrates by grazing. The purpose of the present study was to clarify the interspecific differences in grazing ability of five parrotfish species (Chlorurus sordidus, C. bowersi, Scarus rivulatus, S. niger and S. forsteni) in relation to interspecific differences in jaw-lever mechanics and the relative weight of the adductor mandibulae (muscles operating jaw closing). The grazing ability was calculated by using stomach contents (CaCO3 weight/organic matter weight) defined as the grazing ability index (GAI). There were significant interspecific differences in GAI (C. sordidus = C. bowersi > S. rivulatus > S. niger = S. forsteni). Teeth of C. sordidus and C. bowersi were protrusive-shape whereas teeth of S. rivulatus, S. niger and S. forsteni were flat-shape. C. sordidus and C. bowersihave jaw-lever mechanics producing a greater biting force and have a larger weight of adductor mandibulae. S. rivulatus has jaw-lever mechanics producing a greater biting force but a smaller weight of adductor mandibulae that produce an intermediate biting force. In contrast, S. niger and S. forsteni have jaw-lever mechanics producing a lesser biting force and have a smaller weight of adductor mandibulae. Feeding rates and foray size of S. rivulatus, S. niger and S. forsteni were greater than C. sordidus and C. bowersi. The degree in bioerosion (GAI × feeding rate) was the largest for S. rivulatusand the smallest for S. forsteni. The degree in bioerosion for C. sordidus was larger than S. niger whereas relatively equal between C. bowersi and S. niger. These results suggest that interspecific difference in GAI was explained by interspecific differences in teeth shape, jaw-lever mechanics and relative weight of adductor mandibulae. The interspecific difference in the degree of bioerosion suggests the

  18. Time-Course of the Ethanol-like Discriminative Stimulus Effects of Abused Inhalants in Mice

    PubMed Central

    Bowen, Scott E.

    2009-01-01

    Abused solvents have effects similar to those of abused depressant drugs. This experiment evaluated the time course of the discriminative stimulus effects of toluene and 1,1,1-trichloroethane (TRI). Mice were trained to discriminate between i.p. injections of ethanol (EtOH;1.25 g/kg) and saline in a two-lever operant task in which responding was under the control of a fixed-ratio 20 schedule. After 20-min inhalation exposures to toluene (500–6000 ppm) or TRI (1,000–12,000 ppm), stimulus generalization was examined at 0, 5, 10, 20, and 40 min post-exposure. Ethanol doses ≥ 0.25 g/kg produced increases in EtOH-lever responding with full substitution occurring immediately after testing for doses between 1.25 and 2.5 g/kg. Toluene and TRI produced increased EtOH-lever responding at 0–10 min post exposure with some EtOH-lever responding occurring up to 20-min post exposure. Response rates were not decreased for any concentration of toluene or TRI immediately following inhalant exposure but several concentrations elevated rates from 5–40 min post exposure. These results confirm and extend previous studies and show these solvents produce similar effects in EtOH-lever responding but with potency differences. The time-dependent differences in EtOH-lever responding suggest that as solvents are cleared from the body, the EtOH-like subjective effects also fade. PMID:18722399

  19. Establishment of auditory discrimination and detection of tinnitus induced by salicylic acid and intense tone exposure in the rat.

    PubMed

    Sederholm, Fredrik; Swedberg, Michael D B

    2013-05-13

    Rats were trained in a two lever food reinforced operant procedure to discriminate a 8000 Hz pure tone stimulus from its absence. Responding on one lever was reinforced in the presence of the tone and responding on the other lever was reinforced when the tone was absent. Frequency generalization testing yielded an inverted U-shaped function, whereas sound pressure level generalization testing yielded a continuous decrease in responding on the tone associated lever with decreasing sound pressure levels. The administration of sodium salicylic acid (150-450 mg/kg) generated responding on the tone associated lever suggesting that salicylic acid induced an experience that had commonalities with the percept of the training tone stimulus. After exposure to intense sound, responding consistent with the presence of tinnitus was achieved and Lidocaine failed to reduce tinnitus behavior. The use of a two choice design helped avoid confounding factors induced by drug induced side effects. Further, since no auditory cues were employed in the test situation the model achieves resistance to potential bias due to hearing impairment and hyperacusis. We propose that this model may be useful in detecting tinnitus. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Cue-induced reinstatement of ethanol seeking in Sardinian alcohol-preferring rats.

    PubMed

    Maccioni, Paola; Orrú, Alessandro; Korkosz, Agnieszka; Gessa, Gian Luigi; Carai, Mauro A M; Colombo, Giancarlo; Bienkowski, Przemyslaw

    2007-02-01

    The purpose of the present study was to characterize cue-induced reinstatement of ethanol seeking in selectively bred Sardinian alcohol-preferring (sP) rats trained to lever press for ethanol in 30-min self-administration sessions. Four responses on an "active" lever led to presentation of 0.1 ml of 15% (vol/vol) ethanol by a liquid dipper and concurrent activation of a set of discrete light and auditory cues. In a 70-min extinction/reinstatement session, responding was first extinguished for 60 min. Subsequently, different stimuli were delivered in a noncontingent manner and reinstatement of nonreinforced responding was assessed. Fifteen presentations of the ethanol-predictive stimulus complex, including the dipper cup containing 5 or 15% ethanol, potently reinstated responding on the previously active lever. The magnitude of reinstatement increased with the number of stimulus presentations and concentration of ethanol presented by the dipper cup. Fifteen presentations of the ethanol-predictive stimulus complex, including the dipper cup filled with water (0% ethanol), did not produce any reinstatement. These results indicate that (1) noncontingent presentations of the ethanol-predictive stimulus complex may reinstate ethanol seeking in sP rats and (2) the orosensory properties of ethanol may play an important role in reinstatement of ethanol seeking in sP rats. The latter finding concurs with clinical observations that odor and taste of alcoholic beverages elicit immediate craving responses in abstinent alcoholics.

  1. The sensory features of a food cue influence its ability to act as an incentive stimulus and evoke dopamine release in the nucleus accumbens core

    PubMed Central

    Bryan, Myranda A.; Popov, Pavlo; Scarff, Raymond; Carter, Cody; Wright, Erin; Aragona, Brandon J.; Robinson, Terry E.

    2016-01-01

    The sensory properties of a reward-paired cue (a conditioned stimulus; CS) may impact the motivational value attributed to the cue, and in turn influence the form of the conditioned response (CR) that develops. A cue with multiple sensory qualities, such as a moving lever-CS, may activate numerous neural pathways that process auditory and visual information, resulting in CRs that vary both within and between individuals. For example, CRs include approach to the lever-CS itself (rats that “sign-track”; ST), approach to the location of reward delivery (rats that “goal-track”; GT), or an “intermediate” combination of these behaviors. We found that the multimodal sensory features of the lever-CS were important to the development and expression of sign-tracking. When the lever-CS was covered, and thus could only be heard moving, STs not only continued to approach the lever location but also started to approach the food cup during the CS period. While still predictive of reward, the auditory component of the lever-CS was a much weaker conditioned reinforcer than the visible lever-CS. This plasticity in behavioral responding observed in STs closely resembled behaviors normally seen in rats classified as “intermediates.” Furthermore, the ability of both the lever-CS and the reward-delivery to evoke dopamine release in the nucleus accumbens was also altered by covering the lever—dopamine signaling in STs resembled neurotransmission observed in rats that normally only GT. These data suggest that while the visible lever-CS was attractive, wanted, and had incentive value for STs, when presented in isolation, the auditory component of the cue was simply predictive of reward, lacking incentive salience. Therefore, the specific sensory features of cues may differentially contribute to responding and ensure behavioral flexibility. PMID:27918279

  2. [Levers in Primary Health Care - Identifying Strategic Success Factors for Improved Primary Care in Upper Austria].

    PubMed

    Kriegel, J; Rebhandl, E; Reckwitz, N; Hockl, W

    2016-12-01

    Current and projected general practitioner (GP) and primary care in Austria shows structural and process inadequacies in the quality as well as assurance of healthcare supply. The aim is therefore to develop solution- and patient-oriented measures that take patient-related requirements and medical perspectives into account. Using an effect matrix, subjective expert and user priorities were ascertained, cause and effect relationships were examined, and an expanded circle of success for the optimization of GP and primary care in Upper Austria was developed. Through this, the relevant levers for target-oriented development and optimization of the complex system of GP and primary care in Upper Austria were identified; these are training to become general practitioners, entrepreneurs as well as management and coordination. It is necessary to further adapt the identified levers conceptually and operationally in a targeted approach. This is to be achieved by means of the primary health care (PHC) concept as well as management tools and information and communication technologies (ICT) associated with it. © Georg Thieme Verlag KG Stuttgart · New York.

  3. The effects of physical activity on impulsive choice: Influence of sensitivity to reinforcement amount and delay.

    PubMed

    Strickland, Justin C; Feinstein, Max A; Lacy, Ryan T; Smith, Mark A

    2016-05-01

    Impulsive choice is a diagnostic feature and/or complicating factor for several psychological disorders and may be examined in the laboratory using delay-discounting procedures. Recent investigators have proposed using quantitative measures of analysis to examine the behavioral processes contributing to impulsive choice. The purpose of this study was to examine the effects of physical activity (i.e., wheel running) on impulsive choice in a single-response, discrete-trial procedure using two quantitative methods of analysis. To this end, rats were assigned to physical activity or sedentary groups and trained to respond in a delay-discounting procedure. In this procedure, one lever always produced one food pellet immediately, whereas a second lever produced three food pellets after a 0, 10, 20, 40, or 80-s delay. Estimates of sensitivity to reinforcement amount and sensitivity to reinforcement delay were determined using (1) a simple linear analysis and (2) an analysis of logarithmically transformed response ratios. Both analyses revealed that physical activity decreased sensitivity to reinforcement amount and sensitivity to reinforcement delay. These findings indicate that (1) physical activity has significant but functionally opposing effects on the behavioral processes that contribute to impulsive choice and (2) both quantitative methods of analysis are appropriate for use in single-response, discrete-trial procedures. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. A Comparison of Active Student Responding Modalities in a General Psychology Course

    ERIC Educational Resources Information Center

    Zayac, Ryan M.; Ratkos, Thom; Frieder, Jessica E.; Paulk, Amber

    2016-01-01

    Research on teaching has shown that incorporating active student responding (ASR) into classroom instruction facilitates learning and should be considered best practice. Nevertheless, few published studies have examined ASR using a within-participant design across a semester. Using a counterbalanced alternating treatment design, a direct…

  5. Lateral, not medial, prefrontal cortex contributes to punishment and aversive instrumental learning

    PubMed Central

    Jean-Richard-dit-Bressel, Philip

    2016-01-01

    Aversive outcomes punish behaviors that cause their occurrence. The prefrontal cortex (PFC) has been implicated in punishment learning and behavior, although the exact roles for different PFC regions in instrumental aversive learning and decision-making remain poorly understood. Here, we assessed the role of the orbitofrontal (OFC), rostral agranular insular (RAIC), prelimbic (PL), and infralimbic (IL) cortex in instrumental aversive learning and decision-making. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused mild punishment (punished lever) but continued pressing the other lever that did not cause punishment (unpunished lever). Inactivations of OFC, RAIC, IL, or PL via the GABA agonists baclofen and muscimol (BM) had no effect on the acquisition of instrumental learning. OFC inactivations increased responding on the punished lever during expression of well-learned instrumental aversive learning, whereas RAIC inactivations increased responding on the punished lever when both levers were presented simultaneously in an unpunished choice test. There were few effects of medial PFC (PL and IL) inactivation. These results suggest that lateral PFC, notably OFC and RAIC, have complementary functions in aversive instrumental learning and decision-making; OFC is important for using established aversive instrumental memories to guide behavior away from actions that cause punishment, whereas RAIC is important for aversive decision-making under conditions of choice. PMID:27918280

  6. The effects of nicotine exposure during Pavlovian conditioning in rats on several measures of incentive motivation for a conditioned stimulus paired with water.

    PubMed

    Guy, Elizabeth Glenn; Fletcher, Paul J

    2014-06-01

    Nicotine enhances approach toward and operant responding for conditioned stimuli (CSs), but the effect of exposure during different phases of Pavlovian incentive learning on these measures remains to be determined. These studies examined the effects of administering nicotine early, late or throughout Pavlovian conditioning trials on discriminated approach behavior, nicotine-enhanced responding for conditioned reinforcement, extinction, and the reinstatement of responding for conditioned reinforcement. We also tested the effect of nicotine on approach to a lever-CS in a Pavlovian autoshaping procedure and for this CS to serve as a conditioned reinforcer. Thirsty rats were exposed to 13 conditioning sessions where a light/tone CS was paired with the delivery of water. Nicotine was administered either prior to the first or last seven sessions, or throughout the entire conditioning procedure. Responding for conditioned reinforcement, extinction, and the reinstatement of responding by the stimulus and nicotine were compared across exposure groups. Separately, the effects of nicotine on conditioned approach toward a lever-CS during autoshaping, and responding for that CS as a conditioned reinforcer, were examined. Nicotine exposure was necessary for nicotine-enhanced responding for conditioned reinforcement and the ability for nicotine and the stimulus to additively reinstate responding on the reinforced lever. Nicotine increased contacts with a lever-CS during autoshaping, and removal of nicotine abolished this effect. Prior nicotine exposure was necessary for nicotine-enhanced responding reinforced by the lever. Enhancements in the motivating properties of CSs by nicotine occur independently from duration and timing effects of nicotine exposure during conditioning.

  7. Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned Responding.

    PubMed

    Boeke, Emily A; Moscarello, Justin M; LeDoux, Joseph E; Phelps, Elizabeth A; Hartley, Catherine A

    2017-05-03

    Patients with anxiety disorders often experience a relapse in symptoms after exposure therapy. Similarly, threat responses acquired during Pavlovian threat conditioning often return after extinction learning. Accordingly, there is a need for alternative methods to persistently reduce threat responding. Studies in rodents have suggested that exercising behavioral control over an aversive stimulus can persistently diminish threat responses, and that these effects are mediated by the amygdala, ventromedial prefrontal cortex, and striatum. In this fMRI study, we attempted to translate these findings to humans. Subjects first underwent threat conditioning. We then contrasted two forms of safety learning: active avoidance, in which participants could prevent the shock through an action, and yoked extinction, with shock presentation matched to the active condition, but without instrumental control. The following day, we assessed subjects' threat responses (measured by skin conductance) to the conditioned stimuli without shock. Subjects next underwent threat conditioning with novel stimuli. Yoked extinction subjects showed an increase in conditioned response to stimuli from the previous day, but the active avoidance group did not. Additionally, active avoidance subjects showed reduced conditioned responding during novel threat conditioning, but the extinction group did not. We observed between-group differences in striatal BOLD responses to shock omission in Avoidance/Extinction. These findings suggest a differential role for the striatum in human active avoidance versus extinction learning, and indicate that active avoidance may be more effective than extinction in persistently diminishing threat responses. SIGNIFICANCE STATEMENT Extinguished threat responses often reemerge with time, highlighting the importance of identifying more enduring means of attenuation. We compared the effects of active avoidance learning and yoked extinction on threat responses in humans and

  8. Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned Responding

    PubMed Central

    Boeke, Emily A.; Moscarello, Justin M.; Phelps, Elizabeth A.

    2017-01-01

    Patients with anxiety disorders often experience a relapse in symptoms after exposure therapy. Similarly, threat responses acquired during Pavlovian threat conditioning often return after extinction learning. Accordingly, there is a need for alternative methods to persistently reduce threat responding. Studies in rodents have suggested that exercising behavioral control over an aversive stimulus can persistently diminish threat responses, and that these effects are mediated by the amygdala, ventromedial prefrontal cortex, and striatum. In this fMRI study, we attempted to translate these findings to humans. Subjects first underwent threat conditioning. We then contrasted two forms of safety learning: active avoidance, in which participants could prevent the shock through an action, and yoked extinction, with shock presentation matched to the active condition, but without instrumental control. The following day, we assessed subjects' threat responses (measured by skin conductance) to the conditioned stimuli without shock. Subjects next underwent threat conditioning with novel stimuli. Yoked extinction subjects showed an increase in conditioned response to stimuli from the previous day, but the active avoidance group did not. Additionally, active avoidance subjects showed reduced conditioned responding during novel threat conditioning, but the extinction group did not. We observed between-group differences in striatal BOLD responses to shock omission in Avoidance/Extinction. These findings suggest a differential role for the striatum in human active avoidance versus extinction learning, and indicate that active avoidance may be more effective than extinction in persistently diminishing threat responses. SIGNIFICANCE STATEMENT Extinguished threat responses often reemerge with time, highlighting the importance of identifying more enduring means of attenuation. We compared the effects of active avoidance learning and yoked extinction on threat responses in humans and

  9. Sensing cantilever beam bending by the optical lever technique and its application to surface stress.

    PubMed

    Evans, Drew R; Craig, Vincent S J

    2006-03-23

    Cantilever beams, both microscopic and macroscopic, are used as sensors in a great variety of applications. An optical lever system is commonly employed to determine the deflection and thereby the profile of the cantilever under load. The sensitivity of the optical lever must be calibrated, and this is usually achieved by application of a known load or deflection to the free end of the cantilever. When the sensing operation involves a different type of load or a combination of types of loadings, the calibration and the deflection values derived from it become invalid. Here we develop a master equation that permits the true deflection of the cantilever to be obtained simply from the measurement of the apparent deflection for uniformly distributed loadings and end-moment loadings. These loadings are relevant to the uniform adsorption or application of material to the cantilever or the application of a surface stress to the cantilever and should assist experimentalists using the optical lever, such as in the atomic force microscope, to measure cantilever deflections in a great variety of sensing applications. We then apply this treatment to the experimental evaluation of surface stress. Three forms of Stoney's equation that relate the apparent deflection to the surface stress, which is valid for both macroscopic and microscopic experiments, are derived. Analysis of the errors arising from incorrect modeling of the loading conditions of the cantilever currently applied in experiments is also presented. It is shown that the reported literature values for surface stress in microscopic experiments are typically 9% smaller than their true value. For macroscopic experiments, we demonstrate that the added mass of the film or coating generally dominates the measured deflection and must be accounted for accurately if surface stress measurements are to be made. Further, the reported measurements generally use a form of Stoney's equation that is in error, resulting in an

  10. Visual and auditory cue integration for the generation of saccadic eye movements in monkeys and lever pressing in humans.

    PubMed

    Schiller, Peter H; Kwak, Michelle C; Slocum, Warren M

    2012-08-01

    This study examined how effectively visual and auditory cues can be integrated in the brain for the generation of motor responses. The latencies with which saccadic eye movements are produced in humans and monkeys form, under certain conditions, a bimodal distribution, the first mode of which has been termed express saccades. In humans, a much higher percentage of express saccades is generated when both visual and auditory cues are provided compared with the single presentation of these cues [H. C. Hughes et al. (1994) J. Exp. Psychol. Hum. Percept. Perform., 20, 131-153]. In this study, we addressed two questions: first, do monkeys also integrate visual and auditory cues for express saccade generation as do humans and second, does such integration take place in humans when, instead of eye movements, the task is to press levers with fingers? Our results show that (i) in monkeys, as in humans, the combined visual and auditory cues generate a much higher percentage of express saccades than do singly presented cues and (ii) the latencies with which levers are pressed by humans are shorter when both visual and auditory cues are provided compared with the presentation of single cues, but the distribution in all cases is unimodal; response latencies in the express range seen in the execution of saccadic eye movements are not obtained with lever pressing. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  11. Enhancing Academic Engagement: Providing Opportunities for Responding and Influencing Students to Choose to Respond

    ERIC Educational Resources Information Center

    Skinner, Christopher H.; Pappas, Danielle N.; Davis, Kai A.

    2005-01-01

    Although educators often provide opportunities for students to engage in active academic responding, in many situations, students either cannot or will not respond. In the current article, we analyze the reasons students fail to respond. Practical procedures educators can use to prevent "can't do" problems are provided. "Won't do" problems are…

  12. Responding to the active and passive patient: flexibility is the key

    PubMed Central

    Brown, Rhonda F.; Butow, Phyllis N.; Henman, Michael; Dunn, Stewart M.; Boyle, Francis; Tattersall, Martin H.N.

    2002-01-01

    Abstract Background  Patients vary widely in their preferences and capacity for participation in medical decision‐making. This study aimed to document oncologist responses to more extreme presentations and identify helpful and unhelpful strategies for clinicians. Patients and methods  A trained actor played the role of a patient with early stage breast cancer who was attending her first consultation with a medical oncologist. She adopted in random order two different consultation participation styles: that of a very anxious, active patient, and that of a depressed, passive patient. Medical consultations between the actor and 16 medical oncologists were videotaped and then analysed qualitatively by two trained raters. Results  Strategies that facilitated shared decision‐making with both patient types and were positively endorsed by the actor/patient included explicit agenda‐setting, active listening, checking understanding, endorsing question‐asking, offering decisional delay, and non‐verbal behaviours conveying empathy and warmth. Oncologists successfully negotiated with the active patient to share control of the consultation, and responded to emotional cues from the passive patient. Unhelpful strategies were also identified. Conclusions  Few clinicians receive training in responding to differing communication styles in their patients that could potentially cause conflict and hinder optimal treatment decision‐making. This study suggests some useful strategies for oncologists to consider, to widen their behavioural repertoire in the cancer consultation. PMID:12199662

  13. Drug versus sweet reward: greater attraction to and preference for sweet versus drug cues.

    PubMed

    Madsen, Heather B; Ahmed, Serge H

    2015-05-01

    Despite the unique ability of addictive drugs to directly activate brain reward circuits, recent evidence suggests that drugs induce reinforcing and incentive effects that are comparable to, or even lower than some nondrug rewards. In particular, when rats have a choice between pressing a lever associated with intravenous cocaine or heroin delivery and another lever associated with sweet water delivery, most respond on the latter. This outcome suggests that sweet water is more reinforcing and attractive than either drug. However, this outcome may also be due to the differential ability of sweet versus drug levers to elicit Pavlovian feeding-like conditioned responses that can cause involuntary lever pressing, such as pawing and biting the lever. To test this hypothesis, rats first underwent Pavlovian conditioning to associate one lever with sweet water (0.2% saccharin) and a different lever with intravenous cocaine (0.25 mg) or heroin (0.01 mg). Choice between these two levers was then assessed under two operant choice procedures: one that permitted the expression of Pavlovian-conditioned lever press responses during choice, the other not. During conditioning, Pavlovian-conditioned lever press responses were considerably higher on the sweet lever than on either drug lever, and slightly greater on the heroin lever than on the cocaine lever. Importantly, though these differences in Pavlovian-conditioned behavior predicted subsequent preference for sweet water during choice, they were not required for its expression. Overall, this study confirms that rats prefer the sweet lever because sweet water is more reinforcing and attractive than cocaine or heroin. © 2014 Society for the Study of Addiction.

  14. Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats

    PubMed Central

    García-Fuster, M. Julia; Parsegian, Aram; Watson, Stanley J.; Akil, Huda; Flagel, Shelly B.

    2018-01-01

    Rationale Environmental challenges during adolescence, such as drug exposure, can cause enduring behavioral and molecular changes that contribute to life-long maladaptive behaviors, including addiction. Selectively bred high-responder (bHR) and low-responder (bLR) rats represent a unique model for assessing the long-term impact of adolescent environmental manipulations, as they inherently differ on a number of addiction-related traits. bHR rats are considered “addiction-prone”, whereas bLR rats are “addiction-resilient”, at least under baseline conditions. Moreover, relative to bLRs, bHR rats are more likely to attribute incentive motivational value to reward cues, or to “sign-track”. Objectives We utilized bHR and bLR rats to determine whether adolescent cocaine exposure can alter their inborn behavioral and neurobiological profiles, with a specific focus on Pavlovian conditioned approach behavior (i.e. sign- vs. goal-tracking) and hippocampal neurogenesis. Methods bHR and bLR rats were administered cocaine (15 mg/kg) or saline for 7 days during adolescence (postnatal day, PND 33–39) and subsequently tested for Pavlovian conditioned approach behavior in adulthood (PND 62–75), wherein an illuminated lever (conditioned stimulus) was followed by the response-independent delivery of a food pellet (unconditioned stimulus). Behaviors directed towards the lever and the food cup were recorded as sign- and goal-tracking, respectively. Hippocampal cell genesis was evaluated on PND 77 by immunohistochemistry. Results Adolescent cocaine exposure impaired hippocampal cell genesis (proliferation and survival) and enhanced the inherent propensity to goal-track in adult bLR, but not bHR, rats. Conclusions Adolescent cocaine exposure elicits long-lasting changes in stimulus-reward learning and enduring deficits in hippocampal neurogenesis selectively in adult bLR rats. PMID:28210781

  15. Long-range coupling between ATP-binding and lever-arm regions in myosin via dielectric allostery

    NASA Astrophysics Data System (ADS)

    Sato, Takato; Ohnuki, Jun; Takano, Mitsunori

    2017-12-01

    A protein molecule is a dielectric substance, so the binding of a ligand is expected to induce dielectric response in the protein molecule, considering that ligands are charged or polar in general. We previously reported that binding of adenosine triphosphate (ATP) to molecular motor myosin actually induces such a dielectric response in myosin due to the net negative charge of ATP. By this dielectric response, referred to as "dielectric allostery," spatially separated two regions in myosin, the ATP-binding region and the actin-binding region, are allosterically coupled. In this study, from the statistically stringent analyses of the extensive molecular dynamics simulation data obtained in the ATP-free and the ATP-bound states, we show that there exists the dielectric allostery that transmits the signal of ATP binding toward the distant lever-arm region. The ATP-binding-induced electrostatic potential change observed on the surface of the main domain induced a movement of the converter subdomain from which the lever arm extends. The dielectric response was found to be caused by an underlying large-scale concerted rearrangement of the electrostatic bond network, in which highly conserved charged/polar residues are involved. Our study suggests the importance of the dielectric property for molecular machines in exerting their function.

  16. Experimental and Theoretical Investigations of a Mechanical Lever System Driven by a DC Motor

    NASA Astrophysics Data System (ADS)

    Nana, B.; Fautso Kuiate, G.; Yamgoué, S. B.

    This paper presents theoretical and experimental results on the investigation of the dynamics of a nonlinear electromechanical system made of a lever arm actuated by a DC motor and controlled through a repulsive magnetic force. We use the method of harmonic balance to derive oscillatory solutions. Theoretical tools such as, bifurcation diagrams, Lyapunov exponents, phase portraits, are used to unveil the rich nonlinear behavior of the system including chaos and hysteresis. The experimental results are in close accordance with the theoretical predictions.

  17. Ethanol-reinforced responding by AA and ANA rats following the sucrose-substitution initiation procedure.

    PubMed

    Files, F J; Denning, C E; Hyytia, P; Kiianmaa, K; Samson, H H

    1997-06-01

    Ethanol-reinforced responding was initiated in male AA and ANA rats using the sucrose-substitution procedure. Before the initiation procedure, a homecage, two-bottle preference test was conducted. The rats were then trained to respond on an Fixed-Ratio 1 schedule with sucrose reinforcement. Over sessions, ethanol was added gradually to the sucrose solution as the concentration of sucrose was reduced until 10% ethanol (v/v) alone functioned as the reinforcer for lever pressing. The schedule of reinforcement was then increased to Fixed-Ratio 4. Next, the ethanol concentration presented as the reinforcer was increased over weeks to 15%, 20%, 30%, and then returned to 10%. A second homecage test was then performed. The results showed that the AA and ANA lines differed significantly on preference and intake (g/kg) during the homecage preference tests. There was a significant increase in preference during the second homecage test. During sucrose substitution, initial large differences in responding were observed between the lines. When the ethanol concentration was increased, intake (grams per kilogram) increased for the AA line but not for the ANA line. These effects were a function of no change in responding by the AA rats as concentration was increased and a decrease in responding by the ANA rats at the higher concentrations (20% and 30%). Taken together, data indicate that ethanol can function as a positive reinforcer for the behavior of AA and ANA rats. Even though 10% ethanol functioned as a reinforcer similarly for the two lines, ethanol intake in the AA line was significantly greater at the higher concentrations of ethanol, suggesting that ethanol functioned as a qualitatively different reinforcer for the AA rats, compared with the ANA rats.

  18. α-Conotoxin MII-Sensitive Nicotinic Acetylcholine Receptors in the Nucleus Accumbens Shell Regulate Progressive Ratio Responding Maintained by Nicotine

    PubMed Central

    Brunzell, Darlene H; Boschen, Karen E; Hendrick, Elizabeth S; Beardsley, Patrick M; McIntosh, J Michael

    2010-01-01

    β2 subunit containing nicotinic acetylcholine receptors (β2*nAChRs; asterisk (*) denotes assembly with other subunits) are critical for nicotine self-administration and nicotine-associated dopamine (DA) release that supports nicotine reinforcement. The α6 subunit assembles with β2 on DA neurons where α6β2*nAChRs regulate nicotine-stimulated DA release at neuron terminals. Using local infusion of α-conotoxin MII (α-CTX MII), an antagonist with selectivity for α6β2*nAChRs, the purpose of these experiments was to determine if α6β2*nAChRs in the nucleus accumbens (NAc) shell are required for motivation to self-administer nicotine. Long-Evans rats lever-pressed for 0.03 mg/kg, i.v., nicotine accompanied by light+tone cues (NIC) or for light+tone cues unaccompanied by nicotine (CUEonly). Following extensive training, animals were tested under a progressive ratio (PR) schedule that required an increasing number of lever presses for each nicotine infusion and/or cue delivery. Immediately before each PR session, rats received microinfusions of α-CTX MII (0, 1, 5, or 10 pmol per side) into the NAc shell or the overlying anterior cingulate cortex. α-CTX MII dose dependently decreased break points and number of infusions earned by NIC rats following infusion into the NAc shell but not the anterior cingulate cortex. Concentrations of α-CTX MII that were capable of attenuating nicotine self-administration did not disrupt locomotor activity. There was no effect of infusion on lever pressing in CUEonly animals and NAc infusion α-CTX MII did not affect locomotor activity in an open field. These data suggest that α6β2*nAChRs in the NAc shell regulate motivational aspects of nicotine reinforcement but not nicotine-associated locomotor activation. PMID:19890263

  19. Reinstatement in a Cocaine vs. Food Choice Situation: Reversal of Preference between Drug and Non-Drug Rewards

    PubMed Central

    Tunstall, Brendan J.; Kearns, David N.

    2013-01-01

    Recent studies (for review see Ahmed, 2010; 2012) show that when given a mutually exclusive choice between cocaine and food, rats almost exclusively choose food. The present experiment investigated potential shifts in preference between levers associated with either food or cocaine which might occur during extinction (food and cocaine no longer available) and during footshock-induced, cocaine-primed, and food-primed reinstatement. During self-administration sessions where food and cocaine were simultaneously available, rats demonstrated a stable food preference, choosing food over cocaine on 83% of trials. During extinction when neither reinforcer was available, no preference between levers was evident and responding decreased until rats responded on the previously food- and cocaine-associated levers at equally low rates. Footshock resulted in a non-specific reinstatement of responding upon both levers, while cocaine priming resulted in a significant preference for cocaine seeking over food seeking. This suggests that the mechanism underlying footshock-induced reinstatement is distinct from that of cocaine-primed reinstatement. Food priming engendered a mild, non-specific increase in responding on both levers. Although rats generally prefer food over cocaine when presented with a choice between these primary reinforcers, the present results suggest that in certain situations cocaine-seeking behavior prevails over food-seeking behavior. PMID:23551949

  20. Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

    PubMed Central

    Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

    2012-01-01

    Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

  1. Responding for sucrose and wheel-running reinforcement: effect of D-amphetamine.

    PubMed

    Belke, T W; Oldford, A C; Forgie, M Y; Beye, J A

    2005-07-01

    The present study assessed the effect of D-amphetamine on responding maintained by wheel-running and sucrose reinforcement. Six male albino Wistar rats were placed in running wheels and exposed to a fixed-interval 30-s schedule that produced either a drop of 5% sucrose solution or the opportunity to run for 15 s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. Doses of 0.25, 0.5, 1.0, 1.5, and 3.0 mg/kg D-amphetamine were administered by i.p. injection 20 min prior to a session. As the dose increased, index of curvature values decreased toward zero and rate-dependency plots revealed increases in lower rates early in the interval and decreases in higher rates toward the end of the interval. Effects were similar in the presence of both stimuli. However, an analysis of post-reinforcement pauses and local response rates broken down by transitions revealed a differential effect. As the dose increased, local response rates following a wheel-running reinforcer were affected more than those following a sucrose reinforcer.

  2. Activation of Exchange Protein Activated by cAMP in the Rat Basolateral Amygdala Impairs Reconsolidation of a Memory Associated with Self-Administered Cocaine

    PubMed Central

    Sanchez, Hayde; Nairn, Angus C.; Taylor, Jane R.

    2014-01-01

    The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling. These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac), as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex. Here we investigated how activation of Epac with 8-pCPT-cAMP (8-CPT) impacts reconsolidation of a memory that had been associated with cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-associated memory. Immediate bilateral infusions of 8-CPT into the basolateral amygdala (BLA) following reactivation disrupted subsequent cue-induced reinstatement in a dose-dependent manner, and modestly reduced responding for conditioned reinforcement. When 8-CPT infusions were delayed for 3 hours after the cue reactivation session or were given after a cue extinction session, no effect on cue-induced reinstatement was observed. Co-administration of 8-CPT and the PKA activator 6-Bnz-cAMP (10 nmol/side) rescued memory reconsolidation while 6-Bnz alone had no effect, suggesting an antagonizing interaction between the two cAMP signaling substrates. Taken together, these studies suggest that activation of Epac represents a parallel cAMP-dependent pathway that can inhibit reconsolidation of cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior. PMID:25259911

  3. Activation of exchange protein activated by cAMP in the rat basolateral amygdala impairs reconsolidation of a memory associated with self-administered cocaine.

    PubMed

    Wan, Xun; Torregrossa, Mary M; Sanchez, Hayde; Nairn, Angus C; Taylor, Jane R

    2014-01-01

    The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling. These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac), as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex. Here we investigated how activation of Epac with 8-pCPT-cAMP (8-CPT) impacts reconsolidation of a memory that had been associated with cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-associated memory. Immediate bilateral infusions of 8-CPT into the basolateral amygdala (BLA) following reactivation disrupted subsequent cue-induced reinstatement in a dose-dependent manner, and modestly reduced responding for conditioned reinforcement. When 8-CPT infusions were delayed for 3 hours after the cue reactivation session or were given after a cue extinction session, no effect on cue-induced reinstatement was observed. Co-administration of 8-CPT and the PKA activator 6-Bnz-cAMP (10 nmol/side) rescued memory reconsolidation while 6-Bnz alone had no effect, suggesting an antagonizing interaction between the two cAMP signaling substrates. Taken together, these studies suggest that activation of Epac represents a parallel cAMP-dependent pathway that can inhibit reconsolidation of cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior.

  4. The dopamine β-hydroxylase inhibitor, nepicastat, suppresses chocolate self-administration and reinstatement of chocolate seeking in rats.

    PubMed

    Zaru, Alessandro; Maccioni, Paola; Colombo, Giancarlo; Gessa, Gian Luigi

    2013-10-01

    Craving for chocolate is a common phenomenon, which may evolve to an addictive-like behaviour and contribute to obesity. Nepicastat is a selective dopamine β-hydroxylase (DBH) inhibitor that suppresses cocaine-primed reinstatement of cocaine seeking in rats. We verified whether nepicastat was able to modify the reinforcing and motivational properties of a chocolate solution and to prevent the reinstatement of chocolate seeking in rats. Nepicastat (25, 50 and 100 mg/kg, intraperitoneal) produced a dose-related inhibition of operant self-administration of the chocolate solution in rats under fixed-ratio 10 (FR10) and progressive-ratio schedules of reinforcement, measures of the reinforcing and motivational properties of the chocolate solution, respectively. The effect of nepicastat on the reinstatement of chocolate seeking was studied in rats in which lever-responding had been extinguished by removing the chocolate solution for approximately 8 d. Nepicastat dose-dependently suppressed the reinstatement of lever-responding triggered by a 'priming' of the chocolate solution together with cues previously associated with the availability of the reward. In a separate group of food-restricted rats trained to lever-respond for regular food pellets, nepicastat reduced FR10 lever-responding with the same potency as for the chocolate solution. Spontaneous locomotor activity was not modified by nepicastat doses that reduced self-administration of the chocolate solution and regular food pellets and suppressed the reinstatement of chocolate seeking. The results indicate that nepicastat reduces motivation to food consumption sustained by appetite or palatability. Moreover, the results suggest that DBH inhibitors may be a new class of pharmacological agents potentially useful in the prevention of relapse to food seeking in human dieters.

  5. Visualizing Key Hinges and a Potential Major Source of Compliance in the Lever Arm of Myosin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    J Brown; V Senthil Kumar; E ONeall-Hennessey

    2011-12-31

    We have determined the 2.3-{angstrom}-resolution crystal structure of a myosin light chain domain, corresponding to one type found in sea scallop catch ('smooth') muscle. This structure reveals hinges that may function in the 'on' and 'off' states of myosin. The molecule adopts two different conformations about the heavy chain 'hook' and regulatory light chain (RLC) helix D. This conformational change results in extended and compressed forms of the lever arm whose lengths differ by 10 {angstrom}. The heavy chain hook and RLC helix D hinges could thus serve as a potential major and localized source of cross-bridge compliance during themore » contractile cycle. In addition, in one of the molecules of the crystal, part of the RLC N-terminal extension is seen in atomic detail and forms a one-turn alpha-helix that interacts with RLC helix D. This extension, whose sequence is highly variable in different myosins, may thus modulate the flexibility of the lever arm. Moreover, the relative proximity of the phosphorylation site to the helix D hinge suggests a potential role for conformational changes about this hinge in the transition between the on and off states of regulated myosins.« less

  6. Visualizing key hinges and a potential major source of compliance in the lever arm of myosin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brown, J.H.; Robinson, H.; Senthil Kumar, V. S.

    2011-01-04

    We have determined the 2.3-{angstrom}-resolution crystal structure of a myosin light chain domain, corresponding to one type found in sea scallop catch ('smooth') muscle. This structure reveals hinges that may function in the 'on' and 'off' states of myosin. The molecule adopts two different conformations about the heavy chain 'hook' and regulatory light chain (RLC) helix D. This conformational change results in extended and compressed forms of the lever arm whose lengths differ by 10 {angstrom}. The heavy chain hook and RLC helix D hinges could thus serve as a potential major and localized source of cross-bridge compliance during themore » contractile cycle. In addition, in one of the molecules of the crystal, part of the RLC N-terminal extension is seen in atomic detail and forms a one-turn alpha-helix that interacts with RLC helix D. This extension, whose sequence is highly variable in different myosins, may thus modulate the flexibility of the lever arm. Moreover, the relative proximity of the phosphorylation site to the helix D hinge suggests a potential role for conformational changes about this hinge in the transition between the on and off states of regulated myosins.« less

  7. CHARACTERIZATION OF THE DISCRIMINATIVE STIMULUS EFFECTS OF LORCASERIN IN RATS

    PubMed Central

    Serafine, Katherine M.; Rice, Kenner C.; France, Charles P.

    2016-01-01

    Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0.178–1.0 mg/kg) dose-dependently increased lorcaserin-lever responding. The 5-HT2C receptor agonist mCPP and the 5-HT2A receptor agonist DOM each occasioned greater than 90% lorcaserin-lever responding in seven of eight rats. The 5-HT1A receptor agonist 8-OH-DPAT occasioned greater than 90% lorcaserin-lever responding in four of seven rats. The 5-HT2C receptor selective antagonist SB 242084 attenuated lorcaserin-lever responding in all eight rats and the 5-HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin-lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5-HT2C receptors, lorcaserin also has agonist properties at 5-HT2A and 5-HT1A receptors. Because some drugs with 5-HT2A receptor agonist properties are abused, it is important to fully understand the behavioral effects of lorcaserin while considering its potential for treating substance use disorders. PMID:27640338

  8. Characterization of the discriminative stimulus effects of lorcaserin in rats.

    PubMed

    Serafine, Katherine M; Rice, Kenner C; France, Charles P

    2016-09-01

    Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0.178-1.0 mg/kg) dose-dependently increased lorcaserin-lever responding. The 5-HT2C receptor agonist mCPP and the 5-HT2A receptor agonist DOM each occasioned greater than 90% lorcaserin-lever responding in seven of eight rats. The 5-HT1A receptor agonist 8-OH-DPAT occasioned greater than 90% lorcaserin-lever responding in four of seven rats. The 5-HT2C receptor selective antagonist SB 242084 attenuated lorcaserin-lever responding in all eight rats and the 5-HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin-lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5-HT2C receptors, lorcaserin also has agonist properties at 5-HT2A and 5-HT1A receptors. Because some drugs with 5-HT2A receptor agonist properties are abused, it is important to fully characterize the behavioral effects of lorcaserin while considering its potential for treating substance use disorders. © 2016 Society for the Experimental Analysis of Behavior.

  9. A strong static-magnetic field alters operant responding by rats.

    PubMed

    Nakagawa, M; Matsuda, Y

    1988-01-01

    Forty male rats of the Wistar ST strain were trained and observed for Sidman avoidance (SA) for 7 weeks or for discriminative avoidance (DA) for 14 weeks to determine the effects of exposure to a strong static-magnetic field. Before avoidance conditioning was completed, rats in the SA group were exposed to the static field at 0.6 T, 16 h/day for 4 days during the fifth week, and those in the DA group were exposed for 6 h/day for 4 days during the seventh week. In the SA conditioning, frequency of lever-pressing by exposed rats gradually decreased during 1 week of exposure and stayed low for at least 2 weeks after exposure. Frequencies of electric shocks received by the rats increased dramatically during the second day of exposure and consistently stayed higher than those of control rats. In the DA condition, exposed rats responded at lower rates than did control rats throughout the observation period. They received more shocks during the 2 weeks following exposure. The data indicate that performance of avoidance responses was inhibited by a comparatively long exposure to a strong magnetic field.

  10. Establishing Networks to Lever Investments in Developing Capacity for Agricultural Monitoring: A GEOGLAM Perspective

    NASA Astrophysics Data System (ADS)

    Whitcraft, A. K.; Becker-Reshef, I.

    2016-12-01

    Since 2011, the Group on Earth Observations Global Agricultural Monitoring (GEOGLAM) Initiative has been working to strengthen the international community's capacity to use Earth observation (EO) data to derive timely, accurate, and transparent information on agriculture. A key component of GEOGLAM is the development of individual and institutional capacity for EO-based agricultural monitoring at multiple scales, from national to regional to global, in low-, middle-, and high-income countries. Despite the fact that the need for enhancing capacity is frequently acknowledged, there is little formal or informal literature documenting best practices for developing and implementing comprehensive capacity development strategies around Earth observations knowledge sharing. As a result, many projects and activities develop knowledge-sharing strategies on an ad hoc basis, and may be missing out on levering lessons, techniques, and toolsets already developed. In the past year, GEOGLAM has aimed to spur relationships and collaborations with capacity development initiatives and networks, toward sharing and documenting strategies and tactical experiences in this domain. This presentation will provide some perspective on challenges and opportunities encountered so far, from the GEOGLAM perspective, with the goal of continued dialogue and coordination with other session participants.

  11. Evaluation of respondent-driven sampling.

    PubMed

    McCreesh, Nicky; Frost, Simon D W; Seeley, Janet; Katongole, Joseph; Tarsh, Matilda N; Ndunguse, Richard; Jichi, Fatima; Lunel, Natasha L; Maher, Dermot; Johnston, Lisa G; Sonnenberg, Pam; Copas, Andrew J; Hayes, Richard J; White, Richard G

    2012-01-01

    Respondent-driven sampling is a novel variant of link-tracing sampling for estimating the characteristics of hard-to-reach groups, such as HIV prevalence in sex workers. Despite its use by leading health organizations, the performance of this method in realistic situations is still largely unknown. We evaluated respondent-driven sampling by comparing estimates from a respondent-driven sampling survey with total population data. Total population data on age, tribe, religion, socioeconomic status, sexual activity, and HIV status were available on a population of 2402 male household heads from an open cohort in rural Uganda. A respondent-driven sampling (RDS) survey was carried out in this population, using current methods of sampling (RDS sample) and statistical inference (RDS estimates). Analyses were carried out for the full RDS sample and then repeated for the first 250 recruits (small sample). We recruited 927 household heads. Full and small RDS samples were largely representative of the total population, but both samples underrepresented men who were younger, of higher socioeconomic status, and with unknown sexual activity and HIV status. Respondent-driven sampling statistical inference methods failed to reduce these biases. Only 31%-37% (depending on method and sample size) of RDS estimates were closer to the true population proportions than the RDS sample proportions. Only 50%-74% of respondent-driven sampling bootstrap 95% confidence intervals included the population proportion. Respondent-driven sampling produced a generally representative sample of this well-connected nonhidden population. However, current respondent-driven sampling inference methods failed to reduce bias when it occurred. Whether the data required to remove bias and measure precision can be collected in a respondent-driven sampling survey is unresolved. Respondent-driven sampling should be regarded as a (potentially superior) form of convenience sampling method, and caution is required

  12. Evaluation of Respondent-Driven Sampling

    PubMed Central

    McCreesh, Nicky; Frost, Simon; Seeley, Janet; Katongole, Joseph; Tarsh, Matilda Ndagire; Ndunguse, Richard; Jichi, Fatima; Lunel, Natasha L; Maher, Dermot; Johnston, Lisa G; Sonnenberg, Pam; Copas, Andrew J; Hayes, Richard J; White, Richard G

    2012-01-01

    Background Respondent-driven sampling is a novel variant of link-tracing sampling for estimating the characteristics of hard-to-reach groups, such as HIV prevalence in sex-workers. Despite its use by leading health organizations, the performance of this method in realistic situations is still largely unknown. We evaluated respondent-driven sampling by comparing estimates from a respondent-driven sampling survey with total-population data. Methods Total-population data on age, tribe, religion, socioeconomic status, sexual activity and HIV status were available on a population of 2402 male household-heads from an open cohort in rural Uganda. A respondent-driven sampling (RDS) survey was carried out in this population, employing current methods of sampling (RDS sample) and statistical inference (RDS estimates). Analyses were carried out for the full RDS sample and then repeated for the first 250 recruits (small sample). Results We recruited 927 household-heads. Full and small RDS samples were largely representative of the total population, but both samples under-represented men who were younger, of higher socioeconomic status, and with unknown sexual activity and HIV status. Respondent-driven-sampling statistical-inference methods failed to reduce these biases. Only 31%-37% (depending on method and sample size) of RDS estimates were closer to the true population proportions than the RDS sample proportions. Only 50%-74% of respondent-driven-sampling bootstrap 95% confidence intervals included the population proportion. Conclusions Respondent-driven sampling produced a generally representative sample of this well-connected non-hidden population. However, current respondent-driven-sampling inference methods failed to reduce bias when it occurred. Whether the data required to remove bias and measure precision can be collected in a respondent-driven sampling survey is unresolved. Respondent-driven sampling should be regarded as a (potentially superior) form of convenience

  13. Premature responding is associated with approach to a food cue in male and female heterogeneous stock rats.

    PubMed

    King, Christopher P; Palmer, Abraham A; Woods, Leah C Solberg; Hawk, Larry W; Richards, Jerry B; Meyer, Paul J

    2016-07-01

    Disorders of behavioral regulation, including attention deficit hyperactivity disorder (ADHD) and drug addiction, are in part due to poor inhibitory control, attentional deficits, and hyper-responsivity to reward-associated cues. To determine whether these traits are related, we tested genetically variable male and female heterogeneous stock rats in the choice reaction time (CRT) task and Pavlovian conditioned approach (PavCA). Sex differences in the response to methylphenidate during the CRT were also assessed. In the CRT task, rats were required to withhold responding until one of two lights indicated whether responses into a left or right port would be reinforced with water. Reaction time on correct trials and premature responses were the operational definitions of attention and response inhibition, respectively. Rats were also pretreated with oral methylphenidate (0, 2, 4 mg/kg) during the CRT task to determine whether this drug would improve performance. Subsequently, during PavCA, presentation of an illuminated lever predicted the delivery of a food pellet into a food-cup. Lever-directed approach (sign-tracking) and food-cup approach (goal-tracking) were the primary measures, and rats were categorized as "sign-trackers" and "goal-trackers" using an index based on these measures. Sign-trackers made more premature responses than goal-trackers but showed no differences in reaction time. There were sex differences in both tasks, with females having higher sign-tracking, completing more CRT trials, and making more premature responses after methylphenidate administration. These results indicate that response inhibition is related to reward-cue responsivity, suggesting that these traits are influenced by common genetic factors.

  14. Wheel-running reinforcement in free-feeding and food-deprived rats.

    PubMed

    Belke, Terry W; Pierce, W David

    2016-03-01

    Rats experiencing sessions of 30min free access to wheel running were assigned to ad-lib and food-deprived groups, and given additional sessions of free wheel activity. Subsequently, both ad-lib and deprived rats lever pressed for 60s of wheel running on fixed ratio (FR) 1, variable ratio (VR) 3, VR 5, and VR 10 schedules, and on a response-initiated variable interval (VI) 30s schedule. Finally, the ad-lib rats were switched to food deprivation and the food-deprived rats were switched to free food, as rats continued responding on the response-initiated VI 30-s schedule. Wheel running functioned as reinforcement for both ad-lib and food-deprived rats. Food-deprived rats, however, ran faster and had higher overall lever-pressing rates than free-feeding rats. On the VR schedules, wheel-running rates positively correlated with local and overall lever pressing rates for deprived, but not ad-lib rats. On the response-initiated VI 30s schedule, wheel-running rates and lever-pressing rates changed for ad-lib rats switched to food deprivation, but not for food-deprived rats switched to free-feeding. The overall pattern of results suggested different sources of control for wheel running: intrinsic motivation, contingencies of automatic reinforcement, and food-restricted wheel running. An implication is that generalizations about operant responding for wheel running in food-deprived rats may not extend to wheel running and operant responding of free-feeding animals. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Physiological and subjective measures of workload when shovelling with a conventional and two-handled ('levered') shovel.

    PubMed

    Bridger, R S; Cabion, N; Goedecke, J; Rickard, S; Schabort, E; Westgarth-Taylor, C; Lambert, M I

    1997-11-01

    Previous studies have suggested that the two-handled (levered) shovel is advantageous over the conventional spade from a biomechanical point of view. The aim of this experiment was to determine whether less energy was consumed while shovelling a load of sand with this shovel compared to a conventional tool. Accordingly, an experiment was designed in which subjects (n = 10) shovelled 1815 kg sand under laboratory conditions using either a conventional or a levered shovel. Heart rate and oxygen consumption were measured continuously during the trial and subjective data on perceived exertion, general fatigue and body discomfort were recorded after the trial. Although total energy expenditure was similar under both conditions (120 +/- 20 and 125 +/- 25 kcal; conventional versus two-handled spade), average heart rate was 4% higher when the two-handled shovel was used (p < 0.05). In addition, the mass of sand per scoop was 4% less with the two-handled shovel (p < 0.05). In conclusion, subjects used similar energy expenditure to shovel 1815 kg sand with the conventional shovel and the two-handled tool despite lower mass of sand per scoop with the latter. This can be explained by the fact that the increased mass of the additional handle compensated for the lower mass of sand per scoop. The higher average heart rate while shovelling with the two-handled shovel can be explained by the more erect posture.

  16. The effects of transverse rotation angle on compression and effective lever arm of prosthetic feet during simulated stance.

    PubMed

    Major, Matthew J; Howard, David; Jones, Rebecca; Twiste, Martin

    2012-06-01

    Unlike sagittal plane prosthesis alignment, few studies have observed the effects of transverse plane alignment on gait and prosthesis behaviour. Changes in transverse plane rotation angle will rotate the points of loading on the prosthesis during stance and may alter its mechanical behaviour. This study observed the effects of increasing the external transverse plane rotation angle, or toe-out, on foot compression and effective lever arm of three commonly prescribed prosthetic feet. The roll-over shape of a SACH, Flex and single-axis foot was measured at four external rotation angle conditions (0°, 5°, 7° and 12° relative to neutral). Differences in foot compression between conditions were measured as average distance between roll-over shapes. Increasing the transverse plane rotation angle did not affect foot compression. However, it did affect the effective lever arm, which was maximized with the 5° condition, although differences between conditions were small. Increasing the transverse plane rotation angle of prosthetic feet by up to 12° beyond neutral has minimal effects on their mechanical behaviour in the plane of walking progression during weight-bearing.

  17. The effect of reinforcement differences on choice and response distribution during stimulus compounding.

    PubMed

    Bushnell, M C; Weiss, S J

    1977-03-01

    In Experiments I and II, rats were trained to respond on one lever during light and another during tone. The absence of tone and light controlled response cessation. In the multiple schedule of Experiment I, all reinforcements were received for responding in tone or light; in the chain schedule of Experiment II, all reinforcements were received in no tone + no light for not responding. Experiment I subjects, for which tone and light were associated with response and reinforcement increase, responded significantly more to tone-plus-light than to tone or light alone (additive summation). Experiment II subjects, for which tone and light were associated with response increase and reinforcement decrease, responded comparably to tone, light, and tone + light. Thus, additive summation was observed when stimulus-response and stimulus-reinforcer associations in tone and light were both positive, but not when they were conflicting. All subjects in both experiments responded predominantly on the light-correlated lever during tone + light, even when light intensity was reduced in testing. Furthermore, when a light was presented to a subject engaged in tone-associated responding, all subjects immediately switched the locus of responding to the light-correlated lever. No change in locus occurred when a tone was presented to a subject engaged in light-associated responding, irrespective of the stimulus-reinforcer association conditioned to tone. The light-lever preference in tone + light indicates that the heightened responding observed in Experiment I was not the summation of tone-associated behavior with light-associated behavior. Rather, it appears to be the result of a facilitation of one operant (light-associated responding) by the reinforcement-associated cue for the other.

  18. Incubation of extinction responding and cue-induced reinstatement, but not context- or drug priming-induced reinstatement, after withdrawal from methamphetamine

    PubMed Central

    Adhikary, Sweta; Caprioli, Daniele; Venniro, Marco; Kallenberger, Paige; Shaham, Yavin; Bossert, Jennifer M.

    2016-01-01

    In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats’ response to methamphetamine priming incubates after withdrawal. We trained rats to self-administer methamphetamine in a distinct context (context A) for 14 days (6-h/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non-drug context (context B) after 1 day, 1 week, or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25, and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context-independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue-induced reinstatement, but not context- or drug priming-induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time-dependent increases in non-reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues. PMID:26989042

  19. Chemogenetic activation of the lateral hypothalamus reverses early life stress-induced deficits in motivational drive.

    PubMed

    Campbell, Erin J; Mitchell, Caitlin S; Adams, Cameron D; Yeoh, Jiann Wei; Hodgson, Deborah M; Graham, Brett A; Dayas, Christopher V

    2017-10-01

    Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions including mood disorders. One well-characterized antecedent to the development of mood disorders is exposure to early life stress (ELS). A key brain substrate controlling motivated behaviour is the lateral hypothalamus (LH). Here, we examined the effect of ELS on LH activation and the motivation to self-administer sucrose. We tested whether chemogenetic activation of LH circuits could modify sucrose responding in ELS rats and examined the impact on LH cell populations. Male rat pups were maternally separated for 0 or 3 h on postnatal days 2-14. During adolescence, rats received bilateral injections of hM3D(Gq), the excitatory designer receptor exclusively activated by designer drugs, into LH. In adulthood, rats were trained to self-administer sucrose and tested under a progressive ratio schedule to determine their motivation for reward following injection with either vehicle or 5 mg/kg clozapine-N-oxide. Brains were processed for Fos-protein immunohistochemistry. ELS significantly suppressed lever responding for sucrose, indicating a long-lasting impact of ELS on motivation circuits. hM3D(Gq) activation of LH increased responding, normalizing deficits in ELS rats, and increased Fos-positive orexin and MCH cell numbers within LH. Our findings indicate that despite being susceptible to environmental stressors, LH circuits retain the capacity to overcome ELS-induced deficits in motivated behaviour. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  20. Intravenous nicotine self-administration and cue-induced reinstatement in mice: Effects of nicotine dose, rate of drug infusion and prior instrumental training

    PubMed Central

    Fowler, Christie D.; Kenny, Paul J.

    2011-01-01

    Intravenous nicotine self-administration is the most direct measure of nicotine reinforcement in laboratory animals, but this procedure has proven difficult to establish in mice. We found that stable responding for nicotine in C57BL6/J mice was facilitated by prior instrumental training for food reward, initial exposure of mice to a lower unit dose of nicotine (0.03 mg/kg/infusion) before access to higher doses, a slower rate of drug delivery (3-sec versus 1-sec infusion), consistency in schedule of daily testing, and low extraneous noise during testing. Under these conditions, we found that mice lever-pressing for nicotine (0.03–0.4 mg/kg/infusion; 60-min test sessions) under a fixed-ratio 5 time-out 20-sec (FR5TO20) reinforcement schedule consumed the drug according to an inverted ‘U’-shaped dose-response curve. Mice switched their responding onto a previously non-reinforced lever to continue earning nicotine infusions when the active/inactive lever assignment was reversed. The nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine decreased responding for nicotine, but not food rewards, verifying that nAChRs regulate nicotine self-administration in mice. The cue-light paired with nicotine delivery did not support responding when delivered independently of nicotine infusions, further verifying that mice responded selectivity for the drug. Nicotine-seeking responses extinguished when nicotine infusions and the cue-light were withheld, and exposure to the cue-light reinstated responding. Finally, mice without prior instrumental food training acquired stable responding for nicotine under the FR5TO20 schedule, but required a greater number of sessions. These data demonstrate that nicotine is an effective reinforcer in mice and establish conditions under which the drug is reliably self-administered by mice. PMID:21640128

  1. Study of Lever-Arm Effect Using Embedded Photogrammetry and On-Board GPS Receiver on Uav for Metrological Mapping Purpose and Proposal of a Free Ground Measurements Calibration Procedure

    NASA Astrophysics Data System (ADS)

    Daakir, M.; Pierrot-Deseilligny, M.; Bosser, P.; Pichard, F.; Thom, C.; Rabot, Y.

    2016-03-01

    Nowadays, Unmanned Aerial Vehicle (UAV) on-board photogrammetry knows a significant growth due to the democratization of using drones in the civilian sector. Also, due to changes in regulations laws governing the rules of inclusion of a UAV in the airspace which become suitable for the development of professional activities. Fields of application of photogrammetry are diverse, for instance: architecture, geology, archaeology, mapping, industrial metrology, etc. Our research concerns the latter area. Vinci-Construction- Terrassement is a private company specialized in public earthworks that uses UAVs for metrology applications. This article deals with maximum accuracy one can achieve with a coupled camera and GPS receiver system for direct-georeferencing of Digital Surface Models (DSMs) without relying on Ground Control Points (GCPs) measurements. This article focuses specially on the lever-arm calibration part. This proposed calibration method is based on two steps: a first step involves the proper calibration for each sensor, i.e. to determine the position of the optical center of the camera and the GPS antenna phase center in a local coordinate system relative to the sensor. A second step concerns a 3d modeling of the UAV with embedded sensors through a photogrammetric acquisition. Processing this acquisition allows to determine the value of the lever-arm offset without using GCPs.

  2. Attenuation of nicotine's discriminative stimulus effects in rats and its locomotor activity effects in mice by serotonergic 5-HT2A/2C receptor agonists.

    PubMed

    Batman, Angela M; Munzar, Patrik; Beardsley, Patrick M

    2005-05-01

    Reports have indicated that administration of nicotine inhibits, while withdrawal of chronically administered nicotine augments effects of serotonergic 5HT2A/2C agonists. It was our objective to determine whether 5HT2A/2C agonists can modulate the discriminative stimulus effects of nicotine in rats or its locomotor activity effects in mice. Adult male Sprague-Dawley rats were trained to discriminate 0.3 mg/kg nicotine base from saline in a two-lever, fixed-ratio (FR10), food-reinforced, operant-conditioning task during daily (Monday-Friday) 15-min experimental sessions. After characterizing a dose-response curve for nicotine, we tested the ability of the 5HT(2A/2C) agonists (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCL (DOI; 0.18-1.0 mg/kg) and 1-(4-bromo-2, 5-dimethoxyphenyl)-2-aminopropane (DOB; 0.1-1.0 mg/kg), the 5HT2C agonist 6-chloro-2-(1-piperazinyl)pyrazine hydrochloride (MK 212; 0.1 mg/kg-1.0 mg/kg), and the 5HT1A agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 0.01 mg/kg-1.0 mg/kg) to modulate nicotine's discriminative stimulus effects. After finding that DOI was able to attenuate the percentage nicotine lever responding (%NLR), we tested for it to also reverse nicotine's effects on locomotor activity in mice. The 5HT2A/2C agonists-in particular DOI-dose dependently attenuated %NLR. The effects of DOI were reversed by the 5HT2A/2C antagonist ketanserin. MK 212 and 8-OH-DPAT had irregular effects among rats and only reduced %NLR to below 50% levels at doses markedly suppressing responding. DOI also dose dependently blocked nicotine's acute rate-lowering locomotor activity effects. These results indicate that activation of serotonin 5HT2A/2C receptors can blunt the discriminative stimulus and locomotor activity effects of nicotine and presents the possibility that activation of these receptors might also be able to attenuate other effects of nicotine.

  3. Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task

    PubMed Central

    Miller, Rikki L.A.

    2017-01-01

    Abstract The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior. PMID:29034318

  4. Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task.

    PubMed

    Miller, Rikki L A; Francoeur, Miranda J; Gibson, Brett M; Mair, Robert G

    2017-01-01

    The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior.

  5. Levers and linkages: mechanical trade-offs in a power-amplified system.

    PubMed

    Anderson, Philip S L; Claverie, Thomas; Patek, S N

    2014-07-01

    Mechanical redundancy within a biomechanical system (e.g., many-to-one mapping) allows morphologically divergent organisms to maintain equivalent mechanical outputs. However, most organisms depend on the integration of more than one biomechanical system. Here, we test whether coupled mechanical systems follow a pattern of amplification (mechanical changes are congruent and evolve toward the same functional extreme) or independence (mechanisms evolve independently). We examined the correlated evolution and evolutionary pathways of the coupled four-bar linkage and lever systems in mantis shrimp (Stomatopoda) ultrafast raptorial appendages. We examined models of character evolution in the framework of two divergent groups of stomatopods-"smashers" (hammer-shaped appendages) and "spearers" (bladed appendages). Smashers tended to evolve toward force amplification, whereas spearers evolved toward displacement amplification. These findings show that coupled biomechanical systems can evolve synergistically, thereby resulting in functional amplification rather than mechanical redundancy. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  6. Premature responding is associated with approach to a food cue in male and female heterogeneous stock rats

    PubMed Central

    King, Christopher P.; Palmer, Abraham A.; Solberg Woods, Leah C.; Hawk, Larry W.; Richards, Jerry B.; Meyer, Paul J.

    2016-01-01

    Rationale Disorders of behavioral regulation, including attention deficit hyperactivity disorder (ADHD) and drug addiction, are in part due to poor inhibitory control, attentional deficits, and hyper-responsivity to reward-associated cues. Objectives To determine whether these traits are related, we tested genetically variable male and female heterogeneous stock rats in the choice reaction time (CRT) task and Pavlovian conditioned approach (PavCA). Sex differences in the response to methylphenidate during the CRT were also assessed. Methods In the CRT task, rats were required to withhold responding until one of two lights indicated whether responses into a left or right port would be reinforced with water. Reaction time on correct trials and premature responses were the operational definitions of attention and response inhibition, respectively. Rats were also pre-treated with oral methylphenidate (0, 2, 4 mg/kg) during the CRT task to determine whether this drug would improve performance. Subsequently, during PavCA, presentation of an illuminated lever predicted the delivery of a food pellet into a food-cup. Lever-directed approach (sign-tracking) and food-cup approach (goal-tracking) were the primary measures, and rats were categorized as “sign-trackers” and “goal-trackers” using an index based on these measures. Results Sign-trackers made more premature responses than goal-trackers, but showed no differences in reaction time. There were sex differences in both tasks, with females having higher sign-tracking, completing more CRT trials, and making more premature responses after methylphenidate administration. Conclusions These results indicate that response inhibition is related to reward-cue responsivity, suggesting that these traits are influenced by common genetic factors. PMID:27146401

  7. Suppressing effect of saikosaponin A, an active ingredient of Bupleurum falcatum, on chocolate self-administration and reinstatement of chocolate seeking in rats.

    PubMed

    Lorrai, Irene; Maccioni, Paola; Carai, Mauro A M; Capra, Alessandro; Castelli, M Paola; Riva, Antonella; Morazzoni, Paolo; Gessa, Gian Luigi; Colombo, Giancarlo

    2017-01-18

    Recent lines of experimental evidence have indicated that saikosaponin A (SSA) - a bioactive ingredient of the medicinal plant, Bupleurum falcatum L. - suppressed alcohol, morphine, and cocaine self-administration in rats. The present paper was designed to assess whether the protective properties of SSA on addiction-related behaviors generalize to a hyperpalatable food such as a chocolate-flavored beverage (CFB). To this end, rats were initially trained to lever-respond for CFB [5% (w/v) Nesquik ® powder in water] under fixed ratio (FR) 10 (FR10) schedule of reinforcement. Once lever-responding reached stable levels, rats were treated acutely with two different dose ranges of SSA (0, 0.25, 0.5, and 1mg/kg; 0, 1, 2.5, and 5mg/kg; i.p.) and exposed to the FR10 and progressive ratio (PR) schedules of reinforcement in four independent experiments. The effect of acutely administered SSA (0, 0.25, 0.5, and 1mg/kg; i.p.) on cue-induced reinstatement of seeking behavior for CFB was also assessed. Under the FR and PR schedules of reinforcement, treatment with SSA diminished lever-responding for CFB, amount of self-administered CFB, and breakpoint for CFB. All variables were virtually completely suppressed after treatment with 5mg/kg SSA. Treatment with SSA also suppressed reinstatement of CFB-seeking behavior. No dose of SSA altered rat motor-performance, evaluated exposing all rats to an inverted screen test immediately after the self-administration session. These results demonstrate that acute treatment with SSA potently suppressed several addictive-like behaviors motivated by highly hedonic nourishment. These data extend to a highly rewarding natural stimulus the anti-addictive properties of SSA recently disclosed in rats self-administering alcohol, morphine, and cocaine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Repeated Activation of a CS-US-Contingency Memory Results in Sustained Conditioned Responding

    PubMed Central

    Joos, Els; Vansteenwegen, Debora; Vervliet, Bram; Hermans, Dirk

    2013-01-01

    Individuals seem to differ in conditionability, i.e., the ease by which the contingent presentation of two stimuli will lead to a conditioned response. In contemporary learning theory, individual differences in the etiology and maintenance of anxiety disorders are, among others, explained by individual differences in temperamental variables (Mineka and Zinbarg, 2006). One such individual difference variable is how people process a learning experience when the conditioning stimuli are no longer present. Repeatedly thinking about the conditioning experience, as in worry or rumination, might prolong the initial (fear) reactions and as such, might leave certain individuals more vulnerable to developing an anxiety disorder. However, in human conditioning research, relatively little attention has been devoted to the processing of a memory trace after its initial acquisition, despite its potential influences on subsequent performance. Post-acquisition processing can be induced by mental reiteration of a conditioned stimulus-unconditioned stimulus (CS-US)-contingency. Using a human conditioned suppression paradigm, we investigated the effect of repeated activations of a CS-US-contingency memory on the level of conditioned responding at a later test. Results of three experiments showed more sustained responding to a “rehearsed” CS+ as compared to a “non-rehearsed” CS+. Moreover, the second experiment showed no effect of rehearsal when only the CS was rehearsed instead of the CS-US-contingency. The third experiment demonstrated that mental CS-US-rehearsal has the same effect regardless of whether it was cued by the CS and a verbal reference to the US or by a neutral signal, making the rehearsal “purely mental.” In sum, it was demonstrated that post-acquisition activation of a CS-US-contingency memory can impact conditioned responding, underlining the importance of post-acquisition processes in conditioning. This might indicate that individuals who are more prone

  9. Repeated Activation of a CS-US-Contingency Memory Results in Sustained Conditioned Responding.

    PubMed

    Joos, Els; Vansteenwegen, Debora; Vervliet, Bram; Hermans, Dirk

    2013-01-01

    Individuals seem to differ in conditionability, i.e., the ease by which the contingent presentation of two stimuli will lead to a conditioned response. In contemporary learning theory, individual differences in the etiology and maintenance of anxiety disorders are, among others, explained by individual differences in temperamental variables (Mineka and Zinbarg, 2006). One such individual difference variable is how people process a learning experience when the conditioning stimuli are no longer present. Repeatedly thinking about the conditioning experience, as in worry or rumination, might prolong the initial (fear) reactions and as such, might leave certain individuals more vulnerable to developing an anxiety disorder. However, in human conditioning research, relatively little attention has been devoted to the processing of a memory trace after its initial acquisition, despite its potential influences on subsequent performance. Post-acquisition processing can be induced by mental reiteration of a conditioned stimulus-unconditioned stimulus (CS-US)-contingency. Using a human conditioned suppression paradigm, we investigated the effect of repeated activations of a CS-US-contingency memory on the level of conditioned responding at a later test. Results of three experiments showed more sustained responding to a "rehearsed" CS+ as compared to a "non-rehearsed" CS+. Moreover, the second experiment showed no effect of rehearsal when only the CS was rehearsed instead of the CS-US-contingency. The third experiment demonstrated that mental CS-US-rehearsal has the same effect regardless of whether it was cued by the CS and a verbal reference to the US or by a neutral signal, making the rehearsal "purely mental." In sum, it was demonstrated that post-acquisition activation of a CS-US-contingency memory can impact conditioned responding, underlining the importance of post-acquisition processes in conditioning. This might indicate that individuals who are more prone to mentally

  10. Effects of Distant Green Space on Physical Activity in Sydney, Australia.

    PubMed

    Chong, Shanley; Byun, Roy; Mazumdar, Soumya; Bauman, Adrian; Jalaludin, Bin

    2017-01-01

    The aim was to investigate the association between distant green space and physical activity modified by local green space. Information about physical activity, demographic and socioeconomic background at the individual level was extracted from the New South Wales Population Health Survey. The proportion of a postcode that was parkland was used as a proxy measure for access to parklands and was calculated for each individual. There was a significant relationship between distant green space and engaging in moderate-to-vigorous physical activity (MVPA) at least once a week. No significant relationship was found between adequate physical activity and distant green space. No significant relationships were found between adequate physical activity, engaging in MVPA, and local green space. However, if respondents lived in greater local green space (≥25%), there was a significant relationship between engaging in MVPA at least once a week and distance green space of ≥20%. This study highlights the important effect of distant green space on physical activity. Our findings also suggest that moderate size of local green space together with moderate size of distant green space are important levers for participation of physical activity.

  11. Incubation of extinction responding and cue-induced reinstatement, but not context- or drug priming-induced reinstatement, after withdrawal from methamphetamine.

    PubMed

    Adhikary, Sweta; Caprioli, Daniele; Venniro, Marco; Kallenberger, Paige; Shaham, Yavin; Bossert, Jennifer M

    2017-07-01

    In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats' response to methamphetamine priming incubates after withdrawal. We trained rats to self-administer methamphetamine in a distinct context (context A) for 14 days (6 hours/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non-drug context (context B) after 1 day, 1 week or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25 and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context-independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue-induced reinstatement, but not context- or drug priming-induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time-dependent increases in non-reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  12. Fostering development of nursing practices to support integrated care when implementing integrated care pathways: what levers to use?

    PubMed

    Longpré, Caroline; Dubois, Carl-Ardy

    2017-11-29

    Care integration has been the focus of recent health system reforms. Given their functions at all levels of the care continuum, nurses have a substantial and primordial role to play in such integration processes. The aim of this study was to identify levers and strategies that organizations can use to support the development of a nursing practice aligned with the requirements of care integration in a health and social services centre (HSSC) in Quebec. The research design was a cross-sectional descriptive qualitative study based on a single case study with nested levels of analysis. The case was a public, multi-disciplinary HSSC in a semi-urban region of Quebec. Semi-structured interviews with 37 persons (nurses, professionals, managers, administrators) allowed for data saturation and ensured theoretical representation by covering four care pathways constituting different care integration contexts. Analysis involved four steps: preparing a predetermined list of codes based on the reference framework developed by Minkman (2011); coding transcript content; developing general and summary matrices to group observations for each care pathway; and creating a general model showing the overall results for the four pathways. The organization's capacity for response with regard to developing an integrated system of services resulted in two types of complementary interventions. The first involved investing in key resources and renewing organizational structures; the second involved deploying a series of organizational and clinical-administrative processes. In resource terms, integration efforts resulted in setting up new strategic services, re-arranging physical infrastructures, and deploying new technological resources. Organizational and clinical-administrative processes to promote integration involved renewing governance, improving the flow of care pathways, fostering continuous quality improvement, developing new roles, promoting clinician collaboration, and strengthening

  13. Role of ventral medial prefrontal cortex in incubation of cocaine craving

    PubMed Central

    Koya, Eisuke; Uejima, Jamie L.; Wihbey, Kristina A.; Bossert, Jennifer M.; Hope, Bruce T.; Shaham, Yavin

    2009-01-01

    Cue-induced drug-seeking in rodents progressively increases after withdrawal from cocaine, suggesting that cue-induced cocaine craving incubates over time. Here, we explored the role of the medial prefrontal cortex (mPFC, a brain area previously implicated in cue-induced cocaine seeking) in this incubation. We trained rats to self-administer cocaine for 10 d (6 h/d, infusions were paired with a tone-light cue), and then assessed after 1 or 30 withdrawal days the effect of exposure to cocaine cues on lever presses in extinction tests. We found that cue-induced cocaine-seeking in the extinction tests was higher after 30 withdrawal days than after 1 day. The time-dependent increases in extinction responding were associated with large (ventral mPFC) or modest (dorsal mPFC) increases in ERK phosphorylation (a measure of ERK activity and an index of neuronal activation). After 30 withdrawal days, ventral but not dorsal injections of muscimol+baclofen (GABAa+GABAb receptor agonists that inhibit neuronal activity) decreased extinction responding. After 1 withdrawal day, ventral but not dorsal mPFC injections of bicuculline+saclofen (GABAa+GABAb receptor antagonists that increase neuronal activity) strongly increased extinction responding. Finally, muscimol+baclofen had minimal effect on extinction responding after 1 day, and in cocaine-experienced rats, ventral mPFC injections of muscimol+baclofen or bicuculline+saclofen had no effect on lever presses for an oral sucrose solution. The present results indicate that ventral mPFC neuronal activity plays an important role in the incubation of cocaine craving. PMID:18565549

  14. D1 receptors in the nucleus accumbens-shell, but not the core, are involved in mediating ethanol-seeking behavior of alcohol-preferring (P) rats.

    PubMed

    Hauser, S R; Deehan, G A; Dhaher, R; Knight, C P; Wilden, J A; McBride, W J; Rodd, Z A

    2015-06-04

    Clinical and preclinical research suggest that activation of the mesolimbic dopamine (DA) system is involved in mediating the rewarding actions of drugs of abuse, as well as promoting drug-seeking behavior. Inhibition of DA D1 receptors in the nucleus accumbens (Acb) can reduce ethanol (EtOH)-seeking behavior of non-selective rats triggered by environmental context. However, to date, there has been no research on the effects of D1 receptor agents on EtOH- seeking behavior of high alcohol-preferring (P) rats following prolonged abstinence. The objective of the present study was to examine the effects of microinjecting the D1 antagonist SCH 23390 or the D1 agonist A-77636 into the Acb shell or Acb core on spontaneous recovery of EtOH-seeking behavior. After 10 weeks of concurrent access to EtOH and water, P rats underwent seven extinction sessions (EtOH and water withheld), followed by 2 weeks in their home cages without access to EtOH or operant sessions. In the 2nd week of the home cage phase, rats were bilaterally implanted with guide cannula aimed at the Acb shell or Acb core; rats were allowed 7d ays to recover before EtOH-seeking was assessed by the Pavlovian Spontaneous Recovery (PSR) model. Administration of SCH23390 (1μg/side) into the Acb shell inhibited responding on the EtOH lever, whereas administration of A-77636 (0.125μg/side) increased responding on the EtOH lever. Microinfusion of D1 receptor agents into the Acb core did not alter responding on the EtOH lever. Responses on the water lever were not altered by any of the treatments. The results suggest that activation of D1 receptors within the Acb shell, but not Acb core, are involved in mediating PSR of EtOH-seeking behavior of P rats. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Responding for sucrose and wheel-running reinforcement: effects of sucrose concentration and wheel-running reinforcer duration.

    PubMed

    Belke, Terry W; Hancock, Stephanie D

    2003-03-01

    Six male albino rats were placed in running wheels and exposed to a fixed-interval 30-s schedule of lever pressing that produced either a drop of sucrose solution or the opportunity to run for a fixed duration as reinforcers. Each reinforcer type was signaled by a different stimulus. In Experiment 1, the duration of running was held constant at 15 s while the concentration of sucrose solution was varied across values of 0, 2.5. 5, 10, and 15%. As concentration decreased, postreinforcement pause duration increased and local rates decreased in the presence of the stimulus signaling sucrose. Consequently, the difference between responding in the presence of stimuli signaling wheel-running and sucrose reinforcers diminished, and at 2.5%, response functions for the two reinforcers were similar. In Experiment 2, the concentration of sucrose solution was held constant at 15% while the duration of the opportunity to run was first varied across values of 15, 45, and 90 s then subsequently across values of 5, 10, and 15 s. As run duration increased, postreinforcement pause duration in the presence of the wheel-running stimulus increased and local rates increased then decreased. In summary, inhibitory aftereffects of previous reinforcers occurred when both sucrose concentration and run duration varied; changes in responding were attributable to changes in the excitatory value of the stimuli signaling the two reinforcers.

  16. Aniracetam restores motivation reduced by satiation in a choice reaction task in aged rats.

    PubMed

    Nakamura, K; Kurasawa, M

    2001-01-01

    This study aims to examine the effects of aniracetam on satiation-induced poor performance in a choice reaction task. Aged rats that mastered the task under food restriction stably maintained the task performance for a long period. Satiation by successive free feeding greatly diminished the performance. Satiation resulted in a decreased % correct, increased % omission and prolonged choice reaction time, indicating a reduction in lever response with low choice accuracy and slow responding speed. Repeated administration of aniracetam (30 mg/kg, po, for 14 days) partially recovered the choice accuracy and lever response, but not the responding speed, task-associated motor activity or impulsivity. In addition, aniracetam did not affect the animals' weights. These results indicate that satiation reduces motivation to perform and attain the task. Aniracetam may restore motivation, probably by improving poor behavioral states (daily attentional and vigilance failures), thereby creating the driving force.

  17. A comparison of the effects of psychotomimetics and anxiolytics on punished and unpunished responding maintained by fixed interval schedules of food reinforcement in the rat.

    PubMed

    Evenden, John; Duncan, Bertina; Ko, Tracey

    2006-02-01

    Characterization of anxiolytic drugs often employs conflict paradigms in which the drug effects on punished and unpunished responding can be compared. In this study, a fixed interval schedule generating a range of baseline response rates allowed comparison of the effects of anxiolytic drugs with those of psychotomimetic drugs on equivalent and differing rates of punished and unpunished responding. The first response made by the rat after a 40-s fixed interval elapsed resulted in food pellet delivery. In punished intervals, signalled by the illumination of stimulus lamps above each lever, a 0.6-mA shock was delivered after every 20th response, resulting in a lower rate of responding than that in the unpunished intervals. Three psychotomimetic agents, D-amphetamine, MK801 and DOI were compared with the anxiolytics chlordiazepoxide, NS2710 and pregabalin. The three psychotomimetics preferentially increased rates of unpunished responding compared with those of punished responding. Chlordiazepoxide, NS2710 and, to a lesser extent, pregabalin increased rates of both unpunished and punished responding. In comparison studies, yohimbine also increased rates of both unpunished and punished responding whereas the antidepressant citalopram had no effect. In conclusion, stable baseline performance over many months allowed the direct comparison of several different drugs in the same subjects with no need to adjust shock levels or equate baseline response rates. The drugs had systematic and replicable effects in this procedure, which, in the case of amphetamine and chlordiazepoxide, were similar to those in other species, and psychotomimetic drugs could clearly be distinguished from anxiolytic drugs. The procedure, however, has limited value for characterizing novel anxiolytic agents as the examples used here increased punished and unpunished responding to the same extent, and were indistinguishable in that regard from the clinically anxiogenic agent, yohimbine.

  18. Food deprivation enhances both autoshaping and autoshaping impairment by a latent inhibition procedure.

    PubMed

    Sparber, S B; Bollweg, G L; Messing, R B

    1991-02-01

    The influence of food deprivation on acquisition of autoshaped operant behavior was measured. In one study separate groups of young, male rats that were deprived to 75%, 80%, 85%, 90%, and 95% of ad lib weight were subjected to an autoshaping procedure in which a 6 s delay was interposed between lever retraction (which occurred when rats made a lever touch, or automatically after 15 s) and food pellet delivery. In a second study, groups of rats were deprived to 80% or 90% of ad lib weight prior to testing in a latent inhibition variation of the same autoshaping procedure. This was done to determine if greater food deprivation would enhance learning which, because of the latent inhibition manipulation, is manifest as less lever-directed behavior. Greater food deprivation was associated both with fast acquisition of autoshaped lever responding and with more reliable failure to increase lever responding in the latent inhibition paradigm. Thus, increasing food deprivation was associated with enhanced acquisition regardless of whether the required performance was an increase or a failure to increase the same behavior, indicating a specific effect on learning. Copyright © 1991. Published by Elsevier B.V.

  19. Dynamic Encoding of Incentive Salience in the Ventral Pallidum: Dependence on the Form of the Reward Cue.

    PubMed

    Ahrens, Allison M; Ferguson, Lindsay M; Robinson, Terry E; Aldridge, J Wayne

    2018-01-01

    Some rats are especially prone to attribute incentive salience to a cue (conditioned stimulus, CS) paired with food reward (sign-trackers, STs), but the extent they do so varies as a function of the form of the CS. Other rats respond primarily to the predictive value of a cue (goal-trackers, GTs), regardless of its form. Sign-tracking is associated with greater cue-induced activation of mesolimbic structures than goal-tracking; however, it is unclear how the form of the CS itself influences activity in neural systems involved in incentive salience attribution. Thus, our goal was to determine how different cue modalities affect neural activity in the ventral pallidum (VP), which is known to encode incentive salience attribution, as rats performed a two-CS Pavlovian conditioned approach task in which both a lever-CS and a tone-CS predicted identical food reward. The lever-CS elicited sign-tracking in some rats (STs) and goal-tracking in others (GTs), whereas the tone-CS elicited only goal-tracking in all rats. The lever-CS elicited robust changes in neural activity (sustained tonic increases or decreases in firing) throughout the VP in STs, relative to GTs. These changes were not seen when STs were exposed to the tone-CS, and in GTs there were no differences in firing between the lever-CS and tone-CS. We conclude that neural activity throughout the VP encodes incentive signals and is especially responsive when a cue is of a form that promotes the attribution of incentive salience to it, especially in predisposed individuals.

  20. Effects of an Activity-Based Anorexia Procedure on Within-Session Changes in Nose-Poke Responding

    ERIC Educational Resources Information Center

    Aoyama, Kenjiro

    2012-01-01

    This study tested the effects of an activity-based anorexia (ABA) procedure on within-session changes in responding. In the ABA group (N = 8), rats were given a 60-min feeding session and allowed to run in a running wheel for the remainder of each day. During the daily 60-min feeding session, each nose-poke response was reinforced by a food…

  1. Effects of ethanol on Pavlovian autoshaping in rats.

    PubMed

    Tomie, A; Cunha, C; Mosakowski, E M; Quartarolo, N M; Pohorecky, L A; Benjamin, D

    1998-09-01

    Approach responses, consummatory behaviors, and directed motor responses maintained by food reward resemble autoshaping CRs and are increased by lower doses of ethanol. This study evaluated the effects of presession i.p. injections of ethanol doses (0.00, 0.25, 0.50, 0.70. or 1.00 g/kg) on the acquisition of lever-press autoshaping CR performance in groups of male Long-Evans hooded rats. Paired groups received 15 daily sessions of Pavlovian autoshaping procedures, wherein the insertion of a retractable lever for 5 s (CS) was followed by the response-independent presentation of food (US). Ethanol facilitated lever-press autoshaping CR acquisition, as revealed by dose-related increases in the number of trials on which CRs were performed. The form of the dose-effect curve was inverted U-shaped with maximal responding induced during sessions 1-5 by the 0.70 g/kg ethanol dose. A similar dose-effect curve was observed during sessions 11-15, revealing that the effects of ethanol on autoshaping CR performance were relatively stable. A pseudoconditioning control group injected presession with 0.50 g/kg ethanol received training wherein the food US was presented randomly with respect to the lever CS. Few lever-presses were performed by the Random 0.50 group, indicating that ethanol's effects on autoshaping CR acquisition and maintenance observed in the Paired 0.50 group were not due to its psychomotor activating effects. A non-injection control group performed more autoshaping CRs than did the control group injected presession with saline, indicating that daily presession i.p. injections per se suppress autoshaping CR performance. Results reveal that low doses of ethanol enhance Pavlovian conditioning of directed motor and consummatory-like responding maintained by food reward. Implications for autoshaping accounts of impulsivity and drug abuse are considered.

  2. [Therapeutic education in pediatric dentistry: analysis of obstacles and levers to the development of programmes in France in 2016].

    PubMed

    Marquillier, Thomas; Trentesaux, Thomas; Gagnayre, Rémi

    2017-01-01

    Over recent years, therapeutic patient education has become part of dental medicine. Management of early childhood caries, known to be a very common chronic disease, has evolved to include an educational dimension. The objective of this study was to identify the levers and barriers to the development of formalized therapeutic education programmes and alternatives. A comprehensive exploratory qualitative study was conducted between November 2015 and June 2016 on a targeted sample of 15 people aware of the problem of TPE in dentistry. The study showed that TPE training in dentistry is underdeveloped, despite its numerous benefits: change of the healthcare professional's approach, implementation of structured educational programmes, development of research, etc. There are many obstacles to the development of TPE programmes: insufficient resources, rigid legislation or lack of knowledge of TPE practices. The dental profession is an obstacle itself because of its lack of understanding and variable degrees of integration the medical community. There are multiple levers, but the main ones are changing attitudes of the profession and the provision of resources to develop TPE. Although alternatives to TPE programmes exist (accompanying measures, short educational strategies, connected health), they cannot replace TPE. More educational strategies must be developed in the field of dentistry. However, the framework of TPE must be adapted to the profession to ensure good uptake.

  3. Inactivation of the infralimbic prefrontal cortex in rats reduces the influence of inappropriate habitual responding in a response-conflict task.

    PubMed

    Haddon, J E; Killcross, S

    2011-12-29

    Previous research suggests the infralimbic cortex is important in situations when there is competition between goal-directed and habitual responding. Here we used a response conflict procedure to further explore the involvement of the infralimbic cortex in this relationship. Rats received training on two instrumental biconditional discriminations, one auditory and one visual, in two distinct contexts. One discrimination was "over-trained" relative to the other, "under-trained," discrimination in the ratio 3:1. At test, animals were presented with incongruent audiovisual stimulus compounds of the training stimuli in the under-trained context. The stimulus elements of these test compounds have previously dictated different lever press responses during training. Rats receiving control infusions into the infralimbic cortex showed a significant interference effect, producing more responses to the over-trained (habitual), but context-inappropriate, stimulus element of the incongruent compound. This interference effect was abolished by inactivation of the infralimbic cortex; animals showed a reduced tendency to produce the habitual but inappropriate response compared with animals receiving control infusions. This finding provides evidence that the infralimbic cortex is involved in attenuating the influence of goal-directed behavior, for example context-appropriate responding. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. A Phaseolus vulgaris Extract Reduces Cue-Induced Reinstatement of Chocolate Seeking in Rats

    PubMed Central

    Lorrai, Irene; Piga, Valentina; Carai, Mauro A. M.; Riva, Antonella; Morazzoni, Paolo; Gessa, Gian Luigi; Colombo, Giancarlo; Maccioni, Paola

    2016-01-01

    Previous evidence has suggested that treatment with a standardized dry extract of Phaseolus vulgaris reduced intake and operant self-administration of highly palatable foods and fluids in rats and mice. The present study was designed to assess whether such extract was also effective in reducing seeking behavior for a highly hedonic chocolate-flavored beverage, using a “reinstatement” procedure adopted from the drug addiction research field and modeling relapse behavior. Rats were initially trained to lever-respond for the chocolate-flavored beverage under the Fixed Ratio (FR) 10 schedule of reinforcement. Subsequently, rats were exposed to an extinction responding phase, during which lever-responding – being unreinforced – diminished progressively up to extinction. Lever-responding was then powerfully reinstated by the non-contingent presentation of a complex of gustatory, olfactory, auditory, and visual stimuli previously associated to the availability of the chocolate-flavored beverage. Acute, intragastric administration of P. vulgaris dry extract (100 and 500 mg/kg) reduced lever-responding by 40–45%, in comparison to vehicle condition. These results indicate the ability of P. vulgaris dry extract to reduce seeking behavior for a highly palatable nourishment in an experimental model of relapse into disordered eating of palatable foods. The unavailability of the chocolate-flavored beverage in the reinstatement session tends to exclude that the observed effect of the P. vulgaris dry extract was secondary to any inhibition of carbohydrate metabolism; conversely, it is the likely consequence on a central action on the rewarding and hedonic properties of food. PMID:27199752

  5. Pharmacological Modulation of 5-HT2C Receptor Activity Produces Bidirectional Changes in Locomotor Activity, Responding for a Conditioned Reinforcer, and Mesolimbic DA Release in C57BL/6 Mice.

    PubMed

    Browne, Caleb J; Ji, Xiaodong; Higgins, Guy A; Fletcher, Paul J; Harvey-Lewis, Colin

    2017-10-01

    Converging lines of behavioral, electrophysiological, and biochemical evidence suggest that 5-HT 2C receptor signaling may bidirectionally influence reward-related behavior through an interaction with the mesolimbic dopamine (DA) system. Here we directly test this hypothesis by examining how modulating 5-HT 2C receptor activity affects DA-dependent behaviors and relate these effects to changes in nucleus accumbens (NAc) DA release. In C57BL/6 mice, locomotor activity and responding for a conditioned reinforcer (CRf), a measure of incentive motivation, were examined following treatment with three 5-HT 2C receptor ligands: the agonist CP809101 (0.25-3 mg/kg), the antagonist SB242084 (0.25-1 mg/kg), or the antagonist/inverse agonist SB206553 (1-5 mg/kg). We further tested whether doses of these compounds that changed locomotor activity and responding for a CRf (1 mg/kg CP809101, 0.5 mg/kg SB242084, or 2.5 mg/kg SB206553) also altered NAc DA release using in vivo microdialysis in anesthetized mice. CP809101 reduced locomotor activity, responding for a CRf, and NAc DA release. In contrast, both SB242084 and SB206553 enhanced locomotor activity, responding for a CRf, and NAc DA release, although higher doses of SB206553 produced opposite behavioral effects. Pretreatment with the non-selective DA receptor antagonist α-flupenthixol prevented SB242084 from enhancing responding for a CRf. Thus blocking tonic 5-HT 2C receptor signaling can release serotonergic inhibition of mesolimbic DA activity and enhance reward-related behavior. The observed bidirectional effects of 5-HT 2C receptor ligands may have important implications when considering the 5-HT 2C receptor as a therapeutic target for psychiatric disorders, particularly those presenting with motivational dysfunctions.

  6. Neuronal Activation After Prolonged Immobilization: Do the Same or Different Neurons Respond to a Novel Stressor?

    PubMed

    Marín-Blasco, Ignacio; Muñoz-Abellán, Cristina; Andero, Raül; Nadal, Roser; Armario, Antonio

    2018-04-01

    Despite extensive research on the impact of emotional stressors on brain function using immediate-early genes (e.g., c-fos), there are still important questions that remain unanswered such as the reason for the progressive decline of c-fos expression in response to prolonged stress and the neuronal populations activated by different stressors. This study tackles these 2 questions by evaluating c-fos expression in response to 2 different emotional stressors applied sequentially, and performing a fluorescent double labeling of c-Fos protein and c-fos mRNA on stress-related brain areas. Results were complemented with the assessment of the hypothalamic-pituitary-adrenal axis activation. We showed that the progressive decline of c-fos expression could be related to 2 differing mechanisms involving either transcriptional repression or changes in stimulatory inputs. Moreover, the neuronal populations that respond to the different stressors appear to be predominantly separated in high-level processing areas (e.g., medial prefrontal cortex). However, in low-hierarchy areas (e.g., paraventricular nucleus of the hypothalamus) neuronal populations appear to respond unspecifically. The data suggest that the distinct physiological and behavioral consequences of emotional stressors, and their implication in the development of psychopathologies, are likely to be closely associated with neuronal populations specifically activated by each stressor.

  7. Effects of repeated administration of the monoamine oxidase inhibitor phenelzine on the discriminability of d-lysergic acid diethylamide (LSD) and 1-(m-trifluoromethylphenyl) piperazine (TFMPP).

    PubMed

    Cunningham, K A; Carroll, B A; Appel, J B

    1986-01-01

    Rats trained to discriminate d-lysergic acid diethylamide (LSD; 0.08 mg/kg) or 1-(m-trifluoromethylphenyl) piperazine (TFMPP; 0.8 mg/kg) were treated with the monoamine oxidase inhibitor (MAOI) phenelzine (10 mg/kg/day) for 7 days. After a 24 h "washout" period, they were challenged with the training drug (and dose) or saline, during extinction test sessions. Following 0.08 mg/kg LSD, LSD-trained rats responded primarily on the saline lever (29% drug-appropriate responding) while, after TFMPP (0.8 mg/kg), TFMPP-trained animals responded on the drug lever (75% drug-appropriate responding). These preliminary data suggest that, if serotonin receptors are involved in the behavioral effects of TFMPP, these receptors differ from those involved in the effects of LSD.

  8. Paired-housing selectively facilitates within-session extinction of avoidance behavior, and increases c-Fos expression in the medial prefrontal cortex, in anxiety vulnerable Wistar-Kyoto rats.

    PubMed

    Smith, Ian M; Pang, Kevin C H; Servatius, Richard J; Jiao, Xilu; Beck, Kevin D

    2016-10-01

    The perseveration of avoidance behavior, even in the absence of once threatening stimuli, is a key feature of anxiety and related psychiatric conditions. This phenomenon can be observed in the Wistar-Kyoto (WKY) rat which, in comparison to outbred controls, demonstrates impaired extinction of avoidance behavior. Also characteristic of the WKY rat is abnormalities of the neurocircuitry and neuroplasticity of the medial prefrontal cortex (mPFC). One means of reducing physiological responses to anxiety, and conditioned fear, in social species is the presence of a conspecific animal. The current study investigates whether or not pair-housed WKY rats would show facilitated extinction of avoidance in comparison to individual-housed WKY rats, and whether or not pair-housing influences mPFC activation during lever-press avoidance. Male WKY rats were assigned to individual-housed and pair-housed conditions. Rats were trained in lever-press avoidance. Each session of lever-press avoidance consisted of 20 trials, where pressing a lever in response to a warning tone prevented foot-shocks. Rats received 12 acquisition sessions over 4weeks; followed by 6 extinction sessions over 2weeks, where foot-shocks ceased to be delivered. Brains were harvested 90min after trials 1 and 10 of extinction sessions 1 and 6, and mPFC sections underwent c-Fos staining as a measure of activation. Pair-housed rats showed facilitated lever-press avoidance extinction rates, but the main cause for this overall difference was a selective facilitation of within-session extinction. Similar to individual-housed rats, pair-housed rats continued to avoid during trial 1 of extinction even when the avoidance responding had been significantly reduced by the end of the previous session. Pair-housed rats sacrificed on trial 1 showed greater c-Fos expression in the anterior cingulate cortex and prelimbic cortex subregions of the mPFC compared individual-housed rats sacrificed on trial 1. This data shows pair

  9. Effects of nucleus accumbens core and shell lesions on autoshaped lever-pressing.

    PubMed

    Chang, Stephen E; Holland, Peter C

    2013-11-01

    Certain Pavlovian conditioned stimuli (CSs) paired with food unconditioned stimuli (USs) come to elicit approach and even consumption-like behaviors in rats (sign-tracking). We investigated the effects of lesions of the nucleus accumbens core (ACbC) or shell (ACbS) on the acquisition of sign-tracking in a discriminative autoshaping procedure in which presentation of one lever CS was followed by delivery of sucrose, and another was not. Although we previously found that bilateral lesions of the whole ACb disrupted the initial acquisition of sign-tracking, neither ACbC or ACbS lesions affected the rate or percentage of trials in which rats pressed the CS+. In addition, detailed video analysis showed no effect of either lesion on the topography of the sign-tracking conditioned response (CR). These and other results from lesion studies of autoshaping contrast with those from previous sign-tracking experiments that used purely visual cues (Parkinson et al., 2000a,b), suggesting that the neural circuitry involved in assigning incentive value depends upon the nature of the CS. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Serotonin-3 receptors in the posterior ventral tegmental area regulate ethanol self-administration of alcohol-preferring (P) rats.

    PubMed

    Rodd, Zachary A; Bell, Richard L; Oster, Scott M; Toalston, Jamie E; Pommer, Tylene J; McBride, William J; Murphy, James M

    2010-05-01

    Several studies indicated the involvement of serotonin-3 ([5-hydroxy tryptamine] 5-HT(3)) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT(3) receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers (Coulbourn Instruments, Allentown, PA) were used to examine the effects of seven consecutive bilateral microinfusions of ICS 205-930 (ICS), a 5-HT(3) receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (vol/vol) ethanol self-administration. P rats readily acquired ethanol self-administration by the fourth session. The three highest doses (0.125, 0.25, and 1.25 microg) of ICS prevented acquisition of ethanol self-administration. During the acquisition postinjection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the three highest doses (0.75, 1.0, and 1.25 microg) of ICS significantly increased responding on the ethanol lever; after the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Microinfusion of ICS into the posterior VTA did not alter the low responding on the water lever and did not alter saccharin (0.0125% wt/v) self-administration. Microinfusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT(3) receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration and/or repeated treatments with a 5-HT(3) receptor antagonist may alter neuronal circuitry within the posterior VTA. 2010 Elsevier Inc. All rights reserved.

  11. Fast-responder: Rapid mobile-phone access to recent remote sensing imagery for first responders

    NASA Astrophysics Data System (ADS)

    Talbot, L. M.; Talbot, B. G.

    We introduce Fast-Responder, a novel prototype data-dissemination application and architecture concept to rapidly deliver remote sensing imagery to smartphones to enable situational awareness. The architecture implements a Fast-Earth image caching system on the phone and interacts with a Fast-Earth server. Prototype evaluation successfully demonstrated that National Guard users could select a location, download multiple remote sensing images, and flicker between images, all in less than a minute on a 3G mobile commercial link. The Fast-Responder architecture is a significant advance that is designed to meet the needs of mobile users, such as National Guard response units, to rapidly access information during a crisis, such as a natural or man-made disaster. This paper focuses on the architecture design and advanced user interface concepts for small-screens for highly active mobile users. Novel Fast-Responder concepts can also enable rapid dissemination and evaluation of imagery on the desktop, opening new technology horizons for both desktop and mobile users.

  12. STEM-based workbook: Enhancing students' STEM competencies on lever system

    NASA Astrophysics Data System (ADS)

    Sejati, Binar Kasih; Firman, Harry; Kaniawati, Ida

    2017-05-01

    Twenty-first century is a century of technology, a rapid development of scientific studies and technology make them relied heavily on each other. This research investigated about the effect of STEM-based workbook in enhancing students' STEM competencies in terms of knowledge understanding, problem solving skill, innovative abilities, and responsibility. The workbook was tried on 24 students that applied engineering design processes together with mathematics and science knowledge to design and create an egg cracker. The result showed that the implementation of STEM-based workbook on lever system in human body is effective to improve students' STEM competencies, it can be proven by students' result on their knowledge understanding improvement which can be seen from normalized gain () score is 0.41 and categorized as medium improvement, students' problem solving skill is also improving where it obtained a medium improvement with normalized gain as much as 0.45. Innovative abilities also encountered an the improvement, the workbook analysis obtained a higher score which means students can be more innovative after finishing their workbook. Last, students' responsibility is keep improving day by day, students' effort gain the highest score it means that the students become more responsible after implementation of STEM-based workbook. All of the results are supported with the response of students towards STEM-based workbook implementation which showed positive response in all indicators.

  13. Increased behavioral output but intact goal-directed and habitual responding for food reward following early-life social deprivation in rats.

    PubMed

    Lomanowska, Anna M; Kraemer, Gary W

    2014-09-01

    Early-life social adversity, such as child neglect and institutionalized rearing, is associated with later-life difficulties of inhibitory control that may reflect altered attribution of salience to external stimuli. Studies in rats demonstrate that early-life social deprivation results in enhanced responsiveness to reward stimuli and conditioned reward cues. This study examined whether these effects are related to fundamental changes in appetitive conditioning processes involving instrumental goal-directed and habitual responding for food reward. Rats were reared either by the mother (maternal rearing; MR) or in complete isolation from the mother and litter (artificial rearing; AR) and tested as adults in two appetitive conditioning tasks. AR and MR rats did not differ in the amount of goal-directed effort they exerted to obtain food reward on progressive ratio schedules of reinforcement. AR and MR rats also did not differ in the shift from goal-directed to habitual responding on a random interval schedule and they were equally sensitive to changes in reward value. The major difference between AR and MR rats was that AR rats exhibited more non-instrumental responses (empty food magazine entries, ineffective lever presses). Thus, early-life social deprivation of rats through AR affects the expression of unreinforced extraneous behaviors when motivational requirements are high, but does not affect conditioned goal-directed and habitual responding to reward. The findings have implications for understanding what aspects of responsiveness to external stimuli may be selectively affected in disorders of inhibition associated with early-life social adversity. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Win-stay and win-shift lever-press strategies in an appetitively reinforced task for rats.

    PubMed

    Reed, Phil

    2016-12-01

    Two experiments examined acquisition of win-stay, win-shift, lose-stay, and lose-shift rules by which hungry rats could earn food reinforcement. In Experiment 1, two groups of rats were trained in a two-lever operant task that required them to follow either a win-stay/lose-shift or a win-shift/lose-stay contingency. The rates of acquisition of the individual rules within each contingency differed: lose-shift and lose-stay rules were acquired faster than win-stay and win-shift rules. Contrary to a number of previous reports, the win-shift rule was acquired less rapidly than any of the other rules. In Experiment 2, the four rules were taught separately, but subjects still acquired the win-shift rule more slowly than any of the other rules.

  15. Differences in change in coping styles between good responders, moderate responders and non-responders to pulmonary rehabilitation.

    PubMed

    Stoilkova-Hartmann, Ana; Janssen, Daisy J A; Franssen, Frits M E; Wouters, Emiel F M

    2015-12-01

    Pulmonary rehabilitation (PR) improves exercise tolerance and health status in patients with chronic obstructive pulmonary disease (COPD). Data on the effects of PR on coping styles are limited. Aim of the present study was to compare changes in coping styles between patients who had a good, moderate and no improvement in either exercise tolerance or health status after PR. Coping styles of 439 COPD patients undergoing PR were assessed by the Utrecht Coping List (UCL) at baseline and after PR. Patients' pulmonary function, six-minute walking distance (6MWD), St. George's Respiratory Questionnaire (SGRQ) and Hospital Anxiety and Depression Scale (HADS-A and HADS-D) were recorded. Good, moderate and non-responders were defined on the basis of minimally clinically important difference (MCID) for SGRQ total score and/or 6MWD. Overall, 54.0% of the patients fulfilled the criteria for good responders, while 22.1% were moderate responders. Change in passive reaction pattern coping style differed significantly between good responders and non-responders following PR (p < 0.001). Moreover, within the groups, changes in coping styles after PR occurred among the good responders, whereas the majority of moderate responders' and non-responders' coping styles were not significantly influenced by PR. Good responders decreased their passive reaction pattern coping style in contrast to non-responders after PR. In general, PR did not change the coping among moderate and non-responders. Further research is warranted to determine whether including interventions targeting coping styles may modify coping behaviour of COPD patients, as well as improvement in exercise tolerance or health status after PR. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Assessing the Role of Effort Reduction in the Reinforcing Efficacy of Timeout from Avoidance

    ERIC Educational Resources Information Center

    Galuska, Chad M.; Mikorski, Jeff; Perone, Michael

    2012-01-01

    Rats responded on concurrent schedules of shock-postponement or deletion (avoidance) and timeout from avoidance. In Experiment 1, 3 rats' responses on one lever postponed shocks for 20 s and responses on a second lever produced a 1-min timeout according to a variable-interval 45-s schedule. Across conditions, a warning signal (white noise) was…

  17. Autoshaping, random control, and omission training in the rat1

    PubMed Central

    Locurto, Charles; Terrace, H. S.; Gibbon, John

    1976-01-01

    The role of the stimulus-reinforcer contingency in the development and maintenance of lever contact responding was studied in hooded rats. In Experiment I, three groups of experimentally naive rats were trained either on autoshaping, omission training, or a random-control procedure. Subjects trained by the autoshaping procedure responded more consistently than did either random-control or omission-trained subjects. The probability of at least one lever contact per trial was slightly higher in subjects trained by the omission procedure than by the random-control procedure. However, these differences were not maintained during extended training, nor were they evident in total lever-contact frequencies. When omission and random-control subjects were switched to the autoshaping condition, lever contacts increased in all animals, but a pronounced retardation was observed in omission subjects relative to the random-control subjects. In addition, subjects originally exposed to the random-control procedure, and later switched to autoshaping, acquired more rapidly than naive subjects that were exposed only on the autoshaping procedure. In Experiment II, subjects originally trained by an autoshaping procedure were exposed either to an omission, a random-control, or an extinction procedure. No differences were observed among the groups either in the rate at which lever contacts decreased or in the frequency of lever contacts at the end of training. These data implicate prior experience in the interpretation of omission-training effects and suggest limitations in the influence of stimulus-reinforcer relations in autoshaping. PMID:16811960

  18. Autoshaping, random control, and omission training in the rat.

    PubMed

    Locurto, C; Terrace, H S; Gibbon, J

    1976-11-01

    The role of the stimulus-reinforcer contingency in the development and maintenance of lever contact responding was studied in hooded rats. In Experiment I, three groups of experimentally naive rats were trained either on autoshaping, omission training, or a random-control procedure. Subjects trained by the autoshaping procedure responded more consistently than did either random-control or omission-trained subjects. The probability of at least one lever contact per trial was slightly higher in subjects trained by the omission procedure than by the random-control procedure. However, these differences were not maintained during extended training, nor were they evident in total lever-contact frequencies. When omission and random-control subjects were switched to the autoshaping condition, lever contacts increased in all animals, but a pronounced retardation was observed in omission subjects relative to the random-control subjects. In addition, subjects originally exposed to the random-control procedure, and later switched to autoshaping, acquired more rapidly than naive subjects that were exposed only on the autoshaping procedure. In Experiment II, subjects originally trained by an autoshaping procedure were exposed either to an omission, a random-control, or an extinction procedure. No differences were observed among the groups either in the rate at which lever contacts decreased or in the frequency of lever contacts at the end of training. These data implicate prior experience in the interpretation of omission-training effects and suggest limitations in the influence of stimulus-reinforcer relations in autoshaping.

  19. Effect of GABA agonists and GABA-A receptor modulators on cocaine- and food-maintained responding and cocaine discrimination in rats.

    PubMed

    Barrett, Andrew C; Negus, S Stevens; Mello, Nancy K; Caine, S Barak

    2005-11-01

    Recent studies indicate that GABAergic ligands modulate abuse-related effects of cocaine. The goal of this study was to evaluate the effects of a mechanistically diverse group of GABAergic ligands on the discriminative stimulus and reinforcing effects of cocaine in rats. One group of rats was trained to discriminate 5.6 mg/kg cocaine from saline in a two-lever, food-reinforced, drug discrimination procedure. In two other groups, responding was maintained by cocaine (0-3.2 mg/kg/injection) or liquid food (0-100%) under a fixed ratio 5 schedule. Six GABA agonists were tested: the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, the GABA transaminase inhibitor gamma-vinyl-GABA (GVG), and three GABA-A receptor modulators (the barbiturate pentobarbital, the high-efficacy benzodiazepine midazolam, and the low-efficacy benzodiazepine enazenil). When tested alone, none of the compounds substituted fully for the discriminative stimulus effects of cocaine. As acute pretreatments, select doses of midazolam and pentobarbital produced 2.2- to 3.6-fold rightward shifts in the cocaine dose-effect function. In contrast, muscimol, baclofen, GVG, and enazenil failed to alter the discriminative stimulus effects of cocaine. In assays of cocaine- and food-maintained responding, midazolam and pentobarbital decreased cocaine self-administration at doses 9.6- and 3.3-fold lower, respectively, than those that decreased food-maintained responding. In contrast, muscimol, baclofen, and GVG decreased cocaine self-administration at doses that also decreased food-maintained responding. Enazenil failed to alter cocaine self-administration. Together with previous studies, these data suggest that among mechanistically diverse GABA agonists, high-efficacy GABA-A modulators may be the most effective for modifying the abuse-related effects of cocaine.

  20. The effects of anorexic drugs on free-fed rats responding under a second-order FI15-min (FR10:S) schedule for high incentive foods.

    PubMed

    Evenden, John; Ko, Tracey

    2007-02-01

    Many similarities exist between the overconsumption of food, which results in obesity, and drug addiction. The present study investigated the effects of anorectic drugs on responding maintained by high incentive, but nutritionally unnecessary, food reinforcers using an FI15(fixed-ratio 10:S) schedule of reinforcement, similar to that used in studies on the incentive properties of drugs of abuse. Rats were trained to respond on a lever to gain access to two high incentive foods--chocolate chip cookies and cheese. Under the FI15(FR10:S) schedule, every 10th response (fixed-ratio 10) delivered a tone and light conditioned stimulus. The first ratio completed 15 min after the start of the session produced the conditioned stimulus and opened a door to give access to a piece of cookie. After 5 min to consume the high incentive food, a second 15-min interval was started, terminating in access to a second reinforcer, cheese. Once trained, the rats were given free access to laboratory chow in the home cage. They continued to work for the high incentive foods for a period of over 1 year, showing a pattern of responding appropriate to an FI(fixed-ratio) schedule. Naloxone (1.0 mg/kg), fenfluramine (1 and 2 mg/kg), D-amphetamine (0.25 and 0.5 mg/kg), and rimonabant (3 mg/kg) significantly reduced responding, especially in the second interval. In contrast, complete removal of the high incentive food from the test procedure did not immediately reduce the rate of responding, tending to increase it in the second of the intervals. Apparently, the drugs did not reduce responding by reducing the experienced magnitude of the high incentive food, but more probably by reducing the animals' motivation.

  1. Feeding condition and the relative contribution of different dopamine receptor subtypes to the discriminative stimulus effects of cocaine in rats.

    PubMed

    Baladi, Michelle G; Newman, Amy H; France, Charles P

    2014-02-01

    The contribution of dopamine receptor subtypes in mediating the discriminative stimulus effects of cocaine is not fully established. Many drug discrimination studies use food to maintain responding, necessitating food restriction, which can alter drug effects. This study established stimulus control with cocaine (10 mg/kg) in free-feeding and food-restricted rats responding under a schedule of stimulus shock termination (SST) and in food-restricted rats responding under a schedule of food presentation to examine whether feeding condition or the reinforcer used to maintain responding impacts the effects of cocaine. Dopamine receptor agonists and antagonists were examined for their ability to mimic or attenuate, respectively, the effects of cocaine. Apomorphine, quinpirole, and lisuride occasioned >90 % responding on the cocaine-associated lever in free-feeding rats responding under a schedule of SST; apomorphine, but not quinpirole or lisuride, occasioned >90 % responding on the cocaine lever in food-restricted rats responding under a schedule of SST. In food-restricted rats responding for food these drugs occasioned little cocaine lever responding and were comparatively more potent in decreasing responding. In free-feeding rats, the effects of cocaine were attenuated by the D2/D3 receptor antagonist raclopride and the D3 receptor-selective antagonist PG01037. In food-restricted rats, raclopride and the D2 receptor-selective antagonist L-741,626 attenuated the effects of cocaine. Raclopride antagonized quinpirole in all groups while PG01037 antagonized quinpirole only in free-feeding rats. These results demonstrate significant differences in the discriminative stimulus of cocaine that are due to feeding conditions and not to the use of different reinforcers across procedures.

  2. Feeding condition and the relative contribution of different dopamine receptor subtypes to the discriminative stimulus effects of cocaine in rats

    PubMed Central

    Baladi, Michelle G; Newman, Amy H; France, Charles P

    2013-01-01

    Rationale The contribution of dopamine receptor subtypes in mediating the discriminative stimulus effects of cocaine is not fully established. Many drug discrimination studies use food to maintain responding, necessitating food restriction, which can alter drug effects. Objective This study established stimulus control with cocaine (10 mg/kg) in free-feeding and food-restricted rats responding under a schedule of stimulus shock termination (SST) and in food-restricted rats responding under a schedule of food presentation to examine whether feeding condition or the reinforcer used to maintain responding impacts the effects of cocaine. Method Dopamine receptor agonists and antagonists were examined for their ability to mimic or attenuate, respectively, the effects of cocaine. Result Apomorphine, quinpirole, and lisuride occasioned >90% responding on the cocaine-associated lever in free-feeding rats responding under a schedule of SST; apomorphine, but not quinpirole or lisuride, occasioned >90% responding on the cocaine lever in food-restricted rats responding under a schedule of SST. In food-restricted rats responding for food these drugs occasioned little cocaine lever responding and were comparatively more potent in decreasing responding. In free-feeding rats, the effects of cocaine were attenuated by the D2/D3 receptor antagonist raclopride and the D3 receptor-selective antagonist PG01037. In food-restricted rats, raclopride and the D2 receptor-selective antagonist L-741,626 attenuated the effects of cocaine. Raclopride antagonized quinpirole in all groups while PG01037 antagonized quinpirole only in free-feeding rats. Conclusion These results demonstrate significant differences in the discriminative stimulus of cocaine that are due to feeding conditions and not to the use of different reinforcers across procedures. PMID:24030470

  3. Reinstatement of MDMA (ecstasy) seeking by exposure to discrete drug-conditioned cues

    PubMed Central

    Ball, Kevin T.; Walsh, Kelly M.; Rebec, George V.

    2007-01-01

    The widely used recreational drug MDMA (ecstasy) supports self-administration in animals, but it is not known whether MDMA-associated cues are able to reinstate drug seeking in a relapse model of drug addiction. To assess this possibility, drug-naïve rats were trained to press a lever for MDMA infusions (0.30 mg/kg/infusion, i.v.) paired with a compound cue (light and tone) in daily 2 hr sessions. Responding was reinforced contingent on a modified fixed-ratio 5 schedule of reinforcement. Conditioned cue-induced reinstatement tests were conducted after lever pressing was extinguished in the absence of MDMA and the conditioned cues. Conditioned cues reinstated lever pressing after extinction, and the magnitude of reinstatement was positively correlated with the level of responding during MDMA self-administration. These results show for the first time that conditioned cues can trigger reinstatement of MDMA-seeking behavior in rats, and that individual differences in the pattern of MDMA self-administration can predict the magnitude of reinstatement responding. PMID:17602729

  4. Creative Climate: A Leadership Lever for Innovation

    ERIC Educational Resources Information Center

    Isaksen, Scott G.; Akkermans, Hans J.

    2011-01-01

    The working atmosphere within an organization has an important influence on its level of innovative productivity. Organizational leaders influence innovative productivity as well as the climate for creativity and innovation. This exploratory study included 140 respondents from 103 different organizations, 31 industries, and 10 countries, all of…

  5. A comparison of physical and psychological features of responders and non-responders to cervical facet blocks in chronic whiplash

    PubMed Central

    2013-01-01

    Background Cervical facet block (FB) procedures are often used as a diagnostic precursor to radiofrequency neurotomies (RFN) in the management of chronic whiplash associated disorders (WAD). Some individuals will respond to the FB procedures and others will not respond. Such responders and non-responders provided a sample of convenience to question whether there were differences in their physical and psychological features. This information may inform future predictive studies and ultimately the clinical selection of patients for FB procedures. Methods This cross-sectional study involved 58 individuals with chronic WAD who responded to cervical FB procedures (WAD_R); 32 who did not respond (WAD_NR) and 30 Healthy Controls (HC)s. Measures included: quantitative sensory tests (pressure; thermal pain thresholds; brachial plexus provocation test); nociceptive flexion reflex (NFR); motor function (cervical range of movement (ROM); activity of the superficial neck flexors during the cranio-cervical flexion test (CCFT). Self-reported measures were gained from the following questionnaires: neuropathic pain (s-LANSS); psychological distress (General Health Questionnaire-28), post-traumatic stress (PDS) and pain catastrophization (PCS). Individuals with chronic whiplash attended the laboratory once the effects of the blocks had abated and symptoms had returned. Results Following FB procedures, both WAD groups demonstrated generalized hypersensitivity to all sensory tests, decreased neck ROM and increased superficial muscle activity with the CCFT compared to controls (p < 0.05). There were no significant differences between WAD groups (all p > 0.05). Both WAD groups demonstrated psychological distress (GHQ-28; p < 0.05), moderate post-traumatic stress symptoms and pain catastrophization. The WAD_NR group also demonstrated increased medication intake and elevated PCS scores compared to the WAD_R group (p < 0.05). Conclusions Chronic WAD responders and non-responders to FB

  6. Staminal Evolution in the Genus Salvia (Lamiaceae): Molecular Phylogenetic Evidence for Multiple Origins of the Staminal Lever

    PubMed Central

    Walker, Jay B.; Sytsma, Kenneth J.

    2007-01-01

    Background and Aims The genus Salvia has traditionally included any member of the tribe Mentheae (Lamiaceae) with only two stamens and with each stamen expressing an elongate connective. The recent demonstration of the non-monophyly of the genus presents interesting implications for staminal evolution in the tribe Mentheae. In the context of a molecular phylogeny, the staminal morphology of the various lineages of Salvia and related genera is characterized and an evolutionary interpretation of staminal variation within the tribe Mentheae is presented. Methods Two molecular analyses are presented in order to investigate phylogenetic relationships in the tribe Mentheae and the genus Salvia. The first presents a tribal survey of the Mentheae and the second concentrates on Salvia and related genera. Schematic sketches are presented for the staminal morphology of each major lineage of Salvia and related genera. Key Results These analyses suggest an independent origin of the staminal elongate connective on at least three different occasions within the tribe Mentheae, each time with a distinct morphology. Each independent origin of the lever mechanism shows a similar progression of staminal change from slight elongation of the connective tissue separating two fertile thecae to abortion of the posterior thecae and fusion of adjacent posterior thecae. A monophyletic lineage within the Mentheae is characterized consisting of the genera Lepechinia, Melissa, Salvia, Dorystaechas, Meriandra, Zhumeria, Perovskia and Rosmarinus. Conclusions Based on these results the following are characterized: (1) the independent origin of the staminal lever mechanism on at least three different occasions in Salvia, (2) that Salvia is clearly polyphyletic, with five other genera intercalated within it, and (3) staminal evolution has proceeded in different ways in each of the three lineages of Salvia but has resulted in remarkably similar staminal morphologies. PMID:16926227

  7. Role of educational institutions in identifying and responding to emerging health human resources needs.

    PubMed

    Tzountzouris, John-Paul; Gilbert, John H V

    2009-01-01

    The healthcare system continues to evolve, requiring innovation to promote patient-centred, fiscally responsible healthcare delivery. This evolution includes changes to the skills and competencies required of the health human resources (HHR), both regulated and unregulated, who are central supports to healthcare delivery. This has become a priority agenda item at the international, national, provincial, regional and local levels. This paper describes the system factors that drive the emergence of HHR skill and competency needs, and explores the roles of various institutions in the identification of and response to HHR needs. Educational institutions play an important role in responding to emerging HHR needs. Their actual response to HHR skill and competency needs will ultimately depend on the risk posed to the organizations of either addressing, or not addressing, these needs. These decisions are complex and are balanced against strategic, operational and educational risks, benefits and realities within each given educational institution. Educational institutions - through their linkages with the workplace, industry, professional organizations and government - have a unique view and understanding of many facets of the complexity of HHR planning. This paper proposes that educational institutions play a pivotal role as levers in a more coordinated response to emerging HHR needs and, as such, should be intimately involved in comprehensive HHR planning.

  8. Hsp31, a member of the DJ-1 superfamily, is a multitasking stress responder with chaperone activity

    PubMed Central

    Aslam, Kiran; Hazbun, Tony R.

    2016-01-01

    ABSTRACT Among different types of protein aggregation, amyloids are a biochemically well characterized state of protein aggregation that are associated with a large number of neurodegenerative diseases including Parkinson's disease, Alzheimer and Creutzfeldt-Jakob disease. Yeast, Saccharomyces cerevisiae is an insightful model to understand the underlying mechanism of protein aggregation. Many yeast molecular chaperones can modulate aggregation and misfolding of proteins including α-Syn and the Sup35 prion. Hsp31 is a homodimeric protein structurally similar to human DJ-1, a Parkinson's disease-linked protein, and both are members of the DJ-1/ThiJ/PfpI superfamily. An emerging view is that Hsp31 and its associated superfamily members each have divergent multitasking functions that have the common theme of responding and managing various types of cellular stress. Hsp31 has several biochemical activities including chaperone and detoxifying enzyme activities that modulate at various points of a stress pathway such as toxicity associated with protein misfolding. However, we have shown the protective role of Hsp31's chaperone activity can operate independent of detoxifying enzyme activities in preventing the early stages of protein aggregate formation and associated cellular toxicities. We provide additional data that collectively supports the multiple functional roles that can be accomplished independent of each other. We present data indicating Hsp31 purified from yeast is more active compared to expression and purification from E. coli suggesting that posttranslational modifications could be important for Hsp31 to be fully active. We also compare the similarities and differences in activities among paralogs of Hsp31 supporting a model in which this protein family has overlapping but diverging roles in responding to various sources of cellular stresses. PMID:27097320

  9. Do "placebo responders" exist?

    PubMed

    Kaptchuk, Ted J; Kelley, John M; Deykin, Aaron; Wayne, Peter M; Lasagna, Louis C; Epstein, Ingrid O; Kirsch, Irving; Wechsler, Michael E

    2008-07-01

    The placebo effect has been the subject of much controversy. For a scientific investigation of placebo effects to advance it is important to establish whether a placebo response in any particular illness is reliable - i.e., if there is a response to a single placebo administration there will also be a placebo response to the repeated administration of a similar placebo in similar conditions. A positive answer would allow more sophisticated clinical trial designs and more precise basic research experiments on the placebo effect. This article reviews experiments that used multiple administrations of placebo to answer the question "do reliable placebo responders exist?" This paper also examines the evidence for the existence of a consistent placebo responder, i.e. a person who responds to placebo in one situation will respond in another condition or using a different type of placebo ritual. Much of the existing evidence for these two questions was performed before 1967. This early evidence is contradictory, methodologically weak and is sufficiently old to be considered medical history. Since 1969, at least eight experiments exposed asthma patients to multiple administrations of placebo given with deceptive suggestions that the "treatment" was an active medication. While the results of this research are not unequivocal, and may not be equivalent to non-deceptive conditions, this line of inquiry suggests that if a reliable and consistent placebo response exists it could be detected within this population. Finally, this paper proposes one model to rigorously investigate the stability of placebo responses.

  10. Effect of yohimbine on reinstatement of operant responding in rats is dependent on cue contingency but not food reward history.

    PubMed

    Chen, Yu-Wei; Fiscella, Kimberly A; Bacharach, Samuel Z; Tanda, Gianluigi; Shaham, Yavin; Calu, Donna J

    2015-07-01

    Yohimbine is an alpha-2 adrenoceptor antagonist that has been used in numerous studies as a pharmacological stressor in rodents, monkeys and humans. Recently, yohimbine has become the most common stress manipulation in studies on reinstatement of drug and food seeking. However, the wide range of conditions under which yohimbine promotes reward seeking is significantly greater than that of stressors like intermittent footshock. Here, we addressed two fundamental questions regarding yohimbine's effect on reinstatement of reward seeking: (1) whether the drug's effect on operant responding is dependent on previous reward history or cue contingency, and (2) whether yohimbine is aversive or rewarding under conditions typically used in reinstatement studies. We also used in vivo microdialysis to determine yohimbine's effect on dopamine levels in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). We found that the magnitude of yohimbine-induced (0.5, 1.0, 2.0 mg/kg) operant responding during the reinstatement tests was critically dependent on the contingency between lever pressing and discrete tone-light cue delivery but not the previous history with food reward during training. We also found that yohimbine (2 mg/kg) did not cause conditioned place aversion. Finally, we found that yohimbine modestly increased dopamine levels in mPFC but not NAc. Results suggest that yohimbine's effects on operant responding in reinstatement studies are likely independent of the history of contingent self-administration of food or drug rewards and may not be related to the commonly assumed stress-like effects of yohimbine. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  11. Reduced expression of IL-12 p35 by SJL/J macrophages responding to Theiler's virus infection is associated with constitutive activation of IRF-3

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dahlberg, Angela; Auble, Mark R.; Petro, Thomas M.

    2006-09-30

    Macrophages responding to viral infections may contribute to autoimmune demyelinating diseases (ADD). Macrophages from ADD-susceptible SJL/J mice responding to Theiler's Virus (TMEV) infection, the TLR7 agonist loxoribine, or the TLR4 agonist-LPS expressed less IL-12 p35 but more IL-12/23 p40 and IFN-{beta} than macrophages from ADD-resistant B10.S mice. While expression of IRF-1 and -7 was similar between B10.S and SJL/J TMEV-infected macrophages, SJL/J but not B10.S macrophages exhibited constitutively active IRF-3. In contrast to overexpressed IRF-1, IRF-5, and IRF-7, which stimulated p35 promoter reporter activity, overexpressed IRF-3 repressed p35 promoter activity in response to TMEV infection, loxoribine, IFN-{gamma}/LPS, but not IFN-{gamma}more » alone. IRF-3 lessened but did not eliminate IRF-1-stimulated p35 promoter activity. Repression by IRF-3 required bp -172 to -122 of the p35 promoter. The data suggest that pre-activated IRF-3 is a major factor in the differences in IL-12 production between B10.S and SJL/J macrophages responding to TMEV.« less

  12. The effects of differing response-force requirements on fixed-ratio responding of rats.

    PubMed Central

    Alling, K; Poling, A

    1995-01-01

    Rats were exposed to two-component multiple schedules of food delivery. In the first experiment, 15 responses were required to produce food in both components. A downward force of 0.25 N (25 g) was always required to operate the response lever in one component. In the other, the required force was 0.25, 0.50, 1.00, or 2.00 N (25, 50, 100, or 200 g). In the second experiment, 0.25 N of force operated the lever in one component, but in the other, the force requirement for five consecutive responses at the beginning, middle, or end of each ratio was increased from 0.25 to 2.00 N. In the third experiment, the number of responses required to produce food was reduced from 15 to 5, and then to 1. Again, the effects of altering response force from 0.25 to 2.00 N were examined. In general, as response force increased in all experiments, mean response rates decreased and mean interresponse times increased. PMID:7751836

  13. Conservative treatment of torn medial meniscus via mechanical force, manually assisted short lever chiropractic adjusting procedures.

    PubMed

    Polkinghorn, B S

    1994-09-01

    To present the first reported case of successful chiropractic intervention in treatment of a torn medial meniscus of the knee, the meniscal tear being documented by magnetic resonance imaging (MRI). A 54-yr-old woman complaining of right knee pain of several months' duration with accompanying marked functional impairment was diagnosed as having a tear in the posterior horn of the ipsilateral medial meniscus, verified by MRI studies of the same. Independent consultation with three medical specialists resulted in the unanimous decision that surgical intervention for the purpose of meniscectomy provided the only therapeutic approach indicated for the problem. However, the patient was reticent to undergo said surgical procedure and chose, instead, to utilize chiropractic care and conservative management in an effort to resolve her condition without having to resort to surgery. The patient received chiropractic treatment to the knee via mechanical force, manually assisted short lever chiropractic adjusting procedures (MFMA) utilizing an Activator Adjusting Instrument. Auxiliary treatment included the use of homeopathic therapy as an adjunct to chiropractic care. Said treatment resulted in a complete resolution of the patient's disability, the patient recovering full function of the knee joint and achieving an asymptomatic status without having to submit to surgical intervention and its possible adverse sequelae. Conservative management of meniscal tears via chiropractic treatment may provide a therapeutically effective and financially cost containing alternative to routine meniscectomy in certain cases involving torn medial menisci of the knee.

  14. PUNISHING AND CARDIOVASCULAR EFFECTS OF INTRAVENOUS HISTAMINE IN RATS: PHARMACOLOGICAL SELECTIVITY

    PubMed Central

    Podlesnik, Christopher A.; Jimenez-Gomez, Corina

    2014-01-01

    Although drugs may serve as reinforcers or punishers of operant behavior, the punishing function has received much less experimental attention than the reinforcing function. A sensitive method for studying drug-induced punishment is to assess choice for a punished response over an unpunished response. In these experiments, rats chose between pressing one lever and receiving a sucrose pellet or pressing another lever and receiving a sucrose pellet plus an intravenous injection of histamine. When sucrose was delivered equally frequently for either the punished or the unpunished response, rats selected the unpunished lever consistently, but decreases in the punished response did not differ as a function of intravenous histamine dose (0.1–1 mg/kg/inj). Changing the procedure so that sucrose was delivered on the unpunished lever with p = .5 increased the rats’ responding on the punished lever with saline injections. In addition, the same range of histamine doses produced a much larger range of responses on the punished lever that was dose dependent. Using these procedures to assess the receptors mediating histamine’s effects, the histamine H1-receptor antagonists, pyrilamine and ketotifen, antagonized the punishing effect of histamine, but the histamine H2-receptor antagonist ranitidine did not. However, ranitidine pretreatments reduced histamine-induced heart-rate increases to a greater extent than did the histamine H1-receptor antagonists when administered at the same doses examined under conditions of histamine punishment. Overall, the present findings extend the general hypothesis that activation of histamine H1-receptors mediates the punishing effects of histamine. They also introduce methods for rapidly assessing pharmacological mechanisms underlying drug-induced punishment. PMID:23982898

  15. Using Indices of Fidelity to Intervention Core Components to Identify Program Active Ingredients

    ERIC Educational Resources Information Center

    Abry, Tashia; Hulleman, Chris S.; Rimm-Kaufman, Sara E.

    2015-01-01

    Identifying the active ingredients of an intervention--intervention-specific components serving as key levers of change--is crucial for unpacking the intervention black box. Measures of intervention fidelity can be used to identify specific active ingredients, yet such applications are rare. We illustrate how fidelity measures can be used to…

  16. Oral operant ethanol self-administration in the absence of explicit cues, food restriction, water restriction and ethanol fading in C57BL/6J mice

    PubMed Central

    Stafford, Alexandra M.; Anderson, Shawn M.; Shelton, Keith L.; Brunzell, Darlene H.

    2015-01-01

    Rationale Mouse models of EtOH self-administration are useful to identify genetic and biological underpinnings of alcohol use disorder. Objectives These experiments developed a novel method of oral operant EtOH self-administration in mice without explicitly paired cues, food/water restriction, or EtOH fading. Methods Following magazine and lever training for 0.2% saccharin (SAC), mice underwent 9 weekly overnight sessions with lever pressing maintained by dipper presentation of 0, 3, 10 or 15% EtOH in SAC or water vehicle. Ad libitum water was available from a bottle. Results Water vehicle mice ingested most fluid from the water bottle in contrast to SAC vehicle mice, which despite lever pressing demands, drank most of their fluid from the liquid dipper. Although EtOH in SAC vehicle mice showed concentration-dependent increases of g/kg EtOH intake, lever pressing decreased with increasing EtOH concentration and did not exceed that of SAC vehicle alone at any EtOH concentration. Mice reinforced with EtOH in water ingested less EtOH than mice reinforced with EtOH in SAC. EtOH in water mice, however, showed concentration-dependent increases in g/kg EtOH intake and lever presses. 15% EtOH in water mice showed significantly greater levels of lever pressing than water vehicle mice and a significant escalation of responding across weeks of exposure. Naltrexone pretreatment reduced EtOH self-administration and intake in these mice without altering responding in the vehicle control condition during the first hour of the session. Conclusions SAC facilitated EtOH intake but prevented observation of EtOH reinforcement. Water vehicle unmasked EtOH's reinforcing effects. PMID:26268145

  17. Oral operant ethanol self-administration in the absence of explicit cues, food restriction, water restriction and ethanol fading in C57BL/6J mice.

    PubMed

    Stafford, Alexandra M; Anderson, Shawn M; Shelton, Keith L; Brunzell, Darlene H

    2015-10-01

    Mouse models of ethanol (EtOH) self-administration are useful to identify genetic and biological underpinnings of alcohol use disorder. These experiments developed a novel method of oral operant EtOH self-administration in mice without explicitly paired cues, food/water restriction, or EtOH fading. Following magazine and lever training for 0.2 % saccharin (SAC), mice underwent nine weekly overnight sessions with lever pressing maintained by dipper presentation of 0, 3, 10, or 15 % EtOH in SAC or water vehicle. Ad libitum water was available from a bottle. Water vehicle mice ingested most fluid from the water bottle in contrast to SAC vehicle mice, which despite lever pressing demands, drank most of their fluid from the liquid dipper. Although EtOH in SAC vehicle mice showed concentration-dependent increases of g/kg EtOH intake, lever pressing decreased with increasing EtOH concentration and did not exceed that of SAC vehicle alone at any EtOH concentration. Mice reinforced with EtOH in water ingested less EtOH than mice reinforced with EtOH in SAC. EtOH in water mice, however, showed concentration-dependent increases in g/kg EtOH intake and lever presses. Fifteen percent EtOH in water mice showed significantly greater levels of lever pressing than water vehicle mice and a significant escalation of responding across weeks of exposure. Naltrexone pretreatment reduced EtOH self-administration and intake in these mice without altering responding in the vehicle control condition during the first hour of the session. SAC facilitated EtOH intake but prevented observation of EtOH reinforcement. Water vehicle unmasked EtOH's reinforcing effects.

  18. Responding to Student Essays: A Conversation.

    ERIC Educational Resources Information Center

    Teichmann, Sandra Gail; Fike, Darrell

    Two college writing teachers share their viewpoint that people outside the academic setting often misunderstand the time-consuming activities involved with responding to student writing. They agree that teachers should envision evaluation as conducting a conversation with the writer of the essay. The key component of this conversation, depending…

  19. The lupus impact tracker is responsive to changes in clinical activity measured by the systemic lupus erythematosus responder index.

    PubMed

    Devilliers, H; Bonithon-Kopp, C; Jolly, M

    2017-04-01

    Objective The lupus impact tracker (LIT) is a 10-item patient reported outcome tool to measure the impact of systemic lupus erythematosus or its treatment on patients' daily lives. Herein, we describe the responsiveness of the LIT and LupusQoL to changes in disease activity, using the systemic lupus erythematosus responder index (SRI). Methods A total of 325 adult systemic lupus erythematosus patients were enrolled in an observational, longitudinal, multicentre study, conducted across the USA and Canada. Data (demographics, LIT, LupusQoL, BILAG, SELENA-SLEDAI) were obtained three months apart. Modified SRI was defined as: a decrease in SELENA-SLEDAI (4 points); no new BILAG A, and no greater than one new BILAG B; and no increase in the physician global assessment. Standardised response mean and effect size for LIT and LupusQoL domains were calculated among SRI responders and non-responders. Wilcoxon's test was used to compare the LIT and LupusQoL variation by SRI responder status. Results Of the participants 90% were women, 53% were white, 33% were of African descendant and 17% were Hispanic. Mean (SD) age and SELENA-SLEDAI at baseline were 42.3 (16.2) years and 4.3 (3.8), respectively. Mean (SD) LIT score at baseline was 39.4 (22.9). LIT standardised response mean (effect size) among SRI responders and non-responders were -0.69 (-0.36) and -0.20 (-0.12), respectively ( P = 0.02). For LupusQoL, two domains were responsive to SRI: standardised response mean (effect size) for physical health and pain domains were 0.42 (0.23) and 0.65 (0.44), respectively. Conclusions LIT is moderately responsive to SRI in patients with systemic lupus erythematosus. Inclusion of this tool in clinical care and clinical trials may provide further insights into its responsiveness. This is the first systemic lupus erythematosus patient reported outcome tool to be evaluated against composite responder index (SRI) used in clinical trials.

  20. Comparison of MicroRNAs Mediated in Reactivation of the γ-Globin in β-Thalassemia Patients, Responders and Non-Responders to Hydroxyurea.

    PubMed

    Hojjati, Mohammad T; Azarkeivan, Azita; Pourfathollah, Ali A; Amirizadeh, Naser

    2017-03-01

    Drug induction of Hb F seems to be an ideal therapy for patients with hemoglobin (Hb) disorders, and many efforts have been made to reveal the mechanism behind it. Thus, we examined in vivo expression of some microRNAs (miRNAs) that are thought to be involved in this process. Among β-thalassemia (β-thal) patients who were undergoing hydroxyurea (HU) therapy in the past 3 months and five healthy individuals, five responders and five non-responders, were also included in the study. Erythroid progenitors were isolated by magnetic activated cell sorting (MACS) and miRNA expression analyzed using reverse transcription-polymerase chain reaction (RT-PCR). We showed that γ-globin, miR-210 and miR-486-3p had higher levels in the responders than the non-responders group. Moreover, miR-150 and miR-320 had higher levels in the healthy group than both non-responders and responders groups, but the expression of miR-96 did not show any significant difference between the study groups. To the best of our knowledge, this is the first study proposing that 'induction of cellular hypoxic condition by Hb F inducing agents' could be the milestone of possible mechanisms that explain why responders are able to reactivate γ-globin genes and subsequently, more production of Hb F, in response to these agents in comparison to non-responders. However, further investigations need to be performed to verify this hypothesis.

  1. NF-κB DNA-binding activity in embryos responding to a teratogen, cyclophosphamide

    PubMed Central

    Torchinsky, Arkady; Lishanski, Lucy; Wolstein, Orit; Shepshelovich, Jeanne; Orenstein, Hasida; Savion, Shoshana; Zaslavsky, Zeev; Carp, Howard; Brill, Alexander; Dikstein, Rivka; Toder, Vladimir; Fein, Amos

    2002-01-01

    Background The Rel/NF-κB transcription factors have been shown to regulate apoptosis in different cell types, acting as inducers or blockers in a stimuli- and cell type-dependent fashion. One of the Rel/NF-κB subunits, RelA, has been shown to be crucial for normal embryonic development, in which it functions in the embryonic liver as a protector against TNFα-induced physiological apoptosis. This study assesses whether NF-κB may be involved in the embryo's response to teratogens. Fot this, we evaluated how NF-KappaB DNA binding activity in embryonic organs demonstraiting differential sensitivity to a reference teratogen, cyclophosphamide, correlates with dysmorphic events induced by the teratogen at the cellular level (excessive apoptosis) and at the organ level (structural anomalies). Results The embryonic brain and liver were used as target organs. We observed that the Cyclophosphamide-induced excessive apoptosis in the brain, followed by the formation of severe craniofacial structural anomalies, was accompanied by suppression of NF-κB DNA-binding activity as well as by a significant and lasting increase in the activity of caspases 3 and 8. However, in the liver, in which cyclophosphamide induced transient apoptosis was not followed by dysmorphogenesis, no suppression of NF-κB DNA-binding activity was registered and the level of active caspases 3 and 8 was significantly lower than in the brain. It has also been observed that both the brain and liver became much more sensitive to the CP-induced teratogenic insult if the embryos were exposed to a combined treatment with the teratogen and sodium salicylate that suppressed NF-κB DNA-binding activity in these organs. Conclusion The results of this study demonstrate that suppression of NF-κB DNA-binding activity in embryos responding to the teratogenic insult may be associated with their decreased resistance to this insult. They also suggest that teratogens may suppress NF-κB DNA-binding activity in the

  2. Policy initiation and political levers in health policy: lessons from Ghana’s health insurance

    PubMed Central

    2012-01-01

    Background Understanding the health policy formulation process over the years has focused on the content of policy to the neglect of context. This had led to several policy initiatives having a still birth or ineffective policy choices with sub-optimal outcomes when implemented. Sometimes, the difficulty has been finding congruence between different values and interests of the various stakeholders. How can policy initiators leverage the various subtle mechanisms that various players draw on to leverage their interests during policy formulation. This paper attempts to conceptualise these levers of policy formulation to enhance an understanding of this field of work based on lived experience. Methodology This is a qualitative participant observation case study based on retrospective recollection of the policy process and political levers involved in developing the Ghana National Health Insurance Scheme. The study uses a four-concept framework which is agenda setting, symbols manipulation, constituency preservation and coalition building to capture the various issues, negotiations and nuanced approaches used in arriving at desired outcomes. Results Technical experts, civil society, academicians and politicians all had significant influence on setting the health insurance agenda. Each of these various stakeholders carefully engaged in ways that preserved their constituency interests through explicit manoeuvres and subtle engagements. Where proposals lend themselves to various interpretations, stakeholders were quick to latch on the contentious issues to preserve their constituency and will manipulate the symbols that arise from the proposals to their advantage. Where interests are contested and the price of losing out will leave government worse off which will favour its political opponent, it will push for divergent interests outside parliamentary politics through intense negotiations to build coalitions so a particular policy may pass. Conclusions This paper has

  3. Mi Segundo Libro de Maquinas Simples: Las Palancas. Escuela Intermedia Grados 7, 8 y 9 (My Second Book of Simple Machines: Levers. Intermediate School Grades 7, 8, and 9).

    ERIC Educational Resources Information Center

    Alvarado, Patricio R.; Montalvo, Luis

    This is the second book in a five-book physical science series on simple machines. The books are designed for Spanish-speaking junior high school students. By suggesting experiments and posing questions concerning drawings in the book which illustrate the scientific principles, this book explains the workings of three types of levers. Resistance…

  4. Suppressing effect of COR659 on alcohol, sucrose, and chocolate self-administration in rats: involvement of the GABAB and cannabinoid CB1 receptors.

    PubMed

    Maccioni, Paola; Colombo, Giancarlo; Lorrai, Irene; Zaru, Alessandro; Carai, Mauro A M; Gessa, Gian Luigi; Brizzi, Antonella; Mugnaini, Claudia; Corelli, Federico

    2017-09-01

    COR659 [methyl2-(4-chlorophenylcarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate] is a new, positive allosteric modulator (PAM) of the GABA B receptor. This study evaluated whether COR659 shared with previously tested GABA B PAMs the capacity to reduce alcohol self-administration in rats. Treatment with non-sedative doses of COR659 (2.5, 5, and 10 mg/kg; i.p.) suppressed lever-responding for alcohol (15% v/v) in Sardinian alcohol-preferring (sP) rats under the fixed ratio (FR) 4 (FR4) and progressive ratio (PR) schedules of reinforcement; COR659 was more potent and effective than the reference GABA B PAM, GS39783. Treatment with COR659, but not GS39783, suppressed (a) lever-responding for a sucrose solution (1-3% w/v) in sP rats under the FR4 and PR schedules, (b) lever-responding for a chocolate solution [5% (w/v) Nesquik®] in Wistar rats under the FR10 and PR schedules, and (c) cue-induced reinstatement of chocolate seeking in Wistar rats. Treatment with COR659 was completely ineffective on lever-responding (FR10) for regular food pellets in food-deprived Wistar rats. Pretreatment with the GABA B receptor antagonist, SCH50911, partially blocked COR659-induced reduction of alcohol self-administration, being ineffective on reduction of chocolate self-administration. Pretreatment with the cannabinoid CB 1 receptor antagonist, AM4113, fully blocked COR659-induced reduction of chocolate self-administration, being ineffective on reduction of alcohol self-administration. COR659 might exert its behavioral effects via a composite mechanism: (i) positive allosteric modulation of the GABA B receptor, responsible for a large proportion of reduction of alcohol self-administration; (ii) an action at other receptor system(s), including the cannabinoid CB 1 receptor, through which COR659 affects seeking and consumption of highly palatable foods.

  5. Contributions of basolateral amygdala and nucleus accumbens subregions to mediating motivational conflict during punished reward-seeking.

    PubMed

    Piantadosi, Patrick T; Yeates, Dylan C M; Wilkins, Mathew; Floresco, Stan B

    2017-04-01

    The involvement of different nodes within meso-cortico-limbic-striatal circuitry in mediating reward-seeking has been well described, yet comparatively less is known about how such circuitry may regulate appetitively-motivated behaviors that may be punished. The basolateral amygdala (BLA) is one nucleus that has been implicated in suppressing punished reward-seeking, and this structure can modulate goal-directed behavior via projections to subregions of the nucleus accumbens (NAc). Here, we examined the effects of reversible inactivations of the BLA, NAc Shell (NAcS), and core (NAcC) on performance of a "Conflict" task where rats pressed a lever for sucrose reinforcement during three distinct 5min phases. During the first and last phases of a session, rats lever-pressed for food reward delivered on a VI-15/FR5 schedule. In between these phases was a signaled "Conflict" period, where each lever-press yielded food, but 50% of presses were also punished with foot-shock. Under control conditions, well-trained rats responded vigorously during the two "safe" VI-15/FR5 periods, but reduced responding during the punished Conflict period. Inactivation of either the BLA or the NAcS via infusions of baclofen/muscimol disinhibited punished seeking, increasing lever-pressing during the conflict period, while attenuating pressing during VI-15/FR5 phases. In contrast, NAcC inactivation markedly decreased responding across all three phases. Similar inactivation of the BLA or NAcS did not alter responding in a separate control experiment where rats pressed for food on schedules identical to the Conflict task in the absence of any punishment, while NAcC inactivation again suppressed responding. These results imply that BLA and NAcS are part of a circuit that suppresses reward-seeking in the face of danger, which in turn may have implications for disorders characterized by punishment resistance, including substance abuse and obsessive-compulsive disorder. Copyright © 2017 Elsevier

  6. The effects of psychotomimetics and psychomotor stimulants on two schedules promoting response switching in the rat.

    PubMed

    Evenden, John

    2002-10-01

    Psychosis and psychotomimetic drugs result in a disorganisation of the structure of thought and behaviour. Normalising these is one of the objects of antipsychotic therapy, and methods for predicting such a therapeutic effect would be of value. The effects of a number of psychotomimetic agents were examined on the way in which rats distributed responding over two response levers using two different procedures, to assay their effects on behavioural organisation. Previously, amphetamine has been found to increase response switching using these schedules. In the first, the random reinforcement procedure, one of the two levers was selected at random as "correct", and responses on this lever were reinforced with food under a random ratio schedule. No signal was given to distinguish the levers. Responding could also result in the food tray being illuminated, but no food pellet was delivered ("no-food" event). Responses on the second lever ("incorrect") had no programmed consequences. After each food delivery or "no-food" event the levers designated as "correct" and "incorrect" were reassigned at random, and the rat had to open the food tray to restart the schedule. In the second procedure, the rats were required to make 21 responses before a switch between the two levers resulted in food delivery [Fixed Ratio (FR) 21-switch]. The responses making up the FR could be distributed freely between the two levers. Phencyclidine (PCP), scopolamine, caffeine and ethanol increased switching under the random reinforcement procedure, but (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and atropine did not. PCP, caffeine, lysergic acid diethylamide (LSD) and atropine increased switching under the FR21-switch procedure, but ethanol did not. The increases in switching produced by PCP, LSD and the anticholinergics were accompanied by marked reductions in response rate, whereas those produced by amphetamine and caffeine were not. The effects of amphetamine, and PCP were

  7. World Trade Center disaster: assessment of responder occupations, work locations, and job tasks.

    PubMed

    Woskie, Susan R; Kim, Hyun; Freund, Alice; Stevenson, Lori; Park, Bo Y; Baron, Sherry; Herbert, Robin; de Hernández, Micki Siegel; Teitelbaum, Susan; de la Hoz, Rafael E; Wisnivesky, Juan P; Landrigan, Phillip

    2011-09-01

    To date there have been no comprehensive reports of the work performedby 9/11 World Trade Center responders. 18,969 responders enrolled in the WTC Medical Monitoring and Treatment Program were used to describe workers’ pre-9/11 occupations, WTC work activities and locations from September 11, 2001 to June 2002. The most common pre-9/11 occupation was protective services (47%); other common occupations included construction, telecommunications, transportation, and support services workers. 14% served as volunteers. Almost one-half began work on 9/11 and >80% reported working on or adjacent to the ‘‘pile’’ at Ground Zero. Initially,the most common activity was search and rescue but subsequently, the activities of most responders related to their pre-9/11 occupations. Other major activities included security; personnel support; buildings and grounds cleaning; and telecommunications repair. The spatial, temporal, occupational, and task-related taxonomy reported here will aid the development of a job-exposure matrix, assist in assessment of disease risk, and improve planning and training for responders in future urban disasters.

  8. Responder analysis without dichotomization.

    PubMed

    Zhang, Zhiwei; Chu, Jianxiong; Rahardja, Dewi; Zhang, Hui; Tang, Li

    2016-01-01

    In clinical trials, it is common practice to categorize subjects as responders and non-responders on the basis of one or more clinical measurements under pre-specified rules. Such a responder analysis is often criticized for the loss of information in dichotomizing one or more continuous or ordinal variables. It is worth noting that a responder analysis can be performed without dichotomization, because the proportion of responders for each treatment can be derived from a model for the original clinical variables (used to define a responder) and estimated by substituting maximum likelihood estimators of model parameters. This model-based approach can be considerably more efficient and more effective for dealing with missing data than the usual approach based on dichotomization. For parameter estimation, the model-based approach generally requires correct specification of the model for the original variables. However, under the sharp null hypothesis, the model-based approach remains unbiased for estimating the treatment difference even if the model is misspecified. We elaborate on these points and illustrate them with a series of simulation studies mimicking a study of Parkinson's disease, which involves longitudinal continuous data in the definition of a responder.

  9. Autoshaping in micrencephalic rats.

    PubMed

    Goldstein, L H; Oakley, D A

    1989-06-01

    An autoshaping procedure in which the illumination of a lever was predictive of food reinforcement was used to compare learning in rats with micrencephaly induced by irradiation on the 16th day of gestation and in sham-irradiated controls. Both groups showed equivalent levels of lever-directed activity, and the micrencephalic animals differentiated as well as the control animals between the predictive lever and a nonpredictive lever. The micrencephalic animals were able to redistribute their lever-directed activity when the significance of the levers was reversed and did so more readily than the control animals. Results support the claim that association learning survives either traumatic or developmental neocortical damage and have implications for remedial procedures following both head injury and developmental cerebral pathology in humans.

  10. Discriminant cognitive factors in responder and non-responder patients with schizophrenia.

    PubMed

    Stip, E; Lussier, I; Ngan, E; Mendrek, A; Liddle, P

    1999-12-01

    To identify which improvements in cognitive function are associated with symptom resolution in schizophrenic patients treated with atypical antipsychotics. a prospective open trial with atypical neuroleptics (risperidone, clozapine, quetiapine). Inpatient and outpatient units, Institute of Psychiatry. Thirty-nine patients with schizophrenia according to DSM-IV criteria were included. Clinical and cognitive assessment were done at baseline (T0) and again after six months of treatment (T2). Twenty-five patients completed the trial. New-generation antipsychotics during six months. Patients were considered as responders if their PANSS score decreased at least 20% (n = 15) and non-responders if it did not (n = 10). a computerized cognitive assessment comprised tests of short-term-memory (digit span), explicit long-term memory (word pair learning), divided attention, selective attention and verbal fluency (orthographic and semantic). Clinical assessment included PANSS and ESRS. A discriminant function analysis was performed to determine which changes in cognitive performance predicted symptomatic response status. Semantic fluency and orthographic fluency were significant predictors. Together they correctly predicted responder status in 88% of cases. Memory was not a significant predictor of symptomatic response. Verbal fluency discriminated the responder from the non-responder group during a pharmacological treatment.

  11. Reduction by the Positive Allosteric Modulator of the GABAB Receptor, GS39783, of Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats Exposed to the “Sipper” Procedure

    PubMed Central

    Maccioni, Paola; Flore, Paolo; Carai, Mauro A. M.; Mugnaini, Claudia; Pasquini, Serena; Corelli, Federico; Gessa, Gian Luigi; Colombo, Giancarlo

    2010-01-01

    The present study was designed to evaluate (a) alcohol self-administration behavior of selectively bred, Sardinian alcohol-preferring (sP) rats exposed to the so-called “sipper” procedure (characterized by the temporal separation between alcohol-seeking and -taking phases), and (b) the effect of the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in sP rats exposed to this procedure. To this end, sP rats were initially trained to lever-respond under a reinforcement requirement (RR) 55 (RR55) for alcohol. Achievement of RR55 resulted in the 20-min presentation of the alcohol (15%, v/v)-containing sipper bottle. Once stable levels of lever-responding and alcohol consumption were reached, rats were treated with 0, 25, 50, and 100 mg/kg GS39783 (i.g.) 60 min before the self-administration session. Rats displayed robust alcohol-seeking (as suggested by relatively short latencies to the first lever-response and high frequencies of lever-responding) and -taking (as suggested by alcohol intakes averaging approximately 1.5 g/kg) behaviors. Pretreatment with GS39783 inhibited both alcohol-seeking (the number of rats achieving RR55 and the mean RR value were virtually halved) and -taking (the amount of self-administered alcohol was reduced by approximately 60%). The results of the present study suggest the power of the “sipper” procedure in triggering high levels of alcohol-seeking and -taking behavior in sP rats. Further, these results extend to this additional procedure of alcohol self-administration the capacity of GS39783 to reduce the motivational properties of alcohol and alcohol consumption in sP rats. PMID:21423431

  12. Discriminative stimulus effects of cocaine and amphetamine in rats following developmental exposure to polychlorinated biphenyls (PCBs)

    PubMed Central

    Sable, Helen J. K.; Monaikul, Supida; Poon, Emily; Eubig, Paul A.; Schantz, Susan L.

    2010-01-01

    Polychlorinated biphenyls (PCBs) are environmental neurotoxicants known to affect the brain dopaminergic (DA) system. This project investigated whether developmental exposure to PCBs would alter the discriminative stimulus effects of psychostimulant drugs known to act on the DA system. Female Long-Evans rats were orally exposed to 0, 3, or 6 mg/kg/day of an environmentally relevant PCB mixture from four weeks prior to breeding through weaning of their litters on PND 21. When they reached adulthood one male and female/litter were trained to discriminate cocaine (10.0 mg/kg, IP) from saline by repeatedly pairing cocaine injections with reinforcement on one operant response lever, and saline injections with reinforcement on the other lever. After response training, generalization tests to four lower doses of cocaine (7.5, 5.0, 2.5, and 1.25 mg/kg, IP) and to amphetamine (1.0, 0.5, 0.25, and 0.125 mg/kg, IP) were given two days/week, with additional training dose days in-between. Percent responding of the PCB-exposed rats on the cocaine-paired lever was significantly higher than that of controls for the highest generalization dose of cocaine, and lower than that of controls for the highest dose of amphetamine. Response rate and percent responding on the cocaine lever did not differ among the exposure groups on the days when the training dose of cocaine was given, suggesting the generalization test results were not due to pre-existing differences in discrimination ability or rate of responding. These findings suggest developmental PCB exposure can alter the interoceptive cues of psychostimulants. PMID:20933596

  13. Levers and Mixtures: An Integrated Science and Mathematics Activity to Solve Problems

    ERIC Educational Resources Information Center

    Alpaslan, Muhammet Mustafa

    2017-01-01

    In recent years, the integration of science and mathematics has become popular among educators because of its potential benefits for student learning. The purpose of this study is to introduce a two-day interdisciplinary lesson that brings science and mathematics concepts together, actively engaging students in working with percentages of the…

  14. Deep brain stimulation of the subcallosal cingulate gyrus for depression: anatomical location of active contacts in clinical responders and a suggested guideline for targeting.

    PubMed

    Hamani, Clement; Mayberg, Helen; Snyder, Brian; Giacobbe, Peter; Kennedy, Sidney; Lozano, Andres M

    2009-12-01

    Deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG), including Brodmann area 25, is currently being investigated for the treatment of major depressive disorder (MDD). As a potential emerging therapy, optimal target selection within the SCG has still to be determined. The authors compared the location of the electrode contacts in responders and nonresponders to DBS of the SCG and correlated the results with clinical outcome to help in identifying the optimal target within the region. Based on the location of the active contacts used for long-term stimulation in responders, the authors suggest a standardized method of targeting the SCG in patients with MDD. Postoperative MR imaging studies of 20 patients with MDD treated with DBS of the SCG were analyzed. The authors assessed the location of the active contacts relative to the midcommissural point and in relation to anatomical landmarks within the medial aspect of the frontal lobe. For this, a grid with 2 main lines was designed, with 1 line in the anterior-posterior and 1 line in the dorsal-ventral axis. Each of these lines was divided into 100 units, and data were converted into percentages. The anterior-posterior line extended from the anterior commissure (AC) to the projection of the anterior aspect of the corpus callosum (CCa). The dorsal-ventral line extended from the inferior portion of the CC (CCi) to the most ventral aspect of the frontal lobe (abbreviated "Fr" for the formula). Because the surgical technique did not vary across patients, differences in stereotactic coordinates between responders and nonresponders did not exceed 1.5 mm in any axis (x, y, or z). In patients who responded to the procedure, contacts used for long-term stimulation were in close approximation within the SCG. In the anterior-posterior line, these contacts were located within a 73.2 +/- 7.7 percentile distance from the AC (with the AC center being 0% and the line crossing the CCa being 100%). In the dorsal

  15. Subject competency of teachers and level of dependence on resource packs to teach levers, gears and pulleys

    NASA Astrophysics Data System (ADS)

    Jarvis, Tina; Cavendish, Sue

    1994-12-01

    This pilot study set out to ascertain whether the level of dependence on resource material is related to teaching experience, existing understanding in mechanics, and perceived self confidence in science and technology. Details of teaching experience and qualifications were obtained from 11 experienced teachers and 10 initial teacher trainees, and understanding of mechanics was assessed by a written test. Each teacher worked through one commercially produced inservice pack about levers, pulleys or gears, and then prepared a 30 minute session for 4 ten year old children. Videos of the sessions were analysed with respect to the extent to which the pack was the sole focus; the amount of integration with other teaching aids and approaches; and the extent individual children's needs were satisfied. Although science qualifications influenced teacher confidence, they were not accurate predictors of relevant knowledge and teaching competence. As the majority of teachers followed pack instructions closely, the children's needs were not always well matched.

  16. Communication: Listening and Responding. Affective 4.0.

    ERIC Educational Resources Information Center

    Borgers, Sherry B., Comp.; Ward, G. Robert, Comp.

    This module is designed to provide practice in listening effectively and in responding to messages sent by another. The module is divided into two sets of activities, the first is the formation of a triad enabling the student to investigate the following: do you listen, listening and the unrelated response, incomplete listening, listening for…

  17. The Effect of Varying Biting Position on Relative Jaw Muscle EMG activity

    DTIC Science & Technology

    1988-09-01

    with muscle force is the key to 13 this approach as it allows inference of muscle contraction activity from EMG data. This relationship has been the...5! 15 LITERATURE REVIEW Introduction: The study of the physiology of bite force, muscle contraction force, joint reaction force and the lever system...Currently, the best method of indirectly observing muscle contraction activity is through electromyography. Although there appears to be a time delay

  18. Serial Killers: Academic Libraries Respond to Soaring Costs.

    ERIC Educational Resources Information Center

    McCarthy, Paul

    1994-01-01

    Discusses ways in which academic libraries are responding to rising costs of serials. Topics addressed include pricing by publishers; the effect of journal cancellations on research activities; interlibrary loans and document delivery services; coordinated cancelling; electronic journals; and experiences at the University of Arizona. (LRW)

  19. Resilience among first responders.

    PubMed

    Pietrantoni, Luca; Prati, Gabriele

    2008-12-01

    Emergency rescue personnel can be considered a "high risk" occupational group in that they could experience a broad range of health and mental health consequences as a result of work-related exposures to critical incidents. This study examined the resilience factors that protect mental health among first responders. Nine hundred and sixty-one first responders filled out an on-line questionnaire, containing measure of sense of community, collective efficacy, self-efficacy and work-related mental health outcomes (compassion fatigue, burnout and compassion satisfaction). First responders reported high level of compassion satisfaction and low level of burnout and compassion fatigue. Compassion fatigue was predicted by self-efficacy, burnout was predicted by self-efficacy, collective efficacy and sense of community, compassion satisfaction was predicted by self-efficacy and sense of community. Resilience following critical events is common among first responders. Self-efficacy, collective efficacy and sense of community could be considered resilience factors that preserve first responders' work-related mental health.

  20. The effects of amphetamine sensitization on conditioned inhibition during a Pavlovian-instrumental transfer task in rats.

    PubMed

    Shiflett, Michael W; Riccie, Meaghan; DiMatteo, RoseMarie

    2013-11-01

    Psychostimulant sensitization heightens behavioral and motivational responses to reward-associated stimuli; however, its effects on stimuli associated with reward absence are less understood. We examined whether amphetamine sensitization alters performance during Pavlovian-instrumental transfer (PIT) to conditioned excitors and inhibitors. We further sought to characterize the effects of amphetamine sensitization on learning versus performance by exposing rats to amphetamine prior to Pavlovian training or between training and test. Adult male Long-Evans rats were given conditioned inhibition (A+/AX-) and Pavlovian (B+) training, followed by variable-interval instrumental conditioning. Rats were sensitized to D-amphetamine (2 mg/kg daily injections for 7 days) or served as non-exposed controls. Rats were given a PIT test, in which they were presented with stimulus B alone or in compound with the conditioned inhibitor (BX). During the PIT test, control rats significantly reduced instrumental responding on BX trials (to approximately 50 % of responding to B). Amphetamine sensitization prior to Pavlovian conditioning increased lever pressing on BX trials and reduced lever pressing on B trials compared to controls. Amphetamine sensitization between training and test increased lever pressing on B and BX trials compared to controls. No effects of sensitization were observed on conditioned food cup approach. Amphetamine sensitization increases instrumental responding during PIT to a conditioned inhibitor by enhancing the excitation of conditioned stimuli and reducing the inhibition of conditioned inhibitors.

  1. Feeling good: autonomic nervous system responding in five positive emotions.

    PubMed

    Shiota, Michelle N; Neufeld, Samantha L; Yeung, Wan H; Moser, Stephanie E; Perea, Elaine F

    2011-12-01

    Although dozens of studies have examined the autonomic nervous system (ANS) aspects of negative emotions, less is known about ANS responding in positive emotion. An evolutionary framework was used to define five positive emotions in terms of fitness-enhancing function, and to guide hypotheses regarding autonomic responding. In a repeated measures design, participants viewed sets of visual images eliciting these positive emotions (anticipatory enthusiasm, attachment love, nurturant love, amusement, and awe) plus an emotionally neutral state. Peripheral measures of sympathetic and vagal parasympathetic activation were assessed. Results indicated that the emotion conditions were characterized by qualitatively distinct profiles of autonomic activation, suggesting the existence of multiple, physiologically distinct positive emotions. (c) 2011 APA, all rights reserved.

  2. Comparison between male and female rats in a model of self-administration of a chocolate-flavored beverage: Behavioral and neurochemical studies.

    PubMed

    Contini, Andrea; Sanna, Fabrizio; Maccioni, Paola; Colombo, Giancarlo; Argiolas, Antonio

    2018-05-15

    The existence of sex differences was studied in a rat model of operant self-administration of a chocolate-flavored beverage (CFB), which possesses strong reinforcing properties and is avidly consumed by rats. Whether these differences occurred concomitantly to changes in extracellular dopamine in the dialysate obtained from the nucleus accumbens, was assessed by intracerebral microdialysis. Male, ovariectomized and intact female rats showed similar self-administration profiles, with minor differences in both acquisition and maintenance phases. Intact females self-administered larger amounts of CFB, when expressed per body weight, than males and ovariectomized females, in spite of similar values of lever-responding, latency to the first lever-response and consumption efficiency (a measure of rat's licking effectiveness) in males, ovariectomized and intact females and no difference in breakpoint value and number of lever-responses emerged when males, ovariectomized and intact females were exposed to a progressive ratio schedule of reinforcement. Intracerebral microdialysis revealed a slight but significant increase in dopamine activity in the shell of the nucleus accumbens of male rats when compared to intact female rats during CFB self-administration. The above differences may be caused by the hormonal (mainly estradiol) fluctuations that occur during the estrus cycle in intact females. Accordingly, in intact females CFB self-administration and dopamine activity were found to fluctuate across the estrus cycle, with lower parameters of CFB self-administration and lower dopamine activity in the Proestrus and Estrus phases vs. the Metestrus and Diestrus phases of the cycle. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Freeze or flee? Negative stimuli elicit selective responding.

    PubMed

    Estes, Zachary; Verges, Michelle

    2008-08-01

    Humans preferentially attend to negative stimuli. A consequence of this automatic vigilance for negative valence is that negative words elicit slower responses than neutral or positive words on a host of cognitive tasks. Some researchers have speculated that negative stimuli elicit a general suppression of motor activity, akin to the freezing response exhibited by animals under threat. Alternatively, we suggest that negative stimuli only elicit slowed responding on tasks for which stimulus valence is irrelevant for responding. To discriminate between these motor suppression and response-relevance hypotheses, we elicited both lexical decisions and valence judgments of negative words and positive words. Relative to positive words (e.g., kitten), negative words (e.g., spider) elicited slower lexical decisions but faster valence judgments. Results therefore indicate that negative stimuli do not cause a generalized motor suppression. Rather, negative stimuli elicit selective responding, with faster responses on tasks for which stimulus valence is response-relevant.

  4. Pavlovian conditioning with ethanol: sign-tracking (autoshaping), conditioned incentive, and ethanol self-administration.

    PubMed

    Krank, Marvin D

    2003-10-01

    Conditioned incentive theories of addictive behavior propose that cues signaling a drug's reinforcing effects activate a central motivational state. Incentive motivation enhances drug-taking and drug-seeking behavior. We investigated the behavioral response to cues associated with ethanol and their interaction with operant self-administration of ethanol. In two experiments, rats received operant training to press a lever for a sweetened ethanol solution. After operant training, the animals were given Pavlovian pairings of a brief and localized cue light with the sweetened ethanol solution (no lever present). Lever pressing for ethanol was then re-established, and the behavioral effects of the cue light were tested during an ethanol self-administration session. The conditioned responses resulting from pairing cue lights with the opportunity to ingest ethanol had three main effects: (1) induction of operant behavior reinforced by ethanol, (2) stimulation of ethanol-seeking behavior (magazine entries), and (3) signal-directed behavior (i.e., autoshaping, or sign-tracking). Signal-directed behavior interacted with the other two effects in a manner predicted by the location of the cue light. These conditioned responses interact with operant responding for ethanol reinforcement. These findings demonstrate the importance of Pavlovian conditioning effects on ethanol self-administration and are consistent with conditioned incentive theories of addictive behavior.

  5. Effects of pramipexole on the acquisition of responding with opioid-conditioned reinforcement in the rat

    PubMed Central

    Bertz, Jeremiah W.; Chen, Jianyong; Woods, James H.

    2014-01-01

    Rationale Dopamine D3 receptor-preferring ligands may be able to modify the conditioned reinforcing effects of drug-associated stimuli. In evaluating the effects of these compounds, it is important to clarify the extent to which responding depends on (1) conditioned reinforcement vs. other behavioral mechanisms and (2) dopamine D3 vs. D2 receptor activity. Objectives Use behaviorally stringent new-response acquisition procedures to characterize the effects of the D3-preferring agonist, pramipexole, on the conditioned reinforcing effects of a stimulus paired with the opioid agonist, remifentanil. Methods First, in Pavlovian conditioning (PAV) sessions, rats received response-independent IV injections of remifentanil and presentations of a light–noise stimulus. In separate groups, injections and stimuli either always co-occurred (“paired PAV”) or occurred with no consistent relationship (“random PAV” control). Next, in instrumental acquisition (ACQ) sessions, all animals could respond in two nose-poke manipulanda: an active nose-poke, which produced the stimulus alone, or an inactive nose-poke. Pramipexole was injected SC prior to ACQ sessions with or without pretreatments of the D3-preferring antagonist, SB-277011A, or the dopamine D2-preferring antagonist, L-741,626. Results After paired PAV, but not random PAV, rats acquired nose-poke responding during ACQ (i.e., active > inactive). Pramipexole dose-dependently increased active responding without changing inactive responding. Pramipexole-induced increases in responding were blocked by pretreatment with L-741,626, but not SB-277011A. Conclusions Pramipexole specifically enhanced remifentanil-conditioned reinforcement: active responding was selectively increased only after the stimulus was paired with remifentanil. Although pramipexole is D3-preferring, the antagonist effects obtained presently suggest an important role for the D2 receptor in opiod-conditioned reinforcement. PMID:24985891

  6. "Responding to Climate Change" Course: Research Integration

    NASA Astrophysics Data System (ADS)

    Pfirman, S. L.; Bowman, J. S.

    2015-12-01

    The "Responding to Climate Change" Barnard/Columbia course integrates current research as well as hands-on research-based activities modified for a classroom environment. The course covers the major response themes of adaptation, mitigation and communication. In the spring of 2015 the course was oriented around Arctic and Antarctic case studies. Each week a different theme is addressed, such as the physical setting, changing ecosystems, governance issues, perspectives of residents and indigenous peoples, geoengineering, commercial interests, security, and health and developmental issues. Frequent guest lectures from thematic experts keep the course grounded in realities and present the students with cutting edge issues. Activities match the weekly theme, for example during the week on Arctic development, students engage with the marine spatial planning simulation Arctic SMARTIC (Strategic Management of Resources in Times of Change) based on research on Arctic sea ice trends and projections coupled with current and projected developmental interests of stakeholders. Created under the Polar Learning and Responding: PoLAR Climate Change Education Partnership (thepolarhub.org), a complete set of SMARTIC resources is available on line for use by others (http://www.camelclimatechange.org/view/article/175297/). The Responding to Climate Change course is designed to be current and respond to events. For the Arctic case study, students developed proposals for the US State Department as the upcoming Chair of the Arctic Council. Student evaluations indicated that they appreciated the opportunity to connect science with policy and presentation of preliminary proposals in a workshop format was valued as a way to develop and hone their ideas. An additional finding was that students were surprisingly tolerant of technical issues when guest lecturers were linked in via Skype, allowing interaction with thematic experts across the US. Students commented positively on this exposure to

  7. The effects of exercise on cocaine self-administration, food-maintained responding, and locomotor activity in female rats: importance of the temporal relationship between physical activity and initial drug exposure.

    PubMed

    Smith, Mark A; Witte, Maryam A

    2012-12-01

    Previous studies have reported that exercise decreases cocaine self-administration in rats with long-term access (8+ weeks) to activity wheels in the home cage. The purpose of this study was to (a) examine the importance of the temporal relationship between physical activity and initial drug exposure, (b) determine the effects of exercise on responding maintained by a nondrug reinforcer (i.e., food), and (c) investigate the effects of exercise on cocaine-induced increases in locomotor activity. To this end, female rats were obtained at weaning and divided into 4 groups: (a) EXE-SED rats were housed in exercise cages for 6 weeks and then transferred to sedentary cages after the first day of behavioral testing; (b) SED-EXE rats were housed in sedentary cages for 6 weeks and then transferred to exercise cages after the first day of behavioral testing; (c) SED-SED rats remained in sedentary cages for the duration of the study; and (d) EXE-EXE rats remained in exercise cages for the duration of the study. Relative to the sedentary group (SED-SED), exercise reduced cocaine self-administration in both groups with access to activity wheels after initial drug exposure (EXE-EXE, SED-EXE) but did not reduce cocaine self-administration in the group with access to activity wheels only before drug exposure (EXE-SED). Exercise also decreased the effects of cocaine on locomotor activity but did not reduce responding maintained by food. These data suggest that exercise may reduce cocaine use in drug-experienced individuals with no prior history of aerobic activity without decreasing other types of positively reinforced behaviors.

  8. Exploring community resilience in workforce communities of first responders serving Katrina survivors.

    PubMed

    Wyche, Karen Fraser; Pfefferbaum, Rose L; Pfefferbaum, Betty; Norris, Fran H; Wisnieski, Deborah; Younger, Hayden

    2011-01-01

    Community resilience activities were assessed in workplace teams that became first responders for Hurricane Katrina survivors. Community resilience was assessed by a survey, focus groups, and key informant interviews. On the survey, 90 first responders ranked their team's disaster response performance as high on community resilience activities. The same participants, interviewed in 11 focus groups and 3 key informant interviews, discussed how their teams engaged in community resilience activities to strengthen their ability to deliver services. Specifically, their resilient behaviors were characterized by: shared organizational identity, purpose, and values; mutual support and trust; role flexibility; active problem solving; self-reflection; shared leadership; and skill building. The implications for research, policy, practice, and education of professionals are discussed. © 2011 American Orthopsychiatric Association.

  9. Comparison of the effect of the GABAB receptor agonist, baclofen, and the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in three different lines of alcohol-preferring rats

    PubMed Central

    Maccioni, Paola; Zaru, Alessandro; Loi, Barbara; Lobina, Carla; Carai, Mauro A.M.; Gessa, Gian Luigi; Capra, Alessandro; Mugnaini, Claudia; Pasquini, Serena; Corelli, Federico; Hyytiä, Petri; Lumeng, Lawrence; Colombo, Giancarlo

    2012-01-01

    Background Administration of the GABAB receptor agonist, baclofen, and positive allosteric modulator (PAM), GS39783, has been repeatedly reported to suppress multiple alcohol-related behaviors, including operant oral alcohol self-administration, in rats. The present study was designed to compare the effect of baclofen and GS39783 on alcohol self-administration in three lines of selectively bred, alcohol-preferring rats: Indiana alcohol-preferring (P), Sardinian alcohol-preferring (sP), and Alko Alcohol (AA). Methods Rats of each line were initially trained to respond on a lever, on a fixed ratio (FR) 4 (FR4) schedule of reinforcement, to orally self-administer alcohol (15%, v/v) in daily 30-min sessions. Once responding reached stable levels, rats were exposed to a sequence of experiments testing baclofen (0, 1, 1.7, and 3 mg/kg; i.p.) and GS39783 (0, 25, 50, and 100 mg/kg; i.g.) on FR4 and progressive ratio (PR) schedules of reinforcement. Finally, to assess the specificity of baclofen and GS39783 action, rats were slightly food-deprived and trained to lever-respond for food pellets. Results The rank of order of the reinforcing and motivational properties of alcohol was: P>sP>AA rats. Under both FR and PR schedules of reinforcement, the rank of order of potency and efficacy of baclofen and GS39783 in suppressing alcohol self-administration was: P>sP>AA rats. Only the highest dose of baclofen reduced lever-responding for food pellets; this effect was common to all three rat lines. Conversely, no dose of GS39783 altered lever-responding for food in any rat line. Conclusions These results suggest that: (a) the strength of the reinforcing and motivational properties of alcohol differ among P, sP, and AA rats; (b) the reinforcing and motivational properties of alcohol in P, sP, and AA rats are differentially sensitive to treatment with baclofen and GS39783; (c) the heterogeneity in sensitivity to baclofen and GS39783 of alcohol self-administration in P, sP, and AA rats

  10. Aid and Innovation: How Federal Financial Aid Policy Impacts Student Success and How States Can Respond. Policy Bulletin

    ERIC Educational Resources Information Center

    Reichert, Katrina

    2012-01-01

    From Washington to Connecticut, Arkansas to Indiana, state policymakers and community college leaders are focused on building completion pathways to ensure that more students succeed in postsecondary education and make smooth transitions to careers. Financial aid is both an effective and a necessary policy lever to promote this goal. Not only do…

  11. Acute ethanol effects on neural encoding of reward size and delay in the nucleus accumbens

    PubMed Central

    Gutman, Andrea L.

    2016-01-01

    Acute ethanol administration can cause impulsivity, resulting in increased preference for immediately available rewards over delayed but more valuable alternatives. The manner in which reward size and delay are represented in neural firing is not fully understood, and very little is known about ethanol effects on this encoding. To address this issue, we used in vivo electrophysiology to characterize neural firing in the core of the nucleus accumbens (NAcc) in rats responding for rewards that varied in size or delay after vehicle or ethanol administration. The NAcc is a central element in the circuit that governs decision-making and importantly, promotes choice of delayed rewards. We found that NAcc firing in response to reward-predictive cues encoded anticipated reward value after vehicle administration, but ethanol administration disrupted this encoding, resulting in a loss of discrimination between immediate and delayed rewards in cue-evoked neural responses. In addition, NAcc firing occurring at the time of the operant response (lever pressing) was inversely correlated with behavioral response latency, such that increased firing rates were associated with decreased latencies to lever press. Ethanol administration selectively attenuated this lever press-evoked firing when delayed but not immediate rewards were expected. These effects on neural firing were accompanied by increased behavioral latencies to respond for delayed rewards. Our results suggest that ethanol effects on NAcc cue- and lever press-evoked encoding may contribute to ethanol-induced impulsivity. PMID:27169507

  12. Promoter activity of polypyrimidine tract-binding protein genes of potato responds to environmental cues.

    PubMed

    Butler, Nathaniel M; Hannapel, David J

    2012-12-01

    Polypyrimidine tract-binding (PTB) proteins are RNA-binding proteins that target specific RNAs for post-transcriptional processing by binding cytosine/uracil motifs. PTBs have established functions in a range of RNA processes including splicing, translation, stability and long-distance transport. Six PTB-like genes identified in potato have been grouped into two clades based on homology to other known plant PTBs. StPTB1 and StPTB6 are closely related to a PTB protein discovered in pumpkin, designated CmRBP50, and contain four canonical RNA-recognition motifs. CmRBP50 is expressed in phloem tissues and functions as the core protein of a phloem-mobile RNA/protein complex. Sequence from the potato genome database was used to clone the upstream sequence of these two PTB genes and analyzed to identify conserved cis-elements. The promoter of StPTB6 was enriched for regulatory elements for light and sucrose induction and defense. Upstream sequence of both PTB genes was fused to β-glucuronidase and monitored in transgenic potato lines. In whole plants, the StPTB1 promoter was most active in leaf veins and petioles, whereas StPTB6 was most active in leaf mesophyll. Both genes are active in new tubers and tuber sprouts. StPTB6 expression was induced in stems and stolon sections in response to sucrose and in leaves or petioles in response to light, heat, drought and mechanical wounding. These results show that CmRBP50-like genes of potato exhibit distinct expression patterns and respond to both developmental and environmental cues.

  13. 22 CFR 1006.1000 - Respondent.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Respondent. 1006.1000 Section 1006.1000 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 1006.1000 Respondent. Respondent means a person against whom an agency has initiated a debarment or...

  14. 29 CFR 1471.1000 - Respondent.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Respondent. 1471.1000 Section 1471.1000 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 1471.1000 Respondent. Respondent means a person against whom an...

  15. 22 CFR 1508.1000 - Respondent.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Respondent. 1508.1000 Section 1508.1000 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 1508.1000 Respondent. Respondent means a person against whom an agency has initiated a debarment...

  16. Recovery of Pavlovian sign-tracking (autoshaping) following the discontinuation of inter-trial interval food in rats.

    PubMed

    Kearns, David N; Weiss, Stanley J

    2007-07-01

    In pigeons, Pavlovian autoshaped keypecking produced by keylight-food pairings has been eliminated by introducing food during periods between CS presentations (i.e., during the inter-trial intervals). Keypecking eliminated in this manner reappears when the inter-trial USs are discontinued even though the CS is no longer paired with US. The present experiment investigated whether this recovery of responding produced by discontinuing unpaired inter-trial US presentations could be extended to another species, rats, within a Pavlovian sign-tracking paradigm. Rats were initially trained on a procedure where insertion of one retractable lever (CS(+)) was followed, response independently, with food, while insertion of another lever (CS(-)) was not paired with food. Rats quickly came to contact the CS(+) lever at high rates, but contacted the CS(-) lever infrequently. In the next phase, CS(+) was no longer followed by food. Explicitly unpaired food was presented only during the inter-trial intervals when both levers were absent. This treatment essentially eliminated the sign-tracking response. In the final phase, the unpaired inter-trial food presentations were discontinued while both CSs continued to be presented without food. This produced a significant recovery of the sign-tracking elicited by the CS(+) lever, extending the species generality of the Pavlovian resurgence phenomenon that has previously only been reported in pigeons, to rats.

  17. Development of responder criteria for multicomponent non-pharmacological treatment in fibromyalgia.

    PubMed

    Vervoort, Vera M; Vriezekolk, Johanna E; van den Ende, Cornelia H

    2017-01-01

    There is a need to identify individual treatment success in patients with fibromyalgia (FM) who received non-pharmacological treatment. The present study described responder criteria for multicomponent non-pharmacological treatment in FM, and estimated and compared their sensitivity and specificity. Candidate responder sets were 1) identified in literature; and 2) formulated by expert group consensus. All candidate responder sets were tested in a cohort of 129 patients with FM receiving multicomponent non-pharmacological treatment. We used two gold standards (both therapist's and patient's perspective), assessed at six months after the start of treatment. Seven responder sets were defined (three identified in literature and four formulated by expert group consensus), and comprised combinations of domains of 1) pain; 2) fatigue; 3) patient global assessment (PGA); 4) illness perceptions; 5) limitations in activities of daily living (ADL); and 6) sleep. The sensitivity and specificity of literature-based responder sets (n=3) ranged between 17%-99% and 15%-95% respectively, whereas the expert-based responder sets (n=4) performed slightly better with regard to sensitivity (range 41%-81%) and specificity (range 50%-96%). Of the literature-based responder sets the OMERACT-OARSI responder set with patient's gold standard performed best (sensitivity 63%, specificity 75% and ROC area = 0.69). Overall, the expert-based responder set comprising the domains illness perceptions and limitations in ADL with patient's gold standard performed best (sensitivity 47%, specificity 96% and ROC area = 0.71). We defined sets of responder criteria for multicomponent non-pharmacological treatment in fibromyalgia. Further research should focus on the validation of those sets with acceptable performance.

  18. 29 CFR 98.1000 - Respondent.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Respondent. 98.1000 Section 98.1000 Labor Office of the Secretary of Labor GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 98.1000 Respondent. Respondent means a person against whom an agency has initiated a debarment or suspension action. ...

  19. 21 CFR 1404.1000 - Respondent.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Respondent. 1404.1000 Section 1404.1000 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 1404.1000 Respondent. Respondent means a person against whom an agency has initiated a debarment...

  20. Amitriptyline converts non-responders into responders to low-frequency electroacupuncture-induced analgesia in rats.

    PubMed

    Fais, Rafael S; Reis, G M; Rossaneis, A C; Silveira, J W S; Dias, Q M; Prado, W A

    2012-07-26

    The purpose of this study was to examine whether the use of intraperitoneal or intrathecal amitriptyline combined with electroacupuncture modifies the tail-flick reflex and incision pain in rats that normally do not have analgesia to electroacupuncture in the tail-flick test (non-responder rats). Changes in the nociceptive threshold of intraperitoneal or intrathecal saline- or amitriptyline-treated non-responder rats were evaluated using the tail-flick or incision pain tests before, during and after a 20-min period of electroacupuncture, applied at 2 Hz to the Zusanli and Sanynjiao acupoints. Amitriptyline was used at doses of 0.8 mg/kg or 30 μg/kg by intraperitoneal or intrathecal route, respectively. At these doses, amitriptyline has no effect against thermal or incision pain in rats. Rats selected as non-responders to the analgesic effect of electroacupuncture 2 Hz in tail-flick and incision pain tests become responders after an intraperitoneal or intrathecal injection of amitriptyline. Amitriptyline converts non-responder rats to rats that respond to electroacupuncture with analgesia in a model of thermal phasic pain and anti-hyperalgesia in a model of incision pain. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Emergency responders' critical infrared (ERCI)

    NASA Astrophysics Data System (ADS)

    Konsin, Larry S.

    2004-08-01

    Emergency Responders (Fire, Police, Medical, and Emergency Management) face a high risk of injury or death. Even before September 11, 2001, public and private organizations have been driven to better protect Emergency Responders through education, training and improved technology. Recent research on Emergency Responder safety, health risks, and personal protective requirements, shows infrared (IR) imaging as a critical need. Today"s Emergency Responders are increasingly challenged to do more, facing demands requiring technological assistance and/or solutions. Since the introduction of Fire Service IR imaging in the mid 1990s, applications have increased. Emergency response IR is no longer just seeing through smoke to find victims or the seat of a fire. Many more mission critical needs now exist across the broad spectrum of emergency response. At the same time, Emergency Responder injuries and deaths are increasing. The Office of Domestic Preparedness (ODP) has also recognized IR imaging as critical in protecting our communities -- and in preventing many of the injuries and deaths of Emergency Responders. Currently, only 25% of all fire departments (or less than 7% of individual firefighters) have IR imaging. Availability to Police, EMS and Emergency Management is even lower. Without ERCI, Emergency Responders and our communities are at risk.

  2. Exceptional responders in conservation.

    PubMed

    Post, Gerald; Geldmann, Jonas

    2017-08-30

    Conservation operates within complex systems with incomplete knowledge of the system and the interventions utilized. This frequently results in the inability to find generally applicable methods to alleviate threats to Earth's vanishing wildlife. One approach used in medicine and the social sciences has been to develop a deeper understanding of positive outliers. Where such outliers share similar characteristics, they may be considered exceptional responders. We devised a 4-step framework for identifying exceptional responders in conservation: identification of the study system, identification of the response structure, identification of the threshold for exceptionalism, and identification of commonalities among outliers. Evaluation of exceptional responders provides additional information that is often ignored in randomized controlled trials and before-after control-intervention experiments. Interrogating the contextual factors that contribute to an exceptional outcome allow exceptional responders to become valuable pieces of information leading to unexpected discoveries and novel hypotheses. © 2017 Society for Conservation Biology.

  3. Parametric changes in response equilibrium during an intra-cranial self stimulation (ICSS) task: can reward value be assessed independently of absolute threshold?

    PubMed

    Easterling, K W; Holtzman, S G

    1997-01-01

    Traditional ICSS methodologies have attempted to evaluate changes in the rewarding value of brain stimulation by assessing the lowest value of the stimulation that will support responding. However, orderly changes in suprathreshold indicants of hedonic magnitude such as titration point have been shown. In the present experiments, rats were trained to respond on two ICSS autotitration schedules in which every response on one lever produced stimulation of the medial forebrain bundle, and every Xth response decreased either the stimulation current or the stimulation frequency. At any time, a response on a second "reset" lever restored the stimulation current or frequency available on the stimulation lever to its starting level and operationally defined changes in "reward value". In order to study this titration point measure, two response requirements (responses/stepdown; step size) and two stimulation parameters (initial stimulation level; train duration) were systematically varied. Under both current and frequency titration schedules, data indicated that response rate and titration point remained stable over repeated trials and multiple testing days--parameters being constant. Across all conditions, compared to the frequency titration schedule, subjects responding under the current titration schedule showed significantly higher titration points and lower rates of responding. Indicating the independence of rate and titration point data, parametric manipulations did not affect titration point and rate data concurrently. Results support the conclusion that titration point is a relative measure of "reward value" that is generally independent of response rate, but that is affected by manipulations that alter the amount of stimulation available between "resets". Additional work is needed in order to determine the relationship between the magnitude of stimulation needed to maintain minimal responding and that needed to maintain response equilibrium in an autotitration task.

  4. The role of the basolateral amygdala in punishment

    PubMed Central

    Jean-Richard-Dit-Bressel, Philip

    2015-01-01

    Aversive stimuli not only support fear conditioning to their environmental antecedents, they also punish behaviors that cause their occurrence. The amygdala, especially the basolateral nucleus (BLA), has been critically implicated in Pavlovian fear learning but its role in punishment remains poorly understood. Here, we used a within-subjects punishment task to assess the role of the BLA in the acquisition and expression of punishment as well as aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of GABA agonists baclofen and muscimol (BM) into the BLA significantly impaired the acquisition of this suppression. BLA inactivations using BM also reduced the expression of well-trained punishment. There was anatomical segregation within the BLA so that caudal, not rostral, BLA was implicated in punishment. However, when presented with punished and unpunished levers simultaneously in a choice test without deliveries of shock punisher, rats expressed a preference for unpunished over the punished lever and BLA inactivations had no effect on this preference. Taken together, these findings indicate that the BLA is important for both the acquisition and expression of punishment but not for aversive choice. This role appears to be linked to neurons in the caudal BLA, rather than rostral BLA, although the circuitry that contributes to this functional segregation is currently unknown, and is most parsimoniously interpreted as a role for caudal BLA in determining the aversive value of the shock punisher. PMID:25593299

  5. Access to a running wheel inhibits the acquisition of cocaine self-administration.

    PubMed

    Smith, Mark A; Pitts, Elizabeth G

    2011-12-01

    Physical activity decreases cocaine self-administration in laboratory animals and is associated with positive outcomes in substance abuse treatment programs; however, less is known about its efficacy in preventing the establishment of regular patterns of substance use in drug-naive individuals. The purpose of the present study was to examine the effects of access to a running wheel on the acquisition of cocaine self-administration in experimentally naive rats. Male, Long-Evans rats were obtained at weaning and assigned to sedentary (no wheel) or exercising (access to wheel) conditions immediately upon arrival. After six weeks, rats were surgically implanted with intravenous catheters and placed in operant conditioning chambers for 2 h/day for 15 consecutive days. Each session began with a noncontingent priming infusion of cocaine, followed by a free-operant period in which each response on the active lever produced an infusion of cocaine on a fixed ratio (FR1) schedule of reinforcement. For days 1-5, responding was reinforced with 0.25 mg/kg/infusion cocaine; for days 6-15, responding was reinforced with 0.75 mg/kg/infusion cocaine. In addition, all rats were calorically restricted during days 11-15 to 85% to 95% of their free-feeding body weight. Compared to sedentary rats, exercising rats acquired cocaine self-administration at a significantly slower rate and emitted significantly fewer active lever presses during the 15 days of behavioral testing. These data indicate that access to a running wheel inhibits the acquisition of cocaine self-administration, and that physical activity may be an effective intervention in substance abuse prevention programs. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Brain Changes in Responders vs. Non-Responders in Chronic Migraine: Markers of Disease Reversal

    PubMed Central

    Hubbard, Catherine S.; Becerra, Lino; Smith, Jonathan H.; DeLange, Justin M.; Smith, Ryan M.; Black, David F.; Welker, Kirk M.; Burstein, Rami; Cutrer, Fred M.; Borsook, David

    2016-01-01

    The aim of this study was to identify structural and functional brain changes that accompanied the transition from chronic (CM; ≥15 headache days/month) to episodic (EM; <15 headache days/month) migraine following prophylactic treatment with onabotulinumtoxinA (BoNT-A). Specifically, we examined whether CM patients responsive to prophylaxis (responders; n = 11), as evidenced by a reversal in disease status (defined by at least a 50% reduction in migraine frequency and <15 headache days/month), compared to CM patients whose migraine frequency remained unchanged (non-responders; n = 12), showed differences in cortical thickness using surface-based morphometry. We also investigated whether areas showing group differences in cortical thickness displayed altered resting-state functional connectivity (RS-FC) using seed-to-voxel analyses. Migraine characteristics measured across groups included disease duration, pain intensity and headache frequency. Patient reports of headache frequency over the 4 weeks prior to (pre-treatment) and following (post-treatment) prophylaxis were compared (post minus pre) and this measure served as the clinical endpoint that determined group assignment. All patients were scanned within 2 weeks of the post-treatment visit. Results revealed that responders showed significant cortical thickening in the right primary somatosensory cortex (SI) and anterior insula (aINS), and left superior temporal gyrus (STG) and pars opercularis (ParsOp) compared to non-responders. In addition, disease duration was negatively correlated with cortical thickness in fronto-parietal and temporo-occipital regions in responders but not non-responders, with the exception of the primary motor cortex (MI) that showed the opposite pattern; disease duration was positively associated with MI cortical thickness in responders versus non-responders. Our seed-based RS-FC analyses revealed anti-correlations between the SI seed and lateral occipital (LOC) and dorsomedial

  7. Responding to Patients' Concerns.

    ERIC Educational Resources Information Center

    Henrich, Ann P.; Bernheim, Kayla F.

    1981-01-01

    Discusses a staff development program for nurses at an acute care hospital, aimed at responding to patient comments. Elements included (1) listening skills before training, (2) a formula to help nurses respond empathetically, (3) a pre- and posttest, (4) a followup class, and (5) program evaluation. (CT)

  8. Progesterone attenuates impulsive action in a Go/No-Go task for sucrose pellets in female and male rats

    PubMed Central

    Swalve, Natashia; Smethells, John R.; Carroll, Marilyn E.

    2016-01-01

    Impulsivity, or a tendency to act without anticipation of future consequences, is associated with drug abuse. Impulsivity is typically separated into two main measures, impulsive action and impulsive choice. Given the association of impulsivity and drug abuse, treatments that reduce impulsivity have been proposed as an effective method for countering drug addiction. Progesterone has emerged as a promising treatment, as it is associated with decreased addiction-related behaviors and impulsive action. The goal of the present study was to determine the effects of progesterone (PRO) on impulsive action for food: a Go/No-Go task. Female and male rats responded for sucrose pellets during a Go component when lever pressing was reinforced on a variable-interval 30-s schedule. During the alternate No-Go component, withholding a lever press was reinforced on a differential reinforcement of other (DRO) behavior 30-s schedule, where a lever press reset the DRO timer. Impulsive action was operationally defined as the inability to withhold a response during the No-Go component (i.e. the number of DRO resets). Once Go/No-Go behavior was stable, responding between rats treated with PRO (0.5 mg/kg) or vehicle was examined. Progesterone significantly decreased the total number of DRO resets in both males and females, but it did not affect VI responding for sucrose pellets. This suggests that PRO decreases motor impulsivity for sucrose pellets without affecting motivation for food. Thus, PRO may reduce motor impulsivity, a behavior underlying drug addiction. PMID:27497836

  9. The effects of amphetamine sensitization on conditioned inhibition during a Pavlovian-instrumental transfer task in rats

    PubMed Central

    Shiflett, Michael W.; Riccie, Meaghan; DiMatteo, RoseMarie

    2013-01-01

    Rationale Psychostimulant sensitization heightens behavioral and motivational responses to reward-associated stimuli; however, its effects on stimuli associated with reward absence are less understood. Objectives We examined whether amphetamine sensitization alters performance during Pavlovian-instrumental transfer (PIT) to conditioned excitors and inhibitors. We further sought to characterize the effects of amphetamine sensitization on learning versus performance by exposing rats to amphetamine prior to Pavlovian training or between training and test. Methods Adult male Long Evans rats were given conditioned inhibition (A+/AX−) and Pavlovian (B+) training, followed by variable-interval instrumental conditioning. Rats were sensitized to d-amphetamine (2 mg/kg daily injections for seven days), or served as non-exposed controls. Rats were given a PIT test, in which they were presented with stimulus B alone or in compound with the conditioned inhibitor (BX). Results During the PIT test, control rats significantly reduced instrumental responding on BX trials (to approximately 50% of responding to B). Amphetamine sensitization prior to Pavlovian conditioning increased lever-pressing on BX trials and reduced lever-pressing on B trials compared to controls. Amphetamine sensitization between training and test increased lever-pressing on B and BX trials compared to controls. No effects of sensitization were observed on conditioned food-cup approach. Conclusions Amphetamine sensitization increases instrumental responding during PIT to a conditioned inhibitor, by enhancing excitation of conditioned stimuli and reducing inhibition of conditioned inhibitors. PMID:23715640

  10. The 1984 ARI Survey of Army Recruits. Codebook for Summer 84 Active Army Survey Respondents

    DTIC Science & Technology

    1986-05-01

    ARMY SURVEY RESPONDENTS T261 - DO YOU HATCH ANY OF THE FOLLOWING PROGRAMS OR PROGRAMMING TYPES ON TV? - NBA BASKETBALL . RAN DATA ICARD i1 COLS ILENGTHII... BASKETBALL 280 T262 WATCH TV PROG:COLLEGE BASKETBALL 281 T263 WATCH TV PROG:NHL HOCKEY 282 T264 WATCH TV PROG:PROFESSIONAL WRESTLING 283 T265 WATCH TV...SURVEY RESPONDENTS T262 - DO YOU HATCH ANY OF THE FOLLOWING PROGRAMS OR PROGRAMMING TYPES ON TV? - COLLEGE BASKETBALL . RAW DATA ICARD #1 COLS ILENGTHII

  11. 37 CFR 41.68 - Respondent's brief.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Respondent's brief. 41.68... Respondent's brief. (a)(1) Respondent(s) in an appeal may once, within the time limit for filing set forth in... title. (2) The brief must be signed by the party, or the party's duly authorized attorney or agent, and...

  12. CBT for childhood anxiety disorders: differential changes in selective attention between treatment responders and non-responders.

    PubMed

    Legerstee, Jeroen S; Tulen, Joke H M; Dierckx, Bram; Treffers, Philip D A; Verhulst, Frank C; Utens, Elisabeth M W J

    2010-02-01

    This study examined whether treatment response to stepped-care cognitive-behavioural treatment (CBT) is associated with changes in threat-related selective attention and its specific components in a large clinical sample of anxiety-disordered children. Ninety-one children with an anxiety disorder were included in the present study. Children received a standardized stepped-care CBT. Three treatment response groups were distinguished: initial responders (anxiety disorder free after phase one: child-focused CBT), secondary responders (anxiety disorder free after phase two: child-parent-focused CBT), and treatment non-responders. Treatment response was determined using a semi-structured clinical interview. Children performed a pictorial dot-probe task before and after stepped-care CBT (i.e., before phase one and after phase two CBT). Changes in selective attention to severely threatening pictures, but not to mildly threatening pictures, were significantly associated with treatment success. At pre-treatment assessment, initial responders selectively attended away from severely threatening pictures, whereas secondary responders selectively attended toward severely threatening pictures. After stepped-care CBT, initial and secondary responders did not show any selectivity in the attentional processing of severely threatening pictures. Treatment non-responders did not show any changes in selective attention due to CBT. Initial and secondary treatment responders showed a reduction of their predisposition to selectively attend away or toward severely threatening pictures, respectively. Treatment non-responders did not show any changes in selective attention. The pictorial dot-probe task can be considered a potentially valuable tool in assigning children to appropriate treatment formats as well as for monitoring changes in selective attention during the course of CBT.

  13. Using drug combinations to assess potential contributions of non-GABAA receptors in the discriminative stimulus effects of the neuroactive steroid pregnanolone in rats.

    PubMed

    Eppolito, Amy K; Kodeih, Hanna R; Gerak, Lisa R

    2014-10-01

    Neuroactive steroids are increasingly implicated in the development of depression and anxiety and have been suggested as possible treatments for these disorders. While neuroactive steroids, such as pregnanolone, act primarily at γ-aminobutyric acidA (GABAA) receptors, other mechanisms might contribute to their behavioral effects and could increase their clinical effectiveness, as compared with drugs acting exclusively at GABAA receptors (e.g., benzodiazepines). The current study examined the role of non-GABAA receptors, including N-methyl-d-aspartate (NMDA) and serotonin3 (5-HT3) receptors, in the discriminative stimulus effects of pregnanolone. Separate groups of rats discriminated either 3.2mg/kg pregnanolone from vehicle or 0.32mg/kg of the benzodiazepine midazolam from vehicle while responding under a fixed-ratio 10 schedule for food pellets. When administered alone in both groups, pregnanolone and midazolam produced ≥80% drug-lever responding, the NMDA receptor antagonists dizocilpine and phencyclidine produced ≥60 and ≥30% drug-lever responding, respectively, and the 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (CPBG) and morphine produced <20% drug-lever responding up to doses that markedly decreased response rates. When studied together, neither dizocilpine, phencyclidine, CPBG nor morphine significantly altered the midazolam dose-effect curve in either group. Given that CPBG is without effect, it is unlikely that 5-HT3 receptors contribute substantially to the discriminative stimulus effects of pregnanolone. Similarities across groups in effects of dizocilpine and phencyclidine suggest that NMDA receptors do not differentially contribute to the effects of pregnanolone. Thus, NMDA and 5-HT3 receptors are not involved in the discriminative stimulus effects of pregnanolone. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Empathy-related responding and prosocial behaviour.

    PubMed

    Eisenberg, Nancy

    2007-01-01

    In this paper I differentiate among empathy, sympathy and personal distress and discuss the central role of empathy-related responding in positive (including moral) development. Empathy-related responding, especially sympathy, is likely an important source of prosocial, other-oriented motivation. In fact, empathy-related responding, especially sympathy, has been associated with prosocial behaviour (voluntary behaviour intended to benefit another, e.g. helping, sharing); this relation has been obtained for both specific instances of empathy-related responding and for dispositional sympathy. In addition, sympathy (or sometimes empathy) has been linked to relatively high levels of moral reasoning and social competence, and to low levels of aggression and antisocial behaviour. In my talk, I will review research on the relation of empathy-related responding to prosocial behaviour, the consistency of costly prosocial behaviour over time and the possible role of sympathy in its consistency, and the relation of empathy-related responding to moral reasoning, antisocial behaviour and social competence. Examples of research, including longitudinal research in our laboratory, are provided to illustrate these relations. Because of its close relations to social and prosocial responding, an understanding of empathy-related responding contributes to efforts to promote children's moral development.

  15. Medial Orbitofrontal Cortex Mediates Effort-related Responding in Rats.

    PubMed

    Münster, Alexandra; Hauber, Wolfgang

    2017-11-17

    The medial orbitofrontal cortex (mOFC) is known to support flexible control of goal-directed behavior. However, limited evidence suggests that the mOFC also mediates the ability of organisms to work with vigor towards a selected goal, a hypothesis that received little consideration to date. Here we show that excitotoxic mOFC lesion increased responding under a progressive ratio (PR) schedule of reinforcement, that is, the highest ratio achieved, and increased the preference for the high effort-high reward option in an effort-related decision-making task, but left intact outcome-selective Pavlovian-instrumental transfer and outcome-specific devaluation. Moreover, pharmacological inhibition of the mOFC increased, while pharmacological stimulation reduced PR responding. In addition, pharmacological mOFC stimulation attenuated methylphenidate-induced increase of PR responding. Intact rats tested for PR responding displayed higher numbers of c-Fos positive mOFC neurons than appropriate controls; however, mOFC neurons projecting to the nucleus accumbens did not show a selective increase in neuronal activation implying that they may not play a major role in regulating PR responding. Collectively, these results suggest that the mOFC plays a major role in mediating effort-related motivational functions. Moreover, our data demonstrate for the first time that the mOFC modulates effort-related effects of psychostimulant drugs. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Effects of baclofen and raclopride on reinstatement of cocaine self-administration in the rat.

    PubMed

    Froger-Colléaux, Christelle; Castagné, Vincent

    2016-04-15

    At present there is no satisfactory treatment against relapse of drug-seeking behavior. Relapse can be modeled in laboratory animals using reinstatement procedures, whereby previously extinguished self-administration for a drug is reinstated by different factors, such as exposure to cues or drug priming. It is thought that activation of gamma-aminobutyric acid (GABA) B receptor complexes could represent a promising approach to pharmacotherapy for diminishing relapse potential with drugs possessing reinforcing properties. The effects of baclofen (a prototypic GABAB receptor agonist) on cue-induced cocaine reinstatement were evaluated in the rat with or without a priming injection of cocaine. The effects of raclopride (an antagonist of dopamine D2 receptors) were also evaluated. Cue-induced reinstatement under vehicle resulted in a significant increase in the number of presses on the active lever, as compared with extinction lever responding. This effect was accentuated in rats receiving a priming injection of cocaine (cocaine-plus-cue-induced reinstatement). Baclofen, at doses without effects on food-motivated operant behavior (2.5 and 5mg/kg i.p.), dose-dependently decreased the number of active lever presses during cue-induced reinstatement. Baclofen had slightly weaker effects on cocaine-plus-cue-induced reinstatement. Raclopride (0.08 and 0.15 mg/kg s.c.) had similar effects against cue-induced reinstatement although it failed to inhibit cocaine-plus-cue-induced reinstatement at the lower dose. Baclofen dose-dependently and selectively decreased reinstatement of cocaine self-administration. The data obtained provide support for the potential anti-craving efficacy of baclofen in the treatment of cocaine drug-seeking. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. 24 CFR 103.202 - Notification of respondent; joinder of additional or substitute respondents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....42, the Assistant Secretary will serve a notice on each respondent by certified mail or by personal service. A person who is not named as a respondent in a complaint, but who is identified in the course of... Regulations Relating to Housing and Urban Development OFFICE OF ASSISTANT SECRETARY FOR EQUAL OPPORTUNITY...

  18. 24 CFR 103.202 - Notification of respondent; joinder of additional or substitute respondents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ....42, the Assistant Secretary will serve a notice on each respondent by certified mail or by personal service. A person who is not named as a respondent in a complaint, but who is identified in the course of... Regulations Relating to Housing and Urban Development OFFICE OF ASSISTANT SECRETARY FOR EQUAL OPPORTUNITY...

  19. 24 CFR 103.202 - Notification of respondent; joinder of additional or substitute respondents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....42, the Assistant Secretary will serve a notice on each respondent by certified mail or by personal service. A person who is not named as a respondent in a complaint, but who is identified in the course of... Regulations Relating to Housing and Urban Development OFFICE OF ASSISTANT SECRETARY FOR EQUAL OPPORTUNITY...

  20. 24 CFR 103.202 - Notification of respondent; joinder of additional or substitute respondents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....42, the Assistant Secretary will serve a notice on each respondent by certified mail or by personal service. A person who is not named as a respondent in a complaint, but who is identified in the course of... Regulations Relating to Housing and Urban Development OFFICE OF ASSISTANT SECRETARY FOR EQUAL OPPORTUNITY...

  1. 24 CFR 103.202 - Notification of respondent; joinder of additional or substitute respondents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....42, the Assistant Secretary will serve a notice on each respondent by certified mail or by personal service. A person who is not named as a respondent in a complaint, but who is identified in the course of... Regulations Relating to Housing and Urban Development OFFICE OF ASSISTANT SECRETARY FOR EQUAL OPPORTUNITY...

  2. The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs

    PubMed Central

    Randall, Patrick A.; Lee, Christie A.; Nunes, Eric J.; Yohn, Samantha E.; Nowak, Victoria; Khan, Bilal; Shah, Priya; Pandit, Saagar; Vemuri, V. Kiran; Makriyannis, Alex; Baqi, Younis; Müller, Christa E.; Correa, Merce; Salamone, John D.

    2014-01-01

    Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of

  3. The VMAT-2 inhibitor tetrabenazine affects effort-related decision making in a progressive ratio/chow feeding choice task: reversal with antidepressant drugs.

    PubMed

    Randall, Patrick A; Lee, Christie A; Nunes, Eric J; Yohn, Samantha E; Nowak, Victoria; Khan, Bilal; Shah, Priya; Pandit, Saagar; Vemuri, V Kiran; Makriyannis, Alex; Baqi, Younis; Müller, Christa E; Correa, Merce; Salamone, John D

    2014-01-01

    Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of

  4. Ultrastructural cytochemical prospective study of adult acute lymphoblastic leukemia: detection of peroxidase activity in patients failing to respond to treatment.

    PubMed

    Reiffers, J; Darmendrail, V; Larrue, J; Villenave, I; Bernard, P; Boisseau, M; Broustet, A

    1981-08-15

    Ultrastructural cytochemical studies revealed peroxidase activity in five of 25 adult patients with apparent null lymphoblastic leukemia (ALL) in whom the peroxidase reaction studied with light microscopy was negative. None of these 5 patients responded to a chemotherapy regimen used for adult ALL. The importance of ultrastructural cytochemistry which allows the recognition of myeloblastic differentiation in undifferentiated blast cells is also demonstrated. The correct classification of such cases may be important for prognosis because they appear to be resistant to the chemotherapy used in treating ALL.

  5. Jaw Function in Smilodon fatalis: A Reevaluation of the Canine Shear-Bite and a Proposal for a New Forelimb-Powered Class 1 Lever Model

    PubMed Central

    Brown, Jeffrey G.

    2014-01-01

    The jaw function of Smilodon fatalis has long been a source of debate. Although modern-day lions subdue large prey through the use of a suffocating throat bite, the dramatically elongated maxillary canines of S. fatalis suggest an alternative bite mechanism. The current literature favors a “canine shear-bite,” in which the depression of the cranium by the ventral neck flexors assists the mandibular adductors in closing the jaws. Although the model makes intuitive sense and appears to be supported by scientific data, the mechanical feasibility of “neck-powered” biting has not been experimentally demonstrated. In the present study, the computer-assisted manipulation of digitized images of a high-quality replica of an S. fatalis neck and skull shows that a rotation of the cranium by the ventral neck flexors will not result in jaw closure. Instead, the cranium and mandible rotate ventrally together (at the atlantooccipital joint), and the jaws remain in an open configuration. The only manner by which rotation of the cranium can simultaneously result in jaw closure is by an anterior rotation at the temporomandibular joint. Based on this finding, the author proposes a new Class 1 lever mechanism for S. fatalis jaw function. In this model, the mandible is immobilized against the neck of the prey and a dorsally directed force from the extension of the forelimbs rotates the cranium anteriorly at the temporomandibular joint. The maxillary canines pierce the prey’s neck and assist in clamping the ventral neck structures. The model is based on a maximum gape angle of approximately 90° and incorporates a secondary virtual point of rotation located slightly anteroventral to the temporomandibular joint. The Class 1 Lever Model is mechanically feasible, consistent with current data on S. fatalis anatomy and ecology, and may provide a basis for similar studies on other fossil taxa. PMID:25272032

  6. Development and testing of responder : phase III.

    DOT National Transportation Integrated Search

    2017-06-28

    This report documents the research project Development and Testing of Responder Phase III. Under previous research, a Responder system has been developed to provide relevant and timely information to first responders, allow responders to provid...

  7. The role of the basolateral amygdala in punishment.

    PubMed

    Jean-Richard-Dit-Bressel, Philip; McNally, Gavan P

    2015-02-01

    Aversive stimuli not only support fear conditioning to their environmental antecedents, they also punish behaviors that cause their occurrence. The amygdala, especially the basolateral nucleus (BLA), has been critically implicated in Pavlovian fear learning but its role in punishment remains poorly understood. Here, we used a within-subjects punishment task to assess the role of the BLA in the acquisition and expression of punishment as well as aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of GABA agonists baclofen and muscimol (BM) into the BLA significantly impaired the acquisition of this suppression. BLA inactivations using BM also reduced the expression of well-trained punishment. There was anatomical segregation within the BLA so that caudal, not rostral, BLA was implicated in punishment. However, when presented with punished and unpunished levers simultaneously in a choice test without deliveries of shock punisher, rats expressed a preference for unpunished over the punished lever and BLA inactivations had no effect on this preference. Taken together, these findings indicate that the BLA is important for both the acquisition and expression of punishment but not for aversive choice. This role appears to be linked to neurons in the caudal BLA, rather than rostral BLA, although the circuitry that contributes to this functional segregation is currently unknown, and is most parsimoniously interpreted as a role for caudal BLA in determining the aversive value of the shock punisher. © 2015 Jean-Richard-Dit-Bressel and McNally; Published by Cold Spring Harbor Laboratory Press.

  8. Deepened extinction following compound stimulus presentation: Noradrenergic modulation

    PubMed Central

    Janak, Patricia H.; Corbit, Laura H.

    2011-01-01

    Behavioral extinction is an active form of new learning involving the prediction of nonreward where reward has previously been present. The expression of extinction learning can be disrupted by the presentation of reward itself or reward-predictive stimuli (reinstatement) as well as the passage of time (spontaneous recovery) or contextual changes (renewal). The following experiments replicated the demonstration that presenting multiple previously rewarded stimuli in compound during extinction enhances extinction learning. To explore the pharmacological basis for this we next examined the effects of pharmacological treatments that either facilitated or blocked noradrenergic activity to test the hypothesis that increased noradrenergic activity at the time of extinction training would improve, whereas blockade of noradrenergic activity would impair the extinction of appetitive stimulus–reward memories. Different groups of rats were trained in a discriminative stimulus paradigm to lever-press for food reward. Once stable responding was achieved, responding was extinguished for 2 d. Prior to a third extinction session, rats received systemic administration of either saline, yohimbine (α2 antagonist), atomoxetine (norepinephrine reuptake inhibitor), or propranolol (β-receptor antagonist). Spontaneous recovery of responding to the stimuli was tested 4 wk later. Our results indicate that increasing noradrenergic activity during extinction augments extinction learning resulting in less recovery of responding at test. These results have important implications for models of relapse to drug seeking and the development of extinction-based therapies. PMID:21224211

  9. What Respondents Really Expect from Researchers

    ERIC Educational Resources Information Center

    Kolar, Tomaz; Kolar, Iztok

    2008-01-01

    This article addresses the issue of falling response rates in telephone surveys. To better understand and maintain respondent goodwill, concepts of psychological contract and respondent expectations are introduced and explored. Results of the qualitative study show that respondent expectations are not only socially contingent but also…

  10. Long-lasting resistance to extinction of response reinstatement induced by ethanol-related stimuli: role of genetic ethanol preference.

    PubMed

    Ciccocioppo, R; Angeletti, S; Weiss, F

    2001-10-01

    The conditioning of ethanol's reinforcing effects with specific environmental stimuli is thought to be a critical factor in long-lasting relapse risk associated with alcoholism. To study the significance of such learning factors in the addictive potential of ethanol, this experiment was designed (1) to characterize the effects of stimuli associated with alcohol availability on the reinstatement of responding at a previously ethanol-paired lever in rats with genetically determined ethanol preference versus nonpreference and (2) to examine the persistence of the motivating effects of these stimuli over time. Male alcohol-preferring (P) and alcohol-nonpreferring (NP) rats were trained to operantly self-administer ethanol (10% w/v) or water on a fixed-ratio 1 schedule in a 30-min daily session. Ethanol and water sessions were scheduled in random sequence across training days. Ethanol availability was signaled by an olfactory discriminative stimulus (banana extract, S+), and each lever press was paired with brief presentation of the conditioning chamber's house light (CS+). The discriminative stimulus signaling water availability (i.e., nonreward) consisted of anise odor (S-), and lever-responses during water sessions were paired with a brief white noise generation (CS-). The rats then were placed on extinction conditions during which ethanol and water, as well as the corresponding stimuli, were withheld. The effects of noncontingent exposure to the S+ versus S- paired with response-contingent presentation of the CS+ versus CS- on responding at the previously active lever were then determined in 30-min reinstatement sessions. To study the resistance to extinction of the effects of the ethanol-associated stimuli, additional tests were conducted at 3-day intervals for a total of 50 days. The number of ethanol-reinforced responses during self-administration training was significantly greater in P than in NP rats (p < 0.01). After extinction, a significant recovery of

  11. Redding Responder Field Test - UTC

    DOT National Transportation Integrated Search

    2008-10-30

    This UTC project facilitated field testing and evaluation of the "Responder" system between Phases 1 and 2 of the Redding Responder Project, sponsored by the California Department of Transportation. A pilot system, with hardware purchased by Caltrans...

  12. Exceptional Responders Initial Feasibility Results

    Cancer.gov

    A pilot study evaluating identification of cancer patients who respond to treatment that is ineffective in at least 90 percent of patients found that it was indeed able to confirm a majority of proposed patients as exceptional responders based on clinical

  13. Behavioral Momentum Theory Fails to Account for the Effects of Reinforcement Rate on Resurgence

    PubMed Central

    Craig, Andrew R.; Shahan, Timothy A.

    2017-01-01

    The behavioral-momentum model of resurgence predicts reinforcer rates within a resurgence preparation should have three effects on target behavior. First, higher reinforcer rates in baseline (Phase 1) produce more persistent target behavior during extinction plus alternative reinforcement. Second, higher rate alternative reinforcement during Phase 2 generates greater disruption of target responding during extinction. Finally, higher rates of either reinforcement source should produce greater responding when alternative reinforcement is suspended in Phase 3. Recent empirical reports have produced mixed results in terms of these predictions. Thus, the present experiment further examined reinforcer-rate effects on persistence and resurgence. Rats pressed target levers for high-rate or low-rate variable-interval food during Phase 1. In Phase 2, target-lever pressing was extinguished, an alternative nose-poke became available, and nose-poking produced either high-rate variable-interval, low-rate variable-interval, or no (an extinction control) alternative reinforcement. Alternative reinforcement was suspended in Phase 3. For groups that received no alternative reinforcement, target-lever pressing was less persistent following high-rate than low-rate Phase-1 reinforcement. Target behavior was more persistent with low-rate alternative reinforcement than with high-rate alternative reinforcement or extinction alone. Finally, no differences in Phase-3 responding were observed for groups that received either high-rate or low-rate alternative reinforcement, and resurgence occurred only following high-rate alternative reinforcement. These findings are inconsistent with the momentum-based model of resurgence. We conclude this model mischaracterizes the effects of rein-forcer rates on persistence and resurgence of operant behavior. PMID:27193242

  14. 7 CFR 3017.1000 - Respondent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Respondent. 3017.1000 Section 3017.1000 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF THE CHIEF FINANCIAL OFFICER, DEPARTMENT OF AGRICULTURE GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 3017.1000 Respondent...

  15. Food quality and motivation: a refined low-fat diet induces obesity and impairs performance on a progressive ratio schedule of instrumental lever pressing in rats.

    PubMed

    Blaisdell, Aaron P; Lau, Yan Lam Matthew; Telminova, Ekatherina; Lim, Hwee Cheei; Fan, Boyang; Fast, Cynthia D; Garlick, Dennis; Pendergrass, David C

    2014-04-10

    Purified high-fat diet (HFD) feeding causes deleterious metabolic and cognitive effects when compared with unrefined low-fat diets in rodent models. These effects are often attributed to the diet's high content of fat, while less attention has been paid to other mechanisms associated with the diet's highly refined state. Although the effects of HFD feeding on cognition have been explored, little is known about the impact of refined vs. unrefined food on cognition. We tested the hypothesis that a refined low-fat diet (LFD) increases body weight and adversely affects cognition relative to an unrefined diet. Rats were allowed ad libitum access to unrefined rodent chow (CON, Lab Diets 5001) or a purified low-fat diet (REF, Research Diets D12450B) for 6 months, and body weight and performance on an instrumental lever pressing task were recorded. After six months on their respective diets, group REF gained significantly more weight than group CON. REF rats made significantly fewer lever presses and exhibited dramatically lower breaking points than CON rats for sucrose and water reinforcement, indicating a chronic reduction of motivation for instrumental performance. Switching the rats' diet for 9 days had no effect on these measures. Diet-induced obesity produces a substantial deficit in motivated behavior in rats, independent of dietary fat content. This holds implications for an association between obesity and motivation. Specifically, behavioral traits comorbid with obesity, such as depression and fatigue, may be effects of obesity rather than contributing causes. To the degree that refined foods contribute to obesity, as demonstrated in our study, they may play a significant contributing role to other behavioral and cognitive disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. The monoamine-oxidase B inhibitor deprenyl increases selection of high-effort activity in rats tested on a progressive ratio/chow feeding choice procedure: Implications for treating motivational dysfunctions.

    PubMed

    Yohn, Samantha E; Reynolds, Shanika; Tripodi, Giuseppe; Correa, Merce; Salamone, John D

    2018-04-16

    Motivated behaviors often are characterized by a high degree of behavioral activation and work output, and organisms frequently make effort-related decisions based upon cost/benefit analyses. Moreover, people with depression and other disorders frequently show effort-related motivational symptoms, such as anergia, psychomotor retardation, and fatigue. Tasks measuring effort-related choice are being used as animal models of these motivational symptoms. The present studies characterized the ability of the monoamine oxidase -B (MAO-B) inhibitor deprenyl (selegiline) to enhance selection of high-effort lever pressing in rats tested on a concurrent progressive ratio (PROG)/chow feeding choice task. Deprenyl is widely used as an antiparkinsonian drug, but it also has been shown to have antidepressant effects in humans, and to induce antidepressant-like effects in traditional rodent models of depression. Systemic administration of deprenyl (1.5-12.0 mg/kg IP) shifted choice behavior, significantly increasing markers of PROG lever pressing at a moderate dose (6.0 mg/kg), and decreasing chow intake at 6.0 and 12.0 mg/kg. Intracranial injections of deprenyl into nucleus accumbens (2.0 and 4.0 μg) also increased PROG lever pressing and decreased chow intake. Microdialysis studies showed that the dose of deprenyl that was effective at increasing PROG lever pressing (6.0 mg/kg) also significantly elevated extracellular dopamine in nucleus accumbens. Thus, similar to the well-known antidepressant bupropion, deprenyl is capable of increasing selection of high-effort PROG lever pressing at doses that increase extracellular dopamine in nucleus accumbens. These studies have implications for the potential use of MAO-B inhibitors as treatments for the motivational symptoms of depression and Parkinsonism. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. TCR hypervariable regions expressed by T cells that respond to effective tumor vaccines.

    PubMed

    Jordan, Kimberly R; Buhrman, Jonathan D; Sprague, Jonathan; Moore, Brandon L; Gao, Dexiang; Kappler, John W; Slansky, Jill E

    2012-10-01

    A major goal of immunotherapy for cancer is the activation of T cell responses against tumor-associated antigens (TAAs). One important strategy for improving antitumor immunity is vaccination with peptide variants of TAAs. Understanding the mechanisms underlying the expansion of T cells that respond to the native tumor antigen is an important step in developing effective peptide-variant vaccines. Using an immunogenic mouse colon cancer model, we compare the binding properties and the TCR genes expressed by T cells elicited by peptide variants that elicit variable antitumor immunity directly ex vivo. The steady-state affinity of the natural tumor antigen for the T cells responding to effective peptide vaccines was higher relative to ineffective peptides, consistent with their improved function. Ex vivo analysis showed that T cells responding to the effective peptides expressed a CDR3β motif, which was also shared by T cells responding to the natural antigen and not those responding to the less effective peptide vaccines. Importantly, these data demonstrate that peptide vaccines can expand T cells that naturally respond to tumor antigens, resulting in more effective antitumor immunity. Future immunotherapies may require similar stringent analysis of the responding T cells to select optimal peptides as vaccine candidates.

  18. The solid-solution region for the langasite-type Ca3TaGa3Si2O14 crystal as determined by a lever rule

    NASA Astrophysics Data System (ADS)

    Zhao, Hengyu; Uda, Satoshi; Maeda, Kensaku; Nozawa, Jun; Koizumi, Haruhiko; Fujiwara, Kozo

    2015-04-01

    A lever rule was applied to data concerning the compositions and proportions of secondary phases coexisting with a Ca3TaGa3Si2O14 (CTGS) matrix to determine the boundary compositions of the solid-solution region for CTGS at 1320 °C, as a means of ascertaining the solid-solution for the langasite-type phase in the quaternary CaO-Ta2O5-Ga2O3-SiO2 system. The compositions and proportions of secondary phases were assessed by electron probe micro-analysis as well as through back-scattered electron images. The experimental results showed that the narrow solid-solution region for CTGS is located in a Ta-poor, Ga-poor and Si-rich region relative to its stoichiometric composition.

  19. Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone.

    PubMed

    DeNoble, Victor J; Mele, Paul C

    2006-03-01

    The rate and pattern of lever pressing were studied in 18 rats during 24-h sessions in which responding resulted in intravenous infusions of nicotine. There were four indications of the positive reinforcing effect of nicotine: (1) a greater number of lever presses when nicotine was response-contingent compared to when saline was available; (2) a greater number of responses on the lever resulting in an infusion of nicotine than on the control lever; (3) systematic decreases in the number of contingent nicotine infusions when nicotine was delivered noncontingently; and (4) systematic changes in the frequency of lever pressing as a function of dose. Under a fixed ratio 1 (FR 1) schedule, the number of infusions first increased and then decreased as the dose of nicotine was decreased (64, 32, 16, and 8 microg/kg infusion) and nicotine intake (mg/kg every 24 h) was directly related to the infusion dose. As the FR size was increased from 1 to 6, the number of lever presses increased and the number of infusions (32 microg/kg) remained stable. At FR values greater than 6, both the number of lever presses and infusions decreased. Presession injections of mecamylamine (0.75, 1.5, and 3.0 mg/kg, s.c.) decreased the number of infusions in a dose-related manner. Presession injections of hexamethonium (1.5 and 3.0 mg/kg, s.c.) or naloxone (0.75, 1.5, and 3.0 mg/kg, s.c.) did not alter the within- or between-session patterns of nicotine self-administration. Under the conditions of the present experiment, nicotine served as an effective reinforcer and the behavior was shown to be sensitive to both FR size and infusion dose. In addition, the results suggest that nicotine self-administration involves central nicotinic receptors and that opioid receptor antagonism has no effect on nicotine's reinforcing effects in rats.

  20. Responder Technology Alert (February 2015)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Upton, Jaki F.; Stein, Steven L.

    2015-04-10

    As part of technology foraging for the Responder Technology Alliance, established by the Department of Homeland Science and Technologies First Responders Group, this report summarizes technologies that are relevant in the area of “wearables,” with the potential for use by first responders. The content was collected over the previous month(s) and reproduced from a general Internet search using the term wearables. Additional information is available at the websites provided. This report is not meant to be an exhaustive list nor an endorsement of any technology described herein. Rather, it is meant to provide useful information about current developments in themore » areas wearable technology.« less

  1. Time-Intensity Curves Obtained after Microbubble Injection Can Be Used to Differentiate Responders from Nonresponders among Patients with Clinically Active Crohn Disease after 6 Weeks of Pharmacologic Treatment.

    PubMed

    Quaia, Emilio; Sozzi, Michele; Angileri, Roberta; Gennari, Antonio Giulio; Cova, Maria Assunta

    2016-11-01

    Purpose To assess whether contrast material-enhanced ultrasonography (US) can be used to differentiate responders from nonresponders among patients with clinically active Crohn disease after 6 weeks of pharmacologic treatment. Materials and Methods This prospective study was approved by our ethics committee, and written informed consent was obtained from all patients. Fifty consecutive patients (26 men and 24 women; mean age, 34.76 years ± 9) with a proved diagnosis of active Crohn disease who were scheduled to begin therapy with biologics (infliximab or adalimumab) were included, with enrollment from June 1, 2013, to June 1, 2015. In each patient, the terminal ileal loop was imaged with contrast-enhanced US before the beginning and at the end of week 6 of pharmacologic treatment. Time-intensity curves obtained in responders (those with a decrease in the Crohn disease endoscopic index of severity score of 25-44 before treatment to 10-15 after treatment, an inflammatory score <7, and/or a decrease ≥70 in the Crohn disease activity index score compared with baseline) and nonresponders were compared with Mann-Whitney test. Results Responders (n = 31) and nonresponders (n = 19) differed (P < .05) in the percent change of peak enhancement (-40.78 ± 62.85 vs 53.21 ± 72.5; P = .0001), wash-in (-34.8 ± 67.72 vs 89.44 ± 145.32; P = .001) and washout (-5.64 ± 130.71 vs 166.83 ± 204.44; P = .002) rate, wash-in perfusion index (-42.29 ± 59.21 vs 50.96 ± 71.13; P = .001), area under the time-intensity curve (AUC; -46.17 ± 48.42 vs 41.78 ± 87.64; P = .001), AUC during wash-in (-43.93 ± 54.29 vs 39.79 ± 70.85; P = .001), and AUC during washout (-49.36 ± 47.42 vs 42.65 ± 97.09; P = .001). Responders and nonresponders did not differ in the percent change of rise time (5.09 ± 49.13 vs 6.24 ± 48.06; P = .93) and time to peak enhancement (8.82 ± 54.5 vs 10.21 ± 43.25; P = .3). Conclusion Analysis of time-intensity curves obtained after injection of microbubble

  2. Levers for change: an investigation of how accreditation programmes can promote consumer engagement in healthcare.

    PubMed

    Hinchcliff, Reece; Greenfield, David; Hogden, Anne; Sarrami-Foroushani, Pooria; Travaglia, Joanne; Braithwaite, Jeffrey

    2016-10-01

    To examine how consumer engagement (CE) can be promoted through Australian accreditation programmes. A nation-wide qualitative study completed in 2012. All eight Australian States and Territories. Two-hundred and fifty-eight healthcare stakeholders from the acute, primary and aged care sectors. Forty-seven individual and group interviews were undertaken. Questions elicited views on the dimensions and utility of CE promotion by accreditation programmes. Healthcare stakeholders' views on the dimensions and utility of CE promotion by accreditation programmes. Four mechanisms of CE promotion were identified. Two involved requirements for health service organizations to meet CE-related standards related to consumer experience and satisfaction surveys, and consumer participation in organizational governance processes. Two mechanisms for promoting CE through accreditation processes were also identified, concerning consumer participation in the development and revision of standards, and the implementation of accreditation surveys. Accreditation programmes were viewed as important drivers of CE, yet concerns were raised regarding the organizational investments needed to meet programmes' requirements. Accreditation programmes use diverse mechanisms as levers for change to promote CE in healthcare. These mechanisms and their inter-relationships require careful consideration by accreditation agencies and health policymakers to maximize their potential benefits, while maintaining stakeholder engagement in programmes. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Cocaine Self-Administration in Male and Female Rats Perinatally Exposed to PCBs: Evaluating Drug Use in an Animal Model of Environmental Contaminant Exposure

    PubMed Central

    Miller, Mellessa M.; Meyer, Abby E.; Sprowles, Jenna L. N.; Sable, Helen J. K.

    2017-01-01

    Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxicants known to adversely impact human health. Ortho-substituted PCBs affect the nervous system, including the brain dopaminergic system. The reinforcing effects of psychostimulants are typically modulated via the dopaminergic system, so this study used a preclinical (i.e., rodent) model to evaluate whether developmental contaminant exposure altered intravenous self-administration (i.v. SA) for the psychostimulant cocaine. Long Evans rats were perinatally exposed to 6 or 3 mg/kg/day of PCBs throughout gestation and lactation and compared to non-exposed controls. Rats were trained to lever press for a food reinforcer in an operant chamber under a fixed-ratio 5 (FR5) schedule and later underwent jugular catheterization. Food reinforcers were switched for infusions of 250 μg of cocaine, but the response requirement to earn the reinforcer remained. Active lever presses and infusions were higher in males during response acquisition and maintenance. The same sex effect was observed during later sessions which evaluated responding for cocaine doses ranging from 31.25 – 500 μg. PCB-exposed males (not females) exhibited an increase in cocaine infusions (with a similar trend in active lever presses) during acquisition, but no PCB-related differences were observed during maintenance, examination of the cocaine dose-response relationship, or progressive ratio sessions. Overall, these results indicated perinatal PCB exposure enhanced early cocaine drug-seeking in this preclinical model of developmental contaminant exposure (particularly the males), but no differences were seen during later cocaine SA sessions. As such, additional questions regarding substance abuse proclivity may be warranted in epidemiological studies evaluating environmental contaminant exposures. PMID:28287790

  4. The Road to Resilience: Insights on Training Community Coalitions in the Los Angeles County Community Disaster Resilience Project.

    PubMed

    Cha, Biblia S; Lawrence, Rachel I; Bliss, Jesse C; Wells, Kenneth B; Chandra, Anita; Eisenman, David P

    2016-12-01

    Local health departments (LHDs) have little guidance for operationalizing community resilience (CR). We explored how community coalitions responded to 4 CR levers (education, engagement, partnerships, and community self-sufficiency) during the first planning year of the Los Angeles County Community Disaster Resilience (LACCDR) Project. Sixteen communities were selected and randomly assigned to the experimental CR group or the control preparedness group. Eight CR coalitions met monthly to plan CR-building activities or to receive CR training from a public health nurse. Trained observers documented the coalitions' understanding and application of CR at each meeting. Qualitative content analysis was used to analyze structured observation reports around the 4 levers. Analysis of 41 reports suggested that coalitions underwent a process of learning about and applying CR concepts in the planning year. Groups resonated with ideas of education, community self-sufficiency, and engagement, but increasing partnerships was challenging. LHDs can support coalitions by anticipating the time necessary to understand CR and by facilitating engagement. Understanding the issues that emerge in the early phases of planning and implementing CR-building activities is critical. LHDs can use the experience of the LACCDR Project's planning year as a guide to navigate challenges and issues that emerge as they operationalize the CR model. (Disaster Med Public Health Preparedness. 2016;10:812-821).

  5. The probability of reinforcement per trial affects posttrial responding and subsequent extinction but not within-trial responding.

    PubMed

    Harris, Justin A; Kwok, Dorothy W S

    2018-01-01

    During magazine approach conditioning, rats do not discriminate between a conditional stimulus (CS) that is consistently reinforced with food and a CS that is occasionally (partially) reinforced, as long as the CSs have the same overall reinforcement rate per second. This implies that rats are indifferent to the probability of reinforcement per trial. However, in the same rats, the per-trial reinforcement rate will affect subsequent extinction-responding extinguishes more rapidly for a CS that was consistently reinforced than for a partially reinforced CS. Here, we trained rats with consistently and partially reinforced CSs that were matched for overall reinforcement rate per second. We measured conditioned responding both during and immediately after the CSs. Differences in the per-trial probability of reinforcement did not affect the acquisition of responding during the CS but did affect subsequent extinction of that responding, and also affected the post-CS response rates during conditioning. Indeed, CSs with the same probability of reinforcement per trial evoked the same amount of post-CS responding even when they differed in overall reinforcement rate and thus evoked different amounts of responding during the CS. We conclude that reinforcement rate per second controls rats' acquisition of responding during the CS, but at the same time, rats also learn specifically about the probability of reinforcement per trial. The latter learning affects the rats' expectation of reinforcement as an outcome of the trial, which influences their ability to detect retrospectively that an opportunity for reinforcement was missed, and, in turn, drives extinction. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  6. Suppressive and Facilitative Effects of Shock Intensity and Interresponse Times Followed by Shock

    ERIC Educational Resources Information Center

    Everly, Jessica B.; Perone, Michael

    2012-01-01

    Although response-dependent shock often suppresses responding, response facilitation can occur. In two experiments, we examined the suppressive and facilitative effects of shock by manipulating shock intensity and the interresponse times that produced shock. Rats' lever presses were reinforced on a variable-interval 40-s schedule of food…

  7. The comparison respond of braking torque control between PID and SMC controller for electric powered wheelchair descending on slope condition

    NASA Astrophysics Data System (ADS)

    Asyraf, S. M.; Heerwan, P. M.; Izhar, I. M.

    2018-04-01

    During descending on a slope, the speed of Electric Powered Wheelchair (EPW) tends to changed rapidly. Normally, most EPW is provided with mechanical braking system which transfers human pulling force of the lever creating friction at the tire. However, the task is difficult for the users are elderly or paralyses. However, even for normal user with good strength, in fear condition they tend to give sudden braking which leads to tire locking up and skidding, eventually EPW unstable. These problems will cause accident and injuries to the users if speed does not properly control. In this paper, the automated braking torque control method was proposed in EPW as alternative to solve this problem and increase the mobility and stability especially during descending on slope in other to help the user of the EPW as their daily transportation. In this research, Proportional-Integral-Derivative and Sliding Mode Control controller are compared to determine the best response for torque braking control. The rapid change of speed can be controlled by the braking torque using proposed controllers based on the desired constant speed set by the control designer. Moreover, the sudden braking that caused tire to lock up and skid can be avoided. Furthermore, result from SMC shows this controller have good time respond to maintain the speed based on desired value when descending at slope condition by controlling the braking torque compared to the PID controller.

  8. R(+)-Baclofen, but Not S(-)-Baclofen, Alters Alcohol Self-Administration in Alcohol-Preferring Rats.

    PubMed

    Lorrai, Irene; Maccioni, Paola; Gessa, Gian Luigi; Colombo, Giancarlo

    2016-01-01

    Racemic baclofen [(±)-baclofen] has repeatedly been reported to suppress several -alcohol-motivated behaviors, including alcohol drinking and alcohol -self-administration, in rats and mice. Recent data suggested that baclofen may have bidirectional, stereospecific effects, with the more active enantiomer, R(+)-baclofen, suppressing alcohol intake and the less active enantiomer, S(-)-baclofen, stimulating alcohol intake in mice. The present study was designed to investigate whether this enantioselectivity of baclofen effects may also extend to the reinforcing properties of alcohol in rats. To this end, selectively bred Sardinian alcohol-preferring (sP) rats were initially trained to lever respond on a fixed ratio 4 (FR4) schedule of reinforcement for alcohol (15%, v/v) in daily 30-min sessions. Once responding had stabilized, rats were tested with vehicle, (±)-baclofen (3 mg/kg), R(+)-baclofen (0.75, 1.5, and 3 mg/kg), and S(-)-baclofen (6, 12, and 24 mg/kg) under the FR4 schedule of reinforcement. Treatment with 3 mg/kg (±)-baclofen reduced the number of lever responses for alcohol and estimated amount of self-administered alcohol by approximately 60% in comparison to vehicle treatment. R(+)-baclofen was approximately twice as active as (±)-baclofen: treatment with 1.5 mg/kg R(+)-baclofen decreased both variables to an extent similar to that of the decreasing effect of 3 mg/kg (±)-baclofen. Conversely, treatment with all doses of S(-)-baclofen failed to affect alcohol self administration. These results (a) confirm that non-sedative doses of (±)-baclofen effectively suppressed the reinforcing properties of alcohol in sP rats and (b) apparently do not extend to operant alcohol self-administration in sP rats the capability of S(-)-baclofen to stimulate alcohol drinking in mice.

  9. If Not You, Who? Responding to Emergencies in Physical Education and Physical Activity Settings

    ERIC Educational Resources Information Center

    Howe, Matthew A.; Brewer, Joan D.; Shane, Shawna D.

    2013-01-01

    Injuries can occur anywhere and anytime in physical education. Physical educators should do all they can to prevent injuries from occurring and must be prepared for such an occurrence. Many physical educators have limited knowledge about how to respond to injury and emergency situations. The purpose of this article is to provide information for…

  10. The characteristics of non-respondents and respondents of a mental health survey among evacuees in a disaster: The Fukushima Health Management Survey

    PubMed Central

    Horikoshi, Naoko; Iwasa, Hajime; Yasumura, Seiji; Maeda, Masaharu

    2017-01-01

    Abstract The Fukushima Medical University conducted a mental health care program for evacuees after the Fukushima Daiichi nuclear power plant accident. However, the mental health status of non-respondents has not been considered for surveys using questionnaires. Therefore, the aim of this study was to clarify the characteristics of non-respondents and respondents. The target population of the survey (FY2011-2013) is people living in the nationally designated evacuation zone of Fukushima prefecture. Among these, the participants were 967 people (20 years or older). We examined factors that affected the difference between the groups of participants (i.e., non-respondents and respondents) using multivariate logistic regression analysis. Employment was higher in non-respondents (p=0.022) and they were also more socially isolated (p=0.047) when compared to respondents; non-respondents had a higher proportional risk of psychological distress compared to respondents (p<0.033). The results of the multivariate logistic regression analysis showed that, within the participants there was a significant association between employment status (OR=1.99, 95% confidence interval [CI]:1.12-3.51) and psychological distress (OR=2.17, 95% CI: 1.01-4.66). We found that non-respondents had a significantly higher proportion of psychological distress compared to the respondents. Although the non-respondents were the high-risk group, it is not possible to grasp the complexity of the situation by simply using questionnaire surveys. Therefore, in the future it is necessary to direct our efforts towards the mental health of non-respondents and respondents alike. PMID:29237989

  11. The characteristics of non-respondents and respondents of a mental health survey among evacuees in a disaster: The Fukushima Health Management Survey.

    PubMed

    Horikoshi, Naoko; Iwasa, Hajime; Yasumura, Seiji; Maeda, Masaharu

    2017-12-19

    The Fukushima Medical University conducted a mental health care program for evacuees after the Fukushima Daiichi nuclear power plant accident. However, the mental health status of non-respondents has not been considered for surveys using questionnaires. Therefore, the aim of this study was to clarify the characteristics of non-respondents and respondents. The target population of the survey (FY2011-2013) is people living in the nationally designated evacuation zone of Fukushima prefecture. Among these, the participants were 967 people (20 years or older). We examined factors that affected the difference between the groups of participants (i.e., non-respondents and respondents) using multivariate logistic regression analysis. Employment was higher in non-respondents (p=0.022) and they were also more socially isolated (p=0.047) when compared to respondents; non-respondents had a higher proportional risk of psychological distress compared to respondents (p<0.033). The results of the multivariate logistic regression analysis showed that, within the participants there was a significant association between employment status (OR=1.99, 95% confidence interval [CI]:1.12-3.51) and psychological distress (OR=2.17, 95% CI:1.01-4.66). We found that non-respondents had a significantly higher proportion of psychological distress compared to the respondents. Although the non-respondents were the high-risk group, it is not possible to grasp the complexity of the situation by simply using questionnaire surveys. Therefore, in the future it is necessary to direct our efforts towards the mental health of non-respondents and respondents alike.

  12. Dampening Positive Affect and Neural Reward Responding in Healthy Children: Implications for Affective Inflexibility

    PubMed Central

    Gilbert, Kirsten; Luking, Katherine; Pagliaccio, David; Luby, Joan L.; Barch, Deanna M.

    2017-01-01

    OBJECTIVE Blunted reward processing is evident in and may contribute to the onset of major depressive disorder. However, it is unclear what mechanisms contribute to the development of blunted reward-response prior to depression onset. METHOD The current study examined how individual differences in the tendency to dampen positive affect, an affect regulation strategy that decreases positive affect, are associated with reward responding and related brain activation in 39 healthy children (age 7–10; 51% female; 79% white). To do this, we examined neural responses to winning a reward (candy) within the context of a previous loss, win, or neutral outcome. RESULTS Whole brain regression analyses revealed that self-reported tendencies to engage in dampening were associated with blunted striatum and thalamic activation during a winning outcome when following a previous loss outcome, as compared to when following a neutral outcome. This finding was above and beyond the influence of current depressive symptoms. However, tendencies to dampen positive affect were not associated with neural activity during the second of two consecutive win outcomes, and thus did not support the notion that dampening is associated with an inability to maintain reward responding. CONCLUSIONS In youth, tendencies to dampen positive affect may be associated with less ability to flexibly upregulate neural reward responding following a loss, possibly leading to the development of affective inflexibility and increased vulnerability to depression. Dampening positive affect may be one mechanism that contributes to aberrant neural reward responding via affective inflexibility and may be a target for prevention in youth. PMID:27819484

  13. 45 CFR 1152.9 - How does the Chairman receive and respond to comments?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE ARTS INTERGOVERNMENTAL REVIEW OF NATIONAL ENDOWMENT FOR THE ARTS PROGRAMS AND ACTIVITIES § 1152.9 How does the Chairman receive and respond...

  14. 45 CFR 1152.9 - How does the Chairman receive and respond to comments?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE ARTS INTERGOVERNMENTAL REVIEW OF NATIONAL ENDOWMENT FOR THE ARTS PROGRAMS AND ACTIVITIES § 1152.9 How does the Chairman receive and respond...

  15. Insulin resistance in clomiphene responders and non-responders with polycystic ovarian disease and therapeutic effects of metformin.

    PubMed

    Parsanezhad, M E; Alborzi, S; Zarei, A; Dehbashi, S; Omrani, G

    2001-10-01

    To evaluate the clinical features, endocrine and metabolic profiles in clomiphene (CC) responders and non-responders with polycystic ovarian disease (PCOD), and to examine the effects of metformin (MTF) on the above parameters of CC resistance. A prospective clinical trial was undertaken at the infertility division of a university teaching hospital. Forty-one CC responders were selected and their hormonal and clinical features were determined. Forty-one CC-resistant PCOD women were also selected and clinical features; metabolic and hormonal profiles before and after treatment with MTF 1500 mg/day for 6-8 weeks were evaluated. Women who failed to conceive were treated by CC while continuing to take MTF. CC responders had higher insulin levels while non-responders were hyperinsulinemic. Menstrual irregularities improved in 30%. Mean+/-S.D. area under curve of insulin decreased from 297.58+/-191.33 to 206+/-0.1 mIU/ml per min (P=0.005). Only 39.39% ovulated and 24.24% conceived. PCOD is associated with insulin resistance (IR) particularly in CC-resistant women. Insulin resistance and androgen levels are significantly higher in obese patients. MTF therapy improved hyperandrogenemia, IR, and pregnancy rate.

  16. Discrimination of Variable Schedules Is Controlled by Interresponse Times Proximal to Reinforcement

    ERIC Educational Resources Information Center

    Tanno, Takayuki; Silberberg, Alan; Sakagami, Takayuki

    2012-01-01

    In Experiment 1, food-deprived rats responded to one of two schedules that were, with equal probability, associated with a sample lever. One schedule was always variable ratio, while the other schedule, depending on the trial within a session, was: (a) a variable-interval schedule; (b) a tandem variable-interval,…

  17. Responding To and Recovering From an Active Shooter Incident That Turns Into a Hostage Situation. Lessons Learned From School Crises and Emergencies, Volume 2, Issue 6, 2007

    ERIC Educational Resources Information Center

    US Department of Education, 2007

    2007-01-01

    "Lessons Learned" is a series of publications that are a brief recounting of actual school emergencies and crises. This "Lessons Learned" issue focuses on an active shooter situation that escalated to a hostage situation that required multiple law enforcement agencies and other first responders and agencies to coordinate response and recovery…

  18. Effects of lorcaserin (Belviq®) on nicotine- and food-maintained responding in non-human primates.

    PubMed

    Jacobs, David S; Barkin, Claire E; Kohut, Michelle R; Bergman, Jack; Kohut, Stephen J

    2017-12-01

    Accumulating evidence suggests that the FDA-approved serotonin 5-HT 2C receptor agonist, lorcaserin (Belviq ® ), may be a promising candidate for the management of substance use disorders, including nicotine addiction. The present study was conducted to determine the efficacy and selectivity of acute or continuous lorcaserin treatment for decreasing the reinforcing effects of nicotine in a primate species. Adult rhesus monkeys (n=4) with a history of nicotine self-administration (>2years) responded for injections of nicotine (0.32-100μg/kg IV) or food pellets under a fixed-ratio schedule of reinforcement during daily 100-min sessions. When responding was stable, lorcaserin was administered either as an acute pretreatment (0.1-1.0mg/kg, IM) or by continuous infusion (0.1mg/kg/hr, SC for 3-5days). Daily activity patterns were also monitored immediately following experimental sessions. Results indicate that acute lorcaserin pretreatment produced significant and dose-dependent decreases in nicotine-maintained responding across a >100-fold range of self-administered nicotine doses. Continuous lorcaserin treatment decreased intake of 10μg/kg/inj nicotine to about 50% of baseline values. Food-maintained responding was only moderately decreased in 3 of 4 subjects after acute administration and unaffected in all subjects during continuous treatment. Daily activity also was significantly decreased-to ≤50% of control values-following experimental sessions in which acute lorcaserin was administered. These data indicate that lorcaserin reduces IV self-administration of nicotine at a dose that decreases motoric activity but less consistently disrupts food-maintained responding. Further research into lorcaserin's potential utility for the management of nicotine dependence is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Active Laplacian electrode for the data-acquisition system of EHG

    NASA Astrophysics Data System (ADS)

    Li, G.; Wang, Y.; Lin, L.; Jiang, W.; Wang, L. L.; C-Y Lu, Stephen; Besio, Walter G.

    2005-01-01

    EHG (electrohysterogram) is the recording of uterine electromyogram with external electrodes located on the abdomen of pregnant woman. Derived from the electrical activity generated at the muscle fiber lever, it provides complementary information from the muscle, and appears to be a very promising technique for clinical or physiologic investigation of uterine activity, compared with current monitoring which can't give us complementary phase information of uterine activity. In this article we have shown the disadvantages of the conventional electrodes for EHG data-acquisition system and put forward a new type of electrode that is called active Laplacian electrode. It integrates concentric rings electrode with a bioelectricity preamplifier and is capable of acquiring localized information. We can localise the EHG signals source more easily by using this new electrode.

  20. Patterns of fMRI activity dissociate overlapping functional brain areas that respond to biological motion.

    PubMed

    Peelen, Marius V; Wiggett, Alison J; Downing, Paul E

    2006-03-16

    Accurate perception of the actions and intentions of other people is essential for successful interactions in a social environment. Several cortical areas that support this process respond selectively in fMRI to static and dynamic displays of human bodies and faces. Here we apply pattern-analysis techniques to arrive at a new understanding of the neural response to biological motion. Functionally defined body-, face-, and motion-selective visual areas all responded significantly to "point-light" human motion. Strikingly, however, only body selectivity was correlated, on a voxel-by-voxel basis, with biological motion selectivity. We conclude that (1) biological motion, through the process of structure-from-motion, engages areas involved in the analysis of the static human form; (2) body-selective regions in posterior fusiform gyrus and posterior inferior temporal sulcus overlap with, but are distinct from, face- and motion-selective regions; (3) the interpretation of region-of-interest findings may be substantially altered when multiple patterns of selectivity are considered.

  1. Ginkgo biloba Responds to Herbivory by Activating Early Signaling and Direct Defenses

    PubMed Central

    Atsbaha Zebelo, Simon; Foti, Maria; Fliegmann, Judith; Bossi, Simone; Maffei, Massimo E.; Bertea, Cinzia M.

    2012-01-01

    Background Ginkgo biloba (Ginkgoaceae) is one of the most ancient living seed plants and is regarded as a living fossil. G. biloba has a broad spectrum of resistance or tolerance to many pathogens and herbivores because of the presence of toxic leaf compounds. Little is known about early and late events occurring in G. biloba upon herbivory. The aim of this study was to assess whether herbivory by the generalist Spodoptera littoralis was able to induce early signaling and direct defense in G. biloba by evaluating early and late responses. Methodology/Principal Findings Early and late responses in mechanically wounded leaves and in leaves damaged by S. littoralis included plasma transmembrane potential (Vm) variations, time-course changes in both cytosolic calcium concentration ([Ca2+]cyt) and H2O2 production, the regulation of genes correlated to terpenoid and flavonoid biosynthesis, the induction of direct defense compounds, and the release of volatile organic compounds (VOCs). The results show that G. biloba responded to hebivory with a significant Vm depolarization which was associated to significant increases in both [Ca2+]cyt and H2O2. Several defense genes were regulated by herbivory, including those coding for ROS scavenging enzymes and the synthesis of terpenoids and flavonoids. Metabolomic analyses revealed the herbivore-induced production of several flavonoids and VOCs. Surprisingly, no significant induction by herbivory was found for two of the most characteristic G. biloba classes of bioactive compounds; ginkgolides and bilobalides. Conclusions/Significance By studying early and late responses of G. biloba to herbivory, we provided the first evidence that this “living fossil” plant responds to herbivory with the same defense mechanisms adopted by the most recent angiosperms. PMID:22448229

  2. Appraisal of the Operation Respond Emergency Information System (OREIS)

    DOT National Transportation Integrated Search

    1998-04-01

    The Operation Respond Institute has been instrumental in developing the Operation Respond Emergency Information System (OREIS) for first responders to hazardous material incidents in transportation. The Operation Respond system aims to facilitate rap...

  3. Responder Technology Alert Monthly (January 2015)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Upton, Jaki F.; Stein, Steven L.

    As part of technology foraging for the Responder Technology Alliance, established by the Department of Homeland Science and Technologies First Responders Group, this report summarizes technologies that are relevant in the area of “wearables,” with the potential for use by first responders. The content was collected over the previous month(s) and reproduced from a general Internet search using the term wearables. Additional information is available at the websites provided. This report is not meant to be an exhaustive list nor an endorsement of any technology described herein. Rather, it is meant to provide useful information about current developments in themore » areas wearable technology.« less

  4. The Farm Crisis: Who's in Trouble, How to Respond. National Issues Forum.

    ERIC Educational Resources Information Center

    Bulletin of Science, Technology & Society, 1987

    1987-01-01

    Provides a synopsis of information about the current crises in American agriculture. Addresses national farm policy, political activities, surplus crops, subsidy programs, the loss of smaller family-operated farms, and farm markets. Includes an opinion instrument that invites the reader to respond to the issues. (TW)

  5. Bidirectional effects of inhibiting or activating NMDA receptors on extinction after cocaine self-administration in rats

    PubMed Central

    Hafenbreidel, Madalyn; Todd, Carolynn Rafa; Twining, Robert C.; Tuscher, Jennifer J.; Mueller, Devin

    2014-01-01

    Rationale Extinction of drug seeking is facilitated by NMDA receptor (NMDAr) agonists, but it remains unclear whether extinction is dependent on NMDAr activity. Objectives We investigated the necessity of NMDArs for extinction of cocaine seeking, and whether extinction altered NMDAr expression within extinction-related neuroanatomical loci. Methods Rats were trained to lever press for i.v. infusions of cocaine or sucrose reinforcement prior to extinction training or withdrawal. Results Administration of the NMDAr competitive antagonist CPP prior to four brief extinction sessions impaired subsequent extinction retention. In contrast, post-extinction administration of the NMDAr coagonist D-serine attenuated lever pressing across days as compared to saline administration, indicative of facilitated consolidation of extinction. Furthermore, expression of the NMDAr subunits, GluN2A and GluN2B, was not altered in the ventromedial prefrontal cortex. However, both GluN2A and GluN2B subunit expression in the nucleus accumbens was increased following cocaine self-administration, and this increased expression was relatively resistant to modulation by extinction. Conclusions Our findings demonstrate that extinction of cocaine seeking is bidirectionally mediated by NMDArs and suggest that selective modulation of NMDAr activity could facilitate extinction-based therapies for treatment of cocaine abuse. PMID:24847958

  6. Non-specific effects and clusters of women with painful TMD responders and non-responders to LLLT: double-blind randomized clinical trial.

    PubMed

    Magri, Laís Valencise; Carvalho, Vinícius Almeida; Rodrigues, Flávia Cássia Cabral; Bataglion, César; Leite-Panissi, Christie Ramos Andrade

    2018-02-01

    The aim was to analyze the non-specific effects (placebo, spontaneous remission, and regression to the mean) of the low-level laser therapy (LLLT) in women with myofascial pain (painful temporomandibular disorder (TMD)), as well as to differentiate between responders and non-responder clusters to active and placebo LLLT according to the anxiety levels, salivary cortisol, use of oral contraceptives, and premenstrual period. Sixty-four women diagnosed with myofascial pain (Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD)) were included, divided into laser (n = 20), placebo group (n = 21), and 23 controls (without treatment (WT)). The LLLT applied was 780 nm, masseter and temporal = 5 J/cm 2 (20 mW-0.5 W/cm 2 ), and TMJ area = 7.5 J/cm 2 (30 mW-0.8 W/cm 2 ), eight sessions, twice a week. The pain intensity (visual analogue scale (VAS)), anxiety (Beck Anxiety Inventory), salivary cortisol, and menstrual cycle's data at the baseline, T1-T8, and 30 days after LLLT (follow-up) were evaluated. The laser group showed 80% of pain reduction, placebo 85%, and WT 43% in T8. Women with severe anxiety and at the premenstrual period did not reduce pain with any LLLT. Active and placebo LLLT had similar effectiveness during the treatment period; however, women with moderate anxiety, cortisol levels above 10 ng/ml, and without contraceptive use maintain analgesia longer with active LLLT than placebo (follow-up 30 days). Women with low levels of anxiety, salivary cortisol below 10 ng/ml, and with contraceptive use showed the higher pain reduction. The analgesia promoted by LLLT in women with myofascial pain is a result of non-specific effects during the treatment period, although active LLLT is more effective in maintaining the analgesia after treatment (30 days) for the cluster of women with moderate anxiety, salivary cortisol above 10 ng/ml, and without contraceptive use.

  7. The N Terminus of Monoamine Transporters Is a Lever Required for the Action of Amphetamines*

    PubMed Central

    Sucic, Sonja; Dallinger, Stefan; Zdrazil, Barbara; Weissensteiner, René; Jørgensen, Trine N.; Holy, Marion; Kudlacek, Oliver; Seidel, Stefan; Cha, Joo Hwan; Gether, Ulrik; Newman, Amy H.; Ecker, Gerhard F.; Freissmuth, Michael; Sitte, Harald H.

    2010-01-01

    The serotonin transporter (SERT) terminates neurotransmission by removing serotonin from the synaptic cleft. In addition, it is the site of action of antidepressants (which block the transporter) and of amphetamines (which induce substrate efflux). We explored the functional importance of the N terminus in mediating the action of amphetamines by focusing initially on the highly conserved threonine residue at position 81, a candidate site for phosphorylation by protein kinase C. Molecular dynamics simulations of the wild type SERT, compared with its mutations SERTT81A and SERTT81D, suggested structural changes in the inner vestibule indicative of an opening of the inner vestibule. Predictions from this model (e.g. the preferential accumulation of SERTT81A in the inward conformation, its reduced turnover number, and a larger distance between its N and C termini) were verified. Most importantly, SERTT81A (and the homologous mutations in noradrenaline and dopamine) failed to support amphetamine-induced efflux, and this was not remedied by aspartate at this position. Amphetamine-induced currents through SERTT81A were comparable with those through the wild type transporter. Both abundant Na+ entry and accumulation of SERTT81A in the inward facing conformation ought to favor amphetamine-induced efflux. Thus, we surmised that the N terminus must play a direct role in driving the transporter into a state that supports amphetamine-induced efflux. This hypothesis was verified by truncating the first 64 amino acids and by tethering the N terminus to an additional transmembrane helix. Either modification abolished amphetamine-induced efflux. We therefore conclude that the N terminus of monoamine transporters acts as a lever that sustains reverse transport. PMID:20118234

  8. Responding for a conditioned reinforcer or unconditioned sensory reinforcer in mice: interactions with environmental enrichment, social isolation, and monoamine reuptake inhibitors.

    PubMed

    Browne, Caleb J; Fletcher, Paul J; Zeeb, Fiona D

    2016-03-01

    Environmental factors influence the etiology of many psychiatric disorders. Likewise, environmental factors can alter processes central to motivation. Therefore, motivational deficits present in many disorders may be influenced by early life environmental conditions. We examined whether housing animals in different environmental conditions influenced the ability of sensory stimuli to acquire incentive value and whether elevated monoamine activity altered responsing for these stimuli. Isolation-housed (IH), pair-housed (PH), and environmentally enriched (EE) male C57BL/6N mice were examined in tests of responding for a conditioned reinforcer (CRf) or an unconditioned sensory reinforcer (USRf). The CRf was previously paired with saccharin delivery through Pavlovian conditioning, while the USRf was not conditioned with a reward. Following baseline tests of responding for the CRf or USRf, the effects of elevated monoamine activity were examined. At baseline, PH and EE mice responded similarly for the CRf or USRf. IH mice responded more for the CRf but exhibited slower acquisition of responding for the USRf. Administration of citalopram, a serotonin transporter blocker, or atomoxetine, a norepinephrine transporter blocker, decreased responding for the CRf and USRf in all groups. The dopamine transporter blocker GBR 12909 generally increased responding for the CRf and USRf, but further analysis revealed enhanced responding for both reinforcers only in EE mice. Baseline incentive motivation is strongly influenced by the social component of housing conditions. Furthermore, environmental enrichment increased the sensitivity to elevated dopamine activity, while acute elevations in serotonin and norepinephrine inhibit incentive motivation irrespective of housing condition.

  9. The quantified EEG characteristics of responders and non-responders to long-term treatment with atomoxetine in children with attention deficit hyperactivity disorders.

    PubMed

    Chiarenza, Giuseppe Augusto; Chabot, Robert; Isenhart, Robert; Montaldi, Luciano; Chiarenza, Marco Paolo; Torto, Maria Grazia Lo; Prichep, Leslie S

    2016-06-01

    The aim of our study is to examine quantitative Electroencephalogram (QEEG) differences between ADHD patients that are responders and non-responders to long-term treatment with Atomoxetine at baseline and after 6 and 12months of treatment. Patients with attention deficit hyperactivity disorder (ADHD) received atomoxetine titrated, over 7days, from 0.5 to 1.2mg/kg/day. QEEG and Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV) scores were recorded before treatment and after therapy. Twenty minutes of eyes closed resting EEG was recorded from 19 electrodes referenced to linked earlobes. Full frequency and narrow band spectra of two minutes of artifact-free EEG were computed as well as source localization using Variable Resolution Electrical Tomography (VARETA). Abnormalities were identified using Z-spectra relative to normative values. Patients were classified as responders, non-responders and partial responders based upon the SNAP-IV findings. At baseline, the responders showed increased absolute power in alpha and delta in frontal and temporal regions, whereas, non-responders showed increased absolute power in all frequency bands that was widely distributed. With treatment responders' absolute power values moved toward normal values, whereas, non-responders remained at baseline values. Patients with increased power in the alpha band with no evidence of alterations in the beta or theta range, might be responders to treatment with atomoxetine. Increased power in the beta band coupled with increased alpha seems to be related to non-responders and one should consider atomoxetine withdrawal, especially if there is persistence of increased alpha and beta accompanied by an increase of theta. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Individualized controlled ovarian stimulation in expected poor-responders: an update.

    PubMed

    Haahr, Thor; Esteves, Sandro C; Humaidan, Peter

    2018-03-09

    Controlled ovarian stimulation with subsequent multi-follicular development continues to be a keystone in ART. Evidence supports an individualized approach to ovarian stimulation, usually involving combinations of ovarian reserve tests, body mass index and age to tailor the exogenous gonadotropin dose, and potentially adjuvant treatment aiming for high safety and a shortening of time to live birth. While stimulation and trigger concepts have been developed successfully in normo- and hyperresponder patients, the poor responder patient remains difficult to manage. However, recent advances in definition and classification of the expected poor ovarian responder patient might enable a more accurate and clinically useful interpretation of new treatment concepts in a more homogenous study population. In the present review, we discuss the classification of the expected poor ovarian responder patient as well as clinically useful measurements of efficacy for controlled ovarian stimulation, and finally, we discuss the evidence for clinical management of patients with expected poor ovarian response, including adjuvant treatments such as growth hormone, androgens, and LH activity.In conclusion, the best available evidence supports that the treatment of the expected poor ovarian response patient should be individualized in all steps of ART, including the choice of GnRH analogue, the gonadotropin type and dose, ovulation trigger, and the possible use of adjuvant therapies.

  11. Improving Situational Awareness for First Responders via Mobile Computing

    NASA Technical Reports Server (NTRS)

    Betts, Bradley J.; Mah, Robert W.; Papasin, Richard; Del Mundo, Rommel; McIntosh, Dawn M.; Jorgensen, Charles

    2005-01-01

    This project looks to improve first responder situational awareness using tools and techniques of mobile computing. The prototype system combines wireless communication, real-time location determination, digital imaging, and three-dimensional graphics. Responder locations are tracked in an outdoor environment via GPS and uploaded to a central server via GPRS or an 802.11 network. Responders can also wirelessly share digital images and text reports, both with other responders and with the incident commander. A pre-built three dimensional graphics model of a particular emergency scene is used to visualize responder and report locations. Responders have a choice of information end points, ranging from programmable cellular phones to tablet computers. The system also employs location-aware computing to make responders aware of particular hazards as they approach them. The prototype was developed in conjunction with the NASA Ames Disaster Assistance and Rescue Team and has undergone field testing during responder exercise at NASA Ames.

  12. Improving Situational Awareness for First Responders via Mobile Computing

    NASA Technical Reports Server (NTRS)

    Betts, Bradley J.; Mah, Robert W.; Papasin, Richard; Del Mundo, Rommel; McIntosh, Dawn M.; Jorgensen, Charles

    2006-01-01

    This project looks to improve first responder incident command, and an appropriately managed flow of situational awareness using mobile computing techniques. The prototype system combines wireless communication, real-time location determination, digital imaging, and three-dimensional graphics. Responder locations are tracked in an outdoor environment via GPS and uploaded to a central server via GPRS or an 802. II network. Responders can also wireless share digital images and text reports, both with other responders and with the incident commander. A pre-built three dimensional graphics model of the emergency scene is used to visualize responder and report locations. Responders have a choice of information end points, ranging from programmable cellular phones to tablet computers. The system also employs location-aware computing to make responders aware of particular hazards as they approach them. The prototype was developed in conjunction with the NASA Ames Disaster Assistance and Rescue Team and has undergone field testing during responder exercises at NASA Ames.

  13. Responding to Tragedy

    ERIC Educational Resources Information Center

    Coopman, J. T.

    2009-01-01

    In this article, the author, a superintendent of Clark-Pleasant School Corporation in Whiteland, Indiana, relates how she and the school community responded to a car accident that killed two students. The author stresses the need to develop a comprehensive crisis plan. It is also important to be sensitive to the needs of family members who are…

  14. 78 FR 53124 - First Responder Network Authority Filing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-28

    ...-229; and WT Docket No. 06-150; DA 13-1775] First Responder Network Authority Filing AGENCY: Federal... public comment on a filing submitted by the First Responder Network Authority (FirstNet) on August 2... Commission provides seven days for public comment on matters raised by the First Responder Network Authority...

  15. 28 CFR 115.64 - Staff first responder duties.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Staff first responder duties. 115.64....64 Staff first responder duties. (a) Upon learning of an allegation that an inmate was sexually abused, the first security staff member to respond to the report shall be required to: (1) Separate the...

  16. 28 CFR 115.364 - Staff first responder duties.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Staff first responder duties. 115.364....364 Staff first responder duties. (a) Upon learning of an allegation that a resident was sexually abused, the first staff member to respond to the report shall be required to: (1) Separate the alleged...

  17. 28 CFR 115.64 - Staff first responder duties.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Staff first responder duties. 115.64....64 Staff first responder duties. (a) Upon learning of an allegation that an inmate was sexually abused, the first security staff member to respond to the report shall be required to: (1) Separate the...

  18. 28 CFR 115.64 - Staff first responder duties.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Staff first responder duties. 115.64....64 Staff first responder duties. (a) Upon learning of an allegation that an inmate was sexually abused, the first security staff member to respond to the report shall be required to: (1) Separate the...

  19. 28 CFR 115.364 - Staff first responder duties.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Staff first responder duties. 115.364....364 Staff first responder duties. (a) Upon learning of an allegation that a resident was sexually abused, the first staff member to respond to the report shall be required to: (1) Separate the alleged...

  20. 28 CFR 115.364 - Staff first responder duties.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Staff first responder duties. 115.364....364 Staff first responder duties. (a) Upon learning of an allegation that a resident was sexually abused, the first staff member to respond to the report shall be required to: (1) Separate the alleged...

  1. Remote control of molecular motors using light-activated gearshifting

    NASA Astrophysics Data System (ADS)

    Bryant, Zev

    2013-03-01

    Engineering molecular motors with dynamically controllable properties will allow selective perturbation of mechanical processes in vivo and provide sophisticated components for directed nanoscale transport in vitro. We previously constructed myosin motors that respond to a change in [Ca++] by reversing their direction of motion along the polarized actin filament. To expand the potential applications of controllable molecular motors, we have now developed myosins that shift gears in response to blue light illumination. Light is a versatile control signal that can be readily modulated in time and space, and is generally orthogonal to cellular signaling. Using structure-guided protein engineering, we have incorporated LOV photoreceptor domains into the lever arms of chimeric myosins, resulting in motors that robustly speed up, slow down, or switch directions upon illumination. These genetically encoded motors should be directly deployable inside living cells. Our successful designs include constructs based on two different myosin classes, and we show that optical velocity control can be implemented in motors that move at microns/sec speeds, enabling practical biological and bioengineering applications.

  2. Functional states of rat cortical circuits during the unpredictable availability of a reward-related cue

    PubMed Central

    Fernández-Lamo, Iván; Sánchez-Campusano, Raudel; Gruart, Agnès; Delgado-García M, José M.

    2016-01-01

    Proper performance of acquired abilities can be disturbed by the unexpected occurrence of external changes. Rats trained with an operant conditioning task (to press a lever in order to obtain a food pellet) using a fixed-ratio (1:1) schedule were subsequently placed in a Skinner box in which the lever could be removed randomly. Field postsynaptic potentials (fPSPs) were chronically evoked in perforant pathway-hippocampal CA1 (PP-CA1), CA1-subiculum (CA1-SUB), CA1-medial prefrontal cortex (CA1-mPFC), mPFC-nucleus accumbens (mPFC-NAc), and mPFC-basolateral amygdala (mPFC-BLA) synapses during lever IN and lever OUT situations. While lever presses were accompanied by a significant increase in fPSP slopes at the five synapses, the unpredictable absence of the lever were accompanied by decreased fPSP slopes in all, except PP-CA1 synapses. Spectral analysis of local field potentials (LFPs) recorded when the animal approached the corresponding area in the lever OUT situation presented lower spectral powers than during lever IN occasions for all recording sites, apart from CA1. Thus, the unpredictable availability of a reward-related cue modified the activity of cortical and subcortical areas related with the acquisition of operant learning tasks, suggesting an immediate functional reorganization of these neural circuits to address the changed situation and to modify ongoing behaviors accordingly. PMID:27869181

  3. 28 CFR 115.264 - Staff first responder duties.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Staff first responder duties. 115.264... Report § 115.264 Staff first responder duties. (a) Upon learning of an allegation that a resident was sexually abused, the first security staff member to respond to the report shall be required to: (1...

  4. 28 CFR 115.264 - Staff first responder duties.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Staff first responder duties. 115.264... Report § 115.264 Staff first responder duties. (a) Upon learning of an allegation that a resident was sexually abused, the first security staff member to respond to the report shall be required to: (1...

  5. 28 CFR 115.264 - Staff first responder duties.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Staff first responder duties. 115.264... Report § 115.264 Staff first responder duties. (a) Upon learning of an allegation that a resident was sexually abused, the first security staff member to respond to the report shall be required to: (1...

  6. The motivators and barriers to a smoke-free home among disadvantaged caregivers: identifying the positive levers for change.

    PubMed

    Jones, Laura L; Atkinson, Olesya; Longman, Jo; Coleman, Tim; McNeill, Ann; Lewis, Sarah A

    2011-06-01

    The aims of this study were to explore home smoking behaviors and the motivators and barriers to smoke-free homes among a group of disadvantaged caregivers for young children and to identify the positive levers that health care professionals can utilize when supporting smoking behavior change. In-depth qualitative interviews were conducted between July and September 2009, with 22 disadvantaged smoking caregivers, accessing Children's Centre Services in Nottingham, UK. Interviews were audiorecorded and transcribed verbatim. Data were coded and analyzed thematically to identify emergent main and subthemes. Caregivers had some general understanding of the dangers of secondhand smoke (SHS), but their knowledge appeared incomplete and confused. All interviewees described rules around smoking in the home; however, these tended to be transient and fluid and unlikely to be effective. Caregivers were often living in difficult and complex circumstances and experienced significant barriers to creating a smoke-free home. The motivators for change were more strongly linked to house decor and smell than children's health, suggesting that visible evidence of the harm done by SHS to children might help promote smoke-free homes. Findings suggest that further tailored information on the effect of SHS is required, but to instigate caregiver behavior change, providing demonstrable evidence of the impact that their smoking is having on their children's health is more likely to be effective.

  7. Community first responders and responder schemes in the United Kingdom: systematic scoping review.

    PubMed

    Phung, Viet-Hai; Trueman, Ian; Togher, Fiona; Orner, Roderick; Siriwardena, A Niroshan

    2017-06-19

    Community First Responder (CFR) schemes support lay people to respond to medical emergencies, working closely with ambulance services. They operate widely in the UK. There has been no previous review of UK literature on these schemes. This is the first systematic scoping review of UK literature on CFR schemes, which identifies the reasons for becoming a CFR, requirements for training and feedback and confusion between the CFR role and that of ambulance service staff. This study also reveals gaps in the evidence base for CFR schemes. We conducted a systematic scoping review of the published literature, in the English language from 2000 onwards using specific search terms in six databases. Narrative synthesis was used to analyse article content. Nine articles remained from the initial search of 15,969 articles after removing duplicates, title and abstract and then full text review. People were motivated to become CFRs through an altruistic desire to help others. They generally felt rewarded by their work but recognised that the help they provided was limited by their training compared with ambulance staff. There were concerns about the possible emotional impact on CFRs responding to incidents. CFRs felt that better feedback would enhance their learning. Ongoing training and support were viewed as essential to enable CFRs to progress. They perceived that public recognition of the CFR role was low, patients sometimes confusing them with ambulance staff. Relationships with the ambulance service were sometimes ambivalent due to confusion over roles. There was support for local autonomy of CFR schemes but with greater sharing of best practice. Most studies dated from 2005 and were descriptive rather than analytical. In the UK and Australia CFRs are usually lay volunteers equipped with basic skills for responding to medical emergencies, whereas in the US they include other emergency staff as well as lay people. Opportunities for future research include exploring

  8. How tree roots respond to drought

    PubMed Central

    Brunner, Ivano; Herzog, Claude; Dawes, Melissa A.; Arend, Matthias; Sperisen, Christoph

    2015-01-01

    The ongoing climate change is characterized by increased temperatures and altered precipitation patterns. In addition, there has been an increase in both the frequency and intensity of extreme climatic events such as drought. Episodes of drought induce a series of interconnected effects, all of which have the potential to alter the carbon balance of forest ecosystems profoundly at different scales of plant organization and ecosystem functioning. During recent years, considerable progress has been made in the understanding of how aboveground parts of trees respond to drought and how these responses affect carbon assimilation. In contrast, processes of belowground parts are relatively underrepresented in research on climate change. In this review, we describe current knowledge about responses of tree roots to drought. Tree roots are capable of responding to drought through a variety of strategies that enable them to avoid and tolerate stress. Responses include root biomass adjustments, anatomical alterations, and physiological acclimations. The molecular mechanisms underlying these responses are characterized to some extent, and involve stress signaling and the induction of numerous genes, leading to the activation of tolerance pathways. In addition, mycorrhizas seem to play important protective roles. The current knowledge compiled in this review supports the view that tree roots are well equipped to withstand drought situations and maintain morphological and physiological functions as long as possible. Further, the reviewed literature demonstrates the important role of tree roots in the functioning of forest ecosystems and highlights the need for more research in this emerging field. PMID:26284083

  9. Forum: Communication Activism Pedagogy. Turning Communication Activism Pedagogy Teaching into Communication Activism Pedagogy Research

    ERIC Educational Resources Information Center

    Frey, Lawrence R.; Palmer, David L.

    2017-01-01

    In this rejoinder to this forum's respondents to the stimulus essay, "Communication Activism Pedagogy and Research: Communication Education Scholarship to Promote Social Justice," Lawrence Frey and David Palmer state that the forum editors asked them and the invited respondents to focus on communication activism pedagogy (CAP) research…

  10. Pavlovian-Instrumental Transfer of the Discriminative Stimulus Effects of Nicotine and Ethanol in Rats

    ERIC Educational Resources Information Center

    Troisi, Joseph R., II

    2006-01-01

    To date, only 1 study has evaluated the impact of a Pavlovian drug conditional stimulus (CS) on operant responding. A within-subject operant 1-lever go/no-go (across sessions) design was used to evaluate the impact of Pavlovian contingencies on the discriminative stimulus effects of nicotine (0.4 mg/kg) and ethanol (800 mg/kg) in male Sprague…

  11. HOW PEOPLE RESPOND TO CONTINGENT VALUATION QUESTIONS

    EPA Science Inventory

    The purpose of the project is to understand better how individuals interpret and respond to contingent valuation (CV) questions. The research will address three issues: the reliability of the referendum questions format, the importance of reminding respondents about subst...

  12. "Visual" Cortex of Congenitally Blind Adults Responds to Syntactic Movement.

    PubMed

    Lane, Connor; Kanjlia, Shipra; Omaki, Akira; Bedny, Marina

    2015-09-16

    Human cortex is comprised of specialized networks that support functions, such as visual motion perception and language processing. How do genes and experience contribute to this specialization? Studies of plasticity offer unique insights into this question. In congenitally blind individuals, "visual" cortex responds to auditory and tactile stimuli. Remarkably, recent evidence suggests that occipital areas participate in language processing. We asked whether in blindness, occipital cortices: (1) develop domain-specific responses to language and (2) respond to a highly specialized aspect of language-syntactic movement. Nineteen congenitally blind and 18 sighted participants took part in two fMRI experiments. We report that in congenitally blind individuals, but not in sighted controls, "visual" cortex is more active during sentence comprehension than during a sequence memory task with nonwords, or a symbolic math task. This suggests that areas of occipital cortex become selective for language, relative to other similar higher-cognitive tasks. Crucially, we find that these occipital areas respond more to sentences with syntactic movement but do not respond to the difficulty of math equations. We conclude that regions within the visual cortex of blind adults are involved in syntactic processing. Our findings suggest that the cognitive function of human cortical areas is largely determined by input during development. Human cortex is made up of specialized regions that perform different functions, such as visual motion perception and language processing. How do genes and experience contribute to this specialization? Studies of plasticity show that cortical areas can change function from one sensory modality to another. Here we demonstrate that input during development can alter cortical function even more dramatically. In blindness a subset of "visual" areas becomes specialized for language processing. Crucially, we find that the same "visual" areas respond to a highly

  13. MINER - A Mobile Imager of Neutrons for Emergency Responders

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Goldsmith, John E. M.; Brennan, James S.; Gerling, Mark D

    2014-10-01

    We have developed a mobile fast neutron imaging platform to enhance the capabilities of emergency responders in the localization and characterization of special nuclear material. This mobile imager of neutrons for emergency responders (MINER) is based on the Neutron Scatter Camera, a large segmented imaging system that was optimized for large-area search applications. Due to the reduced size and power requirements of a man-portable system, MINER has been engineered to fit a much smaller form factor, and to be operated from either a battery or AC power. We chose a design that enabled omnidirectional (4π) imaging, with only a ~twofoldmore » decrease in sensitivity compared to the much larger neutron scatter cameras. The system was designed to optimize its performance for neutron imaging and spectroscopy, but it does also function as a Compton camera for gamma imaging. This document outlines the project activities, broadly characterized as system development, laboratory measurements, and deployments, and presents sample results in these areas. Additional information can be found in the documents that reside in WebPMIS.« less

  14. On the automatic link between affect and tendencies to approach and avoid: Chen and Bargh (1999) revisited

    PubMed Central

    Rotteveel, Mark; Gierholz, Alexander; Koch, Gijs; van Aalst, Cherelle; Pinto, Yair; Matzke, Dora; Steingroever, Helen; Verhagen, Josine; Beek, Titia F.; Selker, Ravi; Sasiadek, Adam; Wagenmakers, Eric-Jan

    2015-01-01

    Within the literature on emotion and behavioral action, studies on approach-avoidance take up a prominent place. Several experimental paradigms feature successful conceptual replications but many original studies have not yet been replicated directly. We present such a direct replication attempt of two seminal experiments originally conducted by Chen and Bargh (1999). In their first experiment, participants affectively evaluated attitude objects by pulling or pushing a lever. Participants who had to pull the lever with positively valenced attitude objects and push the lever with negatively valenced attitude objects (i.e., congruent instruction) did so faster than participants who had to follow the reverse (i.e., incongruent) instruction. In Chen and Bargh's second experiment, the explicit evaluative instructions were absent and participants merely responded to the attitude objects by either always pushing or always pulling the lever. Similar results were obtained as in Experiment 1. Based on these findings, Chen and Bargh concluded that (1) attitude objects are evaluated automatically; and (2) attitude objects automatically trigger a behavioral tendency to approach or avoid. We attempted to replicate both experiments and failed to find the effects reported by Chen and Bargh as indicated by our pre-registered Bayesian data analyses; nevertheless, the evidence in favor of the null hypotheses was only anecdotal, and definitive conclusions await further study. PMID:25883572

  15. Stimulus generalization, discrimination learning, and peak shift in horses.

    PubMed Central

    Dougherty, D M; Lewis, P

    1991-01-01

    Using horses, we investigated three aspects of the stimulus control of lever-pressing behavior: stimulus generalization, discrimination learning, and peak shift. Nine solid black circles, ranging in size from 0.5 in. to 4.5 in. (1.3 cm to 11.4 cm) served as stimuli. Each horse was shaped, using successive approximations, to press a rat lever with its lip in the presence of a positive stimulus, the 2.5-in. (6.4-cm) circle. Shaping proceeded quickly and was comparable to that of other laboratory organisms. After responding was maintained on a variable-interval 30-s schedule, stimulus generalization gradients were collected from 2 horses prior to discrimination training. During discrimination training, grain followed lever presses in the presence of a positive stimulus (a 2.5-in circle) and never followed lever presses in the presence of a negative stimulus (a 1.5-in. [3.8-cm] circle). Three horses met a criterion of zero responses to the negative stimulus in fewer than 15 sessions. Horses given stimulus generalization testing prior to discrimination training produced symmetrical gradients; horses given discrimination training prior to generalization testing produced asymmetrical gradients. The peak of these gradients shifted away from the negative stimulus. These results are consistent with discrimination, stimulus generalization, and peak-shift phenomena observed in other organisms. PMID:1940765

  16. The effects of the novel DA D3 receptor antagonist SR 21502 on cocaine reward, cocaine seeking and cocaine-induced locomotor activity in rats.

    PubMed

    Galaj, E; Ananthan, S; Saliba, M; Ranaldi, Robert

    2014-02-01

    There is a focus on developing D3 receptor antagonists as cocaine addiction treatments. We investigated the effects of a novel selective D3 receptor antagonist, SR 21502, on cocaine reward, cocaine-seeking, food reward, spontaneous locomotor activity and cocaine-induced locomotor activity in rats. In Experiment 1, rats were trained to self-administer cocaine under a progressive ratio (PR) schedule of reinforcement and tested with vehicle or one of three doses of SR 21502. In Experiment 2, animals were trained to self-administer cocaine under a fixed ratio schedule of reinforcement followed by extinction of the response. Then, animals were tested with vehicle or one of the SR 21502 doses on cue-induced reinstatement of responding. In Experiment 3, animals were trained to lever press for food under a PR schedule and tested with vehicle or one dose of the compound. In Experiments 4 and 5, in separate groups of animals, the vehicle and three doses of SR 21502 were tested on spontaneous or cocaine (10 mg/kg, IP)-induced locomotor activity, respectively. SR 21502 produced significant, dose-related (3.75, 7.5 and 15 mg/kg) reductions in breakpoint for cocaine self-administration, cue-induced reinstatement (3.75, 7.5 and 15 mg/kg) and cocaine-induced locomotor activity (3.75, 7.5 and 15 mg/kg) but failed to reduce food self-administration and spontaneous locomotor activity. SR 21502 decreases cocaine reward, cocaine-seeking and locomotor activity at doses that have no effect on food reward or spontaneous locomotor activity. These data suggest SR 21502 may selectively inhibit cocaine's rewarding, incentive motivational and stimulant effects.

  17. Responding to Mechanical Antigravity

    NASA Technical Reports Server (NTRS)

    Millis, Marc G.; Thomas, Nicholas E.

    2006-01-01

    Based on the experiences of the NASA Breakthrough Propulsion Physics Project, suggestions are offered for constructively responding to proposals that purport breakthrough propulsion using mechanical devices. Because of the relatively large number of unsolicited submissions received (about 1 per workday) and because many of these involve similar concepts, this report is offered to help the would-be submitters make genuine progress as well as to help reviewers respond to such submissions. Devices that use oscillating masses or gyroscope falsely appear to create net thrust through differential friction or by misinterpreting torques as linear forces. To cover both the possibility of an errant claim and a genuine discovery, reviews should require that submitters meet minimal thresholds of proof before engaging in further correspondence; such as achieving sustained deflection of a level-platform pendulum in the case of mechanical thrusters.

  18. Individual differences in gene expression of vasopressin, D2 receptor, POMC and orexin: vulnerability to relapse to heroin-seeking in rats

    PubMed Central

    Zhou, Yan; Leri, Francesco; Cummins, Erin; Jeanne Kreek, Mary

    2014-01-01

    Individual vulnerability to stress-induced relapse during abstinence from chronic heroin exposure is a key feature of opiate addiction, with limited studies on this topic. Arginine vasopressin (AVP) and its V1b receptor, components of the brain stress responsive systems, play a role in heroin-seeking behavior triggered by foot shock (FS) stress in rats. In this study, we tested whether individual differences in the FS-induced heroin-seeking were associated with alterations of AVP and V1b, as well as other stress responsive systems, including pro-opiomelanocortin (POMC), orexin, plasma ACTH and corticosterone, as well as dopamine D2 receptor (D2) and plasma prolactin. Sprague-Dawley rats were subjected to 3-hour intravenous heroin self-administration (SA) and then tested in extinction, FS-induced and heroin priming-induced reinstatements. The rats that self-administered heroin were divided to high and low reinstatement responders induced by FS (H-RI; L-RI). Over SA sessions, both the H-RI and L-RI displayed similar active lever responding, heroin infusion and total heroin intake. Compared to the L-RI, however, the H-RI showed greater active lever responses during stress-induced reinstatement, with higher AVP mRNA levels in medial/basolateral amygdala and lower D2 mRNA levels in caudate putamen. However, heroin priming resulted in similar reinstatement in both groups and produced similarly low POMC and high orexin mRNA levels in hypothalamus. Our results indicate that: 1) enhanced amygdalar AVP and reduced striatal D2 expression may be related to individual vulnerability to stress-induced reinstatement of heroin- seeking; and 2) heroin abstinence-associated alterations of hypothalamic orexin and POMC expression may be involved in drug priming-induced heroin-seeking. PMID:25446223

  19. First responder and physician liability during an emergency.

    PubMed

    Eddy, Amanda

    2013-01-01

    First responders, especially emergency medical technicians and paramedics, along with physicians, will be expected to render care during a mass casualty event. It is highly likely that these medical first responders and physicians will be rendering care in suboptimal conditions due to the mass casualty event. Furthermore, these individuals are expected to shift their focus from individually based care to community- or population-based care when assisting disaster response. As a result, patients may feel they have not received adequate care and may seek to hold the medical first responder or physician liable, even if they did everything they could given the emergency circumstances. Therefore, it is important to protect medical first responders and physicians rendering care during a mass casualty event so that their efforts are not unnecessarily impeded by concerns about civil liability. In this article, the author looks at the standard of care for medical first responders and physicians and describes the current framework of laws limiting liability for these persons during an emergency. The author concludes that the standard of care and current laws fail to offer adequate liability protection for medical first responders and physicians, especially those in the private sector, and recommends that states adopt clear laws offering liability protection for all medical first responders and physicians who render assistance during a mass casualty event.

  20. The Mean as the Balance Point: Thought Experiments with Measuring Sticks

    ERIC Educational Resources Information Center

    Flores, A.

    2008-01-01

    This article presents activities to help students establish a connection between the mean and the balance point of a lever. The lever and its law are discussed briefly. Thought experiments with a meterstick are presented to emphasize different properties of the mean and weighted averages. (Contains 16 figures.)

  1. Dopamine modulates reward expectancy during performance of a slot machine task in rats: evidence for a 'near-miss' effect.

    PubMed

    Winstanley, Catharine A; Cocker, Paul J; Rogers, Robert D

    2011-04-01

    Cognitive accounts of gambling suggest that the experience of almost winning-so-called 'near-misses'-encourage continued play and accelerate the development of pathological gambling (PG) in vulnerable individuals. One explanation for this effect is that near-misses signal imminent winning outcomes and heighten reward expectancy, galvanizing further play. Determining the neurochemical processes underlying the drive to gamble could facilitate the development of more effective treatments for PG. With this aim in mind, we evaluated rats' performance on a novel model of slot machine play, a form of gambling in which near-miss events are particularly salient. Subjects responded to a series of three flashing lights, loosely analogous to the wheels of a slot machine, causing the lights to set to 'on' or 'off'. A winning outcome was signaled if all three lights were illuminated. At the end of each trial, rats chose between responding on the 'collect' lever, resulting in reward on win trials, but a time penalty on loss trials, or starting a new trial. Rats showed a marked preference for the collect lever when both two and three lights were illuminated, indicating heightened reward expectancy following near-misses similar to wins. Erroneous collect responses were increased by amphetamine and the D(2) receptor agonist quinpirole, but not by the D(1) receptor agonist SKF 81297 or receptor subtype selective antagonists. These data suggest that dopamine modulates reward expectancy following the experience of almost winning during slot machine play, via activity at D(2) receptors, and this may result in an enhancement of the near-miss effect and facilitate further gambling.

  2. 45 CFR 660.9 - How does the Director receive and respond to comments?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 false How does the Director receive and respond to comments? 660.9 Section 660.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION INTERGOVERNMENTAL REVIEW OF THE NATIONAL SCIENCE FOUNDATION PROGRAMS AND ACTIVITIES...

  3. 45 CFR 660.9 - How does the Director receive and respond to comments?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false How does the Director receive and respond to comments? 660.9 Section 660.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION INTERGOVERNMENTAL REVIEW OF THE NATIONAL SCIENCE FOUNDATION PROGRAMS AND ACTIVITIES...

  4. 45 CFR 660.9 - How does the Director receive and respond to comments?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false How does the Director receive and respond to comments? 660.9 Section 660.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION INTERGOVERNMENTAL REVIEW OF THE NATIONAL SCIENCE FOUNDATION PROGRAMS AND ACTIVITIES...

  5. 45 CFR 660.9 - How does the Director receive and respond to comments?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false How does the Director receive and respond to comments? 660.9 Section 660.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION INTERGOVERNMENTAL REVIEW OF THE NATIONAL SCIENCE FOUNDATION PROGRAMS AND ACTIVITIES...

  6. 45 CFR 660.9 - How does the Director receive and respond to comments?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false How does the Director receive and respond to comments? 660.9 Section 660.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION INTERGOVERNMENTAL REVIEW OF THE NATIONAL SCIENCE FOUNDATION PROGRAMS AND ACTIVITIES...

  7. DECONTAMINATION WIPES FOR FIRST RESPONDERS - PHASE I

    EPA Science Inventory

    The threat of chemical or biological (CB) attack is real, and there is a recognized need for improved technologies to better respond to these situations. During a CB emergency, first responder units are critical for handling the emergency, and then restoring the environment wh...

  8. A smartphone application for dispatch of lay responders to out-of-hospital cardiac arrests.

    PubMed

    Berglund, Ellinor; Claesson, Andreas; Nordberg, Per; Djärv, Therese; Lundgren, Peter; Folke, Fredrik; Forsberg, Sune; Riva, Gabriel; Ringh, Mattias

    2018-05-01

    Dispatch of lay volunteers trained in cardiopulmonary resuscitation (CPR) and equipped with automated external defibrillators (AEDs) may improve survival in cases of out-of-hospital cardiac arrest (OHCA). The aim of this study was to investigate the functionality and performance of a smartphone application for locating and alerting nearby trained laymen/women in cases of OHCA. A system using a smartphone application activated by Emergency Dispatch Centres was used to locate and alert laymen/women to nearby suspected OHCAs. Lay responders were instructed either to perform CPR or collect a nearby AED. An online survey was carried out among the responders. From February to August 2016, the system was activated in 685 cases of suspected OHCA. Among these, 224 cases were Emergency Medical Services (EMSs)-treated OHCAs (33%). EMS-witnessed cases (n = 11) and cases with missing survey data (n = 15) were excluded. In the remaining 198 OHCAs, lay responders arrived at the scene in 116 cases (58%), and prior to EMSs in 51 cases (26%). An AED was attached in 17 cases (9%) and 4 (2%) were defibrillated. Lay responders performed CPR in 54 cases (27%). Median distance to the OHCA was 560 m (IQR 332-860 m), and 1280 m (IQR 748-1776 m) via AED pick-up. The survey-answering rate was 82%. A smartphone application can be used to alert CPR-trained lay volunteers to OHCAs for CPR. Further improvements are needed to shorten the time to defibrillation before EMS arrival. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Agreement in functional assessment: graphic approaches to displaying respondent effects.

    PubMed

    Haley, Stephen M; Ni, Pengsheng; Coster, Wendy J; Black-Schaffer, Randie; Siebens, Hilary; Tao, Wei

    2006-09-01

    The objective of this study was to examine the agreement between respondents of summary scores from items representing three functional content areas (physical and mobility, personal care and instrumental, applied cognition) within the Activity Measure for Postacute Care (AM-PAC). We compare proxy vs. patient report in both hospital and community settings as represented by intraclass correlation coefficients and two graphic approaches. The authors conducted a prospective, cohort study of a convenience sample of adults (n = 47) receiving rehabilitation services either in hospital (n = 31) or community (n = 16) settings. In addition to using intraclass correlation coefficients (ICC) as indices of agreement, we applied two graphic approaches to serve as complements to help interpret the direction and magnitude of respondent disagreements. We created a "mountain plot" based on a cumulative distribution curve and a "survival-agreement plot" with step functions used in the analysis of survival data. ICCs on summary scores between patient and proxy report were physical and mobility ICC = 0.92, personal care and instrumental ICC = 0.93, and applied cognition ICC = 0.77. Although combined respondent agreement was acceptable, graphic approaches helped interpret differences in separate analyses of clinician and family agreement. Graphic analyses allow for a simple interpretation of agreement data and may be useful in determining the meaningfulness of the amount and direction of interrespondent variation.

  10. Event-related oscillations (ERO) during an active discrimination task: Effects of lesions of the Nucleus Basalis Magnocellularis

    PubMed Central

    Sanchez-Alavez, Manuel; Ehlers, Cindy L.

    2015-01-01

    The cholinergic system in the brain is involved in attentional processes that are engaged for the identification and selection of relevant information in the environment and the formation of new stimulus associations. In the present study we determined the effects of cholinergic lesions of nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs) generated in an auditory active discrimination task in rats. Rats were trained to press a lever to begin a series of 1K Hz tones and to release the lever upon hearing a 2 kHz tone. A time-frequency based representation was used to determine ERO energy and phase synchronization (phase lock index, PLI) across trials, recorded within frontal cortical structures. Lesions in NBM produced by an infusion of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) resulted in (1) a reduction of the number of correct behavioral responses in the active discrimination task, (2) an increase in ERO energy in the delta frequency bands (3) an increase in theta, alpha and beta ERO energy in the N1, P3a and P3b regions of interest (ROI), and (4) an increase in PLI in the theta frequency band in the N1 ROIs. These studies suggest that the NBM cholinergic system is involved in maintaining the synchronization/phase resetting of oscillations in different frequencies in response to the presentation of the target stimuli in an active discrimination task. PMID:25660307

  11. 49 CFR 17.9 - How does the Secretary receive and respond to comments?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false How does the Secretary receive and respond to comments? 17.9 Section 17.9 Transportation Office of the Secretary of Transportation INTERGOVERNMENTAL REVIEW OF DEPARTMENT OF TRANSPORTATION PROGRAMS AND ACTIVITIES § 17.9 How does the Secretary receive and...

  12. Differences in baseline and process variables between non-responders and responders in Internet-based cognitive behavior therapy for chronic tinnitus.

    PubMed

    Probst, Thomas; Weise, Cornelia; Andersson, Gerhard; Kleinstäuber, Maria

    2018-06-06

    Although Internet-based cognitive behavior therapy (iCBT) is an effective treatment for chronic tinnitus, several patients do not improve. In the current study, baseline and process variables were compared between non-responders and responders. Data from patients participating in two randomized controlled trials on iCBT for chronic tinnitus were re-analyzed. Based on the literature, a pre-post difference on the "Tinnitus Handicap Inventory" (THI) of less than seven points improvement was used to operationalize non-response. Associations between non-response and baseline variables (age, gender, and questionnaire scores), patient progress (THI), the process of the therapeutic alliance ("Working Alliance Inventory-Short Revised"; WAI-SR), as well as other process variables (number of logins, amount of messages sent from therapists to patients) were investigated. The results showed that non-responders had a less favorable change on the THI than responders already at mid-treatment (p < .05). The alliance (WAI-SR) during iCBT was not associated with non-response. Non-responders showed more severe sleep disturbances, logged in less in the iCBT platform, and received fewer messages from the therapists than responders, but these differences were mostly not significant anymore when correcting for multiple testing. To conclude, no symptom change in the first half of iCBT for chronic tinnitus patients is a risk factor of not benefiting from iCBT.

  13. 18 CFR 1301.55 - Responding to demands.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... information to be withheld. (c) Factors to be considered in determining whether requested testimony or records... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Responding to demands... Proceedings § 1301.55 Responding to demands. Generally, authorization to provide the requested material or...

  14. Pre-deployment Heat Acclimatization Guidelines for Disaster Responders.

    PubMed

    Brearley, Matt B

    2016-02-01

    Minimal preparation time is a feature of responding to sudden onset disasters. While equipment and supplies are prepared for deployment at short notice, less is known of the physical preparation of medical responders. With many disaster-prone areas classified as tropical regions, there is potential for responders to endure a combination of high ambient temperatures and relative humidity during deployment. Heat acclimatization, defined as the physiological and perceptual adaptations to frequent elevations of core body temperature (Tc), is a key strategy to improve tolerance of hot conditions by medical responders. Pre-deployment heat acclimatization guidelines were developed based upon the duration of physical training and the subjective rate of perceived exertion (session RPE). An objective of individual training sessions was the perception of body temperature as warm to hot. The guidelines were implemented for Team Bravo (2nd rotation) of the Australian Medical Assistance Team (AusMAT) deployed to Tacloban, Philippines following Typhoon Haiyan in November 2013. The guidelines were distributed electronically five to seven days prior to deployment and were followed by a consultation. A group training session in hot conditions was undertaken prior to departure. The AusMAT responders to utilize the guidelines were based in cool or temperate climates that required extra layers of clothing, training during warmer parts of the days, or warm indoor conditions to achieve session objectives. Responders reported the guidelines were simple to use, applicable to their varied training regimens, and had improved their confidence to work in the heat despite not completing the entire 14 day period. The pre-deployment heat acclimatization guidelines provided AusMAT responders the ability to quantify their physical training and promoted physiological adaptations to maximize health, safety, and performance during deployment. While maintaining year-round heat acclimatization is

  15. No Difference in Myosin Kinetics and Spatial Distribution of the Lever Arm in the Left and Right Ventricles of Human Hearts

    PubMed Central

    Duggal, Divya; Requena, S.; Nagwekar, Janhavi; Raut, Sangram; Rich, Ryan; Das, Hriday; Patel, Vipul; Gryczynski, Ignacy; Fudala, Rafal; Gryczynski, Zygmunt; Blair, Cheavar; Campbell, Kenneth S.; Borejdo, Julian

    2017-01-01

    The systemic circulation offers larger resistance to the blood flow than the pulmonary system. Consequently, the left ventricle (LV) must pump blood with more force than the right ventricle (RV). The question arises whether the stronger pumping action of the LV is due to a more efficient action of left ventricular myosin, or whether it is due to the morphological differences between ventricles. Such a question cannot be answered by studying the entire ventricles or myocytes because any observed differences would be wiped out by averaging the information obtained from trillions of myosin molecules present in a ventricle or myocyte. We therefore searched for the differences between single myosin molecules of the LV and RV of failing hearts In-situ. We show that the parameters that define the mechanical characteristics of working myosin (kinetic rates and the distribution of spatial orientation of myosin lever arm) were the same in both ventricles. These results suggest that there is no difference in the way myosin interacts with thin filaments in myocytes of failing hearts, and suggests that the difference in pumping efficiencies are caused by interactions between muscle proteins other than myosin or that they are purely morphological. PMID:29081749

  16. Responder Technology Alert Monthly (Oct-Nov 2014)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Upton, Jaki F.; Stein, Steven L.

    As part of technology foraging for the Responder Technology Alliance, established by the Department of Homeland Science and Technologies First Responders Group, this report summarizes technologies that are relevant in the area of “wearables,” with the potential for use by first responders. The content was collected over the previous month(s) and reproduced from a general Internet search using the term wearables. Additional information is available at the websites provided. This report is not meant to be an exhaustive list nor an endorsement of any technology described herein. Rather, it is meant to provide useful information about current developments in themore » areas wearable technology.« less

  17. Autoshaping i.v. cocaine self-administration in rats: effects of nondrug alternative reinforcers on acquisition.

    PubMed

    Carroll, M E; Lac, S T

    1993-01-01

    The purpose of this experiment was to examine the effects of a nondrug alternative reinforcer and feeding conditions on the acquisition of cocaine self-administration. Rats were autoshaped to press a lever that resulted in a 0.2 mg/kg i.v. cocaine infusion. Responses on the lever were monitored during six consecutive autoshaping sessions that occurred each day. A retractable lever was inserted into the operant chamber on a random time 60 s schedule 10 times per session for six sessions that began each hour. Each day the six autoshaping sessions were followed by a 6-h cocaine self-administration session. During self-administration the lever remained extended, and each response on the lever resulted in a cocaine infusion (0.2 mg/kg). The criterion for acquisition of cocaine-reinforced behavior was met when there were 5 consecutive days during which the mean number of infusions during the 6-h self-administration session was at least 100. This procedure was repeated daily until the criterion was met or 30 days elapsed. The rats were also trained to respond on lick-operated automatic drinking devices that delivered 0.05 ml water or a glucose and saccharin solution (G + S) contingent upon each lick response. Five groups of 12-14 rats were compared. The first four groups constituted a 2 x 2 factorial design whereby either G + S or water was available in the home cage for 3 weeks before autoshaping began and G + S or water was available in the operant chamber during autoshaping. These groups were limited to 20 g food per day and all had free access to water.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Effects of alcohol and saccharin deprivations on concurrent ethanol and saccharin operant self-administration by alcohol-preferring (P) rats.

    PubMed

    Toalston, Jamie E; Oster, Scott M; Kuc, Kelly A; Pommer, Tylene J; Murphy, James M; Lumeng, Lawrence; Bell, Richard L; McBride, William J; Rodd, Zachary A

    2008-06-01

    Consumption of sweet solutions has been associated with a reduction in withdrawal symptoms and alcohol craving in humans. The objective of the present study was to determine the effects of ethanol and saccharin (SACC) deprivations on operant oral self-administration. Alcohol-preferring (P) rats were allowed to lever press concurrently self-administer ethanol (15% vol/vol) and SACC (0.0125% g/vol) for 8 weeks. Rats were then maintained on daily operant access (nondeprived), deprived of both fluids (2 weeks), deprived of SACC and given 2 ml of ethanol daily, or deprived of ethanol and given 2 ml of SACC daily. All groups were then given 2 weeks of daily operant access to ethanol and SACC, followed by an identical second deprivation period. P rats responded more for ethanol than SACC. All deprived groups increased responding on the ethanol lever, but not on the SACC lever. Daily consumption of 2 ml ethanol decreased the duration of the alcohol deprivation effect (ADE). Home cage access to 2 ml of SACC also decreased the ADE but to a lesser extent than access to ethanol. A second deprivation period further increased and prolonged the expression of an ADE. These results show ethanol is a more salient reinforcer than SACC. With concurrent access to ethanol and SACC, P rats do not display a saccharin deprivation effect. Depriving P rats of both ethanol and SACC had the most pronounced effect on the magnitude and duration of the ADE, suggesting that there may be some interactions between ethanol and SACC in their CNS reinforcing effects.

  19. Precipitated withdrawal from nicotine reduces reinforcing effects of a visual stimulus for rats.

    PubMed

    Weaver, Matthew T; Sweitzer, Maggie; Coddington, Sarah; Sheppard, Jaimee; Verdecchia, Nicole; Caggiula, Anthony R; Sved, Alan F; Donny, Eric C

    2012-07-01

    Research has identified at least two positive reinforcement-related effects of nicotine: (a) primary reinforcement and (b) enhancement of reinforcement from concurrently available stimuli. Prior examples of the reinforcement-enhancing effects with rats showed that repeated, intermittent nicotine exposure increased responding for non-nicotine reinforcers, and this effect remained robust over several weeks. However, the effects of continuous nicotine exposure on responding for a non-nicotine reinforcer are unknown, as are the effects of abruptly withdrawing continuous nicotine on behavior maintained by the same reinforcer. Lever pressing for a visual reinforcer under a fixed ratio schedule was assessed while rats were maintained on a chronic, continuous infusion of nicotine (3.16 mg/kg/day; osmotic minipump). The effects of precipitated withdrawal on responding, following 16 days of continuous nicotine exposure, were assessed by pre-session subcutaneous injections of mecamylamine (1.0 mg/kg). Continuous nicotine initially increased active responding for the visual reinforcer; however, continued exposure resulted in an attenuation of this effect. Precipitated withdrawal from nicotine resulted in a significant decline in active responding. The initial increase in responding for the visual reinforcer with chronic nicotine exposure is consistent with prior research showing that intermittent exposure to nicotine acts as a reinforcement enhancer. However, the attenuation of this enhancement following prolonged nicotine exposure is in contrast with the persistent effects previously reported. Finally, the decrease in visual reinforcers below control levels (nicotine-naive animals) following nicotine withdrawal highlights a potential for affective withdrawal, which may serve as a motive for continued nicotine use.

  20. Who Defines "Democratic Leadership?": Three High School Principals Respond to Site-Based Reforms.

    ERIC Educational Resources Information Center

    Brouillette, Liane

    1997-01-01

    Focuses on behaviors and activities of three high school principals as they respond to district's decision to implement a shared decision-making model designed to give teachers and parents a larger voice. Describes these administrators' varying responses, along with varied ways democratic leadership was multilaterally defined in each school by…

  1. Reduction in Responding for Sucrose and Cocaine Reinforcement by Disruption of Memory Reconsolidation1,2,3

    PubMed Central

    2015-01-01

    Abstract Stored memories are dynamic and, when reactivated, can undergo a process of destabilization and reconsolidation to update them with new information. Reconsolidation has been shown for a variety of experimental settings; most recently for well-learned instrumental memories, a class of memory previously thought not to undergo reconsolidation. Here we tested, in rats, whether a weakly-trained lever-pressing memory destabilized following a shift in reinforcement contingency. We show that lever-pressing memory for both sucrose and cocaine reinforcement destabilized under appropriate conditions, and that the reconsolidation of this memory was impaired by systemic administration of the NMDA receptor (NMDAR) antagonist [5R,10S]-[+]-5-methyl-10,1-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801). We went on to investigate the potential role of the nucleus accumbens (NAc) in the reconsolidation of sucrose-reinforced instrumental memories, showing that co-infusion of the NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP-5) and the dopamine-1 receptor (D1R) antagonist 7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol (SCH23390) into the NAc prior to memory reactivation impaired reconsolidation; however, there was no effect when these drugs were infused alone. Further investigation of this effect suggests the combined infusion disrupted the reconsolidation of pavlovian components of memory, and we hypothesize that coactivation of accumbal D1Rs and NMDARs may contribute to both the destabilization and reconsolidation of appetitive memory. Our work demonstrates that weakly-trained instrumental memories undergo reconsolidation under similar parameters to well-trained ones, and also suggests that receptor coactivation in the NAc may contribute to memory destabilization. Furthermore, it provides an important demonstration of the therapeutic potential of reconsolidation-based treatments that target the instrumental components of memory in maladaptive

  2. Acute Chemical Incidents With Injured First Responders, 2002-2012.

    PubMed

    Melnikova, Natalia; Wu, Jennifer; Yang, Alice; Orr, Maureen

    2018-04-01

    IntroductionFirst responders, including firefighters, police officers, emergency medical services, and company emergency response team members, have dangerous jobs that can bring them in contact with hazardous chemicals among other dangers. Limited information is available on responder injuries that occur during hazardous chemical incidents. We analyzed 2002-2012 data on acute chemical incidents with injured responders from 2 Agency for Toxic Substances and Disease Registry chemical incident surveillance programs. To learn more about such injuries, we performed descriptive analysis and looked for trends. The percentage of responders among all injured people in chemical incidents has not changed over the years. Firefighters were the most frequently injured group of responders, followed by police officers. Respiratory system problems were the most often reported injury, and the respiratory irritants, ammonia, methamphetamine-related chemicals, and carbon monoxide were the chemicals more often associated with injuries. Most of the incidents with responder injuries were caused by human error or equipment failure. Firefighters wore personal protective equipment (PPE) most frequently and police officers did so rarely. Police officers' injuries were mostly associated with exposure to ammonia and methamphetamine-related chemicals. Most responders did not receive basic awareness-level hazardous material training. All responders should have at least basic awareness-level hazardous material training to recognize and avoid exposure. Research on improving firefighter PPE should continue. (Disaster Med Public Health Preparedness. 2018;12:211-221).

  3. Peptide vaccines prevent tumor growth by activating T cells that respond to native tumor antigens.

    PubMed

    Jordan, Kimberly R; McMahan, Rachel H; Kemmler, Charles B; Kappler, John W; Slansky, Jill E

    2010-03-09

    Peptide vaccines enhance the response of T cells toward tumor antigens and represent a strategy to augment antigen-independent immunotherapies of cancer. However, peptide vaccines that include native tumor antigens rarely prevent tumor growth. We have assembled a set of peptide variants for a mouse-colon tumor model to determine how to improve T-cell responses. These peptides have similar affinity for MHC molecules, but differ in the affinity of the peptide-MHC/T-cell receptor interaction with a tumor-specific T-cell clone. We systematically demonstrated that effective antitumor responses are generated after vaccination with variant peptides that stimulate the largest proportion of endogenous T cells specific for the native tumor antigen. Importantly, we found some variant peptides that strongly stimulated a specific T-cell clone in vitro, but elicited fewer tumor-specific T cells in vivo, and were not protective. The T cells expanded by the effective vaccines responded to the wild-type antigen by making cytokines and killing target cells, whereas most of the T cells expanded by the ineffective vaccines only responded to the peptide variants. We conclude that peptide-variant vaccines are most effective when the peptides react with a large responsive part of the tumor-specific T-cell repertoire.

  4. Withdrawal, tolerance, and sensitization to dopamine mediated interoceptive cues in rats trained on a three-lever drug-discrimination task.

    PubMed

    Barrett, Robert J; Caul, William F; Smith, Randy

    2005-05-01

    In the present experiment rats were trained on a three-lever, drug-discrimination task to discriminate the cues associated with 0.30 mg/kg of the indirect dopamine (DA) agonist, amphetamine (AMPH), saline (SAL), and 0.03 mg/kg of the DA, D2 receptor antagonist, haloperidol (HAL). Choice behavior determined from tests on 0.30 and 0.15 mg/kg AMPH, SAL 0.03 and 0.015 mg/kg HAL provided a behavioral baseline presumed to represent changes along a continuum of DA mediated, interoceptive cues. Results from separate groups tested on 0.30 and 0.15 mg/kg AMPH, SAL, 0.03 and 0.015 mg/kg HAL, 24 h post-treatment with an acute 7.5 mg/kg dose of AMPH, showed rapid tolerance and withdrawal to the AMPH cue and sensitization to the HAL cue. The same tests 24 h following treatment with 1.0 mg/kg HAL showed rapid tolerance to the HAL cue, sensitization to the AMPH cue, but not AMPH-like withdrawal cues. Analysis of the results showed that tolerance to the AMPH and HAL cues reflected neuroadaptive baseline shifts and not weaker cue properties. These findings are consistent with predictions from opponent process theory of motivation and provide an animal model to study the motivational consequences that aversive symptoms of AMPH withdrawal such as dysphoria and anhedonia can have on drug-taking behavior.

  5. An integrated command control and communications center for first responders

    NASA Astrophysics Data System (ADS)

    Messner, Richard A.; Hludik, Frank; Vidacic, Dragan; Melnyk, Pavlo

    2005-05-01

    First responders to a major incident include many different agencies. These may include law enforcement officers, multiple fire departments, paramedics, HAZMAT response teams, and possibly even federal personnel such as FBI and FEMA. Often times multiple jurisdictions respond to the incident which causes interoperability issues with respect to communication and dissemination of time critical information. Accurate information from all responding sources needs to be rapidly collected and made available to the current on site responders as well as the follow-on responders who may just be arriving on scene. The creation of a common central database with a simple easy to use interface that is dynamically updated in real time would allow prompt and efficient information distribution between different jurisdictions. Such a system is paramount to the success of any response to a major incident. First responders typically arrive in mobile vehicles that are equipped with communications equipment. Although the first responders may make reports back to their specific home based command centers, the details of those reports are not typically available to other first responders who are not a part of that agencies infrastructure. Furthermore, the collection of information often occurs outside of the first responder vehicle and the details of the scene are normally either radioed from the field or written down and then disseminated after significant delay. Since first responders are not usually on the same communications channels, and the fact that there is normally a considerable amount of confusion during the first few hours on scene, it would be beneficial if there were a centralized location for the repository of time critical information which could be accessed by all the first responders in a common fashion without having to redesign or add significantly to each first responders hardware/software systems. Each first responder would then be able to provide information

  6. Preparing Teachers to Respond to Student Writing

    ERIC Educational Resources Information Center

    Ferris, Dana

    2007-01-01

    Responding to student writing is one of the most challenging aspects of the writing instructor's job, and it is certainly the most time-consuming. Preparing future teachers to respond to L2 writing thus becomes an important aspect of any pre-service training course. In this paper, the author describes her own approach to training writing…

  7. 33 CFR 20.310 - Default by respondent.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Pleadings and Motions § 20.310 Default by respondent. (a) The ALJ may find a respondent in default upon failure to file a timely answer to the complaint or, after motion, upon failure to appear at a conference or hearing without good cause shown. (b) Each motion for default must conform to the rules of form...

  8. 33 CFR 20.310 - Default by respondent.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Pleadings and Motions § 20.310 Default by respondent. (a) The ALJ may find a respondent in default upon failure to file a timely answer to the complaint or, after motion, upon failure to appear at a conference or hearing without good cause shown. (b) Each motion for default must conform to the rules of form...

  9. Responding to a Literary Work of Art.

    ERIC Educational Resources Information Center

    Washburn, William V.

    A study was conducted to examine three fundamental aspects of the process of responding to a literary work of art: the nature of the reader's response to literature, the processes of response to literature, and the relationship of a reader's personal construct system to the way in which the reader responds to a literary work of art. The subjects…

  10. The prepared emotional reflex: intentional preparation of automatic approach and avoidance tendencies as a means to regulate emotional responding.

    PubMed

    Eder, Andreas B; Rothermund, Klaus; Proctor, Robert W

    2010-08-01

    Advance preparation of action courses toward emotional stimuli is an effective means to regulate impulsive emotional behavior. Our experiment shows that performing intentional acts of approach and avoidance in an evaluation task influences the unintended activation of approach and avoidance tendencies in another task in which stimulus valence is irrelevant. For the evaluation-relevant blocks, participants received either congruent (positive-approach, negative-avoidance) or incongruent (positive-avoidance, negative-approach) mapping instructions. In the evaluation-irrelevant blocks, approach- and avoidance-related lever movements were selected in response to a stimulus feature other than valence (affective Simon task). Response mapping in the evaluation task influenced performance in the evaluation-irrelevant task: An enhanced affective Simon effect was observed with congruent mapping instructions; in contrast, the effect was reversed when the evaluation task required incongruent responses. Thus, action instructions toward affective stimuli received in one task determined affective response tendencies in another task where these instructions were not in effect. These findings suggest that intentionally prepared short-term links between affective valence and motor responses elicit associated responses without a deliberate act of will, operating like a "prepared reflex." Copyright 2010 APA

  11. Sixteen Textbook Authors Respond.

    ERIC Educational Resources Information Center

    Hewitt, John P.; And Others

    1988-01-01

    The articles on textbook publication written by Sheryl Fullerton and Franklin C. Graham were responded to by: John Hewitt, Henry Tischler, George Ritzer, Paul Baker, Erich Goode, D. Stanley Eitzen, Jon Shepard, Richard Schaefer, Caroline Persell, Beth Hess, Paul Zopf, Jr., Jeanne Ballantine, Duane Monette, Mary Ann Lamanna, John Macionis, and…

  12. What information strategy responding to social needs should be?

    NASA Astrophysics Data System (ADS)

    Fujii, Kunihiko

    With the contemporary social phenomena that people think much of diversity of value, they are concerned with differentiation from others. Consumers' tendency to seek unique goods is common to all, giving impetus to makers' attitude that they try to produce varieties of goods but small amount for each. Consequently, life cycle of goods has become smaller than ever, and rapid and creative information gathering and utilization have become essential when makers produce goods responding to consumers' need. The author discusses how information strategy should be worked in the comprehensive business activities, and how information should be located as the powerful management resource.

  13. Rhesus leg muscle EMG activity during a foot pedal pressing task on Bion 11

    NASA Technical Reports Server (NTRS)

    Hodgson, J. A.; Riazansky, S. N.; Goulet, C.; Badakva, A. M.; Kozlovskaya, I. B.; Recktenwald, M. R.; McCall, G.; Roy, R. R.; Fanton, J. W.; Edgerton, V. R.

    2000-01-01

    Rhesus monkeys (Macaca mulatta) were trained to perform a foot lever pressing task for a food reward. EMG activity was recorded from selected lower limb muscles of 2 animals before, during, and after a 14-day spaceflight and from 3 animals during a ground-based simulation of the flight. Integrated EMG activity was calculated for each muscle during the 20-min test. Comparisons were made between data recorded before any experimental manipulations and during flight or flight simulation. Spaceflight reduced soleus (Sol) activity to 25% of preflight levels, whereas it was reduced to 50% of control in the flight simulation. During flight, medial gastrocnemius (MG) activity was reduced to 25% of preflight activity, whereas the simulation group showed normal activity levels throughout all tests. The change in MG activity was apparent in the first inflight recording, suggesting that some effect of microgravity on MG activity was immediate.

  14. 43 CFR 9.9 - How does the Secretary receive and respond to comments?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... to comments? 9.9 Section 9.9 Public Lands: Interior Office of the Secretary of the Interior INTERGOVERNMENTAL REVIEW OF DEPARTMENT OF THE INTERIOR PROGRAMS AND ACTIVITIES § 9.9 How does the Secretary receive and respond to comments? (a) The Secretary follows the procedures in § 9.10 if: (1) A state office or...

  15. Chronic restraint stress causes a delayed increase in responding for palatable food cues during forced abstinence via a dopamine D1-like receptor-mediated mechanism

    PubMed Central

    Ball, Kevin T.; Best, Olivia; Luo, Jonathan; Miller, Leah R.

    2016-01-01

    Relapse to unhealthy eating habits in dieters is often triggered by stress. Animal models, moreover, have confirmed a causal role for acute stress in relapse. The role of chronic stress in relapse vulnerability, however, has received relatively little attention. Therefore, in the present study, we used an abstinence-based relapse model in rats to test the hypothesis that exposure to chronic stress increases subsequent relapse vulnerability. Rats were trained to press a lever for highly palatable food reinforcers in daily 3-hr sessions and then tested for food seeking (i.e., responding for food associated cues) both before and after an acute or chronic restraint stress procedure (3 h/day × 1 day or 10 days, respectively) or control procedure (unstressed). The second food seeking test was conducted either 1 day or 7 days after the last restraint. Because chronic stress causes dopamine D1-like receptor-mediated alterations in prefrontal cortex (a relapse node), we also assessed dopaminergic involvement by administering either SCH-23390 (10.0 μg/kg; i.p.), a dopamine D1-like receptor antagonist, or vehicle prior to daily treatments. Results showed that chronically, but not acutely, stressed rats displayed increased food seeking 7 days, but not 1 day, after the last restraint. Importantly, SCH-23390 combined with chronic stress reversed this effect. These results suggest that drugs targeting D1-like receptors during chronic stress may help to prevent future relapse in dieters. PMID:27845229

  16. Assisted extraction of the energy level spacings and lever arms in direct current bias measurements of one-dimensional quantum wires, using an image recognition routine

    NASA Astrophysics Data System (ADS)

    Lesage, A. A. J.; Smith, L. W.; Al-Taie, H.; See, P.; Griffiths, J. P.; Farrer, I.; Jones, G. A. C.; Ritchie, D. A.; Kelly, M. J.; Smith, C. G.

    2015-01-01

    A multiplexer technique is used to individually measure an array of 256 split gates on a single GaAs/AlGaAs heterostructure. This results in the generation of large volumes of data, which requires the development of automated data analysis routines. An algorithm is developed to find the spacing between discrete energy levels, which form due to transverse confinement from the split gate. The lever arm, which relates split gate voltage to energy, is also found from the measured data. This reduces the time spent on the analysis. Comparison with estimates obtained visually shows that the algorithm returns reliable results for subband spacing of split gates measured at 1.4 K. The routine is also used to assess direct current bias spectroscopy measurements at lower temperatures (50 mK). This technique is versatile and can be extended to other types of measurements. For example, it is used to extract the magnetic field at which Zeeman-split 1D subbands cross one another.

  17. Methamphetamine, d-amphetamine and p-chloroamphetamine induced neurotoxicity differentially effect impulsive responding on the stop-signal task in rats

    PubMed Central

    Furlong, Teri M.; Leavitt, Lee S.; Keefe, Kristen A.; Son, Jong-Hyun

    2016-01-01

    Abused amphetamines, such as d-amphetamine (AMPH) and methamphetamine (METH), are highly addictive and destructive to health and productive lifestyles. The abuse of these drugs is associated with impulsive behavior, which is likely to contribute to addiction. The amphetamines also differentially damage dopamine (DA) and serotonin (5-HT) systems, which regulate impulsive behavior; therefore, exposure to these drugs may differentially alter impulsive behavior to effect the progression of addiction. We examined the impact of neurotoxicity induced by three amphetamines on impulsive action using a stop-signal task in rats. Animals were rewarded with a food pellet after lever pressing (i.e. a go trial), unless an auditory cue was presented and withholding lever press gained reward (i.e. a stop trial). Animals were trained on the task and then exposed to a neurotoxic regimen of either AMPH, p-chloroamphetamine (PCA), or METH. These regimens preferentially reduced DA transporter levels in striatum, 5-HT transporter levels in prefrontal cortex, or both, respectively. Assessment of performance on the stop-signal task beginning one week after the treatment revealed that AMPH produced a deficit in go-trial performance, whereas PCA did not alter performance on either trial type. In contrast, METH produced a deficit in stop-trial performance (i.e. impulsive action) but not go-trial performance. These findings suggest that the different neurotoxic consequences of substituted amphetamines are associated with different effects on inhibitory control over behavior. Thus, the course of addiction and maladaptive behavior resulting from exposure to these substances is likely to differ. PMID:26846719

  18. Emotional Risks to Respondents in Survey Research: Some Empirical Evidence

    PubMed Central

    Labott, Susan M.; Johnson, Timothy P.; Fendrich, Michael; Feeny, Norah C.

    2014-01-01

    Some survey research has documented distress in respondents with pre-existing emotional vulnerabilities, suggesting the possibility of harm. In this study, respondents were interviewed about a personally distressing event; mood, stress, and emotional reactions were assessed. Two days later, respondents participated in interventions to either enhance or alleviate the effects of the initial interview. Results indicated that distressing interviews increased stress and negative mood, although no adverse events occurred. Between the interviews, moods returned to baseline. Respondents who again discussed a distressing event reported moods more negative than those who discussed a neutral or a positive event. This study provides evidence that, among nonvulnerable survey respondents, interviews on distressing topics can result in negative moods and stress, but they do not harm respondents. PMID:24169422

  19. Emergency First Responders' Experience with Colorimetric Detection Methods

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sandra L. Fox; Keith A. Daum; Carla J. Miller

    2007-10-01

    Nationwide, first responders from state and federal support teams respond to hazardous materials incidents, industrial chemical spills, and potential weapons of mass destruction (WMD) attacks. Although first responders have sophisticated chemical, biological, radiological, and explosive detectors available for assessment of the incident scene, simple colorimetric detectors have a role in response actions. The large number of colorimetric chemical detection methods available on the market can make the selection of the proper methods difficult. Although each detector has unique aspects to provide qualitative or quantitative data about the unknown chemicals present, not all detectors provide consistent, accurate, and reliable results. Includedmore » here, in a consumer-report-style format, we provide “boots on the ground” information directly from first responders about how well colorimetric chemical detection methods meet their needs in the field and how they procure these methods.« less

  20. Project Responder: technology needs for local emergency response

    NASA Astrophysics Data System (ADS)

    Beakley, Guy; Garwin, Thomas; Pollard, Neal A.; Singley, George T., III; Tuohy, Robert V.; Lupo, Jasper

    2003-09-01

    Since April 2001, the Oklahoma City National Memorial Institute for the Prevention of Terrorism has funded an effort by Hicks &Associates, Inc. and the Terrorism Research Center, Inc., aimed ultimately at improving local, state, and federal emergency responders" capabilities for mitigating the effects of chemical, biological, radiological, nuclear or explosive/ incendiary (CBRNE) terrorism. This effort, titled "Project Responder," began by developing an understanding of how state and local responders view their current capabilities, shortfalls, and needs. This paper discusses some of the results of this first phase of the effort that has resulted in a comprehensive report titled "Emergency Responders" Needs, Goals, and Priorities." This paper addresses two of the capabilities from that report which we believe are of most interest to this conference. There are ten other capabilities discussed in the report, which may also be of interest.

  1. Empowering First Responders - Peer-to-Peer Technology

    DTIC Science & Technology

    2004-04-01

    the scene was challenging. Radio traffic overwhelmed the system to the extent that foot messengers became the most reliable means of communicating...sources of information critical to the incident at hand without the intervening “dispatcher” levels of interference. 14 The Challenge of Limited... hands of the front-line first responders. The proliferation of wireless communications and computers in the hands of first-responders continues

  2. Rats with congenital learned helplessness respond less to sucrose but show no deficits in activity or learning.

    PubMed

    Vollmayr, Barbara; Bachteler, Daniel; Vengeliene, Valentina; Gass, Peter; Spanagel, Rainer; Henn, Fritz

    2004-04-02

    Inbred rat strains for congenital learned helplessness (cLH) and for congenital resistance to learned helplessness (cNLH) were investigated as a model to study genetic predisposition to major depression. Congenitally helpless rats respond less to sucrose under a progressive ratio schedule. This is not confounded by locomotor hypoactivity: in contrast, cLH rats show a slight hyperactivity during the first 5 min of an open field test. cLH rats acquire operant responding to sucrose as readily as cNLH rats and exhibit normal memory acquisition and retrieval in the Morris water maze, thus ruling out general learning deficits as the cause of the decreased response to sucrose. Reduced total responses and reduced breaking points for sucrose in the cLH strain argue for anhedonia, which is an analogue to loss of pleasure essential for the diagnosis of major depressive episodes, and thus confirm the validity of congenitally learned helpless rats as a model of major depression.

  3. Responding to Children's Drawings

    ERIC Educational Resources Information Center

    Watts, Robert

    2010-01-01

    This article aims to explore the issues that face primary school teachers when responding to children's drawings. Assessment in art and design is an ongoing concern for teachers with limited experience and confidence in the area and, although children's drawings continue to be a focus of much research, the question of what it is that teachers say…

  4. 76 FR 68828 - Pipeline Safety: Emergency Responder Forum

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-07

    ... PHMSA-2011-0295] Pipeline Safety: Emergency Responder Forum AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA), DOT. ACTION: Notice of Forum. SUMMARY: PHMSA is co-sponsoring a one-day Emergency Responder Forum with the National Association of Pipeline Safety Representatives and the United...

  5. Tips for Disaster Responders: Preventing and Managing Stress

    MedlinePlus

    ... are called upon to respond, as well as approaches you can apply to manage stress during your deployment. You can also download SAMHSA’s new Disaster Behavioral Health App and access resources specific to pre- and post-deployment (for responders, supervisors, and family members). Stress ...

  6. Chronic blockade or constitutive deletion of the serotonin transporter reduces operant responding for food reward.

    PubMed

    Sanders, Amy Cecilia; Hussain, Ali J; Hen, René; Zhuang, Xiaoxi

    2007-11-01

    The therapeutic effects of chronic selective serotonin reuptake inhibitors (SSRIs) are well documented, yet the elementary behavioral processes that are affected by such treatment have not been fully investigated. We report here the effects of chronic fluoxetine treatment and genetic deletion of the serotonin transporter (SERT) on food reinforced behavior in three paradigms: the progressive ratio operant task, the concurrent choice operant task, and the Pavlovian-to-Instrumental transfer task. We consistently find that chronic pharmacological blockade or genetic deletion of SERT result in similar behavioral consequences: reduced operant responding for natural reward. This is in line with previous studies reporting declines in operant responding for drugs and intracranial self-stimulation with fluoxetine treatment, suggesting that the effect of SERT blockade can be generalized to different reward types. Detailed analyses of behavioral parameters indicate that this reduction in operant responding affect both goal-directed and non-goal-directed behaviors without affecting the Pavlovian cue-triggered excessive operant responding. In addition, both pharmacological and genetic manipulations reduce locomotor activity in the open field novel environment. Our data contrast with the effect of dopamine in increasing operant responding for natural reward specifically in goal-directed behaviors and in increasing Pavlovian cue-triggered excessive operant responding. Serotonin and dopamine have been proposed to serve opposing functions in motivational processes. Our data suggest that their interactions do not result in simple opponency. The fact that pharmacological blockade and genetic deletion of SERT have similar behavioral consequences reinforces the utility of the SERT null mice for investigation of the mechanisms underlying chronic SSRIs treatment.

  7. Responding to a Suicide Emergency

    MedlinePlus

    ... Share this! Home » Health Tips Responding To A Suicide Emergency Suicide takes the lives of nearly 40,000 Americans ... year saving those who try to kill themselves. "Suicide can be prevented if people learn to recognize ...

  8. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study.

    PubMed

    Gurbel, Paul A; Bliden, Kevin P; Butler, Kathleen; Antonino, Mark J; Wei, Cheryl; Teng, Renli; Rasmussen, Lars; Storey, Robert F; Nielsen, Tonny; Eikelboom, John W; Sabe-Affaki, Georges; Husted, Steen; Kereiakes, Dean J; Henderson, David; Patel, Dharmendra V; Tantry, Udaya S

    2010-03-16

    The antiplatelet effects of the Platelet Inhibition and Patient Outcomes (PLATO) trial dose of ticagrelor in patients nonresponsive to clopidogrel and after they switch agents are unknown. Patients with stable coronary artery disease on aspirin therapy received a 300-mg clopidogrel load; nonresponders were identified by light transmittance aggregometry. In a 2-way crossover design, nonresponders (n=41) and responders (n=57) randomly received clopidogrel (600 mg/75 mg once daily) or ticagrelor (180 mg/90 mg twice daily) for 14 days during period 1. In period 2, all nonresponders switched treatment; half of the responders continued the same treatment, whereas the others switched treatment. Inhibition of platelet aggregation was higher in nonresponders treated with ticagrelor compared with clopidogrel (P<0.05). Treatment with ticagrelor among nonresponders resulted in a >10%, >30%, and >50% decrease in platelet aggregation from baseline in 100%, 75%, and 13% of patients, respectively. Platelet aggregation fell from 59+/-9% to 35+/-11% in patients switched from clopidogrel to ticagrelor and increased from 36+/-14% to 56+/-9% in patients switched from ticagrelor to clopidogrel (P<0.0001 for both). Platelet reactivity was below the cut points previously associated with ischemic risk measured by light transmittance aggregometry, VerifyNow P2Y(12) assay, and vasodilator-stimulated phosphoprotein phosphorylation in 98% to 100% of patients after ticagrelor therapy versus 44% to 76% of patients after clopidogrel therapy. Ticagrelor therapy overcomes nonresponsiveness to clopidogrel, and its antiplatelet effect is the same in responders and nonresponders. Nearly all clopidogrel nonresponders and responders treated with ticagrelor will have platelet reactivity below the cut points associated with ischemic risk. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique Identifier: NCT00642811.

  9. Preference pulses and the win-stay, fix-and-sample model of choice.

    PubMed

    Hachiga, Yosuke; Sakagami, Takayuki; Silberberg, Alan

    2015-11-01

    Two groups of six rats each were trained to respond to two levers for a food reinforcer. One group was trained on concurrent variable-ratio 20 extinction schedules of reinforcement. The second group was trained on a concurrent variable-interval 27-s extinction schedule. In both groups, lever-schedule assignments changed randomly following reinforcement; a light cued the lever providing the next reinforcer. In the next condition, the light cue was removed and reinforcer assignment strictly alternated between levers. The next two conditions redetermined, in order, the first two conditions. Preference pulses, defined as a tendency for relative response rate to decline to the just-reinforced alternative with time since reinforcement, only appeared during the extinction schedule. Although the pulse's functional form was well described by a reinforcer-induction equation, there was a large residual between actual data and a pulse-as-artifact simulation (McLean, Grace, Pitts, & Hughes, 2014) used to discern reinforcer-dependent contributions to pulsing. However, if that simulation was modified to include a win-stay tendency (a propensity to stay on the just-reinforced alternative), the residual was greatly reduced. Additional modifications of the parameter values of the pulse-as-artifact simulation enabled it to accommodate the present results as well as those it originally accommodated. In its revised form, this simulation was used to create a model that describes response runs to the preferred alternative as terminating probabilistically, and runs to the unpreferred alternative as punctate with occasional perseverative response runs. After reinforcement, choices are modeled as returning briefly to the lever location that had been just reinforced. This win-stay propensity is hypothesized as due to reinforcer induction. © Society for the Experimental Analysis of Behavior.

  10. Hezbollah: Social Services as a Source of Power

    DTIC Science & Technology

    2010-06-01

    USSOF conducts special operations to prepare the oper- ational environment, prevent crisis, and respond with speed, aggression, and lethality to...International Relations from Troy State University, and Master of Military Arts and Science in Campaign Design from the U.S. Army Command and General Staff...movement into a stateless government that lever- ages charity to meet the needs of the neglected, oppressed, and marginalized Lebanese Shi’a

  11. Interviewer-Respondent Interactions in Conversational and Standardized Interviewing

    ERIC Educational Resources Information Center

    Mittereder, Felicitas; Durow, Jen; West, Brady T.; Kreuter, Frauke; Conrad, Frederick G.

    2018-01-01

    Standardized interviewing (SI) and conversational interviewing are two approaches to collect survey data that differ in how interviewers address respondent confusion. This article examines interviewer-respondent interactions that occur during these two techniques, focusing on requests for and provisions of clarification. The data derive from an…

  12. Telephone survey respondents' reactions to questions regarding interpersonal violence.

    PubMed

    Black, Michele C; Kresnow, Marcie-jo; Simon, Thomas R; Arias, Ileana; Shelley, Gene

    2006-08-01

    Concerns have been raised regarding the appropriateness of asking about violence victimization in telephone interviews and whether asking such questions increases respondents' distress or risk for harm. However, no large-scale studies have evaluated the impact of asking such questions during a telephone interview. This study explored respondents' reactions to questions regarding violence in two large recently completed telephone surveys. After respondents were asked about violence, they were asked if they thought surveys should ask such questions and whether they felt upset or afraid because of the questions. In both surveys, the majority of respondents (regardless of their victimization history) were willing to answer questions about violence and were not upset or afraid because of the questions. More than 92% of respondents thought such questions should be asked. These results challenge commonly held beliefs and assumptions and provide some assurance to those concerned with the ethical collection of data on violent victimization.

  13. Dopamine Modulates Reward Expectancy During Performance of a Slot Machine Task in Rats: Evidence for a ‘Near-miss' Effect

    PubMed Central

    Winstanley, Catharine A; Cocker, Paul J; Rogers, Robert D

    2011-01-01

    Cognitive accounts of gambling suggest that the experience of almost winning—so-called ‘near-misses'—encourage continued play and accelerate the development of pathological gambling (PG) in vulnerable individuals. One explanation for this effect is that near-misses signal imminent winning outcomes and heighten reward expectancy, galvanizing further play. Determining the neurochemical processes underlying the drive to gamble could facilitate the development of more effective treatments for PG. With this aim in mind, we evaluated rats' performance on a novel model of slot machine play, a form of gambling in which near-miss events are particularly salient. Subjects responded to a series of three flashing lights, loosely analogous to the wheels of a slot machine, causing the lights to set to ‘on' or ‘off'. A winning outcome was signaled if all three lights were illuminated. At the end of each trial, rats chose between responding on the ‘collect' lever, resulting in reward on win trials, but a time penalty on loss trials, or starting a new trial. Rats showed a marked preference for the collect lever when both two and three lights were illuminated, indicating heightened reward expectancy following near-misses similar to wins. Erroneous collect responses were increased by amphetamine and the D2 receptor agonist quinpirole, but not by the D1 receptor agonist SKF 81297 or receptor subtype selective antagonists. These data suggest that dopamine modulates reward expectancy following the experience of almost winning during slot machine play, via activity at D2 receptors, and this may result in an enhancement of the near-miss effect and facilitate further gambling. PMID:21209612

  14. Effects of fendiline on cocaine-seeking behavior in the rat.

    PubMed

    Cunningham, Jonathan J; Orr, Erin; Lothian, Barbara C; Morgen, Jennifer; Brebner, Karen

    2015-12-01

    L-type Ca(2+) channels (LTCC) and GABAB receptors are both possible targets in the development of new pharmacological compounds for cocaine addiction. Drugs that target either receptor attenuate a wide range of cocaine-seeking behaviors in the rat. However, there is no current human-approved pharmacotherapeutic intervention for psychostimulant addiction. This study examined the effects of a human-approved LTCC blocker, fendiline, on cocaine-taking and cocaine-seeking behavior in rats. The effects of combining fendiline with the GABAB receptor agonist baclofen on cocaine self-administration were also tested. Male Wistar rats were trained to self-administer cocaine, and the effects of fendiline pretreatment (vehicle, 1.78, 3.16, 5.62 mg/kg, intraperitoneal (IP)) were tested on progressive ratio responding and cue- and drug-induced reinstatement. The effects of baclofen (vehicle, 0.56, 1.78, 3.16, 5.62 mg/kg, IP) combined with fendiline (5.62 mg/kg, IP) were tested on progressive ratio responding. Control experiments measured locomotor activity and lever pressing for food in rats that received both baclofen and fendiline prior to the test session. Acute injections of fendiline prior to cue- or drug-induced reinstatement significantly attenuated lever-pressing behavior (p < 0.05). Fendiline and baclofen, but not fendiline alone, not only significantly attenuated breakpoints, but also impaired general motor behavior and naturalistic reinforcement (p < 0.05). These data suggest that the LTCC blocker fendiline may represent a novel pharmacotherapeutic intervention to prevent reinstatement to cocaine seeking. Also, co-administration of fendiline and baclofen not only can attenuate the motivation to take cocaine, but also impairs general motor behavior and naturalistic reinforcement.

  15. Mischievous responding in Internet Gaming Disorder research.

    PubMed

    Przybylski, Andrew K

    2016-01-01

    The most recent update to the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-5) included Internet Gaming Disorder as a new potential psychiatric condition that merited further scientific study. The present research was conducted in response to the APA Substance-Related Disorders Working Group's research call to estimate the extent to which mischievous responding-a known problematic pattern of participant self-report responding in questionnaires-is relevant to Internet Gaming Disorder research. In line with a registered sampling and analysis plan, findings from two studies (n tot = 11,908) provide clear evidence that mischievous responding is positively associated with the number of Internet Gaming Disorder indicators participants report. Results are discussed in the context of ongoing problem gaming research and the discussion provides recommendations for improving the quality of scientific practice in this area.

  16. BIOHAZ: Rapid On-Site Biological Detection for First Responders

    DTIC Science & Technology

    2001-09-01

    numbers comprise the compilation report: ADP013371 thru ADP013468 UNCLASSIFIED 84. BIORAZ: Rapid On- Site Biological Detection for First Responders Randall... responders an integated capability to collect an environmental sample and to rapidly screen that sample on site for the presence of biological material. This...further analyzed on site with immunoassay tickets before being sent to a laboratory. This system provides the emergency responders with a capability that

  17. The Principal Spectrum Runs from Initiators to Responders.

    ERIC Educational Resources Information Center

    Rutherford, William L.

    1990-01-01

    Most principals are either initiators, responders, or managers. Initiators seek out new information, take control of situations, and intervene to support teachers or correct problems. Responders ignore new information, have vague goals, and enact programs initiated by the central office. Manager principals have a hybrid style that generally…

  18. 28 CFR 115.164 - Staff first responder duties.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Staff first responder duties. 115.164... NATIONAL STANDARDS Standards for Lockups Official Response Following A Detainee Report § 115.164 Staff... first law enforcement staff member to respond to the report shall be required to: (1) Separate the...

  19. 28 CFR 115.164 - Staff first responder duties.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Staff first responder duties. 115.164... NATIONAL STANDARDS Standards for Lockups Official Response Following A Detainee Report § 115.164 Staff... first law enforcement staff member to respond to the report shall be required to: (1) Separate the...

  20. 28 CFR 115.164 - Staff first responder duties.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Staff first responder duties. 115.164... NATIONAL STANDARDS Standards for Lockups Official Response Following A Detainee Report § 115.164 Staff... first law enforcement staff member to respond to the report shall be required to: (1) Separate the...

  1. 77 GHz radar for first responders

    NASA Astrophysics Data System (ADS)

    Kosowsky, L. H.; Aronoff, A. D.; Ferraro, R.; Alland, S.; Fleischman, E.

    2017-02-01

    First responders have the dangerous task of responding to emergency situations in firefighting scenarios involving homes and offices. The importance of this radar is its ability to see through walls and into adjacent areas to provide the first responder with information to assess the status of a building fire, its occupants, and to supplement his thermal camera which is obstructed by the wall. For the firefighter looking into an adjacent room containing unknown objects including humans, the challenge is to recognize what is in that room, the configuration of the room, and potential escape routes. We have just concluded a series of experiments to illustrate the performance of 77GHz radar in buildings. The experiments utilized the Delphi Automotive radar as the mm wave sensor and included display software developed by L. H. Kosowsky and Associates. The system has demonstrated the capability of seeing through walls consisting of sheetrock separated by two by four pieces of wood. It has demonstrated the ability to see into the adjacent room and to display the existence of persons and furniture Based on published data, the radar will perform well in a smoke, haze, and/or fog environment.

  2. First-Class Inquiry

    ERIC Educational Resources Information Center

    Hesser, Kathi; Buck, Gayle; Dopp, Sandra

    2005-01-01

    In the activity described in this article, students will explore how variables in a first-class lever, specifically arm length, position of the fulcrum, and placement of the load, affect the effort needed to lift the load. To begin the lesson, demonstrate to the class how a first-class lever works and review what is meant by the terms fulcrum,…

  3. The role of the cholinergic system in the signal attenuation rat model of obsessive-compulsive disorder.

    PubMed

    Yankelevitch-Yahav, Roni; Roni, Yankelevitch-Yahav; Joel, Dapha; Daphna, Joel

    2013-11-01

    In comparison to studies of the involvement of the serotonergic, dopaminergic, and glutamatergic systems in the pathophysiology of obsessive-compulsive disorder (OCD), research on the involvement of the cholinergic system in this disorder has remained sparse. The aim of this study was to test the role of the cholinergic system in compulsive behavior using the signal attenuation rat model of OCD. In this model, "compulsive" behavior is induced by attenuating a signal indicating that a lever-press response was effective in producing food. The acetylcholinesterase inhibitor physostigmine (0.05, 0.10, and 0.15 mg/kg), the nicotinic agonist nicotine (0.03, 0.06, 0.10, 0.30, 0.60, and 1.00 mg/kg), the nicotinic antagonist mecamylamine (1, 3, 5, and 8 mg/kg), the muscarinic agonist oxotremorine (0.0075, 0.0150, and 0.0300 mg/kg), and the muscarinic antagonist scopolamine (0.15, 0.50, 1.00, and 1.50 mg/kg) were acutely administered to rats just before assessing their lever-press responding following signal attenuation (experiments 1, 3, 5, 7, and 9, respectively). Because the effects of signal attenuation are assessed under extinction conditions, drug doses that were effective in the above experiments were also tested in an extinction session of lever-press responding that was not preceded by signal attenuation (experiments 2, 4, 6, 8, and 10). Acute systemic administration of the cholinergic agents did not exert a selective anti- or pro-compulsive effect in the signal attenuation model. Acetylcholine does not seem to play a role in the signal attenuation rat model of OCD.

  4. Self-administration of cocaine and remifentanil by monkeys under concurrent-access conditions.

    PubMed

    Huskinson, Sally L; Freeman, Kevin B; Woolverton, William L

    2015-01-01

    Cocaine and opioids are often co-abused. Laboratory research has focused largely on the reinforcing effects of mixtures of drugs relative to the drugs alone. Less research has examined drug mixing by the subject under concurrent-access conditions. Self-administration of various doses of cocaine and remifentanil was examined under concurrent-access conditions. It was hypothesized that if cocaine and opioid combinations were more effective reinforcers than the single drugs, subjects would mix the two drugs by adjusting their responding to cocaine and an opioid alternative to maintain an optimal ratio of cocaine/remifentanil intake. Three male rhesus monkeys were allowed to self-administer cocaine (0.05-0.2 mg/kg/inj) or saline on one lever and remifentanil (0.05-0.4 μg/kg/inj) or saline on the other lever under concurrent fixed-ratio (FR) 10 schedules. Daily sessions lasted 2 h, and there was a 1-s timeout after every 10-s injection. When saline and drug were concurrently available, responding on the saline-associated lever was low relative to the drug alternative. When cocaine and remifentanil were concurrently available, both drugs were self-administered above saline levels. Cocaine intake decreased, and remifentanil intake increased as a function of the remifentanil dose that was available. Conversely, cocaine intake and remifentanil intake did not change systematically as a function of the cocaine dose that was available. Monkeys will mix cocaine and an opioid when the two drugs are available concurrently. However, there was no indication that monkeys titrated drug intake to maintain an optimal ratio of intake of the two compounds.

  5. Disruptions in effort-based decision-making and consummatory behavior following antagonism of the dopamine D2 receptor.

    PubMed

    Robles, Cindee F; Johnson, Alexander W

    2017-03-01

    Dopamine is known to influence motivational processes, however the precise role of this neurotransmitter remains a contentious issue. In the current study we sought to further characterize dopamine signaling in reward-based decision-making and consummatory behavior in mice, via lateral ventricle infusion of the dopamine D2 receptor antagonist eticlopride. In Experiment 1, we examined effort-based decision-making, in which mice had a choice between one lever, where a single response led to the delivery of a low value reward (2% sucrose); and a second lever, which led to a higher value reward (20% sucrose) that gradually required more effort to obtain. As the response schedule for the high value reward became more strict, low dose (4μg in 0.5μl) central infusions of eticlopride biased preference away from the high value reward, and toward the lever that led to the low value reward. Similarly, a higher dose of eticlopride (8μg in 0.5μl) also disrupted choice responding for the high value reward, however it did so by increasing omissions. In Experiment 2, we assessed the effects of eticlopride on consumption of 20% sucrose. The antagonist led to a dose-dependent reduction in intake, and through an analysis of licking microstructure, it was revealed that this in part reflected a reduction in the motivation to engage in consummatory behavior, rather than alterations in the evaluation of the reward. These results suggest that disruptions in D2 receptor signaling reduce the willingness to engage in effortful operant responding and consumption of a desirable outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Normative social influence is underdetected.

    PubMed

    Nolan, Jessica M; Schultz, P Wesley; Cialdini, Robert B; Goldstein, Noah J; Griskevicius, Vladas

    2008-07-01

    The present research investigated the persuasive impact and detectability of normative social influence. The first study surveyed 810 Californians about energy conservation and found that descriptive normative beliefs were more predictive of behavior than were other relevant beliefs, even though respondents rated such norms as least important in their conservation decisions. Study 2, a field experiment, showed that normative social influence produced the greatest change in behavior compared to information highlighting other reasons to conserve, even though respondents rated the normative information as least motivating. Results show that normative messages can be a powerful lever of persuasion but that their influence is underdetected.

  7. The operant-respondent distinction: Future directions

    PubMed Central

    Pear, Joseph J.; Eldridge, Gloria D.

    1984-01-01

    The operant-respondent distinction has provided a major organizing framework for the data generated through the experimental analysis of behavior. Problems have been encountered, however, in using it as an explanatory concept for such phenomena as avoidance and conditioned suppression. Data now exist that do not fit neatly into the framework. Moreover, the discovery of autoshaping has highlighted difficulties in isolating the two types of behavior and conditioning. Despite these problems, the operant-respondent framework remains the most successful paradigm currently available for organizing behavioral data. Research and theoretical efforts should therefore probably be directed to modifying the framework to account for disparate data. PMID:16812402

  8. International Scavenging for First Responder Guidance and Tools: IAEA Products

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stern, W.; Berthelot, L.; Bachner, K.

    In fiscal years (FY) 2016 and 2017, with support from the U.S. Department of Homeland Security (DHS), Brookhaven National Laboratory (BNL) examined the International Atomic Energy Agency (IAEA) radiological emergency response and preparedness products (guidance and tools) to determine which of these products could be useful to U.S. first responders. The IAEA Incident and Emergency Centre (IEC), which is responsible for emergency preparedness and response, offers a range of tools and guidance documents for responders in recognizing, responding to, and recovering from radiation emergencies and incidents. In order to implement this project, BNL obtained all potentially relevant tools and productsmore » produced by the IAEA IEC and analyzed these materials to determine their relevance to first responders in the U.S. Subsequently, BNL organized and hosted a workshop at DHS National Urban Security Technology Laboratory (NUSTL) for U.S. first responders to examine and evaluate IAEA products to consider their applicability to the United States. This report documents and describes the First Responder Product Evaluation Workshop, and provides recommendations on potential steps the U.S. federal government could take to make IAEA guidance and tools useful to U.S. responders.« less

  9. Distinct populations of neurons respond to emotional valence and arousal in the human subthalamic nucleus.

    PubMed

    Sieger, Tomáš; Serranová, Tereza; Růžička, Filip; Vostatek, Pavel; Wild, Jiří; Štastná, Daniela; Bonnet, Cecilia; Novák, Daniel; Růžička, Evžen; Urgošík, Dušan; Jech, Robert

    2015-03-10

    Both animal studies and studies using deep brain stimulation in humans have demonstrated the involvement of the subthalamic nucleus (STN) in motivational and emotional processes; however, participation of this nucleus in processing human emotion has not been investigated directly at the single-neuron level. We analyzed the relationship between the neuronal firing from intraoperative microrecordings from the STN during affective picture presentation in patients with Parkinson's disease (PD) and the affective ratings of emotional valence and arousal performed subsequently. We observed that 17% of neurons responded to emotional valence and arousal of visual stimuli according to individual ratings. The activity of some neurons was related to emotional valence, whereas different neurons responded to arousal. In addition, 14% of neurons responded to visual stimuli. Our results suggest the existence of neurons involved in processing or transmission of visual and emotional information in the human STN, and provide evidence of separate processing of the affective dimensions of valence and arousal at the level of single neurons as well.

  10. Effects of tailoring health messages on physical activity.

    PubMed

    Smeets, Tamara; Brug, J; de Vries, H

    2008-06-01

    Computer-tailored printed education can be a promising way of promoting physical activity. The present study tested whether computer-tailored feedback on physical activity is effective and whether there are differences between respondents with low and high motivation to change. Respondents (n = 487) were randomly assigned to a tailored intervention group or a no information control group. Physical activity and determinants were measured at baseline and after 3 months. At post-test, the motivated respondents in the control group were more likely not to meet the recommendation for physical activity than to meet it, and motivated respondents in the experimental group were more likely to engage in transport-related activities and showed more improvement over time for the total activity score than respondents in the control group (beta = 0.24, P = 0.02). Both groups improved their behaviour over time. No group differences in physical activity were found for the unmotivated respondents. The results showed that the effects of the tailored feedback were restricted to respondents who had a positive motivation to change at baseline. Possible explanations could be that unmotivated respondents were unwilling to read and process the information because they felt 'no need to change'. Alternatively, one tailored feedback letter may not have been sufficient for this unmotivated group.

  11. Effectiveness of a high-throughput genetic analysis in the identification of responders/non-responders to CYP2D6-metabolized drugs.

    PubMed

    Savino, Maria; Seripa, Davide; Gallo, Antonietta P; Garrubba, Maria; D'Onofrio, Grazia; Bizzarro, Alessandra; Paroni, Giulia; Paris, Francesco; Mecocci, Patrizia; Masullo, Carlo; Pilotto, Alberto; Santini, Stefano A

    2011-01-01

    Recent studies investigating the single cytochrome P450 (CYP) 2D6 allele *2A reported an association with the response to drug treatments. More genetic data can be obtained, however, by high-throughput based-technologies. Aim of this study is the high-throughput analysis of the CYP2D6 polymorphisms to evaluate its effectiveness in the identification of patient responders/non-responders to CYP2D6-metabolized drugs. An attempt to compare our results with those previously obtained with the standard analysis of CYP2D6 allele *2A was also made. Sixty blood samples from patients treated with CYP2D6-metabolized drugs previously genotyped for the allele CYP2D6*2A, were analyzed for the CYP2D6 polymorphisms with the AutoGenomics INFINITI CYP4502D6-I assay on the AutoGenomics INFINITI analyzer. A higher frequency of mutated alleles in responder than in non-responder patients (75.38 % vs 43.48 %; p = 0.015) was observed. Thus, the presence of a mutated allele of CYP2D6 was associated with a response to CYP2D6-metabolized drugs (OR = 4.044 (1.348 - 12.154). No difference was observed in the distribution of allele *2A (p = 0.320). The high-throughput genetic analysis of the CYP2D6 polymorphisms better discriminate responders/non-responders with respect to the standard analysis of the CYP2D6 allele *2A. A high-throughput genetic assay of the CYP2D6 may be useful to identify patients with different clinical responses to CYP2D6-metabolized drugs.

  12. End effector of the Discovery's RMS with tools moves toward Syncom-IV

    NASA Image and Video Library

    1985-04-17

    51D-44-046 (17 April 1985) --- The Space Shuttle Discovery's Remote Manipulator System (RMS) arm and two specially designed extensions move toward the troubled Syncom-IV (LEASAT) communications satellite during a station keeping mode of the two spacecraft in Earth orbit. Inside the Shuttle's cabin, astronaut Rhea Seddon, 51D mission specialist, controlled the Canadian-built arm in an attempt to move an external lever on the satellite. Crewmembers learned of the satellite's problems shortly after it was deployed from the cargo bay on April 13, 1985. The arm achieved physical contact with the lever as planned. However, the satellite did not respond to the contact as hoped. A 70mm handheld Hassellblad camera, aimed through Discovery's windows, recorded this frame -- one of the first to be released to news media following return of the seven-member crew on April 17, 1985.

  13. Understanding and Responding to Adolescent Girls' Online Cruelty

    ERIC Educational Resources Information Center

    Sokal, Laura

    2012-01-01

    Many school counsellors have identified "cyber-bullying" among adolescent girls as a growing concern. In order to respond to this issue, this article begins with a new model of cyber-communications from the unique perspective of adolescent girls. Next, it explores the limitations of responding to this model, based on current understandings of…

  14. A Simple Evacuation Modeling and Simulation Tool for First Responders

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koch, Daniel B; Payne, Patricia W

    2015-01-01

    Although modeling and simulation of mass evacuations during a natural or man-made disaster is an on-going and vigorous area of study, tool adoption by front-line first responders is uneven. Some of the factors that account for this situation include cost and complexity of the software. For several years, Oak Ridge National Laboratory has been actively developing the free Incident Management Preparedness and Coordination Toolkit (IMPACT) to address these issues. One of the components of IMPACT is a multi-agent simulation module for area-based and path-based evacuations. The user interface is designed so that anyone familiar with typical computer drawing tools canmore » quickly author a geospatially-correct evacuation visualization suitable for table-top exercises. Since IMPACT is designed for use in the field where network communications may not be available, quick on-site evacuation alternatives can be evaluated to keep pace with a fluid threat situation. Realism is enhanced by incorporating collision avoidance into the simulation. Statistics are gathered as the simulation unfolds, including most importantly time-to-evacuate, to help first responders choose the best course of action.« less

  15. 28 CFR 30.9 - How does the Attorney General receive and respond to comments?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false How does the Attorney General receive and... REVIEW OF DEPARTMENT OF JUSTICE PROGRAMS AND ACTIVITIES § 30.9 How does the Attorney General receive and respond to comments? (a) The Attorney General follows the procedures in § 30.10 if: (1) A state office or...

  16. Neural mechanisms mediating the effects of expectation in visceral placebo analgesia: an fMRI study in healthy placebo responders and nonresponders.

    PubMed

    Elsenbruch, Sigrid; Kotsis, Vassilios; Benson, Sven; Rosenberger, Christina; Reidick, Daniel; Schedlowski, Manfred; Bingel, Ulrike; Theysohn, Nina; Forsting, Michael; Gizewski, Elke R

    2012-02-01

    This functional magnetic resonance imaging study analysed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects. In N=36 healthy subjects, the blood oxygen level-dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing expectations regarding the probability of receiving an analgesic drug to 0%, 50%, and 100%. Placebo responders were identified by median split based on pain reduction (0% to 100% conditions), and changes in neural activation correlating with pain reduction in the 0% and 100% conditions were assessed in a regions-of-interest analysis. Expectation of pain relief resulted in overall reductions in pain and urge to defecate, and this response was significantly more pronounced in responders. Within responders, pain reduction correlated with reduced activation of dorsolateral and ventrolateral prefrontal cortices, somatosensory cortex, and thalamus during cued anticipation (paired t tests on the contrast 0%>100%); during painful stimulation, pain reduction correlated with reduced activation of the thalamus. Compared with nonresponders, responders demonstrated greater placebo-induced decreases in activation of dorsolateral prefrontal cortex during anticipation and in somatosensory cortex, posterior cingulate cortex, and thalamus during pain. In conclusion, the expectation of pain relief can substantially change perceived painfulness of visceral stimuli, which is associated with activity changes in the thalamus, prefrontal, and somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate psychological components of the pain response relevant to the pathophysiology and treatment of chronic abdominal pain. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  17. Characterizing Hospital Workers' Willingness to Respond to a Radiological Event

    PubMed Central

    Balicer, Ran D.; Catlett, Christina L.; Barnett, Daniel J.; Thompson, Carol B.; Hsu, Edbert B.; Morton, Melinda J.; Semon, Natalie L.; Watson, Christopher M.; Gwon, Howard S.; Links, Jonathan M.

    2011-01-01

    Introduction Terrorist use of a radiological dispersal device (RDD, or “dirty bomb”), which combines a conventional explosive device with radiological materials, is among the National Planning Scenarios of the United States government. Understanding employee willingness to respond is critical for planning experts. Previous research has demonstrated that perception of threat and efficacy is key in the assessing willingness to respond to a RDD event. Methods An anonymous online survey was used to evaluate the willingness of hospital employees to respond to a RDD event. Agreement with a series of belief statements was assessed, following a methodology validated in previous work. The survey was available online to all 18,612 employees of the Johns Hopkins Hospital from January to March 2009. Results Surveys were completed by 3426 employees (18.4%), whose demographic distribution was similar to overall hospital staff. 39% of hospital workers were not willing to respond to a RDD scenario if asked but not required to do so. Only 11% more were willing if required. Workers who were hesitant to agree to work additional hours when required were 20 times less likely to report during a RDD emergency. Respondents who perceived their peers as likely to report to work in a RDD emergency were 17 times more likely to respond during a RDD event if asked. Only 27.9% of the hospital employees with a perception of low efficacy declared willingness to respond to a severe RDD event. Perception of threat had little impact on willingness to respond among hospital workers. Conclusions Radiological scenarios such as RDDs are among the most dreaded emergency events yet studied. Several attitudinal indicators can help to identify hospital employees unlikely to respond. These risk-perception modifiers must then be addressed through training to enable effective hospital response to a RDD event. PMID:22046238

  18. Simulation analysis of operation respond in a field setting

    DOT National Transportation Integrated Search

    1997-01-01

    The Operation Respond system aims to facilitate rapid access to transportation carrier databases containing information on hazardous material cargo. As a consequence, first responders, such as police and fire department personnel, are expected to res...

  19. CLL Cells Respond to B-Cell Receptor Stimulation with a MicroRNA/mRNA Signature Associated with MYC Activation and Cell Cycle Progression

    PubMed Central

    Pede, Valerie; Rombout, Ans; Vermeire, Jolien; Naessens, Evelien; Mestdagh, Pieter; Robberecht, Nore; Vanderstraeten, Hanne; Van Roy, Nadine; Vandesompele, Jo; Speleman, Frank; Philippé, Jan; Verhasselt, Bruno

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is a disease with variable clinical outcome. Several prognostic factors such as the immunoglobulin heavy chain variable genes (IGHV) mutation status are linked to the B-cell receptor (BCR) complex, supporting a role for triggering the BCR in vivo in the pathogenesis. The miRNA profile upon stimulation and correlation with IGHV mutation status is however unknown. To evaluate the transcriptional response of peripheral blood CLL cells upon BCR stimulation in vitro, miRNA and mRNA expression was measured using hybridization arrays and qPCR. We found both IGHV mutated and unmutated CLL cells to respond with increased expression of MYC and other genes associated with BCR activation, and a phenotype of cell cycle progression. Genome-wide expression studies showed hsa-miR-132-3p/hsa-miR-212 miRNA cluster induction associated with a set of downregulated genes, enriched for genes modulated by BCR activation and amplified by Myc. We conclude that BCR triggering of CLL cells induces a transcriptional response of genes associated with BCR activation, enhanced cell cycle entry and progression and suggest that part of the transcriptional profiles linked to IGHV mutation status observed in isolated peripheral blood are not cell intrinsic but rather secondary to in vivo BCR stimulation. PMID:23560086

  20. Chronic restraint stress causes a delayed increase in responding for palatable food cues during forced abstinence via a dopamine D1-like receptor-mediated mechanism.

    PubMed

    Ball, Kevin T; Best, Olivia; Luo, Jonathan; Miller, Leah R

    2017-02-15

    Relapse to unhealthy eating habits in dieters is often triggered by stress. Animal models, moreover, have confirmed a causal role for acute stress in relapse. The role of chronic stress in relapse vulnerability, however, has received relatively little attention. Therefore, in the present study, we used an abstinence-based relapse model in rats to test the hypothesis that exposure to chronic stress increases subsequent relapse vulnerability. Rats were trained to press a lever for highly palatable food reinforcers in daily 3-h sessions and then tested for food seeking (i.e., responding for food associated cues) both before and after an acute or chronic restraint stress procedure (3h/day×1day or 10days, respectively) or control procedure (unstressed). The second food seeking test was conducted either 1day or 7days after the last restraint. Because chronic stress causes dopamine D1-like receptor-mediated alterations in prefrontal cortex (a relapse node), we also assessed dopaminergic involvement by administering either SCH-23390 (10.0μg/kg; i.p.), a dopamine D1-like receptor antagonist, or vehicle prior to daily treatments. Results showed that chronically, but not acutely, stressed rats displayed increased food seeking 7days, but not 1day, after the last restraint. Importantly, SCH-23390 combined with chronic stress reversed this effect. These results suggest that drugs targeting D 1 -like receptors during chronic stress may help to prevent future relapse in dieters. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. SATURN (Situational Awareness Tool for Urban Responder Networks)

    DTIC Science & Technology

    2012-07-01

    timeline. SATURN is applicable to a broad set of law enforcement, security, and counterterrorism missions typically addressed by urban responders...Keywords-video analytics; sensor fusion; video; urban responders I. INTRODUCTION Urban authorities have a broad set of missions . Duties vary in...both the frequency of occurrence and in the complexity of execution. They include everyday public safety missions such as traffic enforcement as

  2. First responder tracking and visualization for command and control toolkit

    NASA Astrophysics Data System (ADS)

    Woodley, Robert; Petrov, Plamen; Meisinger, Roger

    2010-04-01

    In order for First Responder Command and Control personnel to visualize incidents at urban building locations, DHS sponsored a small business research program to develop a tool to visualize 3D building interiors and movement of First Responders on site. 21st Century Systems, Inc. (21CSI), has developed a toolkit called Hierarchical Grid Referenced Normalized Display (HiGRND). HiGRND utilizes three components to provide a full spectrum of visualization tools to the First Responder. First, HiGRND visualizes the structure in 3D. Utilities in the 3D environment allow the user to switch between views (2D floor plans, 3D spatial, evacuation routes, etc.) and manually edit fast changing environments. HiGRND accepts CAD drawings and 3D digital objects and renders these in the 3D space. Second, HiGRND has a First Responder tracker that uses the transponder signals from First Responders to locate them in the virtual space. We use the movements of the First Responder to map the interior of structures. Finally, HiGRND can turn 2D blueprints into 3D objects. The 3D extruder extracts walls, symbols, and text from scanned blueprints to create the 3D mesh of the building. HiGRND increases the situational awareness of First Responders and allows them to make better, faster decisions in critical urban situations.

  3. Finding Respondents from Minority Groups

    ERIC Educational Resources Information Center

    Mier, Nelda; Medina, Alvaro A.; Bocanegra-Alonso, Anabel; Castillo-Ruiz, Octelina; Acosta-Gonzalez, Rosa I.; Ramirez, Jose A.

    2006-01-01

    The recruitment of respondents belonging to ethnic minorities poses important challenges in social and health research. This paper reflects on the enablers and barriers to recruitment that we encountered in our research work with persons belonging to ethnic minorities. Additionally, we applied the Matching Model of Recruitment, a theoretical…

  4. The effects of varied extinction procedures on contingent cue-induced reinstatement in Sprague-Dawley rats.

    PubMed

    Buffalari, Deanne M; Feltenstein, Matthew W; See, Ronald E

    2013-11-01

    Cue exposure therapy, which attempts to limit relapse by reducing reactivity to cocaine-paired cues through repeated exposures, has had limited success. The current experiments examined cocaine cue-induced anxiogenesis and investigated whether a model of cue exposure therapy would reduce reinstatement of cocaine seeking in rats with a history of cocaine self-administration. Male rats experienced daily intravenous cocaine self-administration. Rats then experienced exposure to either the self-administration context or the context plus noncontingent presentations of cocaine-paired cues. Immediately following exposure, anxiety-like behavior was measured using elevated plus maze and defensive burying tests. In a second group of rats, self-administration was followed by 7 days of exposure to the context, context + noncontingent cue exposure, lever extinction, or cue + lever extinction. All animals then underwent two contingent cue-induced reinstatement tests separated by 7 days of lever extinction. Exposure to noncontingent cocaine-paired cues in the self-administration context increased anxiety-like behavior on the defensive burying test. Animals that experienced lever + cue extinction displayed the least cocaine seeking on the first reinstatement test, and lever extinction reduced cocaine seeking below context exposure or context + noncontingent cue exposure. All animals had similar levels of cocaine seeking on the second reinstatement test. Noncontingent cue exposure causes anxiety, and noncontingent cue and context exposure are less effective at reducing contingent cue-induced reinstatement than lever or lever + cue extinction. These data indicate that active extinction of the drug-taking response may be critical for reduction of relapse proclivity in former cocaine users.

  5. In vivo myosin step-size from zebrafish skeletal muscle

    PubMed Central

    Ajtai, Katalin; Sun, Xiaojing; Takubo, Naoko; Wang, Yihua

    2016-01-01

    Muscle myosins transduce ATP free energy into actin displacement to power contraction. In vivo, myosin side chains are modified post-translationally under native conditions, potentially impacting function. Single myosin detection provides the ‘bottom-up’ myosin characterization probing basic mechanisms without ambiguities inherent to ensemble observation. Macroscopic muscle physiological experimentation provides the definitive ‘top-down’ phenotype characterizations that are the concerns in translational medicine. In vivo single myosin detection in muscle from zebrafish embryo models for human muscle fulfils ambitions for both bottom-up and top-down experimentation. A photoactivatable green fluorescent protein (GFP)-tagged myosin light chain expressed in transgenic zebrafish skeletal muscle specifically modifies the myosin lever-arm. Strychnine induces the simultaneous contraction of the bilateral tail muscles in a live embryo, causing them to be isometric while active. Highly inclined thin illumination excites the GFP tag of single lever-arms and its super-resolution orientation is measured from an active isometric muscle over a time sequence covering many transduction cycles. Consecutive frame lever-arm angular displacement converts to step-size by its product with the estimated lever-arm length. About 17% of the active myosin steps that fall between 2 and 7 nm are implicated as powerstrokes because they are beyond displacements detected from either relaxed or ATP-depleted (rigor) muscle. PMID:27249818

  6. A New Rhythm for Responding

    ERIC Educational Resources Information Center

    Walsh, Jackie Acree; Sattes, Beth Dankert

    2015-01-01

    The authors have seen an inspiring phenomenon in certain classrooms--students thinking through their answers to teacher questions, responding thoughtfully to other students' answers, even self-correcting or providing more information after they've answered a teacher aloud. The strategy behind these student actions is a skillful use of "wait…

  7. Heartbeat and economic decisions: observing mental stress among proposers and responders in the ultimatum bargaining game.

    PubMed

    Dulleck, Uwe; Schaffner, Markus; Torgler, Benno

    2014-01-01

    The ultimatum bargaining game (UBG), a widely used method in experimental economics, clearly demonstrates that motives other than pure monetary reward play a role in human economic decision making. In this study, we explore the behaviour and physiological reactions of both responders and proposers in an ultimatum bargaining game using heart rate variability (HRV), a small and nonintrusive technology that allows observation of both sides of an interaction in a normal experimental economics laboratory environment. We find that low offers by a proposer cause signs of mental stress in both the proposer and the responder; that is, both exhibit high ratios of low to high frequency activity in the HRV spectrum.

  8. Relationships Among Attention Networks and Physiological Responding to Threat

    PubMed Central

    Sarapas, Casey; Weinberg, Anna; Langenecker, Scott A.

    2016-01-01

    Although researchers have long hypothesized a relationship between attention and anxiety, theoretical and empirical accounts of this relationship have conflicted. We attempted to resolve these conflicts by examining relationships of attentional abilities with responding to predictable and unpredictable threat, related but distinct motivational process implicated in a number of anxiety disorders. Eighty-one individuals completed a behavioral task assessing efficiency of three components of attention – alerting, orienting, and executive control (Attention Network Test - Revised). We also assessed startle responding during anticipation of both predictable, imminent threat (of mild electric shock) and unpredictable contextual threat. Faster alerting and slower disengaging from non-emotional attention cues were related to heightened responding to unpredictable threat, whereas poorer executive control of attention was related to heightened responding to predictable threat. This double dissociation helps to integrate models of attention and anxiety and may be informative for treatment development. PMID:27816781

  9. Cost per responder of TNF-α therapies in Germany.

    PubMed

    Gissel, Christian; Repp, Holger

    2013-12-01

    Tumor necrosis factor α (TNF-α) inhibitors ranked highest in German pharmaceutical expenditure in 2011. Their most important application is the treatment of rheumatoid arthritis (RA). Our objective is to analyze cost per responder of TNF-α inhibitors for RA from the German Statutory Health Insurance funds' perspective. We aim to conduct the analysis based on randomized comparative effectiveness studies of the relevant treatments for the German setting. For inclusion of effectiveness studies, we require results in terms of response rates as defined by European League Against Rheumatism (EULAR) or American College of Rheumatology (ACR) criteria. We identify conventional triple therapy as the relevant comparator. We calculate cost per responder based on German direct medical costs. Direct clinical comparisons could be identified for both etanercept and infliximab compared to triple therapy. For infliximab, cost per responder was 216,392 euros for ACR50 and 432,784 euros for ACR70 responses. For etanercept, cost per ACR70 responder was 321,527 euros. Cost was lower for response defined by EULAR criteria, but data was only available for infliximab. Cost per responder is overestimated by 40% due to inclusion of taxes and mandatory rebates in German drugs' list prices. Our analysis shows specific requirements for cost-effectiveness analysis in Germany. Cost per responder for TNF-α treatment in the German setting is more than double the cost estimated in a similar analysis for the USA, which measured against placebo. The difference in results shows the critical role of the correct comparator for a specific setting.

  10. The Hv1 proton channel responds to mechanical stimuli.

    PubMed

    Pathak, Medha M; Tran, Truc; Hong, Liang; Joós, Béla; Morris, Catherine E; Tombola, Francesco

    2016-11-01

    The voltage-gated proton channel, Hv1, is expressed in tissues throughout the body and plays important roles in pH homeostasis and regulation of NADPH oxidase. Hv1 operates in membrane compartments that experience strong mechanical forces under physiological or pathological conditions. In microglia, for example, Hv1 activity is potentiated by cell swelling and causes an increase in brain damage after stroke. The channel complex consists of two proton-permeable voltage-sensing domains (VSDs) linked by a cytoplasmic coiled-coil domain. Here, we report that these VSDs directly respond to mechanical stimuli. We find that membrane stretch facilitates Hv1 channel opening by increasing the rate of activation and shifting the steady-state activation curve to less depolarized potentials. In the presence of a transmembrane pH gradient, membrane stretch alone opens the channel without the need for strong depolarizations. The effect of membrane stretch persists for several minutes after the mechanical stimulus is turned off, suggesting that the channel switches to a "facilitated" mode in which opening occurs more readily and then slowly reverts to the normal mode observed in the absence of membrane stretch. Conductance simulations with a six-state model recapitulate all the features of the channel's response to mechanical stimulation. Hv1 mechanosensitivity thus provides a mechanistic link between channel activation in microglia and brain damage after stroke. © 2016 Pathak et al.

  11. Responding to Bullying: What Works?

    ERIC Educational Resources Information Center

    Craig, Wendy; Pepler, Debra; Blais, Julie

    2007-01-01

    Children who are bullied are often told to "solve the problems themselves"; however, when bullying is repeated over time, it becomes increasingly difficult for victimized children to stop the torment because of their relative lack of power. We examine the ways in which children respond to bullying and their evaluations of the…

  12. Responding to Change From Without.

    ERIC Educational Resources Information Center

    Hall, Carroll L.

    This paper first discusses similarities between the medical profession and the present status of the education profession. Discussion centers on changes in education in New Mexico generated by external agencies to which colleges are having to respond, as did medical schools in the past. The New Mexico State Department of Education developed the…

  13. 78 FR 57621 - First Responder Network Authority Board Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-19

    ... Network Authority Board Meeting AGENCY: National Telecommunications and Information Administration, U.S. Department of Commerce. ACTION: Notice of special meeting of the First Responder Network Authority. SUMMARY: The Board of the First Responder Network Authority (FirstNet) will hold a Special Board meeting via...

  14. 78 FR 5422 - First Responder Network Authority Board Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-25

    ... Network Authority Board Meeting AGENCY: National Telecommunications and Information Administration, U.S... information regarding the public meeting of the Board of the First Responder Network Authority (FirstNet) to... confidential, to discuss personnel matters, or to discuss legal matters affecting the First Responder Network...

  15. 78 FR 72667 - First Responder Network Authority Board Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-03

    ... Network Authority Board Meeting AGENCY: National Telecommunications and Information Administration, U.S. Department of Commerce. ACTION: Notice of Open Public Meeting of the First Responder Network Authority. SUMMARY: The Board of the First Responder Network Authority (FirstNet) will convene an open public meeting...

  16. 49 CFR 630.7 - Failure to respond to questions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Failure to respond to questions. 630.7 Section 630.7 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION NATIONAL TRANSIT DATABASE § 630.7 Failure to respond to questions...

  17. 49 CFR 630.7 - Failure to respond to questions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Failure to respond to questions. 630.7 Section 630.7 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION NATIONAL TRANSIT DATABASE § 630.7 Failure to respond to questions...

  18. 49 CFR 630.7 - Failure to respond to questions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Failure to respond to questions. 630.7 Section 630.7 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION NATIONAL TRANSIT DATABASE § 630.7 Failure to respond to questions...

  19. 49 CFR 630.7 - Failure to respond to questions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Failure to respond to questions. 630.7 Section 630.7 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION NATIONAL TRANSIT DATABASE § 630.7 Failure to respond to questions...

  20. 49 CFR 630.7 - Failure to respond to questions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Failure to respond to questions. 630.7 Section 630.7 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION NATIONAL TRANSIT DATABASE § 630.7 Failure to respond to questions...

  1. Distinct populations of neurons respond to emotional valence and arousal in the human subthalamic nucleus

    PubMed Central

    Sieger, Tomáš; Serranová, Tereza; Růžička, Filip; Vostatek, Pavel; Wild, Jiří; Šťastná, Daniela; Bonnet, Cecilia; Novák, Daniel; Růžička, Evžen; Urgošík, Dušan; Jech, Robert

    2015-01-01

    Both animal studies and studies using deep brain stimulation in humans have demonstrated the involvement of the subthalamic nucleus (STN) in motivational and emotional processes; however, participation of this nucleus in processing human emotion has not been investigated directly at the single-neuron level. We analyzed the relationship between the neuronal firing from intraoperative microrecordings from the STN during affective picture presentation in patients with Parkinson’s disease (PD) and the affective ratings of emotional valence and arousal performed subsequently. We observed that 17% of neurons responded to emotional valence and arousal of visual stimuli according to individual ratings. The activity of some neurons was related to emotional valence, whereas different neurons responded to arousal. In addition, 14% of neurons responded to visual stimuli. Our results suggest the existence of neurons involved in processing or transmission of visual and emotional information in the human STN, and provide evidence of separate processing of the affective dimensions of valence and arousal at the level of single neurons as well. PMID:25713375

  2. Interaction in the Research Interview and Drug-Related Disclosures among Respondents.

    ERIC Educational Resources Information Center

    Myers, Vincent

    1979-01-01

    Interviewers and respondents judged interview interactions during a survey of drug-related sentiments. Pronounced variability in interviewer-respondent judgements occurred in unanticipated ways related to gender, role, and ethnicity of participants. Positive interaction yielded different respondent cognitions and reports of illicit drug ingestion…

  3. Analysis of TLR7, SOCS1 and ISG15 immune genes expression in the peripheral blood of responder and non-responder patients with chronic Hepatitis C

    PubMed Central

    Dowran, Razieh; Sarvari, Jamal; Moattari, Afagh; Fattahi, Mohammad-Reza; Ramezani, Amin; Hosseini, Seyed Younes

    2017-01-01

    Aim: To evaluate the baseline expression of the immune genes in PBMCs of responder and non-responder patients with chronic Hepatitis C. Background: Although the contribution of peripheral blood mononuclear cell (PBMC) gene expression in treatment outcome of hepatitis C virus (HCV) infection is supposed, it has remained to be distinctly delineated. The baseline expression of the immune genes inside PBMCs may reflect the responsiveness status following IFN treatment. Methods: Totally, 22 chronic HCV encompasses 10 responders and 12 non-responsive cases enrolled randomly regarding medical records. The PBMCs from the peripheral blood samples were isolated and then incubated for 6 hours in the culture media. The baseline expression of TLR7, SOCS1 and ISG15 was measured by Real time PCR. Results: The gene expression pattern in PBMCs of both groups showed a similar trend. The expression of SOCS1 and TLR7 genes showed higher levels in non-responder group (P>0.05). The result of ISG15 showed a higher but non-significant expression in the responder group (P>0.05). Conclusion: The similar pattern of TLR7, SOCS1 and ISG15 expression in the responder and non-responder patients indicated their poor discriminating and predictive value in PBMCs sample. PMID:29379591

  4. High responders and low responders: factors associated with individual variation in response to standardized training.

    PubMed

    Mann, Theresa N; Lamberts, Robert P; Lambert, Michael I

    2014-08-01

    The response to an exercise intervention is often described in general terms, with the assumption that the group average represents a typical response for most individuals. In reality, however, it is more common for individuals to show a wide range of responses to an intervention rather than a similar response. This phenomenon of 'high responders' and 'low responders' following a standardized training intervention may provide helpful insights into mechanisms of training adaptation and methods of training prescription. Therefore, the aim of this review was to discuss factors associated with inter-individual variation in response to standardized, endurance-type training. It is well-known that genetic influences make an important contribution to individual variation in certain training responses. The association between genotype and training response has often been supported using heritability estimates; however, recent studies have been able to link variation in some training responses to specific single nucleotide polymorphisms. It would appear that hereditary influences are often expressed through hereditary influences on the pre-training phenotype, with some parameters showing a hereditary influence in the pre-training phenotype but not in the subsequent training response. In most cases, the pre-training phenotype appears to predict only a small amount of variation in the subsequent training response of that phenotype. However, the relationship between pre-training autonomic activity and subsequent maximal oxygen uptake response appears to show relatively stronger predictive potential. Individual variation in response to standardized training that cannot be explained by genetic influences may be related to the characteristics of the training program or lifestyle factors. Although standardized programs usually involve training prescribed by relative intensity and duration, some methods of relative exercise intensity prescription may be more successful in creating

  5. Redding Responder phase I final report.

    DOT National Transportation Integrated Search

    2005-12-19

    The Redding Responder Study was initiated as a component of the Redding Incident : Management Enhancement (RIME) Program. The goals of the RIME program are to leverage : technology and communications deployments for emergency communication providers ...

  6. Relationships among attention networks and physiological responding to threat.

    PubMed

    Sarapas, Casey; Weinberg, Anna; Langenecker, Scott A; Shankman, Stewart A

    2017-02-01

    Although researchers have long hypothesized a relationship between attention and anxiety, theoretical and empirical accounts of this relationship have conflicted. We attempted to resolve these conflicts by examining relationships of attentional abilities with responding to predictable and unpredictable threat - related but distinct motivational process implicated in a number of anxiety disorders. Eighty-one individuals completed a behavioral task assessing efficiency of three components of attention - alerting, orienting, and executive control (Attention Network Test - Revised). We also assessed startle responding during anticipation of both predictable, imminent threat (of mild electric shock) and unpredictable contextual threat. Faster alerting and slower disengaging from non-emotional attention cues were related to heightened responding to unpredictable threat, whereas poorer executive control of attention was related to heightened responding to predictable threat. This double dissociation helps to integrate models of attention and anxiety and may be informative for treatment development. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Moral anger, but not moral disgust, responds to intentionality.

    PubMed

    Russell, Pascale Sophie; Giner-Sorolla, Roger

    2011-04-01

    We propose that, when people judge moral situations, anger responds to the contextual cues of harm and intentionality. On the other hand, disgust responds uniquely to whether or not a bodily norm violation has occurred; its apparent response to harm and intent is entirely explained by the coactivation of anger. We manipulated intent, harm, and bodily norm violation (eating human flesh) within a vignette describing a scientific experiment. Participants then rated their anger, disgust, and moral judgment, as well as various appraisals. Anger responded independently of disgust to harm and intentionality, whereas disgust responded independently of anger only to whether or not the act violated the bodily norm of cannibalism. Theoretically relevant appraisals accounted for the effects of harm and intent on anger; however, appraisals of abnormality did not fully account for the effects of the manipulations on disgust. Our results show that anger and disgust are separately elicited by different cues in a moral situation. PsycINFO Database Record (c) 2011 APA, all rights reserved.

  8. The acquisition of conditioned responding.

    PubMed

    Harris, Justin A

    2011-04-01

    This report analyzes the acquisition of conditioned responses in rats trained in a magazine approach paradigm. Following the suggestion by Gallistel, Fairhurst, and Balsam (2004), Weibull functions were fitted to the trial-by-trial response rates of individual rats. These showed that the emergence of responding was often delayed, after which the response rate would increase relatively gradually across trials. The fit of the Weibull function to the behavioral data of each rat was equaled by that of a cumulative exponential function incorporating a response threshold. Thus, the growth in conditioning strength on each trial can be modeled by the derivative of the exponential--a difference term of the form used in many models of associative learning (e.g., Rescorla & Wagner, 1972). Further analyses, comparing the acquisition of responding with a continuously reinforced stimulus (CRf) and a partially reinforced stimulus (PRf), provided further evidence in support of the difference term. In conclusion, the results are consistent with conventional models that describe learning as the growth of associative strength, incremented on each trial by an error-correction process.

  9. The Influence of Agreeableness and Ego Depletion on Emotional Responding.

    PubMed

    Finley, Anna J; Crowell, Adrienne L; Harmon-Jones, Eddie; Schmeichel, Brandon J

    2017-10-01

    Agreeable individuals report more intense withdrawal-oriented negative emotions across aversive situations. Two studies tested the hypothesis that self-regulatory depletion (i.e., ego depletion) moderates the relationship between trait Agreeableness and negative emotional responding. Ego depletion was manipulated using a writing task. Emotional responding was measured with startle eye-blink responses (Study 1, N = 71) and self-reported valence, arousal, and empathic concern (Study 2, N = 256) during emotional picture viewing. Trait Agreeableness was measured using a questionnaire. In Study 1, Agreeableness predicted especially large startle responses during aversive images and especially small startles during appetitive images. After exercising self-control, the relationship between startle magnitudes and Agreeableness decreased. In Study 2, Agreeableness predicted more empathic concern for aversive images, which in turn predicted heightened self-reported negative emotions. After exercising self-control, the relationship between Agreeableness and empathic concern decreased. Agreeable individuals exhibit heightened negative emotional responding. Ego depletion reduced the link between Agreeableness and negative emotional responding in Study 1 and moderated the indirect effect of Agreeableness on negative emotional responding via empathic concern in Study 2. Empathic concern appears to be a resource-intensive process underlying heightened responding to aversive stimuli among agreeable persons. © 2016 Wiley Periodicals, Inc.

  10. Disruptive effects of prefeeding and haloperidol administration on multiple measures of food-maintained behavior in rats

    PubMed Central

    Hayashi, Yusuke; Wirth, Oliver

    2015-01-01

    Four rats responded under a choice reaction-time procedure. At the beginning of each trial, the rats were required to hold down a center lever for a variable duration, release it following a high- or low-pitched tone, and press either a left or right lever, conditionally on the tone. Correct choices were reinforced with a probability of .95 or .05 under blinking or static houselights, respectively. After performance stabilized, disruptive effects of free access to food pellets prior to sessions (prefeeding) and intraperitoneal injection of haloperidol were examined on multiple behavioral measures (i.e., the number of trials completed, percent of correct responses, and reaction time). Resistance to prefeeding depended on the probability of food delivery for the number of trials completed and reaction time. Resistance to haloperidol, on the other hand, was not systematically affected by the probability of food delivery for all dependent measures. PMID:22209910

  11. Dual-mass vibratory rate gyroscope with suppressed translational acceleration response and quadrature-error correction capability

    NASA Technical Reports Server (NTRS)

    Clark, William A. (Inventor); Juneau, Thor N. (Inventor); Lemkin, Mark A. (Inventor); Roessig, Allen W. (Inventor)

    2001-01-01

    A microfabricated vibratory rate gyroscope to measure rotation includes two proof-masses mounted in a suspension system anchored to a substrate. The suspension has two principal modes of compliance, one of which is driven into oscillation. The driven oscillation combined with rotation of the substrate about an axis perpendicular to the substrate results in Coriolis acceleration along the other mode of compliance, the sense-mode. The sense-mode is designed to respond to Coriolis accelerationwhile suppressing the response to translational acceleration. This is accomplished using one or more rigid levers connecting the two proof-masses. The lever allows the proof-masses to move in opposite directions in response to Coriolis acceleration. The invention includes a means for canceling errors, termed quadrature error, due to imperfections in implementation of the sensor. Quadrature-error cancellation utilizes electrostatic forces to cancel out undesired sense-axis motion in phase with drive-mode position.

  12. Reducing effect of a combination of Phaseolus vulgaris and Cynara scolymus extracts on operant self-administration of a chocolate-flavoured beverage in rats.

    PubMed

    Zaru, Alessandro; Maccioni, Paola; Riva, Antonella; Morazzoni, Paolo; Bombardelli, Ezio; Gessa, Gian Luigi; Carai, Mauro A M; Colombo, Giancarlo

    2013-06-01

    Treatment with a rational combination of standardized extracts of Phaseolus vulgaris and Cynara scolymus reduced food intake and glycemia in rats. The present study was designed to assess the effect of this extract combination and of each single extract in an experimental model of food craving, made up of rats displaying exaggerated seeking and taking behaviors for a chocolate-flavoured beverage. After training to lever-respond for the chocolate-flavoured beverage, rats were treated with vehicle, Phaseolus vulgaris extract alone (200 mg/kg), Cynara scolymus extract alone (400 mg/kg), or combination of Phaseolus vulgaris (200 mg/kg) and Cynara scolymus (400 mg/kg) extracts. The Phaseolus vulgaris extract and the extract combination exerted similar and substantial decrements in the number of lever-responses and amount of self-administered chocolate-flavoured beverage; conversely, the Cynara scolymus extract was totally ineffective. These results suggest that (i) the capacity of the extract combination to reduce the self-administration of the chocolate-flavoured beverage entirely relied on the Phaseolus vulgaris extract, (ii) Phaseolus vulgaris extract may interfere with the mechanisms regulating food-related addictive-like behaviors, and (iii) combinations of Phaseolus vulgaris and Cynara scolymus extracts may possess a broad spectrum of activities, from treatment of metabolic syndrome to overweight, obesity, and possibly food-related addictive disorders. Copyright © 2012 John Wiley & Sons, Ltd.

  13. THE THYROID HORMONE TRANSPORTER, MCT8, SELECTIVELY RESPONDS TO THYROID HORMONE INSUFFICIENCY IN THE DEVELOPMENT RAT BRAIN.

    EPA Science Inventory

    Thyroid hormone (TH) is essential for normal brain development. Therefore, it is not surprising that a variety of adaptive mechanisms are activated in response to TH insufficiency. However, not all brain regions respond in the same fashion to TH insufficiency. This observation...

  14. Identifying Careless Responding With the Psychopathic Personality Inventory-Revised Validity Scales.

    PubMed

    Marcus, David K; Church, Abere Sawaqdeh; O'Connell, Debra; Lilienfeld, Scott O

    2018-01-01

    The Psychopathic Personality Inventory-Revised (PPI-R) includes validity scales that assess Deviant Responding (DR), Virtuous Responding, and Inconsistent Responding. We examined the utility of these scales for identifying careless responding using data from two online studies that examined correlates of psychopathy in college students (Sample 1: N = 583; Sample 2: N = 454). Compared with those below the cut scores, those above the cut on the DR scale yielded consistently lower validity coefficients when PPI-R scores were correlated with corresponding scales from the Triarchic Psychopathy Measure. The other three PPI-R validity scales yielded weaker and less consistent results. Participants who completed the studies in an inordinately brief amount of time scored significantly higher on the DR and Virtuous Responding scales than other participants. Based on the findings from the current studies, researchers collecting PPI-R data online should consider identifying and perhaps screening out respondents with elevated scores on the DR scale.

  15. Transforming Higher Education in the Information Age: Presidents Respond.

    ERIC Educational Resources Information Center

    Breslin, Richard D.; And Others

    1991-01-01

    College presidents respond to an article by Richard Nolan challenging college and university presidents and chancellors to transform their campuses for survival and competitive advantage in the information age. Respondents include Richard D. Breslin, David M. Clarke, Joseph Cronin, Thomas Ehrlich, Donald N. Langenberg, Harold McAninch, and Donald…

  16. Blood pressure in firefighters, police officers, and other emergency responders.

    PubMed

    Kales, Stefanos N; Tsismenakis, Antonios J; Zhang, Chunbai; Soteriades, Elpidoforos S

    2009-01-01

    Elevated blood pressure is a major risk factor for cardiovascular morbidity and mortality. Increased risk begins in the prehypertensive range and increases further with higher pressures. The strenuous duties of emergency responders (firefighters, police officers, and emergency medical services (EMS) personnel) can interact with their personal risk profiles, including elevated blood pressure, to precipitate acute cardiovascular events. Approximately three-quarters of emergency responders have prehypertension or hypertension, a proportion which is expected to increase, based on the obesity epidemic. Elevated blood pressure is also inadequately controlled in these professionals and strongly linked to cardiovascular disease morbidity and mortality. Notably, the majority of incident cardiovascular disease events occur in responders who are initially prehypertensive or only mildly hypertensive and whose average premorbid blood pressures are in the range in which many physicians would hesitate to prescribe medications (140-146/88-92). Laws mandating public benefits for emergency responders with cardiovascular disease provide an additional rationale for aggressively controlling their blood pressure. This review provides a background on emergency responders, summarizes occupational risk factors for hypertension and the metabolic syndrome, their prevalence of elevated blood pressure, and evidence linking hypertension with adverse outcomes in these professions. Next, discrepancies between relatively outdated medical standards for emergency responders and current, evidence-based guidelines for blood pressure management in the general public are highlighted. Finally, a workplace-oriented approach for blood pressure control among emergency responders is proposed, based on the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

  17. Discriminative stimulus effects of the imidazoline I2 receptor ligands BU224 and phenyzoline in rats.

    PubMed

    Qiu, Yanyan; Zhang, Yanan; Li, Jun-Xu

    2015-02-15

    Although imidazoline I2 receptor ligands have been used as discriminative stimuli, the role of efficacy of I2 receptor ligands as a critical determinant in drug discrimination has not been explored. This study characterized the discriminative stimulus effects of selective imidazoline I2 receptor ligands BU224 (a low-efficacy I2 receptor ligand) and phenyzoline (a higher efficacy I2 receptor ligand) in rats. Two groups of male Sprague-Dawley rats were trained to discriminate 5.6mg/kg BU224 or 32mg/kg phenyzoline (i.p.) from their vehicle in a two-lever food-reinforced drug discrimination procedure, respectively. All rats acquired the discriminations after an average of 18 (BU224) and 56 (phenyzoline) training sessions, respectively. BU224 and phenyzoline completely substituted for one another symmetrically. Several I2 receptor ligands (tracizoline, CR4056, RS45041, and idazoxan) all occasioned>80% drug-associated lever responding in both discriminations. The I2 receptor ligand 2-BFI and a monoamine oxidase inhibitor harmane occasioned>80% drug-associated lever responding in rats discriminating BU224. Other drugs that occasioned partial or less substitution to BU224 cue included clonidine, methamphetamine, ketamine, morphine, methadone and agmatine. Clonidine, methamphetamine and morphine also only produced partial substitution to phenyzoline cue. Naltrexone, dopamine D2 receptor antagonist haloperidol and serotonin (5-HT)2A receptor antagonist MDL100907 failed to alter the discriminative stimulus effects of BU224 or phenyzoline. Combined, these results are the first to demonstrate that BU224 and phenyzoline can serve as discriminative stimuli and that the low-efficacy I2 receptor ligand BU224 shares similar discriminative stimulus effects with higher-efficacy I2 receptor ligands such as phenyzoline and 2-BFI. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. The Burden of Research on Trauma for Respondents: A Prospective and Comparative Study on Respondents Evaluations and Predictors

    PubMed Central

    van der Velden, Peter G.; Bosmans, Mark W. G.; Scherpenzeel, Annette C.

    2013-01-01

    The possible burden of participating in trauma research is an important topic for Ethical Committees (EC's), Review Boards (RB's) and researchers. However, to what extent research on trauma is more burdensome than non-trauma research is unknown. Little is known about which factors explain respondents evaluations on the burden: to what extent are they trauma-related or dependent on other factors such as personality and how respondents evaluate research in general? Data of a large probability based multi-wave internet panel, with surveys on politics and values, personality and health in 2009 and 2011, and a survey on trauma in 2012 provided the unique opportunity to address these questions. Results among respondents confronted with these events in the past 2 years (N = 950) showed that questions on trauma were significantly and systematically evaluated as less pleasant (enjoyed less), more difficult, but also stimulated respondents to think about things more than almost all previous non-trauma surveys. Yet, the computed effect sizes indicated that the differences were (very) small and often meaningless. No differences were found between users and non-users of mental services, in contrast to posttraumatic stress symptoms. Evaluations of the burden of previous surveys in 2011 on politics and values, personality and health most strongly, systematically and independently predicted the burden of questions on trauma, and not posttraumatic stress symptoms, event-related coping self-efficacy and personality factors. For instance, multiple linear regression analyses showed that 30% of the variance of how (un)pleasant questions on trauma and life-events were evaluated, was explained by how (un)pleasant the 3 surveys in 2011 were evaluated, in contrast to posttraumatic stress symptoms (not significant) and coping self-efficacy (5%). Findings question why EC's, RB's and researchers should be more critical of the possible burden of trauma research than of the possible burden

  19. The Proton Pump Inhibitor Non-Responder: A Clinical Conundrum

    PubMed Central

    Hussain, Zilla H; Henderson, Emily E; Maradey-Romerao, Carla; George, Nina; Fass, Ronnie; Lacy, Brian E

    2015-01-01

    Gastroesophageal reflux disease (GERD) is a highly prevalent chronic condition where in stomach contents reflux into the esophagus causing symptoms, esophageal injury, and subsequent complications. Proton pump inhibitors (PPI) remain the mainstay of therapy for acid suppression. Despite their efficacy, significant proportions of GERD patients are either partial or non-responders to PPI therapy. Patients should be assessed for mechanisms that can lead to PPI failure and may require further evaluation to investigate for alternative causes. This monograph will outline a diagnostic approach to the PPI non-responder, review mechanisms associated with PPI failure, and discuss therapeutic options for those who fail to respond to PPI therapy. PMID:26270485

  20. 6 CFR 5.4 - Responsibility for responding to requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Responsibility for responding to requests. 5.4 Section 5.4 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY DISCLOSURE OF RECORDS AND INFORMATION Freedom of Information Act § 5.4 Responsibility for responding to requests. (a) In...

  1. Characterization of the discriminative stimulus produced by the dopamine antagonist tiapride.

    PubMed

    Cohen, C; Sanger, D J; Perrault, G

    1997-11-01

    The ability of tiapride, a selective D2/D3 dopamine receptor antagonist, to exert discriminative stimulus control of responding was investigated by training rats to discriminate this drug (30 mg/kg) from saline in a two-lever, food-reinforcement procedure. Acquisition of tiapride discrimination required a relatively lengthy training period (mean of 76 sessions) but stable performance was maintained throughout the 18- month study. The dose of tiapride eliciting 50% tiapride-lever choice (ED50) was 2.2 mg/kg. After determination of the dose-effect curve with tiapride, substitution tests with several dopamine antagonists and other reference compounds were performed. All dopamine antagonists, including amisulpride (ED50 4 mg/kg), sulpiride (18 mg/kg), sultopride (1.5 mg/kg), clebopride (0.13 mg/kg), raclopride (0.16 mg/kg), metoclopramide (1.4 mg/kg), remoxipride (4.8 mg/kg), pimozide (2.7 mg/kg), thioridazine (3.4 mg/kg), olanzapine (0.97 mg/kg), chlorpromazine (1.9 mg/kg), risperidone (0.22 mg/kg) and haloperidol (0.14 mg/kg), except clozapine (>10 mg/kg), produced dose-dependent substitution for tiapride. Tiapride-like stimulus effects were observed at doses that decreased response rates. However, ED50 values for substitution by tiapride, amisulpride, sulpiride, sultopride, pimozide, clebopride and thioridazine were lower than ED50 values for decreasing responding. Additional studies were conducted to evaluate the ability of direct and indirect dopamine agonists to attenuate the tiapride discriminative stimulus. Pretreatment with d-amphetamine and nomifensine antagonized the discriminative stimulus effects of tiapride. Quinpirole, 7-OH-DPAT, bromocriptine and apomorphine partially blocked the stimulus effects of tiapride whereas SKF 38393 did not affect the discrimination. These results from substitution and antagonism tests indicated that the discriminative effects of tiapride are mediated by activity at D2/D3 dopamine receptors.

  2. Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor.

    PubMed

    Bryce, Courtney A; Floresco, Stan B

    2016-07-01

    Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One-hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision-making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger vs smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression.

  3. The PulsePoint Respond mobile device application to crowdsource basic life support for patients with out-of-hospital cardiac arrest: Challenges for optimal implementation.

    PubMed

    Brooks, Steven C; Simmons, Graydon; Worthington, Heather; Bobrow, Bentley J; Morrison, Laurie J

    2016-01-01

    PulsePoint Respond is a novel mobile device application that notifies citizens within 400 m (∼ 1/4 mile) of a suspected cardiac arrest to facilitate resuscitation. Our objectives were to (1) characterize users, and (2) understand their behavior after being sent a notification. We sought to identify challenges for optimal implementation of PulsePoint-mediated bystander resuscitation. PulsePoint Respond users who sent a notification between 04/07/2012 and 06/16/2014 were invited to participate in an online survey. At the beginning of our study, PulsePoint Respond was active in more than 600 US communities. There were 1274 completed surveys (response rate 1448/6777, 21.4%). Respondents were firefighters (28%), paramedics (18%), emergency medical technicians (9%), nurses (7%), MDs (1%), other health care professionals (12%), and non-health care professionals (42%). Of those who received a PulsePoint notification, only 23% (189/813) responded to the PulsePoint notification. Of those who responded, 28% (52/187) did not arrive on scene. Of those who did arrive on scene, only 32% (44/135) found a person unconscious and not breathing normally. Of those who arrived on scene prior to emergency medical services and found a cardiac arrest victim, 79% (11/14) performed bystander cardiopulmonary resuscitation. Challenges for optimal implementation of PulsePoint Respond include technical aspects of the notifications (audio volume, precision of location information), excessive activation radii, insufficient user density in the community, and suboptimal cardiac arrest notification specificity. PulsePoint Respond has the potential to improve the community response to cardiac arrest, with 80% of responders attempting basic life support when they found a cardiac arrest victim prior to EMS. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Traffic control procedures for emergency responders.

    DOT National Transportation Integrated Search

    2006-10-01

    The objective of this study was to develop a training course and handbook to guide on-scene emergency responders responsible for controlling traffic during a roadway crash and subsequent clearance. : Traffic control is an essential component of incid...

  5. Prevent, Counter, and Respond - A Strategic Plan to Reduce Global Nuclear Threats (FY 2016-FY2020)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    None

    2015-03-01

    NNSA’s second core mission is reducing global nuclear dangers by preventing the acquisition of nuclear weapons or weapons-usable materials, countering efforts to acquire such weapons or materials, and responding to nuclear or radiological incidents. In 2015, NNSA reorganized its nonproliferation activities based on core competencies and realigned its counterterrorism and counterproliferation functions to more efficiently address both current and emerging threats and challenges. The reorganization accompanied the March 2015 release of the first ever Prevent, Counter, and Respond – A Strategic Plan to Reduce Global Nuclear Threats. This report, which NNSA will update annually, highlights key nuclear threat trends andmore » describes NNSA’s integrated threat reduction strategy.« less

  6. Training Law Enforcement Officials on Responding to Equine Calls

    ERIC Educational Resources Information Center

    Anderson, Kathleen P.; Stauffer, Gary; Stauffer, Monte; Anderson, Doug; Biodrowski, Kristie

    2016-01-01

    The occurrence of equine abuse/neglect cases is an ongoing issue. However, officials responding to equine cases are rarely experienced in handling horses. Therefore, workshops teaching basic horse husbandry were offered to better equip and prepare officials to respond to equine cases. Trainings consisted of both classroom and hands-on sessions.…

  7. Meta-Analysis and Inadequate Responders to Intervention: A Reply

    ERIC Educational Resources Information Center

    Swanson, H. Lee

    2012-01-01

    A meta-analysis by Tran, Sanchez, Arellano, and Swanson (2011) of the published RTI literature found that the magnitude of effect size (ES) between responders and low responders at posttest was significantly moderated by the pretest ES and the type of dependent measure administered, whereas no significant moderating effects were found in the mixed…

  8. Atypical neural responding to hearing one's own name in adults with ASD.

    PubMed

    Nijhof, Annabel D; Dhar, Monica; Goris, Judith; Brass, Marcel; Wiersema, Jan R

    2018-01-01

    Diminished responding to hearing one's own name is one of the earliest and strongest predictors of autism spectrum disorder (ASD). Here, we studied, for the first time, the neural correlates of hearing one's own name in ASD. Based on existing research, we hypothesized enhancement of late parietal positive activity specifically for the own name in neurotypicals, and for this effect to be reduced in adults with ASD. Source localization analyses were conducted to estimate group differences in brain regions underlying this effect. Twenty-one adults with ASD, and 21 age- and gender-matched neurotypicals were presented with 3 categories of names (own name, close other, unknown other) as task-irrelevant deviant stimuli in an auditory oddball paradigm while electroencephalogram was recorded. As expected, late parietal positivity was observed specifically for own names in neurotypicals, indicating enhanced attention to the own name. This preferential effect was absent in the ASD group. This group difference was associated with diminished activation in the right temporoparietal junction (rTPJ) in adults with ASD. Further, a familiarity effect was found for N1 amplitude, with larger amplitudes for familiar names (own name and close other). However, groups did not differ for this effect. These findings provide evidence of atypical neural responding to hearing one's own name in adults with ASD, suggesting a deficit in self-other distinction associated with rTPJ dysfunction. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  9. Immunotherapy, an evolving approach for the management of triple negative breast cancer: Converting non-responders to responders.

    PubMed

    Tolba, Mai F; Omar, Hany A

    2018-02-01

    Immunotherapy comprises a promising new era in cancer therapy. Immune checkpoint inhibitors targeting either the programmed death (PD)-1 receptor or its ligand PD-L1 were first approved by the Food and Drug Administration (FDA) for the management of metastatic melanoma in 2011. The approval of this class is being extended to include other types of immunogenic tumors. Although breast cancer (BC) was first categorized as non-immunogenic tumor type, there are certain subsets of BC that showed a high level of tumor infiltrating lymphocytes (TILs). Those subsets include the triple negative breast cancer (TNBC) and HER-2 positive breast tumors. Preliminary data from clinical trials presented promising outcomes for patients with advanced stage/metastatic TNBC. While the objective response rate (ORR) was relatively low, it is still promising because of the observation that the patients who respond to the treatment with immune checkpoint blockade have favorable prognosis and often show a significant increase in the overall survival. Therefore, the main challenge is to find ways to enhance the tumor response to such therapy and to convert the non-responders to responders. This will consequently bring new hopes for patients with advanced stage metastatic TNBC and help to decrease death tolls from this devastating disease. In the current review, we are highlighting and discussing the up-to-date strategies adopted at either the preclinical or the clinical settings to enhance tumor responsiveness to immunotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. How to respond to referee comments for scientific articles?

    PubMed

    Kalemci, Mustafa Serdar; Turna, Burak

    2013-09-01

    Currently, the increasing number of article submissions to scientific journals forces editors to be more selective in their acceptance of papers. Consequently, editors have increased the frequency of their use of scientific referee mechanisms. For many researchers, the publication of a scientific article in a high impact factor journal is a gradual and difficult process. After preparation and submission of a manuscript, one of the most important issue is responding to the comments of referees. However, there is a paucity of published reports in the literature describing how to respond to these comments. The aim of this review is to assist researchers/authors in responding to referee comments as part of the publication process for scientific articles.

  11. Repeated Alcohol Extinction Sessions in Conjunction with MK-801, but not Yohimbine or Propranolol, Reduces Subsequent Alcohol Cue-Induced Responding in Rats

    PubMed Central

    Williams, Keith L.; Harding, Kaitlyn M.

    2014-01-01

    Cues associated with alcohol can stimulate subjective states that increase relapse. Alcohol-cue associations may be strengthened by enhancing adrenergic activity with yohimbine or weakened by blocking adrenergic activity with propranolol. Alcohol-cue associations may also be weakened by long cue exposure sessions or strengthened by short cue exposure sessions. A useful treatment approach for alcoholism may combine adrenergic manipulation with cue exposure sessions of a specific duration. The present study sought to determine if cue exposure during long- or short-duration extinction sessions with post-session yohimbine or propranolol would alter alcohol cue-induced responding and self-administration. Rats were trained to respond for alcohol during sessions that included an olfactory cue given at the beginning of the session and a visual/auditory cue complex delivered concurrently with alcohol. Cue-induced responding was assessed before and after the repeated extinction sessions. Repeated alcohol extinction sessions of long duration (45 min) or short duration (5 min) were followed immediately by injections of saline, yohimbine, or propranolol. After the second set of cue-induced responding tests, reacquisition of operant alcohol self-administration was examined. To determine if the experimental procedures were sensitive to memory manipulation through other pharmacological mechanisms, the NMDA receptor antagonist MK-801 was given 20 min prior to long-duration extinction sessions. Both the long- and short-duration extinction sessions decreased cue-induced responding. Neither yohimbine nor propranolol, given post-session, had subsequent effects on cue-induced responding or alcohol self-administration. MK-801 blocked the effect of extinction sessions on cue-induced responding but had no effect on self-administration. The present study shows that manipulation of the NMDA system in combination with alcohol cue exposure therapy during extinction-like sessions may be more

  12. EIA responds to Nature article on shale gas projections

    EIA Publications

    2014-01-01

    EIA has responded to a December 4, 2014 Nature article on projections of shale gas production made by EIA and by the Bureau of Economic Geology of the University of Texas at Austin (BEG/UT) with a letter to the editors of Nature. BEG/UT has also responded to the article in their own letter to the editor.

  13. 40 CFR 1515.9 - Extending CEQ's time to respond.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Extending CEQ's time to respond. 1515... ACT PROCEDURES Procedures for Requesting Records § 1515.9 Extending CEQ's time to respond. (a) In... request (§§ 1515.6(a) and 1515.8(d)) may be extended by the Council for not more than 10 working days...

  14. 40 CFR 1515.9 - Extending CEQ's time to respond.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Extending CEQ's time to respond. 1515... ACT PROCEDURES Procedures for Requesting Records § 1515.9 Extending CEQ's time to respond. (a) In... request (§§ 1515.6(a) and 1515.8(d)) may be extended by the Council for not more than 10 working days...

  15. 40 CFR 1515.9 - Extending CEQ's time to respond.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Extending CEQ's time to respond. 1515... ACT PROCEDURES Procedures for Requesting Records § 1515.9 Extending CEQ's time to respond. (a) In... request (§§ 1515.6(a) and 1515.8(d)) may be extended by the Council for not more than 10 working days...

  16. 40 CFR 1515.9 - Extending CEQ's time to respond.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Extending CEQ's time to respond. 1515... ACT PROCEDURES Procedures for Requesting Records § 1515.9 Extending CEQ's time to respond. (a) In... request (§§ 1515.6(a) and 1515.8(d)) may be extended by the Council for not more than 10 working days...

  17. Accelerated Maternal Responding Following Intra-VTA Pertussis Toxin Treatment

    PubMed Central

    Byrnes, John J.; Gleason, Erin D.; Schoen, Mathew K.; Lovelock, Dennis F.; Carini, Lindsay M.; Byrnes, Elizabeth M.; Bridges, Robert S.

    2011-01-01

    Prior studies have supported a role for mesolimbic dopaminergic mechanisms in the regulation of maternal behavior. Accordingly, the ventral tegmental area (VTA) and its dopaminergic projections to the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in both the onset and maintenance of normal maternal behavior. To date, studies of direct manipulation of VTA neurochemistry at the onset of maternal behavior have been limited. The current study was undertaken to directly test the hypothesis that enhancement of dopaminergic transmission in the mesolimbic dopamine system can stimulate maternal activity using a pup-induced virgin model. Nulliparous female rats were stereotaxically infused with pertussis toxin (PTX 0, 0.1, or 0.3 μg/hemisphere) into the VTA to chronically stimulate the activity of dopaminergic projection neurons. After 3 days of recovery, maternal responding to donor pups was tested daily, and latency (in days) to full maternal behavior was recorded. Intra-VTA PTX treatment produced a robust dose-dependent decrease in maternal behavior latency, and a long-lasting increase in locomotor activity. These effects were associated with significantly decreased dopamine D1 receptor mRNA expression in the NAc. No effects of PTX treatment on mesolimbic dopamine utilization or mPFC receptor expression were observed. The findings indicate that chronic neural activation in the VTA accelerates the onset of maternal behavior in virgin female rats via modification of the NAc dopamine D1 receptor. PMID:21571006

  18. RESPONDENT-DRIVEN SAMPLING AS MARKOV CHAIN MONTE CARLO

    PubMed Central

    GOEL, SHARAD; SALGANIK, MATTHEW J.

    2013-01-01

    Respondent-driven sampling (RDS) is a recently introduced, and now widely used, technique for estimating disease prevalence in hidden populations. RDS data are collected through a snowball mechanism, in which current sample members recruit future sample members. In this paper we present respondent-driven sampling as Markov chain Monte Carlo (MCMC) importance sampling, and we examine the effects of community structure and the recruitment procedure on the variance of RDS estimates. Past work has assumed that the variance of RDS estimates is primarily affected by segregation between healthy and infected individuals. We examine an illustrative model to show that this is not necessarily the case, and that bottlenecks anywhere in the networks can substantially affect estimates. We also show that variance is inflated by a common design feature in which sample members are encouraged to recruit multiple future sample members. The paper concludes with suggestions for implementing and evaluating respondent-driven sampling studies. PMID:19572381

  19. Evidence for impulsivity in the Spontaneously Hypertensive Rat drawn from complementary response-withholding tasks

    PubMed Central

    Sanabria, Federico; Killeen, Peter R

    2008-01-01

    Background The inability to inhibit reinforced responses is a defining feature of ADHD associated with impulsivity. The Spontaneously Hypertensive Rat (SHR) has been extolled as an animal model of ADHD, but there is no clear experimental evidence of inhibition deficits in SHR. Attempts to demonstrate these deficits may have suffered from methodological and analytical limitations. Methods We provide a rationale for using two complementary response-withholding tasks to doubly dissociate impulsivity from motivational and motor processes. In the lever-holding task (LHT), continual lever depression was required for a minimum interval. Under a differential reinforcement of low rates schedule (DRL), a minimum interval was required between lever presses. Both tasks were studied using SHR and two normotensive control strains, Wistar-Kyoto (WKY) and Long Evans (LE), over an overlapping range of intervals (1 – 5 s for LHT and 5 – 60 s for DRL). Lever-holding and DRL performance was characterized as the output of a mixture of two processes, timing and iterative random responding; we call this account of response inhibition the Temporal Regulation (TR) model. In the context of TR, impulsivity was defined as a bias toward premature termination of the timed intervals. Results The TR model provided an accurate description of LHT and DRL performance. On the basis of TR parameter estimates, SHRs were more impulsive than LE rats across tasks and target times. WKY rats produced substantially shorter timed responses in the lever-holding task than in DRL, suggesting a motivational or motor deficit. The precision of timing by SHR, as measured by the variance of their timed intervals, was excellent, flouting expectations from ADHD research. Conclusion This research validates the TR model of response inhibition and supports SHR as an animal model of ADHD-related impulsivity. It indicates, however, that SHR's impulse-control deficit is not caused by imprecise timing. The use of ad hoc

  20. Visual Motor Integration as a Screener for Responders and Non-Responders in Preschool and Early School Years: Implications for Inclusive Assessment in Oman

    ERIC Educational Resources Information Center

    Emam, Mahmoud Mohamed; Kazem, Ali Mahdi

    2016-01-01

    Visual motor integration (VMI) is the ability of the eyes and hands to work together in smooth, efficient patterns. In Oman, there are few effective methods to assess VMI skills in children in inclusive settings. The current study investigated the performance of preschool and early school years responders and non-responders on a VMI test. The full…